LECTURE OUTLINE. B. AGENT: Varicella-zoster virus. Human herpes virus 3. DNA virus.

Transcription

1 Viral Vaccines II LECTURE OUTLINE 5/24/04 I. CASE HISTORY A 5-year old comes home from school with a red skin rash on his chest that spreads to over 300 itchy blisters that spread further to his face, arms and legs. II. DISEASE: Varicella (aka Chicken Pox or shingles). A. CHARACTERISTICS: The patient will have a large number of lesions, which are usually first seen on the face, scalp or trunk. The lesions can lead to scarring. Fever accompanies up to 70% of the cases. B. AGENT: Varicella-zoster virus. Human herpes virus 3. DNA virus. C. HOST & HIGH RISK POPULATIONS: Humans. Incidence peaks in 5-9 year olds during March, April and May in temperate climates. D. VECTOR & TRANSMISSION Transmission: Generally by direct contact with the infected person through fluid from broken blisters. Varicella can also be transmitted through the air when an infected person coughs or sneezes. Also, transmission can occur through direct contact with sores from a person with shingles. Highly contagious. E. INCIDENCE USA secular trends: From the incidence rate was % of the children acquire chickenpox. In a trial of the new vaccine with > 4000 kids the incidence dropped to 3.6%. Recent number of cases (USA cumulative): million cases of varicella and 300,000 cases of herpes zoster, 1997 [98,727], 1998[82,455], 2000 [27,382] F. IMMUNITY AFTER ACTIVE DISEASE: Lifelong, but may develop shingles later in life. III. TREATMENT Mostly supportive. Acetaminophen for fever (no aspirin). Creams to relieve itching, avoid diphenylhydramine (potential for systemic absorption and no good evidence that it works). Can prescribe Acyclovir and other antivirals for patients at risk of developing severe chickenpox (mostly just adults). Acyclovir, valacyclovir, famiciclovir (adults only), and foscarnet must be given within 24 hours of the onset of the rash. Sometimes it will lessen the severity of the symptoms and decrease the time of the infection. Also, pain relievers for shingles. Passive immunization, VZIG within 96 hours of exposure to immunocompromised kids and adults, newborns from moms with varicella at birth, particularly premies (also postnatal exposure). VZIG = homologous hyperimmune, $ Vaccine has also been shown to prevent infection if given within 3 days of exposure. Can be done on individual basis or for outbreak control. 1

2 IV. VACCINE A. TYPE OF VACCINE: LIVE attenuated virus. Varivax (Merck Vaccine Division). $45.56/dose B. SCHEDULE AND ROUTE OF ADMINISTRATION Route: 0.5 ml, subcutaneous injection. Reconstituted, lyophilized material, use within 30 minutes Schedule: Children, months. Try to give with MMR, if can t space out by at least 4 weeks. Adults or older unvaccinated children ( 13 yrs), two doses given at least 4 weeks apart. C. EFFICACY AND DURATION OF IMMUNITY Efficacy: 97%. >95% of the children and 75-94% of the adults will develop antibodies after the first dose. After the second dose the numbers rise to nearly 100%. Duration: Unknown, at least 7-10 years. D. COMPLICATIONS ~10% of those vaccinated develop fever % experience soreness at the site of injection. 5% develop a varicella-like rash. E. CONTRAINDICATIONS Previous anaphylactic reaction to varivax, gelatin or neomycin Blood products within 5 months Severe illness (postpone giving vaccine) Pregnancy at time or within 1 month Untreated and active TB Immunocompromised----except asymptomatic HIV kids 2

