IMMUNIZATIONfinal years Aug 2013

U. Ghosh

VaccinationInfectionImmunoglobulin Rxmaternal antibodies

What is a vaccine? Vaccines are harmless agents, perceived as enemies

They are molecules that elicit an immune response, thereby providing protective immunity against a potential pathogen

Immunological Memory

After an immune response, memory cells are produced. These lay dormant in the lymphatic system for many years if they detect a pathogen with the specific antigen they can clone rapidly and secrete antibodiesThis means that secondary exposure to a pathogen produces a much more rapid secondary response which means you are not as badly affected the second time

EpidemiologyPre and post vaccine incidence of common infectious diseases

Herd immunity is the proportion immune in a herd ( deduced from the vaccination coverage)

Herd effect is the protection offered to unvaccinated members when goodproportion (usually more than 85%) of the herd is vaccinated- reduced carriage of the causative microorganism by the vaccinated cohort - only with vaccines against those diseases where humans are the only source (there is no herd effect for tetanus) - effective vaccine is a prerequisite for good herd effect (OPV in India, BCG and unconjugated polysaccharide vaccines have no herd effect)

Epidemiologic Shift refers to an upward shift in age of infection/disease incommunities with partial immunization coverage. (Owing to vaccination the natural circulation of the pathogen decreases and the age of acquisition of infection advances - especially important for diseases like rubella, varicella and hepatitis A wherein severity of disease worsens with advancing age.)

Current UIP schedule

BACILLUS CALMETTE GUERIN (BCG) VACCINE1921 - continues to be the only vaccine against tuberculosis lyophilized (freeze-dried) live attenuated reconstituted vaccine should be stored at 2 to 8C, protected from light and discarded within 4 hours of reconstitution with normal saline. 0.1 ml in tuberculin syringeclean area with sterile waterintradermal to raise wheal of 5 mmjust above insertion of left deltoid - preferred for easy visualization of the BCG scar and for optimum lymphatic drainage.

S/E :abscess, disseminated Tb in immunocompromised C/I :immunocmpromised; HIV with CD4 < 25%Efficacy? 0 - 80 % protection in different trialsmeta-analysis: 50% less risk of active Tbless risk of disseminated Tb & Tb menigitis in children

3 wks papule6 wks size increases to 4 8 mm12 wks subsides / shallow ulcer with crust24 wks heals with scaripsilateral axillary LNE usually heals spontaneously

ORAL POLIO VACCINEtrivalent vaccine with live attenuated poliovirus types 1, 2, 3very heat sensitive vaccine : store at 20 C at district level and in the freezer at the clinic. The vaccine must reach the outreach facility at 2 to 8 C in vaccine carriers with ice packs. Dose: 2 drops orallyseroconversion rates after 3 doses of OPV average roughly 30% per dose - Multiple doses of OPV are necessary before 90-95% of children develop immune responses to all three poliovirus types. S/E: vaccine associated paralytic poliomyelitis (VAPP). rare (1 per 4.1 to 4.6 million doses) but serious, may occur in the vaccine recipient or contact of the vaccine recipient. C/I :immunodeficient patients and their household contacts.

DIPHTHERIA, TETANUS AND PERTUSSIS VACCINESDTwP(triple antigen)is composed of tetanus and diphtheria toxoids as well as killed whole cell pertussis bacilli adsorbed on insoluble aluminium salts which act as adjuvants. stored at 2 to 8 C - should never be frozen 0.5 ml intramuscularly anterolateral aspect of the thigh. immunogenicity against diphtheria/tetanus of 3 doses exceeds 95%; against pertussis ranges from 70-90% Immunity against all three components wanes over the next 6-12 years and thus regular boosting is needed immunize even those recovering from diphtheria, tetanus and pertussis as natural disease does not offer complete protection.

