Tips and Techniques in Immunization

Tips and Techniques in Immunization

Ma. Liza M. Gonzales, MD, MSc Infectious and

Tropical Disease Section, Department of Pediatrics, PGH-CM

University of the Philippines

Objectives• To present practical TIPS on

• Vaccine timing and interval• Vaccine storage and handling• Vaccine safety

• To review proper TECHNIQUES on vaccine administration

Vaccines

“With the exception of safe water, no other modality, not even

antibiotics, has had such a major effect on mortality reduction…”

Plotkin S, Orenstein W, Offit P. Vaccines, 5th ed. Saunders, 2008.

Classification of Vaccines• Live attenuated vaccines

• Viral• Bacterial

• Inactivated• Whole • Fractional

• Protein-based• Polysaccharide-based

Live attenuated Vaccines• Attenuated

(weakened)form of the “wild”virus or acterium

• Must replicate to be effective

• Immune response similar to natural infection

• Usually produce immunity with one dose (except vaccines given orally)

Live Attenuated Vaccines

• Viral : measles, mumps, rubella, varicella zoster, yellow fever, rotavirus, oral polio, intranasal influenza

• Bacterial: BCG, oral typhoid

Inactivated Vaccines• Cannot replicate • Less interference

from circulating antibody than live vaccines

• Generally require 3-5 doses

• Immune response mostly humoral

• Antibody titer diminishes with time

Inactivated Whole Cell Vaccines

• Viral : polio, hep A, rabies, influenza

• Bacterial: pertussis, typhoid, cholera

Inactivated Whole Cell Vaccines

• Subunit: hep B, influenza, acellular pertussis, HPV

• Toxoid: diphtheria, tetanus

Inactivated Vaccines• Polysaccharide

Vaccines - unique type of inactivated subunit vaccine composed of long chains of sugar molecules that make up the surface capsule of certain bacteria

Pure Polysaccharide Vaccines

• Pneumococcal, meningococcal, Salmonella typhi(Vi)

Conjugate Polysaccharide Vaccines

• Hib, pneumococcal, meningococcal

Timing and Spacing of Vaccines: Simultaneous and

Nonsimultaneous Administration

All vaccines can be administered at the same visit following the minimum age for each vaccine.

Vaccines not given simultaneously should follow appropriate intervals

Spacing and Administration of Live and Inactivated Antigen

Dennehy PH et al. In Feigin and Cherry”s Textbook of Pediatric Infectious Diseases.6 th ed. 2009

a. Exception is diphtheria-reduced tetanus toxoid-acellular pertussis vaccine (Tdap) and meningococcal polysaccharide-protein conjugate vaccine (MCV4) vaccines which should be separated by at least 4 weeks if simultaneous administration is not feasible

b. Live oral vaccines, e.g., oral poliovirus vaccine, rotavirus vaccine, Ty21a typhoid vaccine, can be administered simultaneously or at any interval before or after inactivated or live parenteral vaccines

Antigen Combination Recommended Minimum Interval between Doses

≥ 2 inactivateda None; may be administered simultaneously or at any interval between doses

Inactivated and Live None; may be administered simultaneously or at any interval between doses

≥ 2 live parenteral 4-week minimum interval if not administered simultaneously

≥ 2 live oralb None; may be administered simultaneously or at any interval between doses

Interval Between Doses of the Same Vaccine

Decreasing the interval between doses of a multidose vaccine may interfere with antibody response and protection.

Increasing the interval between doses of a multidose vaccine does not diminish the effectiveness of the vaccine.

Intervals between Ab-containing products and Measles or Varicella Containing

VaccinesProduct and Indication Dose IgG concentration

(mg/kg)

Recommended interval * (months)

Hepatitis A prophylaxis

- Contact prophylaxis 0.02 ml/kg IM 3.3 3

- International travel 0.06 ml/kg IM 10 3

Hepatitis B prophylaxis (HBIG) 0.06 ml/kg IM 10 3

Measles prophylaxis 0.25-0.50 ml/kg IM 40-80 5-6

Rabies prophylaxis (HRIG) 20 IU/kg IM 22 4

Tetanus prophylaxis (TIG) 250 U IM 10 3

Intravenous IG (IVIG)

- Replacement therapy immune deficiencies

300-400 mg/kg IV 300-400 mg/kg IV

8

- ITP 400 mg/kg IV 400 mg/kg IV 8

- ITP 1000 mg/kg IV 1000 mg/kg IV 10

- Varicella postexposure prophylaxis 400 mg/kg IV 400 mg/kg IV 8

- Kawasaki Disease 2 g/kg IV 2 g/kg IV 11

Intervals between Ab-containing products and Measles or Varicella Containing

VaccinesBlood Product Dose IgG

concentration (mg/kg)

