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BUILDING A FOUNDATION OF IMMUNITYPRESENTED BY ELIAS KASS ND
DISCLOSURES
This activity is jointly provided by Cardea and the Washington Department of Health
This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Institute for Medical QualityCalifornia Medical Association (IMQCMA) through the joint providership of Cardea and the Washington Department of Health Cardea is accredited by the IMQCMA to provide continuing medical education for physicians
Cardea designates this webinar for a maximum of 1 AMA PRA category 1 credit(s)TM Physicians should claim credit commensurate with the extent of their participation in the activity
DISCLOSURES AND OBTAINING CONTINUING MEDICAL EDUCATION CREDIT
bull Successful completion of this continuing education activity includes the following
bull Attending the entire CE activity
bull Completing the online evaluation
bull At the end of the evaluation there are links to request the CME certificate
If you have any questions about this CE activity please contact Trang Kuss at trangkussdohwagov
The planners and presenters of this activity have no relevant financial relationships with any commercial interest pertaining to this activity
The following off label use will be discussed
bull Tdap vaccine (Adacel Boostrix)
CONFLICT OF INTEREST
BACKGROUND
bull Former software engineer graduated from the University of Michigan
bull Bastyr 2010 in Naturopathic Medicine and Midwifery
bull Away training in Vanuatu
bull Dual practice midwifery and naturopathic primary care 2010-2014
bull Now specializing in pediatric primary care and specialty infant feeding (breastfeeding tongue tie)
bull CDC Childhood Immunization Champion for Washington State in 2017
VACCINES ARE NATUROPATHIC
bull When we prevent disease we donrsquot need to treat
bull Vaccines reduce use of antibiotics and antibiotic resistance
bull Vaccines prevent misery suffering and death
WE STILL NEED VACCINES
bull Vaccine-preventable diseases still kill here and elsewhere
bull There are plenty of other diseases available to exercise the immune system
UNIVERSAL DISEASES
bull A universal disease affected nearly everyone at some point in their life
bull Measles mumps polio many others are universal
bull If a disease was universal how bad can it be Would Mother Nature really do something destructive
bull Yes
MEASLES A CASE STUDY
MORBIDITY VS MORTALITY
bull When the internet argues that the death rate was going down before vaccines that is true
bull But only because we developed treatments for the complications from measles
bull The case rate didnrsquot go down until the vaccine was introduced
MORTALITY VS CASES
SIMPLE RASH
bull Measles complications in 40 of cases
bull Diarrhea
bull Middle ear infection
bull Bronchopneumonia
bull Encephalitis in 11000
bull Death in 21000 usually pneumonia or encephalitis
bull In developing countries up to 25 fatality rate
bull Subacute sclerosing panencephalitis (fatal) in 110000 or morebull Kids who get the measles before age 5 have a one in 1387 chance of developing SSPE (Wendorf et al 2016)
bull Kids who get the measles before age 1 have a one in 609 chance
VACCINErsquoS CONTINUED CONTRIBUTION
bull Measles remains a leading cause of vaccine-preventable infant mortality but progress is being made
bull From 2000-2016
bull Reported measles incidence decreased 87 from 145 to 19 cases per million persons
bull Annual estimated measles deaths decreased 84 (204 million deaths prevented)
MMWR Oct 27 2017 Vol 66 No 42
PROS AND CONS OF NATURAL INFECTION
bull Immunity from natural infection often lasts longer (though this is questionable)
bull But in order to get that immunity you need to experience the disease
bull Suffering
bull Transmission to others
bull Complications
bull Death
bull Long term complications of measles include
bull SSPE (fatal)
bull Immunosuppression increasing deaths from other infectious diseases
bull More severe COPD in smokers who experienced measles
IMMUNOSUPPRESSION
bull After measles infection immunologic memory is suppressed for 2-3 years which increases all-cause mortality
bull Measles BCG and polio immunization reduced all-cause mortality rate by roughly half
Mina MJ Measles immune suppression and vaccination direct and indirect nonspecific vaccine benefits J Infect 201774 Suppl 1S10ndash7
NON-SPECIFIC EFFECTS OF MEASLES AND OTHER VACCINES
1 Higgins JPT Soares-Weiser K Reingold A Systematic review of the non-specific effects of BCG DTP and measles containing vaccines httpwwwwhointimmunizationsagemeetings2014april (accessed 1 Jun 2014)
2 Strategic Advisory Group of Experts on Immunization Meeting of the Strategic Advisory Group of Experts on Immunization April 2014 - conclusions and recommendations Week Epidemiol Rec201489221ndash36 [PubMed]
3Aaby P Martins CL Garly ML et al Non-specific effects of standard measles vaccine at 45 and 9 months of age on childhood mortality randomised controlled trial BMJ 2010341c6495doi101136bmjc6495 [PMC free article] [PubMed]
4Aaby P Samb B Simondon F et al Non-specific beneficial effect of measles immunisation analysis of mortality studies from developing countries BMJ 1995311481ndash5 doi101136bmj3117003481[PMC free article] [PubMed]
5 Kristensen I Aaby P Jensen H Routine vaccinations and child survival follow up study in Guinea-Bissau West Africa BMJ 20003211435ndash8 doi101136bmj32172741435 [PMC free article] [PubMed]
6 Benn CS Netea MG Selin LK et alA small jabmdasha big effect non-specific immunomodulation by vaccinesTrends Immunol 201334431ndash9 doi101016jit201304004 [PubMed]
CONCERN TH1 VS TH2
bull Th1 cells decrease the production of IgE
bull Th2 cells increase the production of IgE
bull Babies are born with a predominance of Th2 a bias towards allergic responses
bull To reduce allergic responses stimulate Th1
bull Infection with bacteria and viruses stimulates production of Th1
bull Infection with worms and helminths stimulate production of Th2
bull If babieskids donrsquot experience infection will they develop more allergies
VACCINES DO NOT CAUSE ALLERGIES
bull Vaccines do not prevent all diseases
bull Babies and kids still experience lots of infections
bull Large well-controlled epidemiologic studies do not support the hypothesis that vaccines cause allergies
bull ldquoHigher cumulative vaccine antigen doses were associated with less allergic sensitization allergic disease and less severe infant eczemardquo
Offit PA Hackett CJ Addressing Parentsrsquo Concerns Do Vaccines Cause Allergic or Autoimmune Diseases Pediatrics 2003111(3)653ndash9
CONCERN VS ACTUAL EFFECT
bull There are many valid questions and concerns about vaccines
bull For the most part we have the data to answer these questions
bull Donrsquot stop at the question Keep going to the answer
MECHANISMPATHWAY VS ACTUAL EFFECT
bull Many concerns about vaccines are based on biochemical pathways or mechanism
bull Donrsquot stop there Just because something is possible or even plausible doesnrsquot mean it actually happens that way
bull Look at the clinical data and the large body of literature
CONCERN VARICELLA VS ZOSTER
Question Does varicella immunization increase the risk of shingles in the unvaccinated population because of lack of immune stimulationviral suppression
Answer No zoster rates were going up before varicella program and were not affected by varicella immunization (Hales 2013) (Siedler 2014)
Plus varicella immunization seems to reduce the risk of shingles in immunized people (Baxter 2013)
SAFETY MONITORING
bull Pre-licensure trials including phase I II and III
bull Post-licensure studies and surveillance
bull Vaccine Safety Datalink (VSD)
bull Vaccine Adverse Event Reporting System (VAERS)
bull Clinical Immunization Safety Assessment (CISA) project ndash investigation into possible events in specific people certain populations excluded by pre-licensure studies
bull httpswwwhistoryofvaccinesorgcontentarticlesvaccine-development-testing-and-regulation
bull httpswwwcdcgovvaccinesbasicstest-approvehtml
SAFETY MONITORING VAERS
bull Vaccine Adverse Event Reporting System
bull ldquoSpontaneous (passive) surveillance means that no active effort is made to search for identify and collect information but rather information is passively received from those who choose to voluntarily report their experiencerdquo (Shimabukuro 2015)
bull Anyone can file any report
bull All reports are reviewed
bull ldquo[VAERS] reporting is incomplete requires follow-up investigation and cannot directly distinguish temporal associations from causal associations Consequently VAERS functions as a hypothesis-generating mechanism an early-warning signal of potential problems regarding vaccine safetyrdquo (Schwartz 2012)
Shimabukuro TT Nguyen M Martin D DeStefano F Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 201533(36)4398ndash405Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
SAFETY MONITORING VACCINE SAFETY DATALINK (VSD)
bull Includes multiple large HMOsMCOs covering 88 million people in 2011
bull Huge numbers allow for detection of rareserious events
bull Objectives of the Vaccine Safety Datalinkbull To conduct research on important vaccine safety questions in large populations
bull To conduct vaccine safety studies that come from questions or concerns in the medical literature or from other vaccine safety systems like VAERS
bull To monitor possible adverse events when new vaccines are licensed or when there are new vaccine recommendations
bull To provide information to committees who make recommendations for the nation
httpswwwcdcgovvaccinesafetyensuringsafetymonitoringvsdindexhtml
VACCINE SAFETY CASE ROTAVIRUS
bull In 1999 based on reports of 15 infants (of 15 million doses administered) experiencing intussusception after immunization with Rotashield the CDC recommended suspending use temporarily while investigation proceeded
bull Researchers found statistically significant differences in RotaShield vaccination rates between the two groups hellip Based on these results and estimates of the background rate of intussusception among US infants the research team estimated one additional case of intussusception attributable to the vaccine for every 4670 to 9474 infants vaccinated
bull Wyeth pulled the vaccine from the market when it was clear ACIP would vote against its use
Side bar Interesting moral questions about ldquoslamming the doorrdquo on a rotavirus vaccine that stood to save many lives internationally where the risk benefit ratio might be different (Schwartz 2012)
Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
VACCINE SAFETY CASE ROTAVIRUS
bull Rotateq (pentavalent) licensed in 2006
bull Rotarix (monovalent) licensed in 2008
bull Studies of the two new vaccines included 60000 to 70000 infants each in which no increased risk of intussusception was identified
VSD ROTAVIRUS (2014)
RESULTS
During the study period 207955 doses of monovalent rotavirus vaccine (including 115908 first doses and 92047 second doses) were administered in the VSD population We identified 6 cases of intussusception within 7 days after the administration of either dose of vaccine For the two doses combined the expected number of intussusception cases was 072 resulting in a significant relative risk of 84 For the pentavalent rotavirus vaccine 1301810 doses were administered duringthe study period with 8 observed intussusception cases (711 expected) for a nonsignificant relative risk of 11 The relativerisk of chart-confirmed intussusception within 7 days after monovalent rotavirus vaccination as compared with the risk after pentavalent rotavirus vaccination was 94 (95 confidence interval 14 to 1038) The attributable risk of intussusception after the administration of two doses of monovalent rotavirus vaccine was estimated to be 53 per 100000 infants vaccinated
Action
bull Rotavirus was pulled out of the multi-vaccine VIS
bull Rotavirus VIS was updated with specific information about the risks of rotavirus and clinical presentation
ROTAVIRUS WHY BOTHER
PRE-VACCINEbull Every year globally
bull 111 million episodes of gastroenteritis requiring only home care
bull 25 million outpatient medical visits
bull 2 million hospitalizations
bull 400000 deaths
POST-VACCINEbull A dramatic decrease (gt80) in the incidence of
severe rotavirus diarrhea has been reported in high-income countries
bull A decrease of about 50 has been reported in low-income settings
bull Reductions in diarrhea-associated deaths of 31 in infants younger than 1 year old and 42 in children younger than 5 years old in countries with low child mortality
OrsquoRyan M Rotavirus Vaccines a story of success with challenges ahead F1000 Research 20176 Parashar et al Global illness and deaths caused by rotavirus disease in children Emerg Infect Dis 2003 May9(5)565-72
EFFICACY CASE LAIV (FLUMIST)
bull ldquoIn light of low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013ndash14 and 2015ndash16 seasons for the 2016ndash17 season ACIP makes the interim recommendation that LAIV4 should not be usedrdquo
bull Even though it would cost the manufacturer as the ACIP recommendation drives usage and insurance coverage
Grohskopf LA Prevention and Control of Seasonal Influenza with Vaccines MMWR Recomm Rep 201665
WHO IS ACIP
bull The Advisory Committee on Immunization Practices ldquoincludes 15 voting members responsible for making vaccine recommendations The Secretary of the US Department of Health and Human Services (DHHS) selects these members following an application and nomination process Fourteen of the members have expertise in vaccinology immunology pediatrics internal medicine nursing family medicine virology public health infectious diseases andor preventive medicine one member is a consumer representative who provides perspectives on the social and community aspects of vaccination
bull In addition to the 15 voting members ACIP includes 8 ex officio members who represent other federal agencies with responsibility for immunization programs in the United States and 30 non-voting representatives of liaison organizations that bring related immunization expertiserdquo
httpswwwcdcgovvaccinesacipabouthtml
ACIP - SCHEDULE
bull How do vaccines get added Do vaccines ever get taken offbull Work group convene to work on one vaccine-preventable disease or group of diseases
bull Work group members collect and review data on disease epidemiology vaccine efficacy effectiveness safety feasibility of program implementation and economic aspects of immunization policy to include in written policy statements
bull Insurance companies and Medicaid generally pay for whatrsquos on the ACIP schedule so these recommendations have financial repercussions
bull Because immunity is not inherited we need to immunize each persongeneration until the disease is truly eradicated
bull ACIP meetings are open to the public and can be viewed by streaming webcast
bull If recommendations are accepted by the CDC they are published in the MMWR
httpswwwcdcgovvaccinesacipabouthtml
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
DISCLOSURES
This activity is jointly provided by Cardea and the Washington Department of Health
This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Institute for Medical QualityCalifornia Medical Association (IMQCMA) through the joint providership of Cardea and the Washington Department of Health Cardea is accredited by the IMQCMA to provide continuing medical education for physicians
Cardea designates this webinar for a maximum of 1 AMA PRA category 1 credit(s)TM Physicians should claim credit commensurate with the extent of their participation in the activity
DISCLOSURES AND OBTAINING CONTINUING MEDICAL EDUCATION CREDIT
bull Successful completion of this continuing education activity includes the following
bull Attending the entire CE activity
bull Completing the online evaluation
bull At the end of the evaluation there are links to request the CME certificate
If you have any questions about this CE activity please contact Trang Kuss at trangkussdohwagov
The planners and presenters of this activity have no relevant financial relationships with any commercial interest pertaining to this activity
The following off label use will be discussed
bull Tdap vaccine (Adacel Boostrix)
CONFLICT OF INTEREST
BACKGROUND
bull Former software engineer graduated from the University of Michigan
bull Bastyr 2010 in Naturopathic Medicine and Midwifery
bull Away training in Vanuatu
bull Dual practice midwifery and naturopathic primary care 2010-2014
bull Now specializing in pediatric primary care and specialty infant feeding (breastfeeding tongue tie)
bull CDC Childhood Immunization Champion for Washington State in 2017
VACCINES ARE NATUROPATHIC
bull When we prevent disease we donrsquot need to treat
bull Vaccines reduce use of antibiotics and antibiotic resistance
bull Vaccines prevent misery suffering and death
WE STILL NEED VACCINES
bull Vaccine-preventable diseases still kill here and elsewhere
bull There are plenty of other diseases available to exercise the immune system
UNIVERSAL DISEASES
bull A universal disease affected nearly everyone at some point in their life
bull Measles mumps polio many others are universal
bull If a disease was universal how bad can it be Would Mother Nature really do something destructive
bull Yes
MEASLES A CASE STUDY
MORBIDITY VS MORTALITY
bull When the internet argues that the death rate was going down before vaccines that is true
bull But only because we developed treatments for the complications from measles
bull The case rate didnrsquot go down until the vaccine was introduced
MORTALITY VS CASES
SIMPLE RASH
bull Measles complications in 40 of cases
bull Diarrhea
bull Middle ear infection
bull Bronchopneumonia
bull Encephalitis in 11000
bull Death in 21000 usually pneumonia or encephalitis
bull In developing countries up to 25 fatality rate
bull Subacute sclerosing panencephalitis (fatal) in 110000 or morebull Kids who get the measles before age 5 have a one in 1387 chance of developing SSPE (Wendorf et al 2016)
bull Kids who get the measles before age 1 have a one in 609 chance
VACCINErsquoS CONTINUED CONTRIBUTION
bull Measles remains a leading cause of vaccine-preventable infant mortality but progress is being made
bull From 2000-2016
bull Reported measles incidence decreased 87 from 145 to 19 cases per million persons
bull Annual estimated measles deaths decreased 84 (204 million deaths prevented)
MMWR Oct 27 2017 Vol 66 No 42
PROS AND CONS OF NATURAL INFECTION
bull Immunity from natural infection often lasts longer (though this is questionable)
bull But in order to get that immunity you need to experience the disease
bull Suffering
bull Transmission to others
bull Complications
bull Death
bull Long term complications of measles include
bull SSPE (fatal)
bull Immunosuppression increasing deaths from other infectious diseases
bull More severe COPD in smokers who experienced measles
IMMUNOSUPPRESSION
bull After measles infection immunologic memory is suppressed for 2-3 years which increases all-cause mortality
bull Measles BCG and polio immunization reduced all-cause mortality rate by roughly half
Mina MJ Measles immune suppression and vaccination direct and indirect nonspecific vaccine benefits J Infect 201774 Suppl 1S10ndash7
NON-SPECIFIC EFFECTS OF MEASLES AND OTHER VACCINES
1 Higgins JPT Soares-Weiser K Reingold A Systematic review of the non-specific effects of BCG DTP and measles containing vaccines httpwwwwhointimmunizationsagemeetings2014april (accessed 1 Jun 2014)
2 Strategic Advisory Group of Experts on Immunization Meeting of the Strategic Advisory Group of Experts on Immunization April 2014 - conclusions and recommendations Week Epidemiol Rec201489221ndash36 [PubMed]
3Aaby P Martins CL Garly ML et al Non-specific effects of standard measles vaccine at 45 and 9 months of age on childhood mortality randomised controlled trial BMJ 2010341c6495doi101136bmjc6495 [PMC free article] [PubMed]
4Aaby P Samb B Simondon F et al Non-specific beneficial effect of measles immunisation analysis of mortality studies from developing countries BMJ 1995311481ndash5 doi101136bmj3117003481[PMC free article] [PubMed]
5 Kristensen I Aaby P Jensen H Routine vaccinations and child survival follow up study in Guinea-Bissau West Africa BMJ 20003211435ndash8 doi101136bmj32172741435 [PMC free article] [PubMed]
6 Benn CS Netea MG Selin LK et alA small jabmdasha big effect non-specific immunomodulation by vaccinesTrends Immunol 201334431ndash9 doi101016jit201304004 [PubMed]
CONCERN TH1 VS TH2
bull Th1 cells decrease the production of IgE
bull Th2 cells increase the production of IgE
bull Babies are born with a predominance of Th2 a bias towards allergic responses
bull To reduce allergic responses stimulate Th1
bull Infection with bacteria and viruses stimulates production of Th1
bull Infection with worms and helminths stimulate production of Th2
bull If babieskids donrsquot experience infection will they develop more allergies
VACCINES DO NOT CAUSE ALLERGIES
bull Vaccines do not prevent all diseases
bull Babies and kids still experience lots of infections
bull Large well-controlled epidemiologic studies do not support the hypothesis that vaccines cause allergies
bull ldquoHigher cumulative vaccine antigen doses were associated with less allergic sensitization allergic disease and less severe infant eczemardquo
Offit PA Hackett CJ Addressing Parentsrsquo Concerns Do Vaccines Cause Allergic or Autoimmune Diseases Pediatrics 2003111(3)653ndash9
CONCERN VS ACTUAL EFFECT
bull There are many valid questions and concerns about vaccines
bull For the most part we have the data to answer these questions
bull Donrsquot stop at the question Keep going to the answer
MECHANISMPATHWAY VS ACTUAL EFFECT
bull Many concerns about vaccines are based on biochemical pathways or mechanism
bull Donrsquot stop there Just because something is possible or even plausible doesnrsquot mean it actually happens that way
bull Look at the clinical data and the large body of literature
CONCERN VARICELLA VS ZOSTER
Question Does varicella immunization increase the risk of shingles in the unvaccinated population because of lack of immune stimulationviral suppression
Answer No zoster rates were going up before varicella program and were not affected by varicella immunization (Hales 2013) (Siedler 2014)
Plus varicella immunization seems to reduce the risk of shingles in immunized people (Baxter 2013)
SAFETY MONITORING
bull Pre-licensure trials including phase I II and III
bull Post-licensure studies and surveillance
bull Vaccine Safety Datalink (VSD)
bull Vaccine Adverse Event Reporting System (VAERS)
bull Clinical Immunization Safety Assessment (CISA) project ndash investigation into possible events in specific people certain populations excluded by pre-licensure studies
bull httpswwwhistoryofvaccinesorgcontentarticlesvaccine-development-testing-and-regulation
bull httpswwwcdcgovvaccinesbasicstest-approvehtml
SAFETY MONITORING VAERS
bull Vaccine Adverse Event Reporting System
bull ldquoSpontaneous (passive) surveillance means that no active effort is made to search for identify and collect information but rather information is passively received from those who choose to voluntarily report their experiencerdquo (Shimabukuro 2015)
bull Anyone can file any report
bull All reports are reviewed
bull ldquo[VAERS] reporting is incomplete requires follow-up investigation and cannot directly distinguish temporal associations from causal associations Consequently VAERS functions as a hypothesis-generating mechanism an early-warning signal of potential problems regarding vaccine safetyrdquo (Schwartz 2012)
Shimabukuro TT Nguyen M Martin D DeStefano F Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 201533(36)4398ndash405Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
SAFETY MONITORING VACCINE SAFETY DATALINK (VSD)
bull Includes multiple large HMOsMCOs covering 88 million people in 2011
bull Huge numbers allow for detection of rareserious events
bull Objectives of the Vaccine Safety Datalinkbull To conduct research on important vaccine safety questions in large populations
bull To conduct vaccine safety studies that come from questions or concerns in the medical literature or from other vaccine safety systems like VAERS
bull To monitor possible adverse events when new vaccines are licensed or when there are new vaccine recommendations
bull To provide information to committees who make recommendations for the nation
httpswwwcdcgovvaccinesafetyensuringsafetymonitoringvsdindexhtml
VACCINE SAFETY CASE ROTAVIRUS
bull In 1999 based on reports of 15 infants (of 15 million doses administered) experiencing intussusception after immunization with Rotashield the CDC recommended suspending use temporarily while investigation proceeded
bull Researchers found statistically significant differences in RotaShield vaccination rates between the two groups hellip Based on these results and estimates of the background rate of intussusception among US infants the research team estimated one additional case of intussusception attributable to the vaccine for every 4670 to 9474 infants vaccinated
bull Wyeth pulled the vaccine from the market when it was clear ACIP would vote against its use
Side bar Interesting moral questions about ldquoslamming the doorrdquo on a rotavirus vaccine that stood to save many lives internationally where the risk benefit ratio might be different (Schwartz 2012)
Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
VACCINE SAFETY CASE ROTAVIRUS
bull Rotateq (pentavalent) licensed in 2006
bull Rotarix (monovalent) licensed in 2008
bull Studies of the two new vaccines included 60000 to 70000 infants each in which no increased risk of intussusception was identified
VSD ROTAVIRUS (2014)
RESULTS
During the study period 207955 doses of monovalent rotavirus vaccine (including 115908 first doses and 92047 second doses) were administered in the VSD population We identified 6 cases of intussusception within 7 days after the administration of either dose of vaccine For the two doses combined the expected number of intussusception cases was 072 resulting in a significant relative risk of 84 For the pentavalent rotavirus vaccine 1301810 doses were administered duringthe study period with 8 observed intussusception cases (711 expected) for a nonsignificant relative risk of 11 The relativerisk of chart-confirmed intussusception within 7 days after monovalent rotavirus vaccination as compared with the risk after pentavalent rotavirus vaccination was 94 (95 confidence interval 14 to 1038) The attributable risk of intussusception after the administration of two doses of monovalent rotavirus vaccine was estimated to be 53 per 100000 infants vaccinated
Action
bull Rotavirus was pulled out of the multi-vaccine VIS
bull Rotavirus VIS was updated with specific information about the risks of rotavirus and clinical presentation
ROTAVIRUS WHY BOTHER
PRE-VACCINEbull Every year globally
bull 111 million episodes of gastroenteritis requiring only home care
bull 25 million outpatient medical visits
bull 2 million hospitalizations
bull 400000 deaths
POST-VACCINEbull A dramatic decrease (gt80) in the incidence of
severe rotavirus diarrhea has been reported in high-income countries
bull A decrease of about 50 has been reported in low-income settings
bull Reductions in diarrhea-associated deaths of 31 in infants younger than 1 year old and 42 in children younger than 5 years old in countries with low child mortality
OrsquoRyan M Rotavirus Vaccines a story of success with challenges ahead F1000 Research 20176 Parashar et al Global illness and deaths caused by rotavirus disease in children Emerg Infect Dis 2003 May9(5)565-72
EFFICACY CASE LAIV (FLUMIST)
bull ldquoIn light of low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013ndash14 and 2015ndash16 seasons for the 2016ndash17 season ACIP makes the interim recommendation that LAIV4 should not be usedrdquo
bull Even though it would cost the manufacturer as the ACIP recommendation drives usage and insurance coverage
Grohskopf LA Prevention and Control of Seasonal Influenza with Vaccines MMWR Recomm Rep 201665
WHO IS ACIP
bull The Advisory Committee on Immunization Practices ldquoincludes 15 voting members responsible for making vaccine recommendations The Secretary of the US Department of Health and Human Services (DHHS) selects these members following an application and nomination process Fourteen of the members have expertise in vaccinology immunology pediatrics internal medicine nursing family medicine virology public health infectious diseases andor preventive medicine one member is a consumer representative who provides perspectives on the social and community aspects of vaccination
bull In addition to the 15 voting members ACIP includes 8 ex officio members who represent other federal agencies with responsibility for immunization programs in the United States and 30 non-voting representatives of liaison organizations that bring related immunization expertiserdquo
httpswwwcdcgovvaccinesacipabouthtml
ACIP - SCHEDULE
bull How do vaccines get added Do vaccines ever get taken offbull Work group convene to work on one vaccine-preventable disease or group of diseases
bull Work group members collect and review data on disease epidemiology vaccine efficacy effectiveness safety feasibility of program implementation and economic aspects of immunization policy to include in written policy statements
bull Insurance companies and Medicaid generally pay for whatrsquos on the ACIP schedule so these recommendations have financial repercussions
bull Because immunity is not inherited we need to immunize each persongeneration until the disease is truly eradicated
bull ACIP meetings are open to the public and can be viewed by streaming webcast
bull If recommendations are accepted by the CDC they are published in the MMWR
httpswwwcdcgovvaccinesacipabouthtml
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
DISCLOSURES AND OBTAINING CONTINUING MEDICAL EDUCATION CREDIT
bull Successful completion of this continuing education activity includes the following
bull Attending the entire CE activity
bull Completing the online evaluation
bull At the end of the evaluation there are links to request the CME certificate
If you have any questions about this CE activity please contact Trang Kuss at trangkussdohwagov
The planners and presenters of this activity have no relevant financial relationships with any commercial interest pertaining to this activity
The following off label use will be discussed
bull Tdap vaccine (Adacel Boostrix)
CONFLICT OF INTEREST
BACKGROUND
bull Former software engineer graduated from the University of Michigan
bull Bastyr 2010 in Naturopathic Medicine and Midwifery
bull Away training in Vanuatu
bull Dual practice midwifery and naturopathic primary care 2010-2014
bull Now specializing in pediatric primary care and specialty infant feeding (breastfeeding tongue tie)
bull CDC Childhood Immunization Champion for Washington State in 2017
VACCINES ARE NATUROPATHIC
bull When we prevent disease we donrsquot need to treat
bull Vaccines reduce use of antibiotics and antibiotic resistance
bull Vaccines prevent misery suffering and death
WE STILL NEED VACCINES
bull Vaccine-preventable diseases still kill here and elsewhere
bull There are plenty of other diseases available to exercise the immune system
UNIVERSAL DISEASES
bull A universal disease affected nearly everyone at some point in their life
bull Measles mumps polio many others are universal
bull If a disease was universal how bad can it be Would Mother Nature really do something destructive
bull Yes
MEASLES A CASE STUDY
MORBIDITY VS MORTALITY
bull When the internet argues that the death rate was going down before vaccines that is true
bull But only because we developed treatments for the complications from measles
bull The case rate didnrsquot go down until the vaccine was introduced
MORTALITY VS CASES
SIMPLE RASH
bull Measles complications in 40 of cases
bull Diarrhea
bull Middle ear infection
bull Bronchopneumonia
bull Encephalitis in 11000
bull Death in 21000 usually pneumonia or encephalitis
bull In developing countries up to 25 fatality rate
bull Subacute sclerosing panencephalitis (fatal) in 110000 or morebull Kids who get the measles before age 5 have a one in 1387 chance of developing SSPE (Wendorf et al 2016)
bull Kids who get the measles before age 1 have a one in 609 chance
VACCINErsquoS CONTINUED CONTRIBUTION
bull Measles remains a leading cause of vaccine-preventable infant mortality but progress is being made
bull From 2000-2016
bull Reported measles incidence decreased 87 from 145 to 19 cases per million persons
bull Annual estimated measles deaths decreased 84 (204 million deaths prevented)
MMWR Oct 27 2017 Vol 66 No 42
PROS AND CONS OF NATURAL INFECTION
bull Immunity from natural infection often lasts longer (though this is questionable)
bull But in order to get that immunity you need to experience the disease
bull Suffering
bull Transmission to others
bull Complications
bull Death
bull Long term complications of measles include
bull SSPE (fatal)
bull Immunosuppression increasing deaths from other infectious diseases
bull More severe COPD in smokers who experienced measles
IMMUNOSUPPRESSION
bull After measles infection immunologic memory is suppressed for 2-3 years which increases all-cause mortality
bull Measles BCG and polio immunization reduced all-cause mortality rate by roughly half
Mina MJ Measles immune suppression and vaccination direct and indirect nonspecific vaccine benefits J Infect 201774 Suppl 1S10ndash7
NON-SPECIFIC EFFECTS OF MEASLES AND OTHER VACCINES
1 Higgins JPT Soares-Weiser K Reingold A Systematic review of the non-specific effects of BCG DTP and measles containing vaccines httpwwwwhointimmunizationsagemeetings2014april (accessed 1 Jun 2014)
2 Strategic Advisory Group of Experts on Immunization Meeting of the Strategic Advisory Group of Experts on Immunization April 2014 - conclusions and recommendations Week Epidemiol Rec201489221ndash36 [PubMed]
3Aaby P Martins CL Garly ML et al Non-specific effects of standard measles vaccine at 45 and 9 months of age on childhood mortality randomised controlled trial BMJ 2010341c6495doi101136bmjc6495 [PMC free article] [PubMed]
4Aaby P Samb B Simondon F et al Non-specific beneficial effect of measles immunisation analysis of mortality studies from developing countries BMJ 1995311481ndash5 doi101136bmj3117003481[PMC free article] [PubMed]
5 Kristensen I Aaby P Jensen H Routine vaccinations and child survival follow up study in Guinea-Bissau West Africa BMJ 20003211435ndash8 doi101136bmj32172741435 [PMC free article] [PubMed]
6 Benn CS Netea MG Selin LK et alA small jabmdasha big effect non-specific immunomodulation by vaccinesTrends Immunol 201334431ndash9 doi101016jit201304004 [PubMed]
CONCERN TH1 VS TH2
bull Th1 cells decrease the production of IgE
bull Th2 cells increase the production of IgE
bull Babies are born with a predominance of Th2 a bias towards allergic responses
bull To reduce allergic responses stimulate Th1
bull Infection with bacteria and viruses stimulates production of Th1
bull Infection with worms and helminths stimulate production of Th2
bull If babieskids donrsquot experience infection will they develop more allergies
VACCINES DO NOT CAUSE ALLERGIES
bull Vaccines do not prevent all diseases
bull Babies and kids still experience lots of infections
bull Large well-controlled epidemiologic studies do not support the hypothesis that vaccines cause allergies
bull ldquoHigher cumulative vaccine antigen doses were associated with less allergic sensitization allergic disease and less severe infant eczemardquo
Offit PA Hackett CJ Addressing Parentsrsquo Concerns Do Vaccines Cause Allergic or Autoimmune Diseases Pediatrics 2003111(3)653ndash9
CONCERN VS ACTUAL EFFECT
bull There are many valid questions and concerns about vaccines
bull For the most part we have the data to answer these questions
bull Donrsquot stop at the question Keep going to the answer
MECHANISMPATHWAY VS ACTUAL EFFECT
bull Many concerns about vaccines are based on biochemical pathways or mechanism
bull Donrsquot stop there Just because something is possible or even plausible doesnrsquot mean it actually happens that way
bull Look at the clinical data and the large body of literature
CONCERN VARICELLA VS ZOSTER
Question Does varicella immunization increase the risk of shingles in the unvaccinated population because of lack of immune stimulationviral suppression
Answer No zoster rates were going up before varicella program and were not affected by varicella immunization (Hales 2013) (Siedler 2014)
Plus varicella immunization seems to reduce the risk of shingles in immunized people (Baxter 2013)
SAFETY MONITORING
bull Pre-licensure trials including phase I II and III
bull Post-licensure studies and surveillance
bull Vaccine Safety Datalink (VSD)
bull Vaccine Adverse Event Reporting System (VAERS)
bull Clinical Immunization Safety Assessment (CISA) project ndash investigation into possible events in specific people certain populations excluded by pre-licensure studies
bull httpswwwhistoryofvaccinesorgcontentarticlesvaccine-development-testing-and-regulation
bull httpswwwcdcgovvaccinesbasicstest-approvehtml
SAFETY MONITORING VAERS
bull Vaccine Adverse Event Reporting System
bull ldquoSpontaneous (passive) surveillance means that no active effort is made to search for identify and collect information but rather information is passively received from those who choose to voluntarily report their experiencerdquo (Shimabukuro 2015)
bull Anyone can file any report
bull All reports are reviewed
bull ldquo[VAERS] reporting is incomplete requires follow-up investigation and cannot directly distinguish temporal associations from causal associations Consequently VAERS functions as a hypothesis-generating mechanism an early-warning signal of potential problems regarding vaccine safetyrdquo (Schwartz 2012)
Shimabukuro TT Nguyen M Martin D DeStefano F Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 201533(36)4398ndash405Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
SAFETY MONITORING VACCINE SAFETY DATALINK (VSD)
bull Includes multiple large HMOsMCOs covering 88 million people in 2011
bull Huge numbers allow for detection of rareserious events
bull Objectives of the Vaccine Safety Datalinkbull To conduct research on important vaccine safety questions in large populations
bull To conduct vaccine safety studies that come from questions or concerns in the medical literature or from other vaccine safety systems like VAERS
bull To monitor possible adverse events when new vaccines are licensed or when there are new vaccine recommendations
bull To provide information to committees who make recommendations for the nation
httpswwwcdcgovvaccinesafetyensuringsafetymonitoringvsdindexhtml
VACCINE SAFETY CASE ROTAVIRUS
bull In 1999 based on reports of 15 infants (of 15 million doses administered) experiencing intussusception after immunization with Rotashield the CDC recommended suspending use temporarily while investigation proceeded
bull Researchers found statistically significant differences in RotaShield vaccination rates between the two groups hellip Based on these results and estimates of the background rate of intussusception among US infants the research team estimated one additional case of intussusception attributable to the vaccine for every 4670 to 9474 infants vaccinated
bull Wyeth pulled the vaccine from the market when it was clear ACIP would vote against its use
Side bar Interesting moral questions about ldquoslamming the doorrdquo on a rotavirus vaccine that stood to save many lives internationally where the risk benefit ratio might be different (Schwartz 2012)
Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
VACCINE SAFETY CASE ROTAVIRUS
bull Rotateq (pentavalent) licensed in 2006
bull Rotarix (monovalent) licensed in 2008
bull Studies of the two new vaccines included 60000 to 70000 infants each in which no increased risk of intussusception was identified
VSD ROTAVIRUS (2014)
RESULTS
During the study period 207955 doses of monovalent rotavirus vaccine (including 115908 first doses and 92047 second doses) were administered in the VSD population We identified 6 cases of intussusception within 7 days after the administration of either dose of vaccine For the two doses combined the expected number of intussusception cases was 072 resulting in a significant relative risk of 84 For the pentavalent rotavirus vaccine 1301810 doses were administered duringthe study period with 8 observed intussusception cases (711 expected) for a nonsignificant relative risk of 11 The relativerisk of chart-confirmed intussusception within 7 days after monovalent rotavirus vaccination as compared with the risk after pentavalent rotavirus vaccination was 94 (95 confidence interval 14 to 1038) The attributable risk of intussusception after the administration of two doses of monovalent rotavirus vaccine was estimated to be 53 per 100000 infants vaccinated
Action
bull Rotavirus was pulled out of the multi-vaccine VIS
bull Rotavirus VIS was updated with specific information about the risks of rotavirus and clinical presentation
ROTAVIRUS WHY BOTHER
PRE-VACCINEbull Every year globally
bull 111 million episodes of gastroenteritis requiring only home care
bull 25 million outpatient medical visits
bull 2 million hospitalizations
bull 400000 deaths
POST-VACCINEbull A dramatic decrease (gt80) in the incidence of
severe rotavirus diarrhea has been reported in high-income countries
bull A decrease of about 50 has been reported in low-income settings
bull Reductions in diarrhea-associated deaths of 31 in infants younger than 1 year old and 42 in children younger than 5 years old in countries with low child mortality
OrsquoRyan M Rotavirus Vaccines a story of success with challenges ahead F1000 Research 20176 Parashar et al Global illness and deaths caused by rotavirus disease in children Emerg Infect Dis 2003 May9(5)565-72
EFFICACY CASE LAIV (FLUMIST)
bull ldquoIn light of low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013ndash14 and 2015ndash16 seasons for the 2016ndash17 season ACIP makes the interim recommendation that LAIV4 should not be usedrdquo
bull Even though it would cost the manufacturer as the ACIP recommendation drives usage and insurance coverage
Grohskopf LA Prevention and Control of Seasonal Influenza with Vaccines MMWR Recomm Rep 201665
WHO IS ACIP
bull The Advisory Committee on Immunization Practices ldquoincludes 15 voting members responsible for making vaccine recommendations The Secretary of the US Department of Health and Human Services (DHHS) selects these members following an application and nomination process Fourteen of the members have expertise in vaccinology immunology pediatrics internal medicine nursing family medicine virology public health infectious diseases andor preventive medicine one member is a consumer representative who provides perspectives on the social and community aspects of vaccination
bull In addition to the 15 voting members ACIP includes 8 ex officio members who represent other federal agencies with responsibility for immunization programs in the United States and 30 non-voting representatives of liaison organizations that bring related immunization expertiserdquo
httpswwwcdcgovvaccinesacipabouthtml
ACIP - SCHEDULE
bull How do vaccines get added Do vaccines ever get taken offbull Work group convene to work on one vaccine-preventable disease or group of diseases
bull Work group members collect and review data on disease epidemiology vaccine efficacy effectiveness safety feasibility of program implementation and economic aspects of immunization policy to include in written policy statements
bull Insurance companies and Medicaid generally pay for whatrsquos on the ACIP schedule so these recommendations have financial repercussions
bull Because immunity is not inherited we need to immunize each persongeneration until the disease is truly eradicated
bull ACIP meetings are open to the public and can be viewed by streaming webcast
bull If recommendations are accepted by the CDC they are published in the MMWR
httpswwwcdcgovvaccinesacipabouthtml
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
The planners and presenters of this activity have no relevant financial relationships with any commercial interest pertaining to this activity
The following off label use will be discussed
bull Tdap vaccine (Adacel Boostrix)
CONFLICT OF INTEREST
BACKGROUND
bull Former software engineer graduated from the University of Michigan
bull Bastyr 2010 in Naturopathic Medicine and Midwifery
bull Away training in Vanuatu
bull Dual practice midwifery and naturopathic primary care 2010-2014
bull Now specializing in pediatric primary care and specialty infant feeding (breastfeeding tongue tie)
bull CDC Childhood Immunization Champion for Washington State in 2017
VACCINES ARE NATUROPATHIC
bull When we prevent disease we donrsquot need to treat
bull Vaccines reduce use of antibiotics and antibiotic resistance
bull Vaccines prevent misery suffering and death
WE STILL NEED VACCINES
bull Vaccine-preventable diseases still kill here and elsewhere
bull There are plenty of other diseases available to exercise the immune system
UNIVERSAL DISEASES
bull A universal disease affected nearly everyone at some point in their life
bull Measles mumps polio many others are universal
bull If a disease was universal how bad can it be Would Mother Nature really do something destructive
bull Yes
MEASLES A CASE STUDY
MORBIDITY VS MORTALITY
bull When the internet argues that the death rate was going down before vaccines that is true
bull But only because we developed treatments for the complications from measles
bull The case rate didnrsquot go down until the vaccine was introduced
MORTALITY VS CASES
SIMPLE RASH
bull Measles complications in 40 of cases
bull Diarrhea
bull Middle ear infection
bull Bronchopneumonia
bull Encephalitis in 11000
bull Death in 21000 usually pneumonia or encephalitis
bull In developing countries up to 25 fatality rate
