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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
45
1995: Vaccine Licensed
40
1996: ACIP recommendations
Rate per 100,000
35
30
1999 ACIP
recommendations
25
20
15
10
5
0
52
56
60
64
68
72
76
Year
Source: NNDSS, CDC
80
84
88
92
96 2002
States with Hepatitis A Rates > 10/100,000 1987-97
Rate > 20/100,000
Rate 10-20/100,000
Rate < 10/100,000
Number of years that Reported Incidence of
Hepatitis A Exceeded 10 Cases per 100,000,
by County, 1987-1997
0-1
2-3
4-5
6-7
8-10
Hepatitis A Incidence, United States
1987-97 average incidence
2002 incidence
NYC
DC
NYC
DC
rate per 100,000
0-4
>=20
5-9
10-19
Rate per 100,000
> = 20
10 - 19
5-9
0-4
rate per 100,000
0-4
>=20
5-9
10-19
Top 10 States With the Highest Hepatitis A Rates
Avg. rate
THEN
1987-1997
Rate
Arizona
48
D.C.
14
NOW
Alaska
45
Georgia
12
2001
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
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:
Average 30 days
Range 15-50 days
• Jaundice by age group:
< 6 yrs
6 – 14 yrs
> 14 yrs
<10%
40%-50%
70%-80%
• Rare Complications:
Fulminant hepatitis
Cholestatic hepatitis
Relapsing hepatitis
• Chronic sequelae:
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.
Events In Hepatitis A Virus Infection
Clinical illness
Infection
ALT
Response
IgM
IgG
Viremia
HAV in stool
0
1
2
3
4
5
6
Week
7
8
9
10
11
12
13
Concentration of Hepatitis A Virus
in Various Body Fluids
Body Fluids
Feces
Serum
Saliva
Urine
100
102
104
106
Infectious Doses per mL
Source:
Viral Hepatitis and Liver Disease 1984;9-22
J Infect Dis 1989;160:887-890
108
1010
Hepatitis A Virus Transmission
•
Fecal-oral
•
Close personal contact
•
Contaminated food, water
•
Blood exposure (rare)
(e.g., household contact, sex
contact, child day care centers)
(e.g., infected food handlers)
(e.g., injecting drug use,
transfusion)
Global Patterns of
Hepatitis A Virus Transmission
Endemicity
High
Moderate
Low
Very low
Disease
Rate
Peak Age
of Infection
Transmission
Patterns
Low to high Early childhood Person to person;
outbreaks uncommon
High
Late childhood/
young adults
Person to person;
food and waterborne
outbreaks
Low
Young adults
Very low
Adults
Person to person;
food and waterborne
outbreaks
Travelers; outbreaks
uncommon
Risk Factors Associated with
Reported Hepatitis A,
1990-2000, United States
Sexual or
Household
Contact 14%
Unknown
46%
International
travel 5%
Men who have
sex with men
10%
Injection drug use
6%
Child/employee in
day-care 2%
Other Contact
8%
Contact of daycare
child/employee
6%
Source: NNDSS/VHSP
Food- or
waterborne
outbreak 4%
Prevention of Hepatitis A
•
•
•
•
Vaccination (pre-exposure)
Immune globulin
Good hygiene
Clean water systems; avoidance of food
contamination
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
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)
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
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 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
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.
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
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