Recommended interval * (months)

-Washed RBCs 10 ml/kg IV Negligible None-Packed RBCs 10 ml/kg IV 20-60 mg/kg 6-Whole blood 10 ml/kg IV 80-100 mg/kg 6-Plasma or platelet products

10 ml/kg IV 160 mg/kg 7

*Recommended interval before administration of measles- or varicella-containing vaccine (months)**Rates of antibody clearance after receipt of an immune globulin preparation might vary

CDC. Epidemiology and Prevention of Vaccine-Preventable Diseases. Atkinson W et al, eds. 11th ed. Washington DC: Public Health Foundation, 2009

Tips on Timing and Interval of Vaccines

Other combination of vaccines (live and inactivated, > 2 inactivated, live oral and live parenteral), can be given simultaneously or at any interval between vaccines

For > 2 live parenteral vaccines (measles, MMR, MMRV, varicella) not given at the same visit, minimum interval between vaccines is at least 4 weeks

Follow the recommended minimum AGE and INTERVAL for each vaccine.

WHO recommended vaccine storage conditions

Sensitive to Heat• OPV• Measles• DTP, yellow

fever• BCG• Hib,DT• Td,TT, Hep

B

Sensitive to Cold• Hep B• Hib

(liquid)• DTP• DT• DT• Td• TT

Most sensitive

Least sensitive

Most sensitive

Least sensitive

WHO IVB. Temperature sensitivity of vaccines 2006. WHO/IVB/06.10

WHO recommended vaccine storage conditions

• ALL vaccines are recommended to be transported and stored at +2°C to +8°C• Exception: OPV which alternatively may be

stored at -15°C to -25°C• It is unnecessary to store freeze-dried

vaccines at -20°C• Vaccines sensitive to cold and diluents

must NEVER be frozen• ALWAYS store the vaccine with their

diluent between +2°C and +8°CWHO IVB. Temperature sensitivity of vaccines 2006. WHO/IVB/06.10

Vaccine Storage and Handling • Follow recommendations found in each

vaccine’s package insert for storage, handling, and administration

• Inspect vaccines upon delivery and monitor refrigerator and freezer temperatures to ensure maintenance of cold chain

• Rotate vaccine stock so the oldest vaccines are used first

• Never administer a vaccine later than the expiration date


Tips on Vaccine Storage and Handling

Always maintain proper cold chain during transport and storage.

Store all vaccines in a separate refrigerator in good working condition with uninterrupted power supply.

Rotate vaccine stock, use the oldest vaccines first. Never administer a vaccine later than the expiration date

Vaccine Administration Errors• Wrong diluent• Administration of the wrong

formulation• Incorrect route or site of

administration

www.who.int/injection_safety/en/index.htm

Importance of Proper Vaccine Administration Technique

• Promote optimal antibody response

• Reduce risk of local adverse reactions• Deep IM preferable for

vaccines with adjuvants • depot effect and less granuloma

formation• SC/Intradermal- better for live

vaccines• lessen risk of neurovascular

injury but still immunogenic (e.g. BCG)

Vaccine Injection Techniques

Intramuscular Subcutaneous

Intradermal

Preferred Sites of Vaccine Administration

Anterolateral Thigh (vastus lateralis muscle) Deltoid muscle

Infants and children with inadequate muscle mass

Older children and adolescents

http://www.cdc.gov/vaccines

Best Infection Control Practices for ID, IM and SQ Injections

• Use sterile injection equipment

• Prevent needle-sticks

• Prevent access to used needles

• Place in puncture-proof containers

• Prevent contamination of equipment and medication


Unsafe practices with multidose vaccine vials

Infection Control• Hand hygiene

• recommended between patients• alcohol-based waterless antiseptic

can be used• Gloves

• not required by OSHA unless • potential for exposure to blood or body fluids

• open lesions on the hands

• agency policyStaphylococcal contamination of a multidose vial led to the septic deaths


Follow Open Vial Policy


Vaccine Administration• Administer vaccines within the prescribed time

periods following reconstitution• Draw vaccines into syringes immediately prior

to administration• NEVER mix vaccines in the same syringe

unless they are specifically approved for mixing

• Record vaccine and administration information, including lot numbers and injection sites, in the patient’s record (may use pre-printed vaccine labels)


Other Vaccine Administration Issues

• Not necessary to change needles between drawing or reconstituting vaccine and administration unless needle is bent or contaminated

• Injection sites in same limb should be separated by at least 1 inch

• Aspiration is not required• no reports of injury from failure to

aspirate

CDC/ACIP MMWR 2006; www.who.int/injection_safety/en/index.htm

Tips on Vaccine Administration Always read the package labels to avoid vaccine administration errors (wrong diluent, wrong formulation).

