Hepatitis A epidemiology and demographics

Prevaccine Era
Hepatitis A epidemiology in the United States has fundamentally changed with licensure of hepatitis A vaccine and implementation of national ACIP recommendations for its use. Before vaccine licensure during 1995-1996, hepatitis A incidence was primarily cyclic, with peaks occurring every 10-15 years. In the United States, during 1980-1995, approximately 22,000-36,000 hepatitis A cases were reported annually to CDC (rate: 9.0-14.5 cases per 100,000 population), but incidence models indicate that the number of infections was substantially higher. One such analysis estimated an average of 271,000 infections per year during 1980-1999, representing 10.4 times the reported number of cases. Each year in the United States, an estimated 100 persons died as a result of acute liver failure attributed to hepatitis A.

The costs associated with hepatitis A are substantial. Surveillance data indicate that 11%-22% of persons with hepatitis A are hospitalized. The average duration of work loss for adults who become ill has been estimated at 15.5 days for nonhospitalized patients and 33.2 days for hospitalized patients. Estimates of the annual direct and indirect costs of hepatitis A in the United States have ranged from $300 million to $488.8 million in 1997 dollars. A recent Markov model analysis estimated economic costs of $133.5 million during the lifetime of a single age cohort of children born in 2005, in the absence of vaccination.

Variation by Age, Race/Ethnicity, and Region
During the prevaccine era, the reported incidence of hepatitis A was highest among children aged 5-14 years, with approximately one third of reported cases involving children aged <15 years. Because young children frequently have unrecognized or asymptomatic infection, a relatively smaller proportion of infections among children than adults are detected by routine disease surveillance. Incidence models indicate that during 1980-1999, the majority of HAV infections occurred among children aged <10 years, and the highest incidence was among those aged 0-4 years. Before the use of hepatitis A vaccine, rates among American Indians and Alaska Natives were more than five times higher than rates in other racial/ethnic populations, and rates among Hispanics were approximately three times higher than rates among non-Hispanics.

Since the 1960s, the highest hepatitis A rates and the majority of cases occurred in a limited number of states and counties concentrated in the western and southwestern United States. Despite year-to-year fluctuations, rates in these areas consistently remained above the national average. In 11 states (Alaska, Arizona, California, Idaho, Nevada, New Mexico, Oklahoma, Oregon, South Dakota, Utah, and Washington) with consistently elevated rates, representing 22% of the U.S. population, average annual hepatitis A incidence was >20 cases per 100,000 during 1987-1997 (twice the national average of approximately 10 cases per 100,000 population); cases among residents of these states accounted for an average of 50% of reported cases. An additional 18% of cases occurred among residents of six states (Arkansas, Colorado, Missouri, Montana, Texas, and Wyoming) with average annual rates above (but less than twice) the national average during this time.

Approximately 31% of the U.S. population had serologic evidence of previous HAV infection, when measured in the Third National Health and Nutrition Examination Survey (NHANES-III) conducted during 1988-1994 (50). Anti-HAV prevalence varied directly with age: among persons aged 6-11 years, prevalence was 9%; 20--29 years, 19%; 40--49 years, 33%; and >70 years, 75%. Age-adjusted anti-HAV prevalence was considerably higher among Mexican-American (70%) compared with black (39%) and white (23%) participants, and among foreign-born (69%) compared with U.S.-born (25%) participants.

Sources of Infection
In the prevaccine era, the majority of U.S. cases of hepatitis A resulted from person-to-person transmission of HAV during communitywide outbreaks. The most frequently reported source of infection (in 12%-26% of cases) was household or sexual contact with a person with hepatitis A. Cyclic outbreaks occurred among users of injection and noninjection drugs and among men who have sex with men (MSM)   , and up to 15% of nationally reported cases occurred among persons reporting one or more of these behaviors. Other potential sources of infection (e.g., international travel and recognized foodborne outbreaks) were reported among 3%--6% of cases. For approximately 50% of persons with hepatitis A, no source was identified for their infection.

Communitywide Epidemics
During communitywide epidemics, infection was transmitted from person to person in households and extended family settings. These epidemics typically spread throughout the community, and no single risk factor or risk group could be identified that accounted for the majority of cases. Once initiated, epidemics often persisted for 1--2 years and proved difficult to control. Because children often have unrecognized or asymptomatic infection, they played a key role in sustaining HAV transmission during these epidemics.

Vaccine Era
With the licensure of inactivated hepatitis A vaccines by the Food and Drug Administration (FDA) during 1995-1996, hepatitis A became a disease that was not only common but also vaccine-preventable. Since 1996, and particularly since ACIP's 1999 recommendations for routine vaccination of children living in areas with consistently elevated hepatitis A rates, national hepatitis A rates have declined sharply. The 1999 recommendations called for routine vaccination of children living in states and communities in which the average hepatitis A rate during a baseline period of 1987-1997 was >20 cases per 100,000 population, approximately twice the national average, and for consideration of hepatitis A vaccination of children in those states and communities in which the average rate during the baseline period was at least the national average.

In 2004, a total of 5,683 cases (rate: 1.9 cases per 100,000 population) were reported, representing an estimated 24,000 acute clinical cases when underreporting is taken into account. This rate was the lowest ever recorded and was 79% lower than the previously recorded low in 1992. This decline is reflected in other fundamental shifts in hepatitis A epidemiology.

Variation by Age, Race/Ethnicity, and Region
Beginning in the late 1990s, national age-specific rates declined more rapidly among children than adults; as a result, in recent years, rates have been similar among all age groups. Historic differences in rates among racial/ethnic populations also have narrowed in the vaccine era. For example, recent rates among American Indians and Alaska Natives represent a 99% decline compared with the prevaccine era and are now approximately the same or lower than those of other racial/ethnic populations. Rates among Hispanics also declined 87% during this period, from 20.6 cases per 100,000 population during 1990-1997 to 2.7 per 100,000 in 2004, but remain higher than those for non-Hispanics. Elimination of historic geographic differences in incidence rates has also occurred, and since 2001, rates in states where vaccination was recommended have been approximately equal to the rest of the United States. In recent years, counties with higher rates have varied from year to year and have been distributed throughout the country.

Incidence declined sharply in states with historically consistently elevated rates included in the 1999 ACIP recommendations for routine vaccination of children. As a result, the majority of hepatitis A cases during recent years have been reported from states with historically low rates in which hepatitis A vaccination of children has not been widely implemented. In addition, the narrowing or elimination of national differences in age, race/ethnicity, and state-specific rates can be attributed largely to changes that occurred in the states in which routine hepatitis A vaccination of children was recommended and implemented. In 2004, for example, approximately two thirds of the nearly 6,000 cases were reported from states without childhood vaccination recommendations. The 2004 rate among all Hispanics in these states remained four times higher than among non-Hispanics and was seven times higher among Hispanic compared with non-Hispanic children. The highest rate in any demographic subgroup occurred among Hispanic children in states for which routine hepatitis A vaccination of children is not recommended.

Sources of Infection
In recent years, sexual or household contact with a person with hepatitis A has been reported in a smaller proportion of cases but continued to account for 13% of cases during 2002-2004 (5). The proportion of persons with hepatitis A reporting exposure to child care centers also has declined to approximately 9%. The number of international travel-associated cases has remained approximately the same, but as overall incidence has declined, the proportion of cases attributable to this exposure has increased, accounting for an average of 13% of cases during 2002-2004. During this time, >25% of cases among children aged <15 years could be attributed to international travel. Approximately 75% of all travel-related cases were associated with travel to Mexico or to Central or South America. Outbreaks among MSM and users of illicit drugs also continue to occur.