a Department of Defense Center for Deployment Health Research at the Naval Health Research Center, San Diego, CA, USA.
b Current affiliation: University of Iowa College of Public Health, Department of Epidemiology, Iowa City, IA, USA.
c Preventive Medicine Division, Naval Hospital, Great Lakes, IL, USA.
d Uniformed Services University of the Health Sciences, Department of Preventive Medicine and Biometrics, Division of Epidemiology and Biostatistics, Bethesda, MD, USA.
Besa Smith, DoD Center for Deployment Health Research, PO Box 85122, Naval Health Research Center, San Diego, CA 921865122, USA. E-mail: besa{at}nhrc.navy.mil
Abstract
Background Tuberculosis (TB) is a re-emerging infectious disease threat worldwide. To protect the health and readiness of US military personnel, policies exist to screen for and treat latent TB infection at the time of service entrance. Results of this screening programme have not been recently described.
Methods Multivariate regression techniques were used to evaluate demographic and medical data associated with TB infection among all young adults entering US Navy enlisted service between 1 October 1997 and 30 September 1998.
Results A total of 44 128 adults (ages 1735, 81% male) were screened for TB during this 12-month period. The prevalence of latent TB infection was 3.5%. Place of birth was very strongly associated with TB infection, with foreign-born recruits eight times more likely to have a reactive tuberculin skin test or history of infection. Those who reported their race as Asian/Pacific Island had 3.8 times the odds of having evidence of TB infection compared with Caucasian recruits, even after adjusting for place of birth.
Conclusions The prevalence of TB infection among Navy recruits was last reported as 2.5% nearly 10 years ago. The apparent increase to 3.5% in this large cohort is likely due to a concurrent increase in the number of foreign-born recruits, and it serves to underscore the importance of comprehensive screening and treatment of latent TB infections in this population.
Keywords Tuberculosis, PPD, tuberculin skin testing
Accepted 1 February 2002
Tuberculosis (TB) has historically caused tremendous morbidity and mortality worldwide. Active disease rates in developed countries declined throughout the 19th and 20th centuries causing some to believe that TB was a disease of the past.13 The resurgence of TB in the US in the late 1980s, along with the emergence of multi-drug resistant strains, refocussed attention on this challenging pathogen.46 Although rates of active disease now are declining again in the US,7 officials have continued to focus more energy on TB prevention programmes with the goal of eventually eliminating this public health threat. Screening for latent TB infections is a key component of most prevention efforts,8 yet the prevalence of latent infections in large populations is rarely described.
The US military has been especially vigilant for TB infection since active disease not only impairs an individuals medical readiness, but can threaten large numbers of troops.9,10 While military members may be at risk for acquiring TB infection because of their worldwide deployment, historically, their greater risk has been exposure to military members with active TB in the close-contact environments in which they live and work.911 The US Navy mandates screening for latent TB infections by skin testing with five tuberculin units of purified protein derivative (PPD Tubersol®, Aventis Pasteur, Swiftwater, PA, USA), among all service members upon induction and periodically thereafter.12 The results associated with the US Navys TB screening programme may be valuable to both military and civilian public health professionals who are concerned about the dynamic epidemiology of TB.
Young adults enlisting in the Navy represent a healthy sample of the general US population. The prevalence of latent TB infection in this group was last reported among 2214 recruits enlisting during a 2-month period in 1990.13 We evaluated the prevalence of TB infection among a much larger cohort who entered service during the 12-month period of fiscal year 1998. Since geographical risk factors for latent TB infection were last extensively reported more than 30 years ago,14 current geographical and demographic risk factors are also described.
Materials and Methods
Population
We evaluated records of all adults who entered the US Navys only recruit training facility, located in Great Lakes, Illinois, during fiscal year 1998 (1 October 1997 through 30 September 1998). Incoming recruits were asked about their history of TB. Those who could provide documented evidence of past TB infection, latent or active, were excluded from skin testing and referred for treatment if appropriate. Those with no known history or inadequate documentation of active or latent TB infection received tuberculin skin testing by the Mantoux method, with five tuberculin units of PPD (Tubersol®, Aventis Pasteur, Swiftwater, PA, USA), injected intradermally on the forearm. Technicians examined the test site 4872 hours later for induration. Recruits with a skin induration 5 mm in diameter received further clinical evaluation including a chest radiograph.12 Once active TB was ruled out, recruits were considered to have latent TB infection if they had (1) a tuberculin induration of
10 mm; (2) a tuberculin induration of 59 mm and radiographic evidence of old granulomatous disease, or known close contact to an active TB case; or (3) a documented history of past TB infection, precluding tuberculin skin testing. Health care providers followed established clinical practices for the evaluation, follow-up, and therapy for latent TB infection, in accordance with the Centers for Disease Control and Prevention guidelines.12,15,16
Data
Results of TB screening were obtained from the Preventive Medicine Division, Naval Hospital, Great Lakes. Most demographic variables (gender, age, race/ethnicity) were acquired from the Sailors Health Inventory Program, a self-completed survey administered to recruits during their initial few days of training.17 Place of birth was obtained from the Defense Manpower Data Center, Monterey Bay, CA, USA.
