Respond

1. Adverse Events Following Immunization Dr S.M.Zahraei Center for Disease Control Ministry of Health and Medical Education Detect Report Respond Investigate

2. TREND OF DIPHTHERIA IMMUNIZATION COVERAGE & CASES (1984 –2003 , I.R.IRAN)

3. TREND OF PERTUSSIS IMMUNIZATION COVERAGE & CASES (1984 –2003,I.R.IRAN)

4. TREND OF NEONATAL TETANUS IMMUNIZATION COVERAGE & CASES (1984 –2003,I.R.IRAN)

5. TREND OF MEASLES IMMUNIZATION COVERAGE & CASES (1984 –2003,I.R.IRAN)

6. TREND OF POLIO IMMUNIZATION COVERAGE & CASES (1984 –2003,I.R.IRAN)

7. TREND OF BCG IMMUNIZATION COVERAGE (1984 –2003,I.R.IRAN)

8. TREND OF HEPATITIS B IMMUNIZATION COVERAGE (1994 –2003,I.R.IRAN) Prevalence rate of H.B : Survey 1991 : 3 % Survey 1999 : 1. 7 %

9. AEFI is a medical incident that takes place after an immunization, causes concern, and is believed to be caused by immunization • Vaccine reaction • caused by vaccine’s inherent properties • Programme error • caused by error in vaccine preparation, handling or administration

10. Coincidental • happens after immunization but not caused by it a chance association • Injection reaction • anxiety or pain of injection not vaccine • Unknown • cause can not be determined

11. Cluster of AEFI >=2 cases of the same adverse event following immunizations related in time, geography or in the vaccine administered • Why is it important to monitor for clustering?

12. Potential Objectives For AEFI Surveillance System • Detect, correct, and prevent programme errors • Identify problems with vaccine lots or brand • Prevent false blame from coincidental events • Maintain confidence by properly responding to parent/community concerns while increasing awareness (public and professional) about vaccine risks

13. Generate new hypotheses about vaccine reactions that are specific to the population • Estimate rates of occurrence on AEFI in the local population, compared with trial and international data (particularly for new vaccines being introduced)

14. DETECTING AND REPORTING AEFIs

15. Which Events To Report? • Death, hospitalization, or other severe/unusual events • Toxic shock syndrome • Severe local reaction • Sepsis • Injection site abscess (bacterial/sterile) • BCG lymphadenitis • AEFIs causing concern or suspicion of vaccine involvement

16. Which Reports To Investigate? Investigate if • possible programme error • serious event of unexplained cause • above expected rate (not just numbers) • potential damage to the immunization programme Certain events (toxic shock syndrome, sepsis, abscess,and BCG lymphadenitis) are likely to arise from programme errors and must always be investigated

17. Programme Errors • Non-sterile injection • infection • Incorrect preparation • abscess (inadequate shaking) • drug effect (use of drug instead of vaccine/diluent)

18. Injection in wrong site • local reaction/abscess (wrong tissue level) • nerve damage • Vaccine frozen • local reaction • Contraindication ignored • avoidable severe reaction

19. Serious Events • Anaphylactoid reaction (acute hypersensitivity reaction) • Anaphylaxis • Persistent (more than 3 hours) inconsolable screaming • Hypotonic hyporesponsive episode • Seizures, including febrile seizures(6-12 days for measles/MMR; 0-2 days for DTP) • Encephalopathy (6-12 days for measles/MMR; 0-2 days for DTP)

20. Serious Events (cont…) • Acute flaccid paralysis • (4-30 days for OPV recipient; 4-75 days for contact) • Brachial neuritis • (2-28 days after tetanus containing vaccine) • Thrombocytopaenia • (15-35 days after measles/MMR) • Disseminated BCG infection • Osteitis/osteomyelitis

21. Contraindications True contraindications are rare • Current serious febrile illness • delay vaccine administration • History of severe AEFI after previous dose • Evolving neurological disease • avoid whole cell pertussis vaccine • (e.g. uncontrolled epilepsy) • Type 1 hypersensitivity to egg - avoid yellow fever & influenza but can use vaccines made in chick fibroblasts • Symptomatic HIV • avoid BCG and yellow fever