Do NOT deviate from recommended route of administration.

Comply with infection control practices during and after vaccination.

Importance of Vaccine Safety• Decreases in disease risk and

increased attention on vaccine risks• Public confidence in vaccine safety

is critical• Higher standard of safety expected of

vaccines• Vaccinees generally healthy• Lower risk tolerance need to search for

rare reactions• Vaccination universally recommended and

mandatedCDC. Epidemiology and Prevention of Vaccine-Preventable Diseases. Atkinson W et al, eds. 11th ed. Washington DC: Public Health Foundation, 2009

What Is an Adverse Event Following Immunisation (AEFI)?

• Vaccine reaction caused by vaccine’s inherent properties and individual response of vaccinee

• Programme error caused by error in vaccine preparation, handling, or administration

• Coincidental happens after immunization but not caused by it - chance occurrence or due to underlying illness

• Injection reaction anxiety or pain of injection not vaccine, e.g. syncope (vasovagal reaction) or fainting, hyperventilation

• Unknown cause cannot be determined

A medical incident that takes place after an immunization, causes concern, and is believed to be caused by immunization

WHO Immunization safety surveillance. 1999 WPRO/EPI/99.01

Vaccine reactions• Common, minor reactions

• Vaccines stimulate immune system• Usually self-limiting• Warn parents and advise how

to manage (e.g. paracetamol, cool cloths, sponging, give extra fluids)

• Rare, more serious reactions• anaphylaxis • vaccine specific reactions


Vaccine Adverse Event• Plausible time period following vaccination• Previously associated with a particular vaccine• Event conforms to a specific clinical syndrome

(strong biologic plausibility )• Laboratory confirmation (e.g., isolation of vaccine

strain)• Recurrence on re-administration of the vaccine

(“positive rechallenge”)• Controlled clinical trial or epidemiologic study

shows greater risk in vaccine recipients vs controls


Precautions during and following Vaccine Administration • Have patients sit or lie down during

injection• Observe patients for 15 -20 minutes

after vaccination• Be prepared for emergency care of a

person who experiences an anaphylactic reaction

• If syncope develops, observe patients until symptoms resolve; never leave patient alone

• Epinephrine and equipment for maintaining an airway should be available for immediate useCDC. MMWR 2006;55(No. RR-15):1–48; AAP. Pickering LK et al, eds., Red Book: 2009

Time Scale of AnaphylaxisTime Scale Signs and symptoms

of AnaphylaxisSeverity

Early Warning Signs

Occurs within a few minutes

Late, life-threateningSymptoms

Dizziness, perineal burning, warmth, pruritus

Flushing, urticaria, nasal congestion, sneezing, lacrimation, angioedema

Hoarseness, abdominal cramps, substernal pressure

Laryngeal edema, dyspnea, abdominal pain

Bronchospasm, stridor, collapse, hypotension, dysrhythmias

Mild

Mild to Moderate

Moderate to severe

Moderate to severe

Severe


Management of AnaphylaxisAge (in years) Dose of Epinephrine

(1:1000)*

Less than 1 year old1 year old2 years old3 – 4 years old5 years old

0.05 ml0.1 ml0.2 ml0.3 ml0.4 ml

*Epinephrine (1:1000) 0.01ml/kg up to max 0.5ml deep IM. May repeat tevery 10–20 minutes up to 3 doses

CDC. MMWR 2006;55(No. RR-15):1–48; WHO Immunization safety surveillance. 1999 WPRO/EPI/99.01

Common, minor vaccine reactions

Vaccine Local reaction (pain, swelling, redness)

Fever >38oC Irritability, malaise, systemic symptoms

BCG 90-95% - -Hib 5-15% 2-10% -Hep B Adults ~15%

Children ~5%1-6% -

Measles/MMR ~10% 5-15% 5% (rash)OPV - <1% <1%TT/DT/Td ~10%* ~10% ~25%Pertussis (DTwP)

