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Army Medical Surveillance Activity, US Army Center for Health Promotion and Preventive Medicine, Washington, DC
Department of Epidemiology, Division of Preventive Medicine
Department of Defense Global Emerging Infections Surveillance and Response System, Walter Reed Army Institute of Research, Silver Spring
Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland
Background.
In 2002, the US Department of Defense (DoD) mandated hepatitis B immunization for military recruits. A DoD study reported that screening for immunity with selective immunization would be cost-effective at a prevalence of immunity of >12%. The prevalence of hepatitis B immunity in the military recruit population was unknown.
Methods.
We studied a random sample of Army, Navy, and Marine Corps new recruits (2400 men and women from all 50 states, Puerto Rico, and US territories). Banked serum samples collected in 2001 were tested for antibody to hepatitis B surface antigen (anti-HBs) by AUSAB enzyme-linked immunoassay (EIA). Results were evaluated by military service branch, age, sex, race, level of education, geographic region of origin, and presence of state immunization laws.
Results.
The overall prevalence of anti-HBs seropositivity, adjusted to the age distribution of the recruit population in 2001, was 31.5% (95% confidence interval [CI], 29.6%33.4%). The prevalence of anti-HBs seropositivity, directly adjusted to the 1835-year-old US population in 2000, was 23.0% (95% CI, 20.7%25.3%). Anti-HBs seropositivity prevalence was highest among the young, decreased with increasing age, and was higher in women, recruits from the Northeast and West, and recruits from states with laws mandating hepatitis B immunization before entry into elementary and middle school.
Conclusions.
Screening new recruits for evidence of immunity before hepatitis B immunization is indicated. The prevalence of immunity increased with successive birth cohorts and may reflect the success of childhood immunization programs.
In 2002, the Office of the Assistant Secretary of Defense (Health Affairs) mandated a hepatitis B immunization program for all new US military recruits [1]. This directive did not specify an immunization strategy but directed that consideration be given to serologic testing as a part of the program. A cost-effectiveness study was conducted by military investigators, who concluded that screening for hepatitis B immunity was cost-effective when the prevalence of immunity was >12% in new recruits [2]. Unfortunately, data on the prevalence of hepatitis B immunity in US military recruits were not available. Survey data on immunization rates and coverage estimates were available for selected groups but were not representative of the young adult workforce [37].
The National Immunization Survey (NIS), a continuous yearly survey of immunization coverage among children aged 1935 months, estimated coverage for the complete 3-dose series of hepatitis B vaccine to be 89.9% (95% SE, ±0.7%) in 2002 [8]. Because of widespread acceptance of Advisory Committee on Immunization Practices (ACIP) recommendations in support of hepatitis B immunization, beginning in 1991, substantial immunity was anticipated in the US military recruit population [916]. Laws in 44 states and the District of Columbia requiring hepatitis B immunization of children before entry into elementary or middle school could also have had a positive impact on the immune status of recruits. In 1994, Virginia passed the first state law requiring hepatitis B immunization before entry into elementary school. In 1997, Colorado, the District of Columbia, Florida, Illinois, Oklahoma, and Wisconsin required immunization before entry into middle school [17]. The Centers for Disease Control and Prevention (CDC) estimated that hepatitis B immunization coverage (3 doses) for children entering kindergarten or first grade during the 20022003 school year was 96.0% [18].
Our study was conducted to determine the prevalence of antibody to hepatitis B surface antigen (anti-HBs) in US Army, Navy, and Marine Corps recruits. Air Force medical leaders elected to conduct their own assessment of the immune status of their recruits [19]. We chose to define immunity as the presence of anti-HBs, although we realize that the population with identifiable antibody may not represent the entire population that is protected against disease. Use of this measure could also overestimate prior immunization, because of the possibility of naturally acquired infection. Since military recruits represent all states and territories, we studied the relationships between anti-HBs seropositivity and geographic region of origin, other demographic variables, and immunization legislation in the recruits' home states.
SUBJECTS AND METHODS
Study population.
