# Presentation: 543584

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

- Epidemiology and Prevention of Viral Hepatitis A to E:

- Hepatitis Branch
- Centers for Disease Control and Prevention

**An Overview**

## Viral Hepatitis - Historical Perspective

**Viral Hepatitis - Historical Perspective**

- A

**“****Infectious”**

**“****Serum”**

**Viral hepatitis**

**Enterically**
**transmitted**

**Parenterally**
**transmitted**

**F, G,**
**? other**

- E

**NANB**

- B

- D

- C

## Viral Hepatitis - Overview

- Viral Hepatitis - Overview

**A**

**B**

**C**

**D**

**E**

- Source of

- virus

- feces

- blood/

- blood-derived

- body fluids

- blood/

- blood-derived

- body fluids

- blood/

- blood-derived

- body fluids

- feces

- Route of

- transmission

- fecal-oral

- percutaneous

- permucosal

- percutaneous

- permucosal

- percutaneous

- permucosal

- fecal-oral

- Chronic

- infection

- no

- yes

- yes

- yes

- no

- Prevention

- pre/post-

- exposure

- immunization

- pre/post-

- exposure

- immunization

- blood donor

- screening;

- risk behavior

- modification

- pre/post-

- exposure

- immunization;

- risk behavior

- modification

- ensure safe

- drinking

- water

**Type of Hepatitis**

## Acute Viral Hepatitis by Type, United States, 1982-1993 

**47%**

**34%**

**16%**

**3%**

**Hepatitis A**

**Hepatitis B**

**Hepatitis C**

**Hepatitis**
**Non-ABC**

**Source: CDC Sentinel Counties Study on Viral Hepatitis**

**Acute Viral Hepatitis by Type, United States, 1982-1993 **

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

**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

- infections

- 0

- 1-1.25

- million

- 3.5

- 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 Virus**

## Hepatitis A - Clinical Features

**Hepatitis A - Clinical Features**

- Incubation period:			Average 30 days
- 								Range 15-50 days
- Jaundice 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-specific Mortality Due to Hepatitis A**

**Age group**

**(years)**

**Case-Fatality**

**(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

**Fecal**
**HAV**

**Symptoms**

**ALT**

**IgM anti-HAV**

**Total anti-HAV**

**Months after Exposure**

**Titer**

**Typical Serologic Course**

**0**

**1**

**2**

**3**

**4**

**5**

**6**

**12**

**24**

**Hepatitis A Virus Infection**

## Concentration of Hepatitis A Virusin Various Body Fluids 

**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**

**Body Fluid**

**Infectious Doses per ml**

**10****0**

**10****2**

**10****4**

**10****6**

**10****8**

**10****10**

## Hepatitis A Virus Transmission

**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 

**Incidence of Hepatitis A, United States, 1952-1993 **

- Source: CDC, National Notifiable Diseases Surveillance System

**40**

**30**

**20**

**10**

**0**

**1952**

**1960**

**1970**

**1980**

**1990**

**Year**

**Rate (per 100,000)**

## Age-specific Incidence of Hepatitis A United States, 1983-93

**Age-specific Incidence of Hepatitis A United States, 1983-93**

- Source: CDC, National Notifiable Diseases Surveillance System

**Year**

**Reported Cases (per 100,000)**

**1983**

**1984**

**1985**

**1986**

**1987**

**1988**

**1989**

**1990**

**1991**

**1992**

**1993**

**0**

**5**

**10**

**15**

**20**

**25**

** ****5-14 years **

**15-24 years **

**25-39 years**** **

**   ****0-4 years**** **

**  ****40+ years **

## Sources of Hepatitis A Virus Infection byMutually Exclusive Groups, United States, 1983-93

**Sources of Hepatitis A Virus Infection by****Mutually Exclusive Groups, United States, 1983-93**

**Percentage of Cases**

- Source: CDC, Viral Hepatitis Surveillance Program

**Year**

**Personal contact**

**Day care center**

**Foreign travel**

**Outbreak**

**Drug use**

**40**

**30**

**20**

**10**

**0**

**1983**

**1984**

**1985**

**1986**

**1987**

**1988**

**1989**

**1990**

**1991**

**1992**

**1993**

## Global Patterns of Hepatitis A Virus Transmission

**Global Patterns of ****Hepatitis A Virus Transmission**

**Endemicity**

**Disease**

**Rate**

**Peak Age**

**of Infection**

**Transmission Patterns**

- High

- Low to

- High

- Early

- childhood

- Person to person;

- outbreaks uncommon

- Moderate

- High

- Late

- childhood/

- young adults

- Person to person;

- food and waterborne

- 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

**Geographic Distribution of HAV Infection**

**Anti-HAV Prevalence**

**High**

**Intermediate**

**Low**

**Very Low**

## Hepatitis A Vaccine Efficacy Studies

**Hepatitis A Vaccine Efficacy Studies**

- JAMA 1994;271:1363-4
- N Engl J Med 1992;327:453-7

**Vaccine**

**Site/Age **

**Group**

**N**

**Vaccine**

**Efficacy**

**(95% CI)**

- HAVRIX

- (SKB)

- 2 doses

- 360 EL.U.

