Epidemiology and Prevention

of Viral Hepatitis A to E:

Hepatitis A Virus

Division of Viral Hepatitis

Hepatitis A Virus

Geographic Distribution of HAV Infection

Reported Cases of Hepatitis A, United States

0

5

10

15

20

25

30

35

40

45

52 56 60 64 68 72 76 80 84 88 92 96 2002

Year

Rate

per

100,0

00

1995: Vaccine Licensed

1996: ACIP recommendations

1999 ACIP recommendations

Source: NNDSS, CDC

Rate > 20/100,000

Rate 10-20/100,000

Rate < 10/100,000

States with Hepatitis A Rates > 10/100,000 1987-97

0-1 2-3 4-5 6-7 8-10

Number of years that Reported Incidence of Hepatitis A Exceeded 10 Cases per 100,000,

by County, 1987-1997

Hepatitis A Incidence, United States

rate per 100,000 0-4 5-9 10-19>=20

DC

NYC

rate per 100,000 0-4 5-9 10-19>=20

DC

NYC

2002 incidence

1987-97 average incidence

> = 20

10 - 19

5 - 9

0 - 4

Rate per 100,000

Top 10 States With the Highest Hepatitis A Rates

7Connecticut33Utah

7Kansas30Washington

6Maryland24Oklahoma

6Massachusetts24South Dakota

6Texas21Idaho

5Florida21Nevada

5California20California

7Rhode Island40New Mexico

8Arizona40Oregon

12Georgia45Alaska

14D.C.48Arizona

RateAvg. rate

THEN1987-1997

NOW2001

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

Hepatitis A – Clinical Features

• Incubation period:

• Jaundice by age group:< 6 yrs6 – 14 yrs> 14 yrs

• Rare Complications:

• Chronic sequelae:

Average 30 days

Range 15-50 days

<10%40%-50%70%-80%

Fulminant hepatitisCholestatic hepatitisRelapsing hepatitis

None

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.

0 1 2 3 4 5 6 7 8 9 10 11 12 13

Week

Res

po

nse

Clinical illness

ALT

IgM IgG

HAV in stool

Infection

Viremia

Events In Hepatitis A Virus Infection

Concentration of Hepatitis A Virusin Various Body Fluids

Source: Viral Hepatitis and Liver Disease 1984;9-22J Infect Dis 1989;160:887-890

Feces

Serum

Saliva

Urine

100 102 104 106 108 1010

Bo

dy

Flu

ids

Infectious Doses per mL

• 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

Endemicity

DiseaseRate

Peak Ageof Infection

Transmission Patterns

Early childhood

Late childhood/ young adults

Young adults

High

Moderate

Low

Very low

Low to high

High

Low

Very low Adults

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

Unknown 46%

Contact of day-care

child/employee 6%

Other Contact 8%

Child/employee in day-care 2%

Food- or waterborne

outbreak 4%

Injection drug use 6%

Sexual or Household

Contact 14%

Men who have sex with men

10%

International travel 5%

Risk Factors Associated with Reported Hepatitis A,

1990-2000, United States

Source: NNDSS/VHSP

Prevention of Hepatitis A

• Vaccination (pre-exposure)

• Immune globulin

• Good hygiene

• Clean water systems; avoidance of food contamination

• 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

• Pre-exposure– travelers to intermediate and high

HAV-endemic regions

• Post-exposure (within 14 days)Routine– household and other intimate contactsSelected situations– institutions (e.g., day care centers)– common source exposure (e.g.,

food prepared by infected food handler)

Hepatitis A Prevention – Immune Globulin

• 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 VaccinePre-exposure Vaccination

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

Hepatitis A VaccineImmunogenicity, Side Effects

• Immunogenicity in children, adolescents, adults:

94-100% positive 1 month after dose 199-100% positive after dose 2

• Most common side effects:

Sore injection site (50%), headache (15%), malaise (7%)No severe reactions knownSafety in pregnancy unknown (risk likely is low)

Currently licensed for aged 1 year and older

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

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.

• 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

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)

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