AFHSC - Peer Review

AFHSC/DMSS/DoDSR-related publications in peer reviewed journals (selected)

Updated: 07 March 2008

Singer DE, Schneerson R, Bautista CT, Rubertone MV, Robbins JB, Taylor DN. Serum IgG antibody response to the protective antigen (PA) of Bacillus anthracis induced by anthrax vaccine adsorbed (AVA) among U.S. military personnel. Vaccine Feb 2008(26);869-873
Summary: The seroconversion rates and geometric mean concentrations (GMC) of IgG anti-PA for stored sera from U.S. military personnel immunized 3, 4, and 6 times with the U.S. licensed anthrax vaccine adsorbed were studied. Anti-PA IgG concentrations were measured by ELISA. All 246 vaccinees had low but detectable pre-immunization anti-PA IgG (GMC 1.83 ug/mL). Three doses elicited a GMC of 59.92 ug/mL and a seroconversion rate of 85.3%, four doses elicited a GMC of 157.44 ug/mL and 67.9% and the sixth of 276.95 ug/mL and 45.5%, respectively. The fourth dose elicited 100% seroconversion compared to the pre-immunization level. These results should facilitate comparison between different immunization schedules and new vaccines.
Nevin RL, Shuping EE, Frick KD, Gaydos JC, Gaydos CA. Cost and effectiveness of chlamydia screening among male military recruits: Markov modeling of complications averted through notification of prior female partners. Sex Transm Dis. 2008 (in press).
Background: Despite rising rates of female screening, a high economic burden remains associated with Chlamydia infection from high rates of undetected asymptomatic disease and its associated sequelae of pelvic inflammatory disease (PID) and chronic pelvic pain. Males comprise the majority of U.S. military recruits and represent an ideal population in which to achieve identification and interruption of sexually transmitted infection among infected partners through mass tandem screening. Methods: We developed a static decision tree incorporating a calibrated Markov model to predict the differences in healthcare payer direct healthcare costs, cases of PID and chronic pain (CP) averted among female partners of male recruits through implementation of either selective (aged 24 and younger) or universal recruit screening policies incorporating partner notification. Results: A policy of selective male screening added $10.30 in direct costs per recruit; while universal male screening added an additional $1.60. A policy of selective male screening yielded an incremental cost-effectiveness ratio (ICER) of $3.7K per case of PID averted, and $7.3K per case of CP averted, while universal screening yielded an ICER of $8.2K per additional case of PID and $16.4K per additional case of CP averted beyond selective screening. Neither policy was dominant, and results were qualitatively robust to singlevariable and probabilistic sensitivity analysis. Conclusions: In consonance with other studies of mass tandem screening, we found both selective and universal male recruit screening cost-effective as compared to other interventions. Our results argue in favor of universal screening of male recruits for Chlamydia infection, linked to partner notification.
Nevin RL, Carbonell I, Thurmond V. Device-specific rates of needlestick injury at a large military teaching hospital.
Am J Infect Control. 2008 (in press).
Abstract: The device-specific needlestick injury (NSI) rate provides a means of comparing rates of injury between work sites and institutions over time. We performed a retrospective study of intravenous (IV) and percutaneous (PC) injection NSI at a large military teaching hospital using electronic purchase records and occupational NSI exposure forms to define action levels for process improvements. A rate of 2.25 NSI per 100,000 IV needles and 2.21 NSI per 100,000 PC needles was found.
Bloom MS, Hu Z, Gaydos JC, Brundage JF, Tobler SK. Differences in outpatient pelvic inflammatory disease rates between Army and Navy recruits. Am J Prev Med. 2008 Jun (in press).
Background: U.S. Navy policy requires Chlamydia trachomatis screening of all females upon entry to recruit training in conjunction with an educational session, and yearly screening thereafter until age 25. Army policy directs only annual screening of asymptomatic women <25 years. Hence, screening of Army recruits may not occur for up to 12 months following accession. Using routinely collected surveillance data, rates of outpatient pelvic inflammatory disease (PID) following accession into the Army or Navy were compared to assess potential implications of these policies. Methods: The population at risk comprised active component women <25 years of age accessioned to the U.S. Army or Navy between 1/1/2001 and 12/31/2005. Subjects were followed up to 60 months from accession, until a first outpatient PID diagnosis occurred, or until departure from military service. Data were collected from 2001 to 2005 and analyzed in 2007. Multiple Poisson regression was used to assess the effects of potentially important covariates. Time to event analysis was employed to characterize risk over time. Results: There were 1,276 and 546 incident outpatient diagnoses of PID among 58,088 Army and 33,046 Navy accessions during 93,918 and 65,863 person-years of follow-up, respectively. The crude incident rate was 64% higher in the Army (13.6/1000 person-years) than Navy (8.3/1000 person-years). Risk for the Army increased soon after accession, followed by a decline, while the Navy remained comparatively uniform. Conclusions: PID rates were higher in the Army than Navy during the first years of active service. A comprehensive study to elucidate the source of this observed difference is warranted.
Nevin RL, Pietrusiak PP, Caci JB. Prevalence of contraindications to mefloquine use among USA military personnel deployed to Afghanistan. Malaria Journal. 2008; 7:30 (epublished 11 Feb 2008 at http://www.malariajournal.com/content/7/1/30).
Background: Mefloquine has historically been considered safe and well-tolerated for long-term malaria chemoprophylaxis, but its prescribing requires careful attention to rule out contraindications to its use, including a history of certain psychiatric and neurological disorders. The prevalence of these disorders has not been defined in cohorts of U.S. military personnel deployed to areas where long-term malaria chemoprophylaxis is indicated. Methods: Military medical surveillance and pharmacosurveillance databases were utilized to identify contraindications to mefloquine use among a cohort of 11,725 active duty U.S. military personnel recently deployed to Afghanistan. Results: A total of 9.6% of the cohort had evidence of a contraindication. Females were more than twice as likely as males to have a contraindication (OR = 2.48, P < 0.001). Conclusions: These findings underscore the importance of proper systematic screening prior to prescribing and dispensing mefloquine, and the need to provide alternatives to mefloquine suitable for long-term administration among deployed U.S. military personnel.
Niebuhr DW, Millikan AM, Cowan DN, Yolken R, Li Y, Weber NS. Selected infectious agents and risk of schizophrenia among U.S. military personnel. Am J Psych. 2008; 165:99-106.
