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Hepatitis B Immunity in United States Military Recruits
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The Journal of Infectious Diseases, June 2005;191:1835-1841
Paul T. Scott,1 David W. Niebuhr,2 John B. McGready,4 and Joel C. Gaydos3
1Army Medical Surveillance Activity, US Army Center for Health Promotion and Preventive Medicine, Washington, DC; 2Department of Epidemiology, Division of Preventive Medicine, and 3Department of Defense Global Emerging Infections Surveillance and Response System, Walter Reed Army Institute of Research, Silver Spring, and 4Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland
ABSTRACT
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%Ð33.4%). The prevalence of anti-HBs seropositivity, directly adjusted to the 18Ð35-year-old US population in 2000, was 23.0% (95% CI, 20.7%Ð25.3%). 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.
INTRODUCTION
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 [3Ð7].
The National Immunization Survey (NIS), a continuous yearly survey of immunization coverage among children aged 19Ð35 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 [9Ð16]. 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 2002Ð2003 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.
Study population. The study population included 2400 men and women, aged 18Ð35 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.
RESULTS
Sample characteristics. Fifty percent of recruits in the sample were 18Ð19 years old, 25% were 20Ð23 years old, and 25% were 24Ð35 years old. 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 [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%Ð31.8%). After adjustment for oversampling of older recruits, the anti-HBs seropositivity prevalence increased to 31.5% (95% CI, 29.6%Ð33.4%). The directly adjusted anti-HBs seropositivity prevalence estimate for the 2000 US adult population (age 18Ð35 years), based on age compositions of the 2000 US Census population, was 23.0% (95% CI, 20.7%Ð25.3%). The anti-HBs seropositivity prevalences in Army, Navy, and Marine Corps recruits were 31.1% (95% CI, 28.6%Ð33.7%), 29.6% (95% CI, 26.0%Ð33.3%), and 27.0% (95% CI, 23.0%Ð31.4%), respectively, with no statistically significant differences between the service branches.
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%Ð45.1%]) among 18 year olds (men and women combined), who were born in 1983, and decreased with increasing age. The oldest recruit stratum, 24Ð35 year olds (1966Ð1977 birth cohorts), had an anti-HBs seropositivity prevalence for both sexes combined of 19.5% (95% CI, 16.4%Ð22.9%). Anti-HBs seropositivity prevalence was significantly higher in women (39.4% [95% CI, 34.8%Ð44.1%]) than in men (27.8% [95% CI, 25.8%Ð29.9%]). 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%Ð45.5%] and 34.3% [95% CI, 30.1%Ð38.8%], respectively) and lowest among recruits from the South (25.9% [95% CI, 23.2%Ð28.8%]). 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%Ð35.4%), compared with 22.7% (95% CI, 19.4%Ð26.4%) in recruits from states in which the immunization law applied only to entry into elementary school and 21.0% (95% CI, 14.2%Ð29.2%) in recruits from states with no immunization law (P < .01).
DISCUSSION
We found an overall prevalence of anti-HBs seropositivity in military recruits, adjusted for age, of 31.5% (95% CI, 29.6%Ð33.4%). 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 1966Ð1982. The first birth cohort subject to a state law mandating immunization before entry into middle school is that from 1985Ð1986. 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 (18Ð35 years old) to be 23.0% (95% CI, 20.7%Ð25.3%). 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.
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