S/E Most due to the pertussis component. Minor adverse effects in almost half the vaccinees: pain, swelling and redness at the local site, fever, fussiness, anorexia, vomiting.Serious adverse effects are rare. fever more than 40.5Cpersistent crying (of more than 3 hours duration) hypotonic hyporesponsive episodes (HHE)seizures encephalopathyC/I absolute : encephalopathy within 7 days of DTwP anaphylaxis relative: Progressive/evolving neurological illnessesDTwP is not recommended in children aged 7 years and older due to increased risk of side effects

MEASLES VACCINElive attenuated vaccines freeze-dried stored frozen or at 2 to 8C Reconstituted vaccine is destroyed by light and is very heat labile - should be used within 4-6 hours of reconstitution0.5 ml subcutaneously or intramuscularly should be given irrespective of prior history of measles as any exanthematous illness is often confused as measles

Seroconversion rates are around 60% at 6 months 80-85% at 9 months beyond 95% at 12-15 monthsantibody titers wane over the years - an additional dose of measles vaccine preferably as MMR vaccine at the age of 15 months is required

In case of an outbreak it can be given to infants as young as 6 months; within 2 days of exposure protects +/or modifies the severity of clinical disease;

C/I : severely immunocompromised, severe allergic reactions

HEPATITIS B (hep B) VACCINEvaccine containing the surface antigen of Hepatitis B is produced by recombinant technology in yeast and adjuvanted with aluminium saltsstored at 2 to 8 C - should not be frozendose: 0.5 ml intramuscularlyseroconversion rates are greater than 90% after 3 dosesextremely safe and well toleratedany schedules:birth, 1 and 6 mths ; birth, 6 and 14 wks; 6, 10 and 14 wks

HEMOPHILUS INFLUENZAE TYPE B (hib)conjugated vaccines Hib capsular polysaccharide (polyribosyl ribitol phosphate or PRP) conjugated with a protein carrierstored at 2 to 8 C dose is 0.5 ml intramuscularly90-100% efficacyimmunological memory is insufficient - booster dose is mandatory for sustained protectionSide effects are mild and usually local

MMR VACCINE live, attenuatedlyophilized - frozen for long-term storage Reconstituted vaccine should be stored at 2 to 8C, protected from light and used within 4-6 hours. dose: 0.5 ml subcutaneously - can be given along with all other childhood vaccines except BCG vaccine efficacy: lifelong protection against rubella in 95% long term protection against mumps is 60-90%introduced in those states where measles coverage is at least 70% S/E local side effects mild rash may develop in 5% arthralgia and arthritis may occur 1-3 weeks later but is usually mild fever more than 39C, 7-12 days later, in 5% Immune thrombocytopenic purpura C/I severely immunocompromised

IAP recommended vaccines (2011)

IAP Immunization Timetable 2012I. IAP recommended vaccines for routine use

AGEVACCINEScommentsBirthBCGOPV 0Hep-B 1Hepatitis-B: Administer Hep-B vaccine to all newbornsbefore hospital discharge6 weeksDTwP 1/DTaP 1IPV 1Hep-B 2Hib 1Rotavirus 1PCV 1Polio: All doses of IPV may be replaced with OPV if former isunaffordable/unavailable Additional doses of OPV on all supplementary immunization activities (SIAs) Two doses IPV instead of 3 for primary series if startedat 8 weeks, and 8 weeks interval between the dosesRotavirus: 2 doses of RV-1 and 3 doses of RV-510 weeksDTwP 2/DTaP 2IPV 2Hib 2Rotavirus 2PCV 214 weeksDTwP 3/DTaP 3IPV 3Hib 3Rotavirus 3PCV 3Rotavirus: Only 2 doses of RV1 are recommended at present.

6 monthsOPV 1Hep-B 3The final (third or fourth) dose in theHepB vaccine series should be administered no earlierthan age 24 weeks and at least 16 weeks after the first dose9 monthsOPV 2Measles12 monthsHep-A 1For both killed and live hepatitis-A vaccines, 2 doses are recommended15 monthsMMR 1Varicella 1PCV boosterThe risk of breakthrough varicella is lower if given 15 months onwards.16 to 18 monthsDTwP B1/DTaP B1IPV B1Hib B1The first booster (4thth dose) may be administered as early as age 12 months, provided at least 6 months have elapsed since the third dose.18 monthsHep-A 2For both killed and live hepatitis-A vaccines 2doses are recommended2 yearsTyphoid 1Typhoid revaccination every 3 years, if Vipolysaccharidevaccine is used.4 to 5 yearsDTwP B2/DTaP B2OPV 3MMR 2Varicella 2Typhoid 2MMR: the 2nd dose can be given at anytime 4-8 weeks afterthe 1st dose.Varicella: the 2nd dose can be given at anytime 3 months afterthe 1st dose10 to 12 yearsTdap/TdHPVTdap: is preferred to Td followed by Td every 10 years. HPV: Only for females, 3 doses at 0, 1-2 and 6 months.