- Thailand

- 1-16 yrs

- 38,157

- 94%

- (79%-99%)

- VAQTA

- (Merck)

- 1 dose

- 25 units

- New York

- 2-16 yrs

- 1,037

- 100%

- (85%-100%)

**®**

**TM**

## Hepatitis A Vaccination Strategies

- 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

**Hepatitis A Vaccination Strategies**
**Epidemiologic Considerations**

## 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

**Routine Childhood Hepatitis A Vaccination**

## 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

**Preexposure Vaccination**

**ACIP Recommendations - Hepatitis A Vaccine**

## Features of Community-wide

**Features of Community-wide**
**Hepatitis A Outbreaks**

**Type of **

**Community**

**Anti-HAV**

**Prevalence**

**Usual Age **

**of Case-**

**patients**

**Annual**

**Incidence/ **

**100,000**

**Outbreak**

**Periodicity**

**Populations**

- High rate

- <5 yrs old

- 30%-40%

- >15 yrs old

- 70% -100%

- 5-14 yrs

- 700-1000

- 5-10yrs

- well defined

- geographically

- or ethnically

- Intermediate

- rate

- <5 yrs old

- 10%-25%

- >15 yrs old

- <50%

- 5-29 yrs

- 50-200

- may be

- periodic

- less defined

- than in

- high-rate

- communities

## Control of Community-wide Outbreaks

- High-rate communities
- Routine vaccination of young children
- Accelerated catch-up vaccination of older children

**Control of Community-wide Outbreaks**

**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

**Control of Community-wide Outbreaks**

**ACIP Recommendations - Hepatitis A Vaccine**

## Prevaccination Testing

- Considerations:
- cost of vaccine
- cost of serologic testing (including visit)
- prevalence of infection
- impact on compliance with vaccination
- Likely 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)

**Prevaccination Testing**

**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

**Postvaccination Testing**

- ACIP Recommendations - Hepatitis A Vaccine

## Recommended Doses and Schedules

**Recommended Doses and Schedules**
**of Hepatitis A Vaccine**

**Group**

**Age**

**No.**

**Doses**

**EL.U.* (ml)**

**Schedule**

**(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

**Doses**

**HAVRIX****®**

- *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 A Prevention - Immune Globulin**

## Hepatitis B Virus

**Hepatitis B Virus**

## Hepatitis B - Clinical Features

**Hepatitis B - Clinical Features**

- Incubation 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 fromchronic liver disease:		15%-25%

## Acute Hepatitis B Virus Infection with Recovery

**Typical Serologic Course**

**Weeks after Exposure**

**Titer**

**Symptoms**

**HBeAg**

**anti-HBe**

**Total anti-HBc**

**IgM anti-HBc**

**anti-HBs**

**HBsAg**

**0**

**4**

**8**

**12**

**16**

**20**

**24**

**28**

**32**

**36**

**52**

**100**

## Progression to Chronic Hepatitis B Virus Infection

**Typical Serologic Course**

**Weeks after Exposure**

**Titer**

**IgM anti-HBc**

**Total anti-HBc**

**HBsAg**

**Acute**
**(6 months)**

**HBeAg**

**Chronic**
**(Years)**

**anti-HBe**

**0**

**4**

**8**

**12**

**16**

**20**

**24**

**28**

**32**

**36**

**52**

**Years**

## Rate of Reported Hepatitis B by Age Group

**Rate of Reported Hepatitis B by Age Group**
**United States, 1990**

**Age Group (Years)**

**Rate (per 100,000)**

**Source: CDC Viral Hepatitis Surveillance Program**

**0-14**

**15-19**

**20-29**

**30-39**

**40+**

**0**

**5**

**10**

**15**

**20**

**25**

## Age at Aquisition of Acute and Chronic HBV Infection

- United States, 1989 Estimates

- Acute HBV Infections

- Chronic HBV Infections

**(4% )  Perinatal  (24%)**
**(4%)  Children  (12%)**
**(1-10 yrs)**
**(8%)  Adolescent  (6%)**

**Adult**
**(83%)**

**Adult**
**(59%)**

## Outcome of Hepatitis B Virus Infection

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

**Symptomatic Infection**

**Chronic Infection**

**Age at Infection**

**Chronic Infection (%)**

**Symptomatic Infection (%)**

**Birth**

**1-6 months**

**7-12 months**

**1-4 years**

**Older Children**
**and Adults**

**0**

**20**

**40**

**60**

**80**

**100**

**100**

**80**

**60**

**40**

**20**

**0**

## 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

**Global Patterns of Chronic HBV Infection**

## Geographic Distribution of Chronic HBV Infection

**Geographic Distribution of Chronic HBV Infection**

**HBsAg Prevalence**

- ≥**8% - High **

**  ****2-7% - Intermediate **

**   ****<2% - Low**