AEFI DEFINITION AND MANAGEMENT

1. EsteghamatiMD, MPH AEFI DEFINITION AND MANAGEMENT

2. 1. Live attenuated (oral polio, BCG, VZV) 2. Killed vaccine (influenza, IPV, hepatitis A, pertussis) 3. Toxoid (tetanus, diphtheria) 4. Purified (subunit) antigen (meningococcalvaccine, Haemophilus influenzae vaccine) 5. Recombinant antigen (hepatitis B) 6. DNA vaccines (in investigational phase) 7. Synthetic peptides (in investigational phase) TYPES OF ANTIGENS

3. Suspending agents e.g. water, saline Preservatives e.g. thiomerosal Stabilisers e.g. sorbitol and hydrolyzed gelatin - MMR Adjuvants e.g. aluminium Salts Other substances which may be present Residuals in the growth medium Antibiotics, e.g. neomycin, streptomycin - IPV, varicella vaccine COMPONENTS OF THE VACCINE FORMULATION • consider these components as well when assessing causality!

4. Diphtheria-tetanus-pertussis (DPT) pertussis component has adjuvant effect for diphtheria and tetanus toxoids Different viruses in one vaccinatione.g. OPV-type 1, 2, 3 polioviruses COMBINATION VACCINES • How will the use of combination vaccines influence investigation of adverse events?

5. allergy or asthma (with the exception of a known allergy to a specific component of the vaccine mentioned above); • any minor illness, such as respiratory tract infections or diarrhoea with temperature below 38.5°C • family history of adverse events following immunization • family history of convulsions, seizures, or faints; • treatment with antibiotics; • known or suspected HIV infection with no signs and symptoms of AIDS; • signs and symptoms of AIDS, except as noted in Table 6.1; • child being breast fed; • chronic illnesses such as chronic diseases of the heart, lung, kidney, or liver • stable neurological conditions, such as cerebral palsy or Down’s Syndrome; • premature or low-birthweight (vaccination should not be postponed); • recent or imminent surgery; • malnutrition; and • history of jaundice at birth. The following are not contraindications. Infants with these conditions should be immunized:

6. Recommendations for immunization of HIV-infected children and women of childbearing age

8. Diluent are not interchangeable, different vaccines have different diluents; mixing and administering the wrong diluent has led to serious adverse events including death. • Always use diluent from the same manufacturer as the vaccine. • Diluents should be cooled before being mixed with the vaccine • Do not reconstitute vaccines until you are ready to immunize. • You must discard reconstituted vaccine after six hours or at the end of the immunization session, whichever comes first. Remember:

11. Position the infant sideways on the mother's lap with the infant’s whole leg bare. • The parent should hold the infant's legs. • Gently stretch the skin flat between your thumb and forefinger. • Insert the needle at a 90° angle. • Quickly push the entire needle straight down through the skin and into the muscle. Inject slowly to reduce pain. DTP or DTP-HepB or HepB, Hib vaccine: intramuscular (IM) injection in thigh

12. Diagram showing how to locate the site to give IM injection to infants

13. For vaccinating older children, adolescents and adults, the deltoid muscle of the upper arm may be used. In infants and young children under 15 months of age the deltoid muscle does not provide a safe intramuscular (IM) site due to the superficiality of the radial nerve and the deltoid muscle being insufficiently developed to absorb medication adequately Intramuscular injections for older children and adults

14. Diagram showing how to locate deltoid

15. Ask the woman to sit down. • Tell her to drop her shoulder and place her left hand behind her back or resting on the hip. This relaxes the muscle in the arm and makes the injection nearly painless. • Put your finger and thumb on the OUTER part of the upper arm. • Use your left hand to squeeze up the muscle of the arm. • Quickly push the needle straight down through the skin between your fingers. Go deep into the muscle. • Press the plunger with your thumb to inject the vaccine. • Pull out the needle quickly and smoothly and ask the woman to press the site gently with a cotton pad in case of bleeding TT vaccine (for women): intramuscular (IM) injection in the left arm

16. Should elicit immune response with minimal risk • Deep IM preferable for vaccines with adjuvants (depot effect and less granuloma formation) • SC/intradermal - better for live vaccines • to lessen risk of neurovascular injury but still immunogenic (e.g. BCG) ROUTE OF ADMINISTRATION