II. IAP recommended vaccines for High-risk* children (Vaccines under special circumstances):1-Influenza Vaccine2-Meningococcal Vaccine3-Japanese Encephalitis Vaccine4-Cholera Vaccine5-Rabies Vaccine6-Yellow Fever Vaccine7-Pneumococcal Polysaccharide vaccine (PPSV 23)* High-risk category of children: Congenital or acquired immunodeficiency (including HIV infection), Chronic cardiac, pulmonary (including asthma if treated with prolonged high-dose oral corticosteroids), hematologic, renal (including nephrotic syndrome), liver disease and diabetes mellitus Children on long term steroids, salicylates, immunosuppressive or radiation therapy Diabetes mellitus, Cerebrospinal fluid leak, Cochlear implant, Malignancies, Children with functional/ anatomic asplenia/ hyposplenia During disease outbreaks

DTaPacellular vaccine incidence of both minor and major adverse effects is reduced by two thirds efficacy and duration of protection, storage, dose, contraindications are same as those for whole cell vaccines DTaP vaccines must not be used in children 7 years or older because of increased reactogenicity. DTuse in children below 7 years of age where pertussis vaccination is contraindicated; in EPI , used as the 2nd childhood booster at the age of 5 years Tdcontains the usual dose of tetanus toxoid and reduced quantity of diphtheria toxoid used to regularly boost adult immunity against diphtheria in addition to tetanus every 10 years. Tdap standard quantity tetanus toxoid and reduced quantity diphtheria and acellular pertussis vaccine (Tdap)efficacy against clinical disease exceeds 90% Serious adverse events have not been reported.

Inactivated Polio Vaccines (IPV)killed poliovirus

stored at 2 to 8C

dose is 0.5 ml intramuscularly/subcutaneously

Seroconversion rates are 90-100% three doses at 6,10 and 14 weeks.

The vaccine is very safe

ROTA VIRUS VACCINEHuman monovalent attenuated live vaccine85-98% efficacy against severe rotavirus gastroenteritisstored at 2 to 8C and must not be frozen.administer promptly after reconstitution as 1 ml orally. first dose can be administered at the age of 6 weeks and should be given no later than at the age of 12 weeks with interval between the 2 doses should be at least 4 weeks.S/E: risk of intussusception if vaccines are given to older infantsC/I: severe allergic reaction (eg, anaphylaxis) after a previous dose of rotavirus vaccine or to a vaccine component or allergy to latex

PNEUMOCOCCAL VACCINEconjugate pneumococcal vaccines (PCV)

intramuscularly as a 0.5 mL dose

can be administered at the same time as other routine childhood vaccinations, if administered in a separate syringe at a separate injection site.

minimum age for administering first dose is 6 weeks

routine use of PCV13 is not recommended for healthy children aged more than 5 years.

HEPATITIS A VACCINEFormalin inactivated adjuvanted with aluminimum hydroxide. intramuscularlymay be safely given with other childhood vaccinesprotective efficacy is around 90-100%Adverse reactions are minor and usually include local pain and swelling.

Live attenuated vaccine1 ml subcutaneously> 95% seroconversion

Two doses 6 months apart are recommended for all vaccinesin children aged 1-15 years

VARICELLA VACCINElive attenuated vaccine0.5 ml subcutaneouslylyophilized, protect from light ,use within 30 minutes of reconstitutionefficacy of 98.3%

S/E: local reactions, injection site rash, fever and a systemic varicella like rash in around 5 %Herpes zoster in vaccine recipients is known to occur due toboth the vaccine virus and the wild virus; however the overall incidence of herpes zoster in vaccinated children much lower than unvaccinated children

C/I: clinically manifested HIV infection and in the immunocompromised

primary immunization: 1st dose at 15 mths + 2nd dose at 4-6 years. catch up vaccination: children below 13 years - 2 doses 3 mths apart 13 years or more - 2 doses at an interval of 4-8 weeks.

