Epidemiology and Prevention of Viral Hepatitis A to E: Hepatitis A Virus

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

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

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

8. Avg. rate Rate Arizona 48 D.C. 14 Alaska 45 Georgia 12 Oregon 40 Arizona 8 New Mexico 40 Rhode Island 7 Utah 33 Connecticut 7 Washington 30 Kansas 7 Oklahoma 24 Maryland 6 South Dakota 24 Massachusetts 6 Idaho 21 Texas 6 Nevada 21 Florida 5 California 20 California 5 Top 10 States With the Highest Hepatitis A Rates NOW 2001 THEN 1987-1997

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. 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 Hepatitis A – Clinical Features

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. Clinical illness Infection ALT IgM IgG Viremia Response HAV in stool 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Week Events In Hepatitis A Virus Infection

13. Concentration of Hepatitis A Virus in Various Body Fluids Feces Serum Body Fluids Saliva Urine 102 104 100 106 108 1010 Infectious Doses per mL Source: Viral Hepatitis and Liver Disease 1984;9-22 J Infect Dis 1989;160:887-890

14. Hepatitis A Virus Transmission • 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)

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

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. Hepatitis A Vaccination Strategy: Epidemiologic Considerations • 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

19. Hepatitis A Prevention – Immune Globulin • 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)

20. ACIP Recommendations – Hepatitis A Vaccine Pre-exposure Vaccination • 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

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 VaccineImmunogenicity, 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. ACIP Recommendations – Hepatitis A Vaccine Post-vaccination Testing • 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

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