Place of birth, used to determine geographical risk factors, represents the state or country recorded as the birthplace of the recruit. For analysis, the primary categorization of place of birth was US-born or foreign-born, but to evaluate global and regional patterns, place of birth was further categorized by global region and region within the US. Age was categorized into approximate tertiles in the following manner: 1718, 1920, 21 years. Available race/ethnicity data classified recruits as Caucasian, African American, Hispanic, Asian/Pacific Island, and Other. For all independent variables, the category with lowest prevalence of TB infection was used as the reference group in all modelling.
Statistical analyses
We conducted three types of statistical analyses. First, we univariately compared potential risk factors with TB infection. Covariates with P-values 0.15 were included in subsequent analyses. Collinearity was assessed using regression diagnostics and cross products were introduced to test for significance of interaction. Next, we studied these same associations using a multivariable manual backward logistic regression process. For this model, recruits were classified as TB-infected or non-infected. Finally, we used manual backward polychotomous logistic regression to study five TB screening categories: not infected, 59 mm induration on skin testing with radiographic evidence of old granulomatous disease or known close contact with a TB case, 1014 mm induration,
15 mm induration, and documented history of past TB infection. An alpha level of 0.05 was used for both logistic models as the criterion of inclusion in final models.
Prevalence was defined as the number of TB infections identified per 100 recruits. Odds ratios (OR) and 95% CI were computed using the Wald statistic for unconditional maximum likelihood estimation, both for the multivariable and polychotomous logistic models, to signify the risk of TB infection in this population.
Data management and all statistical analyses were performed using the SAS® system software (Version 8.0, Cary, NC, USA).
Results
During the study period, 44 128 men and women began recruit training. We captured complete data from 44 092 recruits; 36 had missing demographic data. Missing data analysis indicated that these recruits did not differ significantly from the study population and therefore were dropped from further modelling. The remaining 44 092 trainees were 19% female and ranged in age from 17 to 35 years (mean = 20, SD = 2.7). The majority of the recruits reported their race/ethnicity as Caucasian (55.3%), while 18.6% reported African American, 11.5% reported Hispanic, 5.0% reported Asian/Pacific Island, and 9.4% were categorized as Other race/ethnicity. The population was composed of 90.6% US-born individuals and 9.4% foreign-born individuals. Within the US, 40.3% were born in the Northeast, 32.7% were born in the Southwest, 15.1% were born in the northwest, and the remaining 11.9% were born in the Southeast. Overall, few (0.7%) recruits had a known, documented history of TB infection. The majority (96.2%) of the population had a skin test induration size recorded as zero mm. All other measured induration diameters ranged from 3 to 95 mm (Figure 1), with preferential recordings at 10, 15, 20, and 25 mm.
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With only nine subjects in the category defined as TB infected by a 59 mm induration with radiographic evidence of old granulomatous disease, the five-level polychotomous logistic regression model would not converge. Hence, the nine subjects and this category were removed and a four-level outcome model developed. The resulting polychotomous logistic regression revealed that gender, age, race/ethnicity, and place of birth were each significantly associated with TB infection after adjusting for the other covariates in the model (Table 2). The odds of having an induration of 1014 mm (compared with non-infected) was significantly greater among men compared with women; similarly, men were at increased odds of having an induration
15 mm. However, men were less likely to have had a history of TB than women. As in the logistic model, older recruits were at higher odds of TB infection than younger recruits. Recruits who reported race/ethnicity as African American, Hispanic, Asian/Pacific Island, and Other were all at increased odds of having an induration of 1014 mm or
15 mm and having a history of TB compared with Caucasian recruits. As in the multivariable logistic regression, the covariate that demonstrated the strongest association with TB infection was place of birth. Foreign-born recruits were at increased odds for all levels of induration when compared with US-born recruits; the largest OR was 8.6 (95% CI: 7.210.3) for an induration
15 mm. Within the US, there was very little difference between regions and TB outcome in this model.
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Cross et al.18 reported a 1.6% prevalence of latent TB infection in US Navy and Marine recruits from 1980 to 1986. Trump et al.13 reported the prevalence among Navy recruits in 1990 at 2.5%. Our data reveal a prevalence of TB infection in young adults enlisting in the US Navy in 1998 of 3.5%. The higher prevalence reported in this current study is likely explained by an almost two-fold increase in the percentage of foreign-born recruits in 1998 compared with 1990 (9.4% versus 5.0%, respectively). In fact, the prevalence of infection in foreign-born and US-born subsets of recruits was unchanged between 1990 and 1998, implying that the change in demographic mix was the most important factor in determining overall TB prevalence.
Not surprisingly, place of birth was the strongest predictor of latent TB infection. Other recent studies have had similar findings.13,18,19 Foreign-born recruits had eight times the odds of TB infection compared with US-born recruits. These findings highlight similar concerns about foreign-born TB infection described by other researchers,2023 and the need for special vigilance in screening such populations for TB. Although it is not recommended that the US military screen foreign-born recruits differently than US-born, the changing demographics of the military population underscore the importance of TB screening in the entire group.