The study population included 2400 men and women, aged 1835 years, each of whom initially entered enlisted service in the US Army, Navy, or Marine Corps during the calendar year 2001 and had a stored serum sample available for testing. Sample size was limited by a fixed study budget. Serum samples were routinely obtained from all service members before initial military training and were stored at the DoD Serum Repository, Silver Spring, MD [20]. Available demographic data associated with these serum samples included branch of military service, age, sex, race, highest level of education attained, and home state of origin [21]. Individuals with prior military service were excluded, since prior service could have influenced the likelihood of immunization or exposure to hepatitis B. The definitions of geographic regions were based on the Bureau of the Census Geographic Divisions used by the CDC [22, 23]. This research was conducted under a protocol approved by the Walter Reed Army Institute of Research Institutional Review Board and Human Use Committee.
Sampling.
A random sample of recruits was stratified by service branch, according to the relative size of the new recruit population entering each branch. There were 185,262 new Army, Navy, and Marine Corps recruits in 2001; 55% entered the Army, 26% entered the Navy, and 19% entered the Marine Corps [21]. Thus, 55% of the total sample of 2400 recruits was allocated to the Army, 26% to the Navy, and 19% to the Marine Corps. Fifty-seven percent of the 2001 recruit population was 1819 years old, 29% was 2023 years old, and 14% was 2435 years old [21]. Age was considered to be the most important independent variable in the present study, because of changes in immunization practices aimed at younger people. Within each service branch, the oldest recruits were oversampled, to obtain more-precise estimates of immunity in this smaller group. Arbitrary sampling fractions based on age were used; 50% of each service branch's sample size was allocated to recruits 1819 years old, 25% was allocated to those 2023 years old, and 25% was allocated to those 2435 years old.
Hepatitis B immunization mandates.
Information on laws requiring childhood hepatitis B immunization and mandating hepatitis B immunization before entry into elementary or middle school was obtained from the Immunization Action Coalition, Saint Paul, MN [17]. The data collected included the presence or absence of state immunization laws, target groups for the laws, and the years the laws were passed.
Laboratory testing.
Qualitative testing for anti-HBs was performed in a College of American Pathologistscertified laboratory, by use of AUSAB EIA test kits (Abbott Laboratories), a Food and Drug Administrationcleared test, in accordance with the manufacturer's instructions. Equivocal results were reported as negative. Laboratory personnel were blinded to all personal information. Frozen banked serum samples from the DoD Serum Repository were thawed, and 0.5-ml aliquots were shipped on dry ice to the Immunology Section, US Air Force Institute for Operational Health, Brooks City-Base, TX, for processing.
Statistical analyses.
Estimation of the overall prevalence of anti-HBs seropositivity in the military recruits was performed by generating a point estimate and corresponding 95% confidence interval (CI) for an age-adjusted prevalence estimate, adjusted to the population of year 2001 military recruits. Estimation of the overall prevalence of anti-HBs seropositivity in the entire US population was performed by generating a point estimate and corresponding 95% CI for an age-adjusted prevalence estimate, adjusted to the year 2000 US population. Multiple logistic regression modeling was used to estimate relationships between anti-HBs seropositivity and other recruit variables. Model building was performed in a step-down fashion, beginning with a full model containing all potential predictor variables considered in this study. Wald tests were performed to ascertain the statistical significance of each predictor in the model [24]. This final model was used to estimate anti-HBs seropositivity prevalence for various subgroups of the population.
RESULTS
Sample characteristics.
Fifty percent of recruits in the sample were 1819 years old, 25% were 2023 years old, and 25% were 2435 years old (table 1). Most (82%) were male. Sixty-five percent were white, and 20% were black. Ninety-five percent had a high school diploma or greater. Our sample was significantly different from the 2001 military recruit population with respect to race and geographic region of origin, but the actual differences were not striking [21]. Our study population was similar to the 2000 US Census population with respect to race and geographic region of origin but was significantly different with respect to age, sex, and level of education (table 2) [22].
Anti-HBs seropositivity.
