Hepatitis A in US drops substantially after implementation of vaccination program

July 12, 2005

Following implementation of an expanded program of hepatitis A vaccination of children, the overall hepatitis A rate in the U.S. has declined by 76 percent, according to a study in the July 13 issue of JAMA.

In the United States, an average of 26,000 hepatitis A cases were reported annually to public health agencies during the 1980s and 1990s, representing an estimated 270,000 infections per year when anicteric (without jaundice) disease and asymptomatic infections are taken into account, according to background information in the article. More than half of the estimated infections occurred among children. In 1995, highly effective hepatitis A vaccines became available in the United States for use among persons aged 2 years or older, providing an opportunity to substantially reduce hepatitis A incidence. In 1996 the Advisory Committee on Immunization Practices recommended targeted hepatitis A vaccination of selected high-risk populations and routine vaccination for children living in communities with the highest hepatitis A rates. In 1999, this committee expanded its recommendations for routine vaccination of children to include children living in 17 states that had consistently elevated hepatitis A rates and a distinctive pattern of hepatitis A epidemiology.

Annemarie Wasley, Sc.D., of the Centers for Disease Control and Prevention, Atlanta, and colleagues analyzed data from a national hepatitis A surveillance to determine changes in the incidence and epidemiology of hepatitis A in the United States since 1990 and following implementation of recommendations for hepatitis A vaccination.

The researchers found that between the baseline period (1990-1997) and 2003, overall hepatitis A rates declined 76 percent to 2.6 per 100,000, significantly lower than previous lows in 1983 (9.2/100,000) and 1992 (9.1/100,000). The rate of hepatitis A in vaccinating states declined 88 percent to 2.5 per 100,000 compared with 53 percent elsewhere (to 2.7/100,000). In 2003, cases from vaccinating states accounted for 33 percent of the national total vs. 65 percent during baseline period. Declines were greater among children aged 2 to 18 years (87 percent) than among persons older than age 18 years (69 percent); the proportion of cases in children dropped from 35 percent to 19 percent. Since 2001, rates in adults have been higher than among children, with the highest rates now among men aged 25 through 39 years.

"In summary, we report early apparent impact of implementation of a novel, and to our knowledge, unique vaccination strategy. This strategy is based on distinctive features of hepatitis A epidemiology, including the geographic clustering of areas with consistently elevated rates, the important role of children in sustaining transmission, and the hypothesized large effect of herd immunity. These features lent themselves to a geographically focused strategy using a vaccine that could not be readily integrated into the routine vaccination schedule, and maximized the impact of limited vaccination. The changes we describe represent a transformation in hepatitis A epidemiology in the United States. However, because hepatitis A incidence has historically exhibited a pattern of periodic increases, further monitoring is needed to determine the extent to which the declines that have occurred will be sustained and are attributable to vaccination. In addition, more data on vaccine coverage levels are needed to better describe the relationship between hepatitis A vaccine usage and disease rates," the authors write.

"Sustaining and further reducing hepatitis A incidence can be achieved by improving vaccination coverage in groups for which it is currently recommended, including children living in the historically higher-rate states and children and adults in high-risk groups. Elimination of hepatitis A virus transmission will require expansion of existing recommendations to include routine vaccination of all U.S. children," the researchers conclude.

(JAMA. 2005;294:194-201. Available pre-embargo to the media at www.jamamedia.org.)

Editor's Note: Support for the analyses presented here was provided by the Centers for Disease Control and Prevention.

Universal Immunization of Toddlers in Israel Reduces Hepatitis A Rates Significantly

A national immunization program for infants in Israel has resulted in a 95 percent reduction in overall hepatitis A incidence, according to a study in the July 13 issue of JAMA.