OBJECTIVE: A number of studies have reported associations between Toxoplasma gondii (T. gondii) infection and the risk of schizophrenia. Most existing studies have used small populations and postdiagnosis specimens. As part of a larger research program, the authors conducted a hypothesis-generating case control study of T. gondii antibodies among individuals discharged from the U.S. military with a diagnosis of schizophrenia and serum specimens available from both before and after diagnosis. METHOD: The patients (N=180) were military members who had been hospitalized and discharged from military service with a diagnosis of schizophrenia. Healthy comparison subjects (3:1 matched on several factors) were members of the military who were not discharged. The U.S. military routinely collects and stores serum specimens of military service members. The authors used microplate-enzyme immunoassay to measure immunoglobulin G (IgG) antibody levels to T. gondii, six herpes viruses, and influenza A and B viruses and immunoglobulin M (IgM) antibody levels to T. gondii in pre- and postdiagnosis serum specimens. RESULTS: A significant positive association between the T. gondii IgG antibody and schizophrenia was found; the overall hazard ratio was 1.24. The association between IgG and schizophrenia varied by the time between the serum specimen collection and onset of illness. CONCLUSION: The authors found significant associations between increased levels of scaled T. gondii IgG antibodies and schizophrenia for antibodies measured both prior to and after diagnosis.
Niebuhr DW , Millikan AM, Yolken R, Li Y, Weber NS. Results from a hypothesis generating case-control study: herpes family viruses and schizophrenia among military personnel. Schizophrenia Bulletin. 2007 Dec 21 [Epub ahead of print].
Background: Herpes family viruses can cause central nervous system inflammatory changes that can present with symptoms indistinguishable from schizophrenia and therefore are of interest in schizophrenia research. Most existing studies of herpes viruses have used small populations and postdiagnosis specimens. As part of a larger research program, we conducted a hypothesis-generating case-control study of selected herpes virus antibodies among individuals discharged from the U.S. military with schizophrenia and pre- and postdiagnosis sera. Methods: Cases (n = 180) were servicemembers hospitalized and discharged from military service with schizophrenia. Controls, 3:1 matched on several factors, were members not discharged. The military routinely collects and stores members' serum specimens. We used microplate enzyme immunoassay to measure immunoglobulin G (IgG) antibody levels to 6 herpes viruses in pre- and postdiagnosis specimens. Conditional logistic regression was used, and the measure of association was the hazard ratio (HR). Results: Overall, we found a significant association between human herpes virus type 6 and schizophrenia, with an HR of 1.17 (95% confidence interval [CI] = 1.04, 1.32). Women and blacks had significant negative associations with herpes simplex virus type 2 and cytomegalovirus; among blacks, there was a significant positive association with herpes simplex virus type 1. Among men, there was a HHV-6 temporal effect with an HR of 1.41 (95% CI = 1.02, 1.96) for sera drawn 6–12 months before diagnosis. Discussion: Findings from previous studies of herpes family viruses and schizophrenia have been inconsistent. Our study is based on a larger population than most previous studies and used serum specimens collected before onset of illness. This study adds to the body of knowledge and provides testable hypotheses for follow-on studies.
Eick AA, Hu Z, Wang Z, Nevin RL. Incidence of mumps and immunity to measles, mumps and rubella among U.S. military recruits, 2000-2004. Vaccine. 2007 Dec 4 [Epub ahead of print].
Recent mumps outbreaks have evoked concerns of decreasing mumps immunity among adolescents and adults, including U.S. military recruits subject to differing mumps immunization policies. To compare mumps incidence and to assess initial measles, mumps and rubella seropositivity, we conducted a cohort study among recruits from 2000 to 2004. Mumps incidence in the targeted MMR and universal MMR cohorts was 4.1 and 3.5 per 100,000 person-years, respectively, giving an incidence rate ratio of 1.16 (P=0.67). Measles, mumps, and rubella seropositivity was 84.6%, 89.5%, and 93.2%, respectively. Among recruits with measles and rubella immunity, 92.8% were mumps immune. These findings support the policy of targeting MMR immunization based upon measles and rubella serology alone.
Hsu LL, Nevin RL, Tobler SK, Rubertone MV. Trends in overweight and obesity among 18-year-old applicants to the United States Military, 1993-2006. J Adolesc Health 2007 Dec;41(6):610-2.
We examined trends in overweight and obesity among 756,269 18-year-old civilian applicants to the United States military from 1993-2006. The prevalence of overweight increased from 22.8% in 1993 to 27.1% in 2006, and obesity increased from 2.8% to 6.8%. We conclude the U.S. military is recruiting from an increasingly overweight population.
Milliken CS, Auchterlonie JL, Hoge CW. Longitudinal assessment of mental health problems among active and reserve component soldiers returning from the Iraq War. JAMA. 2007;298(18):2141-2148.
Context: To promote early identification of mental health problems among combat veterans, the Department of Defense initiated population-wide screening at 2 time points, immediately on return from deployment and 3 to 6 months later. A previous article focusing only on the initial screening is likely to have underestimated the mental health burden. Objective: To measure the mental health needs among soldiers returning from Iraq and the association of screening with mental health care utilization. Design, setting, and participants: Population-based, longitudinal descriptive study of the initial large cohort of 88 235 U.S. soldiers returning from Iraq who completed both a Post-Deployment Health Assessment (PDHA) and a Post-Deployment Health Re-Assessment (PDHRA) with a median of 6 months between the 2 assessments. Main outcome measures: Screening positive for posttraumatic stress disorder (PTSD), major depression, alcohol misuse, or other mental health problems; referral and use of mental health services. Results: Soldiers reported more mental health concerns and were referred at significantly higher rates from the PDHRA than from the PDHA. Based on the combined screening, clinicians identified 20.3% of active and 42.4% of reserve component soldiers as requiring mental health treatment. Concerns about interpersonal conflict increased 4-fold. Soldiers frequently reported alcohol concerns, yet very few were referred to alcohol treatment. Most soldiers who used mental health services had not been referred, even though the majority accessed care within 30 days following the screening. Although soldiers were much more likely to report PTSD symptoms on the PDHRA than on the PDHA, 49% to 59% of those who had PTSD symptoms identified on the PDHA improved by the time they took the PDHRA. There was no direct relationship of referral or treatment with symptom improvement. Conclusions: Rescreening soldiers several months after their return from Iraq identified a large cohort missed on initial screening. The large clinical burden recently reported among veterans presenting to Veterans Affairs facilities seems to exist within months of returning home, highlighting the need to enhance military mental health care during this period. Increased relationship problems underscore shortcomings in services for family members. Reserve component soldiers who had returned to civilian status were referred at higher rates on the PDHRA, which could reflect their concerns about their ongoing health coverage. Lack of confidentiality may deter soldiers with alcohol problems from accessing treatment. In the context of an overburdened system of care, the effectiveness of population mental health screening was difficult to ascertain.

