1. Epidemiology and Prevention of Viral Hepatitis A to E: Hepatitis A Virus Division of Viral Hepatitis

2. Hepatitis A Virus

3. Geographic Distribution of HAV Infection

4. Reported Cases of Hepatitis A, United States 1995: Vaccine Licensed 1996: ACIP recommendations 1999 ACIP recommendations Source: NNDSS, CDC

5. Rate > 20/100,000 Rate 10-20/100,000 Rate < 10/100,000 States with Hepatitis A Rates > 10/100,000 1987-97

6. Number of years that Reported Incidence of Hepatitis A Exceeded 10 Cases per 100,000, by County, 1987-1997

7. Hepatitis A Incidence, United States 2002 incidence 1987-97 average incidence > = 20 10 - 19 5 - 9 0 - 4 Rate per 100,000

8. Top 10 States With the Highest Hepatitis A Rates THEN 1987-1997 NOW 2001

9. Basics of Hepatitis A RNA Picornavirus –Single serotype worldwide –Acute disease and asymptomatic infection No chronic infection –Protective antibodies develop in response to infection - confers lifelong immunity

10. Hepatitis A – Clinical Features Incubation period: Jaundice by age group: < 6 yrs 6 – 14 yrs > 14 yrs Rare Complications: Chronic sequelae: Average 30 days Range 15-50 days <10% 40%-50% 70%-80% Fulminant hepatitis Cholestatic hepatitis Relapsing hepatitis None

11. Acute Hepatitis A Case Definition For Surveillance –Clinical criteria of an acute illness with: discrete onset of symptoms (e.g. fatigue, abdominal pain, loss of appetite, intermittent nausea, vomiting), and jaundice or elevated serum aminotransferase levels –Laboratory criteria IgM antibody to hepatitis A virus (anti-HAV) positive –Case Classification Confirmed. A case that meets the clinical case definition and is laboratory confirmed or a case that meets the clinical case definition and occurs in a person who has an epidemiologic link with a person who has laboratory-confirmed hepatitis A during the 15-50 days before the onset of symptoms.

12. Events In Hepatitis A Virus Infection

13. Concentration of Hepatitis A Virus in Various Body Fluids Source:Viral Hepatitis and Liver Disease 1984;9-22 J Infect Dis 1989;160:887-890 Feces Serum Saliva Urine 10 0 10 2 10 4 10 6 10 8 10 Body Fluids Infectious Doses per mL

14. Fecal-oral Close personal contact (e.g., household contact, sex contact, child day care centers) Contaminated food, water (e.g., infected food handlers) Blood exposure (rare) (e.g., injecting drug use, transfusion) Hepatitis A Virus Transmission

15. Endemicity Disease Rate Peak Age of Infection Transmission Patterns Early childhood Late childhood/ young adults Young adults High Moderate Low Very low Low to high High Low Very lowAdults Person to person; outbreaks uncommon Person to person; food and waterborne outbreaks Person to person; food and waterborne outbreaks Travelers; outbreaks uncommon Global Patterns of Hepatitis A Virus Transmission

16. Risk Factors Associated with Reported Hepatitis A, 1990-2000, United States Source: NNDSS/VHSP

17. Prevention of Hepatitis A Vaccination (pre-exposure) Immune globulin Good hygiene Clean water systems; avoidance of food contamination

18. Many cases occur in community-wide outbreaks – no risk factor identified for 40-50% of cases – highest attack rates in 5-14 year olds – children serve as reservoir of infection Groups at increased risk of infection – travelers to developing countries – men who have sex with men – illegal drug users – persons with chronic liver disease Hepatitis A Vaccination Strategy: Epidemiologic Considerations

19. Pre-exposure – travelers to intermediate and high HAV-endemic regions Post-exposure (within 14 days) Routine – household and other intimate contacts Selected situations – institutions (e.g., day care centers) – common source exposure (e.g., food prepared by infected food handler) Hepatitis A Prevention – Immune Globulin

20. Persons at increased risk for infection – travelers to intermediate and high HAV-endemic countries – MSM (Men who have sex with men) – illegal drug users – Persons who have clotting factor disorders – persons with chronic liver disease Communities with historically high rates of hepatitis A - routine childhood vaccination ACIP Recommendations – Hepatitis A Vaccine Pre-exposure Vaccination

21. Duration of Protection after Hepatitis A Vaccination Persistence of antibody –At least 5-8 years among adults and children Efficacy –No cases in vaccinated children at 5-6 years of follow-up Mathematical models of antibody decline suggest protective antibody levels persist for at least 20 years Other mechanisms, such as cellular memory, may contribute

22. Hepatitis A Vaccine Immunogenicity, Side Effects Immunogenicity in children, adolescents, adults: 94-100% positive 1 month after dose 1 99-100% positive after dose 2 Most common side effects: Sore injection site (50%), headache (15%), malaise (7%) No severe reactions known Safety in pregnancy unknown (risk likely is low) Currently licensed for aged 1 year and older

23. Use of Hepatitis A Vaccine for Infants Hepatitis A vaccine is licensed only for persons aged 1 year and older Safe and immunogenic for infants without maternal antibody Presence of passively-acquired maternal antibody blunts immune response –all respond, but with lower final antibody concentrations Age by which maternal antibody disappears is unclear –still present in some infants at one year –probably gone in vast majority by 15 months

24. ACIP Recommendations, 1999 Implementation Children Who Should be Routinely Vaccinated –living in states, counties, and communities where the average hepatitis A rate was  20 cases/100,000 during baseline period. Children Who Should be Considered for Routine Vaccination –living in states, counties, and communities where the average hepatitis A rate was <20 but  10 cases/100,000 during the baseline period.

25. Not recommended because of the high response rate among vaccinees (95% after dose one, 100% after two) No commercially available test to measure vaccine response ACIP Recommendations – Hepatitis A Vaccine Post-vaccination Testing

26. Hepatitis A in the United States-2002 National rate lowest yet recorded –Continued monitoring needed to determine if low rates sustained and due to vaccination –Evaluation of age-specific rates to assess impact of vaccination strategy Rates increasing in some states –Occurring among adults in high risk groups (e.g. MSM, drug users)

27. Long-term Hepatitis A Prevention Strategy Sustain ongoing vaccination Lower disease incidence – Catch-up vaccination of children and adolescents Further reduce incidence – Vaccination of high-risk adults – Routine vaccination of all children nationwide