bull Subacute sclerosing panencephalitis (fatal) in 110000 or morebull Kids who get the measles before age 5 have a one in 1387 chance of developing SSPE (Wendorf et al 2016)
bull Kids who get the measles before age 1 have a one in 609 chance
VACCINErsquoS CONTINUED CONTRIBUTION
bull Measles remains a leading cause of vaccine-preventable infant mortality but progress is being made
bull From 2000-2016
bull Reported measles incidence decreased 87 from 145 to 19 cases per million persons
bull Annual estimated measles deaths decreased 84 (204 million deaths prevented)
MMWR Oct 27 2017 Vol 66 No 42
PROS AND CONS OF NATURAL INFECTION
bull Immunity from natural infection often lasts longer (though this is questionable)
bull But in order to get that immunity you need to experience the disease
bull Suffering
bull Transmission to others
bull Complications
bull Death
bull Long term complications of measles include
bull SSPE (fatal)
bull Immunosuppression increasing deaths from other infectious diseases
bull More severe COPD in smokers who experienced measles
IMMUNOSUPPRESSION
bull After measles infection immunologic memory is suppressed for 2-3 years which increases all-cause mortality
bull Measles BCG and polio immunization reduced all-cause mortality rate by roughly half
Mina MJ Measles immune suppression and vaccination direct and indirect nonspecific vaccine benefits J Infect 201774 Suppl 1S10ndash7
NON-SPECIFIC EFFECTS OF MEASLES AND OTHER VACCINES
1 Higgins JPT Soares-Weiser K Reingold A Systematic review of the non-specific effects of BCG DTP and measles containing vaccines httpwwwwhointimmunizationsagemeetings2014april (accessed 1 Jun 2014)
2 Strategic Advisory Group of Experts on Immunization Meeting of the Strategic Advisory Group of Experts on Immunization April 2014 - conclusions and recommendations Week Epidemiol Rec201489221ndash36 [PubMed]
3Aaby P Martins CL Garly ML et al Non-specific effects of standard measles vaccine at 45 and 9 months of age on childhood mortality randomised controlled trial BMJ 2010341c6495doi101136bmjc6495 [PMC free article] [PubMed]
4Aaby P Samb B Simondon F et al Non-specific beneficial effect of measles immunisation analysis of mortality studies from developing countries BMJ 1995311481ndash5 doi101136bmj3117003481[PMC free article] [PubMed]
5 Kristensen I Aaby P Jensen H Routine vaccinations and child survival follow up study in Guinea-Bissau West Africa BMJ 20003211435ndash8 doi101136bmj32172741435 [PMC free article] [PubMed]
6 Benn CS Netea MG Selin LK et alA small jabmdasha big effect non-specific immunomodulation by vaccinesTrends Immunol 201334431ndash9 doi101016jit201304004 [PubMed]
CONCERN TH1 VS TH2
bull Th1 cells decrease the production of IgE
bull Th2 cells increase the production of IgE
bull Babies are born with a predominance of Th2 a bias towards allergic responses
bull To reduce allergic responses stimulate Th1
bull Infection with bacteria and viruses stimulates production of Th1
bull Infection with worms and helminths stimulate production of Th2
bull If babieskids donrsquot experience infection will they develop more allergies
VACCINES DO NOT CAUSE ALLERGIES
bull Vaccines do not prevent all diseases
bull Babies and kids still experience lots of infections
bull Large well-controlled epidemiologic studies do not support the hypothesis that vaccines cause allergies
bull ldquoHigher cumulative vaccine antigen doses were associated with less allergic sensitization allergic disease and less severe infant eczemardquo
Offit PA Hackett CJ Addressing Parentsrsquo Concerns Do Vaccines Cause Allergic or Autoimmune Diseases Pediatrics 2003111(3)653ndash9
CONCERN VS ACTUAL EFFECT
bull There are many valid questions and concerns about vaccines
bull For the most part we have the data to answer these questions
bull Donrsquot stop at the question Keep going to the answer
MECHANISMPATHWAY VS ACTUAL EFFECT
bull Many concerns about vaccines are based on biochemical pathways or mechanism
bull Donrsquot stop there Just because something is possible or even plausible doesnrsquot mean it actually happens that way
bull Look at the clinical data and the large body of literature
CONCERN VARICELLA VS ZOSTER
Question Does varicella immunization increase the risk of shingles in the unvaccinated population because of lack of immune stimulationviral suppression
Answer No zoster rates were going up before varicella program and were not affected by varicella immunization (Hales 2013) (Siedler 2014)
Plus varicella immunization seems to reduce the risk of shingles in immunized people (Baxter 2013)
SAFETY MONITORING
bull Pre-licensure trials including phase I II and III
bull Post-licensure studies and surveillance
bull Vaccine Safety Datalink (VSD)
bull Vaccine Adverse Event Reporting System (VAERS)
bull Clinical Immunization Safety Assessment (CISA) project ndash investigation into possible events in specific people certain populations excluded by pre-licensure studies
bull httpswwwhistoryofvaccinesorgcontentarticlesvaccine-development-testing-and-regulation
bull httpswwwcdcgovvaccinesbasicstest-approvehtml
SAFETY MONITORING VAERS
bull Vaccine Adverse Event Reporting System
bull ldquoSpontaneous (passive) surveillance means that no active effort is made to search for identify and collect information but rather information is passively received from those who choose to voluntarily report their experiencerdquo (Shimabukuro 2015)
bull Anyone can file any report
bull All reports are reviewed
bull ldquo[VAERS] reporting is incomplete requires follow-up investigation and cannot directly distinguish temporal associations from causal associations Consequently VAERS functions as a hypothesis-generating mechanism an early-warning signal of potential problems regarding vaccine safetyrdquo (Schwartz 2012)
Shimabukuro TT Nguyen M Martin D DeStefano F Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 201533(36)4398ndash405Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
SAFETY MONITORING VACCINE SAFETY DATALINK (VSD)
bull Includes multiple large HMOsMCOs covering 88 million people in 2011
bull Huge numbers allow for detection of rareserious events
bull Objectives of the Vaccine Safety Datalinkbull To conduct research on important vaccine safety questions in large populations
bull To conduct vaccine safety studies that come from questions or concerns in the medical literature or from other vaccine safety systems like VAERS
bull To monitor possible adverse events when new vaccines are licensed or when there are new vaccine recommendations
bull To provide information to committees who make recommendations for the nation
httpswwwcdcgovvaccinesafetyensuringsafetymonitoringvsdindexhtml
VACCINE SAFETY CASE ROTAVIRUS
bull In 1999 based on reports of 15 infants (of 15 million doses administered) experiencing intussusception after immunization with Rotashield the CDC recommended suspending use temporarily while investigation proceeded
bull Researchers found statistically significant differences in RotaShield vaccination rates between the two groups hellip Based on these results and estimates of the background rate of intussusception among US infants the research team estimated one additional case of intussusception attributable to the vaccine for every 4670 to 9474 infants vaccinated
bull Wyeth pulled the vaccine from the market when it was clear ACIP would vote against its use
Side bar Interesting moral questions about ldquoslamming the doorrdquo on a rotavirus vaccine that stood to save many lives internationally where the risk benefit ratio might be different (Schwartz 2012)
Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
VACCINE SAFETY CASE ROTAVIRUS
bull Rotateq (pentavalent) licensed in 2006
bull Rotarix (monovalent) licensed in 2008
bull Studies of the two new vaccines included 60000 to 70000 infants each in which no increased risk of intussusception was identified
VSD ROTAVIRUS (2014)
RESULTS
During the study period 207955 doses of monovalent rotavirus vaccine (including 115908 first doses and 92047 second doses) were administered in the VSD population We identified 6 cases of intussusception within 7 days after the administration of either dose of vaccine For the two doses combined the expected number of intussusception cases was 072 resulting in a significant relative risk of 84 For the pentavalent rotavirus vaccine 1301810 doses were administered duringthe study period with 8 observed intussusception cases (711 expected) for a nonsignificant relative risk of 11 The relativerisk of chart-confirmed intussusception within 7 days after monovalent rotavirus vaccination as compared with the risk after pentavalent rotavirus vaccination was 94 (95 confidence interval 14 to 1038) The attributable risk of intussusception after the administration of two doses of monovalent rotavirus vaccine was estimated to be 53 per 100000 infants vaccinated
Action
bull Rotavirus was pulled out of the multi-vaccine VIS
bull Rotavirus VIS was updated with specific information about the risks of rotavirus and clinical presentation
ROTAVIRUS WHY BOTHER
PRE-VACCINEbull Every year globally
bull 111 million episodes of gastroenteritis requiring only home care
bull 25 million outpatient medical visits
bull 2 million hospitalizations
bull 400000 deaths
POST-VACCINEbull A dramatic decrease (gt80) in the incidence of
severe rotavirus diarrhea has been reported in high-income countries
bull A decrease of about 50 has been reported in low-income settings
bull Reductions in diarrhea-associated deaths of 31 in infants younger than 1 year old and 42 in children younger than 5 years old in countries with low child mortality
OrsquoRyan M Rotavirus Vaccines a story of success with challenges ahead F1000 Research 20176 Parashar et al Global illness and deaths caused by rotavirus disease in children Emerg Infect Dis 2003 May9(5)565-72
EFFICACY CASE LAIV (FLUMIST)
bull ldquoIn light of low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013ndash14 and 2015ndash16 seasons for the 2016ndash17 season ACIP makes the interim recommendation that LAIV4 should not be usedrdquo
bull Even though it would cost the manufacturer as the ACIP recommendation drives usage and insurance coverage
Grohskopf LA Prevention and Control of Seasonal Influenza with Vaccines MMWR Recomm Rep 201665
WHO IS ACIP
bull The Advisory Committee on Immunization Practices ldquoincludes 15 voting members responsible for making vaccine recommendations The Secretary of the US Department of Health and Human Services (DHHS) selects these members following an application and nomination process Fourteen of the members have expertise in vaccinology immunology pediatrics internal medicine nursing family medicine virology public health infectious diseases andor preventive medicine one member is a consumer representative who provides perspectives on the social and community aspects of vaccination
bull In addition to the 15 voting members ACIP includes 8 ex officio members who represent other federal agencies with responsibility for immunization programs in the United States and 30 non-voting representatives of liaison organizations that bring related immunization expertiserdquo
httpswwwcdcgovvaccinesacipabouthtml
ACIP - SCHEDULE
bull How do vaccines get added Do vaccines ever get taken offbull Work group convene to work on one vaccine-preventable disease or group of diseases
bull Work group members collect and review data on disease epidemiology vaccine efficacy effectiveness safety feasibility of program implementation and economic aspects of immunization policy to include in written policy statements
bull Insurance companies and Medicaid generally pay for whatrsquos on the ACIP schedule so these recommendations have financial repercussions
bull Because immunity is not inherited we need to immunize each persongeneration until the disease is truly eradicated
bull ACIP meetings are open to the public and can be viewed by streaming webcast
bull If recommendations are accepted by the CDC they are published in the MMWR
httpswwwcdcgovvaccinesacipabouthtml
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
BACKGROUND
bull Former software engineer graduated from the University of Michigan
bull Bastyr 2010 in Naturopathic Medicine and Midwifery
bull Away training in Vanuatu
bull Dual practice midwifery and naturopathic primary care 2010-2014
bull Now specializing in pediatric primary care and specialty infant feeding (breastfeeding tongue tie)
bull CDC Childhood Immunization Champion for Washington State in 2017
VACCINES ARE NATUROPATHIC
bull When we prevent disease we donrsquot need to treat
bull Vaccines reduce use of antibiotics and antibiotic resistance
bull Vaccines prevent misery suffering and death
WE STILL NEED VACCINES
bull Vaccine-preventable diseases still kill here and elsewhere
bull There are plenty of other diseases available to exercise the immune system
UNIVERSAL DISEASES
bull A universal disease affected nearly everyone at some point in their life
bull Measles mumps polio many others are universal
bull If a disease was universal how bad can it be Would Mother Nature really do something destructive
bull Yes
MEASLES A CASE STUDY
MORBIDITY VS MORTALITY
bull When the internet argues that the death rate was going down before vaccines that is true
bull But only because we developed treatments for the complications from measles
bull The case rate didnrsquot go down until the vaccine was introduced
MORTALITY VS CASES
SIMPLE RASH
bull Measles complications in 40 of cases
bull Diarrhea
bull Middle ear infection
bull Bronchopneumonia
bull Encephalitis in 11000
bull Death in 21000 usually pneumonia or encephalitis
bull In developing countries up to 25 fatality rate
bull Subacute sclerosing panencephalitis (fatal) in 110000 or morebull Kids who get the measles before age 5 have a one in 1387 chance of developing SSPE (Wendorf et al 2016)
bull Kids who get the measles before age 1 have a one in 609 chance
VACCINErsquoS CONTINUED CONTRIBUTION
bull Measles remains a leading cause of vaccine-preventable infant mortality but progress is being made
bull From 2000-2016
bull Reported measles incidence decreased 87 from 145 to 19 cases per million persons
bull Annual estimated measles deaths decreased 84 (204 million deaths prevented)
MMWR Oct 27 2017 Vol 66 No 42
PROS AND CONS OF NATURAL INFECTION
bull Immunity from natural infection often lasts longer (though this is questionable)
bull But in order to get that immunity you need to experience the disease
bull Suffering
bull Transmission to others
bull Complications
bull Death
bull Long term complications of measles include
bull SSPE (fatal)
bull Immunosuppression increasing deaths from other infectious diseases
bull More severe COPD in smokers who experienced measles
IMMUNOSUPPRESSION
bull After measles infection immunologic memory is suppressed for 2-3 years which increases all-cause mortality
bull Measles BCG and polio immunization reduced all-cause mortality rate by roughly half
Mina MJ Measles immune suppression and vaccination direct and indirect nonspecific vaccine benefits J Infect 201774 Suppl 1S10ndash7
NON-SPECIFIC EFFECTS OF MEASLES AND OTHER VACCINES
1 Higgins JPT Soares-Weiser K Reingold A Systematic review of the non-specific effects of BCG DTP and measles containing vaccines httpwwwwhointimmunizationsagemeetings2014april (accessed 1 Jun 2014)
2 Strategic Advisory Group of Experts on Immunization Meeting of the Strategic Advisory Group of Experts on Immunization April 2014 - conclusions and recommendations Week Epidemiol Rec201489221ndash36 [PubMed]
3Aaby P Martins CL Garly ML et al Non-specific effects of standard measles vaccine at 45 and 9 months of age on childhood mortality randomised controlled trial BMJ 2010341c6495doi101136bmjc6495 [PMC free article] [PubMed]
4Aaby P Samb B Simondon F et al Non-specific beneficial effect of measles immunisation analysis of mortality studies from developing countries BMJ 1995311481ndash5 doi101136bmj3117003481[PMC free article] [PubMed]
5 Kristensen I Aaby P Jensen H Routine vaccinations and child survival follow up study in Guinea-Bissau West Africa BMJ 20003211435ndash8 doi101136bmj32172741435 [PMC free article] [PubMed]
6 Benn CS Netea MG Selin LK et alA small jabmdasha big effect non-specific immunomodulation by vaccinesTrends Immunol 201334431ndash9 doi101016jit201304004 [PubMed]
CONCERN TH1 VS TH2
bull Th1 cells decrease the production of IgE
bull Th2 cells increase the production of IgE
bull Babies are born with a predominance of Th2 a bias towards allergic responses
bull To reduce allergic responses stimulate Th1
bull Infection with bacteria and viruses stimulates production of Th1
bull Infection with worms and helminths stimulate production of Th2
bull If babieskids donrsquot experience infection will they develop more allergies
VACCINES DO NOT CAUSE ALLERGIES
bull Vaccines do not prevent all diseases
bull Babies and kids still experience lots of infections
bull Large well-controlled epidemiologic studies do not support the hypothesis that vaccines cause allergies
bull ldquoHigher cumulative vaccine antigen doses were associated with less allergic sensitization allergic disease and less severe infant eczemardquo
Offit PA Hackett CJ Addressing Parentsrsquo Concerns Do Vaccines Cause Allergic or Autoimmune Diseases Pediatrics 2003111(3)653ndash9
CONCERN VS ACTUAL EFFECT
bull There are many valid questions and concerns about vaccines
bull For the most part we have the data to answer these questions
bull Donrsquot stop at the question Keep going to the answer
MECHANISMPATHWAY VS ACTUAL EFFECT
bull Many concerns about vaccines are based on biochemical pathways or mechanism
bull Donrsquot stop there Just because something is possible or even plausible doesnrsquot mean it actually happens that way
bull Look at the clinical data and the large body of literature
CONCERN VARICELLA VS ZOSTER
Question Does varicella immunization increase the risk of shingles in the unvaccinated population because of lack of immune stimulationviral suppression
Answer No zoster rates were going up before varicella program and were not affected by varicella immunization (Hales 2013) (Siedler 2014)
Plus varicella immunization seems to reduce the risk of shingles in immunized people (Baxter 2013)
SAFETY MONITORING
bull Pre-licensure trials including phase I II and III
bull Post-licensure studies and surveillance
bull Vaccine Safety Datalink (VSD)
bull Vaccine Adverse Event Reporting System (VAERS)
bull Clinical Immunization Safety Assessment (CISA) project ndash investigation into possible events in specific people certain populations excluded by pre-licensure studies
bull httpswwwhistoryofvaccinesorgcontentarticlesvaccine-development-testing-and-regulation
bull httpswwwcdcgovvaccinesbasicstest-approvehtml
SAFETY MONITORING VAERS
bull Vaccine Adverse Event Reporting System
bull ldquoSpontaneous (passive) surveillance means that no active effort is made to search for identify and collect information but rather information is passively received from those who choose to voluntarily report their experiencerdquo (Shimabukuro 2015)
bull Anyone can file any report
bull All reports are reviewed
bull ldquo[VAERS] reporting is incomplete requires follow-up investigation and cannot directly distinguish temporal associations from causal associations Consequently VAERS functions as a hypothesis-generating mechanism an early-warning signal of potential problems regarding vaccine safetyrdquo (Schwartz 2012)
Shimabukuro TT Nguyen M Martin D DeStefano F Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 201533(36)4398ndash405Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
SAFETY MONITORING VACCINE SAFETY DATALINK (VSD)
bull Includes multiple large HMOsMCOs covering 88 million people in 2011
bull Huge numbers allow for detection of rareserious events
bull Objectives of the Vaccine Safety Datalinkbull To conduct research on important vaccine safety questions in large populations
bull To conduct vaccine safety studies that come from questions or concerns in the medical literature or from other vaccine safety systems like VAERS
bull To monitor possible adverse events when new vaccines are licensed or when there are new vaccine recommendations
bull To provide information to committees who make recommendations for the nation
httpswwwcdcgovvaccinesafetyensuringsafetymonitoringvsdindexhtml
VACCINE SAFETY CASE ROTAVIRUS
bull In 1999 based on reports of 15 infants (of 15 million doses administered) experiencing intussusception after immunization with Rotashield the CDC recommended suspending use temporarily while investigation proceeded
bull Researchers found statistically significant differences in RotaShield vaccination rates between the two groups hellip Based on these results and estimates of the background rate of intussusception among US infants the research team estimated one additional case of intussusception attributable to the vaccine for every 4670 to 9474 infants vaccinated
bull Wyeth pulled the vaccine from the market when it was clear ACIP would vote against its use
Side bar Interesting moral questions about ldquoslamming the doorrdquo on a rotavirus vaccine that stood to save many lives internationally where the risk benefit ratio might be different (Schwartz 2012)
Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
VACCINE SAFETY CASE ROTAVIRUS
bull Rotateq (pentavalent) licensed in 2006
bull Rotarix (monovalent) licensed in 2008
bull Studies of the two new vaccines included 60000 to 70000 infants each in which no increased risk of intussusception was identified
VSD ROTAVIRUS (2014)
RESULTS
During the study period 207955 doses of monovalent rotavirus vaccine (including 115908 first doses and 92047 second doses) were administered in the VSD population We identified 6 cases of intussusception within 7 days after the administration of either dose of vaccine For the two doses combined the expected number of intussusception cases was 072 resulting in a significant relative risk of 84 For the pentavalent rotavirus vaccine 1301810 doses were administered duringthe study period with 8 observed intussusception cases (711 expected) for a nonsignificant relative risk of 11 The relativerisk of chart-confirmed intussusception within 7 days after monovalent rotavirus vaccination as compared with the risk after pentavalent rotavirus vaccination was 94 (95 confidence interval 14 to 1038) The attributable risk of intussusception after the administration of two doses of monovalent rotavirus vaccine was estimated to be 53 per 100000 infants vaccinated
Action
bull Rotavirus was pulled out of the multi-vaccine VIS
bull Rotavirus VIS was updated with specific information about the risks of rotavirus and clinical presentation
ROTAVIRUS WHY BOTHER
PRE-VACCINEbull Every year globally
bull 111 million episodes of gastroenteritis requiring only home care
bull 25 million outpatient medical visits
bull 2 million hospitalizations
bull 400000 deaths
POST-VACCINEbull A dramatic decrease (gt80) in the incidence of
severe rotavirus diarrhea has been reported in high-income countries
bull A decrease of about 50 has been reported in low-income settings
bull Reductions in diarrhea-associated deaths of 31 in infants younger than 1 year old and 42 in children younger than 5 years old in countries with low child mortality
OrsquoRyan M Rotavirus Vaccines a story of success with challenges ahead F1000 Research 20176 Parashar et al Global illness and deaths caused by rotavirus disease in children Emerg Infect Dis 2003 May9(5)565-72
EFFICACY CASE LAIV (FLUMIST)
bull ldquoIn light of low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013ndash14 and 2015ndash16 seasons for the 2016ndash17 season ACIP makes the interim recommendation that LAIV4 should not be usedrdquo
bull Even though it would cost the manufacturer as the ACIP recommendation drives usage and insurance coverage
Grohskopf LA Prevention and Control of Seasonal Influenza with Vaccines MMWR Recomm Rep 201665
WHO IS ACIP
bull The Advisory Committee on Immunization Practices ldquoincludes 15 voting members responsible for making vaccine recommendations The Secretary of the US Department of Health and Human Services (DHHS) selects these members following an application and nomination process Fourteen of the members have expertise in vaccinology immunology pediatrics internal medicine nursing family medicine virology public health infectious diseases andor preventive medicine one member is a consumer representative who provides perspectives on the social and community aspects of vaccination
bull In addition to the 15 voting members ACIP includes 8 ex officio members who represent other federal agencies with responsibility for immunization programs in the United States and 30 non-voting representatives of liaison organizations that bring related immunization expertiserdquo
httpswwwcdcgovvaccinesacipabouthtml
ACIP - SCHEDULE
bull How do vaccines get added Do vaccines ever get taken offbull Work group convene to work on one vaccine-preventable disease or group of diseases
bull Work group members collect and review data on disease epidemiology vaccine efficacy effectiveness safety feasibility of program implementation and economic aspects of immunization policy to include in written policy statements
bull Insurance companies and Medicaid generally pay for whatrsquos on the ACIP schedule so these recommendations have financial repercussions
bull Because immunity is not inherited we need to immunize each persongeneration until the disease is truly eradicated
bull ACIP meetings are open to the public and can be viewed by streaming webcast
bull If recommendations are accepted by the CDC they are published in the MMWR
httpswwwcdcgovvaccinesacipabouthtml
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
VACCINES ARE NATUROPATHIC
bull When we prevent disease we donrsquot need to treat
bull Vaccines reduce use of antibiotics and antibiotic resistance
bull Vaccines prevent misery suffering and death
WE STILL NEED VACCINES
bull Vaccine-preventable diseases still kill here and elsewhere
bull There are plenty of other diseases available to exercise the immune system
UNIVERSAL DISEASES
bull A universal disease affected nearly everyone at some point in their life
bull Measles mumps polio many others are universal
bull If a disease was universal how bad can it be Would Mother Nature really do something destructive
bull Yes
MEASLES A CASE STUDY
MORBIDITY VS MORTALITY
bull When the internet argues that the death rate was going down before vaccines that is true
bull But only because we developed treatments for the complications from measles
bull The case rate didnrsquot go down until the vaccine was introduced
MORTALITY VS CASES
SIMPLE RASH
bull Measles complications in 40 of cases
bull Diarrhea
bull Middle ear infection
bull Bronchopneumonia
bull Encephalitis in 11000
bull Death in 21000 usually pneumonia or encephalitis
bull In developing countries up to 25 fatality rate
bull Subacute sclerosing panencephalitis (fatal) in 110000 or morebull Kids who get the measles before age 5 have a one in 1387 chance of developing SSPE (Wendorf et al 2016)
bull Kids who get the measles before age 1 have a one in 609 chance
VACCINErsquoS CONTINUED CONTRIBUTION
bull Measles remains a leading cause of vaccine-preventable infant mortality but progress is being made
bull From 2000-2016
bull Reported measles incidence decreased 87 from 145 to 19 cases per million persons
bull Annual estimated measles deaths decreased 84 (204 million deaths prevented)
MMWR Oct 27 2017 Vol 66 No 42
PROS AND CONS OF NATURAL INFECTION
bull Immunity from natural infection often lasts longer (though this is questionable)
bull But in order to get that immunity you need to experience the disease
bull Suffering
bull Transmission to others
bull Complications
bull Death
bull Long term complications of measles include
bull SSPE (fatal)
bull Immunosuppression increasing deaths from other infectious diseases
bull More severe COPD in smokers who experienced measles
IMMUNOSUPPRESSION
bull After measles infection immunologic memory is suppressed for 2-3 years which increases all-cause mortality
bull Measles BCG and polio immunization reduced all-cause mortality rate by roughly half
Mina MJ Measles immune suppression and vaccination direct and indirect nonspecific vaccine benefits J Infect 201774 Suppl 1S10ndash7
NON-SPECIFIC EFFECTS OF MEASLES AND OTHER VACCINES
1 Higgins JPT Soares-Weiser K Reingold A Systematic review of the non-specific effects of BCG DTP and measles containing vaccines httpwwwwhointimmunizationsagemeetings2014april (accessed 1 Jun 2014)
2 Strategic Advisory Group of Experts on Immunization Meeting of the Strategic Advisory Group of Experts on Immunization April 2014 - conclusions and recommendations Week Epidemiol Rec201489221ndash36 [PubMed]
3Aaby P Martins CL Garly ML et al Non-specific effects of standard measles vaccine at 45 and 9 months of age on childhood mortality randomised controlled trial BMJ 2010341c6495doi101136bmjc6495 [PMC free article] [PubMed]
4Aaby P Samb B Simondon F et al Non-specific beneficial effect of measles immunisation analysis of mortality studies from developing countries BMJ 1995311481ndash5 doi101136bmj3117003481[PMC free article] [PubMed]
5 Kristensen I Aaby P Jensen H Routine vaccinations and child survival follow up study in Guinea-Bissau West Africa BMJ 20003211435ndash8 doi101136bmj32172741435 [PMC free article] [PubMed]
6 Benn CS Netea MG Selin LK et alA small jabmdasha big effect non-specific immunomodulation by vaccinesTrends Immunol 201334431ndash9 doi101016jit201304004 [PubMed]
CONCERN TH1 VS TH2
bull Th1 cells decrease the production of IgE
bull Th2 cells increase the production of IgE
bull Babies are born with a predominance of Th2 a bias towards allergic responses
bull To reduce allergic responses stimulate Th1
bull Infection with bacteria and viruses stimulates production of Th1
bull Infection with worms and helminths stimulate production of Th2
bull If babieskids donrsquot experience infection will they develop more allergies
VACCINES DO NOT CAUSE ALLERGIES
bull Vaccines do not prevent all diseases
bull Babies and kids still experience lots of infections
bull Large well-controlled epidemiologic studies do not support the hypothesis that vaccines cause allergies
bull ldquoHigher cumulative vaccine antigen doses were associated with less allergic sensitization allergic disease and less severe infant eczemardquo
Offit PA Hackett CJ Addressing Parentsrsquo Concerns Do Vaccines Cause Allergic or Autoimmune Diseases Pediatrics 2003111(3)653ndash9
CONCERN VS ACTUAL EFFECT
bull There are many valid questions and concerns about vaccines
bull For the most part we have the data to answer these questions
bull Donrsquot stop at the question Keep going to the answer
MECHANISMPATHWAY VS ACTUAL EFFECT
bull Many concerns about vaccines are based on biochemical pathways or mechanism
bull Donrsquot stop there Just because something is possible or even plausible doesnrsquot mean it actually happens that way
bull Look at the clinical data and the large body of literature
CONCERN VARICELLA VS ZOSTER
Question Does varicella immunization increase the risk of shingles in the unvaccinated population because of lack of immune stimulationviral suppression
Answer No zoster rates were going up before varicella program and were not affected by varicella immunization (Hales 2013) (Siedler 2014)
Plus varicella immunization seems to reduce the risk of shingles in immunized people (Baxter 2013)
SAFETY MONITORING
bull Pre-licensure trials including phase I II and III
bull Post-licensure studies and surveillance
bull Vaccine Safety Datalink (VSD)
bull Vaccine Adverse Event Reporting System (VAERS)
bull Clinical Immunization Safety Assessment (CISA) project ndash investigation into possible events in specific people certain populations excluded by pre-licensure studies
bull httpswwwhistoryofvaccinesorgcontentarticlesvaccine-development-testing-and-regulation
bull httpswwwcdcgovvaccinesbasicstest-approvehtml
SAFETY MONITORING VAERS
bull Vaccine Adverse Event Reporting System
bull ldquoSpontaneous (passive) surveillance means that no active effort is made to search for identify and collect information but rather information is passively received from those who choose to voluntarily report their experiencerdquo (Shimabukuro 2015)
bull Anyone can file any report
bull All reports are reviewed
bull ldquo[VAERS] reporting is incomplete requires follow-up investigation and cannot directly distinguish temporal associations from causal associations Consequently VAERS functions as a hypothesis-generating mechanism an early-warning signal of potential problems regarding vaccine safetyrdquo (Schwartz 2012)
Shimabukuro TT Nguyen M Martin D DeStefano F Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 201533(36)4398ndash405Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
SAFETY MONITORING VACCINE SAFETY DATALINK (VSD)
bull Includes multiple large HMOsMCOs covering 88 million people in 2011
bull Huge numbers allow for detection of rareserious events
bull Objectives of the Vaccine Safety Datalinkbull To conduct research on important vaccine safety questions in large populations
bull To conduct vaccine safety studies that come from questions or concerns in the medical literature or from other vaccine safety systems like VAERS
bull To monitor possible adverse events when new vaccines are licensed or when there are new vaccine recommendations
bull To provide information to committees who make recommendations for the nation
httpswwwcdcgovvaccinesafetyensuringsafetymonitoringvsdindexhtml
VACCINE SAFETY CASE ROTAVIRUS
bull In 1999 based on reports of 15 infants (of 15 million doses administered) experiencing intussusception after immunization with Rotashield the CDC recommended suspending use temporarily while investigation proceeded
bull Researchers found statistically significant differences in RotaShield vaccination rates between the two groups hellip Based on these results and estimates of the background rate of intussusception among US infants the research team estimated one additional case of intussusception attributable to the vaccine for every 4670 to 9474 infants vaccinated
bull Wyeth pulled the vaccine from the market when it was clear ACIP would vote against its use
Side bar Interesting moral questions about ldquoslamming the doorrdquo on a rotavirus vaccine that stood to save many lives internationally where the risk benefit ratio might be different (Schwartz 2012)
Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
VACCINE SAFETY CASE ROTAVIRUS
bull Rotateq (pentavalent) licensed in 2006
bull Rotarix (monovalent) licensed in 2008
bull Studies of the two new vaccines included 60000 to 70000 infants each in which no increased risk of intussusception was identified
VSD ROTAVIRUS (2014)
RESULTS
During the study period 207955 doses of monovalent rotavirus vaccine (including 115908 first doses and 92047 second doses) were administered in the VSD population We identified 6 cases of intussusception within 7 days after the administration of either dose of vaccine For the two doses combined the expected number of intussusception cases was 072 resulting in a significant relative risk of 84 For the pentavalent rotavirus vaccine 1301810 doses were administered duringthe study period with 8 observed intussusception cases (711 expected) for a nonsignificant relative risk of 11 The relativerisk of chart-confirmed intussusception within 7 days after monovalent rotavirus vaccination as compared with the risk after pentavalent rotavirus vaccination was 94 (95 confidence interval 14 to 1038) The attributable risk of intussusception after the administration of two doses of monovalent rotavirus vaccine was estimated to be 53 per 100000 infants vaccinated
Action
bull Rotavirus was pulled out of the multi-vaccine VIS
bull Rotavirus VIS was updated with specific information about the risks of rotavirus and clinical presentation
ROTAVIRUS WHY BOTHER
PRE-VACCINEbull Every year globally
bull 111 million episodes of gastroenteritis requiring only home care
bull 25 million outpatient medical visits
bull 2 million hospitalizations
bull 400000 deaths
POST-VACCINEbull A dramatic decrease (gt80) in the incidence of
severe rotavirus diarrhea has been reported in high-income countries
bull A decrease of about 50 has been reported in low-income settings
bull Reductions in diarrhea-associated deaths of 31 in infants younger than 1 year old and 42 in children younger than 5 years old in countries with low child mortality
OrsquoRyan M Rotavirus Vaccines a story of success with challenges ahead F1000 Research 20176 Parashar et al Global illness and deaths caused by rotavirus disease in children Emerg Infect Dis 2003 May9(5)565-72
EFFICACY CASE LAIV (FLUMIST)
bull ldquoIn light of low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013ndash14 and 2015ndash16 seasons for the 2016ndash17 season ACIP makes the interim recommendation that LAIV4 should not be usedrdquo
bull Even though it would cost the manufacturer as the ACIP recommendation drives usage and insurance coverage
Grohskopf LA Prevention and Control of Seasonal Influenza with Vaccines MMWR Recomm Rep 201665
WHO IS ACIP
bull The Advisory Committee on Immunization Practices ldquoincludes 15 voting members responsible for making vaccine recommendations The Secretary of the US Department of Health and Human Services (DHHS) selects these members following an application and nomination process Fourteen of the members have expertise in vaccinology immunology pediatrics internal medicine nursing family medicine virology public health infectious diseases andor preventive medicine one member is a consumer representative who provides perspectives on the social and community aspects of vaccination
bull In addition to the 15 voting members ACIP includes 8 ex officio members who represent other federal agencies with responsibility for immunization programs in the United States and 30 non-voting representatives of liaison organizations that bring related immunization expertiserdquo
httpswwwcdcgovvaccinesacipabouthtml
ACIP - SCHEDULE
bull How do vaccines get added Do vaccines ever get taken offbull Work group convene to work on one vaccine-preventable disease or group of diseases
bull Work group members collect and review data on disease epidemiology vaccine efficacy effectiveness safety feasibility of program implementation and economic aspects of immunization policy to include in written policy statements
bull Insurance companies and Medicaid generally pay for whatrsquos on the ACIP schedule so these recommendations have financial repercussions
bull Because immunity is not inherited we need to immunize each persongeneration until the disease is truly eradicated
bull ACIP meetings are open to the public and can be viewed by streaming webcast
bull If recommendations are accepted by the CDC they are published in the MMWR
httpswwwcdcgovvaccinesacipabouthtml
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
WE STILL NEED VACCINES
bull Vaccine-preventable diseases still kill here and elsewhere
bull There are plenty of other diseases available to exercise the immune system
UNIVERSAL DISEASES
bull A universal disease affected nearly everyone at some point in their life
bull Measles mumps polio many others are universal
bull If a disease was universal how bad can it be Would Mother Nature really do something destructive
bull Yes
MEASLES A CASE STUDY
MORBIDITY VS MORTALITY
bull When the internet argues that the death rate was going down before vaccines that is true
bull But only because we developed treatments for the complications from measles
bull The case rate didnrsquot go down until the vaccine was introduced
MORTALITY VS CASES
SIMPLE RASH
bull Measles complications in 40 of cases
bull Diarrhea
bull Middle ear infection
bull Bronchopneumonia
bull Encephalitis in 11000
bull Death in 21000 usually pneumonia or encephalitis
bull In developing countries up to 25 fatality rate
bull Subacute sclerosing panencephalitis (fatal) in 110000 or morebull Kids who get the measles before age 5 have a one in 1387 chance of developing SSPE (Wendorf et al 2016)
bull Kids who get the measles before age 1 have a one in 609 chance
VACCINErsquoS CONTINUED CONTRIBUTION
bull Measles remains a leading cause of vaccine-preventable infant mortality but progress is being made
bull From 2000-2016
bull Reported measles incidence decreased 87 from 145 to 19 cases per million persons
bull Annual estimated measles deaths decreased 84 (204 million deaths prevented)
MMWR Oct 27 2017 Vol 66 No 42
PROS AND CONS OF NATURAL INFECTION
bull Immunity from natural infection often lasts longer (though this is questionable)
bull But in order to get that immunity you need to experience the disease
bull Suffering
bull Transmission to others
bull Complications
bull Death
bull Long term complications of measles include
bull SSPE (fatal)
bull Immunosuppression increasing deaths from other infectious diseases
bull More severe COPD in smokers who experienced measles
IMMUNOSUPPRESSION
bull After measles infection immunologic memory is suppressed for 2-3 years which increases all-cause mortality
bull Measles BCG and polio immunization reduced all-cause mortality rate by roughly half
Mina MJ Measles immune suppression and vaccination direct and indirect nonspecific vaccine benefits J Infect 201774 Suppl 1S10ndash7
NON-SPECIFIC EFFECTS OF MEASLES AND OTHER VACCINES
1 Higgins JPT Soares-Weiser K Reingold A Systematic review of the non-specific effects of BCG DTP and measles containing vaccines httpwwwwhointimmunizationsagemeetings2014april (accessed 1 Jun 2014)
2 Strategic Advisory Group of Experts on Immunization Meeting of the Strategic Advisory Group of Experts on Immunization April 2014 - conclusions and recommendations Week Epidemiol Rec201489221ndash36 [PubMed]
3Aaby P Martins CL Garly ML et al Non-specific effects of standard measles vaccine at 45 and 9 months of age on childhood mortality randomised controlled trial BMJ 2010341c6495doi101136bmjc6495 [PMC free article] [PubMed]
4Aaby P Samb B Simondon F et al Non-specific beneficial effect of measles immunisation analysis of mortality studies from developing countries BMJ 1995311481ndash5 doi101136bmj3117003481[PMC free article] [PubMed]
5 Kristensen I Aaby P Jensen H Routine vaccinations and child survival follow up study in Guinea-Bissau West Africa BMJ 20003211435ndash8 doi101136bmj32172741435 [PMC free article] [PubMed]
6 Benn CS Netea MG Selin LK et alA small jabmdasha big effect non-specific immunomodulation by vaccinesTrends Immunol 201334431ndash9 doi101016jit201304004 [PubMed]
CONCERN TH1 VS TH2
bull Th1 cells decrease the production of IgE
bull Th2 cells increase the production of IgE
bull Babies are born with a predominance of Th2 a bias towards allergic responses
bull To reduce allergic responses stimulate Th1
bull Infection with bacteria and viruses stimulates production of Th1
bull Infection with worms and helminths stimulate production of Th2
bull If babieskids donrsquot experience infection will they develop more allergies
VACCINES DO NOT CAUSE ALLERGIES
bull Vaccines do not prevent all diseases
bull Babies and kids still experience lots of infections
bull Large well-controlled epidemiologic studies do not support the hypothesis that vaccines cause allergies
bull ldquoHigher cumulative vaccine antigen doses were associated with less allergic sensitization allergic disease and less severe infant eczemardquo
Offit PA Hackett CJ Addressing Parentsrsquo Concerns Do Vaccines Cause Allergic or Autoimmune Diseases Pediatrics 2003111(3)653ndash9
CONCERN VS ACTUAL EFFECT
bull There are many valid questions and concerns about vaccines
bull For the most part we have the data to answer these questions
bull Donrsquot stop at the question Keep going to the answer
MECHANISMPATHWAY VS ACTUAL EFFECT
bull Many concerns about vaccines are based on biochemical pathways or mechanism
bull Donrsquot stop there Just because something is possible or even plausible doesnrsquot mean it actually happens that way
bull Look at the clinical data and the large body of literature
CONCERN VARICELLA VS ZOSTER
Question Does varicella immunization increase the risk of shingles in the unvaccinated population because of lack of immune stimulationviral suppression
Answer No zoster rates were going up before varicella program and were not affected by varicella immunization (Hales 2013) (Siedler 2014)
Plus varicella immunization seems to reduce the risk of shingles in immunized people (Baxter 2013)
SAFETY MONITORING
bull Pre-licensure trials including phase I II and III
bull Post-licensure studies and surveillance
bull Vaccine Safety Datalink (VSD)
bull Vaccine Adverse Event Reporting System (VAERS)
bull Clinical Immunization Safety Assessment (CISA) project ndash investigation into possible events in specific people certain populations excluded by pre-licensure studies
bull httpswwwhistoryofvaccinesorgcontentarticlesvaccine-development-testing-and-regulation
bull httpswwwcdcgovvaccinesbasicstest-approvehtml
SAFETY MONITORING VAERS
bull Vaccine Adverse Event Reporting System
bull ldquoSpontaneous (passive) surveillance means that no active effort is made to search for identify and collect information but rather information is passively received from those who choose to voluntarily report their experiencerdquo (Shimabukuro 2015)
bull Anyone can file any report
bull All reports are reviewed
bull ldquo[VAERS] reporting is incomplete requires follow-up investigation and cannot directly distinguish temporal associations from causal associations Consequently VAERS functions as a hypothesis-generating mechanism an early-warning signal of potential problems regarding vaccine safetyrdquo (Schwartz 2012)
Shimabukuro TT Nguyen M Martin D DeStefano F Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 201533(36)4398ndash405Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
SAFETY MONITORING VACCINE SAFETY DATALINK (VSD)
bull Includes multiple large HMOsMCOs covering 88 million people in 2011
bull Huge numbers allow for detection of rareserious events
bull Objectives of the Vaccine Safety Datalinkbull To conduct research on important vaccine safety questions in large populations