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Brundage JF, Shanks GD. What really happened during the 1918 influenza pandemic? The importance of bacterial secondary infections. (correspondence). J Infect Dis. 2007 Dec 1;196:1717-8.
Cook MB, Zhang Y, Graubard BI, Rubertone MV, Erickson RL, McGlynn KA. Risk of testicular germ-cell tumours in relation to childhood physical activity. Br J Cancer. 2007 Nov 20 [Epub ahead of print]
The U.S. Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) case-control study of testicular germ-cell tumours (TGCTs) enrolled participants and their mothers in 2002-2005. Hours of sports or vigorous childhood physical activity per week were ascertained for three time periods; 1st-5th grades, 6th-8th grades and 9th-12th grades. Son- and mother-reports were analysed separately and included 539 control son-mother pairs and 499 case son-mother pairs. Odds ratios and 95% confidence intervals were produced. The analysis of the sons' responses found no relationship between childhood physical activity and TGCT, while the mothers' analysis found an inverse association, which was solely due to nonseminoma. Future studies should seek to validate responses further using recorded information sources such as school records.
Majka DS, Deane KD, Parrish LA, Lazar AA, Barón AE, Walker CW, Rubertone MV, Gilliland WR, Norris JM, Holers VM.The duration of pre-clinical rheumatoid arthritis-related autoantibody positivity increases in subjects with older age at time of disease diagnosis. Ann Rheum Dis. 2007 Nov 1; [Epub ahead of print]
Objectives: This study investigated factors that may influence the prevalence and timing of appearance of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies during the pre-clinical phase of rheumatoid arthritis (RA) development. Methods: 243 serial pre-diagnosis serum samples from 83 subjects with RA were examined for the presence of RF and anti-CCP antibodies. Results: 57% and 61% of subjects had at least one pre-diagnosis sample positive for RF or anti-CCP, respectively. Gender and race were not significantly associated with the prevalence or timing of pre-clinical antibody appearance. Pre-clinical anti-CCP positivity was strongly associated with the development of erosive RA (OR 4.64; 95% CI 1.71-12.63; p=0.003), but RF was not (p=0.11). Additionally, as age at the time of diagnosis of RA increased the duration of pre-diagnosis antibody positivity for RF and anti-CCP increased, with the longest duration of pre-clinical antibody positivity seen in patients diagnosed with RA over the age of 40. In no subjects did symptom onset precede the appearance of RF or anti-CCP antibodies. Conclusions: The period of time that RF and anti-CCP are present prior to diagnosis lengthens as the age at the time of diagnosis of RA increases. This finding suggests that factors such as genetic risk or environmental exposures influencing the temporal relationship between the development of RA-related autoantibodies and clinically-apparent disease onset may differ with age.
Eckart RE, Shry EA, Atwood JE, Brundage JF, Lay JC, Bateson TF, Grabenstein JD. Smallpox vaccination and ischemic coronary events in healthy adults. Vaccine. 2007 Oct 17; [Epub ahead of print]
Although smallpox vaccine-associated myopericarditis has been reported, the risk of cardiac ischemic events remains uncertain. We identified personnel receiving the smallpox vaccination and compared them to a historical referent population. The rate of cardiac ischemia diagnoses in the 30 days following smallpox vaccination was 140.1 per 100,000 person-years, compared to 143.5 per 100,000 person-years in referent group (RR 1.0 [95% CI: 0.7-1.4]). The rate of cardiac ischemic events in vaccinees was 121.4 per 100,000 person-years before and 175.7 after adopting pre-vaccination cardiac screening (RR 1.4 [95% CI: 0.8-2.7]). Implementation of pre-vaccination cardiac risk factor screening was not associated with a reduction in cardiac events.
Nevin RL, Niebuhr DW. Rising hepatitis A immunity in U.S. military recruits. Mil Med. 2007 Jul;172(7):787-93.
Background: The U.S. military immunizes new recruits against hepatitis A. Since 2001, immunization with the hepatitis A vaccine has been recommended for civilian adolescents in higher risk areas. Recently, the Armed Forces Epidemiological Board recommended serologic screening where feasible to reduce redundant recruit immunizations. Objectives: The purpose of this study was to determine hepatitis A seroprevalence in recruit populations to inform screening policy. Methods: Banked serum from a sample of military recruits (n = 2,592) in 2004 was tested for total antibody to hepatitis A (anti-hepatitis A virus (HAV)). Results: The overall anti-HAV seroprevalence was 12.0% (95% confidence interval, 10.8%-13.3%). Adjusted to the age distribution of the 18- to 34-year-old population, the seroprevalence was 11.9% (10.5%-13.4%). The lowest seroprevalence was noted in the 1984 birth cohort, with significantly higher seroprevalence among younger recruits. Conclusions: Rising hepatitis A immunity among successive birth cohorts suggests increasing compliance with immunization recommendations. In anticipation of rising population immunity, universal screening of military recruits for anti-HAV is recommended.
Ciminera P, Brundage JF. Malaria in U.S. military forces: a description of deployment exposures from 2003 through 2005. Am J Trop Med Hyg. 2007 Feb;76(2):275-9.