Up to 50% Up to 50% up to 55%

*Rate of local reactions likely to increase with booster doses, up to 50-85%


Rare, more serious reactions


Vaccine Reaction Onset interval

Number of doses per reaction

BCG Suppurative lymphadenitisBCG osteitisDisseminated BCG

2-6 months1-12 months1-12 months

1 in 1-10,0001-3,000 to 100 M~1 in 1 M

Hib Nil known

Hep B AnaphylaxisGuillain Barre syndrome

0-1 hour1-6 weeks

1 in 6-900,000~5 in 1 M

Measles/MMR

Febrile seizuresThrombocytopeniaAnaphylaxisEncephalopathy

5-12 days15-35 days0-1 hour6-12 days

1 in 30001 in 30,000~1 in 1 M<1 in 1 M

Rare, more serious reactions


Vaccine Reaction Onset interval

Number of doses per reaction

OPV Vaccine associated paralytic poliomyelitis (VAPP)

4-30 days 1 in 750,000-1.3M (1st dose)1 in 5.1 M (subseq doses)

Tetanus Brachial neuritisAnaphylaxisSterile abscess

2-28 days0-1 hour1-6 weeks

0.5-1 in 100,0001 in 100,000 -2.5M 6-10 in 1 M

DTP Persistent (>3 hrs) inconsolable screamingSeizuresHHEAnaphylaxis/ shockEncephalopathy

0-24 hours

0-3 days0-24 hours0-1 hour0-2 days

1 in 15- 1000

1 in 1750-12,5001 in 1000-33,0001 in 50,0000-1 in 1 M

* Hypotonic hyporesponsive episode

Weighing the Risks and Benefits of Vaccination

DISEASE RISK VACCINE REACTIONDisease Complication Risk

Diphtheria MyocarditisDeath

10-25%2-10%

Pertussis SeizuresCNS sequelaeDeath

1-3%0.1 to 0.3%1 in 200

Tetanus Death 25-70%

Vaccine Reaction No. of doses per reaction

DPT Seizures

HHE

Anaphylaxis

Encephalopathy

1 in 1750-12,5001 in 1000-33,0001 in 50,000

0-1 in 1 M

No evidence that vaccines increase the risk for...

• Diabetes 1, 2

• Multiple sclerosis 3

• Guillain Barre Syndrome 4

• Inflammatory bowel disease 5

• Autism Spectrum Disorder 6,7

• Neurodevelopmental disorders 8

• Sudden Infant death syndrome 9

• Infantile spasm 9

1. Canadian Study Group Diabetes Care 1997; 2. DeStefano F et al. Pediatrics 2001; 3. Ruthschmann OT et al Neurology 2002;4. Stowe J et al. Am J Epidemiol 2009; 5. IOM. National Academy Press, 2002; 6. Halsey N. Pediatrics 2001; 107(5);e84; 7. Wilson K et al. Archives of Pediatric and Adolescent Medicine 2003; 157:628-634; 8. Thompson W et al. N Engl J Med 2007;357:1281-92; 9. Howson CP et al. Pediatrics 1992;89(2): 1448-1453

Vaccination and Autoimmune Disease, Inflammatory Disease, or Autism

Increasingly crowded vaccination calendar

Vaccination in age groups with high incidence of specific disease conditions or autoimmune disorders

• Autoimune disease• Autism Spectrum

Disorder• Atopy or Allergy• Diabetes

Rising incidence or increasing recognition of:

Vaccine Safety: Benefit Risk Communication

High

CARING

Low

Affection TRUST

Distrust Respect

COMPETENCE High

Paling J. BMJ 2003;327:745-74; Alaszewski A, Horlick-Jones T. BMJ 2003;327:728-731

TRUST = Competency + Caring

Tips on Vaccine Safety Prior to Vaccination: Screen patients for contraindications and precautions prior to each vaccine dose; provide information on vaccine to be administered

During Vaccination: Do NOT deviate from recommended route, site and dosage of vaccine

After Vaccination: Observe necessary precautions, be prepared for emergency care of anaphylactic reaction; provide information and advice on vaccine side effects

Conclusion: Role of Immunization Provider

• Timing and spacing of vaccine doses• Proper vaccine storage and

administration• Observe vaccine precautions and

contraindications• Educate patients and parents about

vaccine benefits and risks • Manage vaccine side effects• Report suspected side effects


Thank you and have a good day!

Selected References• CDC. General recommendations on immunization:

recommendations of the Advisory Committee on Immunization Practices. MMWR 2006;55(No. RR-15):1–48.

• AAP. Pickering LK, Baker CJ, Long SS, McMillan J. eds., Red Book: 2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009.

• CDC. Surveillance for safety after immunization. MMWR 2003;52(No.SS-1):1–24.

• CDC. Update: Vaccine side effects, adverse reactions, contraindications and precautions: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1996;45(No. RR-12):1–35. 57

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Tips and Techniques in Immunization