Vi polysaccharide vaccine0.5 ml intramuscularly every 3 years beginning at 2 yearsstored at 2-8C and should not be frozen

S/E: mild and include pain and swelling at injection site

C/E: history of hypersensitivity to the accine can be safely given in the immunocompromised including HIV infected.TYPHOID VACCINES

HUMAN PAPILLOMA VIRUS (HPV) VACCINESrecombinant DNA technology

quadrivalent vaccine

2 to 8C and must not be frozen

0.5 ml intramuscular in deltoid

Three doses at 0, 2 and 6 months

not 100% protective against cervical cancer and not a replacement for periodic screening

Types of VaccinesThere are four basic types of vaccine in use todayKilled vaccines: These are preparations of the normal (wild type) infectious, pathogenic virus that has been rendered non-pathogenic, usually by chemical treatment such as with formalin that cross-links viral proteins.Attenuated vaccines: These are live virus particles that grow in the vaccine recipient but do not cause disease because the vaccine virus has been altered (mutated) to a non-pathogenic form; for example, its tropism has been altered so that it no longer grows at a site that can cause disease. Sub-unit vaccines: These are purified components of the virus, such as a surface antigen. DNA vaccines: These are usually harmless viruses into which a gene for a (supposedly) protective antigen has been spliced. The protective antigen is then made in the vaccine recipient to elicit an immune response

Live attenuatedKilled / inactivatedSubunitDNABCGOPVMMRVaricellaDPT:Diphtheria toxoid (inactivated toxin)Pertussis whole cell (killed organism)Tetanus toxoid (inactivated toxin)conjugated:HIBHepBHepATyphoidpolysaccharide:pneumococcalHPV

WHY VACCINATE ?

POLIOMYELITISTHERE IS NO CURE painful paralysis that may lead to permanent paralysis or death

TUBERCULOSISmiliary tuberculosistuberculosis spineWithout treatment: Death in 3 4 weeksStage I: non-specific signs and symptoms good prognosis with Rx

Stage II: stage of meningeal irritation 75% recover

Stage III: hemiplegia, quadriplegia,coma 50 70% mortality (only 30 50% survive)

20 - 44% 0f survivors have sequelae

neurotuberculosis

DIPHTHERIArespiratory tract:death by suffocationtoxic cardiomyopathy: death by heart failure toxic neuropathy: paralysis, deaththe only cure is by an antitoxin which is difficult to obtain and will only work if givenbefore the free toxin has bound to the tissues

PERTUSSISspasms of cough are so severe that laryngospasm ensues leading to

death by apnoeabrain haemorrhages and hypoxia leading to seizures and encephalopathypulmonary haemorrhage, pulmonary hypertensionpneumothoraxsecondary bacterial pneumonia

ANTIBIOTICS HAVE NOT BEEN PROVED TO HAVE CLINICAL BENEFIT

TETANUStetanus spores are in the environment and cannot be eradicatedtetanus immuneglobulin only neutralizes any remaining free toxin and cannot act on any toxin that has already bound to the tissues

DEATH IN ABSENCE OF INTENSIVE CARE: > 75%

MEASLESpneumonia, seizures, malnutrition, noma

late sequelae: SSPE uncontrolled myoclonic jerks while conscious, later dystonia, dementia, death

NO CURE

MUMPSusually a mild disease but can have serious or painful complications

meningitismeningoencephalitisepidymo-orchitis

NO CURE

RUBELLACongenital rubella syndrome: deafness, cataracts, congenital heart disease,meningoencephalopathy, developmental delay, retardation, autismNO CURE

HEPATITIS Bacute liver cell failurechronic hepatitscirrhosisend-stage liver diseasehepatocellular carcinoma10 100 % times more infective than HIVNo reliably effective therapy

HAEMOPHILUS INFLUENZAE bmeningitis deafness, neurological sequelaepneumonia,bacteraemia cellulitisorbital cellulitisacute epiglottitisarthritispericarditisotitis media

EpidemiologyVaccine preventable diseases: India reported casesimmunization can be credited with saving approximately 9 million lives a year worldwide. A further 16 million deaths a year could be prevented if effective vaccines were deployed against all potentially vaccine-preventable diseases

