Epidemiology and Prevention of

Viral Hepatitis A to E:
An Overview

Hepatitis Branch
Centers for Disease Control and Prevention
 Viral Hepatitis - Historical Perspective

“Infectious” A Enterically
E transmitted

Viral hepatitis NANB

Parenterally
“Serum” B D C transmitted
F, G,
? other
 Viral Hepatitis - Overview
Type of Hepatitis
A B C D E
Source of feces blood/ blood/ blood/ feces
virus blood-derived blood-derived blood-derived
body fluids body fluids body fluids
Route of fecal-oral percutaneous percutaneous percutaneous fecal-oral
transmission permucosal permucosal permucosal

Chronic no yes yes yes no

nfection

Prevention pre/post- pre/post- blood donor pre/post- ensure safe

exposure exposure screening; exposure drinking
immunization immunization risk behavior immunization; water
modification risk behavior
modification
 Acute Viral Hepatitis by Type, United States, 1982-1993

34%

47%
16% Hepatitis A
Hepatitis B
Hepatitis C
3% Hepatitis
Non-ABC

Source: CDC Sentinel Counties Study on Viral Hepatitis

 Estimates of Acute and Chronic Disease
Burden for Viral Hepatitis, United States

HAV HBV HCV HDV

Acute infections
(x 1000)/year* 125-200 140-320 35-180 6-13

Fulminant
deaths/year 100 150 ? 35
Chronic 0 1-1.25 3.5
nfections million million 70,000

Chronic liver disease

deaths/year 0 5,000 8-10,000 1,000

* Range based on estimated annual incidence, 1984-1994.

Hepatitis A Virus
 Hepatitis A - Clinical Features
ncubation period: Average 30 days
Range 15-50 days
aundice by <6 yrs, <10%
age group: 6-14 yrs, 40%-50%
>14 yrs, 70%-80%
Complications: Fulminant hepatitis
Cholestatic hepatitis
Relapsing hepatitis
Chronic sequelae: None
 Age-specific Mortality Due to Hepatitis A
Age group Case-Fatality
(years) (per 1000)

<5 3.0
5-14 1.6
15-29 1.6
30-49 3.8
>49 17.5
Total 4.1
Source: Viral Hepatitis Surveillance Program, 1983-1989
 Hepatitis A Virus Infection
Typical Serologic Course
Symptoms Total anti-HAV

ALT
r

Fecal
HAV
IgM anti-HAV

0 1 2 3 4 5 6 12 24
Months after Exposure
 Concentration of Hepatitis A Virus
in Various Body Fluids

Feces

d
Serum

Saliva

Urine

100 102 104 106 108 1010

Infectious Doses per ml
Source: Viral Hepatitis and Liver Disease 1984;9-22
J Infect Dis 1989;160:887-890
 Hepatitis A Virus Transmission

•Close personal contact

(e.g., household contact, sex contact, child day
care centers)
•Contaminated food, water
(e.g., infected food handlers, raw shellfish)
•Blood exposure (rare)
(e.g., injecting drug use, transfusion)
 Incidence of Hepatitis A, United States, 1952-1993
40

30

r 100,000)
20

10

0
1952 1960 1970 1980 1990
Year
Source: CDC, National Notifiable Diseases Surveillance System
 Age-specific Incidence of Hepatitis A United
States, 1983-93
25

20

15 5-14 years
(per 100,000) 15-24 years
25-39 years
10
0-4 years

5 40+ years

0
1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993
Year
Source: CDC, National Notifiable Diseases Surveillance System
 Sources of Hepatitis A Virus Infection by
Mutually Exclusive Groups, United States, 1983-93
40

30

of Cases Personal contac

20

Day care center

10
Foreign travel
Drug use
0 Outbreak
1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993
Year
Source: CDC, Viral Hepatitis Surveillance Program
 Global Patterns of
Hepatitis A Virus Transmission
Disease Peak Age
Endemicity Rate of Infection Transmission Patterns

High Low to Early Person to person;

High childhood outbreaks uncommon
Moderate High Late Person to person;
childhood/ food and waterborne
young adults outbreaks
Low Low Young adults Person to person;
food and waterborne
outbreaks
Very low Very low Adults Travelers; outbreaks
uncommon
 Geographic Distribution of HAV Infection

nti-HAV Prevalence
High
Intermediate
Low
Very Low
Hepatitis A Vaccine Efficacy Studies
Vaccine
Site/Age Efficacy
Vaccine Group N (95% CI)
HAVRIX ® Thailand 38,157 94%
(SKB) 1-16 yrs (79%-99%)
2 doses
360 EL.U.
VAQTA ™ New York 1,037 100%
(Merck) 2-16 yrs (85%-100%)
1 dose
25 units
JAMA 1994;271:1363-4
N Engl J Med 1992;327:453-7
 Hepatitis A Vaccination Strategies
Epidemiologic Considerations

•Many cases occur in community-wide outbreaks

•no risk factor identified for most cases
•highest attack rates in 5-14 year olds
•children serve as reservoir of infection
•Persons at increased risk of infection
•travelers
•homosexual men
•injecting drug users
Routine Childhood Hepatitis A Vaccination

