Viral Vaccines I 5/17/04 LECTURE OUTLINE I. CASE HISTORY

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1 Viral Vaccines I I. CASE HISTORY LECTURE OUTLINE 5/17/04 A 22-year-old Amish woman became ill with a headache, fever, and generalized muscle pain. Two days later, she developed right and then left lower extremity weakness and decreased deep tendon weakness. She had been to 3 weddings of Amish couples within the past 2 months and these Amish populations were positive for the virus in question. II. DISEASE: POLIO A. CHARACTERISTICS: A local GI tract infection that may develop into a systemic illness with severity ranging from inapparent to a nonparalytic febrile illness, to an aseptic meningitis, to paralytic disease and possibly death (due to respiratory failure). Symptoms include: fever, malaise, headache, nausea, vomiting, neck or back stiffness with or without paralysis. Virus replicates in GI tract and viremia may then follow with CNS invasion resulting in lower extremity flaccid paralysis. Inapparent infections are >100-fold times more common than the paralytic cases. 4-8 % of those exposed contract a minor illness (gastroenteritis or flu-like symptoms). 1-2% get aseptic meningitis. and 0.1-1% become paralytic. Fatality rate for paralytic cases is 2-10%. B. AGENT: Poliovirus types 1, 2, 3. C. HOST & HIGH RISK POPULATIONS Host: Human High risk population: Worldwide, developed countries have a higher risk of serious infections due to lack of exposure in infancy. Characteristically, a disease of children and adolescents in endemic countries. In developed countries, disease is seen in adults. Population not getting vaccines. Outbreaks in preschool children (not yet immunized) or members of religious groups who do not believe in immunization. D. VECTOR & TRANSMISSION: Vector: Humans Transmission: Fecal/oral route in areas of poor sanitation. Usually direct contact (pharyngeal spread) through close association. Rarely, milk and contaminated foodstuff. Flies. E. INCIDENCE , 115,800 cases/year; 1955 and 1963 vaccines introduced. Post Average of cases/year; 1987 [0], 1992 [4], 1993 [0], 1997 [3], 1998[1], 1999[0], 2001[0] F. IMMUNITY AFTER ACTIVE DISEASE Usually type-specific immunity life-long, even from inapparent infections. III. IV. TREATMENT: None VACCINE A. TYPE OF VACCINE: Inactivacted virus. IPOL (Aventis Pasteur). $15.42/dose 1

2 B. SCHEDULE AND ROUTE OF ADMINISTRATION Route: Subcutaneous or intramuscular Schedule: 2, 4, 6-18 months and 4-6 years. C. EFFICACY AND DURATION OF IMMUNITY ~100% D. COMPLICATIONS Swelling < 5% Fever (w/i 48 hr) < 5% E. CONTRAINDICATIONS Previous anaphylactic reaction to IPV Anaphylactic reaction to neomycin, polymyxin B, or streptomycin Severe acute illness 2

3 LECTURE OUTLINE I. CASE HISTORY A 16-year-old Snohomish County man developed fever, bronchitis and Koplik spots on his buccal mucosa while visiting England. One week after his return, his 19-year-old sister developed a rash. Other persons developing the illness were: a 16-year-old friend of the sister, two people sharing the plane flight of the index case, and a 13-month-old contact of one of the plane cases. All had fever >101, generalized rash, cough and conjunctivitis. II. DISEASE: MEASLES. aka: Hard measles, Rubeola, 10 day measles." A. CHARACTERISTICS: Prodromal fever, conjunctivitis, Koplik spots, barking cough, and a blotchy rash. First on the forehead, then to head, then abdomen. Complications of disease include: Otitis media (7%) Diarrhea (8%) Pneumonia (6%) Encephalitis (0.1%), fatality 15%! Residual neurological damage in 25% of survivors. B. AGENT: Measles virus. Genus Morbillivus in the Paramyxovirus family. C. HOST & HIGH RISK POPULATIONS Host: Humans High risk populations: In unvaccinated population, 90% of the children will get measles by the time they are 20 years old. In vaccinated population, outbreaks are sometimes observed in schools and colleges. D. VECTOR & TRANSMISSION Vector: Humans Transmission: Airborne (droplet) - rare. Direct contact of nasal/throat secretions. **Highly contagious, high secondary attack rate. E. INCIDENCE Recent number of cases (USA cumulative): 1986 (6273), 1987 (3579), (56,000 cases), 1993 (312), 1996 (508), 1997 (138), 1998(100), 1999(86), 2001(108) F. IMMUNITY AFTER ACTIVE DISEASE: Lifelong 3