Vaccine preventable diseases 1980 2008Diphtheria39,2316,081Measles114,03648,181Pertussis320,10944,180Polio18,975559(1 in 2011)Tetanus (Neonatal)9,313 (1990)811Tetanus (Total)45,9483,714

Cold ChainThe system of transporting, storing and distributing vaccines in a potent state at the recommended temperature from thepoint of manufacture to the point of use is the cold chainVaccine potency once lost cannot be restoredremains a highly vulnerable point

Sensitivity of Vaccines to Heat - All vaccines are sensitive to heat but to different degrees. Live vaccines are more susceptibleSensitivity of Vaccines to Freezing mainly all aluminum adjuvanted vaccines (DTwP, DTaP, TT, DT, Td, TT, Hepatitis B,Hepatitis A) also other vaccines - The Shake Test can be used to determine if a vaccine vial has been suspected to be frozen at any time Sensitivity of Vaccines to Light Lyophilized and reconstituted BCG, measles, MMR, varicella, most DTaP

Vaccine Vial Monitors (V V M)time and temperature sensitive colored label that provides an indication of the cumulative heat to which the vial has been exposedused especially for temperature monitoring of OPV, which is the most thermo labile of all vaccineschange of color is irreversibleInner square is white, or lighter than outer circle: If the expiry date has not passed, can be usedInner square matches color of outer circle or is darker than outer circle: vaccine should be discarded, regardless of the expiry date

essential components of a cold chain

1. Personnel responsible for vaccine distribution2. Appropriate equipment to store and transport vaccines3. Appropriate transport facilities4. Maintenance of equipment5. Monitoring

Cold Chain EquipmentThe cold chain involves two complementary aspects: 1. The set chain represented by the walk-in cold rooms, deep freezers and refrigerators 2. The mobile chain represented by isothermic boxes and vaccine carriers.Walk in cold rooms (WIC) and Walkin freezers (WIF) are used for bulk storage of vaccines at the manufacturer site, or at major distribution pointsDeep freezers are used for long term storage - Ice lined refrigerators (ILR) are used where the power supply is intermittent.

Domestic Refrigerator - main compartment should have a temp of 2 to 8 C,freezer compartment should have a temp of 5 to 15 Cthermometer should be placed in both the freezer and the main compartment Temperatures should be recorded at least twice a day and a log maintainedIce packs and jars/bottles water should be kept in the freezer and the door of the main compartment and the lowest part (baffle tray) helps maintain temperature during power failures and cuts for at least 3 to 4 hoursEach vaccine pack/vial must be labeled with the expiry date and the principle of FEFO (First expired first out) and FIFO (First in first out)

Domestic Refrigerator

COLD BOXES: are insulated boxes, used for transportation and emergency storage of vaccines and icepacks. Place conditioned ice packs at the bottom and sides of the cold box before loading the vaccines in cartons or polythene bags.Always keep a thermometer inside the cold box.

VACCINE CARRIERS: (with 4 conditioned ice packs) maintain the inside temperature between +20C to +80C for 12 hours, if not opened frequently. They are used for carrying vaccines (16-20 vials) and diluents to session sites.

ICE-PACKS: are plastic containers filled with water. These are frozen in the deep freezer and when placed in nonelectrical cold chain equipment such as vaccine carriers and cold boxes, help increase the holdover time

FEVER OF UNKNOWN ORIGIN

Fever : controlled increase in body temperature over the normal values for an individual

Normal circadian rhythm: diurnal variation of the body temperature where the normal body temperature is 1C higher in the late afternoon and early evening

Fever of unknown origin: Fever documented by a health care worker, the cause of which cannot be identified after 3 weeks of outpatient evaluation or 1 week of inpatient evaluation

Fever without a focus: fever without localizing signs or symptoms and present for less than 1 week in children less than 36 months of age

ETIOLOGY:usually due to an atypical presentation of a common diseaseInfectionsRheumatological disordersNeoplasmsHypersensitivity disordersGranulomatous diseasesHereditary disordersMiscellaneous