U.S. service members are often deployed to regions endemic for malaria. Preventive measures play an important role in mitigating the risk of disease and adverse effects on mission performance. Currently, a large contingent of U.S. forces is deployed in malarious regions in southeast and southwest Asia. The purpose of this study was to describe malaria cases reported by the tri-service reportable medical events system in terms of exposure (deployment history) and latency of infection. We conducted a retrospective analysis of population health data routinely collected for disease surveillance. All malaria reports received into the Defense Medical Surveillance System by January 3, 2006 with a date of onset between January 1, 2000 and December 31, 2005 in which the individual diagnosed is a member of the active or reserve military components linked to personnel and deployment data were analyzed to determine assignment and deployment history. The main outcome measure was the ICD9-CM diagnosis of malaria (Plasmodium vivax, P. falciparum, P. ovale, P. malaria, and unspecified malaria) by date of onset and days from exposure. A total of 423 cases of malaria were reported during the study period. The Army (n = 325) and the Marine Corps (n = 46) had the highest number of reported cases. Plasmodium vivax (n = 242) and P. falciparum (n = 92) caused nearly four-fifths of all reported cases. During the period from 2003 through 2005, 34% of deployed cases were exposed to more than one malaria-endemic region. Seventy-four cases had been assigned in the Republic of Korea, and all were present in Korea during the high risk transmission period. Seventy-eight cases had documented service in Afghanistan; only 4 had off-season exposure and no other documented exposures. Sixty cases had documented exposure during Operation Iraqi Freedom (OIF). Only six seasonally exposed and six off seasonally exposed OIF cases had no other documented exposure. Fifty percent of Korean cases were diagnosed during an exposure season, and only 3% of Afghan cases were diagnosed during an exposure season. Soldiers in today's military can be exposed to more than one malaria-endemic region prior to diagnosis. This presents new complexities for disease monitoring and prevention policy development.
McGlynn KA, Sakoda LC, Rubertone MV, Sesterhenn IA, Lyu C, Graubard BI, Erickson RL. Body size, dairy consumption, puberty, and risk of testicular germ cell tumors. Am J Epidemiol. 2007 Feb 15;165(4):355-63.
The etiology of testicular germ cell tumors (TGCTs) is poorly understood, with cryptorchidism and family history being the only well-established risk factors. Body size, age at puberty, and dairy consumption, however, have been suggested to be related to TGCTs. To clarify the relation of these variables to TGCT risk and to one another, the authors analyzed data from 767 cases and 928 controls enrolled in the Servicemen's Testicular Tumor Environmental and Endocrine Determinants Study (2002-2005). Overall, increased height was significantly related to risk (odds ratio (OR) = 1.83, 95% confidence interval (CI): 1.36, 2.45), though body mass index was not (OR = 1.06, 95% CI: 0.66, 1.69). There was no association with age at puberty, based on ages at first shaving (OR = 1.29, 95% CI: 0.96, 1.73), voice changing (OR = 0.97, 95% CI: 0.71, 1.32), and nocturnal emissions (OR = 1.00, 95% CI: 0.73, 1.37). Similarly, there was no relation with dairy consumption at any age between birth and 12th grade. These results suggest that height is a risk factor for TGCTs, but the relation is unlikely explained by childhood dairy consumption. As adult height is largely determined in the first 2 years of life, increased attention to events in this interval may help elucidate the etiology of TGCTs.
Purdue MP, Sakoda LC, Graubard BI, Welch R, Chanock SJ, Sesterhenn IA, Rubertone MV, Erickson RL, McGlynn KA. A case-control investigation of immune function gene polymorphisms and risk of testicular germ cell tumors. Cancer Epidemiol Biomarkers Prev. 2007 Jan;16(1):77-83.
There is reason to suspect that testicular germ cell tumor (TGCT) development may be influenced by cytokines, secreted proteins that modulate tumor immune surveillance activity as well as a variety of processes in the testis. To address this hypothesis, we conducted a case-control analysis (508 cases, 608 controls) of 32 putatively functional single-nucleotide polymorphisms (SNP) in 16 immune function genes among non-Hispanic Caucasian participants in the U.S. Servicemen's Testicular Tumor Environmental and Endocrine Determinants Study. The TGFB1 Ex5-73C>T variant was positively associated with TGCT (CT/TT versus CC: odds ratio, 1.73; 95% confidence interval, 1.01-2.95; P(trend) = 0.05); additionally, haplotypes of the assessed TGFB1 SNPs (-509C>T, 327C>T, Ex1-282C>G, and Ex5-73C>T) differed in frequency between cases and controls (all TGCT, P 0.07; seminoma, P 0.04; nonseminoma, P 0.11). We also observed excess frequencies among TGCT cases versus controls of LTA 252G (P(trend) = 0.08) and of the TNF variants -1042C (P(trend) = 0.06), -1036T (P(trend) = 0.07), and -238G (P(trend) = 0.09). Analyses of haplotypes for LTA-TNF SNPs (LTA -91C>A, LTA 252A>G, TNF -863C>A, TNF -857C>T, TNF -308G>A, and -238G>A) were similarly suggestive of an association with TGCT (P = 0.06) and nonseminoma (P = 0.04), but not seminoma (P = 0.21). Polymorphisms in other genes were found to be associated only with seminoma (IL2) or nonseminoma (IFNGR2 and IL10). However, none of the associations remained noteworthy after applying the false discovery rate method to control for multiple testing. In conclusion, our findings suggest that polymorphisms in TGFB1 and LTA/TNF, and possibly other immune function genes, may influence susceptibility to TGCT.
Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006 Dec 20;296(23):2832-8.
Context: Epidemiological and experimental evidence suggests that high levels of vitamin D, a potent immunomodulator, may decrease the risk of multiple sclerosis. There are no prospective studies addressing this hypothesis. Objective: To examine whether levels of 25-hydroxyvitamin D are associated with risk of multiple sclerosis. Design, setting, and participants: Prospective, nested case-control study among more than 7 million U.S. military personnel who have serum samples stored in the Department of Defense Serum Repository. Multiple sclerosis cases were identified through Army and Navy physical disability databases for 1992 through 2004, and diagnoses were confirmed by medical record review. Each case (n = 257) was matched to 2 controls by age, sex, race/ethnicity, and dates of blood collection. Vitamin D status was estimated by averaging 25-hydroxyvitamin D levels of 2 or more serum samples collected before the date of initial multiple sclerosis symptoms. Main outcome measures: Odds ratios of multiple sclerosis associated with continuous or categorical levels (quantiles or a priori-defined categories) of serum 25-hydroxyvitamin D within each racial/ethnic group. Results: Among whites (148 cases, 296 controls), the risk of multiple sclerosis significantly decreased with increasing levels of 25-hydroxyvitamin D (odds ratio [OR] for a 50-nmol/L increase in 25-hydroxyvitamin D, 0.59; 95% confidence interval, 0.36-0.97). In categorical analyses using the lowest quintile (<63.3 nmol/L) as the reference, the ORs for each subsequent quintile were 0.57, 0.57, 0.74, and 0.38 (P = .02 for trend across quintiles). Only the OR for the highest quintile, corresponding to 25-hydroxyvitamin D levels higher than 99.1 nmol/L, was significantly different from 1.00 (OR, 0.38; 95% confidence interval, 0.19-0.75; P = .006). The inverse relation with multiple sclerosis risk was particularly strong for 25-hydroxyvitamin D levels measured before age 20 years. Among blacks and Hispanics (109 cases, 218 controls), who had lower 25-hydroxyvitamin D levels than whites, no significant associations between vitamin D and multiple sclerosis risk were found. Conclusion: The results of our study suggest that high circulating levels of vitamin D are associated with a lower risk of multiple sclerosis.
