Prevention of Hepatitis A Through Active or Passive Immunization

Epidemiology of HAV Infection

Routes of Transmission

HAV infection is acquired primarily by the fecal-oral route by either person-to-person contact or ingestion of contaminated food or water. Viremia occurs during the prodromal phase of the illness, and HAV has been transmitted on rare occasions by transfusion ⁽¹⁵⁾. In experimentally infected animals, HAV has been detected in saliva during the incubation period; however, transmission by saliva has not been demonstrated ⁽¹⁶⁾.

Depending on conditions, HAV can be stable in the environment for months ⁽¹⁷⁾. Heating foods at temperatures >185 F (85 C) for 1 minute or disinfecting surfaces with a 1:100 dilution of sodium hypochlorite (i.e., household bleach) in tap water is necessary to inactivate HAV ⁽¹⁸⁾.

Surveillance and Seroprevalence Data

In the United States, cyclic increases in the incidence of hepatitis A have occurred approximately every decade; the last nationwide increase occurred in 1989 ⁽¹⁹⁾. Between epidemics, hepatitis A continues to occur at relatively high rates. In 1994, a total of 26,796 cases were reported to CDC's National Notifiable Diseases Surveillance System (NNDSS) ⁽²⁰⁾. After the data were corrected for underreporting and asymptomatic infections, an estimated 80,000 cases and 134,000 infections occurred in 1994 (CDC, unpublished data). Hepatitis A incidence varies by race/ethnicity, with highest rates among American Indians/Alaskan Natives and lowest rates among Asians; rates among Hispanics are higher than among non-Hispanics (Figure 1). Rates also are substantially higher in the western United States than in other U.S. regions. Racial/ethnic and geographic differences in rates most likely reflect differences in socioeconomic levels and resultant living conditions (e.g., crowding), which facilitate transmission of HAV.

The highest rates of hepatitis A are among children 5-14 years of age (Figure 2). Almost 30% of reported hepatitis A cases occur among children <15 years of age ⁽²¹⁾. Presumably many more children have unrecognized, asymptomatic infection and can be a source of infection for others ^(6,11).

The most frequently reported source of infection (22%-26%) is either house-hold contact or sexual contact with a person who has hepatitis A ⁽²¹⁾. An additional 14%-16% of reported cases occur among children or employees in day care centers or among contacts of children or employees in day care centers; 4%-6% occur among international travelers; and another 2%-3% are associated with recognized food or waterborne disease outbreaks ^(19,21). Person-to-person contact is thought to be the source of infection in outbreaks among injecting- and noninjecting-drug users and among men who have sex with men ^(22,23). Approximately 50% of persons with hepatitis A do not have an identified source of infection ⁽²¹⁾.

In the United States, 33% of the population has serologic evidence of prior HAV infection as determined by Phase 1 of the Third National Health and Nutrition Examination Survey (NHANES-III) conducted during 1988-1991 (CDC, unpublished data). Anti-HAV prevalence is directly related to age: among children <10 years of age, the prevalence is 10%; 20-29 years of age, 18%; 40-49 years of age, 49%; and >70 years of age, 75%. Anti-HAV prevalence is highest among Mexican-Americans (67%), compared with blacks (37%) and whites (29%). Anti-HAV prevalence is inversely related to income. Hepatitis A results in substantial morbidity with associated costs caused by medical care and work loss; 11%-22% of persons who have hepatitis A are hospitalized ⁽²¹⁾. Adults who become ill lose an average of 27 days of work per illness (Table 1). Health departments incur substantial costs in providing postexposure prophylaxis to an average of 11 contacts per case (CDC, unpublished data). Average costs (direct and indirect) of hepatitis A range from $1,817 to $2,459 per case for adults and from $433 to $1,492 per case for children <18 years of age (Table 1). In 1989, the estimated annual cost (direct and indirect) of hepatitis A in the United States was >$200 million ⁽²⁴⁾.

In the United States, an estimated 100 deaths occur each year as a result of fulminant hepatitis A. Data reported to CDC indicate that the case-fatality rate among persons of all ages is approximately 0.3%. However, the risk for death is 1.8% among adults >50 years of age; persons who have chronic liver disease have a high risk of death from fulminant hepatitis A ^(25,26).

Communitywide Outbreaks

In the United States, most hepatitis A occurs through person-to-person transmission during communitywide outbreaks ⁽²⁷⁾ when the highest rates of disease occur among children, adolescents, and young adults. Outbreaks have been difficult to control despite enhanced awareness of preventive measures and postexposure prophylaxis with IG. Experience during most communitywide outbreaks has indicated that widespread postexposure prophylaxis with IG may slow HAV transmission but does not stop the outbreak ^(28,29).

Categorizing communities that experience hepatitis A outbreaks can help determine whether to use hepatitis A vaccine to control or prevent communitywide out-breaks. Communities that experience hepatitis A outbreaks can be considered as either communities that have high rates of hepatitis A or communities that have intermediate rates of hepatitis A, based on certain epidemiologic characteristics (e.g., age-specific rates of infection and temporal patterns of disease incidence) (Table 2). In both types of communities, outbreaks usually have been difficult to control.

Communities That Have High Rates of Hepatitis A

Communities that have high rates of infection typically have epidemics of hepatitis A every 5-10 years that may last for several years, have high rates of disease, and have few cases among persons >15 years of age (Table 2). Seroprevalence data indicate that 30%-40% of children in these communities acquire infection before 5 years of age and almost all persons become infected before reaching young adulthood ^(29-31). These communities often are relatively well defined, either geographically or ethnically, and include American Indian, Alaskan Native, Pacific Islander, and selected Hispanic and religious communities ^{(29,30,32-34)}.

Communities That Have Intermediate Rates of Hepatitis A

In communities that have intermediate rates of hepatitis A, most disease occurs among children, adolescents, and young adults, in contrast to communities that have high rates of hepatitis A, in which the majority of cases occur among children <15 years of age. Communities that have intermediate rates of hepatitis A often are large metropolitan areas, and cases may be concentrated in specific census tracts or neighborhoods (Table 2) ^(28,35). Overall disease rates during epidemic periods typically range from 50 to 200 cases/100,000 population per year; however, within some census tracts, disease rates can be as high as those in communities that have high rates of hepatitis A. Surveillance data indicate epidemics often occur at regular intervals and persist for several years. However, some communities that have intermediate rates of hepatitis A do not have periodic epidemics but instead have sustained elevated rates of disease for many years. The epidemiologic factors associated with these differences in disease patterns have not been determined.

During epidemic periods, hepatitis A rates generally increase among all age groups, indicating widespread disease within the community ⁽³⁶⁾. Occasionally during outbreaks, the number of cases may increase among users of illegal drugs, men who have sex with men, or children and employees in day care centers ^(6,36-38). By examining local surveillance data, each community can determine if such groups represent a substantial source of HAV infection.

Data from some studies indicate that children with asymptomatic HAV infection can be a substantial source of infection for older persons during communitywide out-breaks. Data from a study in California among adults without an identified source of infection indicate that 25% of their asymptomatic contacts <6 years of age were IgM anti-HAV positive (CDC, unpublished data).