bull To conduct vaccine safety studies that come from questions or concerns in the medical literature or from other vaccine safety systems like VAERS
bull To monitor possible adverse events when new vaccines are licensed or when there are new vaccine recommendations
bull To provide information to committees who make recommendations for the nation
httpswwwcdcgovvaccinesafetyensuringsafetymonitoringvsdindexhtml
VACCINE SAFETY CASE ROTAVIRUS
bull In 1999 based on reports of 15 infants (of 15 million doses administered) experiencing intussusception after immunization with Rotashield the CDC recommended suspending use temporarily while investigation proceeded
bull Researchers found statistically significant differences in RotaShield vaccination rates between the two groups hellip Based on these results and estimates of the background rate of intussusception among US infants the research team estimated one additional case of intussusception attributable to the vaccine for every 4670 to 9474 infants vaccinated
bull Wyeth pulled the vaccine from the market when it was clear ACIP would vote against its use
Side bar Interesting moral questions about ldquoslamming the doorrdquo on a rotavirus vaccine that stood to save many lives internationally where the risk benefit ratio might be different (Schwartz 2012)
Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
VACCINE SAFETY CASE ROTAVIRUS
bull Rotateq (pentavalent) licensed in 2006
bull Rotarix (monovalent) licensed in 2008
bull Studies of the two new vaccines included 60000 to 70000 infants each in which no increased risk of intussusception was identified
VSD ROTAVIRUS (2014)
RESULTS
During the study period 207955 doses of monovalent rotavirus vaccine (including 115908 first doses and 92047 second doses) were administered in the VSD population We identified 6 cases of intussusception within 7 days after the administration of either dose of vaccine For the two doses combined the expected number of intussusception cases was 072 resulting in a significant relative risk of 84 For the pentavalent rotavirus vaccine 1301810 doses were administered duringthe study period with 8 observed intussusception cases (711 expected) for a nonsignificant relative risk of 11 The relativerisk of chart-confirmed intussusception within 7 days after monovalent rotavirus vaccination as compared with the risk after pentavalent rotavirus vaccination was 94 (95 confidence interval 14 to 1038) The attributable risk of intussusception after the administration of two doses of monovalent rotavirus vaccine was estimated to be 53 per 100000 infants vaccinated
Action
bull Rotavirus was pulled out of the multi-vaccine VIS
bull Rotavirus VIS was updated with specific information about the risks of rotavirus and clinical presentation
ROTAVIRUS WHY BOTHER
PRE-VACCINEbull Every year globally
bull 111 million episodes of gastroenteritis requiring only home care
bull 25 million outpatient medical visits
bull 2 million hospitalizations
bull 400000 deaths
POST-VACCINEbull A dramatic decrease (gt80) in the incidence of
severe rotavirus diarrhea has been reported in high-income countries
bull A decrease of about 50 has been reported in low-income settings
bull Reductions in diarrhea-associated deaths of 31 in infants younger than 1 year old and 42 in children younger than 5 years old in countries with low child mortality
OrsquoRyan M Rotavirus Vaccines a story of success with challenges ahead F1000 Research 20176 Parashar et al Global illness and deaths caused by rotavirus disease in children Emerg Infect Dis 2003 May9(5)565-72
EFFICACY CASE LAIV (FLUMIST)
bull ldquoIn light of low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013ndash14 and 2015ndash16 seasons for the 2016ndash17 season ACIP makes the interim recommendation that LAIV4 should not be usedrdquo
bull Even though it would cost the manufacturer as the ACIP recommendation drives usage and insurance coverage
Grohskopf LA Prevention and Control of Seasonal Influenza with Vaccines MMWR Recomm Rep 201665
WHO IS ACIP
bull The Advisory Committee on Immunization Practices ldquoincludes 15 voting members responsible for making vaccine recommendations The Secretary of the US Department of Health and Human Services (DHHS) selects these members following an application and nomination process Fourteen of the members have expertise in vaccinology immunology pediatrics internal medicine nursing family medicine virology public health infectious diseases andor preventive medicine one member is a consumer representative who provides perspectives on the social and community aspects of vaccination
bull In addition to the 15 voting members ACIP includes 8 ex officio members who represent other federal agencies with responsibility for immunization programs in the United States and 30 non-voting representatives of liaison organizations that bring related immunization expertiserdquo
httpswwwcdcgovvaccinesacipabouthtml
ACIP - SCHEDULE
bull How do vaccines get added Do vaccines ever get taken offbull Work group convene to work on one vaccine-preventable disease or group of diseases
bull Work group members collect and review data on disease epidemiology vaccine efficacy effectiveness safety feasibility of program implementation and economic aspects of immunization policy to include in written policy statements
bull Insurance companies and Medicaid generally pay for whatrsquos on the ACIP schedule so these recommendations have financial repercussions
bull Because immunity is not inherited we need to immunize each persongeneration until the disease is truly eradicated
bull ACIP meetings are open to the public and can be viewed by streaming webcast
bull If recommendations are accepted by the CDC they are published in the MMWR
httpswwwcdcgovvaccinesacipabouthtml
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
UNIVERSAL DISEASES
bull A universal disease affected nearly everyone at some point in their life
bull Measles mumps polio many others are universal
bull If a disease was universal how bad can it be Would Mother Nature really do something destructive
bull Yes
MEASLES A CASE STUDY
MORBIDITY VS MORTALITY
bull When the internet argues that the death rate was going down before vaccines that is true
bull But only because we developed treatments for the complications from measles
bull The case rate didnrsquot go down until the vaccine was introduced
MORTALITY VS CASES
SIMPLE RASH
bull Measles complications in 40 of cases
bull Diarrhea
bull Middle ear infection
bull Bronchopneumonia
bull Encephalitis in 11000
bull Death in 21000 usually pneumonia or encephalitis
bull In developing countries up to 25 fatality rate
bull Subacute sclerosing panencephalitis (fatal) in 110000 or morebull Kids who get the measles before age 5 have a one in 1387 chance of developing SSPE (Wendorf et al 2016)
bull Kids who get the measles before age 1 have a one in 609 chance
VACCINErsquoS CONTINUED CONTRIBUTION
bull Measles remains a leading cause of vaccine-preventable infant mortality but progress is being made
bull From 2000-2016
bull Reported measles incidence decreased 87 from 145 to 19 cases per million persons
bull Annual estimated measles deaths decreased 84 (204 million deaths prevented)
MMWR Oct 27 2017 Vol 66 No 42
PROS AND CONS OF NATURAL INFECTION
bull Immunity from natural infection often lasts longer (though this is questionable)
bull But in order to get that immunity you need to experience the disease
bull Suffering
bull Transmission to others
bull Complications
bull Death
bull Long term complications of measles include
bull SSPE (fatal)
bull Immunosuppression increasing deaths from other infectious diseases
bull More severe COPD in smokers who experienced measles
IMMUNOSUPPRESSION
bull After measles infection immunologic memory is suppressed for 2-3 years which increases all-cause mortality
bull Measles BCG and polio immunization reduced all-cause mortality rate by roughly half
Mina MJ Measles immune suppression and vaccination direct and indirect nonspecific vaccine benefits J Infect 201774 Suppl 1S10ndash7
NON-SPECIFIC EFFECTS OF MEASLES AND OTHER VACCINES
1 Higgins JPT Soares-Weiser K Reingold A Systematic review of the non-specific effects of BCG DTP and measles containing vaccines httpwwwwhointimmunizationsagemeetings2014april (accessed 1 Jun 2014)
2 Strategic Advisory Group of Experts on Immunization Meeting of the Strategic Advisory Group of Experts on Immunization April 2014 - conclusions and recommendations Week Epidemiol Rec201489221ndash36 [PubMed]
3Aaby P Martins CL Garly ML et al Non-specific effects of standard measles vaccine at 45 and 9 months of age on childhood mortality randomised controlled trial BMJ 2010341c6495doi101136bmjc6495 [PMC free article] [PubMed]
4Aaby P Samb B Simondon F et al Non-specific beneficial effect of measles immunisation analysis of mortality studies from developing countries BMJ 1995311481ndash5 doi101136bmj3117003481[PMC free article] [PubMed]
5 Kristensen I Aaby P Jensen H Routine vaccinations and child survival follow up study in Guinea-Bissau West Africa BMJ 20003211435ndash8 doi101136bmj32172741435 [PMC free article] [PubMed]
6 Benn CS Netea MG Selin LK et alA small jabmdasha big effect non-specific immunomodulation by vaccinesTrends Immunol 201334431ndash9 doi101016jit201304004 [PubMed]
CONCERN TH1 VS TH2
bull Th1 cells decrease the production of IgE
bull Th2 cells increase the production of IgE
bull Babies are born with a predominance of Th2 a bias towards allergic responses
bull To reduce allergic responses stimulate Th1
bull Infection with bacteria and viruses stimulates production of Th1
bull Infection with worms and helminths stimulate production of Th2
bull If babieskids donrsquot experience infection will they develop more allergies
VACCINES DO NOT CAUSE ALLERGIES
bull Vaccines do not prevent all diseases
bull Babies and kids still experience lots of infections
bull Large well-controlled epidemiologic studies do not support the hypothesis that vaccines cause allergies
bull ldquoHigher cumulative vaccine antigen doses were associated with less allergic sensitization allergic disease and less severe infant eczemardquo
Offit PA Hackett CJ Addressing Parentsrsquo Concerns Do Vaccines Cause Allergic or Autoimmune Diseases Pediatrics 2003111(3)653ndash9
CONCERN VS ACTUAL EFFECT
bull There are many valid questions and concerns about vaccines
bull For the most part we have the data to answer these questions
bull Donrsquot stop at the question Keep going to the answer
MECHANISMPATHWAY VS ACTUAL EFFECT
bull Many concerns about vaccines are based on biochemical pathways or mechanism
bull Donrsquot stop there Just because something is possible or even plausible doesnrsquot mean it actually happens that way
bull Look at the clinical data and the large body of literature
CONCERN VARICELLA VS ZOSTER
Question Does varicella immunization increase the risk of shingles in the unvaccinated population because of lack of immune stimulationviral suppression
Answer No zoster rates were going up before varicella program and were not affected by varicella immunization (Hales 2013) (Siedler 2014)
Plus varicella immunization seems to reduce the risk of shingles in immunized people (Baxter 2013)
SAFETY MONITORING
bull Pre-licensure trials including phase I II and III
bull Post-licensure studies and surveillance
bull Vaccine Safety Datalink (VSD)
bull Vaccine Adverse Event Reporting System (VAERS)
bull Clinical Immunization Safety Assessment (CISA) project ndash investigation into possible events in specific people certain populations excluded by pre-licensure studies
bull httpswwwhistoryofvaccinesorgcontentarticlesvaccine-development-testing-and-regulation
bull httpswwwcdcgovvaccinesbasicstest-approvehtml
SAFETY MONITORING VAERS
bull Vaccine Adverse Event Reporting System
bull ldquoSpontaneous (passive) surveillance means that no active effort is made to search for identify and collect information but rather information is passively received from those who choose to voluntarily report their experiencerdquo (Shimabukuro 2015)
bull Anyone can file any report
bull All reports are reviewed
bull ldquo[VAERS] reporting is incomplete requires follow-up investigation and cannot directly distinguish temporal associations from causal associations Consequently VAERS functions as a hypothesis-generating mechanism an early-warning signal of potential problems regarding vaccine safetyrdquo (Schwartz 2012)
Shimabukuro TT Nguyen M Martin D DeStefano F Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 201533(36)4398ndash405Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
SAFETY MONITORING VACCINE SAFETY DATALINK (VSD)
bull Includes multiple large HMOsMCOs covering 88 million people in 2011
bull Huge numbers allow for detection of rareserious events
bull Objectives of the Vaccine Safety Datalinkbull To conduct research on important vaccine safety questions in large populations
bull To conduct vaccine safety studies that come from questions or concerns in the medical literature or from other vaccine safety systems like VAERS
bull To monitor possible adverse events when new vaccines are licensed or when there are new vaccine recommendations
bull To provide information to committees who make recommendations for the nation
httpswwwcdcgovvaccinesafetyensuringsafetymonitoringvsdindexhtml
VACCINE SAFETY CASE ROTAVIRUS
bull In 1999 based on reports of 15 infants (of 15 million doses administered) experiencing intussusception after immunization with Rotashield the CDC recommended suspending use temporarily while investigation proceeded
bull Researchers found statistically significant differences in RotaShield vaccination rates between the two groups hellip Based on these results and estimates of the background rate of intussusception among US infants the research team estimated one additional case of intussusception attributable to the vaccine for every 4670 to 9474 infants vaccinated
bull Wyeth pulled the vaccine from the market when it was clear ACIP would vote against its use
Side bar Interesting moral questions about ldquoslamming the doorrdquo on a rotavirus vaccine that stood to save many lives internationally where the risk benefit ratio might be different (Schwartz 2012)
Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
VACCINE SAFETY CASE ROTAVIRUS
bull Rotateq (pentavalent) licensed in 2006
bull Rotarix (monovalent) licensed in 2008
bull Studies of the two new vaccines included 60000 to 70000 infants each in which no increased risk of intussusception was identified
VSD ROTAVIRUS (2014)
RESULTS
During the study period 207955 doses of monovalent rotavirus vaccine (including 115908 first doses and 92047 second doses) were administered in the VSD population We identified 6 cases of intussusception within 7 days after the administration of either dose of vaccine For the two doses combined the expected number of intussusception cases was 072 resulting in a significant relative risk of 84 For the pentavalent rotavirus vaccine 1301810 doses were administered duringthe study period with 8 observed intussusception cases (711 expected) for a nonsignificant relative risk of 11 The relativerisk of chart-confirmed intussusception within 7 days after monovalent rotavirus vaccination as compared with the risk after pentavalent rotavirus vaccination was 94 (95 confidence interval 14 to 1038) The attributable risk of intussusception after the administration of two doses of monovalent rotavirus vaccine was estimated to be 53 per 100000 infants vaccinated
Action
bull Rotavirus was pulled out of the multi-vaccine VIS
bull Rotavirus VIS was updated with specific information about the risks of rotavirus and clinical presentation
ROTAVIRUS WHY BOTHER
PRE-VACCINEbull Every year globally
bull 111 million episodes of gastroenteritis requiring only home care
bull 25 million outpatient medical visits
bull 2 million hospitalizations
bull 400000 deaths
POST-VACCINEbull A dramatic decrease (gt80) in the incidence of
severe rotavirus diarrhea has been reported in high-income countries
bull A decrease of about 50 has been reported in low-income settings
bull Reductions in diarrhea-associated deaths of 31 in infants younger than 1 year old and 42 in children younger than 5 years old in countries with low child mortality
OrsquoRyan M Rotavirus Vaccines a story of success with challenges ahead F1000 Research 20176 Parashar et al Global illness and deaths caused by rotavirus disease in children Emerg Infect Dis 2003 May9(5)565-72
EFFICACY CASE LAIV (FLUMIST)
bull ldquoIn light of low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013ndash14 and 2015ndash16 seasons for the 2016ndash17 season ACIP makes the interim recommendation that LAIV4 should not be usedrdquo
bull Even though it would cost the manufacturer as the ACIP recommendation drives usage and insurance coverage
Grohskopf LA Prevention and Control of Seasonal Influenza with Vaccines MMWR Recomm Rep 201665
WHO IS ACIP
bull The Advisory Committee on Immunization Practices ldquoincludes 15 voting members responsible for making vaccine recommendations The Secretary of the US Department of Health and Human Services (DHHS) selects these members following an application and nomination process Fourteen of the members have expertise in vaccinology immunology pediatrics internal medicine nursing family medicine virology public health infectious diseases andor preventive medicine one member is a consumer representative who provides perspectives on the social and community aspects of vaccination
bull In addition to the 15 voting members ACIP includes 8 ex officio members who represent other federal agencies with responsibility for immunization programs in the United States and 30 non-voting representatives of liaison organizations that bring related immunization expertiserdquo
httpswwwcdcgovvaccinesacipabouthtml
ACIP - SCHEDULE
bull How do vaccines get added Do vaccines ever get taken offbull Work group convene to work on one vaccine-preventable disease or group of diseases
bull Work group members collect and review data on disease epidemiology vaccine efficacy effectiveness safety feasibility of program implementation and economic aspects of immunization policy to include in written policy statements
bull Insurance companies and Medicaid generally pay for whatrsquos on the ACIP schedule so these recommendations have financial repercussions
bull Because immunity is not inherited we need to immunize each persongeneration until the disease is truly eradicated
bull ACIP meetings are open to the public and can be viewed by streaming webcast
bull If recommendations are accepted by the CDC they are published in the MMWR
httpswwwcdcgovvaccinesacipabouthtml
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
MEASLES A CASE STUDY
MORBIDITY VS MORTALITY
bull When the internet argues that the death rate was going down before vaccines that is true
bull But only because we developed treatments for the complications from measles
bull The case rate didnrsquot go down until the vaccine was introduced
MORTALITY VS CASES
SIMPLE RASH
bull Measles complications in 40 of cases
bull Diarrhea
bull Middle ear infection
bull Bronchopneumonia
bull Encephalitis in 11000
bull Death in 21000 usually pneumonia or encephalitis
bull In developing countries up to 25 fatality rate
bull Subacute sclerosing panencephalitis (fatal) in 110000 or morebull Kids who get the measles before age 5 have a one in 1387 chance of developing SSPE (Wendorf et al 2016)
bull Kids who get the measles before age 1 have a one in 609 chance
VACCINErsquoS CONTINUED CONTRIBUTION
bull Measles remains a leading cause of vaccine-preventable infant mortality but progress is being made
bull From 2000-2016
bull Reported measles incidence decreased 87 from 145 to 19 cases per million persons
bull Annual estimated measles deaths decreased 84 (204 million deaths prevented)
MMWR Oct 27 2017 Vol 66 No 42
PROS AND CONS OF NATURAL INFECTION
bull Immunity from natural infection often lasts longer (though this is questionable)
bull But in order to get that immunity you need to experience the disease
bull Suffering
bull Transmission to others
bull Complications
bull Death
bull Long term complications of measles include
bull SSPE (fatal)
bull Immunosuppression increasing deaths from other infectious diseases
bull More severe COPD in smokers who experienced measles
IMMUNOSUPPRESSION
bull After measles infection immunologic memory is suppressed for 2-3 years which increases all-cause mortality
bull Measles BCG and polio immunization reduced all-cause mortality rate by roughly half
Mina MJ Measles immune suppression and vaccination direct and indirect nonspecific vaccine benefits J Infect 201774 Suppl 1S10ndash7
NON-SPECIFIC EFFECTS OF MEASLES AND OTHER VACCINES
1 Higgins JPT Soares-Weiser K Reingold A Systematic review of the non-specific effects of BCG DTP and measles containing vaccines httpwwwwhointimmunizationsagemeetings2014april (accessed 1 Jun 2014)
2 Strategic Advisory Group of Experts on Immunization Meeting of the Strategic Advisory Group of Experts on Immunization April 2014 - conclusions and recommendations Week Epidemiol Rec201489221ndash36 [PubMed]
3Aaby P Martins CL Garly ML et al Non-specific effects of standard measles vaccine at 45 and 9 months of age on childhood mortality randomised controlled trial BMJ 2010341c6495doi101136bmjc6495 [PMC free article] [PubMed]
4Aaby P Samb B Simondon F et al Non-specific beneficial effect of measles immunisation analysis of mortality studies from developing countries BMJ 1995311481ndash5 doi101136bmj3117003481[PMC free article] [PubMed]
5 Kristensen I Aaby P Jensen H Routine vaccinations and child survival follow up study in Guinea-Bissau West Africa BMJ 20003211435ndash8 doi101136bmj32172741435 [PMC free article] [PubMed]
6 Benn CS Netea MG Selin LK et alA small jabmdasha big effect non-specific immunomodulation by vaccinesTrends Immunol 201334431ndash9 doi101016jit201304004 [PubMed]
CONCERN TH1 VS TH2
bull Th1 cells decrease the production of IgE
bull Th2 cells increase the production of IgE
bull Babies are born with a predominance of Th2 a bias towards allergic responses
bull To reduce allergic responses stimulate Th1
bull Infection with bacteria and viruses stimulates production of Th1
bull Infection with worms and helminths stimulate production of Th2
bull If babieskids donrsquot experience infection will they develop more allergies
VACCINES DO NOT CAUSE ALLERGIES
bull Vaccines do not prevent all diseases
bull Babies and kids still experience lots of infections
bull Large well-controlled epidemiologic studies do not support the hypothesis that vaccines cause allergies
bull ldquoHigher cumulative vaccine antigen doses were associated with less allergic sensitization allergic disease and less severe infant eczemardquo
Offit PA Hackett CJ Addressing Parentsrsquo Concerns Do Vaccines Cause Allergic or Autoimmune Diseases Pediatrics 2003111(3)653ndash9
CONCERN VS ACTUAL EFFECT
bull There are many valid questions and concerns about vaccines
bull For the most part we have the data to answer these questions
bull Donrsquot stop at the question Keep going to the answer
MECHANISMPATHWAY VS ACTUAL EFFECT
bull Many concerns about vaccines are based on biochemical pathways or mechanism
bull Donrsquot stop there Just because something is possible or even plausible doesnrsquot mean it actually happens that way
bull Look at the clinical data and the large body of literature
CONCERN VARICELLA VS ZOSTER
Question Does varicella immunization increase the risk of shingles in the unvaccinated population because of lack of immune stimulationviral suppression
Answer No zoster rates were going up before varicella program and were not affected by varicella immunization (Hales 2013) (Siedler 2014)
Plus varicella immunization seems to reduce the risk of shingles in immunized people (Baxter 2013)
SAFETY MONITORING
bull Pre-licensure trials including phase I II and III
bull Post-licensure studies and surveillance
bull Vaccine Safety Datalink (VSD)
bull Vaccine Adverse Event Reporting System (VAERS)
bull Clinical Immunization Safety Assessment (CISA) project ndash investigation into possible events in specific people certain populations excluded by pre-licensure studies
bull httpswwwhistoryofvaccinesorgcontentarticlesvaccine-development-testing-and-regulation
bull httpswwwcdcgovvaccinesbasicstest-approvehtml
SAFETY MONITORING VAERS
bull Vaccine Adverse Event Reporting System
bull ldquoSpontaneous (passive) surveillance means that no active effort is made to search for identify and collect information but rather information is passively received from those who choose to voluntarily report their experiencerdquo (Shimabukuro 2015)
bull Anyone can file any report
bull All reports are reviewed
bull ldquo[VAERS] reporting is incomplete requires follow-up investigation and cannot directly distinguish temporal associations from causal associations Consequently VAERS functions as a hypothesis-generating mechanism an early-warning signal of potential problems regarding vaccine safetyrdquo (Schwartz 2012)
Shimabukuro TT Nguyen M Martin D DeStefano F Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 201533(36)4398ndash405Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
SAFETY MONITORING VACCINE SAFETY DATALINK (VSD)
bull Includes multiple large HMOsMCOs covering 88 million people in 2011
bull Huge numbers allow for detection of rareserious events
bull Objectives of the Vaccine Safety Datalinkbull To conduct research on important vaccine safety questions in large populations
bull To conduct vaccine safety studies that come from questions or concerns in the medical literature or from other vaccine safety systems like VAERS
bull To monitor possible adverse events when new vaccines are licensed or when there are new vaccine recommendations
bull To provide information to committees who make recommendations for the nation
httpswwwcdcgovvaccinesafetyensuringsafetymonitoringvsdindexhtml
VACCINE SAFETY CASE ROTAVIRUS
bull In 1999 based on reports of 15 infants (of 15 million doses administered) experiencing intussusception after immunization with Rotashield the CDC recommended suspending use temporarily while investigation proceeded
bull Researchers found statistically significant differences in RotaShield vaccination rates between the two groups hellip Based on these results and estimates of the background rate of intussusception among US infants the research team estimated one additional case of intussusception attributable to the vaccine for every 4670 to 9474 infants vaccinated
bull Wyeth pulled the vaccine from the market when it was clear ACIP would vote against its use
Side bar Interesting moral questions about ldquoslamming the doorrdquo on a rotavirus vaccine that stood to save many lives internationally where the risk benefit ratio might be different (Schwartz 2012)
Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
VACCINE SAFETY CASE ROTAVIRUS
bull Rotateq (pentavalent) licensed in 2006
bull Rotarix (monovalent) licensed in 2008
bull Studies of the two new vaccines included 60000 to 70000 infants each in which no increased risk of intussusception was identified
VSD ROTAVIRUS (2014)
RESULTS
During the study period 207955 doses of monovalent rotavirus vaccine (including 115908 first doses and 92047 second doses) were administered in the VSD population We identified 6 cases of intussusception within 7 days after the administration of either dose of vaccine For the two doses combined the expected number of intussusception cases was 072 resulting in a significant relative risk of 84 For the pentavalent rotavirus vaccine 1301810 doses were administered duringthe study period with 8 observed intussusception cases (711 expected) for a nonsignificant relative risk of 11 The relativerisk of chart-confirmed intussusception within 7 days after monovalent rotavirus vaccination as compared with the risk after pentavalent rotavirus vaccination was 94 (95 confidence interval 14 to 1038) The attributable risk of intussusception after the administration of two doses of monovalent rotavirus vaccine was estimated to be 53 per 100000 infants vaccinated
Action
bull Rotavirus was pulled out of the multi-vaccine VIS
bull Rotavirus VIS was updated with specific information about the risks of rotavirus and clinical presentation
ROTAVIRUS WHY BOTHER
PRE-VACCINEbull Every year globally
bull 111 million episodes of gastroenteritis requiring only home care
bull 25 million outpatient medical visits
bull 2 million hospitalizations
bull 400000 deaths
POST-VACCINEbull A dramatic decrease (gt80) in the incidence of
severe rotavirus diarrhea has been reported in high-income countries
bull A decrease of about 50 has been reported in low-income settings
bull Reductions in diarrhea-associated deaths of 31 in infants younger than 1 year old and 42 in children younger than 5 years old in countries with low child mortality
OrsquoRyan M Rotavirus Vaccines a story of success with challenges ahead F1000 Research 20176 Parashar et al Global illness and deaths caused by rotavirus disease in children Emerg Infect Dis 2003 May9(5)565-72
EFFICACY CASE LAIV (FLUMIST)
bull ldquoIn light of low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013ndash14 and 2015ndash16 seasons for the 2016ndash17 season ACIP makes the interim recommendation that LAIV4 should not be usedrdquo
bull Even though it would cost the manufacturer as the ACIP recommendation drives usage and insurance coverage
Grohskopf LA Prevention and Control of Seasonal Influenza with Vaccines MMWR Recomm Rep 201665
WHO IS ACIP
bull The Advisory Committee on Immunization Practices ldquoincludes 15 voting members responsible for making vaccine recommendations The Secretary of the US Department of Health and Human Services (DHHS) selects these members following an application and nomination process Fourteen of the members have expertise in vaccinology immunology pediatrics internal medicine nursing family medicine virology public health infectious diseases andor preventive medicine one member is a consumer representative who provides perspectives on the social and community aspects of vaccination
bull In addition to the 15 voting members ACIP includes 8 ex officio members who represent other federal agencies with responsibility for immunization programs in the United States and 30 non-voting representatives of liaison organizations that bring related immunization expertiserdquo
httpswwwcdcgovvaccinesacipabouthtml
ACIP - SCHEDULE
bull How do vaccines get added Do vaccines ever get taken offbull Work group convene to work on one vaccine-preventable disease or group of diseases
bull Work group members collect and review data on disease epidemiology vaccine efficacy effectiveness safety feasibility of program implementation and economic aspects of immunization policy to include in written policy statements
bull Insurance companies and Medicaid generally pay for whatrsquos on the ACIP schedule so these recommendations have financial repercussions
bull Because immunity is not inherited we need to immunize each persongeneration until the disease is truly eradicated
bull ACIP meetings are open to the public and can be viewed by streaming webcast
bull If recommendations are accepted by the CDC they are published in the MMWR
httpswwwcdcgovvaccinesacipabouthtml
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
MORBIDITY VS MORTALITY
bull When the internet argues that the death rate was going down before vaccines that is true
bull But only because we developed treatments for the complications from measles
bull The case rate didnrsquot go down until the vaccine was introduced
MORTALITY VS CASES
SIMPLE RASH
bull Measles complications in 40 of cases
bull Diarrhea
bull Middle ear infection
bull Bronchopneumonia
bull Encephalitis in 11000
bull Death in 21000 usually pneumonia or encephalitis
bull In developing countries up to 25 fatality rate
bull Subacute sclerosing panencephalitis (fatal) in 110000 or morebull Kids who get the measles before age 5 have a one in 1387 chance of developing SSPE (Wendorf et al 2016)
bull Kids who get the measles before age 1 have a one in 609 chance
VACCINErsquoS CONTINUED CONTRIBUTION
bull Measles remains a leading cause of vaccine-preventable infant mortality but progress is being made
bull From 2000-2016
bull Reported measles incidence decreased 87 from 145 to 19 cases per million persons
bull Annual estimated measles deaths decreased 84 (204 million deaths prevented)
MMWR Oct 27 2017 Vol 66 No 42
PROS AND CONS OF NATURAL INFECTION
bull Immunity from natural infection often lasts longer (though this is questionable)
bull But in order to get that immunity you need to experience the disease
bull Suffering
bull Transmission to others
bull Complications
bull Death
bull Long term complications of measles include
bull SSPE (fatal)
bull Immunosuppression increasing deaths from other infectious diseases
bull More severe COPD in smokers who experienced measles
IMMUNOSUPPRESSION
bull After measles infection immunologic memory is suppressed for 2-3 years which increases all-cause mortality
bull Measles BCG and polio immunization reduced all-cause mortality rate by roughly half
Mina MJ Measles immune suppression and vaccination direct and indirect nonspecific vaccine benefits J Infect 201774 Suppl 1S10ndash7
NON-SPECIFIC EFFECTS OF MEASLES AND OTHER VACCINES
1 Higgins JPT Soares-Weiser K Reingold A Systematic review of the non-specific effects of BCG DTP and measles containing vaccines httpwwwwhointimmunizationsagemeetings2014april (accessed 1 Jun 2014)
2 Strategic Advisory Group of Experts on Immunization Meeting of the Strategic Advisory Group of Experts on Immunization April 2014 - conclusions and recommendations Week Epidemiol Rec201489221ndash36 [PubMed]
3Aaby P Martins CL Garly ML et al Non-specific effects of standard measles vaccine at 45 and 9 months of age on childhood mortality randomised controlled trial BMJ 2010341c6495doi101136bmjc6495 [PMC free article] [PubMed]
4Aaby P Samb B Simondon F et al Non-specific beneficial effect of measles immunisation analysis of mortality studies from developing countries BMJ 1995311481ndash5 doi101136bmj3117003481[PMC free article] [PubMed]
5 Kristensen I Aaby P Jensen H Routine vaccinations and child survival follow up study in Guinea-Bissau West Africa BMJ 20003211435ndash8 doi101136bmj32172741435 [PMC free article] [PubMed]
6 Benn CS Netea MG Selin LK et alA small jabmdasha big effect non-specific immunomodulation by vaccinesTrends Immunol 201334431ndash9 doi101016jit201304004 [PubMed]
CONCERN TH1 VS TH2
bull Th1 cells decrease the production of IgE
bull Th2 cells increase the production of IgE
bull Babies are born with a predominance of Th2 a bias towards allergic responses
bull To reduce allergic responses stimulate Th1
bull Infection with bacteria and viruses stimulates production of Th1
bull Infection with worms and helminths stimulate production of Th2
bull If babieskids donrsquot experience infection will they develop more allergies
VACCINES DO NOT CAUSE ALLERGIES
bull Vaccines do not prevent all diseases
bull Babies and kids still experience lots of infections
bull Large well-controlled epidemiologic studies do not support the hypothesis that vaccines cause allergies
bull ldquoHigher cumulative vaccine antigen doses were associated with less allergic sensitization allergic disease and less severe infant eczemardquo
Offit PA Hackett CJ Addressing Parentsrsquo Concerns Do Vaccines Cause Allergic or Autoimmune Diseases Pediatrics 2003111(3)653ndash9
CONCERN VS ACTUAL EFFECT
bull There are many valid questions and concerns about vaccines
bull For the most part we have the data to answer these questions
bull Donrsquot stop at the question Keep going to the answer
MECHANISMPATHWAY VS ACTUAL EFFECT
bull Many concerns about vaccines are based on biochemical pathways or mechanism
bull Donrsquot stop there Just because something is possible or even plausible doesnrsquot mean it actually happens that way
bull Look at the clinical data and the large body of literature
CONCERN VARICELLA VS ZOSTER
Question Does varicella immunization increase the risk of shingles in the unvaccinated population because of lack of immune stimulationviral suppression
Answer No zoster rates were going up before varicella program and were not affected by varicella immunization (Hales 2013) (Siedler 2014)
Plus varicella immunization seems to reduce the risk of shingles in immunized people (Baxter 2013)
SAFETY MONITORING
bull Pre-licensure trials including phase I II and III
bull Post-licensure studies and surveillance
bull Vaccine Safety Datalink (VSD)
bull Vaccine Adverse Event Reporting System (VAERS)
bull Clinical Immunization Safety Assessment (CISA) project ndash investigation into possible events in specific people certain populations excluded by pre-licensure studies
bull httpswwwhistoryofvaccinesorgcontentarticlesvaccine-development-testing-and-regulation
bull httpswwwcdcgovvaccinesbasicstest-approvehtml
SAFETY MONITORING VAERS
bull Vaccine Adverse Event Reporting System
bull ldquoSpontaneous (passive) surveillance means that no active effort is made to search for identify and collect information but rather information is passively received from those who choose to voluntarily report their experiencerdquo (Shimabukuro 2015)
bull Anyone can file any report
bull All reports are reviewed
bull ldquo[VAERS] reporting is incomplete requires follow-up investigation and cannot directly distinguish temporal associations from causal associations Consequently VAERS functions as a hypothesis-generating mechanism an early-warning signal of potential problems regarding vaccine safetyrdquo (Schwartz 2012)
Shimabukuro TT Nguyen M Martin D DeStefano F Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 201533(36)4398ndash405Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
SAFETY MONITORING VACCINE SAFETY DATALINK (VSD)
bull Includes multiple large HMOsMCOs covering 88 million people in 2011
bull Huge numbers allow for detection of rareserious events
bull Objectives of the Vaccine Safety Datalinkbull To conduct research on important vaccine safety questions in large populations
bull To conduct vaccine safety studies that come from questions or concerns in the medical literature or from other vaccine safety systems like VAERS
bull To monitor possible adverse events when new vaccines are licensed or when there are new vaccine recommendations
bull To provide information to committees who make recommendations for the nation
httpswwwcdcgovvaccinesafetyensuringsafetymonitoringvsdindexhtml
VACCINE SAFETY CASE ROTAVIRUS
bull In 1999 based on reports of 15 infants (of 15 million doses administered) experiencing intussusception after immunization with Rotashield the CDC recommended suspending use temporarily while investigation proceeded
bull Researchers found statistically significant differences in RotaShield vaccination rates between the two groups hellip Based on these results and estimates of the background rate of intussusception among US infants the research team estimated one additional case of intussusception attributable to the vaccine for every 4670 to 9474 infants vaccinated
bull Wyeth pulled the vaccine from the market when it was clear ACIP would vote against its use
Side bar Interesting moral questions about ldquoslamming the doorrdquo on a rotavirus vaccine that stood to save many lives internationally where the risk benefit ratio might be different (Schwartz 2012)
Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
VACCINE SAFETY CASE ROTAVIRUS
bull Rotateq (pentavalent) licensed in 2006
bull Rotarix (monovalent) licensed in 2008
bull Studies of the two new vaccines included 60000 to 70000 infants each in which no increased risk of intussusception was identified
VSD ROTAVIRUS (2014)
RESULTS
During the study period 207955 doses of monovalent rotavirus vaccine (including 115908 first doses and 92047 second doses) were administered in the VSD population We identified 6 cases of intussusception within 7 days after the administration of either dose of vaccine For the two doses combined the expected number of intussusception cases was 072 resulting in a significant relative risk of 84 For the pentavalent rotavirus vaccine 1301810 doses were administered duringthe study period with 8 observed intussusception cases (711 expected) for a nonsignificant relative risk of 11 The relativerisk of chart-confirmed intussusception within 7 days after monovalent rotavirus vaccination as compared with the risk after pentavalent rotavirus vaccination was 94 (95 confidence interval 14 to 1038) The attributable risk of intussusception after the administration of two doses of monovalent rotavirus vaccine was estimated to be 53 per 100000 infants vaccinated
Action
bull Rotavirus was pulled out of the multi-vaccine VIS
bull Rotavirus VIS was updated with specific information about the risks of rotavirus and clinical presentation
ROTAVIRUS WHY BOTHER
PRE-VACCINEbull Every year globally
bull 111 million episodes of gastroenteritis requiring only home care
bull 25 million outpatient medical visits
bull 2 million hospitalizations
bull 400000 deaths
POST-VACCINEbull A dramatic decrease (gt80) in the incidence of
severe rotavirus diarrhea has been reported in high-income countries
bull A decrease of about 50 has been reported in low-income settings
bull Reductions in diarrhea-associated deaths of 31 in infants younger than 1 year old and 42 in children younger than 5 years old in countries with low child mortality
OrsquoRyan M Rotavirus Vaccines a story of success with challenges ahead F1000 Research 20176 Parashar et al Global illness and deaths caused by rotavirus disease in children Emerg Infect Dis 2003 May9(5)565-72
EFFICACY CASE LAIV (FLUMIST)
bull ldquoIn light of low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013ndash14 and 2015ndash16 seasons for the 2016ndash17 season ACIP makes the interim recommendation that LAIV4 should not be usedrdquo
bull Even though it would cost the manufacturer as the ACIP recommendation drives usage and insurance coverage
Grohskopf LA Prevention and Control of Seasonal Influenza with Vaccines MMWR Recomm Rep 201665
WHO IS ACIP
bull The Advisory Committee on Immunization Practices ldquoincludes 15 voting members responsible for making vaccine recommendations The Secretary of the US Department of Health and Human Services (DHHS) selects these members following an application and nomination process Fourteen of the members have expertise in vaccinology immunology pediatrics internal medicine nursing family medicine virology public health infectious diseases andor preventive medicine one member is a consumer representative who provides perspectives on the social and community aspects of vaccination
bull In addition to the 15 voting members ACIP includes 8 ex officio members who represent other federal agencies with responsibility for immunization programs in the United States and 30 non-voting representatives of liaison organizations that bring related immunization expertiserdquo
httpswwwcdcgovvaccinesacipabouthtml
ACIP - SCHEDULE
bull How do vaccines get added Do vaccines ever get taken offbull Work group convene to work on one vaccine-preventable disease or group of diseases
bull Work group members collect and review data on disease epidemiology vaccine efficacy effectiveness safety feasibility of program implementation and economic aspects of immunization policy to include in written policy statements
bull Insurance companies and Medicaid generally pay for whatrsquos on the ACIP schedule so these recommendations have financial repercussions
bull Because immunity is not inherited we need to immunize each persongeneration until the disease is truly eradicated
bull ACIP meetings are open to the public and can be viewed by streaming webcast
bull If recommendations are accepted by the CDC they are published in the MMWR
httpswwwcdcgovvaccinesacipabouthtml
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
MORTALITY VS CASES
SIMPLE RASH
bull Measles complications in 40 of cases
bull Diarrhea
bull Middle ear infection
bull Bronchopneumonia
bull Encephalitis in 11000
bull Death in 21000 usually pneumonia or encephalitis
bull In developing countries up to 25 fatality rate
bull Subacute sclerosing panencephalitis (fatal) in 110000 or morebull Kids who get the measles before age 5 have a one in 1387 chance of developing SSPE (Wendorf et al 2016)
bull Kids who get the measles before age 1 have a one in 609 chance
VACCINErsquoS CONTINUED CONTRIBUTION
bull Measles remains a leading cause of vaccine-preventable infant mortality but progress is being made
bull From 2000-2016
bull Reported measles incidence decreased 87 from 145 to 19 cases per million persons
bull Annual estimated measles deaths decreased 84 (204 million deaths prevented)
MMWR Oct 27 2017 Vol 66 No 42
PROS AND CONS OF NATURAL INFECTION
bull Immunity from natural infection often lasts longer (though this is questionable)
bull But in order to get that immunity you need to experience the disease
bull Suffering
bull Transmission to others
bull Complications
bull Death
bull Long term complications of measles include
bull SSPE (fatal)
bull Immunosuppression increasing deaths from other infectious diseases
bull More severe COPD in smokers who experienced measles
IMMUNOSUPPRESSION
bull After measles infection immunologic memory is suppressed for 2-3 years which increases all-cause mortality
bull Measles BCG and polio immunization reduced all-cause mortality rate by roughly half
Mina MJ Measles immune suppression and vaccination direct and indirect nonspecific vaccine benefits J Infect 201774 Suppl 1S10ndash7
NON-SPECIFIC EFFECTS OF MEASLES AND OTHER VACCINES
1 Higgins JPT Soares-Weiser K Reingold A Systematic review of the non-specific effects of BCG DTP and measles containing vaccines httpwwwwhointimmunizationsagemeetings2014april (accessed 1 Jun 2014)
2 Strategic Advisory Group of Experts on Immunization Meeting of the Strategic Advisory Group of Experts on Immunization April 2014 - conclusions and recommendations Week Epidemiol Rec201489221ndash36 [PubMed]