Until 1999, Israel was considered a country with intermediate hepatitis A virus endemicity (a disease constantly present to greater extent in a particular locality). Although the overall incidence has been progressively decreasing since the 1960s, the annual reported incidence during the 1992-1998 period ranged from 33 to 70 per 100,000 population, with marked fluctuations. Reports of outbreaks, especially those involving young children, increased. Because most young children have asymptomatic or unrecognized infection, they play an important role in hepatitis A virus transmission as a source of infection. Therefore, routine childhood vaccination would theoretically prevent infection in age groups that account for a substantial proportion of cases, eliminate a major source of infection for other children and adults, and eventually prevent infections in older persons as vaccinated children grow to adulthood, because immunity to hepatitis A virus by vaccination is long-lasting.

Health officials in Israel decided to introduce universal vaccination of toddlers against hepatitis A because of epidemiologic evidence and a cost-benefit analysis of the program. The program started in July 1999 and is included in the National Health Services list so that the vaccine is given free of charge. A dose is given at ages 18 and 24 months. Immunization of older high-risk groups, such as drug users, continued.

Ron Dagan, M.D., of Ben-Gurion University of the Negev, Beer-Sheva, Israel, and colleagues examined the impact of the toddlers-only vaccination program of hepatitis A disease in all ages in the 5.5 years following initiation of the program. Overall vaccine coverage in Israel in 2001-2002 was 90 percent for the first dose and 85 percent for the second dose.

A decline in disease rates was observed before 1999 among the Jewish but not the non-Jewish population. The researchers found that after initiation of the program, a sharp decrease in disease rates was observed in both populations. The annual hepatitis A incidence rate of 2.2 to 2.5 per 100,000 during 2002-2004 represents a 95 percent or greater reduction for each year with respect to the average incidence during 1993-1998 (50.4 per 100,000). For children aged 1 through 4 years, a 98.2 percent reduction in hepatitis A disease was observed in 2002-2004, compared with the prevaccination period. However, a sharp decline was also observed in all other age groups (84.3 percent [less than 1 year], 96.5 percent [5-9 years], 95.2 percent [10-14 years], 91.3 percent [15-44 years], 90.6 percent [45-64 years], and 77.3 percent [65 years or older]). Among the Jewish population in the Jerusalem district, in whom the active surveillance program was successfully conducted, a more than 90 percent reduction of disease was demonstrated. Of the 433 cases reported nationwide in 2002-2004 in whom vaccination status could be ascertained, 424 (97.9 percent) received no vaccine and none received 2 doses.

"In the next decade, many regions worldwide will move from a state of high endemicity to a state of intermediate endemicity. The Israeli program of universal toddlers-only vaccination can serve as a paradigm of a simplified model of effective vaccination for both developed and developing countries," the authors conclude.

(JAMA. 2005;294:202-210. Available pre-embargo to the media at www.jamamedia.org.)

Editor's Note: This study was funded in part by an unrestricted grant from GlaxoSmithKline Biologicals.

Editorial: Effect of Hepatitis A Vaccination Programs

In an accompanying editorial, Pierre Van Damme, M.D., Ph.D., and Koen Van Herck, M.D., of the University of Antwerp, Belgium, comment on the studies in this week's JAMA on hepatitis A vaccination programs.

"The baseline differences in disease incidence between vaccinating and nonvaccinating states in the United States on which the universal vaccination recommendations were determined were eliminated and the incidence gap between high and intermediate endemic populations in Israel was narrowed or almost closed. Vaccination was a major contributor to these declines but, as discussed by both sets of authors, it is difficult to evaluate to what extent the observed reduction of the hepatitis A virus incidence rate could be attributed to improved environmental and hygienic conditions or to the epidemic cycles that characterized the epidemiology of hepatitis A virus in the past. Only continued disease surveillance will allow confirmation of the real impact and added value of these mass vaccination programs."

"... if administration of multiple vaccines or combination vaccines is not an issue, and if the vaccine cost is reasonable, toddlers-only or childhood immunization programs could become a realistic strategy in countries and regions where endemicity is shifting from high to intermediate, a situation that will increase in the next decade worldwide," the authors conclude.

(JAMA. 2005;294:246-248. Available pre-embargo to the media at www.jamamedia.org.)

Editor's Note: Drs. Van Damme and Van Herck have been principal investigators of vaccine trials for several vaccine manufacturers for which the University of Antwerp receives research grants.

The JAMA Network Journals

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