22. Vaccine Contraindication All vaccines Anaphylactic reaction to vaccine or vaccine constituent Severe febrile illness DTP Encephalopathy within 7 days of administration OPV Immunodeficiency, or immunodeficient household contact* IPV Anaphylactic reaction to neomicin, streptomycin or polymyxin B Contraindications Adopted from Plotkin pg 66-67 * Risk benefit assessment when administered to HIV positive individuals

23. Vaccine Contraindication MMR Anaphylaxis, pregnancy, immunodeficiency* Hib None Hepatitis B Anaphylactic reaction to common baker’s yeast Yellow fever Anaphylactic reaction to egg, immunodeficiency Contraindications Adopted from Plotkin pg 66-67 * Risk benefit assessment when administered to HIV-positive individuals

24. THANK YOU FOR YOUR ATTENTION

25. Anaphylaxis • Type 1 hypersensitivity reaction • Circulatory failure • Bronchospasm +/- laryngospasm/laryngeal oedema • respiratory distress • May include pruritis, flushing, angioedema, seizures, vomiting, abdominal cramps & incontinence • Occurs in previously sensitized individuals

26. Anaphylaxis • Reported less from developing countries • Less sensitization? • Less reporting? • Anaphylaxis is rare (1/1 000 000 vaccinations) • Fainting is common • Untrained staff may misdiagnose fainting/dizzinessfor anaphylaxis or vice versa • Administration of adrenaline in a faint may bedangerous • PROMPT MANAGEMENT IS VITAL!

27. Seizures • Particularly associated with measles and DTP vaccination (pertussis component) • febrile seizures Temp >38 • afebrile seizures Temp normal • Febrile seizures more common with pertussis • An association with non-febrile seizures has not been proven

28. Adverse Reactions To BCG Disseminated BCGits • widespread infection, 1-12 months after BCG • usually in immunocompromised individual • confirm by isolation of Mycobacterium bovisBCG strain • treat with antituberculous regimen including Rifampicin and Isoniazid Osteitis/osteomyelitis • infection of the bone with M bovis BCG strain • management as above

29. Adverse Reactions To BCG Suppurative lymphadenitis • occurs within 2-6 months of BCG vaccination • Case Definition • 1 lymph node> 1.5 cm in size/draining sinus over a lymph node • usually occurs in the axilla, on the same side as innoculation • Management • heals spontaneously over months • only treat if sticking to skin or draining • surgical drainage and local installation ofantituberculous drug • systemic Rx is ineffective

31. ____________________________________________________________

34. Tetanus Vaccine Brachial neuritis • Presents with pain in shoulder and upper arm • Followed by weakness +/- wasting of arm and shoulder muscles • Sensory loss not prominent • Occurs 2-28 days after vaccination • Possibly a manifestation of immune complex disease • Management is symptomatic

35. Encephalopathy And Encephalitis Possibly associated with measles & pertussis vaccine • Case definition of encephalopathy • 2 out of 3 of • seizures • alteration of consciousness lasting for one day or more • distinct change in behavior for one day or more • Temporal relationship • within 48 hrs with DTP • within 7-12 days after measles or MMR

36. Encephalitis And Measles Vaccination • An analysis of claims for encephalitis following measles vaccine in the USA found clustering of events 8-9 days after vaccination (Wetbel 1998, Duclos 1998) • This supports, but does not prove, thepossibility that measles vaccine was causative • Risk is less than 1 case per million

37. Hypotonic Hypotesive Episode • Mainly associated with DTP • Case definition • Event of sudden onset occurring within 48 (usually less than 12) hours of vaccinationand lasting from one minute to several hours • In a child < 10 years of age • ALL of the following must be present • limpness (hypotonic) • reduced responsiveness • pallor or cyanosis - or failure to observe/recall • Transient, self-limiting, NOT a contraindication to further vaccination

38. Acute Flaccid Paralysis Vaccine associated paralytic poliomyelitis • Occurs within 4-30 days of receipt of OPV or 4-75 days after contact with vaccine recipient Case Following a national immunization day in 1996, cases of paralysis were reported after receiving OPV. On laboratory analysis, the wild virus was found, showing that the children had been infected with wild poliovirus before immunization. The cases of poliovirus were coincidental, and not caused by the vaccine.

