Hepatitis B Virus: The Quest For Global Control And Eradication
There are limited options for controlling the spread of hepatitis B virus infection without the comprehensive use of the hepatitis B vaccine. Because there are no known effective therapies for acute hepatitis B, and treatment of chronic infections with alpha-interferon therapy has shown variable clinical success, the availability of a safe and effective hepatitis B vaccine represents the only major tool for the protection of public health.1 The first hepatitis B vaccine using plasma containing hepatitis B surface antigen (HBsAg) from chronically infected persons became commercially available in 1982. Subsequent research led to the development of hepatitis B vaccines produced by recombinant DNA technology. With this technology, Saccharomyces cerevisiae (common baker's yeast) is used to synthesize quantities of HBsAg. Additionally, a bivalent vaccine containing Haemophilus influenzae type b conjugate (meningococcal protein) and recombinant hepatitis B was recently licensed for use.
The initial recommendation for hepatitis B vaccine use was targeted for groups at high risk for transmission of hepatitis B. However, it became evident after a decade of this approach that the strategy was not as effective as expected.2 In response, other public health recommendations with alternative vaccination strategies were suggested (Table 1).3-7 Because implementation of the various hepatitis B vaccination strategies in the United States is dependent on state and local initiatives, in 1993 the Minnesota Department of Health focused on increasing the state's hepatitis B vaccination coverage. We review here the use of recommended hepatitis B vaccination strategies in Minnesota since that time.
MINNESOTA: PREVENTING HEPATITIS B TRANSMISSION WITH MULTIPLE STRATEGIES
History. Before the introduction of a hepatitis B vaccine, the incidence of acute hepatitis B was relatively low and constant among Minnesota residents who were not employed in hospitals (Fig. 1).8 In addition, extensive infection control efforts in the mid-1970s succeeded in significantly reducing the number of hepatitis B cases seen among high risk hospital personnel (Fig. 1).8 With the availability of a hepatitis B vaccine, the general consensus in the Minnesota public health community was that vaccination of high risk populations would significantly reduce the spread of the hepatitis B virus.
From 1982 to 1991, however, reported acute cases of hepatitis B among all Minnesota residents decreased by less than 30% (123 cases in 1982 compared with 88 cases in 1991) (Minnesota Department of Health, unpublished data). Similarly, on a national level, the number of acute hepatitis B cases declined less than 20% (22 177 cases in 1982 compared with 18 003 cases in 1991).9 This decade also recorded a change in the epidemiology of hepatitis B. Changes in high risk behaviors among homosexual men significantly reduced the number of cases being reported from this high risk group, and health care personnel acquired protection through both the implementation of bloodborne pathogen infection control practices and vaccine use.10 In contrast, intravenous drug use and heterosexual activity emerged as prominent risk factors for hepatitis B transmission.10 Additionally, the percentage of reported cases with unidentifiable risk factors remained constant at 30 to 40%.10
During 1990 to 1992, 69% of the cases of acute hepatitis B were associated with either unknown causes or heterosexual contacts with infectious or multiple partners.5 In contrast, only 2% of the cases were among high risk health care personnel.5 With the majority of cases occurring in population groups that were unattainable or difficult to identify, vaccination programs targeted for high risk groups were destined to be only marginally effective in reducing the overall disease burden of hepatitis B.
Implementation of additional vaccination strategies. In 1993, the Immunization Practices Task Force of the Minnesota Department of Health adopted a policy to use multiple vaccination strategies to prevent the transmission of hepatitis B. New strategies included the implementation of the Advisory Committee on Immunization Practices recommendations for universal HBsAg screening of pregnant women and the universal vaccination of infants and adolescents.
The universal HBsAg screening of all pregnant women had been implemented in 1991 to prevent childhood hepatitis B infections and the associated risk of chronicity. The universal vaccination of infants and adolescents was implemented primarily to protect them during their adolescent and adult years. Initially, hepatitis B vaccination of all Minnesota infants was not considered to have much utility, because the hepatitis B disease burden compared with that of other states was minimal (Fig. 2).11 Demographically, 96% of the population were white and approximately 50% lived in rural areas. Earlier efforts to protect high risk health care personnel had been successful.8 Thus, the general population of Minnesota had minimal identified risk factors for hepatitis B. Without public perception of a major health threat, it was determined that successful implementation of universal hepatitis B vaccination of infants and adolescents would require physician education, case surveillance, continued commitment to ongoing vaccination strategies and facilitation of vaccine use and distribution.
Hepatitis B surveillance data after implementation of multiple vaccination strategies. Minnesota statewide hepatitis B surveillance data show a minimal decrease in the annual incidence of acute hepatitis B during the 1990s (Fig. 3). After implementation of multiple vaccination strategies, Minnesota continued to show a varied epidemiologic pattern with 63 (72%) of the counties reporting no cases of acute hepatitis B for 1994 through 1996 (Fig. 4). Among the 203 acute cases of hepatitis B reported during this time, 147 cases (72%) were from 3 Minneapolis-St. Paul metropolitan counties (Hennepin, Ramsey and Dakota). The annual incidence for this tricounty area was 2.6 cases per 100 000 population. The remaining state population had an annual incidence of 1.4 cases per 100 000 population. Review of incidence by race showed that African-Americans had an annual incidence of 15.8 per 100 000 population compared with 1.0 per 100 000 population for whites. Compared with whites, Native Americans and Asian/Pacific Islanders also had higher annual incidences of 6.9 and 7.4 per 100 000 population, respectively.