Serum samples and data were available for 2391 of the 2400 new recruits. The overall unadjusted anti-HBs seropositivity prevalence was 29.9% (95% CI, 28.1%31.8%). After adjustment for oversampling of older recruits, the anti-HBs seropositivity prevalence increased to 31.5% (95% CI, 29.6%33.4%). The directly adjusted anti-HBs seropositivity prevalence estimate for the 2000 US adult population (age 1835 years), based on age compositions of the 2000 US Census population, was 23.0% (95% CI, 20.7%25.3%) (table 3). The anti-HBs seropositivity prevalences in Army, Navy, and Marine Corps recruits were 31.1% (95% CI, 28.6%33.7%), 29.6% (95% CI, 26.0%33.3%), and 27.0% (95% CI, 23.0%31.4%), respectively, with no statistically significant differences between the service branches (table 4).
Demographic variables.
Anti-HBs seropositivity prevalences by age, sex, race, level of education, geographic region of origin, and service branch are shown in table 4. The anti-HBs seropositivity prevalence was highest (40.9% [95% CI, 36.7%45.1%]) among 18 year olds (men and women combined), who were born in 1983, and decreased with increasing age. The oldest recruit stratum, 2435 year olds (19661977 birth cohorts), had an anti-HBs seropositivity prevalence for both sexes combined of 19.5% (95% CI, 16.4%22.9%). Anti-HBs seropositivity prevalence was significantly higher in women (39.4% [95% CI, 34.8%44.1%]) than in men (27.8% [95% CI, 25.8%29.9%]). The prevalence of anti-HBs seropositivity varied significantly by geographic region of origin and was highest among recruits from the Northeast and West (40.1% [95% CI, 34.9%45.5%] and 34.3% [95% CI, 30.1%38.8%], respectively) and lowest among recruits from the South (25.9% [95% CI, 23.2%28.8%]). There were no statistically significant differences in anti-HBs seropositivity prevalence according to race, level of education, or service branch.
The results from multivariate logistic regression modeling (data not shown) revealed multiple predictors of anti-HBs seropositivity. Recruit age, sex, geographic region of origin, and home state grouped by the presence of laws mandating hepatitis B immunization of children before entry into elementary and middle school were statistically significant predictors of anti-HBs seropositivity.
State immunization laws.
The anti-HBs seropositivity prevalence in recruits from states with laws mandating hepatitis B immunization before entry into elementary and middle school was 33.1% (95% CI, 30.8%35.4%), compared with 22.7% (95% CI, 19.4%26.4%) in recruits from states in which the immunization law applied only to entry into elementary school and 21.0% (95% CI, 14.2%29.2%) in recruits from states with no immunization law (P < .01) (table 5).
DISCUSSION
We found an overall prevalence of anti-HBs seropositivity in military recruits, adjusted for age, of 31.5% (95% CI, 29.6%33.4%). In an earlier study, the DoD determined that screening for anti-HBs is indicated when seropositivity in the recruit population is >12%. Therefore, serologic screening of all new Army, Navy, and Marine Corps recruits for evidence of hepatitis B immunity and targeted immunization of susceptible recruits should be conducted.
Age, sex, geographic region of origin, and home state immunization laws were significant predictors of anti-HBs seropositivity. Anti-HBs seropositivity prevalence was highest in 18 year olds and decreased with increasing age. This is encouraging and may indicate progress toward the goal of increasing hepatitis B immunization levels to meet Healthy People 2010 goals and eradicating hepatitis B transmission in the United States [25]. The higher anti-HBs seropositivity prevalence observed with younger age may reflect increasing adherence to the 1995 and 1997 national immunization guidelines for catch-up immunization of children and adolescents and of all previously unvaccinated children <18 years old. Similar findings were present in a study of 13 year olds enrolled in health maintenance organizations in which hepatitis B coverage increased from 1996 to 1998 and was attributed to adherence to the 1995 ACIP recommendations [26].