It is reasonable to consider whether a past history of receiving Bacille Calmette-Guérin (BCG) vaccine could be responsible for the high rate of tuberculin skin test reactivity found in foreign-born Navy recruits. The BCG vaccine history may have been elicited by preventive medicine professionals caring for recruits, but because such history did not influence clinical decision-making it was not maintained in the recruit database. Without these data, BCG history could not be included in this analysis and this introduces an important limitation in interpreting these results. It is possible that some of the recruits considered TB-infected had skin test reactions because of past BCG vaccination. It may be important to note, however, that 70% of tuberculin reactions in foreign-born recruits were 15 mm induration, and therefore, were more likely to represent true TB infections than past BCG vaccination.8,24
Among US-born recruits, place of birth in the Southwest was marginally significant in the multivariable logistic model. One might hypothesize that this is due to Mexicos higher rate of TB and frequent migration across the US border for employment, commerce, health services and leisure.25 However, place of birth among US-born recruits was not significantly associated with TB infection in the polychotomous model. It is interesting that the prevalence of latent TB infection appeared so homogenous state-to-state within the US, even within the well-represented southwestern border states. Unfortunately, data were not available to distinguish urban versus non-urban settings in these analyses. Such data may have allowed us to validate the US geographical differences in TB infection that have been noted in other reports.26,27
It is notable that race/ethnicity was significantly associated with TB infection, even when controlling for place of birth in the multivariable logistic model. This may imply that some racial groups are more likely to be exposed to TB regardless of geographical location. The association between race/ethnicity and TB is consistent with other studies,26 although past reports have generally been limited to active TB cases and unable to include latent infection as we have analysed here. Socioeconomic status, which we were unfortunately unable to assess here, has confounded the association between race/ethnicity and TB in other reviews.25,27
While the age range of the military recruits was quite limited, 75% being under age 21, it was not surprising to find an increase in odds of TB infection and history of TB with an increase in age. Increasing risk with age is well supported in other reviews,28 and it is notable in this study that the relationship is robust, even in the narrow age range of young adult Navy recruits.
Gender did not appear to be significantly associated with TB infection in the multivariable logistic model, yet gender differences were seen in the polychotomous analysis. Specifically, men appeared more likely to have a tuberculin reaction of 10 mm, while women were more likely to have had a history of past TB infection. These findings might be explained by gender differences others have observed in the use of clinical preventive services.2931 Such findings, and their implications about the use of screening programmes, are even more important when one considers that the incidence of active TB disease has been reported as nearly twice as high in men as in women in the US.28
Our findings are limited by the challenges associated with using tuberculin skin testing to diagnose latent TB infections. The subjective element of skin test interpretation is highlighted by Figure 1, showing the preferential recording of indurations in multiples of 5 mm. Still, some challenges with skin testing may actually have been minimized in the Navy recruit setting where large numbers of tuberculin tests are placed and interpreted by a very experienced preventive medicine team. Another important limitation in interpreting results was our inability to include history of BCG vaccination in the analysis. The primary strength of this analysis lies in its large sample size; the prevalence of latent TB infection was evaluated among the largest group of healthy young adults reported in recent years. Logistic regression modelling provided a quantified description of several demographic risk factors associated with latent TB infection. The polychotomous model further refined the analysis and allowed the description of subtle, but potentially important, gender differences in TB infection.
Screening for latent TB infection among high-risk groups is considered critical to preventing disease morbidity and mortality.8 Results described here are somewhat extendable to the general US population, but the US military is also unique with regard to TB risk. Service members are ostensibly healthy (HIV-negative, free of chronic disease) and low-risk upon induction, yet they deploy worldwide, live in very close-contact settings, and have a critical need to remain disease-free during their careers. These pressures are of fundamental concern in the militarys policy of screening all recruits for TB, treating latent infections, and re-screening service members at regular intervals during their careers.12 Further studies would be helpful in defining how compliant Navy service members are in re-screening and completing treatment of latent TB infections. Recently, a US Navy ships crew member, who had not had regular TB screening, developed active disease while deployed, causing nearly 700 new latent infections and 17 new active cases of TB among his shipmates.10 The unfortunate experience of this Navy ship highlights the importance of compliance with TB prevention programmes after recruit training.
Acknowledgments
We wish to thank the Preventive Medicine Division, Naval Hospital, Great Lakes, IL, for providing recruit medical and demographic data. We also wish to thank Michael A Dove and Scott G Seggerman from the Management Information Division, Defense Manpower Data Center, Monterey Bay, CA, for providing recruit place of birth data. Finally, we wish to thank Dr Donald Slymen and Dr Stephanie Brodine for their contributions to this study.
Notes
This research has been conducted in compliance with all applicable Federal Regulations governing the protection of human subjects in research. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the US Government. Approved for public release; distribution unlimited.
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