3Aaby P Martins CL Garly ML et al Non-specific effects of standard measles vaccine at 45 and 9 months of age on childhood mortality randomised controlled trial BMJ 2010341c6495doi101136bmjc6495 [PMC free article] [PubMed]
4Aaby P Samb B Simondon F et al Non-specific beneficial effect of measles immunisation analysis of mortality studies from developing countries BMJ 1995311481ndash5 doi101136bmj3117003481[PMC free article] [PubMed]
5 Kristensen I Aaby P Jensen H Routine vaccinations and child survival follow up study in Guinea-Bissau West Africa BMJ 20003211435ndash8 doi101136bmj32172741435 [PMC free article] [PubMed]
6 Benn CS Netea MG Selin LK et alA small jabmdasha big effect non-specific immunomodulation by vaccinesTrends Immunol 201334431ndash9 doi101016jit201304004 [PubMed]
CONCERN TH1 VS TH2
bull Th1 cells decrease the production of IgE
bull Th2 cells increase the production of IgE
bull Babies are born with a predominance of Th2 a bias towards allergic responses
bull To reduce allergic responses stimulate Th1
bull Infection with bacteria and viruses stimulates production of Th1
bull Infection with worms and helminths stimulate production of Th2
bull If babieskids donrsquot experience infection will they develop more allergies
VACCINES DO NOT CAUSE ALLERGIES
bull Vaccines do not prevent all diseases
bull Babies and kids still experience lots of infections
bull Large well-controlled epidemiologic studies do not support the hypothesis that vaccines cause allergies
bull ldquoHigher cumulative vaccine antigen doses were associated with less allergic sensitization allergic disease and less severe infant eczemardquo
Offit PA Hackett CJ Addressing Parentsrsquo Concerns Do Vaccines Cause Allergic or Autoimmune Diseases Pediatrics 2003111(3)653ndash9
CONCERN VS ACTUAL EFFECT
bull There are many valid questions and concerns about vaccines
bull For the most part we have the data to answer these questions
bull Donrsquot stop at the question Keep going to the answer
MECHANISMPATHWAY VS ACTUAL EFFECT
bull Many concerns about vaccines are based on biochemical pathways or mechanism
bull Donrsquot stop there Just because something is possible or even plausible doesnrsquot mean it actually happens that way
bull Look at the clinical data and the large body of literature
CONCERN VARICELLA VS ZOSTER
Question Does varicella immunization increase the risk of shingles in the unvaccinated population because of lack of immune stimulationviral suppression
Answer No zoster rates were going up before varicella program and were not affected by varicella immunization (Hales 2013) (Siedler 2014)
Plus varicella immunization seems to reduce the risk of shingles in immunized people (Baxter 2013)
SAFETY MONITORING
bull Pre-licensure trials including phase I II and III
bull Post-licensure studies and surveillance
bull Vaccine Safety Datalink (VSD)
bull Vaccine Adverse Event Reporting System (VAERS)
bull Clinical Immunization Safety Assessment (CISA) project ndash investigation into possible events in specific people certain populations excluded by pre-licensure studies
bull httpswwwhistoryofvaccinesorgcontentarticlesvaccine-development-testing-and-regulation
bull httpswwwcdcgovvaccinesbasicstest-approvehtml
SAFETY MONITORING VAERS
bull Vaccine Adverse Event Reporting System
bull ldquoSpontaneous (passive) surveillance means that no active effort is made to search for identify and collect information but rather information is passively received from those who choose to voluntarily report their experiencerdquo (Shimabukuro 2015)
bull Anyone can file any report
bull All reports are reviewed
bull ldquo[VAERS] reporting is incomplete requires follow-up investigation and cannot directly distinguish temporal associations from causal associations Consequently VAERS functions as a hypothesis-generating mechanism an early-warning signal of potential problems regarding vaccine safetyrdquo (Schwartz 2012)
Shimabukuro TT Nguyen M Martin D DeStefano F Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 201533(36)4398ndash405Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
SAFETY MONITORING VACCINE SAFETY DATALINK (VSD)
bull Includes multiple large HMOsMCOs covering 88 million people in 2011
bull Huge numbers allow for detection of rareserious events
bull Objectives of the Vaccine Safety Datalinkbull To conduct research on important vaccine safety questions in large populations
bull To conduct vaccine safety studies that come from questions or concerns in the medical literature or from other vaccine safety systems like VAERS
bull To monitor possible adverse events when new vaccines are licensed or when there are new vaccine recommendations
bull To provide information to committees who make recommendations for the nation
httpswwwcdcgovvaccinesafetyensuringsafetymonitoringvsdindexhtml
VACCINE SAFETY CASE ROTAVIRUS
bull In 1999 based on reports of 15 infants (of 15 million doses administered) experiencing intussusception after immunization with Rotashield the CDC recommended suspending use temporarily while investigation proceeded
bull Researchers found statistically significant differences in RotaShield vaccination rates between the two groups hellip Based on these results and estimates of the background rate of intussusception among US infants the research team estimated one additional case of intussusception attributable to the vaccine for every 4670 to 9474 infants vaccinated
bull Wyeth pulled the vaccine from the market when it was clear ACIP would vote against its use
Side bar Interesting moral questions about ldquoslamming the doorrdquo on a rotavirus vaccine that stood to save many lives internationally where the risk benefit ratio might be different (Schwartz 2012)
Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
VACCINE SAFETY CASE ROTAVIRUS
bull Rotateq (pentavalent) licensed in 2006
bull Rotarix (monovalent) licensed in 2008
bull Studies of the two new vaccines included 60000 to 70000 infants each in which no increased risk of intussusception was identified
VSD ROTAVIRUS (2014)
RESULTS
During the study period 207955 doses of monovalent rotavirus vaccine (including 115908 first doses and 92047 second doses) were administered in the VSD population We identified 6 cases of intussusception within 7 days after the administration of either dose of vaccine For the two doses combined the expected number of intussusception cases was 072 resulting in a significant relative risk of 84 For the pentavalent rotavirus vaccine 1301810 doses were administered duringthe study period with 8 observed intussusception cases (711 expected) for a nonsignificant relative risk of 11 The relativerisk of chart-confirmed intussusception within 7 days after monovalent rotavirus vaccination as compared with the risk after pentavalent rotavirus vaccination was 94 (95 confidence interval 14 to 1038) The attributable risk of intussusception after the administration of two doses of monovalent rotavirus vaccine was estimated to be 53 per 100000 infants vaccinated
Action
bull Rotavirus was pulled out of the multi-vaccine VIS
bull Rotavirus VIS was updated with specific information about the risks of rotavirus and clinical presentation
ROTAVIRUS WHY BOTHER
PRE-VACCINEbull Every year globally
bull 111 million episodes of gastroenteritis requiring only home care
bull 25 million outpatient medical visits
bull 2 million hospitalizations
bull 400000 deaths
POST-VACCINEbull A dramatic decrease (gt80) in the incidence of
severe rotavirus diarrhea has been reported in high-income countries
bull A decrease of about 50 has been reported in low-income settings
bull Reductions in diarrhea-associated deaths of 31 in infants younger than 1 year old and 42 in children younger than 5 years old in countries with low child mortality
OrsquoRyan M Rotavirus Vaccines a story of success with challenges ahead F1000 Research 20176 Parashar et al Global illness and deaths caused by rotavirus disease in children Emerg Infect Dis 2003 May9(5)565-72
EFFICACY CASE LAIV (FLUMIST)
bull ldquoIn light of low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013ndash14 and 2015ndash16 seasons for the 2016ndash17 season ACIP makes the interim recommendation that LAIV4 should not be usedrdquo
bull Even though it would cost the manufacturer as the ACIP recommendation drives usage and insurance coverage
Grohskopf LA Prevention and Control of Seasonal Influenza with Vaccines MMWR Recomm Rep 201665
WHO IS ACIP
bull The Advisory Committee on Immunization Practices ldquoincludes 15 voting members responsible for making vaccine recommendations The Secretary of the US Department of Health and Human Services (DHHS) selects these members following an application and nomination process Fourteen of the members have expertise in vaccinology immunology pediatrics internal medicine nursing family medicine virology public health infectious diseases andor preventive medicine one member is a consumer representative who provides perspectives on the social and community aspects of vaccination
bull In addition to the 15 voting members ACIP includes 8 ex officio members who represent other federal agencies with responsibility for immunization programs in the United States and 30 non-voting representatives of liaison organizations that bring related immunization expertiserdquo
httpswwwcdcgovvaccinesacipabouthtml
ACIP - SCHEDULE
bull How do vaccines get added Do vaccines ever get taken offbull Work group convene to work on one vaccine-preventable disease or group of diseases
bull Work group members collect and review data on disease epidemiology vaccine efficacy effectiveness safety feasibility of program implementation and economic aspects of immunization policy to include in written policy statements
bull Insurance companies and Medicaid generally pay for whatrsquos on the ACIP schedule so these recommendations have financial repercussions
bull Because immunity is not inherited we need to immunize each persongeneration until the disease is truly eradicated
bull ACIP meetings are open to the public and can be viewed by streaming webcast
bull If recommendations are accepted by the CDC they are published in the MMWR
httpswwwcdcgovvaccinesacipabouthtml
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
SIMPLE RASH
bull Measles complications in 40 of cases
bull Diarrhea
bull Middle ear infection
bull Bronchopneumonia
bull Encephalitis in 11000
bull Death in 21000 usually pneumonia or encephalitis
bull In developing countries up to 25 fatality rate
bull Subacute sclerosing panencephalitis (fatal) in 110000 or morebull Kids who get the measles before age 5 have a one in 1387 chance of developing SSPE (Wendorf et al 2016)
bull Kids who get the measles before age 1 have a one in 609 chance
VACCINErsquoS CONTINUED CONTRIBUTION
bull Measles remains a leading cause of vaccine-preventable infant mortality but progress is being made
bull From 2000-2016
bull Reported measles incidence decreased 87 from 145 to 19 cases per million persons
bull Annual estimated measles deaths decreased 84 (204 million deaths prevented)
MMWR Oct 27 2017 Vol 66 No 42
PROS AND CONS OF NATURAL INFECTION
bull Immunity from natural infection often lasts longer (though this is questionable)
bull But in order to get that immunity you need to experience the disease
bull Suffering
bull Transmission to others
bull Complications
bull Death
bull Long term complications of measles include
bull SSPE (fatal)
bull Immunosuppression increasing deaths from other infectious diseases
bull More severe COPD in smokers who experienced measles
IMMUNOSUPPRESSION
bull After measles infection immunologic memory is suppressed for 2-3 years which increases all-cause mortality
bull Measles BCG and polio immunization reduced all-cause mortality rate by roughly half
Mina MJ Measles immune suppression and vaccination direct and indirect nonspecific vaccine benefits J Infect 201774 Suppl 1S10ndash7
NON-SPECIFIC EFFECTS OF MEASLES AND OTHER VACCINES
1 Higgins JPT Soares-Weiser K Reingold A Systematic review of the non-specific effects of BCG DTP and measles containing vaccines httpwwwwhointimmunizationsagemeetings2014april (accessed 1 Jun 2014)
2 Strategic Advisory Group of Experts on Immunization Meeting of the Strategic Advisory Group of Experts on Immunization April 2014 - conclusions and recommendations Week Epidemiol Rec201489221ndash36 [PubMed]
3Aaby P Martins CL Garly ML et al Non-specific effects of standard measles vaccine at 45 and 9 months of age on childhood mortality randomised controlled trial BMJ 2010341c6495doi101136bmjc6495 [PMC free article] [PubMed]
4Aaby P Samb B Simondon F et al Non-specific beneficial effect of measles immunisation analysis of mortality studies from developing countries BMJ 1995311481ndash5 doi101136bmj3117003481[PMC free article] [PubMed]
5 Kristensen I Aaby P Jensen H Routine vaccinations and child survival follow up study in Guinea-Bissau West Africa BMJ 20003211435ndash8 doi101136bmj32172741435 [PMC free article] [PubMed]
6 Benn CS Netea MG Selin LK et alA small jabmdasha big effect non-specific immunomodulation by vaccinesTrends Immunol 201334431ndash9 doi101016jit201304004 [PubMed]
CONCERN TH1 VS TH2
bull Th1 cells decrease the production of IgE
bull Th2 cells increase the production of IgE
bull Babies are born with a predominance of Th2 a bias towards allergic responses
bull To reduce allergic responses stimulate Th1
bull Infection with bacteria and viruses stimulates production of Th1
bull Infection with worms and helminths stimulate production of Th2
bull If babieskids donrsquot experience infection will they develop more allergies
VACCINES DO NOT CAUSE ALLERGIES
bull Vaccines do not prevent all diseases
bull Babies and kids still experience lots of infections
bull Large well-controlled epidemiologic studies do not support the hypothesis that vaccines cause allergies
bull ldquoHigher cumulative vaccine antigen doses were associated with less allergic sensitization allergic disease and less severe infant eczemardquo
Offit PA Hackett CJ Addressing Parentsrsquo Concerns Do Vaccines Cause Allergic or Autoimmune Diseases Pediatrics 2003111(3)653ndash9
CONCERN VS ACTUAL EFFECT
bull There are many valid questions and concerns about vaccines
bull For the most part we have the data to answer these questions
bull Donrsquot stop at the question Keep going to the answer
MECHANISMPATHWAY VS ACTUAL EFFECT
bull Many concerns about vaccines are based on biochemical pathways or mechanism
bull Donrsquot stop there Just because something is possible or even plausible doesnrsquot mean it actually happens that way
bull Look at the clinical data and the large body of literature
CONCERN VARICELLA VS ZOSTER
Question Does varicella immunization increase the risk of shingles in the unvaccinated population because of lack of immune stimulationviral suppression
Answer No zoster rates were going up before varicella program and were not affected by varicella immunization (Hales 2013) (Siedler 2014)
Plus varicella immunization seems to reduce the risk of shingles in immunized people (Baxter 2013)
SAFETY MONITORING
bull Pre-licensure trials including phase I II and III
bull Post-licensure studies and surveillance
bull Vaccine Safety Datalink (VSD)
bull Vaccine Adverse Event Reporting System (VAERS)
bull Clinical Immunization Safety Assessment (CISA) project ndash investigation into possible events in specific people certain populations excluded by pre-licensure studies
bull httpswwwhistoryofvaccinesorgcontentarticlesvaccine-development-testing-and-regulation
bull httpswwwcdcgovvaccinesbasicstest-approvehtml
SAFETY MONITORING VAERS
bull Vaccine Adverse Event Reporting System
bull ldquoSpontaneous (passive) surveillance means that no active effort is made to search for identify and collect information but rather information is passively received from those who choose to voluntarily report their experiencerdquo (Shimabukuro 2015)
bull Anyone can file any report
bull All reports are reviewed
bull ldquo[VAERS] reporting is incomplete requires follow-up investigation and cannot directly distinguish temporal associations from causal associations Consequently VAERS functions as a hypothesis-generating mechanism an early-warning signal of potential problems regarding vaccine safetyrdquo (Schwartz 2012)
Shimabukuro TT Nguyen M Martin D DeStefano F Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 201533(36)4398ndash405Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
SAFETY MONITORING VACCINE SAFETY DATALINK (VSD)
bull Includes multiple large HMOsMCOs covering 88 million people in 2011
bull Huge numbers allow for detection of rareserious events
bull Objectives of the Vaccine Safety Datalinkbull To conduct research on important vaccine safety questions in large populations
bull To conduct vaccine safety studies that come from questions or concerns in the medical literature or from other vaccine safety systems like VAERS
bull To monitor possible adverse events when new vaccines are licensed or when there are new vaccine recommendations
bull To provide information to committees who make recommendations for the nation
httpswwwcdcgovvaccinesafetyensuringsafetymonitoringvsdindexhtml
VACCINE SAFETY CASE ROTAVIRUS
bull In 1999 based on reports of 15 infants (of 15 million doses administered) experiencing intussusception after immunization with Rotashield the CDC recommended suspending use temporarily while investigation proceeded
bull Researchers found statistically significant differences in RotaShield vaccination rates between the two groups hellip Based on these results and estimates of the background rate of intussusception among US infants the research team estimated one additional case of intussusception attributable to the vaccine for every 4670 to 9474 infants vaccinated
bull Wyeth pulled the vaccine from the market when it was clear ACIP would vote against its use
Side bar Interesting moral questions about ldquoslamming the doorrdquo on a rotavirus vaccine that stood to save many lives internationally where the risk benefit ratio might be different (Schwartz 2012)
Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
VACCINE SAFETY CASE ROTAVIRUS
bull Rotateq (pentavalent) licensed in 2006
bull Rotarix (monovalent) licensed in 2008
bull Studies of the two new vaccines included 60000 to 70000 infants each in which no increased risk of intussusception was identified
VSD ROTAVIRUS (2014)
RESULTS
During the study period 207955 doses of monovalent rotavirus vaccine (including 115908 first doses and 92047 second doses) were administered in the VSD population We identified 6 cases of intussusception within 7 days after the administration of either dose of vaccine For the two doses combined the expected number of intussusception cases was 072 resulting in a significant relative risk of 84 For the pentavalent rotavirus vaccine 1301810 doses were administered duringthe study period with 8 observed intussusception cases (711 expected) for a nonsignificant relative risk of 11 The relativerisk of chart-confirmed intussusception within 7 days after monovalent rotavirus vaccination as compared with the risk after pentavalent rotavirus vaccination was 94 (95 confidence interval 14 to 1038) The attributable risk of intussusception after the administration of two doses of monovalent rotavirus vaccine was estimated to be 53 per 100000 infants vaccinated
Action
bull Rotavirus was pulled out of the multi-vaccine VIS
bull Rotavirus VIS was updated with specific information about the risks of rotavirus and clinical presentation
ROTAVIRUS WHY BOTHER
PRE-VACCINEbull Every year globally
bull 111 million episodes of gastroenteritis requiring only home care
bull 25 million outpatient medical visits
bull 2 million hospitalizations
bull 400000 deaths
POST-VACCINEbull A dramatic decrease (gt80) in the incidence of
severe rotavirus diarrhea has been reported in high-income countries
bull A decrease of about 50 has been reported in low-income settings
bull Reductions in diarrhea-associated deaths of 31 in infants younger than 1 year old and 42 in children younger than 5 years old in countries with low child mortality
OrsquoRyan M Rotavirus Vaccines a story of success with challenges ahead F1000 Research 20176 Parashar et al Global illness and deaths caused by rotavirus disease in children Emerg Infect Dis 2003 May9(5)565-72
EFFICACY CASE LAIV (FLUMIST)
bull ldquoIn light of low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013ndash14 and 2015ndash16 seasons for the 2016ndash17 season ACIP makes the interim recommendation that LAIV4 should not be usedrdquo
bull Even though it would cost the manufacturer as the ACIP recommendation drives usage and insurance coverage
Grohskopf LA Prevention and Control of Seasonal Influenza with Vaccines MMWR Recomm Rep 201665
WHO IS ACIP
bull The Advisory Committee on Immunization Practices ldquoincludes 15 voting members responsible for making vaccine recommendations The Secretary of the US Department of Health and Human Services (DHHS) selects these members following an application and nomination process Fourteen of the members have expertise in vaccinology immunology pediatrics internal medicine nursing family medicine virology public health infectious diseases andor preventive medicine one member is a consumer representative who provides perspectives on the social and community aspects of vaccination
bull In addition to the 15 voting members ACIP includes 8 ex officio members who represent other federal agencies with responsibility for immunization programs in the United States and 30 non-voting representatives of liaison organizations that bring related immunization expertiserdquo
httpswwwcdcgovvaccinesacipabouthtml
ACIP - SCHEDULE
bull How do vaccines get added Do vaccines ever get taken offbull Work group convene to work on one vaccine-preventable disease or group of diseases
bull Work group members collect and review data on disease epidemiology vaccine efficacy effectiveness safety feasibility of program implementation and economic aspects of immunization policy to include in written policy statements
bull Insurance companies and Medicaid generally pay for whatrsquos on the ACIP schedule so these recommendations have financial repercussions
bull Because immunity is not inherited we need to immunize each persongeneration until the disease is truly eradicated
bull ACIP meetings are open to the public and can be viewed by streaming webcast
bull If recommendations are accepted by the CDC they are published in the MMWR
httpswwwcdcgovvaccinesacipabouthtml
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
VACCINErsquoS CONTINUED CONTRIBUTION
bull Measles remains a leading cause of vaccine-preventable infant mortality but progress is being made
bull From 2000-2016
bull Reported measles incidence decreased 87 from 145 to 19 cases per million persons
bull Annual estimated measles deaths decreased 84 (204 million deaths prevented)
MMWR Oct 27 2017 Vol 66 No 42
PROS AND CONS OF NATURAL INFECTION
bull Immunity from natural infection often lasts longer (though this is questionable)
bull But in order to get that immunity you need to experience the disease
bull Suffering
bull Transmission to others
bull Complications
bull Death
bull Long term complications of measles include
bull SSPE (fatal)
bull Immunosuppression increasing deaths from other infectious diseases
bull More severe COPD in smokers who experienced measles
IMMUNOSUPPRESSION
bull After measles infection immunologic memory is suppressed for 2-3 years which increases all-cause mortality
bull Measles BCG and polio immunization reduced all-cause mortality rate by roughly half
Mina MJ Measles immune suppression and vaccination direct and indirect nonspecific vaccine benefits J Infect 201774 Suppl 1S10ndash7
NON-SPECIFIC EFFECTS OF MEASLES AND OTHER VACCINES
1 Higgins JPT Soares-Weiser K Reingold A Systematic review of the non-specific effects of BCG DTP and measles containing vaccines httpwwwwhointimmunizationsagemeetings2014april (accessed 1 Jun 2014)
2 Strategic Advisory Group of Experts on Immunization Meeting of the Strategic Advisory Group of Experts on Immunization April 2014 - conclusions and recommendations Week Epidemiol Rec201489221ndash36 [PubMed]
3Aaby P Martins CL Garly ML et al Non-specific effects of standard measles vaccine at 45 and 9 months of age on childhood mortality randomised controlled trial BMJ 2010341c6495doi101136bmjc6495 [PMC free article] [PubMed]
4Aaby P Samb B Simondon F et al Non-specific beneficial effect of measles immunisation analysis of mortality studies from developing countries BMJ 1995311481ndash5 doi101136bmj3117003481[PMC free article] [PubMed]
5 Kristensen I Aaby P Jensen H Routine vaccinations and child survival follow up study in Guinea-Bissau West Africa BMJ 20003211435ndash8 doi101136bmj32172741435 [PMC free article] [PubMed]
6 Benn CS Netea MG Selin LK et alA small jabmdasha big effect non-specific immunomodulation by vaccinesTrends Immunol 201334431ndash9 doi101016jit201304004 [PubMed]
CONCERN TH1 VS TH2
bull Th1 cells decrease the production of IgE
bull Th2 cells increase the production of IgE
bull Babies are born with a predominance of Th2 a bias towards allergic responses
bull To reduce allergic responses stimulate Th1
bull Infection with bacteria and viruses stimulates production of Th1
bull Infection with worms and helminths stimulate production of Th2
bull If babieskids donrsquot experience infection will they develop more allergies
VACCINES DO NOT CAUSE ALLERGIES
bull Vaccines do not prevent all diseases
bull Babies and kids still experience lots of infections
bull Large well-controlled epidemiologic studies do not support the hypothesis that vaccines cause allergies
bull ldquoHigher cumulative vaccine antigen doses were associated with less allergic sensitization allergic disease and less severe infant eczemardquo
Offit PA Hackett CJ Addressing Parentsrsquo Concerns Do Vaccines Cause Allergic or Autoimmune Diseases Pediatrics 2003111(3)653ndash9
CONCERN VS ACTUAL EFFECT
bull There are many valid questions and concerns about vaccines
bull For the most part we have the data to answer these questions
bull Donrsquot stop at the question Keep going to the answer
MECHANISMPATHWAY VS ACTUAL EFFECT
bull Many concerns about vaccines are based on biochemical pathways or mechanism
bull Donrsquot stop there Just because something is possible or even plausible doesnrsquot mean it actually happens that way
bull Look at the clinical data and the large body of literature
CONCERN VARICELLA VS ZOSTER
Question Does varicella immunization increase the risk of shingles in the unvaccinated population because of lack of immune stimulationviral suppression
Answer No zoster rates were going up before varicella program and were not affected by varicella immunization (Hales 2013) (Siedler 2014)
Plus varicella immunization seems to reduce the risk of shingles in immunized people (Baxter 2013)
SAFETY MONITORING
bull Pre-licensure trials including phase I II and III
bull Post-licensure studies and surveillance
bull Vaccine Safety Datalink (VSD)
bull Vaccine Adverse Event Reporting System (VAERS)
bull Clinical Immunization Safety Assessment (CISA) project ndash investigation into possible events in specific people certain populations excluded by pre-licensure studies
bull httpswwwhistoryofvaccinesorgcontentarticlesvaccine-development-testing-and-regulation
bull httpswwwcdcgovvaccinesbasicstest-approvehtml
SAFETY MONITORING VAERS
bull Vaccine Adverse Event Reporting System
bull ldquoSpontaneous (passive) surveillance means that no active effort is made to search for identify and collect information but rather information is passively received from those who choose to voluntarily report their experiencerdquo (Shimabukuro 2015)
bull Anyone can file any report
bull All reports are reviewed
bull ldquo[VAERS] reporting is incomplete requires follow-up investigation and cannot directly distinguish temporal associations from causal associations Consequently VAERS functions as a hypothesis-generating mechanism an early-warning signal of potential problems regarding vaccine safetyrdquo (Schwartz 2012)
Shimabukuro TT Nguyen M Martin D DeStefano F Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 201533(36)4398ndash405Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
SAFETY MONITORING VACCINE SAFETY DATALINK (VSD)
bull Includes multiple large HMOsMCOs covering 88 million people in 2011
bull Huge numbers allow for detection of rareserious events
bull Objectives of the Vaccine Safety Datalinkbull To conduct research on important vaccine safety questions in large populations
bull To conduct vaccine safety studies that come from questions or concerns in the medical literature or from other vaccine safety systems like VAERS
bull To monitor possible adverse events when new vaccines are licensed or when there are new vaccine recommendations
bull To provide information to committees who make recommendations for the nation
httpswwwcdcgovvaccinesafetyensuringsafetymonitoringvsdindexhtml
VACCINE SAFETY CASE ROTAVIRUS
bull In 1999 based on reports of 15 infants (of 15 million doses administered) experiencing intussusception after immunization with Rotashield the CDC recommended suspending use temporarily while investigation proceeded
bull Researchers found statistically significant differences in RotaShield vaccination rates between the two groups hellip Based on these results and estimates of the background rate of intussusception among US infants the research team estimated one additional case of intussusception attributable to the vaccine for every 4670 to 9474 infants vaccinated
bull Wyeth pulled the vaccine from the market when it was clear ACIP would vote against its use
Side bar Interesting moral questions about ldquoslamming the doorrdquo on a rotavirus vaccine that stood to save many lives internationally where the risk benefit ratio might be different (Schwartz 2012)
Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
VACCINE SAFETY CASE ROTAVIRUS
bull Rotateq (pentavalent) licensed in 2006
bull Rotarix (monovalent) licensed in 2008
bull Studies of the two new vaccines included 60000 to 70000 infants each in which no increased risk of intussusception was identified
VSD ROTAVIRUS (2014)
RESULTS
During the study period 207955 doses of monovalent rotavirus vaccine (including 115908 first doses and 92047 second doses) were administered in the VSD population We identified 6 cases of intussusception within 7 days after the administration of either dose of vaccine For the two doses combined the expected number of intussusception cases was 072 resulting in a significant relative risk of 84 For the pentavalent rotavirus vaccine 1301810 doses were administered duringthe study period with 8 observed intussusception cases (711 expected) for a nonsignificant relative risk of 11 The relativerisk of chart-confirmed intussusception within 7 days after monovalent rotavirus vaccination as compared with the risk after pentavalent rotavirus vaccination was 94 (95 confidence interval 14 to 1038) The attributable risk of intussusception after the administration of two doses of monovalent rotavirus vaccine was estimated to be 53 per 100000 infants vaccinated
Action
bull Rotavirus was pulled out of the multi-vaccine VIS
bull Rotavirus VIS was updated with specific information about the risks of rotavirus and clinical presentation
ROTAVIRUS WHY BOTHER
PRE-VACCINEbull Every year globally
bull 111 million episodes of gastroenteritis requiring only home care
bull 25 million outpatient medical visits
bull 2 million hospitalizations
bull 400000 deaths
POST-VACCINEbull A dramatic decrease (gt80) in the incidence of
severe rotavirus diarrhea has been reported in high-income countries
bull A decrease of about 50 has been reported in low-income settings
bull Reductions in diarrhea-associated deaths of 31 in infants younger than 1 year old and 42 in children younger than 5 years old in countries with low child mortality
OrsquoRyan M Rotavirus Vaccines a story of success with challenges ahead F1000 Research 20176 Parashar et al Global illness and deaths caused by rotavirus disease in children Emerg Infect Dis 2003 May9(5)565-72
EFFICACY CASE LAIV (FLUMIST)
bull ldquoIn light of low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013ndash14 and 2015ndash16 seasons for the 2016ndash17 season ACIP makes the interim recommendation that LAIV4 should not be usedrdquo
bull Even though it would cost the manufacturer as the ACIP recommendation drives usage and insurance coverage
Grohskopf LA Prevention and Control of Seasonal Influenza with Vaccines MMWR Recomm Rep 201665
WHO IS ACIP
bull The Advisory Committee on Immunization Practices ldquoincludes 15 voting members responsible for making vaccine recommendations The Secretary of the US Department of Health and Human Services (DHHS) selects these members following an application and nomination process Fourteen of the members have expertise in vaccinology immunology pediatrics internal medicine nursing family medicine virology public health infectious diseases andor preventive medicine one member is a consumer representative who provides perspectives on the social and community aspects of vaccination
bull In addition to the 15 voting members ACIP includes 8 ex officio members who represent other federal agencies with responsibility for immunization programs in the United States and 30 non-voting representatives of liaison organizations that bring related immunization expertiserdquo
httpswwwcdcgovvaccinesacipabouthtml
ACIP - SCHEDULE
bull How do vaccines get added Do vaccines ever get taken offbull Work group convene to work on one vaccine-preventable disease or group of diseases
bull Work group members collect and review data on disease epidemiology vaccine efficacy effectiveness safety feasibility of program implementation and economic aspects of immunization policy to include in written policy statements
bull Insurance companies and Medicaid generally pay for whatrsquos on the ACIP schedule so these recommendations have financial repercussions
bull Because immunity is not inherited we need to immunize each persongeneration until the disease is truly eradicated
bull ACIP meetings are open to the public and can be viewed by streaming webcast
bull If recommendations are accepted by the CDC they are published in the MMWR
httpswwwcdcgovvaccinesacipabouthtml
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
PROS AND CONS OF NATURAL INFECTION
bull Immunity from natural infection often lasts longer (though this is questionable)
bull But in order to get that immunity you need to experience the disease
bull Suffering
bull Transmission to others
bull Complications
bull Death
bull Long term complications of measles include
bull SSPE (fatal)
bull Immunosuppression increasing deaths from other infectious diseases
bull More severe COPD in smokers who experienced measles
IMMUNOSUPPRESSION
bull After measles infection immunologic memory is suppressed for 2-3 years which increases all-cause mortality
bull Measles BCG and polio immunization reduced all-cause mortality rate by roughly half
Mina MJ Measles immune suppression and vaccination direct and indirect nonspecific vaccine benefits J Infect 201774 Suppl 1S10ndash7
NON-SPECIFIC EFFECTS OF MEASLES AND OTHER VACCINES
1 Higgins JPT Soares-Weiser K Reingold A Systematic review of the non-specific effects of BCG DTP and measles containing vaccines httpwwwwhointimmunizationsagemeetings2014april (accessed 1 Jun 2014)
2 Strategic Advisory Group of Experts on Immunization Meeting of the Strategic Advisory Group of Experts on Immunization April 2014 - conclusions and recommendations Week Epidemiol Rec201489221ndash36 [PubMed]
3Aaby P Martins CL Garly ML et al Non-specific effects of standard measles vaccine at 45 and 9 months of age on childhood mortality randomised controlled trial BMJ 2010341c6495doi101136bmjc6495 [PMC free article] [PubMed]
4Aaby P Samb B Simondon F et al Non-specific beneficial effect of measles immunisation analysis of mortality studies from developing countries BMJ 1995311481ndash5 doi101136bmj3117003481[PMC free article] [PubMed]
5 Kristensen I Aaby P Jensen H Routine vaccinations and child survival follow up study in Guinea-Bissau West Africa BMJ 20003211435ndash8 doi101136bmj32172741435 [PMC free article] [PubMed]
6 Benn CS Netea MG Selin LK et alA small jabmdasha big effect non-specific immunomodulation by vaccinesTrends Immunol 201334431ndash9 doi101016jit201304004 [PubMed]
CONCERN TH1 VS TH2
bull Th1 cells decrease the production of IgE
bull Th2 cells increase the production of IgE
bull Babies are born with a predominance of Th2 a bias towards allergic responses
bull To reduce allergic responses stimulate Th1
bull Infection with bacteria and viruses stimulates production of Th1
bull Infection with worms and helminths stimulate production of Th2
bull If babieskids donrsquot experience infection will they develop more allergies
VACCINES DO NOT CAUSE ALLERGIES
bull Vaccines do not prevent all diseases
bull Babies and kids still experience lots of infections
bull Large well-controlled epidemiologic studies do not support the hypothesis that vaccines cause allergies
bull ldquoHigher cumulative vaccine antigen doses were associated with less allergic sensitization allergic disease and less severe infant eczemardquo
Offit PA Hackett CJ Addressing Parentsrsquo Concerns Do Vaccines Cause Allergic or Autoimmune Diseases Pediatrics 2003111(3)653ndash9
CONCERN VS ACTUAL EFFECT
bull There are many valid questions and concerns about vaccines
bull For the most part we have the data to answer these questions
bull Donrsquot stop at the question Keep going to the answer
MECHANISMPATHWAY VS ACTUAL EFFECT
bull Many concerns about vaccines are based on biochemical pathways or mechanism
bull Donrsquot stop there Just because something is possible or even plausible doesnrsquot mean it actually happens that way
bull Look at the clinical data and the large body of literature
CONCERN VARICELLA VS ZOSTER
Question Does varicella immunization increase the risk of shingles in the unvaccinated population because of lack of immune stimulationviral suppression
Answer No zoster rates were going up before varicella program and were not affected by varicella immunization (Hales 2013) (Siedler 2014)
Plus varicella immunization seems to reduce the risk of shingles in immunized people (Baxter 2013)
SAFETY MONITORING
bull Pre-licensure trials including phase I II and III
bull Post-licensure studies and surveillance
bull Vaccine Safety Datalink (VSD)
bull Vaccine Adverse Event Reporting System (VAERS)
bull Clinical Immunization Safety Assessment (CISA) project ndash investigation into possible events in specific people certain populations excluded by pre-licensure studies
bull httpswwwhistoryofvaccinesorgcontentarticlesvaccine-development-testing-and-regulation
bull httpswwwcdcgovvaccinesbasicstest-approvehtml
SAFETY MONITORING VAERS
bull Vaccine Adverse Event Reporting System
bull ldquoSpontaneous (passive) surveillance means that no active effort is made to search for identify and collect information but rather information is passively received from those who choose to voluntarily report their experiencerdquo (Shimabukuro 2015)
bull Anyone can file any report
bull All reports are reviewed
bull ldquo[VAERS] reporting is incomplete requires follow-up investigation and cannot directly distinguish temporal associations from causal associations Consequently VAERS functions as a hypothesis-generating mechanism an early-warning signal of potential problems regarding vaccine safetyrdquo (Schwartz 2012)
Shimabukuro TT Nguyen M Martin D DeStefano F Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 201533(36)4398ndash405Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
SAFETY MONITORING VACCINE SAFETY DATALINK (VSD)
bull Includes multiple large HMOsMCOs covering 88 million people in 2011
bull Huge numbers allow for detection of rareserious events
bull Objectives of the Vaccine Safety Datalinkbull To conduct research on important vaccine safety questions in large populations
bull To conduct vaccine safety studies that come from questions or concerns in the medical literature or from other vaccine safety systems like VAERS
bull To monitor possible adverse events when new vaccines are licensed or when there are new vaccine recommendations
bull To provide information to committees who make recommendations for the nation
httpswwwcdcgovvaccinesafetyensuringsafetymonitoringvsdindexhtml
VACCINE SAFETY CASE ROTAVIRUS
bull In 1999 based on reports of 15 infants (of 15 million doses administered) experiencing intussusception after immunization with Rotashield the CDC recommended suspending use temporarily while investigation proceeded
bull Researchers found statistically significant differences in RotaShield vaccination rates between the two groups hellip Based on these results and estimates of the background rate of intussusception among US infants the research team estimated one additional case of intussusception attributable to the vaccine for every 4670 to 9474 infants vaccinated
bull Wyeth pulled the vaccine from the market when it was clear ACIP would vote against its use
Side bar Interesting moral questions about ldquoslamming the doorrdquo on a rotavirus vaccine that stood to save many lives internationally where the risk benefit ratio might be different (Schwartz 2012)
Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
VACCINE SAFETY CASE ROTAVIRUS
bull Rotateq (pentavalent) licensed in 2006
bull Rotarix (monovalent) licensed in 2008
bull Studies of the two new vaccines included 60000 to 70000 infants each in which no increased risk of intussusception was identified
VSD ROTAVIRUS (2014)
RESULTS
During the study period 207955 doses of monovalent rotavirus vaccine (including 115908 first doses and 92047 second doses) were administered in the VSD population We identified 6 cases of intussusception within 7 days after the administration of either dose of vaccine For the two doses combined the expected number of intussusception cases was 072 resulting in a significant relative risk of 84 For the pentavalent rotavirus vaccine 1301810 doses were administered duringthe study period with 8 observed intussusception cases (711 expected) for a nonsignificant relative risk of 11 The relativerisk of chart-confirmed intussusception within 7 days after monovalent rotavirus vaccination as compared with the risk after pentavalent rotavirus vaccination was 94 (95 confidence interval 14 to 1038) The attributable risk of intussusception after the administration of two doses of monovalent rotavirus vaccine was estimated to be 53 per 100000 infants vaccinated
Action
bull Rotavirus was pulled out of the multi-vaccine VIS
bull Rotavirus VIS was updated with specific information about the risks of rotavirus and clinical presentation
ROTAVIRUS WHY BOTHER
PRE-VACCINEbull Every year globally
bull 111 million episodes of gastroenteritis requiring only home care
bull 25 million outpatient medical visits
bull 2 million hospitalizations
bull 400000 deaths
POST-VACCINEbull A dramatic decrease (gt80) in the incidence of
severe rotavirus diarrhea has been reported in high-income countries
bull A decrease of about 50 has been reported in low-income settings
bull Reductions in diarrhea-associated deaths of 31 in infants younger than 1 year old and 42 in children younger than 5 years old in countries with low child mortality
OrsquoRyan M Rotavirus Vaccines a story of success with challenges ahead F1000 Research 20176 Parashar et al Global illness and deaths caused by rotavirus disease in children Emerg Infect Dis 2003 May9(5)565-72
EFFICACY CASE LAIV (FLUMIST)
bull ldquoIn light of low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013ndash14 and 2015ndash16 seasons for the 2016ndash17 season ACIP makes the interim recommendation that LAIV4 should not be usedrdquo
bull Even though it would cost the manufacturer as the ACIP recommendation drives usage and insurance coverage
Grohskopf LA Prevention and Control of Seasonal Influenza with Vaccines MMWR Recomm Rep 201665
WHO IS ACIP
bull The Advisory Committee on Immunization Practices ldquoincludes 15 voting members responsible for making vaccine recommendations The Secretary of the US Department of Health and Human Services (DHHS) selects these members following an application and nomination process Fourteen of the members have expertise in vaccinology immunology pediatrics internal medicine nursing family medicine virology public health infectious diseases andor preventive medicine one member is a consumer representative who provides perspectives on the social and community aspects of vaccination
bull In addition to the 15 voting members ACIP includes 8 ex officio members who represent other federal agencies with responsibility for immunization programs in the United States and 30 non-voting representatives of liaison organizations that bring related immunization expertiserdquo
httpswwwcdcgovvaccinesacipabouthtml
ACIP - SCHEDULE
bull How do vaccines get added Do vaccines ever get taken offbull Work group convene to work on one vaccine-preventable disease or group of diseases
bull Work group members collect and review data on disease epidemiology vaccine efficacy effectiveness safety feasibility of program implementation and economic aspects of immunization policy to include in written policy statements
bull Insurance companies and Medicaid generally pay for whatrsquos on the ACIP schedule so these recommendations have financial repercussions
bull Because immunity is not inherited we need to immunize each persongeneration until the disease is truly eradicated
bull ACIP meetings are open to the public and can be viewed by streaming webcast
bull If recommendations are accepted by the CDC they are published in the MMWR
httpswwwcdcgovvaccinesacipabouthtml
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
IMMUNOSUPPRESSION
bull After measles infection immunologic memory is suppressed for 2-3 years which increases all-cause mortality