3 LECTURE OUTLINE I. CASE HISTORY Over Christmas break, a college student develops a sudden onset of fever, chills, cough, headache and muscle pain. Extreme malaise sets in for 6 days and then he feels better. II. DISEASE: INFLUENZA "bad wind" A. CHARACTERISTICS: Acute onset. Respiratory disease. Fever, chills, headache, muscle pain, coryza, mild sore throat. Severe and protracted cough. Self-limited 2-7 days. Fatality due to pneumonia in elderly or debilitated. Children with type B influenza can develop Reye's syndrome (CNS and liver) 1:5000, with 10% fatality, concurrent with aspirin use. B. AGENT: RNA Virus. Influenza virus A, B (both cause outbreaks) and also type C (mild illness with sporatic occurrence.) Influenza Summary: Influenza Type A Named: Type (A, B, C)/geographic origin/strain number/year of isolation/hemagglutinin type (13 types)/neuraminidase type (9 types). Outbreaks: Antigenic shifts. Occurs every 10+ years. At irregular intervals. PANDEMICS. Results from RNA recombinations of new H or N antigens. Antigenic drifts. Every 2-3 years. Milder changes in H or N subtypes. Epidemics of influenza A every 1-3 years and type B every 4-6 years. ANTIGENIC SHIFTS PANDEMICS TYPE CAUSING COMMON NAME 1889 H 2 N H 1 N 1 "Spanish flu", >20 million deaths! Killed more people than all military casualties of WWI and WWII combined, 1% of population 1929 H 0 N H 2 N 2 A/Japan/305/1957 "Asian flu", killed 146,000 people in the US 1968 H 3 N 2 A/Hong Kong/1968 "Hong Kong flu", 50 million cases, 33,000 deaths 1976 Hsw 1 N 1 "Swine flu" Fort Dix outbreak of 100 cases; 1 death. Pop. <58 years susceptible! Massive swine flu vaccination program. 0.5 million doses, no outbreak and 200 cases GBS H 1 N 1 A/USSR/77/H 1 N 1 "Russian flu" C. HOST & HIGH RISK POPULATIONS Host: Type A: humans, swine, horses, birds. Type B and C: humans. 3

4 D. VECTOR & TRANSMISSION Transmission: Airborne droplet spread. E. INCIDENCE Prevalent. Some estimate that everyone gets 3-4 infections a year. F. IMMUNITY AFTER ACTIVE DISEASE: Life-long, but only to exposed type. III. TREATMENT Amantadine, rimantidine (only effective against influenza type A, not B). New neuraminidase inhibitors zanamivir, oseltamivir (types A and B, but not approved for kids). 80% effective, at best. IV. VACCINE A. TYPE OF VACCINE: Fluzone (Aventis Pasteur), Fluvirin (GIV Evans). About $10/dose FluMist (Medimmune) approx. $50/dose The flu vaccine was trivalent and contained the following: A/Texas/36/91 (H 1 N 1 ) A/Johannesberg/33/97 (H 3 N 2 ) The flu vaccine was trivalent and contained the following (15 µg each/0.5 ml): A/Texas/36/91 (H 1 N 1 ) A/Nanchang/933/95 (H 3 N 2 ) The flu vaccine was trivalent and contained the following (15 µg each/0.5 ml): A/Johannesburg/82/96 (H 1 N 1 ) A/Nanchang/933/95 (H 3 N 2 ) The flu vaccine was trivalent and contained the following (15 µg each/0.5 ml): A/New Caledonia/20/99-like (H 1 N 1 ) A/Panama/2007/99-like (H 3 N 2 ) B/Yamanashi/166/98-like A/Moscow/10/99 (H3N2)-like (antigenically equivalent to A/Panama) A/New Caledonia/20/99 (H1N1) B/Sichuan/379/99 (antigenically equivalent to B/Victoria) 4

5 B. SCHEDULE AND ROUTE OF ADMINISTRATION Route: IM in deltoid muscle, one dose per year except first time kids (6 mon 9 yrs, give 2 doses separated by 1 month). Schedule: Given in November (must be given before flu season to be effective). Usually given as a single dose. Given to people at highest risk of flu complications: the elderly (especially those in nursing homes), health care workers, military, adults and children > 6 months with AIDS, chronic illness, kids on aspirin therapy, and pregnant women (>14 weeks). C. EFFICACY AND DURATION OF IMMUNITY Efficacy varies tremendously. Immunity can be short-lived due to constant changes in virus. Efficacy ~90% for same or similar flu strains % in the elderly but 80% effective in reducing death. D. COMPLICATIONS Local: soreness at injection site (30%) Generalized: a. fever, malaise, especially in children who have never had the flu vaccine (1-2 days) b. Guilliain-Barre Syndrome (GBS). Occurred 9-10 weeks after Swine flu vaccination (A/New Jersey/76/swine) during 1976 vaccinations. Rare: 10 cases GBS per 10 6 vaccinations, leads to reversible, self-limited ascending paralysis (5% fatal). E. CONTRAINDICATIONS Anaphylactic response to previous dose or to eggs. F. R & D Better methods to predict the next season's strains. 5