39. Unproven Associations And Public Concerns • Influenza vaccine and Guillaine Barré Syndrome • MMR and autism, Crohn’s disease • Polio and HIV • Hepatitis B and multiple sclerosis • DTP and permanent brain damage • DTP and increased risk of mortality • Aluminium and macrophagic myofasciitis • Bovine spongiform encephalopathy (BSE) • Thiomerosal • Multiple vaccines given simultaneously

40. Common, more reactions Local reaction (pain, swelling, redness) Irritability, malaise & systemic symptoms Vaccine Fever >38C - 90-95% - BCG - Hib 5-15% 2-10% 1-6% - HepB Adults: 15%; Children: 5% Measles/MMR 5% rash ~10% 5-15% Polio (OPV) <1% - <1%** ~10%* ~10% ~25% Tetanus DTP (pertussis) Up to 50% Up to 50% Up to 55% * Rate of local reactions likely to increase with booster doses, up to 50-85% ** Symptoms include diarrhoea, headache, and/or muscle pains

41. Rare, more frequent reactions Vaccine Reaction Onset interval Rate per million doses BCG Suppurative lymphadenitis BCG osteitis Disseminated BCG 2-6 months 1-12 months 1-12 months 100-1000 1-700 2 Hib Nil known Hep B Anaphylaxis Guillain Barré syndrome 0-1 hour 1-6 weeks 1-2 5 Measles /MMR Febrile seizures Thrombocytopaenia Anaphylaxis 5-12 days 15-35 days 0-1 hour 333 33 1-50 OPV Vaccine-associated paralytic poliomyelitis (VAPP) Risk is higher for first dose, adults, and immunocompromised 4-30 days 0.76-1.3 (1st dose) 0.17 (subsequent doses) 0.15 (contacts)

42. Vaccine Reaction Onset interval Rate per million doses Tetanus Brachial neuritis Anaphylaxis Sterile abscess 2-28 days 0-1 hour 1-6 weeks 5-10 1-6 6-10 Tetanus-diphtheria Nil extra to tetanus reactions DTP Persistent (>3 hrs) inconsolable screaming Seizures Hypotonic, hyporesponsive episode (HHE) Anaphylaxis/shock Encephalopathy 0-24 hours 0-3 days 0-24 hours 0-1 hour 0-3 days 1000-60 000 570 570 20 0-1 Rare, more frequent reactions

43. Vaccine Reaction Onset interval Rate per million doses Japanese encephalitis Serious allergic reaction Neurological event 10-1000 1-2.3 Yellow fever Post-vaccination Encephalitis Allergic reaction/anaphylaxis 7-21 days 0-1 hours 500-4000 in infants<6 months 5-20 Rare,more frequent reactions

44. CASE STUDIES An outbreak of lymphadenitis three months after BCG immunization was traced to a switch to a different strain of vaccine. The investigation also highlighted a number of programme errors (vaccines not properly reconstituted, and injections not given intradermally). Cause: Vaccine reaction compounded by programme errors A one-year-old child died within 12 hours of receiving measles vaccine. It was reported as a possible anaphylaxis because of its rapid onset. Investigation found that the vaccine used was likely to have been reconstituted one day prior to this particular use. Cause: Non-sterile injection, not anaphylaxis

45. CASE STUDY Four children died and a fifth was hospitalized after receiving measles vaccine from the same vial. Vaccine was not refrigerated, and was transported house to house for immunization. Reactions began four to five hours after vaccination, with vomiting, unconsciousness, and meningeal irritation. S. aureus was cultivated from the incriminated vial. Cause: Non-sterile injection

46. Programmatic error Insulin given to70 infantsinstead of DTPvaccine with21 deaths DTP T T Insulin vial Vaccine vials Turkey India Algeria Yemen 1997