bull Measles BCG and polio immunization reduced all-cause mortality rate by roughly half
Mina MJ Measles immune suppression and vaccination direct and indirect nonspecific vaccine benefits J Infect 201774 Suppl 1S10ndash7
NON-SPECIFIC EFFECTS OF MEASLES AND OTHER VACCINES
1 Higgins JPT Soares-Weiser K Reingold A Systematic review of the non-specific effects of BCG DTP and measles containing vaccines httpwwwwhointimmunizationsagemeetings2014april (accessed 1 Jun 2014)
2 Strategic Advisory Group of Experts on Immunization Meeting of the Strategic Advisory Group of Experts on Immunization April 2014 - conclusions and recommendations Week Epidemiol Rec201489221ndash36 [PubMed]
3Aaby P Martins CL Garly ML et al Non-specific effects of standard measles vaccine at 45 and 9 months of age on childhood mortality randomised controlled trial BMJ 2010341c6495doi101136bmjc6495 [PMC free article] [PubMed]
4Aaby P Samb B Simondon F et al Non-specific beneficial effect of measles immunisation analysis of mortality studies from developing countries BMJ 1995311481ndash5 doi101136bmj3117003481[PMC free article] [PubMed]
5 Kristensen I Aaby P Jensen H Routine vaccinations and child survival follow up study in Guinea-Bissau West Africa BMJ 20003211435ndash8 doi101136bmj32172741435 [PMC free article] [PubMed]
6 Benn CS Netea MG Selin LK et alA small jabmdasha big effect non-specific immunomodulation by vaccinesTrends Immunol 201334431ndash9 doi101016jit201304004 [PubMed]
CONCERN TH1 VS TH2
bull Th1 cells decrease the production of IgE
bull Th2 cells increase the production of IgE
bull Babies are born with a predominance of Th2 a bias towards allergic responses
bull To reduce allergic responses stimulate Th1
bull Infection with bacteria and viruses stimulates production of Th1
bull Infection with worms and helminths stimulate production of Th2
bull If babieskids donrsquot experience infection will they develop more allergies
VACCINES DO NOT CAUSE ALLERGIES
bull Vaccines do not prevent all diseases
bull Babies and kids still experience lots of infections
bull Large well-controlled epidemiologic studies do not support the hypothesis that vaccines cause allergies
bull ldquoHigher cumulative vaccine antigen doses were associated with less allergic sensitization allergic disease and less severe infant eczemardquo
Offit PA Hackett CJ Addressing Parentsrsquo Concerns Do Vaccines Cause Allergic or Autoimmune Diseases Pediatrics 2003111(3)653ndash9
CONCERN VS ACTUAL EFFECT
bull There are many valid questions and concerns about vaccines
bull For the most part we have the data to answer these questions
bull Donrsquot stop at the question Keep going to the answer
MECHANISMPATHWAY VS ACTUAL EFFECT
bull Many concerns about vaccines are based on biochemical pathways or mechanism
bull Donrsquot stop there Just because something is possible or even plausible doesnrsquot mean it actually happens that way
bull Look at the clinical data and the large body of literature
CONCERN VARICELLA VS ZOSTER
Question Does varicella immunization increase the risk of shingles in the unvaccinated population because of lack of immune stimulationviral suppression
Answer No zoster rates were going up before varicella program and were not affected by varicella immunization (Hales 2013) (Siedler 2014)
Plus varicella immunization seems to reduce the risk of shingles in immunized people (Baxter 2013)
SAFETY MONITORING
bull Pre-licensure trials including phase I II and III
bull Post-licensure studies and surveillance
bull Vaccine Safety Datalink (VSD)
bull Vaccine Adverse Event Reporting System (VAERS)
bull Clinical Immunization Safety Assessment (CISA) project ndash investigation into possible events in specific people certain populations excluded by pre-licensure studies
bull httpswwwhistoryofvaccinesorgcontentarticlesvaccine-development-testing-and-regulation
bull httpswwwcdcgovvaccinesbasicstest-approvehtml
SAFETY MONITORING VAERS
bull Vaccine Adverse Event Reporting System
bull ldquoSpontaneous (passive) surveillance means that no active effort is made to search for identify and collect information but rather information is passively received from those who choose to voluntarily report their experiencerdquo (Shimabukuro 2015)
bull Anyone can file any report
bull All reports are reviewed
bull ldquo[VAERS] reporting is incomplete requires follow-up investigation and cannot directly distinguish temporal associations from causal associations Consequently VAERS functions as a hypothesis-generating mechanism an early-warning signal of potential problems regarding vaccine safetyrdquo (Schwartz 2012)
Shimabukuro TT Nguyen M Martin D DeStefano F Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 201533(36)4398ndash405Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
SAFETY MONITORING VACCINE SAFETY DATALINK (VSD)
bull Includes multiple large HMOsMCOs covering 88 million people in 2011
bull Huge numbers allow for detection of rareserious events
bull Objectives of the Vaccine Safety Datalinkbull To conduct research on important vaccine safety questions in large populations
bull To conduct vaccine safety studies that come from questions or concerns in the medical literature or from other vaccine safety systems like VAERS
bull To monitor possible adverse events when new vaccines are licensed or when there are new vaccine recommendations
bull To provide information to committees who make recommendations for the nation
httpswwwcdcgovvaccinesafetyensuringsafetymonitoringvsdindexhtml
VACCINE SAFETY CASE ROTAVIRUS
bull In 1999 based on reports of 15 infants (of 15 million doses administered) experiencing intussusception after immunization with Rotashield the CDC recommended suspending use temporarily while investigation proceeded
bull Researchers found statistically significant differences in RotaShield vaccination rates between the two groups hellip Based on these results and estimates of the background rate of intussusception among US infants the research team estimated one additional case of intussusception attributable to the vaccine for every 4670 to 9474 infants vaccinated
bull Wyeth pulled the vaccine from the market when it was clear ACIP would vote against its use
Side bar Interesting moral questions about ldquoslamming the doorrdquo on a rotavirus vaccine that stood to save many lives internationally where the risk benefit ratio might be different (Schwartz 2012)
Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
VACCINE SAFETY CASE ROTAVIRUS
bull Rotateq (pentavalent) licensed in 2006
bull Rotarix (monovalent) licensed in 2008
bull Studies of the two new vaccines included 60000 to 70000 infants each in which no increased risk of intussusception was identified
VSD ROTAVIRUS (2014)
RESULTS
During the study period 207955 doses of monovalent rotavirus vaccine (including 115908 first doses and 92047 second doses) were administered in the VSD population We identified 6 cases of intussusception within 7 days after the administration of either dose of vaccine For the two doses combined the expected number of intussusception cases was 072 resulting in a significant relative risk of 84 For the pentavalent rotavirus vaccine 1301810 doses were administered duringthe study period with 8 observed intussusception cases (711 expected) for a nonsignificant relative risk of 11 The relativerisk of chart-confirmed intussusception within 7 days after monovalent rotavirus vaccination as compared with the risk after pentavalent rotavirus vaccination was 94 (95 confidence interval 14 to 1038) The attributable risk of intussusception after the administration of two doses of monovalent rotavirus vaccine was estimated to be 53 per 100000 infants vaccinated
Action
bull Rotavirus was pulled out of the multi-vaccine VIS
bull Rotavirus VIS was updated with specific information about the risks of rotavirus and clinical presentation
ROTAVIRUS WHY BOTHER
PRE-VACCINEbull Every year globally
bull 111 million episodes of gastroenteritis requiring only home care
bull 25 million outpatient medical visits
bull 2 million hospitalizations
bull 400000 deaths
POST-VACCINEbull A dramatic decrease (gt80) in the incidence of
severe rotavirus diarrhea has been reported in high-income countries
bull A decrease of about 50 has been reported in low-income settings
bull Reductions in diarrhea-associated deaths of 31 in infants younger than 1 year old and 42 in children younger than 5 years old in countries with low child mortality
OrsquoRyan M Rotavirus Vaccines a story of success with challenges ahead F1000 Research 20176 Parashar et al Global illness and deaths caused by rotavirus disease in children Emerg Infect Dis 2003 May9(5)565-72
EFFICACY CASE LAIV (FLUMIST)
bull ldquoIn light of low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013ndash14 and 2015ndash16 seasons for the 2016ndash17 season ACIP makes the interim recommendation that LAIV4 should not be usedrdquo
bull Even though it would cost the manufacturer as the ACIP recommendation drives usage and insurance coverage
Grohskopf LA Prevention and Control of Seasonal Influenza with Vaccines MMWR Recomm Rep 201665
WHO IS ACIP
bull The Advisory Committee on Immunization Practices ldquoincludes 15 voting members responsible for making vaccine recommendations The Secretary of the US Department of Health and Human Services (DHHS) selects these members following an application and nomination process Fourteen of the members have expertise in vaccinology immunology pediatrics internal medicine nursing family medicine virology public health infectious diseases andor preventive medicine one member is a consumer representative who provides perspectives on the social and community aspects of vaccination
bull In addition to the 15 voting members ACIP includes 8 ex officio members who represent other federal agencies with responsibility for immunization programs in the United States and 30 non-voting representatives of liaison organizations that bring related immunization expertiserdquo
httpswwwcdcgovvaccinesacipabouthtml
ACIP - SCHEDULE
bull How do vaccines get added Do vaccines ever get taken offbull Work group convene to work on one vaccine-preventable disease or group of diseases
bull Work group members collect and review data on disease epidemiology vaccine efficacy effectiveness safety feasibility of program implementation and economic aspects of immunization policy to include in written policy statements
bull Insurance companies and Medicaid generally pay for whatrsquos on the ACIP schedule so these recommendations have financial repercussions
bull Because immunity is not inherited we need to immunize each persongeneration until the disease is truly eradicated
bull ACIP meetings are open to the public and can be viewed by streaming webcast
bull If recommendations are accepted by the CDC they are published in the MMWR
httpswwwcdcgovvaccinesacipabouthtml
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
NON-SPECIFIC EFFECTS OF MEASLES AND OTHER VACCINES
1 Higgins JPT Soares-Weiser K Reingold A Systematic review of the non-specific effects of BCG DTP and measles containing vaccines httpwwwwhointimmunizationsagemeetings2014april (accessed 1 Jun 2014)
2 Strategic Advisory Group of Experts on Immunization Meeting of the Strategic Advisory Group of Experts on Immunization April 2014 - conclusions and recommendations Week Epidemiol Rec201489221ndash36 [PubMed]
3Aaby P Martins CL Garly ML et al Non-specific effects of standard measles vaccine at 45 and 9 months of age on childhood mortality randomised controlled trial BMJ 2010341c6495doi101136bmjc6495 [PMC free article] [PubMed]
4Aaby P Samb B Simondon F et al Non-specific beneficial effect of measles immunisation analysis of mortality studies from developing countries BMJ 1995311481ndash5 doi101136bmj3117003481[PMC free article] [PubMed]
5 Kristensen I Aaby P Jensen H Routine vaccinations and child survival follow up study in Guinea-Bissau West Africa BMJ 20003211435ndash8 doi101136bmj32172741435 [PMC free article] [PubMed]
6 Benn CS Netea MG Selin LK et alA small jabmdasha big effect non-specific immunomodulation by vaccinesTrends Immunol 201334431ndash9 doi101016jit201304004 [PubMed]
CONCERN TH1 VS TH2
bull Th1 cells decrease the production of IgE
bull Th2 cells increase the production of IgE
bull Babies are born with a predominance of Th2 a bias towards allergic responses
bull To reduce allergic responses stimulate Th1
bull Infection with bacteria and viruses stimulates production of Th1
bull Infection with worms and helminths stimulate production of Th2
bull If babieskids donrsquot experience infection will they develop more allergies
VACCINES DO NOT CAUSE ALLERGIES
bull Vaccines do not prevent all diseases
bull Babies and kids still experience lots of infections
bull Large well-controlled epidemiologic studies do not support the hypothesis that vaccines cause allergies
bull ldquoHigher cumulative vaccine antigen doses were associated with less allergic sensitization allergic disease and less severe infant eczemardquo
Offit PA Hackett CJ Addressing Parentsrsquo Concerns Do Vaccines Cause Allergic or Autoimmune Diseases Pediatrics 2003111(3)653ndash9
CONCERN VS ACTUAL EFFECT
bull There are many valid questions and concerns about vaccines
bull For the most part we have the data to answer these questions
bull Donrsquot stop at the question Keep going to the answer
MECHANISMPATHWAY VS ACTUAL EFFECT
bull Many concerns about vaccines are based on biochemical pathways or mechanism
bull Donrsquot stop there Just because something is possible or even plausible doesnrsquot mean it actually happens that way
bull Look at the clinical data and the large body of literature
CONCERN VARICELLA VS ZOSTER
Question Does varicella immunization increase the risk of shingles in the unvaccinated population because of lack of immune stimulationviral suppression
Answer No zoster rates were going up before varicella program and were not affected by varicella immunization (Hales 2013) (Siedler 2014)
Plus varicella immunization seems to reduce the risk of shingles in immunized people (Baxter 2013)
SAFETY MONITORING
bull Pre-licensure trials including phase I II and III
bull Post-licensure studies and surveillance
bull Vaccine Safety Datalink (VSD)
bull Vaccine Adverse Event Reporting System (VAERS)
bull Clinical Immunization Safety Assessment (CISA) project ndash investigation into possible events in specific people certain populations excluded by pre-licensure studies
bull httpswwwhistoryofvaccinesorgcontentarticlesvaccine-development-testing-and-regulation
bull httpswwwcdcgovvaccinesbasicstest-approvehtml
SAFETY MONITORING VAERS
bull Vaccine Adverse Event Reporting System
bull ldquoSpontaneous (passive) surveillance means that no active effort is made to search for identify and collect information but rather information is passively received from those who choose to voluntarily report their experiencerdquo (Shimabukuro 2015)
bull Anyone can file any report
bull All reports are reviewed
bull ldquo[VAERS] reporting is incomplete requires follow-up investigation and cannot directly distinguish temporal associations from causal associations Consequently VAERS functions as a hypothesis-generating mechanism an early-warning signal of potential problems regarding vaccine safetyrdquo (Schwartz 2012)
Shimabukuro TT Nguyen M Martin D DeStefano F Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 201533(36)4398ndash405Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
SAFETY MONITORING VACCINE SAFETY DATALINK (VSD)
bull Includes multiple large HMOsMCOs covering 88 million people in 2011
bull Huge numbers allow for detection of rareserious events
bull Objectives of the Vaccine Safety Datalinkbull To conduct research on important vaccine safety questions in large populations
bull To conduct vaccine safety studies that come from questions or concerns in the medical literature or from other vaccine safety systems like VAERS
bull To monitor possible adverse events when new vaccines are licensed or when there are new vaccine recommendations
bull To provide information to committees who make recommendations for the nation
httpswwwcdcgovvaccinesafetyensuringsafetymonitoringvsdindexhtml
VACCINE SAFETY CASE ROTAVIRUS
bull In 1999 based on reports of 15 infants (of 15 million doses administered) experiencing intussusception after immunization with Rotashield the CDC recommended suspending use temporarily while investigation proceeded
bull Researchers found statistically significant differences in RotaShield vaccination rates between the two groups hellip Based on these results and estimates of the background rate of intussusception among US infants the research team estimated one additional case of intussusception attributable to the vaccine for every 4670 to 9474 infants vaccinated
bull Wyeth pulled the vaccine from the market when it was clear ACIP would vote against its use
Side bar Interesting moral questions about ldquoslamming the doorrdquo on a rotavirus vaccine that stood to save many lives internationally where the risk benefit ratio might be different (Schwartz 2012)
Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
VACCINE SAFETY CASE ROTAVIRUS
bull Rotateq (pentavalent) licensed in 2006
bull Rotarix (monovalent) licensed in 2008
bull Studies of the two new vaccines included 60000 to 70000 infants each in which no increased risk of intussusception was identified
VSD ROTAVIRUS (2014)
RESULTS
During the study period 207955 doses of monovalent rotavirus vaccine (including 115908 first doses and 92047 second doses) were administered in the VSD population We identified 6 cases of intussusception within 7 days after the administration of either dose of vaccine For the two doses combined the expected number of intussusception cases was 072 resulting in a significant relative risk of 84 For the pentavalent rotavirus vaccine 1301810 doses were administered duringthe study period with 8 observed intussusception cases (711 expected) for a nonsignificant relative risk of 11 The relativerisk of chart-confirmed intussusception within 7 days after monovalent rotavirus vaccination as compared with the risk after pentavalent rotavirus vaccination was 94 (95 confidence interval 14 to 1038) The attributable risk of intussusception after the administration of two doses of monovalent rotavirus vaccine was estimated to be 53 per 100000 infants vaccinated
Action
bull Rotavirus was pulled out of the multi-vaccine VIS
bull Rotavirus VIS was updated with specific information about the risks of rotavirus and clinical presentation
ROTAVIRUS WHY BOTHER
PRE-VACCINEbull Every year globally
bull 111 million episodes of gastroenteritis requiring only home care
bull 25 million outpatient medical visits
bull 2 million hospitalizations
bull 400000 deaths
POST-VACCINEbull A dramatic decrease (gt80) in the incidence of
severe rotavirus diarrhea has been reported in high-income countries
bull A decrease of about 50 has been reported in low-income settings
bull Reductions in diarrhea-associated deaths of 31 in infants younger than 1 year old and 42 in children younger than 5 years old in countries with low child mortality
OrsquoRyan M Rotavirus Vaccines a story of success with challenges ahead F1000 Research 20176 Parashar et al Global illness and deaths caused by rotavirus disease in children Emerg Infect Dis 2003 May9(5)565-72
EFFICACY CASE LAIV (FLUMIST)
bull ldquoIn light of low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013ndash14 and 2015ndash16 seasons for the 2016ndash17 season ACIP makes the interim recommendation that LAIV4 should not be usedrdquo
bull Even though it would cost the manufacturer as the ACIP recommendation drives usage and insurance coverage
Grohskopf LA Prevention and Control of Seasonal Influenza with Vaccines MMWR Recomm Rep 201665
WHO IS ACIP
bull The Advisory Committee on Immunization Practices ldquoincludes 15 voting members responsible for making vaccine recommendations The Secretary of the US Department of Health and Human Services (DHHS) selects these members following an application and nomination process Fourteen of the members have expertise in vaccinology immunology pediatrics internal medicine nursing family medicine virology public health infectious diseases andor preventive medicine one member is a consumer representative who provides perspectives on the social and community aspects of vaccination
bull In addition to the 15 voting members ACIP includes 8 ex officio members who represent other federal agencies with responsibility for immunization programs in the United States and 30 non-voting representatives of liaison organizations that bring related immunization expertiserdquo
httpswwwcdcgovvaccinesacipabouthtml
ACIP - SCHEDULE
bull How do vaccines get added Do vaccines ever get taken offbull Work group convene to work on one vaccine-preventable disease or group of diseases
bull Work group members collect and review data on disease epidemiology vaccine efficacy effectiveness safety feasibility of program implementation and economic aspects of immunization policy to include in written policy statements
bull Insurance companies and Medicaid generally pay for whatrsquos on the ACIP schedule so these recommendations have financial repercussions
bull Because immunity is not inherited we need to immunize each persongeneration until the disease is truly eradicated
bull ACIP meetings are open to the public and can be viewed by streaming webcast
bull If recommendations are accepted by the CDC they are published in the MMWR
httpswwwcdcgovvaccinesacipabouthtml
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
CONCERN TH1 VS TH2
bull Th1 cells decrease the production of IgE
bull Th2 cells increase the production of IgE
bull Babies are born with a predominance of Th2 a bias towards allergic responses
bull To reduce allergic responses stimulate Th1
bull Infection with bacteria and viruses stimulates production of Th1
bull Infection with worms and helminths stimulate production of Th2
bull If babieskids donrsquot experience infection will they develop more allergies
VACCINES DO NOT CAUSE ALLERGIES
bull Vaccines do not prevent all diseases
bull Babies and kids still experience lots of infections
bull Large well-controlled epidemiologic studies do not support the hypothesis that vaccines cause allergies
bull ldquoHigher cumulative vaccine antigen doses were associated with less allergic sensitization allergic disease and less severe infant eczemardquo
Offit PA Hackett CJ Addressing Parentsrsquo Concerns Do Vaccines Cause Allergic or Autoimmune Diseases Pediatrics 2003111(3)653ndash9
CONCERN VS ACTUAL EFFECT
bull There are many valid questions and concerns about vaccines
bull For the most part we have the data to answer these questions
bull Donrsquot stop at the question Keep going to the answer
MECHANISMPATHWAY VS ACTUAL EFFECT
bull Many concerns about vaccines are based on biochemical pathways or mechanism
bull Donrsquot stop there Just because something is possible or even plausible doesnrsquot mean it actually happens that way
bull Look at the clinical data and the large body of literature
CONCERN VARICELLA VS ZOSTER
Question Does varicella immunization increase the risk of shingles in the unvaccinated population because of lack of immune stimulationviral suppression
Answer No zoster rates were going up before varicella program and were not affected by varicella immunization (Hales 2013) (Siedler 2014)
Plus varicella immunization seems to reduce the risk of shingles in immunized people (Baxter 2013)
SAFETY MONITORING
bull Pre-licensure trials including phase I II and III
bull Post-licensure studies and surveillance
bull Vaccine Safety Datalink (VSD)
bull Vaccine Adverse Event Reporting System (VAERS)
bull Clinical Immunization Safety Assessment (CISA) project ndash investigation into possible events in specific people certain populations excluded by pre-licensure studies
bull httpswwwhistoryofvaccinesorgcontentarticlesvaccine-development-testing-and-regulation
bull httpswwwcdcgovvaccinesbasicstest-approvehtml
SAFETY MONITORING VAERS
bull Vaccine Adverse Event Reporting System
bull ldquoSpontaneous (passive) surveillance means that no active effort is made to search for identify and collect information but rather information is passively received from those who choose to voluntarily report their experiencerdquo (Shimabukuro 2015)
bull Anyone can file any report
bull All reports are reviewed
bull ldquo[VAERS] reporting is incomplete requires follow-up investigation and cannot directly distinguish temporal associations from causal associations Consequently VAERS functions as a hypothesis-generating mechanism an early-warning signal of potential problems regarding vaccine safetyrdquo (Schwartz 2012)
Shimabukuro TT Nguyen M Martin D DeStefano F Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 201533(36)4398ndash405Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
SAFETY MONITORING VACCINE SAFETY DATALINK (VSD)
bull Includes multiple large HMOsMCOs covering 88 million people in 2011
bull Huge numbers allow for detection of rareserious events
bull Objectives of the Vaccine Safety Datalinkbull To conduct research on important vaccine safety questions in large populations
bull To conduct vaccine safety studies that come from questions or concerns in the medical literature or from other vaccine safety systems like VAERS
bull To monitor possible adverse events when new vaccines are licensed or when there are new vaccine recommendations
bull To provide information to committees who make recommendations for the nation
httpswwwcdcgovvaccinesafetyensuringsafetymonitoringvsdindexhtml
VACCINE SAFETY CASE ROTAVIRUS
bull In 1999 based on reports of 15 infants (of 15 million doses administered) experiencing intussusception after immunization with Rotashield the CDC recommended suspending use temporarily while investigation proceeded
bull Researchers found statistically significant differences in RotaShield vaccination rates between the two groups hellip Based on these results and estimates of the background rate of intussusception among US infants the research team estimated one additional case of intussusception attributable to the vaccine for every 4670 to 9474 infants vaccinated
bull Wyeth pulled the vaccine from the market when it was clear ACIP would vote against its use
Side bar Interesting moral questions about ldquoslamming the doorrdquo on a rotavirus vaccine that stood to save many lives internationally where the risk benefit ratio might be different (Schwartz 2012)
Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
VACCINE SAFETY CASE ROTAVIRUS
bull Rotateq (pentavalent) licensed in 2006
bull Rotarix (monovalent) licensed in 2008
bull Studies of the two new vaccines included 60000 to 70000 infants each in which no increased risk of intussusception was identified
VSD ROTAVIRUS (2014)
RESULTS
During the study period 207955 doses of monovalent rotavirus vaccine (including 115908 first doses and 92047 second doses) were administered in the VSD population We identified 6 cases of intussusception within 7 days after the administration of either dose of vaccine For the two doses combined the expected number of intussusception cases was 072 resulting in a significant relative risk of 84 For the pentavalent rotavirus vaccine 1301810 doses were administered duringthe study period with 8 observed intussusception cases (711 expected) for a nonsignificant relative risk of 11 The relativerisk of chart-confirmed intussusception within 7 days after monovalent rotavirus vaccination as compared with the risk after pentavalent rotavirus vaccination was 94 (95 confidence interval 14 to 1038) The attributable risk of intussusception after the administration of two doses of monovalent rotavirus vaccine was estimated to be 53 per 100000 infants vaccinated
Action
bull Rotavirus was pulled out of the multi-vaccine VIS
bull Rotavirus VIS was updated with specific information about the risks of rotavirus and clinical presentation
ROTAVIRUS WHY BOTHER
PRE-VACCINEbull Every year globally
bull 111 million episodes of gastroenteritis requiring only home care
bull 25 million outpatient medical visits
bull 2 million hospitalizations
bull 400000 deaths
POST-VACCINEbull A dramatic decrease (gt80) in the incidence of
severe rotavirus diarrhea has been reported in high-income countries
bull A decrease of about 50 has been reported in low-income settings
bull Reductions in diarrhea-associated deaths of 31 in infants younger than 1 year old and 42 in children younger than 5 years old in countries with low child mortality
OrsquoRyan M Rotavirus Vaccines a story of success with challenges ahead F1000 Research 20176 Parashar et al Global illness and deaths caused by rotavirus disease in children Emerg Infect Dis 2003 May9(5)565-72
EFFICACY CASE LAIV (FLUMIST)
bull ldquoIn light of low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013ndash14 and 2015ndash16 seasons for the 2016ndash17 season ACIP makes the interim recommendation that LAIV4 should not be usedrdquo
bull Even though it would cost the manufacturer as the ACIP recommendation drives usage and insurance coverage
Grohskopf LA Prevention and Control of Seasonal Influenza with Vaccines MMWR Recomm Rep 201665
WHO IS ACIP
bull The Advisory Committee on Immunization Practices ldquoincludes 15 voting members responsible for making vaccine recommendations The Secretary of the US Department of Health and Human Services (DHHS) selects these members following an application and nomination process Fourteen of the members have expertise in vaccinology immunology pediatrics internal medicine nursing family medicine virology public health infectious diseases andor preventive medicine one member is a consumer representative who provides perspectives on the social and community aspects of vaccination
bull In addition to the 15 voting members ACIP includes 8 ex officio members who represent other federal agencies with responsibility for immunization programs in the United States and 30 non-voting representatives of liaison organizations that bring related immunization expertiserdquo
httpswwwcdcgovvaccinesacipabouthtml
ACIP - SCHEDULE
bull How do vaccines get added Do vaccines ever get taken offbull Work group convene to work on one vaccine-preventable disease or group of diseases
bull Work group members collect and review data on disease epidemiology vaccine efficacy effectiveness safety feasibility of program implementation and economic aspects of immunization policy to include in written policy statements
bull Insurance companies and Medicaid generally pay for whatrsquos on the ACIP schedule so these recommendations have financial repercussions
bull Because immunity is not inherited we need to immunize each persongeneration until the disease is truly eradicated
bull ACIP meetings are open to the public and can be viewed by streaming webcast
bull If recommendations are accepted by the CDC they are published in the MMWR
httpswwwcdcgovvaccinesacipabouthtml
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
VACCINES DO NOT CAUSE ALLERGIES
bull Vaccines do not prevent all diseases
bull Babies and kids still experience lots of infections
bull Large well-controlled epidemiologic studies do not support the hypothesis that vaccines cause allergies
bull ldquoHigher cumulative vaccine antigen doses were associated with less allergic sensitization allergic disease and less severe infant eczemardquo
Offit PA Hackett CJ Addressing Parentsrsquo Concerns Do Vaccines Cause Allergic or Autoimmune Diseases Pediatrics 2003111(3)653ndash9
CONCERN VS ACTUAL EFFECT
bull There are many valid questions and concerns about vaccines
bull For the most part we have the data to answer these questions
bull Donrsquot stop at the question Keep going to the answer
MECHANISMPATHWAY VS ACTUAL EFFECT
bull Many concerns about vaccines are based on biochemical pathways or mechanism
bull Donrsquot stop there Just because something is possible or even plausible doesnrsquot mean it actually happens that way
bull Look at the clinical data and the large body of literature
CONCERN VARICELLA VS ZOSTER
Question Does varicella immunization increase the risk of shingles in the unvaccinated population because of lack of immune stimulationviral suppression
Answer No zoster rates were going up before varicella program and were not affected by varicella immunization (Hales 2013) (Siedler 2014)
Plus varicella immunization seems to reduce the risk of shingles in immunized people (Baxter 2013)
SAFETY MONITORING
bull Pre-licensure trials including phase I II and III
bull Post-licensure studies and surveillance
bull Vaccine Safety Datalink (VSD)
bull Vaccine Adverse Event Reporting System (VAERS)
bull Clinical Immunization Safety Assessment (CISA) project ndash investigation into possible events in specific people certain populations excluded by pre-licensure studies
bull httpswwwhistoryofvaccinesorgcontentarticlesvaccine-development-testing-and-regulation
bull httpswwwcdcgovvaccinesbasicstest-approvehtml
SAFETY MONITORING VAERS
bull Vaccine Adverse Event Reporting System
bull ldquoSpontaneous (passive) surveillance means that no active effort is made to search for identify and collect information but rather information is passively received from those who choose to voluntarily report their experiencerdquo (Shimabukuro 2015)
bull Anyone can file any report
bull All reports are reviewed
bull ldquo[VAERS] reporting is incomplete requires follow-up investigation and cannot directly distinguish temporal associations from causal associations Consequently VAERS functions as a hypothesis-generating mechanism an early-warning signal of potential problems regarding vaccine safetyrdquo (Schwartz 2012)
Shimabukuro TT Nguyen M Martin D DeStefano F Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 201533(36)4398ndash405Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
SAFETY MONITORING VACCINE SAFETY DATALINK (VSD)
bull Includes multiple large HMOsMCOs covering 88 million people in 2011
bull Huge numbers allow for detection of rareserious events
bull Objectives of the Vaccine Safety Datalinkbull To conduct research on important vaccine safety questions in large populations
bull To conduct vaccine safety studies that come from questions or concerns in the medical literature or from other vaccine safety systems like VAERS
bull To monitor possible adverse events when new vaccines are licensed or when there are new vaccine recommendations
bull To provide information to committees who make recommendations for the nation
httpswwwcdcgovvaccinesafetyensuringsafetymonitoringvsdindexhtml
VACCINE SAFETY CASE ROTAVIRUS
bull In 1999 based on reports of 15 infants (of 15 million doses administered) experiencing intussusception after immunization with Rotashield the CDC recommended suspending use temporarily while investigation proceeded
bull Researchers found statistically significant differences in RotaShield vaccination rates between the two groups hellip Based on these results and estimates of the background rate of intussusception among US infants the research team estimated one additional case of intussusception attributable to the vaccine for every 4670 to 9474 infants vaccinated
bull Wyeth pulled the vaccine from the market when it was clear ACIP would vote against its use
Side bar Interesting moral questions about ldquoslamming the doorrdquo on a rotavirus vaccine that stood to save many lives internationally where the risk benefit ratio might be different (Schwartz 2012)
Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
VACCINE SAFETY CASE ROTAVIRUS
bull Rotateq (pentavalent) licensed in 2006
bull Rotarix (monovalent) licensed in 2008
bull Studies of the two new vaccines included 60000 to 70000 infants each in which no increased risk of intussusception was identified
VSD ROTAVIRUS (2014)
RESULTS
During the study period 207955 doses of monovalent rotavirus vaccine (including 115908 first doses and 92047 second doses) were administered in the VSD population We identified 6 cases of intussusception within 7 days after the administration of either dose of vaccine For the two doses combined the expected number of intussusception cases was 072 resulting in a significant relative risk of 84 For the pentavalent rotavirus vaccine 1301810 doses were administered duringthe study period with 8 observed intussusception cases (711 expected) for a nonsignificant relative risk of 11 The relativerisk of chart-confirmed intussusception within 7 days after monovalent rotavirus vaccination as compared with the risk after pentavalent rotavirus vaccination was 94 (95 confidence interval 14 to 1038) The attributable risk of intussusception after the administration of two doses of monovalent rotavirus vaccine was estimated to be 53 per 100000 infants vaccinated
Action
bull Rotavirus was pulled out of the multi-vaccine VIS
bull Rotavirus VIS was updated with specific information about the risks of rotavirus and clinical presentation
ROTAVIRUS WHY BOTHER
PRE-VACCINEbull Every year globally
bull 111 million episodes of gastroenteritis requiring only home care
bull 25 million outpatient medical visits
bull 2 million hospitalizations
bull 400000 deaths
POST-VACCINEbull A dramatic decrease (gt80) in the incidence of
severe rotavirus diarrhea has been reported in high-income countries
bull A decrease of about 50 has been reported in low-income settings
bull Reductions in diarrhea-associated deaths of 31 in infants younger than 1 year old and 42 in children younger than 5 years old in countries with low child mortality
OrsquoRyan M Rotavirus Vaccines a story of success with challenges ahead F1000 Research 20176 Parashar et al Global illness and deaths caused by rotavirus disease in children Emerg Infect Dis 2003 May9(5)565-72
EFFICACY CASE LAIV (FLUMIST)
bull ldquoIn light of low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013ndash14 and 2015ndash16 seasons for the 2016ndash17 season ACIP makes the interim recommendation that LAIV4 should not be usedrdquo
bull Even though it would cost the manufacturer as the ACIP recommendation drives usage and insurance coverage
Grohskopf LA Prevention and Control of Seasonal Influenza with Vaccines MMWR Recomm Rep 201665
WHO IS ACIP
bull The Advisory Committee on Immunization Practices ldquoincludes 15 voting members responsible for making vaccine recommendations The Secretary of the US Department of Health and Human Services (DHHS) selects these members following an application and nomination process Fourteen of the members have expertise in vaccinology immunology pediatrics internal medicine nursing family medicine virology public health infectious diseases andor preventive medicine one member is a consumer representative who provides perspectives on the social and community aspects of vaccination
bull In addition to the 15 voting members ACIP includes 8 ex officio members who represent other federal agencies with responsibility for immunization programs in the United States and 30 non-voting representatives of liaison organizations that bring related immunization expertiserdquo
httpswwwcdcgovvaccinesacipabouthtml
ACIP - SCHEDULE
bull How do vaccines get added Do vaccines ever get taken offbull Work group convene to work on one vaccine-preventable disease or group of diseases
bull Work group members collect and review data on disease epidemiology vaccine efficacy effectiveness safety feasibility of program implementation and economic aspects of immunization policy to include in written policy statements
bull Insurance companies and Medicaid generally pay for whatrsquos on the ACIP schedule so these recommendations have financial repercussions
bull Because immunity is not inherited we need to immunize each persongeneration until the disease is truly eradicated
bull ACIP meetings are open to the public and can be viewed by streaming webcast
bull If recommendations are accepted by the CDC they are published in the MMWR
httpswwwcdcgovvaccinesacipabouthtml
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
CONCERN VS ACTUAL EFFECT
bull There are many valid questions and concerns about vaccines
bull For the most part we have the data to answer these questions
bull Donrsquot stop at the question Keep going to the answer
MECHANISMPATHWAY VS ACTUAL EFFECT
bull Many concerns about vaccines are based on biochemical pathways or mechanism
bull Donrsquot stop there Just because something is possible or even plausible doesnrsquot mean it actually happens that way
bull Look at the clinical data and the large body of literature
CONCERN VARICELLA VS ZOSTER
Question Does varicella immunization increase the risk of shingles in the unvaccinated population because of lack of immune stimulationviral suppression
Answer No zoster rates were going up before varicella program and were not affected by varicella immunization (Hales 2013) (Siedler 2014)
Plus varicella immunization seems to reduce the risk of shingles in immunized people (Baxter 2013)
SAFETY MONITORING
bull Pre-licensure trials including phase I II and III
bull Post-licensure studies and surveillance
bull Vaccine Safety Datalink (VSD)
bull Vaccine Adverse Event Reporting System (VAERS)
bull Clinical Immunization Safety Assessment (CISA) project ndash investigation into possible events in specific people certain populations excluded by pre-licensure studies
bull httpswwwhistoryofvaccinesorgcontentarticlesvaccine-development-testing-and-regulation
bull httpswwwcdcgovvaccinesbasicstest-approvehtml
SAFETY MONITORING VAERS
bull Vaccine Adverse Event Reporting System
bull ldquoSpontaneous (passive) surveillance means that no active effort is made to search for identify and collect information but rather information is passively received from those who choose to voluntarily report their experiencerdquo (Shimabukuro 2015)
bull Anyone can file any report
bull All reports are reviewed
bull ldquo[VAERS] reporting is incomplete requires follow-up investigation and cannot directly distinguish temporal associations from causal associations Consequently VAERS functions as a hypothesis-generating mechanism an early-warning signal of potential problems regarding vaccine safetyrdquo (Schwartz 2012)
Shimabukuro TT Nguyen M Martin D DeStefano F Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 201533(36)4398ndash405Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
SAFETY MONITORING VACCINE SAFETY DATALINK (VSD)
bull Includes multiple large HMOsMCOs covering 88 million people in 2011
bull Huge numbers allow for detection of rareserious events
bull Objectives of the Vaccine Safety Datalinkbull To conduct research on important vaccine safety questions in large populations
bull To conduct vaccine safety studies that come from questions or concerns in the medical literature or from other vaccine safety systems like VAERS
bull To monitor possible adverse events when new vaccines are licensed or when there are new vaccine recommendations
bull To provide information to committees who make recommendations for the nation
httpswwwcdcgovvaccinesafetyensuringsafetymonitoringvsdindexhtml
VACCINE SAFETY CASE ROTAVIRUS
bull In 1999 based on reports of 15 infants (of 15 million doses administered) experiencing intussusception after immunization with Rotashield the CDC recommended suspending use temporarily while investigation proceeded
bull Researchers found statistically significant differences in RotaShield vaccination rates between the two groups hellip Based on these results and estimates of the background rate of intussusception among US infants the research team estimated one additional case of intussusception attributable to the vaccine for every 4670 to 9474 infants vaccinated
bull Wyeth pulled the vaccine from the market when it was clear ACIP would vote against its use
Side bar Interesting moral questions about ldquoslamming the doorrdquo on a rotavirus vaccine that stood to save many lives internationally where the risk benefit ratio might be different (Schwartz 2012)
Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
VACCINE SAFETY CASE ROTAVIRUS
bull Rotateq (pentavalent) licensed in 2006
bull Rotarix (monovalent) licensed in 2008
bull Studies of the two new vaccines included 60000 to 70000 infants each in which no increased risk of intussusception was identified
VSD ROTAVIRUS (2014)
RESULTS
During the study period 207955 doses of monovalent rotavirus vaccine (including 115908 first doses and 92047 second doses) were administered in the VSD population We identified 6 cases of intussusception within 7 days after the administration of either dose of vaccine For the two doses combined the expected number of intussusception cases was 072 resulting in a significant relative risk of 84 For the pentavalent rotavirus vaccine 1301810 doses were administered duringthe study period with 8 observed intussusception cases (711 expected) for a nonsignificant relative risk of 11 The relativerisk of chart-confirmed intussusception within 7 days after monovalent rotavirus vaccination as compared with the risk after pentavalent rotavirus vaccination was 94 (95 confidence interval 14 to 1038) The attributable risk of intussusception after the administration of two doses of monovalent rotavirus vaccine was estimated to be 53 per 100000 infants vaccinated
Action
bull Rotavirus was pulled out of the multi-vaccine VIS
bull Rotavirus VIS was updated with specific information about the risks of rotavirus and clinical presentation
ROTAVIRUS WHY BOTHER
PRE-VACCINEbull Every year globally
bull 111 million episodes of gastroenteritis requiring only home care
bull 25 million outpatient medical visits
bull 2 million hospitalizations
bull 400000 deaths
POST-VACCINEbull A dramatic decrease (gt80) in the incidence of
severe rotavirus diarrhea has been reported in high-income countries
bull A decrease of about 50 has been reported in low-income settings
bull Reductions in diarrhea-associated deaths of 31 in infants younger than 1 year old and 42 in children younger than 5 years old in countries with low child mortality
OrsquoRyan M Rotavirus Vaccines a story of success with challenges ahead F1000 Research 20176 Parashar et al Global illness and deaths caused by rotavirus disease in children Emerg Infect Dis 2003 May9(5)565-72