Brundage JF, Johnson KE, Lange JL, Rubertone MV. Comparing the population health impacts of medical conditions using routinely collected health care utilization data: nature and sources of variability. Mil Med. 2006 Oct;171(10):937-42.
Prevention activities are designed and resourced based on perceptions of the relative population health impacts of various conditions. We examined the nature and variability of rankings of “conditions” based on how they are defined and how their population health impacts are measured. The first listed diagnosis from all hospitalizations and ambulatory visits of U.S. servicemembers during 2002 were used to rank conditions (as defined by two standard classification systems) using five different measures of population health impacts. Fewer than 10% of all conditions accounted for more than half of total population health impact, regardless of how conditions were defined or impacts measured. However, specific conditions with the largest impacts varied depending on the classification system and impact measure. Four groups of related conditions—acute musculoskeletal injuries, pregnancy-related conditions, respiratory infections, and mental disorders (including substance abuse)—accounted for disproportionately large impacts regardless of the measure. The identification of conditions with the largest population health impacts depends on the nature and degree of aggregation in defining conditions and the measure of impact. The findings are relevant to prevention planning and resourcing.

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McGlynn KA, Zhang Y, Sakoda LC, Rubertone MV, Erickson RL, Graubard BI. Maternal smoking and testicular germ cell tumors. Cancer Epidemiol Biomarkers Prev. 2006 Oct;15(10):1820-4.
Testicular germ cell tumors (TGCT) are the most common cancer among men ages 15 to 35 years in the United States. The well-established TGCT risk factors cryptorchism, prior diagnosis of TGCT, and family history of testicular cancer indicate that exposures in early life and/or in the familial setting may be critical to determining risk. Previous reports of familial clustering of lung cancer in mothers and testicular cancers in sons suggest that passive smoking in childhood may be such an exposure. To clarify the relationship of passive smoking exposure to TGCT risk, data from 754 cases and 928 controls enrolled in the Servicemen's Testicular Tumor Environmental and Endocrine Determinants study were analyzed. Data from 1,086 mothers of the cases and controls were also examined. Overall, there was no relationship between maternal [odds ratio (OR), 1.1; 95% confidence interval (95% CI), 0.9-1.3] or paternal smoking (OR, 1.0; 95% CI, 0.8-1.3) and TGCT risk. Although living with a nonparent smoker was marginally related to risk (OR, 1.4; 95% CI, 1.0-2.1), there was no relationship with number of smokers, amount smoked, or duration of smoking. Responses from both case-control participants and mothers also revealed no relationship between either maternal smoking while pregnant or while breast-feeding. Results did not differ by TGCT histology (seminoma, nonseminoma). These results do not support the hypothesis that passive smoking, either in utero or in childhood, is related to risk of TGCT. Other early life exposures, however, may explain the familial clustering of lung cancer in mothers and TGCT in sons. (Cancer Epidemiol Biomarkers Prev 2006;15(10):1820-4).
Arcari CM, Nelson KE, Netski DM, Nieto FJ, Gaydos CA. No association between hepatitis C virus seropositivity and acute myocardial infarction. Clin Infect Dis. 2006 Sep 15;43(6):e53-6. Epub 2006 Aug 8.
Recent studies have linked hepatitis C virus (HCV) infection with carotid atherosclerosis. We investigated the association between HCV seropositivity and acute myocardial infarction using a well-established cohort of young men in the U.S. military and found no evidence to support this association.
Brundage JF. Cases and deaths during influenza pandemics in the United States. Am J Prev Med. 2006 Sep;31(3):252-6.
Objective: To assess how numbers and age distributions of cases and deaths during an influenza pandemic in the United States would potentially vary from those during the 1918-9 pandemic, given the same virulence of the pandemic strain. Methods: Influenza cases and deaths in two referent populations (U.S. residents in 1917 and 2006) were calculated using clinical case rates from three pandemics (1918-like, 1957-like, and 1968-like) and case fatality rates from the 1918-9 pandemic. Results: Across pandemic scenarios, overall case (“attack”) rates ranged from 24.7% to 34.2%, and overall death rates ranged from 4.4 to 6.7 per 1000. In both referent populations, total cases and deaths were significantly higher when using 1957-like and 1968-like, compared to 1918-like, case rates. Under all pandemic scenarios, the most deaths occurred among 25-29 year olds. However, in the 2006 referent population, there were large numbers and high proportions of deaths in middle-aged and elderly adults (unlike during the 1918-9 pandemic). Conclusions: Numbers and distributions of cases and deaths during influenza pandemics depend on numbers of individuals, clinical case rates, and case fatality rates in relation to age. During a future pandemic in the United States, influenza deaths will likely not be as sharply focused in young adults as in 1918-9 (even if case fatality rates are similar) because of larger proportions of middle-aged and elderly adults and potentially higher case rates among adults older than 30.
Hoge CW, Auchterlonie JL, Milliken CS. (In reply to letters to the editor). Mental health after deployment to Iraq or Afghanistan. JAMA. 2006 Aug 2;296(5):516.
Brundage JF. Interactions between influenza and bacterial respiratory pathogens: implications for pandemic preparedness. Lancet Inf Dis. 2006 May;6(5):303-12.