•Benefits
•established delivery system
•vaccination before risk period
•potential to interrupt transmission
•Unresolved issues/considerations
•immunogenicity in infants
•development of combination vaccines
•duration of protection
•cost-effectiveness
ACIP Recommendations - Hepatitis A Vaccine
Preexposure Vaccination
•Persons at increased risk for infection
•travelers to intermediate and high
HAV-endemic countries
•homosexual and bisexual men
•drug users
•persons with chronic liver disease
•Communities with high rates of hepatitis A
(e.g., Alaska Natives, American Indians)
•routine childhood vaccination
 Features of Community-wide
Hepatitis A Outbreaks
Usual Age Annual
Type of Anti-HAV of Case- Incidence/ Outbreak
Community Prevalence patients 100,000 Periodicity Populations

High rate <5 yrs old 5-14 yrs 700-1000 5-10yrs well defined
30%-40% geographically
>15 yrs old or ethnically
70% -100%

ntermediate <5 yrs old 5-29 yrs 50-200 may be less defined
rate 10%-25% periodic than in
>15 yrs old high-rate
<50% communities
ACIP Recommendations - Hepatitis A Vaccine
Control of Community-wide Outbreaks

High-rate communities
•Routine vaccination of young children
•Accelerated catch-up vaccination of older
children
 ACIP Recommendations - Hepatitis A Vaccine
Control of Community-wide Outbreaks
Intermediate-rate communities
•Targeted vaccination can be considered for groups
or areas with highest disease rates
(e.g., specific age groups, census tracts,
drug users)
•Factors to consider:
•feasibility of vaccinating target groups
•program cost
•ability to sustain vaccination of young children
 ACIP Recommendations - Hepatitis A Vaccine
Prevaccination Testing
onsiderations:
•cost of vaccine
•cost of serologic testing (including visit)
•prevalence of infection
•impact on compliance with vaccination
ikely to be cost-effective for:
•adults born, or who lived in, high endemic areas
•adults >40 years of age
•older adolescents and young adults in certain groups
(American Indians, Alaska Natives, Pacific Islanders)
 ACIP Recommendations - Hepatitis A Vaccine
Postvaccination Testing

•Not recommended because of the high

response rate among vaccinees
•No commercially available test to measure
vaccine response
 Recommended Doses and Schedules
of Hepatitis A Vaccine

HAVRIX®
No. Doses Schedule
Group Age Doses EL.U.* (ml) (months)

Children and
adolescents 2-18 years 3 360 (0.5) 0, 1, 6-12

Adults >18 years 2 1,440 (1.0) 0, 6-12

*ELISA units
Hepatitis A Prevention - Immune Globulin

•Preexposure
•travelers to intermediate and high
HAV-endemic regions
•Postexposure (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 B Virus
 Hepatitis B - Clinical Features
ncubation period: Average 60-90 days
Range 45-180 days
Clinical illness (jaundice): <5 yrs, <10%
≥5 yrs, 30%-50%
Acute case-fatality rate: 0.5%-1%
Chronic infection: <5 yrs, 30%-90%
≥5 yrs, 2%-10%
Premature mortality from
chronic liver disease: 15%-25%
 Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course

Symptoms
HBeAg anti-HBe

Total anti-HBc
Titer

HBsAg IgM anti-HBc anti-HBs

0 4 8 12 16 20 24 28 32 36 52 100
Weeks after Exposure
Progression to Chronic Hepatitis B Virus Infection
Typical Serologic Course
Acute Chronic
(6 months) (Years)
HBeAg anti-HBe
HBsAg
Total anti-HBc
Titer

IgM anti-HBc

0 4 8 12 16 20 24 28 32 36 52 Years
Weeks after Exposure
 Rate of Reported Hepatitis B by Age Group
25 United States, 1990
20

15
100,000)

10

0
0-14 15-19 20-29 30-39 40+
Age Group (Years)
Source: CDC Viral Hepatitis Surveillance Program
Age at Aquisition of Acute and Chronic HBV Infection
United States, 1989 Estimates

(4% ) Perinatal (24%)

(4%) Children (12%)
(1-10 yrs) Adult
Adult (8%) Adolescent (6%)
(83%) (59%)

Acute HBV Infections Chronic HBV Infections

 Outcome of Hepatitis B Virus Infection
100 by Age at Infection 100

80 80

60 60
ection (%) Chronic Infection
Symptomatic
40 40

20 20

Symptomatic Infection
0 0
Birth 1-6 months 7-12 months 1-4 years Older Children
and Adults
Age at Infection
 Global Patterns of Chronic HBV Infection

•High (≥8%): 45% of global population

•lifetime risk of infection >60%
•early childhood infections common
•Intermediate (2%-7%): 43% of global population
•lifetime risk of infection 20%-60%
•infections occur in all age groups
•Low (<2%): 12% of global population
•lifetime risk of infection <20%
•most infections occur in adult risk groups
Geographic Distribution of Chronic HBV Infection

HBsAg Prevalence
≥8% - High
2-7% - Intermediate
<2% - Low