EFFICACY CASE LAIV (FLUMIST)
bull ldquoIn light of low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013ndash14 and 2015ndash16 seasons for the 2016ndash17 season ACIP makes the interim recommendation that LAIV4 should not be usedrdquo
bull Even though it would cost the manufacturer as the ACIP recommendation drives usage and insurance coverage
Grohskopf LA Prevention and Control of Seasonal Influenza with Vaccines MMWR Recomm Rep 201665
WHO IS ACIP
bull The Advisory Committee on Immunization Practices ldquoincludes 15 voting members responsible for making vaccine recommendations The Secretary of the US Department of Health and Human Services (DHHS) selects these members following an application and nomination process Fourteen of the members have expertise in vaccinology immunology pediatrics internal medicine nursing family medicine virology public health infectious diseases andor preventive medicine one member is a consumer representative who provides perspectives on the social and community aspects of vaccination
bull In addition to the 15 voting members ACIP includes 8 ex officio members who represent other federal agencies with responsibility for immunization programs in the United States and 30 non-voting representatives of liaison organizations that bring related immunization expertiserdquo
httpswwwcdcgovvaccinesacipabouthtml
ACIP - SCHEDULE
bull How do vaccines get added Do vaccines ever get taken offbull Work group convene to work on one vaccine-preventable disease or group of diseases
bull Work group members collect and review data on disease epidemiology vaccine efficacy effectiveness safety feasibility of program implementation and economic aspects of immunization policy to include in written policy statements
bull Insurance companies and Medicaid generally pay for whatrsquos on the ACIP schedule so these recommendations have financial repercussions
bull Because immunity is not inherited we need to immunize each persongeneration until the disease is truly eradicated
bull ACIP meetings are open to the public and can be viewed by streaming webcast
bull If recommendations are accepted by the CDC they are published in the MMWR
httpswwwcdcgovvaccinesacipabouthtml
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
CONCERN VS ACTUAL EFFECT
bull There are many valid questions and concerns about vaccines
bull For the most part we have the data to answer these questions
bull Donrsquot stop at the question Keep going to the answer
MECHANISMPATHWAY VS ACTUAL EFFECT
bull Many concerns about vaccines are based on biochemical pathways or mechanism
bull Donrsquot stop there Just because something is possible or even plausible doesnrsquot mean it actually happens that way
bull Look at the clinical data and the large body of literature
CONCERN VARICELLA VS ZOSTER
Question Does varicella immunization increase the risk of shingles in the unvaccinated population because of lack of immune stimulationviral suppression
Answer No zoster rates were going up before varicella program and were not affected by varicella immunization (Hales 2013) (Siedler 2014)
Plus varicella immunization seems to reduce the risk of shingles in immunized people (Baxter 2013)
SAFETY MONITORING
bull Pre-licensure trials including phase I II and III
bull Post-licensure studies and surveillance
bull Vaccine Safety Datalink (VSD)
bull Vaccine Adverse Event Reporting System (VAERS)
bull Clinical Immunization Safety Assessment (CISA) project ndash investigation into possible events in specific people certain populations excluded by pre-licensure studies
bull httpswwwhistoryofvaccinesorgcontentarticlesvaccine-development-testing-and-regulation
bull httpswwwcdcgovvaccinesbasicstest-approvehtml
SAFETY MONITORING VAERS
bull Vaccine Adverse Event Reporting System
bull ldquoSpontaneous (passive) surveillance means that no active effort is made to search for identify and collect information but rather information is passively received from those who choose to voluntarily report their experiencerdquo (Shimabukuro 2015)
bull Anyone can file any report
bull All reports are reviewed
bull ldquo[VAERS] reporting is incomplete requires follow-up investigation and cannot directly distinguish temporal associations from causal associations Consequently VAERS functions as a hypothesis-generating mechanism an early-warning signal of potential problems regarding vaccine safetyrdquo (Schwartz 2012)
Shimabukuro TT Nguyen M Martin D DeStefano F Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 201533(36)4398ndash405Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
SAFETY MONITORING VACCINE SAFETY DATALINK (VSD)
bull Includes multiple large HMOsMCOs covering 88 million people in 2011
bull Huge numbers allow for detection of rareserious events
bull Objectives of the Vaccine Safety Datalinkbull To conduct research on important vaccine safety questions in large populations
bull To conduct vaccine safety studies that come from questions or concerns in the medical literature or from other vaccine safety systems like VAERS
bull To monitor possible adverse events when new vaccines are licensed or when there are new vaccine recommendations
bull To provide information to committees who make recommendations for the nation
httpswwwcdcgovvaccinesafetyensuringsafetymonitoringvsdindexhtml
VACCINE SAFETY CASE ROTAVIRUS
bull In 1999 based on reports of 15 infants (of 15 million doses administered) experiencing intussusception after immunization with Rotashield the CDC recommended suspending use temporarily while investigation proceeded
bull Researchers found statistically significant differences in RotaShield vaccination rates between the two groups hellip Based on these results and estimates of the background rate of intussusception among US infants the research team estimated one additional case of intussusception attributable to the vaccine for every 4670 to 9474 infants vaccinated
bull Wyeth pulled the vaccine from the market when it was clear ACIP would vote against its use
Side bar Interesting moral questions about ldquoslamming the doorrdquo on a rotavirus vaccine that stood to save many lives internationally where the risk benefit ratio might be different (Schwartz 2012)
Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
VACCINE SAFETY CASE ROTAVIRUS
bull Rotateq (pentavalent) licensed in 2006
bull Rotarix (monovalent) licensed in 2008
bull Studies of the two new vaccines included 60000 to 70000 infants each in which no increased risk of intussusception was identified
VSD ROTAVIRUS (2014)
RESULTS
During the study period 207955 doses of monovalent rotavirus vaccine (including 115908 first doses and 92047 second doses) were administered in the VSD population We identified 6 cases of intussusception within 7 days after the administration of either dose of vaccine For the two doses combined the expected number of intussusception cases was 072 resulting in a significant relative risk of 84 For the pentavalent rotavirus vaccine 1301810 doses were administered duringthe study period with 8 observed intussusception cases (711 expected) for a nonsignificant relative risk of 11 The relativerisk of chart-confirmed intussusception within 7 days after monovalent rotavirus vaccination as compared with the risk after pentavalent rotavirus vaccination was 94 (95 confidence interval 14 to 1038) The attributable risk of intussusception after the administration of two doses of monovalent rotavirus vaccine was estimated to be 53 per 100000 infants vaccinated
Action
bull Rotavirus was pulled out of the multi-vaccine VIS
bull Rotavirus VIS was updated with specific information about the risks of rotavirus and clinical presentation
ROTAVIRUS WHY BOTHER
PRE-VACCINEbull Every year globally
bull 111 million episodes of gastroenteritis requiring only home care
bull 25 million outpatient medical visits
bull 2 million hospitalizations
bull 400000 deaths
POST-VACCINEbull A dramatic decrease (gt80) in the incidence of
severe rotavirus diarrhea has been reported in high-income countries
bull A decrease of about 50 has been reported in low-income settings
bull Reductions in diarrhea-associated deaths of 31 in infants younger than 1 year old and 42 in children younger than 5 years old in countries with low child mortality
OrsquoRyan M Rotavirus Vaccines a story of success with challenges ahead F1000 Research 20176 Parashar et al Global illness and deaths caused by rotavirus disease in children Emerg Infect Dis 2003 May9(5)565-72
EFFICACY CASE LAIV (FLUMIST)
bull ldquoIn light of low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013ndash14 and 2015ndash16 seasons for the 2016ndash17 season ACIP makes the interim recommendation that LAIV4 should not be usedrdquo
bull Even though it would cost the manufacturer as the ACIP recommendation drives usage and insurance coverage
Grohskopf LA Prevention and Control of Seasonal Influenza with Vaccines MMWR Recomm Rep 201665
WHO IS ACIP
bull The Advisory Committee on Immunization Practices ldquoincludes 15 voting members responsible for making vaccine recommendations The Secretary of the US Department of Health and Human Services (DHHS) selects these members following an application and nomination process Fourteen of the members have expertise in vaccinology immunology pediatrics internal medicine nursing family medicine virology public health infectious diseases andor preventive medicine one member is a consumer representative who provides perspectives on the social and community aspects of vaccination
bull In addition to the 15 voting members ACIP includes 8 ex officio members who represent other federal agencies with responsibility for immunization programs in the United States and 30 non-voting representatives of liaison organizations that bring related immunization expertiserdquo
httpswwwcdcgovvaccinesacipabouthtml
ACIP - SCHEDULE
bull How do vaccines get added Do vaccines ever get taken offbull Work group convene to work on one vaccine-preventable disease or group of diseases
bull Work group members collect and review data on disease epidemiology vaccine efficacy effectiveness safety feasibility of program implementation and economic aspects of immunization policy to include in written policy statements
bull Insurance companies and Medicaid generally pay for whatrsquos on the ACIP schedule so these recommendations have financial repercussions
bull Because immunity is not inherited we need to immunize each persongeneration until the disease is truly eradicated
bull ACIP meetings are open to the public and can be viewed by streaming webcast
bull If recommendations are accepted by the CDC they are published in the MMWR
httpswwwcdcgovvaccinesacipabouthtml
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
MECHANISMPATHWAY VS ACTUAL EFFECT
bull Many concerns about vaccines are based on biochemical pathways or mechanism
bull Donrsquot stop there Just because something is possible or even plausible doesnrsquot mean it actually happens that way
bull Look at the clinical data and the large body of literature
CONCERN VARICELLA VS ZOSTER
Question Does varicella immunization increase the risk of shingles in the unvaccinated population because of lack of immune stimulationviral suppression
Answer No zoster rates were going up before varicella program and were not affected by varicella immunization (Hales 2013) (Siedler 2014)
Plus varicella immunization seems to reduce the risk of shingles in immunized people (Baxter 2013)
SAFETY MONITORING
bull Pre-licensure trials including phase I II and III
bull Post-licensure studies and surveillance
bull Vaccine Safety Datalink (VSD)
bull Vaccine Adverse Event Reporting System (VAERS)
bull Clinical Immunization Safety Assessment (CISA) project ndash investigation into possible events in specific people certain populations excluded by pre-licensure studies
bull httpswwwhistoryofvaccinesorgcontentarticlesvaccine-development-testing-and-regulation
bull httpswwwcdcgovvaccinesbasicstest-approvehtml
SAFETY MONITORING VAERS
bull Vaccine Adverse Event Reporting System
bull ldquoSpontaneous (passive) surveillance means that no active effort is made to search for identify and collect information but rather information is passively received from those who choose to voluntarily report their experiencerdquo (Shimabukuro 2015)
bull Anyone can file any report
bull All reports are reviewed
bull ldquo[VAERS] reporting is incomplete requires follow-up investigation and cannot directly distinguish temporal associations from causal associations Consequently VAERS functions as a hypothesis-generating mechanism an early-warning signal of potential problems regarding vaccine safetyrdquo (Schwartz 2012)
Shimabukuro TT Nguyen M Martin D DeStefano F Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 201533(36)4398ndash405Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
SAFETY MONITORING VACCINE SAFETY DATALINK (VSD)
bull Includes multiple large HMOsMCOs covering 88 million people in 2011
bull Huge numbers allow for detection of rareserious events
bull Objectives of the Vaccine Safety Datalinkbull To conduct research on important vaccine safety questions in large populations
bull To conduct vaccine safety studies that come from questions or concerns in the medical literature or from other vaccine safety systems like VAERS
bull To monitor possible adverse events when new vaccines are licensed or when there are new vaccine recommendations
bull To provide information to committees who make recommendations for the nation
httpswwwcdcgovvaccinesafetyensuringsafetymonitoringvsdindexhtml
VACCINE SAFETY CASE ROTAVIRUS
bull In 1999 based on reports of 15 infants (of 15 million doses administered) experiencing intussusception after immunization with Rotashield the CDC recommended suspending use temporarily while investigation proceeded
bull Researchers found statistically significant differences in RotaShield vaccination rates between the two groups hellip Based on these results and estimates of the background rate of intussusception among US infants the research team estimated one additional case of intussusception attributable to the vaccine for every 4670 to 9474 infants vaccinated
bull Wyeth pulled the vaccine from the market when it was clear ACIP would vote against its use
Side bar Interesting moral questions about ldquoslamming the doorrdquo on a rotavirus vaccine that stood to save many lives internationally where the risk benefit ratio might be different (Schwartz 2012)
Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
VACCINE SAFETY CASE ROTAVIRUS
bull Rotateq (pentavalent) licensed in 2006
bull Rotarix (monovalent) licensed in 2008
bull Studies of the two new vaccines included 60000 to 70000 infants each in which no increased risk of intussusception was identified
VSD ROTAVIRUS (2014)
RESULTS
During the study period 207955 doses of monovalent rotavirus vaccine (including 115908 first doses and 92047 second doses) were administered in the VSD population We identified 6 cases of intussusception within 7 days after the administration of either dose of vaccine For the two doses combined the expected number of intussusception cases was 072 resulting in a significant relative risk of 84 For the pentavalent rotavirus vaccine 1301810 doses were administered duringthe study period with 8 observed intussusception cases (711 expected) for a nonsignificant relative risk of 11 The relativerisk of chart-confirmed intussusception within 7 days after monovalent rotavirus vaccination as compared with the risk after pentavalent rotavirus vaccination was 94 (95 confidence interval 14 to 1038) The attributable risk of intussusception after the administration of two doses of monovalent rotavirus vaccine was estimated to be 53 per 100000 infants vaccinated
Action
bull Rotavirus was pulled out of the multi-vaccine VIS
bull Rotavirus VIS was updated with specific information about the risks of rotavirus and clinical presentation
ROTAVIRUS WHY BOTHER
PRE-VACCINEbull Every year globally
bull 111 million episodes of gastroenteritis requiring only home care
bull 25 million outpatient medical visits
bull 2 million hospitalizations
bull 400000 deaths
POST-VACCINEbull A dramatic decrease (gt80) in the incidence of
severe rotavirus diarrhea has been reported in high-income countries
bull A decrease of about 50 has been reported in low-income settings
bull Reductions in diarrhea-associated deaths of 31 in infants younger than 1 year old and 42 in children younger than 5 years old in countries with low child mortality
OrsquoRyan M Rotavirus Vaccines a story of success with challenges ahead F1000 Research 20176 Parashar et al Global illness and deaths caused by rotavirus disease in children Emerg Infect Dis 2003 May9(5)565-72
EFFICACY CASE LAIV (FLUMIST)
bull ldquoIn light of low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013ndash14 and 2015ndash16 seasons for the 2016ndash17 season ACIP makes the interim recommendation that LAIV4 should not be usedrdquo
bull Even though it would cost the manufacturer as the ACIP recommendation drives usage and insurance coverage
Grohskopf LA Prevention and Control of Seasonal Influenza with Vaccines MMWR Recomm Rep 201665
WHO IS ACIP
bull The Advisory Committee on Immunization Practices ldquoincludes 15 voting members responsible for making vaccine recommendations The Secretary of the US Department of Health and Human Services (DHHS) selects these members following an application and nomination process Fourteen of the members have expertise in vaccinology immunology pediatrics internal medicine nursing family medicine virology public health infectious diseases andor preventive medicine one member is a consumer representative who provides perspectives on the social and community aspects of vaccination
bull In addition to the 15 voting members ACIP includes 8 ex officio members who represent other federal agencies with responsibility for immunization programs in the United States and 30 non-voting representatives of liaison organizations that bring related immunization expertiserdquo
httpswwwcdcgovvaccinesacipabouthtml
ACIP - SCHEDULE
bull How do vaccines get added Do vaccines ever get taken offbull Work group convene to work on one vaccine-preventable disease or group of diseases
bull Work group members collect and review data on disease epidemiology vaccine efficacy effectiveness safety feasibility of program implementation and economic aspects of immunization policy to include in written policy statements
bull Insurance companies and Medicaid generally pay for whatrsquos on the ACIP schedule so these recommendations have financial repercussions
bull Because immunity is not inherited we need to immunize each persongeneration until the disease is truly eradicated
bull ACIP meetings are open to the public and can be viewed by streaming webcast
bull If recommendations are accepted by the CDC they are published in the MMWR
httpswwwcdcgovvaccinesacipabouthtml
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
CONCERN VARICELLA VS ZOSTER
Question Does varicella immunization increase the risk of shingles in the unvaccinated population because of lack of immune stimulationviral suppression
Answer No zoster rates were going up before varicella program and were not affected by varicella immunization (Hales 2013) (Siedler 2014)
Plus varicella immunization seems to reduce the risk of shingles in immunized people (Baxter 2013)
SAFETY MONITORING
bull Pre-licensure trials including phase I II and III
bull Post-licensure studies and surveillance
bull Vaccine Safety Datalink (VSD)
bull Vaccine Adverse Event Reporting System (VAERS)
bull Clinical Immunization Safety Assessment (CISA) project ndash investigation into possible events in specific people certain populations excluded by pre-licensure studies
bull httpswwwhistoryofvaccinesorgcontentarticlesvaccine-development-testing-and-regulation
bull httpswwwcdcgovvaccinesbasicstest-approvehtml
SAFETY MONITORING VAERS
bull Vaccine Adverse Event Reporting System
bull ldquoSpontaneous (passive) surveillance means that no active effort is made to search for identify and collect information but rather information is passively received from those who choose to voluntarily report their experiencerdquo (Shimabukuro 2015)
bull Anyone can file any report
bull All reports are reviewed
bull ldquo[VAERS] reporting is incomplete requires follow-up investigation and cannot directly distinguish temporal associations from causal associations Consequently VAERS functions as a hypothesis-generating mechanism an early-warning signal of potential problems regarding vaccine safetyrdquo (Schwartz 2012)
Shimabukuro TT Nguyen M Martin D DeStefano F Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 201533(36)4398ndash405Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
SAFETY MONITORING VACCINE SAFETY DATALINK (VSD)
bull Includes multiple large HMOsMCOs covering 88 million people in 2011
bull Huge numbers allow for detection of rareserious events
bull Objectives of the Vaccine Safety Datalinkbull To conduct research on important vaccine safety questions in large populations
bull To conduct vaccine safety studies that come from questions or concerns in the medical literature or from other vaccine safety systems like VAERS
bull To monitor possible adverse events when new vaccines are licensed or when there are new vaccine recommendations
bull To provide information to committees who make recommendations for the nation
httpswwwcdcgovvaccinesafetyensuringsafetymonitoringvsdindexhtml
VACCINE SAFETY CASE ROTAVIRUS
bull In 1999 based on reports of 15 infants (of 15 million doses administered) experiencing intussusception after immunization with Rotashield the CDC recommended suspending use temporarily while investigation proceeded
bull Researchers found statistically significant differences in RotaShield vaccination rates between the two groups hellip Based on these results and estimates of the background rate of intussusception among US infants the research team estimated one additional case of intussusception attributable to the vaccine for every 4670 to 9474 infants vaccinated
bull Wyeth pulled the vaccine from the market when it was clear ACIP would vote against its use
Side bar Interesting moral questions about ldquoslamming the doorrdquo on a rotavirus vaccine that stood to save many lives internationally where the risk benefit ratio might be different (Schwartz 2012)
Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
VACCINE SAFETY CASE ROTAVIRUS
bull Rotateq (pentavalent) licensed in 2006
bull Rotarix (monovalent) licensed in 2008
bull Studies of the two new vaccines included 60000 to 70000 infants each in which no increased risk of intussusception was identified
VSD ROTAVIRUS (2014)
RESULTS
During the study period 207955 doses of monovalent rotavirus vaccine (including 115908 first doses and 92047 second doses) were administered in the VSD population We identified 6 cases of intussusception within 7 days after the administration of either dose of vaccine For the two doses combined the expected number of intussusception cases was 072 resulting in a significant relative risk of 84 For the pentavalent rotavirus vaccine 1301810 doses were administered duringthe study period with 8 observed intussusception cases (711 expected) for a nonsignificant relative risk of 11 The relativerisk of chart-confirmed intussusception within 7 days after monovalent rotavirus vaccination as compared with the risk after pentavalent rotavirus vaccination was 94 (95 confidence interval 14 to 1038) The attributable risk of intussusception after the administration of two doses of monovalent rotavirus vaccine was estimated to be 53 per 100000 infants vaccinated
Action
bull Rotavirus was pulled out of the multi-vaccine VIS
bull Rotavirus VIS was updated with specific information about the risks of rotavirus and clinical presentation
ROTAVIRUS WHY BOTHER
PRE-VACCINEbull Every year globally
bull 111 million episodes of gastroenteritis requiring only home care
bull 25 million outpatient medical visits
bull 2 million hospitalizations
bull 400000 deaths
POST-VACCINEbull A dramatic decrease (gt80) in the incidence of
severe rotavirus diarrhea has been reported in high-income countries
bull A decrease of about 50 has been reported in low-income settings
bull Reductions in diarrhea-associated deaths of 31 in infants younger than 1 year old and 42 in children younger than 5 years old in countries with low child mortality
OrsquoRyan M Rotavirus Vaccines a story of success with challenges ahead F1000 Research 20176 Parashar et al Global illness and deaths caused by rotavirus disease in children Emerg Infect Dis 2003 May9(5)565-72
EFFICACY CASE LAIV (FLUMIST)
bull ldquoIn light of low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013ndash14 and 2015ndash16 seasons for the 2016ndash17 season ACIP makes the interim recommendation that LAIV4 should not be usedrdquo
bull Even though it would cost the manufacturer as the ACIP recommendation drives usage and insurance coverage
Grohskopf LA Prevention and Control of Seasonal Influenza with Vaccines MMWR Recomm Rep 201665
WHO IS ACIP
bull The Advisory Committee on Immunization Practices ldquoincludes 15 voting members responsible for making vaccine recommendations The Secretary of the US Department of Health and Human Services (DHHS) selects these members following an application and nomination process Fourteen of the members have expertise in vaccinology immunology pediatrics internal medicine nursing family medicine virology public health infectious diseases andor preventive medicine one member is a consumer representative who provides perspectives on the social and community aspects of vaccination
bull In addition to the 15 voting members ACIP includes 8 ex officio members who represent other federal agencies with responsibility for immunization programs in the United States and 30 non-voting representatives of liaison organizations that bring related immunization expertiserdquo
httpswwwcdcgovvaccinesacipabouthtml
ACIP - SCHEDULE
bull How do vaccines get added Do vaccines ever get taken offbull Work group convene to work on one vaccine-preventable disease or group of diseases
bull Work group members collect and review data on disease epidemiology vaccine efficacy effectiveness safety feasibility of program implementation and economic aspects of immunization policy to include in written policy statements
bull Insurance companies and Medicaid generally pay for whatrsquos on the ACIP schedule so these recommendations have financial repercussions
bull Because immunity is not inherited we need to immunize each persongeneration until the disease is truly eradicated
bull ACIP meetings are open to the public and can be viewed by streaming webcast
bull If recommendations are accepted by the CDC they are published in the MMWR
httpswwwcdcgovvaccinesacipabouthtml
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
SAFETY MONITORING
bull Pre-licensure trials including phase I II and III
bull Post-licensure studies and surveillance
bull Vaccine Safety Datalink (VSD)
bull Vaccine Adverse Event Reporting System (VAERS)
bull Clinical Immunization Safety Assessment (CISA) project ndash investigation into possible events in specific people certain populations excluded by pre-licensure studies
bull httpswwwhistoryofvaccinesorgcontentarticlesvaccine-development-testing-and-regulation
bull httpswwwcdcgovvaccinesbasicstest-approvehtml
SAFETY MONITORING VAERS
bull Vaccine Adverse Event Reporting System
bull ldquoSpontaneous (passive) surveillance means that no active effort is made to search for identify and collect information but rather information is passively received from those who choose to voluntarily report their experiencerdquo (Shimabukuro 2015)
bull Anyone can file any report
bull All reports are reviewed
bull ldquo[VAERS] reporting is incomplete requires follow-up investigation and cannot directly distinguish temporal associations from causal associations Consequently VAERS functions as a hypothesis-generating mechanism an early-warning signal of potential problems regarding vaccine safetyrdquo (Schwartz 2012)
Shimabukuro TT Nguyen M Martin D DeStefano F Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 201533(36)4398ndash405Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
SAFETY MONITORING VACCINE SAFETY DATALINK (VSD)
bull Includes multiple large HMOsMCOs covering 88 million people in 2011
bull Huge numbers allow for detection of rareserious events
bull Objectives of the Vaccine Safety Datalinkbull To conduct research on important vaccine safety questions in large populations
bull To conduct vaccine safety studies that come from questions or concerns in the medical literature or from other vaccine safety systems like VAERS
bull To monitor possible adverse events when new vaccines are licensed or when there are new vaccine recommendations
bull To provide information to committees who make recommendations for the nation
httpswwwcdcgovvaccinesafetyensuringsafetymonitoringvsdindexhtml
VACCINE SAFETY CASE ROTAVIRUS
bull In 1999 based on reports of 15 infants (of 15 million doses administered) experiencing intussusception after immunization with Rotashield the CDC recommended suspending use temporarily while investigation proceeded
bull Researchers found statistically significant differences in RotaShield vaccination rates between the two groups hellip Based on these results and estimates of the background rate of intussusception among US infants the research team estimated one additional case of intussusception attributable to the vaccine for every 4670 to 9474 infants vaccinated
bull Wyeth pulled the vaccine from the market when it was clear ACIP would vote against its use
Side bar Interesting moral questions about ldquoslamming the doorrdquo on a rotavirus vaccine that stood to save many lives internationally where the risk benefit ratio might be different (Schwartz 2012)
Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
VACCINE SAFETY CASE ROTAVIRUS
bull Rotateq (pentavalent) licensed in 2006
bull Rotarix (monovalent) licensed in 2008
bull Studies of the two new vaccines included 60000 to 70000 infants each in which no increased risk of intussusception was identified
VSD ROTAVIRUS (2014)
RESULTS
During the study period 207955 doses of monovalent rotavirus vaccine (including 115908 first doses and 92047 second doses) were administered in the VSD population We identified 6 cases of intussusception within 7 days after the administration of either dose of vaccine For the two doses combined the expected number of intussusception cases was 072 resulting in a significant relative risk of 84 For the pentavalent rotavirus vaccine 1301810 doses were administered duringthe study period with 8 observed intussusception cases (711 expected) for a nonsignificant relative risk of 11 The relativerisk of chart-confirmed intussusception within 7 days after monovalent rotavirus vaccination as compared with the risk after pentavalent rotavirus vaccination was 94 (95 confidence interval 14 to 1038) The attributable risk of intussusception after the administration of two doses of monovalent rotavirus vaccine was estimated to be 53 per 100000 infants vaccinated
Action
bull Rotavirus was pulled out of the multi-vaccine VIS
bull Rotavirus VIS was updated with specific information about the risks of rotavirus and clinical presentation
ROTAVIRUS WHY BOTHER
PRE-VACCINEbull Every year globally
bull 111 million episodes of gastroenteritis requiring only home care
bull 25 million outpatient medical visits
bull 2 million hospitalizations
bull 400000 deaths
POST-VACCINEbull A dramatic decrease (gt80) in the incidence of
severe rotavirus diarrhea has been reported in high-income countries
bull A decrease of about 50 has been reported in low-income settings
bull Reductions in diarrhea-associated deaths of 31 in infants younger than 1 year old and 42 in children younger than 5 years old in countries with low child mortality
OrsquoRyan M Rotavirus Vaccines a story of success with challenges ahead F1000 Research 20176 Parashar et al Global illness and deaths caused by rotavirus disease in children Emerg Infect Dis 2003 May9(5)565-72
EFFICACY CASE LAIV (FLUMIST)
bull ldquoIn light of low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013ndash14 and 2015ndash16 seasons for the 2016ndash17 season ACIP makes the interim recommendation that LAIV4 should not be usedrdquo
bull Even though it would cost the manufacturer as the ACIP recommendation drives usage and insurance coverage
Grohskopf LA Prevention and Control of Seasonal Influenza with Vaccines MMWR Recomm Rep 201665
WHO IS ACIP
bull The Advisory Committee on Immunization Practices ldquoincludes 15 voting members responsible for making vaccine recommendations The Secretary of the US Department of Health and Human Services (DHHS) selects these members following an application and nomination process Fourteen of the members have expertise in vaccinology immunology pediatrics internal medicine nursing family medicine virology public health infectious diseases andor preventive medicine one member is a consumer representative who provides perspectives on the social and community aspects of vaccination
bull In addition to the 15 voting members ACIP includes 8 ex officio members who represent other federal agencies with responsibility for immunization programs in the United States and 30 non-voting representatives of liaison organizations that bring related immunization expertiserdquo
httpswwwcdcgovvaccinesacipabouthtml
ACIP - SCHEDULE
bull How do vaccines get added Do vaccines ever get taken offbull Work group convene to work on one vaccine-preventable disease or group of diseases
bull Work group members collect and review data on disease epidemiology vaccine efficacy effectiveness safety feasibility of program implementation and economic aspects of immunization policy to include in written policy statements
bull Insurance companies and Medicaid generally pay for whatrsquos on the ACIP schedule so these recommendations have financial repercussions
bull Because immunity is not inherited we need to immunize each persongeneration until the disease is truly eradicated
bull ACIP meetings are open to the public and can be viewed by streaming webcast
bull If recommendations are accepted by the CDC they are published in the MMWR
httpswwwcdcgovvaccinesacipabouthtml
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
SAFETY MONITORING VAERS
bull Vaccine Adverse Event Reporting System
bull ldquoSpontaneous (passive) surveillance means that no active effort is made to search for identify and collect information but rather information is passively received from those who choose to voluntarily report their experiencerdquo (Shimabukuro 2015)
bull Anyone can file any report
bull All reports are reviewed
bull ldquo[VAERS] reporting is incomplete requires follow-up investigation and cannot directly distinguish temporal associations from causal associations Consequently VAERS functions as a hypothesis-generating mechanism an early-warning signal of potential problems regarding vaccine safetyrdquo (Schwartz 2012)
Shimabukuro TT Nguyen M Martin D DeStefano F Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 201533(36)4398ndash405Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
SAFETY MONITORING VACCINE SAFETY DATALINK (VSD)
bull Includes multiple large HMOsMCOs covering 88 million people in 2011
bull Huge numbers allow for detection of rareserious events
bull Objectives of the Vaccine Safety Datalinkbull To conduct research on important vaccine safety questions in large populations
bull To conduct vaccine safety studies that come from questions or concerns in the medical literature or from other vaccine safety systems like VAERS
bull To monitor possible adverse events when new vaccines are licensed or when there are new vaccine recommendations
bull To provide information to committees who make recommendations for the nation
httpswwwcdcgovvaccinesafetyensuringsafetymonitoringvsdindexhtml
VACCINE SAFETY CASE ROTAVIRUS
bull In 1999 based on reports of 15 infants (of 15 million doses administered) experiencing intussusception after immunization with Rotashield the CDC recommended suspending use temporarily while investigation proceeded
bull Researchers found statistically significant differences in RotaShield vaccination rates between the two groups hellip Based on these results and estimates of the background rate of intussusception among US infants the research team estimated one additional case of intussusception attributable to the vaccine for every 4670 to 9474 infants vaccinated
bull Wyeth pulled the vaccine from the market when it was clear ACIP would vote against its use
Side bar Interesting moral questions about ldquoslamming the doorrdquo on a rotavirus vaccine that stood to save many lives internationally where the risk benefit ratio might be different (Schwartz 2012)
Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
VACCINE SAFETY CASE ROTAVIRUS
bull Rotateq (pentavalent) licensed in 2006
bull Rotarix (monovalent) licensed in 2008
bull Studies of the two new vaccines included 60000 to 70000 infants each in which no increased risk of intussusception was identified
VSD ROTAVIRUS (2014)
RESULTS
During the study period 207955 doses of monovalent rotavirus vaccine (including 115908 first doses and 92047 second doses) were administered in the VSD population We identified 6 cases of intussusception within 7 days after the administration of either dose of vaccine For the two doses combined the expected number of intussusception cases was 072 resulting in a significant relative risk of 84 For the pentavalent rotavirus vaccine 1301810 doses were administered duringthe study period with 8 observed intussusception cases (711 expected) for a nonsignificant relative risk of 11 The relativerisk of chart-confirmed intussusception within 7 days after monovalent rotavirus vaccination as compared with the risk after pentavalent rotavirus vaccination was 94 (95 confidence interval 14 to 1038) The attributable risk of intussusception after the administration of two doses of monovalent rotavirus vaccine was estimated to be 53 per 100000 infants vaccinated
Action
bull Rotavirus was pulled out of the multi-vaccine VIS
bull Rotavirus VIS was updated with specific information about the risks of rotavirus and clinical presentation
ROTAVIRUS WHY BOTHER
PRE-VACCINEbull Every year globally
bull 111 million episodes of gastroenteritis requiring only home care
bull 25 million outpatient medical visits
bull 2 million hospitalizations
bull 400000 deaths
POST-VACCINEbull A dramatic decrease (gt80) in the incidence of
severe rotavirus diarrhea has been reported in high-income countries
bull A decrease of about 50 has been reported in low-income settings
bull Reductions in diarrhea-associated deaths of 31 in infants younger than 1 year old and 42 in children younger than 5 years old in countries with low child mortality
OrsquoRyan M Rotavirus Vaccines a story of success with challenges ahead F1000 Research 20176 Parashar et al Global illness and deaths caused by rotavirus disease in children Emerg Infect Dis 2003 May9(5)565-72
EFFICACY CASE LAIV (FLUMIST)
bull ldquoIn light of low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013ndash14 and 2015ndash16 seasons for the 2016ndash17 season ACIP makes the interim recommendation that LAIV4 should not be usedrdquo
bull Even though it would cost the manufacturer as the ACIP recommendation drives usage and insurance coverage
Grohskopf LA Prevention and Control of Seasonal Influenza with Vaccines MMWR Recomm Rep 201665
WHO IS ACIP
bull The Advisory Committee on Immunization Practices ldquoincludes 15 voting members responsible for making vaccine recommendations The Secretary of the US Department of Health and Human Services (DHHS) selects these members following an application and nomination process Fourteen of the members have expertise in vaccinology immunology pediatrics internal medicine nursing family medicine virology public health infectious diseases andor preventive medicine one member is a consumer representative who provides perspectives on the social and community aspects of vaccination
bull In addition to the 15 voting members ACIP includes 8 ex officio members who represent other federal agencies with responsibility for immunization programs in the United States and 30 non-voting representatives of liaison organizations that bring related immunization expertiserdquo
httpswwwcdcgovvaccinesacipabouthtml
ACIP - SCHEDULE
bull How do vaccines get added Do vaccines ever get taken offbull Work group convene to work on one vaccine-preventable disease or group of diseases
bull Work group members collect and review data on disease epidemiology vaccine efficacy effectiveness safety feasibility of program implementation and economic aspects of immunization policy to include in written policy statements
bull Insurance companies and Medicaid generally pay for whatrsquos on the ACIP schedule so these recommendations have financial repercussions
bull Because immunity is not inherited we need to immunize each persongeneration until the disease is truly eradicated
bull ACIP meetings are open to the public and can be viewed by streaming webcast
bull If recommendations are accepted by the CDC they are published in the MMWR
httpswwwcdcgovvaccinesacipabouthtml
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
SAFETY MONITORING VACCINE SAFETY DATALINK (VSD)
bull Includes multiple large HMOsMCOs covering 88 million people in 2011
bull Huge numbers allow for detection of rareserious events
bull Objectives of the Vaccine Safety Datalinkbull To conduct research on important vaccine safety questions in large populations
bull To conduct vaccine safety studies that come from questions or concerns in the medical literature or from other vaccine safety systems like VAERS
bull To monitor possible adverse events when new vaccines are licensed or when there are new vaccine recommendations
bull To provide information to committees who make recommendations for the nation
httpswwwcdcgovvaccinesafetyensuringsafetymonitoringvsdindexhtml
VACCINE SAFETY CASE ROTAVIRUS
bull In 1999 based on reports of 15 infants (of 15 million doses administered) experiencing intussusception after immunization with Rotashield the CDC recommended suspending use temporarily while investigation proceeded
bull Researchers found statistically significant differences in RotaShield vaccination rates between the two groups hellip Based on these results and estimates of the background rate of intussusception among US infants the research team estimated one additional case of intussusception attributable to the vaccine for every 4670 to 9474 infants vaccinated
bull Wyeth pulled the vaccine from the market when it was clear ACIP would vote against its use
Side bar Interesting moral questions about ldquoslamming the doorrdquo on a rotavirus vaccine that stood to save many lives internationally where the risk benefit ratio might be different (Schwartz 2012)
Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
VACCINE SAFETY CASE ROTAVIRUS
bull Rotateq (pentavalent) licensed in 2006
bull Rotarix (monovalent) licensed in 2008
bull Studies of the two new vaccines included 60000 to 70000 infants each in which no increased risk of intussusception was identified
VSD ROTAVIRUS (2014)
RESULTS
During the study period 207955 doses of monovalent rotavirus vaccine (including 115908 first doses and 92047 second doses) were administered in the VSD population We identified 6 cases of intussusception within 7 days after the administration of either dose of vaccine For the two doses combined the expected number of intussusception cases was 072 resulting in a significant relative risk of 84 For the pentavalent rotavirus vaccine 1301810 doses were administered duringthe study period with 8 observed intussusception cases (711 expected) for a nonsignificant relative risk of 11 The relativerisk of chart-confirmed intussusception within 7 days after monovalent rotavirus vaccination as compared with the risk after pentavalent rotavirus vaccination was 94 (95 confidence interval 14 to 1038) The attributable risk of intussusception after the administration of two doses of monovalent rotavirus vaccine was estimated to be 53 per 100000 infants vaccinated
Action
bull Rotavirus was pulled out of the multi-vaccine VIS
bull Rotavirus VIS was updated with specific information about the risks of rotavirus and clinical presentation
ROTAVIRUS WHY BOTHER
PRE-VACCINEbull Every year globally
bull 111 million episodes of gastroenteritis requiring only home care
bull 25 million outpatient medical visits
bull 2 million hospitalizations
bull 400000 deaths
POST-VACCINEbull A dramatic decrease (gt80) in the incidence of
severe rotavirus diarrhea has been reported in high-income countries
bull A decrease of about 50 has been reported in low-income settings
bull Reductions in diarrhea-associated deaths of 31 in infants younger than 1 year old and 42 in children younger than 5 years old in countries with low child mortality
OrsquoRyan M Rotavirus Vaccines a story of success with challenges ahead F1000 Research 20176 Parashar et al Global illness and deaths caused by rotavirus disease in children Emerg Infect Dis 2003 May9(5)565-72
EFFICACY CASE LAIV (FLUMIST)
bull ldquoIn light of low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013ndash14 and 2015ndash16 seasons for the 2016ndash17 season ACIP makes the interim recommendation that LAIV4 should not be usedrdquo
bull Even though it would cost the manufacturer as the ACIP recommendation drives usage and insurance coverage
Grohskopf LA Prevention and Control of Seasonal Influenza with Vaccines MMWR Recomm Rep 201665
WHO IS ACIP
bull The Advisory Committee on Immunization Practices ldquoincludes 15 voting members responsible for making vaccine recommendations The Secretary of the US Department of Health and Human Services (DHHS) selects these members following an application and nomination process Fourteen of the members have expertise in vaccinology immunology pediatrics internal medicine nursing family medicine virology public health infectious diseases andor preventive medicine one member is a consumer representative who provides perspectives on the social and community aspects of vaccination