It is commonly believed that clinical and epidemiologic characteristics of the next influenza pandemic will mimic those of the 1918 pandemic. Determinative beliefs regarding the 1918 pandemic include that infections were typically expressed as primary viral pneumonias and/or acute respiratory distress syndrome (ARDS); that most pandemic-related deaths were the end states of the natural progression of disease caused by the pandemic strain; and that bacterial superinfections caused relatively fewer deaths in 1918 than in subsequent pandemics. In turn, response plans are focused on developing and/or increasing inventories of a strain-specific vaccine, antivirals, intensive care beds, mechanical ventilators, and so on. Yet, there is strong and consistent evidence of epidemiologically and clinically significant interactions between influenza and secondary bacterial respiratory pathogens—including during the 1918 pandemic. Countermeasures (e.g., vaccination against pneumococcal, meningococcal disease prior to a pandemic; mass uses of antibiotic(s) with broad spectrums of activity against common bacterial respiratory pathogens during local epidemics) designed to prevent or mitigate the effects of influenza-bacterial interactions should be major focuses of pandemic-related research, prevention, and response planning.
Isenbarger DW, Atwood JE, Scott PT, Bateson T, Coyle LC, Gillespie DL, Pearse LA, Villines TC, Cassimatis DC, Finelli LN, Taylor AJ, John D. Grabenstein JD. Venous thromboembolism among United States soldiers deployed to southwest Asia. Thromb Res. 2006;117(4):379-83.
Introduction. Military operations may represent a high-risk environment for venous thromboembolism (VTE). We sought to identify and describe cases of venous thromboembolism among U.S. military personnel serving in Southwest Asia, and estimate relative disease rates compared to non-deployed personnel. Materials and Methods. Retrospective review of imaging archives, hospital discharge codes, case logs and autopsy records for the diagnosis of deep vein thrombosis or pulmonary embolism occurring from 1 March 2003 through 29 February 2004 among U.S. military personnel deployed to Southwest Asia. Rates of disease in deployed and non-deployed active-duty soldiers were estimated using personnel data and deployment experience obtained from automated rosters. Results. Forty cases of venous thromboembolism were identified. The case-fatality rate was 16% (3/19) among those with pulmonary embolism. Antecedent trauma followed by prolonged air-evacuation was present in 55% (22/40). Compared to trauma-associated cases, non-trauma cases were more commonly over 40 years old (44% vs. 5%; p<0.05), assigned to a transportation or quartermaster company (56% vs. 14%; p<0.05), or had a history of remote venous thromboembolism (31% vs. 0%; p<0.05). The overall incidence among deployed active-duty soldiers was 22.1/100,000 person-years. Compared to non-deployed active duty soldiers, the age-adjusted incidence rate ratio was 1.06 (CI0.95 0.68-1.67). Conclusions. VTE rates among deployed soldiers are relatively low compared to the general population, and are comparable to non-deployed soldiers. Fatalities from PE are not uncommon, and vigilance among clinicians remains warranted. Trauma followed by prolonged air-evacuation or ground transport during military operations may represent unique interactive risk factors for venous thromboembolism.
Hoge CW, Auchterlonie JL, Milliken CS. Mental health and occupational impact of deployments to Iraq and Afghanistan: findings from population-based post-deployment screening and surveillance. JAMA. 2006 Mar 1;295(9):1023-32.
Background. The U.S. military has conducted population-level screening for mental health problems among all service members returning from deployment to Afghanistan, Iraq, and other locations. To date, no systematic analysis of this program has been conducted, and studies have not assessed the impact of these deployments on mental health care utilization post-deployment. Objective. To determine the relationship between combat deployment and mental health care use during the first year after return, and to assess the lessons learned from the post-deployment mental health screening effort, particularly the correlation between the screening results, actual use of mental health services, and attrition from military service. Design, Setting, and Participants. Population-based descriptive study of all Army soldiers and Marines who completed the routine post-deployment health assessment between May 1st, 2003 and April 30th, 2004 on return from deployment to Operation Enduring Freedom-Afghanistan (n=16,318), Operation Iraqi Freedom (n=222,620), and other locations (n=64,967). Healthcare utilization and occupational outcomes were measured for one year post-deployment or until leaving service if this occurred sooner. Main Outcome Measures. Screening positive for post-traumatic stress disorder, major depression, or other mental health problems; referral for a mental health reason; use of mental health care services after returning from deployment, and attrition from military service. Results. The prevalence of reporting a mental health problem was 19.1% among service members returning from Iraq, compared with 11.3% after returning from Afghanistan, and 8.5% after returning from other locations (p<.001). Mental health problems reported on the post-deployment assessment were significantly correlated with combat experiences, mental health care referral and utilization, and attrition from military service. Thirty-five percent of Iraq war veterans accessed mental health services in the year after returning home; 12% per year were diagnosed with a mental health problem. Over 50% of those referred for a mental health reason were documented to receive follow-up care, although less than 10% of all service members who received mental health treatment were referred through the screening program. Conclusions. Combat duty in Iraq was correlated with high utilization of mental health services and attrition from military service post-deployment. The deployment mental health screening program provided another indicator of the mental health impact of deployment on a population-level, but had limited utility in predicting the level of mental health services that were needed post-deployment. The high rate of utilizing mental health services among OIF veterans post-deployment highlights challenges in assuring that there are adequate resources to meet the mental health needs of returning veterans.
Pablo K, Rooks P, Nevin R. Benefits of serologic screening for hepatitis B immunity in military recruits. (Correspondence) (Letter to the Editor). J Infect Dis. 2005 Dec 15;192(12):2180-1.
Scott PT, Niebuhr DW, McGready JB, Gaydos JC. Hepatitis B immunity in United States military recruits. J Infect Dis. 2005 Jun 1;191(11):1835-41.
Background. In 2002, the U.S. 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 U.S. 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 18 35-year-old U.S. 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.
Levin LI, Munger KL, Rubertone MV, Peck CA, Lennette ET, Spiegelman D, Ascherio A. Temporal relationship between elevation of epstein-barr virus antibody titers and initial onset of neurological symptoms in multiple sclerosis. JAMA. 2005 May 25;293(20):2496-500.