4 III. TREATMENT: None for infected cases. For contacts: Human pooled immunoglobulin (IgG). Passive. The titers are not particularly high. Given <72 hours after exposure. Given to contacts of high risk population (<1-year-old) or who the vaccine is contraindicated: immunosuppressed or pregnant. After IgG administration you need to wait 5-12 months to give the vaccine. IV. VACCINE A. TYPE OF VACCINE: Live attenuated virus. Attenuvax (Merck). A component of MMR. Often produces a mild illness. $10.40/dose for just attenuvax. $28.19 for MMR Refrigerate, don t freeze vaccine. Once it is reconstituted it must be used w/i 8 hrs or throw it out. Note: Killed vaccine given in gave inadequate protection. Recipients should be re-vaccinated. B. SCHEDULE AND ROUTE OF ADMINISTRATION Route: Subcutaneous Schedule: months (earlier the immune system is too immature) and 4-6 years. Any dose given <12 months of age does not count. C. EFFICACY AND DURATION OF IMMUNITY 80-95% Effective in eliciting humoral and cellular immunity 10-20% vaccine failures (2-3,000 cases/yr) [CDC says 2-5% of recipients don t respond] D. COMPLICATIONS Vaccine-related measles 5-15 days after administration (5-15% fever, 5% rash) Diffuse retinopathy and optic problems Neurologic (within 1 month of vaccine) <1/M doses Simple febrile seizures rare. F. CONTRAINDICATIONS Previous anaphylactic reaction to MMR, gelatin or neomycin Pregnancy at time or within 3 months No blood products within 3-11 months Immunocompromised (except asymptomatic HIV) Active, untreated TB Severe illness (postpone giving vaccine) 4

5 LECTURE OUTLINE I. CASE HISTORY An 11 year old boy develops a mild fever, testicular tenderness and swelling and pain around the jaw. He lived. II. DISEASE: MUMPS A. CHARACTERISTICS: Acute viral disease with fever, swelling and tenderness in one or more salivary glands, usually the parotid. Orchitis occurs in 15-25% of males, but does not result in sterility. CNS is often involved (aseptic meningitis, 50-60% of cases, symptomatic meningitis is observed in up to 15% of the cases). Rarely (deafness). B. AGENT: Mumps virus. Paramyxovirus genus. C. HOST & HIGH RISK POPULATIONS Host: Humans. Childhood disease---highest incidence 5-14 years old. One-third have inapparent illness % have just respiratory symptoms. Prodromal symptoms nonspecific, e.g. low-grade fever, headache and respiratory irritation. D. VECTOR & TRANSMISSION Vector: Humans Transmission: Droplet spread. Direct contact with saliva. E. INCIDENCE Recent number of cases (USA cumulative): 212,000 before the vaccine, 1986 [5,411], 1987 [12,259], 1993 [1,692], 1996 [751], 1997 [683], 1998[666], 1999[352], 2001[231] F. IMMUNITY AFTER ACTIVE DISEASE: Life-long. III. IV. TREATMENT: None. Post-exposure prophylaxis is not effective. VACCINE A. TYPE OF VACCINE: Live attenuated vaccine. Introduced in Mumpsvax (Merck). $13.36/dose B. SCHEDULE AND ROUTE OF ADMINISTRATION Route: Subcutaneous Schedule: months, 4-6 years. C. EFFICACY AND DURATION OF IMMUNITY 97% of the children and 93% of the susceptible adults develop immunity. Duration: Persists at least 10 years. Presumably life-long. D. COMPLICATIONS Occasional mild fever. Rarely, febrile seizures. This is one of the safest live viral vaccines available. 5