bull In addition to the 15 voting members ACIP includes 8 ex officio members who represent other federal agencies with responsibility for immunization programs in the United States and 30 non-voting representatives of liaison organizations that bring related immunization expertiserdquo
httpswwwcdcgovvaccinesacipabouthtml
ACIP - SCHEDULE
bull How do vaccines get added Do vaccines ever get taken offbull Work group convene to work on one vaccine-preventable disease or group of diseases
bull Work group members collect and review data on disease epidemiology vaccine efficacy effectiveness safety feasibility of program implementation and economic aspects of immunization policy to include in written policy statements
bull Insurance companies and Medicaid generally pay for whatrsquos on the ACIP schedule so these recommendations have financial repercussions
bull Because immunity is not inherited we need to immunize each persongeneration until the disease is truly eradicated
bull ACIP meetings are open to the public and can be viewed by streaming webcast
bull If recommendations are accepted by the CDC they are published in the MMWR
httpswwwcdcgovvaccinesacipabouthtml
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
VACCINE SAFETY CASE ROTAVIRUS
bull In 1999 based on reports of 15 infants (of 15 million doses administered) experiencing intussusception after immunization with Rotashield the CDC recommended suspending use temporarily while investigation proceeded
bull Researchers found statistically significant differences in RotaShield vaccination rates between the two groups hellip Based on these results and estimates of the background rate of intussusception among US infants the research team estimated one additional case of intussusception attributable to the vaccine for every 4670 to 9474 infants vaccinated
bull Wyeth pulled the vaccine from the market when it was clear ACIP would vote against its use
Side bar Interesting moral questions about ldquoslamming the doorrdquo on a rotavirus vaccine that stood to save many lives internationally where the risk benefit ratio might be different (Schwartz 2012)
Schwartz JL The First Rotavirus Vaccine and the Politics of Acceptable Risk Milbank Q 201290(2)278ndash310
VACCINE SAFETY CASE ROTAVIRUS
bull Rotateq (pentavalent) licensed in 2006
bull Rotarix (monovalent) licensed in 2008
bull Studies of the two new vaccines included 60000 to 70000 infants each in which no increased risk of intussusception was identified
VSD ROTAVIRUS (2014)
RESULTS
During the study period 207955 doses of monovalent rotavirus vaccine (including 115908 first doses and 92047 second doses) were administered in the VSD population We identified 6 cases of intussusception within 7 days after the administration of either dose of vaccine For the two doses combined the expected number of intussusception cases was 072 resulting in a significant relative risk of 84 For the pentavalent rotavirus vaccine 1301810 doses were administered duringthe study period with 8 observed intussusception cases (711 expected) for a nonsignificant relative risk of 11 The relativerisk of chart-confirmed intussusception within 7 days after monovalent rotavirus vaccination as compared with the risk after pentavalent rotavirus vaccination was 94 (95 confidence interval 14 to 1038) The attributable risk of intussusception after the administration of two doses of monovalent rotavirus vaccine was estimated to be 53 per 100000 infants vaccinated
Action
bull Rotavirus was pulled out of the multi-vaccine VIS
bull Rotavirus VIS was updated with specific information about the risks of rotavirus and clinical presentation
ROTAVIRUS WHY BOTHER
PRE-VACCINEbull Every year globally
bull 111 million episodes of gastroenteritis requiring only home care
bull 25 million outpatient medical visits
bull 2 million hospitalizations
bull 400000 deaths
POST-VACCINEbull A dramatic decrease (gt80) in the incidence of
severe rotavirus diarrhea has been reported in high-income countries
bull A decrease of about 50 has been reported in low-income settings
bull Reductions in diarrhea-associated deaths of 31 in infants younger than 1 year old and 42 in children younger than 5 years old in countries with low child mortality
OrsquoRyan M Rotavirus Vaccines a story of success with challenges ahead F1000 Research 20176 Parashar et al Global illness and deaths caused by rotavirus disease in children Emerg Infect Dis 2003 May9(5)565-72
EFFICACY CASE LAIV (FLUMIST)
bull ldquoIn light of low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013ndash14 and 2015ndash16 seasons for the 2016ndash17 season ACIP makes the interim recommendation that LAIV4 should not be usedrdquo
bull Even though it would cost the manufacturer as the ACIP recommendation drives usage and insurance coverage
Grohskopf LA Prevention and Control of Seasonal Influenza with Vaccines MMWR Recomm Rep 201665
WHO IS ACIP
bull The Advisory Committee on Immunization Practices ldquoincludes 15 voting members responsible for making vaccine recommendations The Secretary of the US Department of Health and Human Services (DHHS) selects these members following an application and nomination process Fourteen of the members have expertise in vaccinology immunology pediatrics internal medicine nursing family medicine virology public health infectious diseases andor preventive medicine one member is a consumer representative who provides perspectives on the social and community aspects of vaccination
bull In addition to the 15 voting members ACIP includes 8 ex officio members who represent other federal agencies with responsibility for immunization programs in the United States and 30 non-voting representatives of liaison organizations that bring related immunization expertiserdquo
httpswwwcdcgovvaccinesacipabouthtml
ACIP - SCHEDULE
bull How do vaccines get added Do vaccines ever get taken offbull Work group convene to work on one vaccine-preventable disease or group of diseases
bull Work group members collect and review data on disease epidemiology vaccine efficacy effectiveness safety feasibility of program implementation and economic aspects of immunization policy to include in written policy statements
bull Insurance companies and Medicaid generally pay for whatrsquos on the ACIP schedule so these recommendations have financial repercussions
bull Because immunity is not inherited we need to immunize each persongeneration until the disease is truly eradicated
bull ACIP meetings are open to the public and can be viewed by streaming webcast
bull If recommendations are accepted by the CDC they are published in the MMWR
httpswwwcdcgovvaccinesacipabouthtml
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
VACCINE SAFETY CASE ROTAVIRUS
bull Rotateq (pentavalent) licensed in 2006
bull Rotarix (monovalent) licensed in 2008
bull Studies of the two new vaccines included 60000 to 70000 infants each in which no increased risk of intussusception was identified
VSD ROTAVIRUS (2014)
RESULTS
During the study period 207955 doses of monovalent rotavirus vaccine (including 115908 first doses and 92047 second doses) were administered in the VSD population We identified 6 cases of intussusception within 7 days after the administration of either dose of vaccine For the two doses combined the expected number of intussusception cases was 072 resulting in a significant relative risk of 84 For the pentavalent rotavirus vaccine 1301810 doses were administered duringthe study period with 8 observed intussusception cases (711 expected) for a nonsignificant relative risk of 11 The relativerisk of chart-confirmed intussusception within 7 days after monovalent rotavirus vaccination as compared with the risk after pentavalent rotavirus vaccination was 94 (95 confidence interval 14 to 1038) The attributable risk of intussusception after the administration of two doses of monovalent rotavirus vaccine was estimated to be 53 per 100000 infants vaccinated
Action
bull Rotavirus was pulled out of the multi-vaccine VIS
bull Rotavirus VIS was updated with specific information about the risks of rotavirus and clinical presentation
ROTAVIRUS WHY BOTHER
PRE-VACCINEbull Every year globally
bull 111 million episodes of gastroenteritis requiring only home care
bull 25 million outpatient medical visits
bull 2 million hospitalizations
bull 400000 deaths
POST-VACCINEbull A dramatic decrease (gt80) in the incidence of
severe rotavirus diarrhea has been reported in high-income countries
bull A decrease of about 50 has been reported in low-income settings
bull Reductions in diarrhea-associated deaths of 31 in infants younger than 1 year old and 42 in children younger than 5 years old in countries with low child mortality
OrsquoRyan M Rotavirus Vaccines a story of success with challenges ahead F1000 Research 20176 Parashar et al Global illness and deaths caused by rotavirus disease in children Emerg Infect Dis 2003 May9(5)565-72
EFFICACY CASE LAIV (FLUMIST)
bull ldquoIn light of low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013ndash14 and 2015ndash16 seasons for the 2016ndash17 season ACIP makes the interim recommendation that LAIV4 should not be usedrdquo
bull Even though it would cost the manufacturer as the ACIP recommendation drives usage and insurance coverage
Grohskopf LA Prevention and Control of Seasonal Influenza with Vaccines MMWR Recomm Rep 201665
WHO IS ACIP
bull The Advisory Committee on Immunization Practices ldquoincludes 15 voting members responsible for making vaccine recommendations The Secretary of the US Department of Health and Human Services (DHHS) selects these members following an application and nomination process Fourteen of the members have expertise in vaccinology immunology pediatrics internal medicine nursing family medicine virology public health infectious diseases andor preventive medicine one member is a consumer representative who provides perspectives on the social and community aspects of vaccination
bull In addition to the 15 voting members ACIP includes 8 ex officio members who represent other federal agencies with responsibility for immunization programs in the United States and 30 non-voting representatives of liaison organizations that bring related immunization expertiserdquo
httpswwwcdcgovvaccinesacipabouthtml
ACIP - SCHEDULE
bull How do vaccines get added Do vaccines ever get taken offbull Work group convene to work on one vaccine-preventable disease or group of diseases
bull Work group members collect and review data on disease epidemiology vaccine efficacy effectiveness safety feasibility of program implementation and economic aspects of immunization policy to include in written policy statements
bull Insurance companies and Medicaid generally pay for whatrsquos on the ACIP schedule so these recommendations have financial repercussions
bull Because immunity is not inherited we need to immunize each persongeneration until the disease is truly eradicated
bull ACIP meetings are open to the public and can be viewed by streaming webcast
bull If recommendations are accepted by the CDC they are published in the MMWR
httpswwwcdcgovvaccinesacipabouthtml
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
VSD ROTAVIRUS (2014)
RESULTS
During the study period 207955 doses of monovalent rotavirus vaccine (including 115908 first doses and 92047 second doses) were administered in the VSD population We identified 6 cases of intussusception within 7 days after the administration of either dose of vaccine For the two doses combined the expected number of intussusception cases was 072 resulting in a significant relative risk of 84 For the pentavalent rotavirus vaccine 1301810 doses were administered duringthe study period with 8 observed intussusception cases (711 expected) for a nonsignificant relative risk of 11 The relativerisk of chart-confirmed intussusception within 7 days after monovalent rotavirus vaccination as compared with the risk after pentavalent rotavirus vaccination was 94 (95 confidence interval 14 to 1038) The attributable risk of intussusception after the administration of two doses of monovalent rotavirus vaccine was estimated to be 53 per 100000 infants vaccinated
Action
bull Rotavirus was pulled out of the multi-vaccine VIS
bull Rotavirus VIS was updated with specific information about the risks of rotavirus and clinical presentation
ROTAVIRUS WHY BOTHER
PRE-VACCINEbull Every year globally
bull 111 million episodes of gastroenteritis requiring only home care
bull 25 million outpatient medical visits
bull 2 million hospitalizations
bull 400000 deaths
POST-VACCINEbull A dramatic decrease (gt80) in the incidence of
severe rotavirus diarrhea has been reported in high-income countries
bull A decrease of about 50 has been reported in low-income settings
bull Reductions in diarrhea-associated deaths of 31 in infants younger than 1 year old and 42 in children younger than 5 years old in countries with low child mortality
OrsquoRyan M Rotavirus Vaccines a story of success with challenges ahead F1000 Research 20176 Parashar et al Global illness and deaths caused by rotavirus disease in children Emerg Infect Dis 2003 May9(5)565-72
EFFICACY CASE LAIV (FLUMIST)
bull ldquoIn light of low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013ndash14 and 2015ndash16 seasons for the 2016ndash17 season ACIP makes the interim recommendation that LAIV4 should not be usedrdquo
bull Even though it would cost the manufacturer as the ACIP recommendation drives usage and insurance coverage
Grohskopf LA Prevention and Control of Seasonal Influenza with Vaccines MMWR Recomm Rep 201665
WHO IS ACIP
bull The Advisory Committee on Immunization Practices ldquoincludes 15 voting members responsible for making vaccine recommendations The Secretary of the US Department of Health and Human Services (DHHS) selects these members following an application and nomination process Fourteen of the members have expertise in vaccinology immunology pediatrics internal medicine nursing family medicine virology public health infectious diseases andor preventive medicine one member is a consumer representative who provides perspectives on the social and community aspects of vaccination
bull In addition to the 15 voting members ACIP includes 8 ex officio members who represent other federal agencies with responsibility for immunization programs in the United States and 30 non-voting representatives of liaison organizations that bring related immunization expertiserdquo
httpswwwcdcgovvaccinesacipabouthtml
ACIP - SCHEDULE
bull How do vaccines get added Do vaccines ever get taken offbull Work group convene to work on one vaccine-preventable disease or group of diseases
bull Work group members collect and review data on disease epidemiology vaccine efficacy effectiveness safety feasibility of program implementation and economic aspects of immunization policy to include in written policy statements
bull Insurance companies and Medicaid generally pay for whatrsquos on the ACIP schedule so these recommendations have financial repercussions
bull Because immunity is not inherited we need to immunize each persongeneration until the disease is truly eradicated
bull ACIP meetings are open to the public and can be viewed by streaming webcast
bull If recommendations are accepted by the CDC they are published in the MMWR
httpswwwcdcgovvaccinesacipabouthtml
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
ROTAVIRUS WHY BOTHER
PRE-VACCINEbull Every year globally
bull 111 million episodes of gastroenteritis requiring only home care
bull 25 million outpatient medical visits
bull 2 million hospitalizations
bull 400000 deaths
POST-VACCINEbull A dramatic decrease (gt80) in the incidence of
severe rotavirus diarrhea has been reported in high-income countries
bull A decrease of about 50 has been reported in low-income settings
bull Reductions in diarrhea-associated deaths of 31 in infants younger than 1 year old and 42 in children younger than 5 years old in countries with low child mortality
OrsquoRyan M Rotavirus Vaccines a story of success with challenges ahead F1000 Research 20176 Parashar et al Global illness and deaths caused by rotavirus disease in children Emerg Infect Dis 2003 May9(5)565-72
EFFICACY CASE LAIV (FLUMIST)
bull ldquoIn light of low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013ndash14 and 2015ndash16 seasons for the 2016ndash17 season ACIP makes the interim recommendation that LAIV4 should not be usedrdquo
bull Even though it would cost the manufacturer as the ACIP recommendation drives usage and insurance coverage
Grohskopf LA Prevention and Control of Seasonal Influenza with Vaccines MMWR Recomm Rep 201665
WHO IS ACIP
bull The Advisory Committee on Immunization Practices ldquoincludes 15 voting members responsible for making vaccine recommendations The Secretary of the US Department of Health and Human Services (DHHS) selects these members following an application and nomination process Fourteen of the members have expertise in vaccinology immunology pediatrics internal medicine nursing family medicine virology public health infectious diseases andor preventive medicine one member is a consumer representative who provides perspectives on the social and community aspects of vaccination
bull In addition to the 15 voting members ACIP includes 8 ex officio members who represent other federal agencies with responsibility for immunization programs in the United States and 30 non-voting representatives of liaison organizations that bring related immunization expertiserdquo
httpswwwcdcgovvaccinesacipabouthtml
ACIP - SCHEDULE
bull How do vaccines get added Do vaccines ever get taken offbull Work group convene to work on one vaccine-preventable disease or group of diseases
bull Work group members collect and review data on disease epidemiology vaccine efficacy effectiveness safety feasibility of program implementation and economic aspects of immunization policy to include in written policy statements
bull Insurance companies and Medicaid generally pay for whatrsquos on the ACIP schedule so these recommendations have financial repercussions
bull Because immunity is not inherited we need to immunize each persongeneration until the disease is truly eradicated
bull ACIP meetings are open to the public and can be viewed by streaming webcast
bull If recommendations are accepted by the CDC they are published in the MMWR
httpswwwcdcgovvaccinesacipabouthtml
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
EFFICACY CASE LAIV (FLUMIST)
bull ldquoIn light of low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013ndash14 and 2015ndash16 seasons for the 2016ndash17 season ACIP makes the interim recommendation that LAIV4 should not be usedrdquo
bull Even though it would cost the manufacturer as the ACIP recommendation drives usage and insurance coverage
Grohskopf LA Prevention and Control of Seasonal Influenza with Vaccines MMWR Recomm Rep 201665
WHO IS ACIP
bull The Advisory Committee on Immunization Practices ldquoincludes 15 voting members responsible for making vaccine recommendations The Secretary of the US Department of Health and Human Services (DHHS) selects these members following an application and nomination process Fourteen of the members have expertise in vaccinology immunology pediatrics internal medicine nursing family medicine virology public health infectious diseases andor preventive medicine one member is a consumer representative who provides perspectives on the social and community aspects of vaccination
bull In addition to the 15 voting members ACIP includes 8 ex officio members who represent other federal agencies with responsibility for immunization programs in the United States and 30 non-voting representatives of liaison organizations that bring related immunization expertiserdquo
httpswwwcdcgovvaccinesacipabouthtml
ACIP - SCHEDULE
bull How do vaccines get added Do vaccines ever get taken offbull Work group convene to work on one vaccine-preventable disease or group of diseases
bull Work group members collect and review data on disease epidemiology vaccine efficacy effectiveness safety feasibility of program implementation and economic aspects of immunization policy to include in written policy statements
bull Insurance companies and Medicaid generally pay for whatrsquos on the ACIP schedule so these recommendations have financial repercussions
bull Because immunity is not inherited we need to immunize each persongeneration until the disease is truly eradicated
bull ACIP meetings are open to the public and can be viewed by streaming webcast
bull If recommendations are accepted by the CDC they are published in the MMWR
httpswwwcdcgovvaccinesacipabouthtml
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
WHO IS ACIP
bull The Advisory Committee on Immunization Practices ldquoincludes 15 voting members responsible for making vaccine recommendations The Secretary of the US Department of Health and Human Services (DHHS) selects these members following an application and nomination process Fourteen of the members have expertise in vaccinology immunology pediatrics internal medicine nursing family medicine virology public health infectious diseases andor preventive medicine one member is a consumer representative who provides perspectives on the social and community aspects of vaccination
bull In addition to the 15 voting members ACIP includes 8 ex officio members who represent other federal agencies with responsibility for immunization programs in the United States and 30 non-voting representatives of liaison organizations that bring related immunization expertiserdquo
httpswwwcdcgovvaccinesacipabouthtml
ACIP - SCHEDULE
bull How do vaccines get added Do vaccines ever get taken offbull Work group convene to work on one vaccine-preventable disease or group of diseases
bull Work group members collect and review data on disease epidemiology vaccine efficacy effectiveness safety feasibility of program implementation and economic aspects of immunization policy to include in written policy statements
bull Insurance companies and Medicaid generally pay for whatrsquos on the ACIP schedule so these recommendations have financial repercussions
bull Because immunity is not inherited we need to immunize each persongeneration until the disease is truly eradicated
bull ACIP meetings are open to the public and can be viewed by streaming webcast
bull If recommendations are accepted by the CDC they are published in the MMWR
httpswwwcdcgovvaccinesacipabouthtml
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
ACIP - SCHEDULE
bull How do vaccines get added Do vaccines ever get taken offbull Work group convene to work on one vaccine-preventable disease or group of diseases
bull Work group members collect and review data on disease epidemiology vaccine efficacy effectiveness safety feasibility of program implementation and economic aspects of immunization policy to include in written policy statements
bull Insurance companies and Medicaid generally pay for whatrsquos on the ACIP schedule so these recommendations have financial repercussions
bull Because immunity is not inherited we need to immunize each persongeneration until the disease is truly eradicated
bull ACIP meetings are open to the public and can be viewed by streaming webcast
bull If recommendations are accepted by the CDC they are published in the MMWR
httpswwwcdcgovvaccinesacipabouthtml
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
WALKING THROUGH THE CHILDHOOD SCHEDULE
bull Prevent what we can when it matters most
bull When a child is most likely to encounter a disease
bull And when they are most likely to experience complications
bull Develop immunity before encountering the disease
bull Building a strong foundation of immunity right from the start
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
TYPES OF VACCINES
bull Live attenuated -- retains the ability to replicate (grow) and produce immunity but usually does not cause illnessbull live attenuated viruses ndash eg MMR varicella
bull live attenuated bacteria ndash eg typhoid BCG
bull Inactivatedbull Whole bacteria ndash eg whole cell pertussis
bull Whole viruses ndash eg injected influenza vaccine
bull Fractionalbull protein-based --
bull toxoid (inactivated toxin) ndash eg tetanus
bull subunit or subvirion ndash eg the new shingles vaccine
bull recombinant ndash eg hep B
bull polysaccharide-based
bull pure cell wall polysaccharide from bacteria ndash eg PPSV23
bull Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein ndash eg PCV
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
VACCINES PREVENT DISEASE
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
WHY SHOULD WE EVEN PREVENT DISEASE
bull Depending on when you were born you may say ldquoI had measles why shouldnrsquot theyrdquo or ldquoI had chicken pox why shouldnrsquot theyrdquo
bull Some people diebull This burden falls disproportionately on vulnerable populations
bull Others have serious long-lasting injury (what doesnrsquot kill you doesnrsquot always make you stronger)bull Invasive Hib can cause lasting hearing or brain damage
bull Polio can cause lasting paralysis
bull Meningococcal can cause limb loss
bull Even when we canrsquot prevent all cases we can reduce the risk of severe disease and serious complications
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
HEP B WHYldquoThis is a sexually transmitted
infection why is it given to newbornsrdquo
I get that this is a public health measure but my patients arenrsquot at risk
If the mom doesnrsquot have hep B there is no risk to her baby so baby doesnrsquot
need this vaccine
I donrsquot want to risk a vaccine side effect that might complicate the
newbornrsquos stay
This is given at birth because theyrsquore a captive audience and
itrsquos the only chance to immunize them
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
HEP B STARTS AT BIRTH
ldquoMy baby isnrsquot having sex or doing drugs why should they get this vaccinerdquo
350000000 people in the world have chronic hepatitis B
Most of them contracted the virus when they were kids
Older than 5 when infected -gt fewer than 5 go on to chronic disease
1mdash5 years old -gt 30
Under 1 -gt 90 go on to have chronic disease
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
THE POWER OF HEPATITIS B
bull Tenacity virus can survive dried out on a surface for a week+
bull Highly infectious up to 30 of people who encounter hepatitis B actually get the disease (compared to HIV at 003)
bull Chronic hepatitis B causes 50-60 of all liver cancer
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
PREVENTION
Immunizing only high risk infants didnrsquot work
1Immunizing high risk infants and adolescents didnrsquot work
2Immunizing all infants works
3
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
INFANTS DO HAVE IMMUNE SYSTEMS
bull Maybe not as powerful as it will eventually be but powerful enough to respond appropriately to vaccines
bull Universal hepatitis B vaccine for newborns has reduced acute hepatitis B infections by 94
bull Prevent acute cases and you prevent chronic cases
bull Prevent what we can when it matters most
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
ALUMINUM
Aluminum is ubiquitous in the earthrsquos crust
Aluminum salts have been used as adjuvants since the 1940s with lots of safety data
Adjuvants are needed to lsquoirritatersquo the immune system so it pays attention to the vaccine
Aluminum is cleared by the kidneys
Single doses of aluminum-containing vaccines are different than infants receiving aluminum-containing TPN around the clock
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
ALUMINUM IN TPN
ldquoParenteral nutrition (PN) has long been implicated as a major source of aluminum exposure due to contamination of the component ingredients PN component products are contaminated with aluminum in raw materials as well as byproducts from the manufacturing process where aluminum leaches from glass vials during autoclaving [101112] Patients at greatest risk for aluminum toxicity from PN include those with underlying renal dysfunction and prolonged courses of PN therapy Premature infants are particularly at high risk of aluminum accumulation and toxicity as they often require PN for many days and have immature kidneys incapable of excreting aluminum efficiently Calcium gluconate and phosphate salts are known to be especially high in aluminum content and are often administered to premature infants in substantial amounts to promote bone mineralization [101314]rdquo
Poole RL Pieroni KP Gaskari S Dixon T Kerner JA Aluminum Exposure in Neonatal Patients Using the Least Contaminated Parenteral Nutrition Solution Products Nutrients 20124(11)1566ndash74
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
DOES ALUMINUM BIOACCUMULATE IS IT CORRELATED WITH DEVELOPMENTAL DISABILITYObjective To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunizationhistory and development
Methods We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition Aluminum levels were measured using inductively coupled plasma-mass spectrometry Correlation with Bayley Scales of Infant and Toddler Development Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models
Results The median age of 85 participants was 287 days B-Al (median 154 ngmL range 09ndash952 ngmL) and H-Al (median 42542 ngg range 2758ndash211690 ngg) were weakly correlated (Spearman ρ = 026 P = 03) There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines B-Al was not correlated with BSID composite or subscale scores Although H-Al was notcorrelated with BSID scores in models including all data (n = 85) it was inversely correlated with motor composite (P lt 02 Wald = 588) and the gross motor subscale (P = 04 Wald = 438) in models that excluded an extreme outlying H-Al value
Conclusions Infant B-Al and H-Al varied considerably but did not correlate with their immunization history Likewise there was no correlation between B-Al and infant development or between H-Al and language or cognitive development An inverse correlation between H-Al and BSID motor scores deserves further investigation
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
The Vaccine Page httpswwwfacebookcomthevaccinepage
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
UPDATED ALUMINUM PHARMACOKINETICS FOLLOWING INFANT EXPOSURES THROUGH DIET AND VACCINATION
Mitkus RJ1 King DB Hess MA Forshee RAWalderhaug MO
Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earths surface Exposure of the general population to aluminum occurs primarily through the consumption of food antacids and buffered analgesics Exposure to aluminum in the general population can also occur through vaccination since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants we developed an up-to-date analysis of the safety of aluminum adjuvants Keith et al [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry We updated the analysis of Keith et al [1] with a current pediatric vaccination schedule [2] baseline aluminum levels at birth an aluminum retention function that reflects changing glomerular filtration rates in infants an adjustment for the kinetics of aluminum efflux at the site of injection contemporaneous MRLs and the most recent infant body weight data for children 0-60 months of age [3] Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infants first
year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns
Vaccine 2011 Nov 2829(51)9538-43 doi 101016jvaccine201109124 Epub 2011 Oct 11
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
OVERALL SCHEDULE SAFETY
Question Is it true vaccines are only studied individually
Answer No Vaccines are tested against the other vaccines typically given that day You can find this information in the MMWR
ldquoVaccine administration Pneumococcal [polysaccharide] vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine (6284) Pneumococcal vaccine also may be administered concurrently with other vaccines The administration of pneumococcal vaccine with combined diphtheria tetanus and pertussis (DTP) poliovirus or other vaccines does not increase the severity of reactions or diminish antibody responses (85)rdquo (MMWR April 04 1997 46(RR-08)1-24)
ldquoVaccine Administration PCV13 has been administered concurrently with vaccines containing the following antigens with no adverse effects on immunogenicity or safety diphtheria tetanus acellular pertussis Haemophilus influenzae type b inactivated poliomyelitis rotavirus hepatitis B meningococcal serogroup C measles mumps rubella and varicella (9) PCV13 can be administered at the same time as other routine childhood vaccinations if administered in a separate syringe at a separate injection site The safety and efficacy of concurrent administration of PCV13 and PPV23 has not been studied and concurrent administration is not recommendedrdquo (MMWR December 10 2010 59(RR11)1-18)
IOM study - ldquoThe Childhood Immunization Schedule and Safetyrdquo httpwwwnapeduread13563chapter1
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
DO MULTIPLE VACCINES OVERWHELM OR WEAKEN THE INFANTrsquoS IMMUNE SYSTEM
bull Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines Implicit in this concern is that the infantrsquos immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system In this review we will examine the following 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines 2) the theoretic capacity of an infantrsquos immune system 3) data that demonstrate that mild or moderate illness does not interfere with an infantrsquos ability to generate protective immune responses to vaccines 4) how infants respond to vaccines given in combination compared with the same vaccines given separately 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
Offit PA Quarles J Gerber MA et al Addressing Parentsrsquo Concerns Do Multiple Vaccines Overwhelm or Weaken the Infantrsquos Immune System Pediatrics 2002109(1)124ndash9
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
WHY VACCINATE ON TIME
bull Gets baby protected as soon as possible
bull Preparing not reacting
bull Keeps medical costs down by not adding extra check ups
bull Some vaccines canrsquot be given after a certain age
bull Doses donrsquot get lost
bull Donrsquot need a pile of ldquocatch uprdquo doses before entering school
bull Catching up is complicated
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
INDIVIDUALIZATION IN DOSING
bull ldquoWhy does my little baby get the same dose as an adult The dose is different for medications why not for vaccinesrdquo
bull Vaccine dosing is different than medication dosing
bull Vaccine doses donrsquot need to reach all the tissues of the body
bull They need to properly encounter immune cells which are located throughout the body
bull Immune cells are educated near where the vaccine is given then those immune cells travel throughout the body
bull Therefore we need only tiny quantities of vaccine and donrsquot generally need more or less for bigger or smaller bodies
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
INDIVIDUALIZATION IN SCHEDULING
bull Schedule ndash there is a myth that the vaccine schedule is ldquoone size fits allrdquo and thus providers should change the schedule to suit individual patients
bull The Contraindications and Precautions table lists contraindications and precautions for each vaccine (who should NOT get vaccine)
bull httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
bull Family history of autoimmunity is not a contraindication
bull Some medical conditions warrant ADDITIONAL vaccines
bull Most premature babies can receive vaccines on time for chronological age (donrsquot need to wait for adjusted age)
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
WHO SHOULD RECEIVE EXTRA VACCINE
bull Certain people are at higher risk for certain conditions
bull Some examples
bull Some premature babies are at higher risk of RSV and receive RSV immunoglobulin (passive immunization)
bull People with no spleen or no splenic function (eg sickle cell) are at higher risk for meningococcal pneumococcal Hib and receive additional early extra or special vaccines for those diseases
bull Other examples of high risk conditions cochlear implants HIV immune deficiencies stem cell transplant recipients chronic lung disease (incl severe asthma) CCHD diabetes renal disease cancers hellip see schedule footnotes
bull For adults with special conditions (including pregnancy) therersquos a special chart of recommended immunizations
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
Excerpt from httpswwwcdcgovvaccineshcpacip-recsgeneral-recscontraindicationshtml
Vaccine - Citation ndash Contraindication -- Precaution
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
MULTIPLE PERSPECTIVES ON MULTIPLE VACCINES
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
ANTIGEN COUNTS
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
INOCULATION AGAINST MISINFORMATION
bull When you encounter a web series blog post salacious article Google it and the word ldquodebunkedrdquo
bull httpsthelogicofsciencecom20160823measles-is-not-better-than-autism-debunking-anti-vaccine-arguments
bull Vaxopediaorg
bull Think about other instances of the phenomenon ndash was there a big change in hygienesanitation in the 1990s when Hib meningitis was nearly eradicated Or was it the vaccine
bull How about chicken pox in 1995
bull How about rotavirus in 2006
bull Try to appreciate the large body of literature and not a single studyhellip
bull Learn about journal quality journal impact factors predatory journals
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
PACKAGE INSERTS
bull Legal documents not medical documents
bull List of potential adverse effects include everything that happened to anybody involved in the trial even if it was not causally related
bull Current as of the time of LICENSURE by the FDA
bull Generally updated only with NEGATIVE information eg black box warnings
bull httpsvaxopediaorg20170710how-to-read-a-package-insert-for-a-vaccine
bull If you are tempted to use a package insert for clinical information (other than how to reconstitute) use the MMWR instead
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
COINCIDENCE CONUNDRUM
bull Autism
bull SIDS
bull Autoimmunity
httpsthelogicofsciencecom20160628why-are-there-so-many-reports-of-autism-following-vaccination-a-mathematical-assessment
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
DELAYED IMMUNIZATION
bull No evidence to suggest improved outcomes with delayed vaccination
bull Some vaccines have more side effects if you give them later ndash eg risk of febrile seizures is higher among 16-24 month olds compared to on-time (12-15 months) (Rowhani-Rahbar et al 2013)
bull Hib and PCV schedules change depending on starting age ndash can potentially drop 1-2 doses
bull Rotavirus must be started by 14w6d and completed by 8m0d
bull Primary DTaP series must be completed by 7y if delayed beyond age 6 therersquos no opportunity to have a primary series against pertussis
bull Delaying schedules introduces risk without providing any known benefit
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
SELECTIVE IMMUNIZATION
bull For as long as there has been the idea of vaccines there have been anti-vaccine sentiment of various sorts
bull Recent concerns have centered around ingredients additives preservatives autism and immune system overwhelm
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing pertussis felt remote
bull Families were deliberately skipping pertussis immunization and using DT and Td instead
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
PERTUSSIS OUTBREAK OF 2012
bull Red line in the top graph is lt patients 1 year old
bull Graph on the bottom is cases per monthndash by the end of the year therersquod been 5000+ cases
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
SELECTIVE IMMUNIZATION
bull We definitely know that some diseases are more common than others
bull But this varies depending on region and moment in time
bull In 2010 when Elias started practicing measles felt remotehellip
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
MEASLES RESURGENCE
bull 2008 Several outbreaks including three large outbreaks cases attributed to spread in communities with groups of unvaccinated people 2011 In 2011 more than 30 countries in the WHO European Region reported an increase in measles and France was experiencing a large outbreak Most of the cases that were brought to the US in 2011 came from France
bull WHO 26000 cases of measles in 36 European countries from January-October 2011 with more than 14000 of those in France Despite strong health systems Western European countries have reported 83 of these cases These outbreaks have caused nine deaths including six in France and 7288 hospitalizations
bull 2013 The US experienced 11 outbreaks in 2013 three of which had more than 20 cases including an outbreak with 58 cases
bull 2014 The US experienced 23 measles outbreaks in 2014 including one large outbreak of 383 cases occurring primarily among unvaccinated Amish communities in Ohio Many of the cases in the US in 2014 were associated with cases brought in from the Philippines which experienced a large measles outbreak
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
MEASLES OUTBREAKS
bull 2015 Washington Woman Is First US Measles Death in 12 Years
bull 2015 The United States experienced a large multi-state measles outbreak linked to an amusement park in California The outbreak likely started from a traveler who became infected overseas with measles then visited the amusement park while infectious however no source was identified Analysis by CDC scientists showed that the measles virus type in this outbreak(B3) was identical to the virus type that caused the large measles outbreak in the Philippines in 2014
bull 2017 On April 10 2017 the Minnesota Department of Health (MDH) was notified about a suspected measles case The patient was a hospitalized child aged 25 months who was evaluated for fever and rash with onset on April 8 The child had no historyof receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles In a community with previously high vaccination coverage concerns about autism the perceived increased rates of autism in the Somali-American community and the misunderstanding that autism was related to the measles-mumps-rubella (MMR) vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somali-American community following introduction of the virus By May 31 2017 a total of 65 confirmed measles cases had been reported to MDH
bull 2018 At least 70 children dead in Venezuela measles outbreak
httpswwwcdcgovmeaslescases-outbreakshtml
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
EUROPE 2017
bull 2016 5273
bull 2017 21315
Italy Greece Romania France Germany Belgium Ukraine France Russia Tajikistan
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
FURTHER OUTBREAKS
bull ldquoHepatitis A Outbreaks Appearing Across the Nationrdquo ndash August 8 2017
bull httpswwwhhsgovhepatitisblog20170808hepatitis-a-outbreaks-appearing-across-the-countryhtml
bull Widespread mumps outbreaks
bull Return of diphtheria ldquothe strangling angel of childrenrdquo
bull httpappswhointimmunization_monitoringglobalsummarytimeseriestsincidencediphtheriahtml
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
ALTERNATIVE SCHEDULES
Can you identify where the child is left vulnerable
left vulnerable to bull Poliobull Hibbull Pneumococcalbull Rotavirusbull Hep Bbull Hep Abull Varicellabull Influenza
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
Can you identify where the child is left vulnerable
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
ldquoVACCINE FRIENDLY PLANrdquo (THOMAS)
Can you identify where child is left vulnerable
bull Pertussis when most likely to die
bull Polio
bull Rotavirus
bull Hep B when serious complications most likely
bull Hep A
bull Varicella
bull Influenza
bull MTHFR family history autoimmunity autism are not contraindications for vaccines
bull No combo vaccines = more injections
bull More visits = more car trips more waiting room exposures
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen in 1 5 10 50 years
bull We donrsquot know whatrsquos coming into the countryregionareacounty
bull Vaccine shortages are common in an outbreak
bull It takes time and multiple doses to gain immunity
bull Some vaccines must be startedcompleted by a certain age or yoursquore no longer eligible
bull We donrsquot know when yoursquore going to step on a rusty nail hellip and need not just tetanus vaccine but also immunoglobulin which is a blood product
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
PREPARING VS REACTING
bull We donrsquot know whatrsquos going to happen to the patientrsquos family
bull New baby Preschooler with pertussis could be devastating to that 2-week-old
bull Economic disruption Can you afford a quarantine
bull Going to daycare Regulations plus new exposureshellip
bull Travel If yoursquore behind how many months and doses will it take to catch up plus the vaccines requiredrecommended for the travel region
bull New diagnosis Previously healthy kid now with lots of exposure to the healthcare system or previously healthy parent now with a cancer diagnosis
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
PREPARING VS REACTING
bull Babies grow into kids who grow into teens and young adults who make different decisions than you do
bull Riskier behavior than you think or know
bull College ndash many vaccines are required for college and there are new risks from dorm living
bull Pregnancy ndash what if shersquos not immune to rubella and her fetus develops congenital rubella syndrome
bull Travel ndash ldquoI want to travel with school I donrsquot like shots but I donrsquot want to die of some death disease eitherrdquo ndashunderimmunized 14-year-old patient explaining to his mother his desire to be immunized