BACTERIALTuberculosisSalmonellaMycoplasma BrucellosisListeriosis

B. VIRUSESCytomegalovirusHepatitis virusInfectious mononucleosisHIV

1.INFECTIONS

C. PARASITIC DISEASESmalariatoxoplasmosistoxocaraamoebiasis

D.RICKETTSIAScrub typhusRocky Mountain Spotty Fever

E. SPIROCHAETESLeptospirosisBoreliaSyphilis

F. FUNGAL DISEASESHistoplasmosisCocciodomycosisBlastomycosis

G. CHLAMYDIA2. HYPERSENSITIVITY DISEASESDrug feverSerum sicknessHypersensitivity pneumonitis

3.RHEUMATOLOGICAL DISEASESjuvenile idiopathic arthritisSLERheumatic feverJuvenile DermatomyositisBehcet disease4. GRANULOMATOUS DISEASESSarcoidosisCrohn disease

5. NEOPLASMSLeukaemiaLymphomaNeuroblastomaWilms tumourInflammatory pseudotumorAtrial myxoma6.FAMILIAL / GENETIC DISORDERSAnhydrotic ectodermal dysplasiaIchthyosisFamilial dysautonomiaSickle cell crisisFamilial fever syndromes

7. MISCELLANEOUS

Haemophagocytic syndromesKawasaki diseaseInflammatory Bowel diseaseThrombophlebitisChronic Active HepatitisDiabetes InsipidusHypothalamic central feverThyrotoxicosisKikuchi diseasePancreatitis PoisoningPulmonarry oedema

APPROACH TO A CHILD WITH PUO

HISTORY

Detailed chronological historyAgeAddress / travelDrug intakePets and animalsFamily history

1.Detailed chronological history

Types of fever pattern:Intermittent fever fever with the temperature reaching normal in between

Sustained fever temperature never touches normal and varies 0.5C

Remittent fever - temperature never touches normal and varies > 0.5C

Relapsing fever - temperature normal on some days eg: tertian fever on day 1 and day 3 in malaria due to Pl. vivax quartan fever on day 1 and day 4 in malaria due to Pl. malariae

Biphasic fever (camelback pattern) single illness with a few afebrile days separating 2 periods of febrile days eg: dengue, rickettsial fever, leptospirosis, polio

Periodic fever fever syndromes with regular periodicity eg: cyclic neutropenia, PFAPA

2. Age

6 years :respiatory tract infection, genitourinary tract infection, localised infection ( adscess, osteomyelitis), JIA, leukaemiaAdolescents: inflammatory bowel disease, autoimmune diseases, lymphoma

3. Address / travel : endemic areas

4. Drug intake: eg: atropine eye drops

5.Animals: eg. tick-bourne diseases, zoonosis

6. Family history: contagious diseases, familial disorders

EXAMINATION

1.Eyesred, weeping eyes connective tissue disorderpalpebral conjunctivitis measles, coxsackie virus, tb, EBVbulbar conjunctivitis kawasaki disease, leptospirosisuveitis JIA, SLE, kawasaki disease, sarcoidosis, vasculitischorioretinitis CMV, toxoplasmosis, syphilisproptosis orbital infection, thyrotoxicosis, tumourabsent corneal reflex familial dysautonomia

2. Skin absence of sweat dehydration (AGE, DI), anhidrotic ectodermal dysplasia, familial dysautonomiaRash viral exanthems, rickettsial, bacterial

3. Hyperaemia of pharynx EBV, CMV, Kawasaki disease, leptospirosis

4. Sinus tenderness sinusitis

5.Bone tenderness osteomyelitis, neoplasm Muscle tenderness dermatomyositis Arthritis - infections, rheumatic fever, autoimmine diseases

6. rectal tenderness abcess, adenitis, osteomyelitis

7. teeth dental abscess, anhidrotic ectodermal dysplasia

INVESTIGATIONS

pace should reflect severity of disease

CBCUrinanalysisBlood smearESR or CRPBlood cultureUrine cultureX rays chest, sinuses, mastoidEchocardiography

Serological testsultrasound abdomenbone marrow biosynucleotide scansbiopsyGI scopyCT / MRI

TREATMENT

Antipyretics if teperature above 39C (102.2F)eg: paracetamol 10 15 mg/kg/dose Q4H ibuprofen 5 10 mg/kg/dose

Avoid empirical antibiotics

PROGNOSIS

Depends on the underlying diseaseIn many cases, no diagnosis 75% fever abates spontaneously 25% continue to have fever