One possible explanation for the difference in anti-HBs seropositivity between men and women may be sex-based differences in health care utilization that resulted in more women being offered immunization [27]. Alternatively, this finding may be a statistical anomaly related to the significantly smaller number of women in our study population (443 women vs. 1957 men). This difference may not persist with study of a larger sample of women. Recruits from states in the Northeast and West were more likely to be anti-Hbs seropositive. This finding could not be explained by differences in age, sex, or the presence of state immunization laws. Regional differences may be due to differences in access to preventive services or immunization practices.
Anti-HBs seropositivity prevalence was higher in recruits from states with laws mandating hepatitis B immunization before entry into elementary and middle school than in those from states without immunization laws. There was no difference in anti-HBs seropositivity prevalence between recruits from states with laws mandating hepatitis B immunization before entry into elementary school and those from states without immunization laws. None of the recruits studied were directly impacted by laws mandating hepatitis B immunization of school-age children. Our study population consisted of birth cohorts from 19661982. The first birth cohort subject to a state law mandating immunization before entry into middle school is that from 19851986. Thus, observed differences related to school immunization laws may indicate physician and parent acceptance and compliance with the spirit of ACIP recommendations regarding hepatitis B immunization.
Our results are similar to those reported from an Air Force study of 7222 basic trainees in 2002 [19]. Air Force investigators found an overall anti-HBs seropositivity prevalence of 37% in new recruits. Female sex and young age were associated with higher prevalences. Air Force study subjects from the New England, North Atlantic, and Pacific regions were more likely to be antibody seropositive.
On the basis of our study of Army, Navy, and Marine Corps recruits and using the age compositions of the 2000 US Census, we estimated seropositivity for the 2000 US adult population (1835 years old) to be 23.0% (95% CI, 20.7%25.3%). Our sample of military recruits is a reflection of young adults across the United States, particularly those in the young adult workforce. Compared with the 2000 US Census population, our study group was younger, had more men, and had a smaller percentage of people without a high school diploma. Other unidentified biases related to being fit for military service and wanting to volunteer for military service could be related to the likelihood of being immunized against hepatitis B. Even though the military recruit population differs from the total US population, we believe that military recruits are a good population for use in monitoring the prevalence of immunity to hepatitis B as a measure of the success of immunization programs in the United States.
This study has several limitations. Our sample was significantly different from the 2001 total new recruit population with regard to race and geographic region of origin, and our sample size of 2400 limited subgroup analysis. Even though the race and geographic region variables were found to be statistically significant, the observed differences were not striking. These issues, along with sex, country of origin for foreign-born recruits, and level of education, should be considered in the design of future studies. We considered attempting to differentiate between natural infection and prior immunization. This was beyond the scope of the present study but should also be addressed in future studies. Hepatitis B immunity was defined as the presence of detectable anti-HBs in frozen, stored serum samples. This definition may have resulted in underestimation of hepatitis B immunity. The effect that repeated freezing and thawing involved in storage, aliquoting, shipping, and processing have on laboratory test performance is unknown.
The results of this study may reflect progress toward eradicating hepatitis B transmission in the United States through universal immunization. We anticipate increasing hepatitis B immunity with each successive birth cohort entering military service, as a result of compliance with ACIP childhood immunization guidelines. However, hepatitis B immunization early in life could result in waning antibody levels by the time young adults apply for military service. Therefore, our recommendation for universal serologic screening of new recruits with selective immunization will need to be periodically reexamined. Future surveys of military recruits should include both assessment of antibody status and ascertainment of the date of hepatitis B immunization, to develop data on the persistence of detectable antibody after immunization.
Acknowledgments
We thank Timothy E. Powers, Beverly L. Vaughn, Mary B. Brundage, Kathleen Huycke, Mark V. Rubertone, Margot R. Krauss, Jeffrey D. Gunzenhauser, Patrick W. Kelley, and Benedict M. Diniega, for their assistance in the planning and conduct of this study and the preparation of the manuscript; and Sylvia C. Trevino, Technical Supervisor, Immunology Section, Air Force Institute for Occupational Health, Brooks City-Base, Texas, who supervised the laboratory analysis.
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