bull Providers should continue to offer and recommend vaccines even for families refusing because their circumstances may have changed and everyone should have the chance to make a new decision
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
HPV A CASE IN PREPARATION
bull HPV 9-valent vaccine is estimated to preventbull 85 of cervical cancers
bull 70 of oropharyngeal cancers
bull 80 of anal cancers
bull 60 of penile cancersbull About 25K cancers in US each year prevented
bull A vaccine for cancer is a really incredible thing
bull High risk HPV causes 5 of all the worldrsquos cancer
bull You can prevent misery suffering and death
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
HPV IS DEADLY
bull Only some cancers can be screened for
bull Even if a cancer is caught early with a Pap smear the treatment has its own morbidity
bull Screening is not prevention
bull Immunization is prevention
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
HPV VACCINES ARE HIGHLY EFFECTIVE
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
HPV VACCINE IS SAFE
bull Placebo-controlled studies show that adverse events are primarily sore arms and sycope
bull No increase in auto-immune conditions (Grimaldi-Bensouda et al 2017)
bull Hundreds of studies covering millions of doses and millions of people consistently fail to identify any safety signals associated with HPV vaccines
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
HPV PREPARATION
bull Immunity must be in place beforeexposure
bull 80 of people will be exposed to HPV
bull HPV detected in 50 of women prior to first vaginal sex (Doerfler 2009)
bull You canrsquot predict who or when protect everyone
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
MAKING A STRONG RECOMMENDATION
bull Make your recommendation
bull If there are questions or concerns try your best to respond
bull Make your recommendation again (Opel 2013)
bull Continue to be in relationship ndash you are available for continued conversation and will continue to make the recommendation
bull ldquoIrsquom not going to bully or force you but I am going to continue to talk about it with yourdquo
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
WHAT TO EXPECT AFTER IMMUNIZATIONS
bull Our goal is to induce an immune reaction
bull Mild adverse effects like fever fussiness redness are more common than serious side effects like seizures which are very rare
bull With live vaccines the adverse effects are typically a ldquominirdquo version of the disease (eg chicken pox-like rash)
bull With inactivated vaccines the adverse effects are typically local (redness tenderness at the injection site)
bull Each Vaccine Information Statement (VIS) reviews what to expect at what rate and when to contact your doctor -- httpimmunizeorgvis
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
PROTECTING THE HERD
bull Herd immunity is actually community immunity
bull If enough people are immune then a disease canrsquot reproduce and spread
bull Immunizing everyone who can be immunized helps to protect those who canrsquot be immunized either because theyrsquore too young or because they canrsquot receive the vaccine
bull Each disease has its own ldquocommunity immunity thresholdrdquo for how many people must be immune in order to stop transmission and prevent an outbreak
bull Note that measles and pertussis have the highest community immunity thresholds and these are the vaccine-preventable diseases that are starting to re-emerge as coverage rates have dropped
HERD IMMUNITY ANIMATION
HERD IMMUNITY ANIMATION
CANrsquoT I JUST ____
bull Breastfeed ndash breastfeeding passes along certain antibodies (passive immunity) but they are generally not specific to the disease It is an excellent foundation of health
bull Breastfeeding also seems to yield a better immune response to certain vaccines (Hib and PCV)
bull Avoid sick people ndash most diseases are contagious for days before symptoms arise
bull Immunize specific populations (eg by population density socioeconomic status risk factors) ndash these approaches have been tried (eg early HBV programs influenza) and they are not as effective as broad community coverage
ANTIBODY SOURCES FOR INFANTS amp KIDS
VACCINATIONS IN PREGNANCY
bull Influenza is dangerous to the pregnant person because of the unique load on the heart and lungs during pregnancy
bull Fever is bad for fetuses and depending on timing can cause malformations (including neural tube defects and clefts)
bull Influenza can additionally cause low birth weight and preterm birth
bull Influenza vaccine during pregnancy effectively reduces the risks for the pregnant person and the fetus
bull And additionally reduces the risk of hospital admission for respiratory illness in the first 6 months of life
TDAP IN PREGNANCY
bull Pertussis (whooping cough) is not thought to be additionally dangerous for the pregnant person but is definitely inconvenient
bull Pertussis can be deadly for the newborn with most deaths happening in the first 3 months
bull Decision analysis model showed that Tdap vaccination during pregnancy would prevent more illness and deaths in newborns than a postpartum dose (6) so in 2012 ACIP recommended a dose of Tdap in each pregnancy
bull Ongoing surveillance shows highly effective prevention of severe pertussis in the baby with pregnancy immunization (78)
bull Immunization in the third trimester yields the highest antibody transfer to baby (4)
PREGNANCY TDAP IS HIGHLY EFFECTIVE
bull Vaccine effectiveness vs lab confirmed pertussis in babies under 3 months 91 (95 CI 84 to 95) (Amirthalingam 2014)
bull Vaccine effectiveness in babies under 8 weeks 93 (Dabrera 2015)
bull Vaccine effectiveness against laboratory-confirmed pertussis has been sustained gt90 in the 3 years following its introduction (Amirthalingam 2016)
bull Vaccine effectiveness against infant deaths was estimated at 95 (95 confidence interval 79ndash100) (Amirthalingam 2016)
SAFETY OF PERTUSSISVACCINATION IN PREGNANT WOMEN IN UKOBJECTIVE To examine the safety of pertussis vaccination in pregnancy
DESIGN Observational cohort study
SETTING The UK Clinical Practice Research Datalink
PARTICIPANTS 20074 pregnant women with a median age of 30 who received the pertussis vaccine and a matched historical unvaccinated control group
MAIN OUTCOME MEASURE Adverse events identified from clinical diagnoses during pregnancy with additional data from the matched child record identified through mother-child linkage The primary event of interest was stillbirth (intrauterine death after 24 weeks gestation)
RESULTS There was no evidence of an increased risk of stillbirth in the 14 days immediately after vaccination (incidence rate ratio 069 95 confidence interval 023 to 162) or later in pregnancy (085 044 to 161) compared with historical national rates Compared with a matched historical cohort of unvaccinated pregnant women there was no evidence that vaccination accelerated the time to delivery (hazard ratio 100 097 to 102) Furthermore there was no evidence of an increased risk of stillbirth maternal or neonatal death pre-eclampsia or eclampsia haemorrhage fetal distress uterine rupture placenta or vasa praevia caesarean delivery low birth weight or neonatal renal failure all serious events that can occur naturally in pregnancy
CONCLUSION In women given pertussis vaccination in the third trimester there is no evidence of an increased risk of any of an extensive predefined list of adverse events related to pregnancy In particular there was no evidence of an increased risk of stillbirth Given the recent increases in the rate of pertussis infection and morbidity and mortality in neonates these early data provide initial evidence for evaluating the safety of the vaccine in pregnancy for health professionals and the public and can help to inform vaccination policy making
Donegan K King B Bryan P Safety of pertussis vaccination in pregnant women in UK observational study BMJ 2014349g4219
INFANT HOSPITALIZATIONS AND MORTALITY AFTER MATERNAL VACCINATIONBACKGROUND The Advisory Committee on Immunization Practices currently recommends pregnant women receive influenza and tetanus toxoid reduced diphtheria toxoid and acellular pertussis (Tdap) vaccines There are limited studies of the long-term safety in infants for vaccines administered during pregnancy We evaluate whether maternal receipt of influenza and Tdap vaccines increases the risk of infant hospitalization or death in the first 6 months of life
METHODS We included singleton live birth pregnancies in the Vaccine Safety Datalink between 2004 and 2014 Outcomes were infant hospitalizations and mortality in the first 6 months of life We performed a case-control study matching case patients and controls 11 and used conditional logistic regression to estimate odds ratios for maternal exposure to influenza andor Tdap vaccines in pregnancy
RESULTS There were 413 034 live births in our population Of these 25 222 infants had hospitalizations and 157 infants died in the first 6 months of life We found no association between infant hospitalization and maternal influenza (adjusted odds ratio 100 95 confidence interval [CI] 096ndash104) or Tdap (adjusted odds ratio 094 95 CI 088ndash101) vaccinations We found no association between infant mortality and maternal influenza (adjusted odds ratio 096 95 CI 054ndash169) or Tdap (adjusted odds ratio 044 95 CI 017ndash113) vaccinations
CONCLUSIONS We found no association between vaccination during pregnancy and risk of infant hospitalization or death in the first 6 months of life These findings support the safety of current recommendations for influenza and Tdap vaccination during pregnancy
Sukumaran L McCarthy NL Kharbanda EO et al Infant Hospitalizations and Mortality After Maternal Vaccination Pediatrics 2018
RESOURCES
bull httpwwwNDsforVaccinesorg - NDs writing in support of immunizations
bull httpwwwvaxopediaorg - A Texas pediatrician who writes many short articles addressing vaccine myths concepts evidence
bull httpwwwvaxnorthwestorg - regional parents talking about the importance of vaccination
bull httpwwwimmunizeorg -- extensive resource for disease and vaccine information for HCPs and parents including specific sections targeting questions around alternative schedules autism mercury etc
bull httpwwwcdcgovvaccinesscheduleshcpchild-adolescenthtml -- schedules and catch up schedules
bull httpwwwsoundsofpertussiscom -- outreach site around pertussis
bull httpwwwcdcgovvaccinesvac-gen6mishomehtm - Top 6 Misconceptions
bull httpwwwkingcountygovdeptshealthcommunicable-diseasesimmunizationchildplain-talk-about-childhood-immunizationsaspx ldquoPlain Talk about Childhood Immunizationsrdquo -- fantastic book that addresses just about any question a family might have about vaccines Download in multiple languages
bull httpwwwchopeduservicevaccine-education-centerhomehtml -- Childrenrsquos Hospital of Philadelphia Vaccine Education Center ndash excellent parent-focused information about vaccines and vaccine-preventable disease including an app called Vaccines on the Go
ANTIBODY SOURCES FOR INFANTS amp KIDS
VACCINATIONS IN PREGNANCY
bull Influenza is dangerous to the pregnant person because of the unique load on the heart and lungs during pregnancy
bull Fever is bad for fetuses and depending on timing can cause malformations (including neural tube defects and clefts)
bull Influenza can additionally cause low birth weight and preterm birth
bull Influenza vaccine during pregnancy effectively reduces the risks for the pregnant person and the fetus
bull And additionally reduces the risk of hospital admission for respiratory illness in the first 6 months of life
TDAP IN PREGNANCY
bull Pertussis (whooping cough) is not thought to be additionally dangerous for the pregnant person but is definitely inconvenient
bull Pertussis can be deadly for the newborn with most deaths happening in the first 3 months
bull Decision analysis model showed that Tdap vaccination during pregnancy would prevent more illness and deaths in newborns than a postpartum dose (6) so in 2012 ACIP recommended a dose of Tdap in each pregnancy
bull Ongoing surveillance shows highly effective prevention of severe pertussis in the baby with pregnancy immunization (78)
bull Immunization in the third trimester yields the highest antibody transfer to baby (4)
PREGNANCY TDAP IS HIGHLY EFFECTIVE
bull Vaccine effectiveness vs lab confirmed pertussis in babies under 3 months 91 (95 CI 84 to 95) (Amirthalingam 2014)
bull Vaccine effectiveness in babies under 8 weeks 93 (Dabrera 2015)
bull Vaccine effectiveness against laboratory-confirmed pertussis has been sustained gt90 in the 3 years following its introduction (Amirthalingam 2016)
bull Vaccine effectiveness against infant deaths was estimated at 95 (95 confidence interval 79ndash100) (Amirthalingam 2016)
SAFETY OF PERTUSSISVACCINATION IN PREGNANT WOMEN IN UKOBJECTIVE To examine the safety of pertussis vaccination in pregnancy
DESIGN Observational cohort study
SETTING The UK Clinical Practice Research Datalink
PARTICIPANTS 20074 pregnant women with a median age of 30 who received the pertussis vaccine and a matched historical unvaccinated control group
MAIN OUTCOME MEASURE Adverse events identified from clinical diagnoses during pregnancy with additional data from the matched child record identified through mother-child linkage The primary event of interest was stillbirth (intrauterine death after 24 weeks gestation)
RESULTS There was no evidence of an increased risk of stillbirth in the 14 days immediately after vaccination (incidence rate ratio 069 95 confidence interval 023 to 162) or later in pregnancy (085 044 to 161) compared with historical national rates Compared with a matched historical cohort of unvaccinated pregnant women there was no evidence that vaccination accelerated the time to delivery (hazard ratio 100 097 to 102) Furthermore there was no evidence of an increased risk of stillbirth maternal or neonatal death pre-eclampsia or eclampsia haemorrhage fetal distress uterine rupture placenta or vasa praevia caesarean delivery low birth weight or neonatal renal failure all serious events that can occur naturally in pregnancy
CONCLUSION In women given pertussis vaccination in the third trimester there is no evidence of an increased risk of any of an extensive predefined list of adverse events related to pregnancy In particular there was no evidence of an increased risk of stillbirth Given the recent increases in the rate of pertussis infection and morbidity and mortality in neonates these early data provide initial evidence for evaluating the safety of the vaccine in pregnancy for health professionals and the public and can help to inform vaccination policy making
Donegan K King B Bryan P Safety of pertussis vaccination in pregnant women in UK observational study BMJ 2014349g4219
INFANT HOSPITALIZATIONS AND MORTALITY AFTER MATERNAL VACCINATIONBACKGROUND The Advisory Committee on Immunization Practices currently recommends pregnant women receive influenza and tetanus toxoid reduced diphtheria toxoid and acellular pertussis (Tdap) vaccines There are limited studies of the long-term safety in infants for vaccines administered during pregnancy We evaluate whether maternal receipt of influenza and Tdap vaccines increases the risk of infant hospitalization or death in the first 6 months of life
METHODS We included singleton live birth pregnancies in the Vaccine Safety Datalink between 2004 and 2014 Outcomes were infant hospitalizations and mortality in the first 6 months of life We performed a case-control study matching case patients and controls 11 and used conditional logistic regression to estimate odds ratios for maternal exposure to influenza andor Tdap vaccines in pregnancy
RESULTS There were 413 034 live births in our population Of these 25 222 infants had hospitalizations and 157 infants died in the first 6 months of life We found no association between infant hospitalization and maternal influenza (adjusted odds ratio 100 95 confidence interval [CI] 096ndash104) or Tdap (adjusted odds ratio 094 95 CI 088ndash101) vaccinations We found no association between infant mortality and maternal influenza (adjusted odds ratio 096 95 CI 054ndash169) or Tdap (adjusted odds ratio 044 95 CI 017ndash113) vaccinations
CONCLUSIONS We found no association between vaccination during pregnancy and risk of infant hospitalization or death in the first 6 months of life These findings support the safety of current recommendations for influenza and Tdap vaccination during pregnancy
Sukumaran L McCarthy NL Kharbanda EO et al Infant Hospitalizations and Mortality After Maternal Vaccination Pediatrics 2018
RESOURCES
bull httpwwwNDsforVaccinesorg - NDs writing in support of immunizations
bull httpwwwvaxopediaorg - A Texas pediatrician who writes many short articles addressing vaccine myths concepts evidence
bull httpwwwvaxnorthwestorg - regional parents talking about the importance of vaccination
bull httpwwwimmunizeorg -- extensive resource for disease and vaccine information for HCPs and parents including specific sections targeting questions around alternative schedules autism mercury etc
bull httpwwwcdcgovvaccinesscheduleshcpchild-adolescenthtml -- schedules and catch up schedules
bull httpwwwsoundsofpertussiscom -- outreach site around pertussis
bull httpwwwcdcgovvaccinesvac-gen6mishomehtm - Top 6 Misconceptions
bull httpwwwkingcountygovdeptshealthcommunicable-diseasesimmunizationchildplain-talk-about-childhood-immunizationsaspx ldquoPlain Talk about Childhood Immunizationsrdquo -- fantastic book that addresses just about any question a family might have about vaccines Download in multiple languages
bull httpwwwchopeduservicevaccine-education-centerhomehtml -- Childrenrsquos Hospital of Philadelphia Vaccine Education Center ndash excellent parent-focused information about vaccines and vaccine-preventable disease including an app called Vaccines on the Go
VACCINATIONS IN PREGNANCY
bull Influenza is dangerous to the pregnant person because of the unique load on the heart and lungs during pregnancy
bull Fever is bad for fetuses and depending on timing can cause malformations (including neural tube defects and clefts)
bull Influenza can additionally cause low birth weight and preterm birth
bull Influenza vaccine during pregnancy effectively reduces the risks for the pregnant person and the fetus
bull And additionally reduces the risk of hospital admission for respiratory illness in the first 6 months of life
TDAP IN PREGNANCY
bull Pertussis (whooping cough) is not thought to be additionally dangerous for the pregnant person but is definitely inconvenient
bull Pertussis can be deadly for the newborn with most deaths happening in the first 3 months
bull Decision analysis model showed that Tdap vaccination during pregnancy would prevent more illness and deaths in newborns than a postpartum dose (6) so in 2012 ACIP recommended a dose of Tdap in each pregnancy
bull Ongoing surveillance shows highly effective prevention of severe pertussis in the baby with pregnancy immunization (78)
bull Immunization in the third trimester yields the highest antibody transfer to baby (4)
PREGNANCY TDAP IS HIGHLY EFFECTIVE
bull Vaccine effectiveness vs lab confirmed pertussis in babies under 3 months 91 (95 CI 84 to 95) (Amirthalingam 2014)
bull Vaccine effectiveness in babies under 8 weeks 93 (Dabrera 2015)
bull Vaccine effectiveness against laboratory-confirmed pertussis has been sustained gt90 in the 3 years following its introduction (Amirthalingam 2016)
bull Vaccine effectiveness against infant deaths was estimated at 95 (95 confidence interval 79ndash100) (Amirthalingam 2016)
SAFETY OF PERTUSSISVACCINATION IN PREGNANT WOMEN IN UKOBJECTIVE To examine the safety of pertussis vaccination in pregnancy
DESIGN Observational cohort study
SETTING The UK Clinical Practice Research Datalink
PARTICIPANTS 20074 pregnant women with a median age of 30 who received the pertussis vaccine and a matched historical unvaccinated control group
MAIN OUTCOME MEASURE Adverse events identified from clinical diagnoses during pregnancy with additional data from the matched child record identified through mother-child linkage The primary event of interest was stillbirth (intrauterine death after 24 weeks gestation)
RESULTS There was no evidence of an increased risk of stillbirth in the 14 days immediately after vaccination (incidence rate ratio 069 95 confidence interval 023 to 162) or later in pregnancy (085 044 to 161) compared with historical national rates Compared with a matched historical cohort of unvaccinated pregnant women there was no evidence that vaccination accelerated the time to delivery (hazard ratio 100 097 to 102) Furthermore there was no evidence of an increased risk of stillbirth maternal or neonatal death pre-eclampsia or eclampsia haemorrhage fetal distress uterine rupture placenta or vasa praevia caesarean delivery low birth weight or neonatal renal failure all serious events that can occur naturally in pregnancy
CONCLUSION In women given pertussis vaccination in the third trimester there is no evidence of an increased risk of any of an extensive predefined list of adverse events related to pregnancy In particular there was no evidence of an increased risk of stillbirth Given the recent increases in the rate of pertussis infection and morbidity and mortality in neonates these early data provide initial evidence for evaluating the safety of the vaccine in pregnancy for health professionals and the public and can help to inform vaccination policy making
Donegan K King B Bryan P Safety of pertussis vaccination in pregnant women in UK observational study BMJ 2014349g4219
INFANT HOSPITALIZATIONS AND MORTALITY AFTER MATERNAL VACCINATIONBACKGROUND The Advisory Committee on Immunization Practices currently recommends pregnant women receive influenza and tetanus toxoid reduced diphtheria toxoid and acellular pertussis (Tdap) vaccines There are limited studies of the long-term safety in infants for vaccines administered during pregnancy We evaluate whether maternal receipt of influenza and Tdap vaccines increases the risk of infant hospitalization or death in the first 6 months of life
METHODS We included singleton live birth pregnancies in the Vaccine Safety Datalink between 2004 and 2014 Outcomes were infant hospitalizations and mortality in the first 6 months of life We performed a case-control study matching case patients and controls 11 and used conditional logistic regression to estimate odds ratios for maternal exposure to influenza andor Tdap vaccines in pregnancy
RESULTS There were 413 034 live births in our population Of these 25 222 infants had hospitalizations and 157 infants died in the first 6 months of life We found no association between infant hospitalization and maternal influenza (adjusted odds ratio 100 95 confidence interval [CI] 096ndash104) or Tdap (adjusted odds ratio 094 95 CI 088ndash101) vaccinations We found no association between infant mortality and maternal influenza (adjusted odds ratio 096 95 CI 054ndash169) or Tdap (adjusted odds ratio 044 95 CI 017ndash113) vaccinations
CONCLUSIONS We found no association between vaccination during pregnancy and risk of infant hospitalization or death in the first 6 months of life These findings support the safety of current recommendations for influenza and Tdap vaccination during pregnancy
Sukumaran L McCarthy NL Kharbanda EO et al Infant Hospitalizations and Mortality After Maternal Vaccination Pediatrics 2018
RESOURCES
bull httpwwwNDsforVaccinesorg - NDs writing in support of immunizations
bull httpwwwvaxopediaorg - A Texas pediatrician who writes many short articles addressing vaccine myths concepts evidence
bull httpwwwvaxnorthwestorg - regional parents talking about the importance of vaccination
bull httpwwwimmunizeorg -- extensive resource for disease and vaccine information for HCPs and parents including specific sections targeting questions around alternative schedules autism mercury etc
bull httpwwwcdcgovvaccinesscheduleshcpchild-adolescenthtml -- schedules and catch up schedules
bull httpwwwsoundsofpertussiscom -- outreach site around pertussis
bull httpwwwcdcgovvaccinesvac-gen6mishomehtm - Top 6 Misconceptions
bull httpwwwkingcountygovdeptshealthcommunicable-diseasesimmunizationchildplain-talk-about-childhood-immunizationsaspx ldquoPlain Talk about Childhood Immunizationsrdquo -- fantastic book that addresses just about any question a family might have about vaccines Download in multiple languages
bull httpwwwchopeduservicevaccine-education-centerhomehtml -- Childrenrsquos Hospital of Philadelphia Vaccine Education Center ndash excellent parent-focused information about vaccines and vaccine-preventable disease including an app called Vaccines on the Go
TDAP IN PREGNANCY
bull Pertussis (whooping cough) is not thought to be additionally dangerous for the pregnant person but is definitely inconvenient
bull Pertussis can be deadly for the newborn with most deaths happening in the first 3 months
bull Decision analysis model showed that Tdap vaccination during pregnancy would prevent more illness and deaths in newborns than a postpartum dose (6) so in 2012 ACIP recommended a dose of Tdap in each pregnancy
bull Ongoing surveillance shows highly effective prevention of severe pertussis in the baby with pregnancy immunization (78)
bull Immunization in the third trimester yields the highest antibody transfer to baby (4)
PREGNANCY TDAP IS HIGHLY EFFECTIVE
bull Vaccine effectiveness vs lab confirmed pertussis in babies under 3 months 91 (95 CI 84 to 95) (Amirthalingam 2014)
bull Vaccine effectiveness in babies under 8 weeks 93 (Dabrera 2015)
bull Vaccine effectiveness against laboratory-confirmed pertussis has been sustained gt90 in the 3 years following its introduction (Amirthalingam 2016)
bull Vaccine effectiveness against infant deaths was estimated at 95 (95 confidence interval 79ndash100) (Amirthalingam 2016)
SAFETY OF PERTUSSISVACCINATION IN PREGNANT WOMEN IN UKOBJECTIVE To examine the safety of pertussis vaccination in pregnancy
DESIGN Observational cohort study
SETTING The UK Clinical Practice Research Datalink
PARTICIPANTS 20074 pregnant women with a median age of 30 who received the pertussis vaccine and a matched historical unvaccinated control group
MAIN OUTCOME MEASURE Adverse events identified from clinical diagnoses during pregnancy with additional data from the matched child record identified through mother-child linkage The primary event of interest was stillbirth (intrauterine death after 24 weeks gestation)
RESULTS There was no evidence of an increased risk of stillbirth in the 14 days immediately after vaccination (incidence rate ratio 069 95 confidence interval 023 to 162) or later in pregnancy (085 044 to 161) compared with historical national rates Compared with a matched historical cohort of unvaccinated pregnant women there was no evidence that vaccination accelerated the time to delivery (hazard ratio 100 097 to 102) Furthermore there was no evidence of an increased risk of stillbirth maternal or neonatal death pre-eclampsia or eclampsia haemorrhage fetal distress uterine rupture placenta or vasa praevia caesarean delivery low birth weight or neonatal renal failure all serious events that can occur naturally in pregnancy
CONCLUSION In women given pertussis vaccination in the third trimester there is no evidence of an increased risk of any of an extensive predefined list of adverse events related to pregnancy In particular there was no evidence of an increased risk of stillbirth Given the recent increases in the rate of pertussis infection and morbidity and mortality in neonates these early data provide initial evidence for evaluating the safety of the vaccine in pregnancy for health professionals and the public and can help to inform vaccination policy making
Donegan K King B Bryan P Safety of pertussis vaccination in pregnant women in UK observational study BMJ 2014349g4219
INFANT HOSPITALIZATIONS AND MORTALITY AFTER MATERNAL VACCINATIONBACKGROUND The Advisory Committee on Immunization Practices currently recommends pregnant women receive influenza and tetanus toxoid reduced diphtheria toxoid and acellular pertussis (Tdap) vaccines There are limited studies of the long-term safety in infants for vaccines administered during pregnancy We evaluate whether maternal receipt of influenza and Tdap vaccines increases the risk of infant hospitalization or death in the first 6 months of life
METHODS We included singleton live birth pregnancies in the Vaccine Safety Datalink between 2004 and 2014 Outcomes were infant hospitalizations and mortality in the first 6 months of life We performed a case-control study matching case patients and controls 11 and used conditional logistic regression to estimate odds ratios for maternal exposure to influenza andor Tdap vaccines in pregnancy
RESULTS There were 413 034 live births in our population Of these 25 222 infants had hospitalizations and 157 infants died in the first 6 months of life We found no association between infant hospitalization and maternal influenza (adjusted odds ratio 100 95 confidence interval [CI] 096ndash104) or Tdap (adjusted odds ratio 094 95 CI 088ndash101) vaccinations We found no association between infant mortality and maternal influenza (adjusted odds ratio 096 95 CI 054ndash169) or Tdap (adjusted odds ratio 044 95 CI 017ndash113) vaccinations
CONCLUSIONS We found no association between vaccination during pregnancy and risk of infant hospitalization or death in the first 6 months of life These findings support the safety of current recommendations for influenza and Tdap vaccination during pregnancy
Sukumaran L McCarthy NL Kharbanda EO et al Infant Hospitalizations and Mortality After Maternal Vaccination Pediatrics 2018
RESOURCES
bull httpwwwNDsforVaccinesorg - NDs writing in support of immunizations
bull httpwwwvaxopediaorg - A Texas pediatrician who writes many short articles addressing vaccine myths concepts evidence
bull httpwwwvaxnorthwestorg - regional parents talking about the importance of vaccination
bull httpwwwimmunizeorg -- extensive resource for disease and vaccine information for HCPs and parents including specific sections targeting questions around alternative schedules autism mercury etc
bull httpwwwcdcgovvaccinesscheduleshcpchild-adolescenthtml -- schedules and catch up schedules
bull httpwwwsoundsofpertussiscom -- outreach site around pertussis
bull httpwwwcdcgovvaccinesvac-gen6mishomehtm - Top 6 Misconceptions
bull httpwwwkingcountygovdeptshealthcommunicable-diseasesimmunizationchildplain-talk-about-childhood-immunizationsaspx ldquoPlain Talk about Childhood Immunizationsrdquo -- fantastic book that addresses just about any question a family might have about vaccines Download in multiple languages
bull httpwwwchopeduservicevaccine-education-centerhomehtml -- Childrenrsquos Hospital of Philadelphia Vaccine Education Center ndash excellent parent-focused information about vaccines and vaccine-preventable disease including an app called Vaccines on the Go
PREGNANCY TDAP IS HIGHLY EFFECTIVE
bull Vaccine effectiveness vs lab confirmed pertussis in babies under 3 months 91 (95 CI 84 to 95) (Amirthalingam 2014)
bull Vaccine effectiveness in babies under 8 weeks 93 (Dabrera 2015)
bull Vaccine effectiveness against laboratory-confirmed pertussis has been sustained gt90 in the 3 years following its introduction (Amirthalingam 2016)
bull Vaccine effectiveness against infant deaths was estimated at 95 (95 confidence interval 79ndash100) (Amirthalingam 2016)
SAFETY OF PERTUSSISVACCINATION IN PREGNANT WOMEN IN UKOBJECTIVE To examine the safety of pertussis vaccination in pregnancy
DESIGN Observational cohort study
SETTING The UK Clinical Practice Research Datalink
PARTICIPANTS 20074 pregnant women with a median age of 30 who received the pertussis vaccine and a matched historical unvaccinated control group
MAIN OUTCOME MEASURE Adverse events identified from clinical diagnoses during pregnancy with additional data from the matched child record identified through mother-child linkage The primary event of interest was stillbirth (intrauterine death after 24 weeks gestation)
RESULTS There was no evidence of an increased risk of stillbirth in the 14 days immediately after vaccination (incidence rate ratio 069 95 confidence interval 023 to 162) or later in pregnancy (085 044 to 161) compared with historical national rates Compared with a matched historical cohort of unvaccinated pregnant women there was no evidence that vaccination accelerated the time to delivery (hazard ratio 100 097 to 102) Furthermore there was no evidence of an increased risk of stillbirth maternal or neonatal death pre-eclampsia or eclampsia haemorrhage fetal distress uterine rupture placenta or vasa praevia caesarean delivery low birth weight or neonatal renal failure all serious events that can occur naturally in pregnancy
CONCLUSION In women given pertussis vaccination in the third trimester there is no evidence of an increased risk of any of an extensive predefined list of adverse events related to pregnancy In particular there was no evidence of an increased risk of stillbirth Given the recent increases in the rate of pertussis infection and morbidity and mortality in neonates these early data provide initial evidence for evaluating the safety of the vaccine in pregnancy for health professionals and the public and can help to inform vaccination policy making
Donegan K King B Bryan P Safety of pertussis vaccination in pregnant women in UK observational study BMJ 2014349g4219
INFANT HOSPITALIZATIONS AND MORTALITY AFTER MATERNAL VACCINATIONBACKGROUND The Advisory Committee on Immunization Practices currently recommends pregnant women receive influenza and tetanus toxoid reduced diphtheria toxoid and acellular pertussis (Tdap) vaccines There are limited studies of the long-term safety in infants for vaccines administered during pregnancy We evaluate whether maternal receipt of influenza and Tdap vaccines increases the risk of infant hospitalization or death in the first 6 months of life
METHODS We included singleton live birth pregnancies in the Vaccine Safety Datalink between 2004 and 2014 Outcomes were infant hospitalizations and mortality in the first 6 months of life We performed a case-control study matching case patients and controls 11 and used conditional logistic regression to estimate odds ratios for maternal exposure to influenza andor Tdap vaccines in pregnancy
RESULTS There were 413 034 live births in our population Of these 25 222 infants had hospitalizations and 157 infants died in the first 6 months of life We found no association between infant hospitalization and maternal influenza (adjusted odds ratio 100 95 confidence interval [CI] 096ndash104) or Tdap (adjusted odds ratio 094 95 CI 088ndash101) vaccinations We found no association between infant mortality and maternal influenza (adjusted odds ratio 096 95 CI 054ndash169) or Tdap (adjusted odds ratio 044 95 CI 017ndash113) vaccinations
CONCLUSIONS We found no association between vaccination during pregnancy and risk of infant hospitalization or death in the first 6 months of life These findings support the safety of current recommendations for influenza and Tdap vaccination during pregnancy
Sukumaran L McCarthy NL Kharbanda EO et al Infant Hospitalizations and Mortality After Maternal Vaccination Pediatrics 2018
RESOURCES
bull httpwwwNDsforVaccinesorg - NDs writing in support of immunizations
bull httpwwwvaxopediaorg - A Texas pediatrician who writes many short articles addressing vaccine myths concepts evidence
bull httpwwwvaxnorthwestorg - regional parents talking about the importance of vaccination
bull httpwwwimmunizeorg -- extensive resource for disease and vaccine information for HCPs and parents including specific sections targeting questions around alternative schedules autism mercury etc
bull httpwwwcdcgovvaccinesscheduleshcpchild-adolescenthtml -- schedules and catch up schedules
bull httpwwwsoundsofpertussiscom -- outreach site around pertussis
bull httpwwwcdcgovvaccinesvac-gen6mishomehtm - Top 6 Misconceptions
bull httpwwwkingcountygovdeptshealthcommunicable-diseasesimmunizationchildplain-talk-about-childhood-immunizationsaspx ldquoPlain Talk about Childhood Immunizationsrdquo -- fantastic book that addresses just about any question a family might have about vaccines Download in multiple languages
bull httpwwwchopeduservicevaccine-education-centerhomehtml -- Childrenrsquos Hospital of Philadelphia Vaccine Education Center ndash excellent parent-focused information about vaccines and vaccine-preventable disease including an app called Vaccines on the Go
SAFETY OF PERTUSSISVACCINATION IN PREGNANT WOMEN IN UKOBJECTIVE To examine the safety of pertussis vaccination in pregnancy
DESIGN Observational cohort study
SETTING The UK Clinical Practice Research Datalink
PARTICIPANTS 20074 pregnant women with a median age of 30 who received the pertussis vaccine and a matched historical unvaccinated control group
MAIN OUTCOME MEASURE Adverse events identified from clinical diagnoses during pregnancy with additional data from the matched child record identified through mother-child linkage The primary event of interest was stillbirth (intrauterine death after 24 weeks gestation)
RESULTS There was no evidence of an increased risk of stillbirth in the 14 days immediately after vaccination (incidence rate ratio 069 95 confidence interval 023 to 162) or later in pregnancy (085 044 to 161) compared with historical national rates Compared with a matched historical cohort of unvaccinated pregnant women there was no evidence that vaccination accelerated the time to delivery (hazard ratio 100 097 to 102) Furthermore there was no evidence of an increased risk of stillbirth maternal or neonatal death pre-eclampsia or eclampsia haemorrhage fetal distress uterine rupture placenta or vasa praevia caesarean delivery low birth weight or neonatal renal failure all serious events that can occur naturally in pregnancy
CONCLUSION In women given pertussis vaccination in the third trimester there is no evidence of an increased risk of any of an extensive predefined list of adverse events related to pregnancy In particular there was no evidence of an increased risk of stillbirth Given the recent increases in the rate of pertussis infection and morbidity and mortality in neonates these early data provide initial evidence for evaluating the safety of the vaccine in pregnancy for health professionals and the public and can help to inform vaccination policy making
Donegan K King B Bryan P Safety of pertussis vaccination in pregnant women in UK observational study BMJ 2014349g4219
INFANT HOSPITALIZATIONS AND MORTALITY AFTER MATERNAL VACCINATIONBACKGROUND The Advisory Committee on Immunization Practices currently recommends pregnant women receive influenza and tetanus toxoid reduced diphtheria toxoid and acellular pertussis (Tdap) vaccines There are limited studies of the long-term safety in infants for vaccines administered during pregnancy We evaluate whether maternal receipt of influenza and Tdap vaccines increases the risk of infant hospitalization or death in the first 6 months of life
METHODS We included singleton live birth pregnancies in the Vaccine Safety Datalink between 2004 and 2014 Outcomes were infant hospitalizations and mortality in the first 6 months of life We performed a case-control study matching case patients and controls 11 and used conditional logistic regression to estimate odds ratios for maternal exposure to influenza andor Tdap vaccines in pregnancy
RESULTS There were 413 034 live births in our population Of these 25 222 infants had hospitalizations and 157 infants died in the first 6 months of life We found no association between infant hospitalization and maternal influenza (adjusted odds ratio 100 95 confidence interval [CI] 096ndash104) or Tdap (adjusted odds ratio 094 95 CI 088ndash101) vaccinations We found no association between infant mortality and maternal influenza (adjusted odds ratio 096 95 CI 054ndash169) or Tdap (adjusted odds ratio 044 95 CI 017ndash113) vaccinations
CONCLUSIONS We found no association between vaccination during pregnancy and risk of infant hospitalization or death in the first 6 months of life These findings support the safety of current recommendations for influenza and Tdap vaccination during pregnancy
Sukumaran L McCarthy NL Kharbanda EO et al Infant Hospitalizations and Mortality After Maternal Vaccination Pediatrics 2018
RESOURCES
bull httpwwwNDsforVaccinesorg - NDs writing in support of immunizations
bull httpwwwvaxopediaorg - A Texas pediatrician who writes many short articles addressing vaccine myths concepts evidence
bull httpwwwvaxnorthwestorg - regional parents talking about the importance of vaccination
bull httpwwwimmunizeorg -- extensive resource for disease and vaccine information for HCPs and parents including specific sections targeting questions around alternative schedules autism mercury etc
bull httpwwwcdcgovvaccinesscheduleshcpchild-adolescenthtml -- schedules and catch up schedules
bull httpwwwsoundsofpertussiscom -- outreach site around pertussis
bull httpwwwcdcgovvaccinesvac-gen6mishomehtm - Top 6 Misconceptions
bull httpwwwkingcountygovdeptshealthcommunicable-diseasesimmunizationchildplain-talk-about-childhood-immunizationsaspx ldquoPlain Talk about Childhood Immunizationsrdquo -- fantastic book that addresses just about any question a family might have about vaccines Download in multiple languages
bull httpwwwchopeduservicevaccine-education-centerhomehtml -- Childrenrsquos Hospital of Philadelphia Vaccine Education Center ndash excellent parent-focused information about vaccines and vaccine-preventable disease including an app called Vaccines on the Go
INFANT HOSPITALIZATIONS AND MORTALITY AFTER MATERNAL VACCINATIONBACKGROUND The Advisory Committee on Immunization Practices currently recommends pregnant women receive influenza and tetanus toxoid reduced diphtheria toxoid and acellular pertussis (Tdap) vaccines There are limited studies of the long-term safety in infants for vaccines administered during pregnancy We evaluate whether maternal receipt of influenza and Tdap vaccines increases the risk of infant hospitalization or death in the first 6 months of life
METHODS We included singleton live birth pregnancies in the Vaccine Safety Datalink between 2004 and 2014 Outcomes were infant hospitalizations and mortality in the first 6 months of life We performed a case-control study matching case patients and controls 11 and used conditional logistic regression to estimate odds ratios for maternal exposure to influenza andor Tdap vaccines in pregnancy
RESULTS There were 413 034 live births in our population Of these 25 222 infants had hospitalizations and 157 infants died in the first 6 months of life We found no association between infant hospitalization and maternal influenza (adjusted odds ratio 100 95 confidence interval [CI] 096ndash104) or Tdap (adjusted odds ratio 094 95 CI 088ndash101) vaccinations We found no association between infant mortality and maternal influenza (adjusted odds ratio 096 95 CI 054ndash169) or Tdap (adjusted odds ratio 044 95 CI 017ndash113) vaccinations
CONCLUSIONS We found no association between vaccination during pregnancy and risk of infant hospitalization or death in the first 6 months of life These findings support the safety of current recommendations for influenza and Tdap vaccination during pregnancy
Sukumaran L McCarthy NL Kharbanda EO et al Infant Hospitalizations and Mortality After Maternal Vaccination Pediatrics 2018
RESOURCES
bull httpwwwNDsforVaccinesorg - NDs writing in support of immunizations
bull httpwwwvaxopediaorg - A Texas pediatrician who writes many short articles addressing vaccine myths concepts evidence
bull httpwwwvaxnorthwestorg - regional parents talking about the importance of vaccination
bull httpwwwimmunizeorg -- extensive resource for disease and vaccine information for HCPs and parents including specific sections targeting questions around alternative schedules autism mercury etc
bull httpwwwcdcgovvaccinesscheduleshcpchild-adolescenthtml -- schedules and catch up schedules
bull httpwwwsoundsofpertussiscom -- outreach site around pertussis
bull httpwwwcdcgovvaccinesvac-gen6mishomehtm - Top 6 Misconceptions
bull httpwwwkingcountygovdeptshealthcommunicable-diseasesimmunizationchildplain-talk-about-childhood-immunizationsaspx ldquoPlain Talk about Childhood Immunizationsrdquo -- fantastic book that addresses just about any question a family might have about vaccines Download in multiple languages
bull httpwwwchopeduservicevaccine-education-centerhomehtml -- Childrenrsquos Hospital of Philadelphia Vaccine Education Center ndash excellent parent-focused information about vaccines and vaccine-preventable disease including an app called Vaccines on the Go
RESOURCES
bull httpwwwNDsforVaccinesorg - NDs writing in support of immunizations
bull httpwwwvaxopediaorg - A Texas pediatrician who writes many short articles addressing vaccine myths concepts evidence
bull httpwwwvaxnorthwestorg - regional parents talking about the importance of vaccination
bull httpwwwimmunizeorg -- extensive resource for disease and vaccine information for HCPs and parents including specific sections targeting questions around alternative schedules autism mercury etc
bull httpwwwcdcgovvaccinesscheduleshcpchild-adolescenthtml -- schedules and catch up schedules
bull httpwwwsoundsofpertussiscom -- outreach site around pertussis
bull httpwwwcdcgovvaccinesvac-gen6mishomehtm - Top 6 Misconceptions
bull httpwwwkingcountygovdeptshealthcommunicable-diseasesimmunizationchildplain-talk-about-childhood-immunizationsaspx ldquoPlain Talk about Childhood Immunizationsrdquo -- fantastic book that addresses just about any question a family might have about vaccines Download in multiple languages
bull httpwwwchopeduservicevaccine-education-centerhomehtml -- Childrenrsquos Hospital of Philadelphia Vaccine Education Center ndash excellent parent-focused information about vaccines and vaccine-preventable disease including an app called Vaccines on the Go