CONTEXT: Infection with Epstein-Barr virus (EBV) has been associated with an increased risk of multiple sclerosis (MS), but the temporal relationship remains unclear. OBJECTIVE: To determine whether antibodies to EBV are elevated before the onset of MS. DESIGN, SETTING, AND PARTICIPANTS: Nested case-control study conducted among more than 3 million U.S. military personnel with blood samples collected between 1988 and 2000 and stored in the Department of Defense Serum Repository. Cases were identified as individuals granted temporary or permanent disability because of MS. For each case (n = 83), 2 controls matched by age, sex, race/ethnicity, and dates of blood sample collection were selected. Serial samples collected before the onset of symptoms were available for 69 matched case-control sets. MAIN OUTCOME MEASURES: Antibodies including IgA against EBV viral capsid antigen (VCA), and IgG against VCA, nuclear antigens (EBNA complex, EBNA-1, and EBNA-2), diffuse and restricted early antigens, and cytomegalovirus. RESULTS: The average time between blood collection and MS onset was 4 years (range, <1-11 years). The strongest predictors of MS were serum levels of IgG antibodies to EBNA complex or EBNA-1. Among individuals who developed MS, serum antibody titers to EBNA complex were similar to those of controls before the age of 20 years (geometric mean titers: cases = 245, controls = 265), but 2- to 3-fold higher at age 25 years and older (cases = 684, controls = 282; P<.001). The risk of MS increased with these antibody titers; the relative risk (RR) in persons with EBNA complex titers of at least 1280 compared with those with titers less than 80 was 9.4 (95% confidence interval [CI], 2.5-35.4; P for trend <.001). In longitudinal analyses, a 4-fold increase in anti-EBNA complex or anti-EBNA-1 titers during the follow-up was associated with a 3-fold increase in MS risk (EBNA complex: RR , 3.0; 95% CI, 1.3-6.5; EBNA-1: RR, 3.0; 95% CI, 1.2-7.3). No association was found between cytomegalovirus antibodies and MS. CONCLUSION: These results suggest an age-dependent relationship between EBV infection and development of MS.

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Ascherio A, Rubertone M, Spiegelman D, Levin L, Munger K, Peck C, Lennette E. Notice of retraction: "Multiple sclerosis and Epstein-Barr virus" (JAMA. 2003;289:1533-1536). JAMA. 2005 May 25;293(20):2466.
Arcari CM, Gaydos CA, Nieto FJ, Krauss M, Nelson KE. Association between Chlamydia pneumoniae and acute myocardial infarction in young men in the United States military: the importance of timing of exposure measurement. Clin Infect Dis. 2005 Apr 15;40(8):1123-30. Epub 2005 Mar 14.
Background: Several investigators have found that Chlamydia pneumoniae and cytomegalovirus infections may be risk factors for coronary heart disease. However, the data remain controversial. To address this hypothesis, data and specimens were collected from a well-established prospective cohort of active-duty personnel from the U.S. military. Methods: A nested case-control study was conducted with 300 case patients and 300 matched control subjects. Case patients were men (age, 30-50 years) with a medically documented, first-time hospitalization for acute myocardial infarction (MI) and from whom a serum specimen had been drawn >or=1 year before the time of the acute MI. Population-based control subjects were chosen from the same cohort and were individually matched by age, race, and time of specimen collection. Evidence of past infections with C. pneumoniae and cytomegalovirus were measured by microimmuno -fluorescence assay and enzyme-linked immunosorbent assay, respectively. Results: Significant risk was associated with high titer (>or=1 : 64) to C. pneumoniae immunoglobulin A (IgA) (adjusted relative risk [RR(adj)], 1.67; 95% confidence interval [CI], 1.04-2.70). This increased risk was greatest when specimens were collected 1-5 years before the event (RR(adj), 2.11; 95% CI, 1.06-4.21). High titer (>or=1 : 256) to C. pneumoniae immunoglobulin G (IgG) was also associated with an elevated risk (RR(adj), 1.74; 95% CI, 0.90-3.34) after full adjustment for cardiovascular risk factors, whereas no independent risk for acute MI was associated with cytomegalovirus IgG seropositivity. Conclusions: This study demonstrates a significant association between high titers to C. pneumoniae IgG and IgA and acute MI in a cohort of young men and suggests that recent or chronic active infections could be associated with an increased risk for MI.
Acinetobacter baumannii infections among patients at military medical facilities treating injured U.S. service members, 2002-2004. MMWR. 2004 Nov 19:53(45);1063-6.7-
Arness MK, Eckart RE, Love SS, Atwood JE, Wells TS, Engler RJ, Collins LC, Ludwig SL, Riddle JR, Grabenstein JD, Tornberg DN for the Department of Defense Smallpox Vaccination Clinical Evaluation Team. Myopericarditis following smallpox vaccination. Am J Epidemiol. 2004 Oct 1;160(7):642-51.
Myopericarditis has been a rare or unrecognized event after smallpox vaccinations with the New York City Board of Health strain of vaccinia virus (Dryvax; Wyeth Laboratories, Marietta, Pennsylvania). In this article, the authors report an attributable incidence of at least 140 clinical cases of myopericarditis per million primary smallpox vaccinations with this strain of vaccinia virus. Fifty-eight males and one female aged 21-43 years with confirmed or probable acute myopericarditis were detected following vaccination of 492,730 U.S. Armed Forces personnel from December 15, 2002, through September 30, 2003. The cases were identified through sentinel reporting to military headquarters, active surveillance using the Defense Medical Surveillance System, or reports to the Vaccine Adverse Event Reporting System. The observed incidence (16.11/100,000) of myopericarditis over a 30-day observation window among 347,516 primary vaccinees was nearly 7.5-fold higher than the expected rate of 2.16/100,000 (95% confidence interval: 1.90, 2.34) among nonvaccinated, active-duty military personnel, while the incidence of 2.07/100,000 among 145,155 revaccinees was not statistically different from the expected background rate. The cases were predominantly male (58/59; 98.3%) and White (51/59; 86.4%), both statistically significant associations (p = 0.0147 and p = 0.05, respectively).
Munger KL, DeLorenze GN, Levin LI, Rubertone MV, Vogelman JH, Peck CA, Peeling RW, Orentreich N, Ascherio A. A prospective study of Chlamydia pneumoniae infection and risk of MS in two cohorts. Neurology. 2004;62:1799-1803.