6 G. CONTRAINDICATIONS Previous anaphylactic reaction to MMR, gelatin or neomycin Pregnancy at time or within 3 months No blood products within 3-11 months Immunocompromised (except asymptomatic HIV) Active, untreated TB Severe illness (postpone giving vaccine) 6

7 LECTURE OUTLINE I. CASE HISTORY A pregnant women developed a mild fever and a diffuse macular rash during her first trimester. She recovered completely without seeking medical care. Her baby was born at term with congenital defects ranging from cataracts to cardiac problems to mental retardation. II. DISEASE: Rubella (aka "German measles" and 3-day measles). A. CHARACTERISTICS: Milder form of measles. Prodromal period of headache, low fever, and malaise - lasting 1-5 days. Also, symptoms of upper respiratory infection. Diffuse macular rash in 50-80% of the cases. Muscle pain and arthritis (especially in adult females). Infection during first trimester - wide variety congenital defects (20-25%). Encephalitis (rarely). Arthritis frequently observed with adults (~70% of women) % subclinical infections. B. AGENT: Rubella virus. C. HOST & HIGH RISK POPULATIONS: Humans. High risk Population: Children and adolescents. Outbreaks occur in pre-vaccinated population every 6-9 years. Now outbreaks in: institutions, military and colleges. D. VECTOR & TRANSMISSION Transmission: Airborne (droplet). Direct contact with nasopharyngeal secretions. Indirectcontaminated fomites. Highly contagious. E. INCIDENCE USA secular trends: 1964 before vaccine: 0.5 million cases; 30,000 still births; 20,000 congenital defects. Recent number of cases (USA cumulative): 1986 [ CRS], 1987 [328], 1992 [160], 1993 [192], 1996 [238], 1997 [181 5 CRS], 1998 [364-7 CRS], 1999 [238_8 CRS], 2001[19_2 CRS] All outbreaks since 1996 have been in foreign-born individual. All CRS cases since 1996 have occurred in kids of unvaccinated women born in Latin America. F. IMMUNITY AFTER ACTIVE DISEASE: Lifelong. III. TREATMENT IgG given if infection is in pregnancy (does not prevent infection, but does suppress symptoms). In general, however, post-exposure prophylaxis is ineffective. IV. VACCINE A. TYPE OF VACCINE: Live attenuated virus. Meruvax II (Merck), licensed $11.46/dose 7

8 B. SCHEDULE AND ROUTE OF ADMINISTRATION Route: Subcutaneous Schedule: months and 4-6 years. Give as MMR, women of childbearing age should get it if they have not been vaccinated (must not be pregnant!!). C. EFFICACY AND DURATION OF IMMUNITY Efficacy: 95% Duration: Presumably life-long. High levels of protective antibodies have been observed in people vaccinated in D. COMPLICATIONS Fever and rash. Local: Swelling <48 hrs. Estimated theoretical risk of serious congenital malformations (3%); but none observed. FAR LESS THAN RISK FROM NATURAL INFECTION (20%) Arthritis: Up to 40% of the people who are vaccinated have simple joint pain. Frank arthritis in only 2% of the cases, but 10-15% if female. Persists only 2 weeks and then disappears. E. CONTRAINDICATIONS Previous anaphylactic reaction to MMR, gelatin or neomycin Pregnancy at time or within 3 months No blood products within 3-11 months Immunocompromised (except asymptomatic HIV) Active, untreated TB Severe illness (postpone giving vaccine) Vaccine given to unknowingly pregnant women. From , 1,176 (CDC 321) women were given the vaccine during their first trimester and none of the offspring had congenital defects, but the women got the rubella infection at the rate of 1%. 8