Will Hepatitis A Become a Vaccine-Preventable Disease?

Fifty years ago, hepatitis A was a common disease worldwide and most people had been infected with the hepatitis A virus (HAV) by the time they were young adults. Now, patterns of HAV transmission differ markedly among geographic regions throughout the world. In developing countries, most of the population is infected before 10 years of age, and HAV is the most frequent cause of acute hepatitis in children [1]. Most children less than 5 years of age do not have clinically evident infection, but they efficiently transmit HAV to their contacts in the household and in the community [2]. In more developed countries, the risk for infection is lower and most infections occur in older children and adults [1]. In many countries, changes in sanitation and socioeconomic level appear to have reduced the likelihood of infection with this enterically transmitted virus [1, 3]. Person-to-person contact is the primary mode of transmission, and food and water are infrequently implicated, although a massive outbreak of hepatitis A occurred in China when a susceptible young adult population consumed raw shellfish harvested from virus-contaminated waters [4-6]. In the United States, nationwide epidemics of hepatitis A occurred every 7 to 10 years until the mid-1970s, and approximately 60% of persons born before 1950 have been infected with HAV [6-8]. The endemicity of infection is considered low in this country; approximately 10% of persons less than 20 years of age have serologic evidence of infection [8]. However, low risk for infection is not constant throughout the nation, and rates of infection differ markedly according to age, race and ethnicity, and socioeconomic level [7, 8]. In 1992, 23 112 persons with hepatitis A were reported to the Centers for Disease Control and Prevention (CDC), and at least 70 of these persons died from fulminant liver failure, producing a case fatality rate of 0.3% [6]. Approximately one third of the cases reported to the CDC occur in children or adolescents [6]. Young children with unapparent infection often serve as the virus reservoir that produces symptomatic infection in older persons. Most cases of hepatitis A in the United States are not due to point-source outbreaks, but occur in community-wide epidemics. These epidemics occur with predictable regularity in many communities and primarily affect children and young adults of low socioeconomic status [9]. Contact with a person who has hepatitis A is the most common risk factor for infection in both community-wide epidemic and nonepidemic settings [6, 9]. Although community-wide epidemics occur throughout the United States, the highest rates of infection are in American Indian and Alaskan Native communities [7]. The cyclical epidemic pattern seen in these communities appears to be related to age-specific levels of immunity in the population, suggesting that the maintenance of an appropriate level of herd immunity would stop virus transmission [10-12]. The hepatitis A virus is related to the polio virus (both are picornaviruses) and exists as a single serotype with only a small degree of genetic variation [5, 13, 14]. However, the two viruses have many distinct differences; for example, HAV grows poorly in cell culture and does not replicate in the intestine [5]. Both inactivated and live attenuated HAV vaccines have been developed [5, 14], but the inactivated vaccine, produced in much the same way as inactivated polio vaccine, is now available in much of Europe, parts of Asia, and Canada. Inactivated HAV vaccine has been shown to be highly immunogenic when given to adults and children in various schedules, although passively acquired antibody to HAV (such as that acquired when immune globulin is given simultaneously) reduces immunogenicity [15-19]. In adults, seroconversion rates of more than 95% have been achieved with two doses of vaccine given 4 to 6 months apart. In children, seroconversion rates approaching 95% have been achieved with a single dose of vaccine. However, the ideal number of doses and the optimum dosing schedule have not been determined for all age groups and vaccination settings. The efficacy of preexposure immunization in preventing clinically apparent infection in children has been shown in placebo-controlled clinical trials [18, 19]. Although it has not been fully evaluated in these studies, immunization is presumed to prevent subclinical infection and virus shedding. Evidence from studies of experimentally inoculated animals [20] shows that some degree of postexposure protection may be conferred, but the efficacy of postexposure hepatitis A immunization has yet to be evaluated in clinical trials. Hepatitis A vaccine is expected to be licensed in the United States in 1995. Strategies and specific recommendations for its use are being developed by the Advisory Committee on Immunization Practices of the U.S. Public Health Service and the Committee on Infectious Diseases of the American Academy of Pediatrics. From a public health perspective, if hepatitis A is to become a vaccine-preventable disease, our goal must be the long-term reduction of disease incidence through the elimination of HAV transmission. Some have suggested that the new vaccine should be used for the selective immunization of persons at risk for infection. The only persons for whom such a strategy is feasible, however, are persons from countries with low endemicity for infection who travel or live in countries with high endemicity, but this group accounts for fewer than 10% of all cases of hepatitis A [6]. Fifty percent of persons with hepatitis A have no identifiable risk factor, and of those that do, contact with an infected person is the most common [6]. Similarly, although approximately 15% of reported cases occur in the daycare setting, these infections occur because of contact with an infected person. Contact with a person with hepatitis A can hardly be considered a risk factor for preexposure hepatitis A vaccination. Furthermore, no data exist to suggest that children in daycare have a higher incidence or prevalence of HAV infection or that they should be considered a risk group. Thus, vaccination of targeted risk groups has little chance of lowering the overall incidence of infection in the United States. In populations in which HAV infection is highly endemic (such as American Indians and Alaskan Natives), routine vaccination of successive cohorts of young children or infants, or both, is the only strategy that has the potential to prevent recurrent epidemics of hepatitis A. In these communities, more than 40% of children are infected by 5 years of age, and almost all adults have been infected [10, 12]. Childhood immunization would rapidly eliminate both transmission of HAV and susceptibility to infection. Prevention of hepatitis A in other communities that experience recurrent epidemics, or in the United States in general, is more difficult because of both the wide age range of persons susceptible to HAV infection and the occurrence of infections in all age groups. However, routine vaccination of infants in successive birth cohorts should prevent childhood infections and those infections in adults that are acquired from children. Eventually, this immunization strategy would prevent most adult-acquired infections. The most rapid reduction in the incidence of HAV infection could be achieved through the immunization of infants as well as the catch-up immunization of older children or adolescents, or both. However, before any of these immunization strategies are widely adopted, several issues must be addressed, including estimates of the long-term efficacy of immunization, the ability to combine hepatitis A vaccine with other childhood immunogens, and the cost-effectiveness of preventing HAV infection. Ultimately, if immunization is able to maintain a high level of immunity in the population, hepatitis A could be eliminated and eradication of HAV infection could be possible.