Adults 20 years of age and older account for the majority of acute hepatitis B infections in Minnesota from 1994 to 1996 (Fig. 5). Among the 203 cases of acute hepatitis B, 114 (56%) had no risk factor identified or could not be interviewed (Fig. 6). Of the 114 cases with no known risk factors, 64 (56%) were white, 29 (26%) were African American and 21 (18%) were of other or unknown race. Cases with no known risk factors were distributed fairly evenly among three age groups 20 to 29 years, 30 to 39 years and 40 years or older (Table 2).
The universal HBsAg screening of pregnant women from 1994 to 1996 identified 761 infants born to women who were positive for HBsAg (Table 3). The majority of infants at risk for hepatitis B perinatal transmission were vaccinated (Table 3). The hepatitis B vaccination coverage of children 19 to 35 months of age in 1996 was 78% (± 4.2%, 95% CI) compared with greater than or equal to 83% coverage seen with four or more doses of diphtheria and tetanus toxoids and pertussis, three doses of polio, one dose of measles, mumps, rubella and three doses of H. influenzae type b.12
Based on an increase in vaccine doses obtained through the Vaccines for Children (VFC) program, facilitation of vaccine distribution has been successful in Minnesota for younger children and, to some degree, for adolescents (Table 4). In addition, approximately 90% of the vaccines are delivered through private providers and an increasing proportion of vaccines is acquired through the VFC program.
At this time, changes in the epidemiology of hepatitis B virus infection in Minnesota caused by the recently introduced vaccination programs cannot be assessed by the annual acute hepatitis B incidence data. The majority of acute hepatitis B infections in children younger than age 5 are asymptomatic2 and would not be detected in surveillance data. In addition, only serologic surveys can detect insidious chronic hepatitis B infections that are capable of hepatitis B transmission to susceptible individuals.2 We have demonstrated that chronic hepatitis B is a problem, as 761 infants were born to mothers who were HBsAg-positive during recent years.
Until populations have limited individuals susceptible to hepatitis B virus infection, together with limited cases of chronic hepatitis B, acute hepatitis surveillance data will not reflect the effectiveness of vaccination. Based on increased vaccination coverage, the strategies used in Minnesota have created the foundation for eliminating hepatitis B virus among future generations. Increased hepatitis B vaccination of infants and adolescents will result in a protected generation of young adults in the next decade. Elimination of hepatitis B perinatal transmission to newborns should prevent the highly probable progression to chronicity experienced by children infected before the age of 1 year. However, the positive outcomes of this strategy may take 20 to 30 years to manifest in reduced incidence and HBsAg carriage rates and even longer before decreased cases of cirrhosis of the liver and liver cancer are evident.
Targeted vaccination programs work only if the majority of at risk populations are vaccinated. The Minnesota surveillance data showed a greater number of cases of acute hepatitis B not associated with known risk factors than previously reported.10 Thus, it is essential to use multiple strategies to provide vaccination coverage for various age cohorts. The Minnesota Department of Health has succeeded in implementing numerous hepatitis B vaccination strategies among a generally low risk population. It is evident that universal hepatitis B vaccination strategies can be implemented in populations that have limited perceived health risk.
I thank Lynne Mercedes, Margaret Roddy and Diane Peterson for their assistance with summarizing the epidemiologic and immunization data and for helping to make the Minnesota effort to reduce the risk of hepatitis B infection a reality.
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4. Centers for Disease Control and Prevention. Protection against viral hepatitis. Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 1990;39(RR-2):1-22.
5. Centers for Disease Control and Prevention. Immunization Practices Advisory Committee (ACIP). Prevention of perinatal transmission of hepatitis B virus: prenatal screening of all pregnant women for hepatitis B surface antigen. MMWR 1988;37:341-51.
6. Centers for Disease Control and Prevention. Hepatitis B virus: a comprehensive strategy for eliminating transmission in the United States through universal childhood vaccination. MMWR 1991;40(RR-13):1-25.
7. Centers for Disease Control and Prevention. Immunization of adolescents. Recommendations of the Advisory Committee on Immunization Practices, the American Academy of Pediatrics, the American Academy of Family Physicians, and the American Medical Association. MMWR 1996;45(RR-13):1-16.
8. Osterholm MT, Garayalde SM. Clinical viral hepatitis B among Minnesota hospital personnel: results of a ten-year statewide survey. JAMA 1985;254:3207-12.
9. Centers for Disease Control and Prevention. Summary of notifiable diseases: United States 1996. MMWR 1997;45:1-88.
10. Alter MJ, Hadler SC, Margolis HS, et al. The changing epidemiology of hepatitis B in the United States. JAMA 1990;263:1218-22.
11. Centers for Disease Control and Prevention. Summary of notifiable diseases: United States 1993. MMWR 1994;42:1-91.
12. Centers for Disease Control and Prevention. National, state, and urban area vaccination coverage levels among children aged 19-35 months: United States, July 1996-June 1997. MMWR 1998;47:108-16.
Proceedings of the Satellite Symposium held at the 37th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); Toronto, Ontario, Canada; September, 1997
Keywords:© Williams & Wilkins 1998. All Rights Reserved.
Hepatitis B; vaccination; immunization