17. A medical incident that takes place after an immunization, causes concern, and is believed to be caused by immunization WHAT IS AN ADVERSE EVENT FOLLOWING IMMUNIZATION (AEFI)? • Vaccine reaction - caused by vaccine’s inherent properties • Programme error - caused by error in vaccine preparation, handling, or administration • Coincidental - happens after immunization but notcaused by it (a chance association) • Injection reaction - anxiety or pain of injection notvaccine • Unknown- cause cannot be determined

18. Common, minor reactions • vaccine stimulates immune system • settle on their own • warn parents and advise how to manage • Rare, more serious reactions • anaphylaxis (serious allergic reaction) • vaccine specific reactions VACCINE REACTIONS

19. * Rate of local reactions likely to increase with booster doses, up to 50-85% ** Symptoms include diarrhoea, headache, and/or muscle pains

20. Abscess • Atrophy • Cellulites • Erythema • Granuloma/cyst /nodule • Hematoma/bleeding • Induration • Pain/tenderness • Pigmentation • Pruritus • Swelling • Ulceration • Warmth Different kind of local reaction

29. Color: The color of the lesion should be documented(e.g., skin color, brown, red, yellow, tan or blue). Number: The approximate number of lesions should be recorded. Size: The average size of lesions (with range) should be recorded in centimeters Distribution: The anatomic distribution of the eruption should be documented on a standardized diagram of the human body.

30. Host factors (immune status, medications, etc.) Biologic characteristics of the vaccine (e.g., live attenuated versus inactivated component vaccines) Biologic characteristics of the vaccine-targeted disease Biologic characteristics of the vaccine associated with a mucocutaneous change incidence and pattern of mucocutaneous changes seen in previous trials.

31. Bulla : a fluid filled cavity or elevation >1 cm in diameter fluid can be clear, serous, hemorrhagic or pus Cyst : a closed cavity or sac containing fluid or semisolid material Macule : a flat generally <o.5 cm area of skin of mucous membrane with different color Nodule: a dermal or subcutaneous firm, well defined lesion Papule: a discrete, solid,elevated body usually < o.5 cm in diameter Primary mucocotaneous lesions

32. Erosion: a localized loss of epidermal or mucosal epithelium Crusting : died exudates of plasma Scaling : whitish scale present on the skin Atrophy: thinning or absence of the dermis or subcutaneous fat Excoriation: oval or linear depression of the skin exposing a broad area of red dermis Fissure: linear or wedge shape crack in the epidermis Ulcer : a circumscribed loss of epidermis or mucosa extending to the dermis Secondary mucocotaneous lesions

34. we defined persistence as more than 3 h. It is recognized that this is an arbitrary, historical cut off. Recognizing cultural differences and the subjectivity of qualitative descriptions of crying (e.g., fierce and high-pitched) We agreed to choose the term “persistent crying” for two reasons. First, the term implies the apparent discomfort of the child, a prolonged duration of the episode as well as various futile attempts to comfort the child. Second, it is the combination of these characteristics which concerns parents and thus affects their benefit to risk balance of the immunizationby fearing long term sequelae of the episode.

35. Local reaction • cold cloth at injection site • paracetamol • Fever >38°C • give extra fluids • tepid sponging • paracetamol • Irritability malaise and systemic symptoms • give extra fluids • paracetamol MANAGEMENT OF COMMON, MINOR REACTIONS

36. RARE, MORE SERIOUS 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)

37. 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 SERIOUS REACTIONS (2)

38. 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 SERIOUS REACTIONS (3)

39. 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 * Risk benefit assessment when administered to HIV positive individuals

40. 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

41. WHO case definitions are used here • Lack of standardized case definitions in the literature • e.g. fever • The Brighton collaboration • developing case definitions for AEFI • promoting global implementation of these definitions ADVERSE EVENTS ASSOCIATED WITH SPECIFIC VACCINES secretariat@brightoncollaboration.orghttp://brightoncollaboration.org

42. 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 ANAPHYLAXIS

43. 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! ANAPHYLAXIS

45. Disseminated BCG • 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 ADVERSE REACTIONS TO BCG

46. 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 ADVERSE REACTIONS TO BCG

47. World Health Organization

48. World Health Organization ____________________________________________________________

49. World Health Organization

50. World Health Organization