Background: Chlamydiae pneumoniae (Cpn) has been proposed as a possible etiologic agent in multiple sclerosis (MS). However, previous studies were cross-sectional and could not assess whether Cpn infection preceded the onset of MS. Methods: The authors conducted a prospective nested case-control study among 3 million U.S. Army personnel and 121,466 members of the Kaiser Permanente Medical Care Program (KPMCP) cohort. Two controls were matched to each case on age, sex, and date of blood collection. Microimmunofluorescence was used to measure serum immunoglobulin M (IgM) and immunoglobulin G (IgG) antibody titers to Cpn; IgG titers > 1:16 were considered positive for past Cpn infection. Results: Seropositivity for Cpn was not significantly associated with risk of MS in either cohort (Army: OR = 1.0; 95% CI 0.6, 1.8; KPMCP: OR = 1.5; 95% CI 0.7, 3.1) or in the pooled analysis (OR =1.2; 95% CI 0.8, 1.9). Serum levels of anti-Cpn IgG antibody were also not associated with an increased risk of MS in the Army (OR for a fourfold difference in antibody titers = 0.9; 95% CI 0.7, 1.2) or in the pooled analysis (OR =1.2; 95% CI 0.9, 1.4), but a significant increase in risk was seen in the KPMCP cohort (OR =1.7; 95% CI 1.2, 2.5). The difference between these results in the Army and the KPMCP cohort was significant (p = 0.01). Conclusions: Neither Cpn seropositivity nor serum anti-Cpn IgG antibody titers predicted risk of developing MS. However, due to the heterogeneity of results between cohorts, we cannot exclude the possibility that infection with Cpn may modify the risk of MS.
McClain MT, Arbuckle MR, Heinlen LD, Dennis GJ, Roebuck J, Rubertone MV, Harley JB, James JA. The prevalence, onset, and clinical significance of antiphospholipid antibodies prior to diagnosis of systemic lupus erythematosus. Arthritis Rheum. 2004 Apr;50(4):1226-32.
Objective: To determine whether antiphospholipid antibodies (aPL) occur before the diagnosis of systemic lupus erythematosus (SLE) and before initial clotting events, and whether their presence early in the disease course influences clinical outcome. Methods: Serum samples obtained from 130 lupus patients before and after SLE diagnosis were screened for IgG and IgM aPL using an anticardiolipin (aCL) enzyme-linked immunosorbent assay. Medical records of all patients were carefully reviewed for data on the time of onset of SLE features meeting clinical criteria and on disease manifestations. Results: Twenty-four patients (18.5%) were positive for IgG and/or IgM aCL prior to SLE diagnosis. Anticardiolipin antibodies appeared from 7.6 years prior to SLE diagnosis to within the same month as SLE diagnosis, with a mean onset occurring 3.0 years before SLE diagnosis. Additionally, aCL presence early in the disease process seemed to predict a more severe clinical outcome; these patients eventually met an average of 6.1 of the 11 classification criteria for SLE, compared with 4.9 criteria for other patients (P < 0.001). The early aCL-positive population also had more frequent renal disease, central nervous system disease, thrombocytopenia, and clotting events. In this population, aCL preceded initial thrombotic events by a mean of 3.1 years. Conclusion: Anticardiolipin antibodies in SLE patients tend to precede initial clotting events by several years. Furthermore, the presence of early, prediagnosis aPL seems to herald a more varied, severe clinical course with earlier onset in patients with SLE.
Arbuckle MR, James JA, Dennis GJ, Rubertone MV, McClain MT, Kim XR, Harley JB. Rapid clinical progression to diagnosis among African-American men with systemic lupus erythematosus. Lupus. 2003;12(2):99-106.
The initial clinical course of systemic lupus erythematosus (SLE) is variable, ranging from relatively minor manifestations progressing over years to rapid onset of fulminate disease. We sought to identify factors associated with the rapid manifestation of SLE. Chart review of military medical records was used to identify 130 patients who met the American College of Rheumatology classification criteria for SLE. Demographics, clinical criteria date of occurrence, and the date of SLE classification (at least four clinical criteria) met were documented. Prospectively stored serum samples prior to the diagnosis were evaluated for SLE autoantibodies. Median time from the first recorded criteria to diagnosis was significantly shorter in African-American (AA) males compared with AA females and European American (EA) females and males combined. AA males were more likely to have nephritis as their first clinical symptom. Also, less time transpired between the first clinical criterion and SLE diagnosis in AA males with nephritis than in other groups presenting with nephritis. Even when cases presenting with nephritis were excluded, a diagnosis of SLE was made more rapidly in AA males. African-American men progress from initial clinical manifestations to SLE diagnosis more rapidly than other ethnic or gender groups.
Lange JL, Campbell KE, Brundage JF. Respiratory illnesses in relation to military assignments in the Mojave Desert: retrospective surveillance over a ten-year period. Mil Med. 2003;168:1039-43.
Military training exercises are conducted routinely in the Mojave Desert. To determine if assignment in this desert environment increases risk of respiratory illnesses, hospitalization rates were compared between two matched cohorts of soldiers during three intervals of follow-up during a ten-year surveillance period. The exposed cohort (n=21,543) included all soldiers who were ever assigned to the Mojave Desert during the surveillance period. The control cohort (n=86,172) included soldiers matched on demographic characteristics who were never assigned to the Mojave Desert during the surveillance period. Three follow-up intervals (“before”, “during”, “after”) were defined relative to times when exposed soldiers were assigned to the desert. Rates of respiratory hospitalizations were similar between the cohorts for the “before” and “during” intervals but were higher in the exposed cohort for the “after” interval (rate ratio = 1.31, 95% CI 1.07-1.59). This difference was largely attributable to excess pneumonia and influenza hospitalizations in the exposed cohort. Healthy, young adults may have increased susceptibility to respiratory infectious illnesses after prolonged exposures to desert environments.
Arbuckle MR, McClain MT, Rubertone MV, Scofield RH, Dennis GJ, James JA, Harley JB. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. New Eng J Med. 2003 Oct 16;349:1526-33.
Background. Although much is known about the natural history of systemic lupus erythematosus (SLE), the development of SLE autoantibodies before the diagnosis of the disease has not been extensively explored. We investigated the onset and progression of autoantibody development before the clinical diagnosis. Methods The Department of Defense Serum Repository contains approximately 30 million specimens prospectively collected from more than 5 million U.S. Armed Forces personnel. We evaluated serum samples obtained from 130 persons before they received a diagnosis of SLE, along with samples from matched controls. Results In 115 of the 130 patients with SLE (88 percent), at least one SLE autoantibody tested was present before the diagnosis (up to 9.4 years earlier; mean, 3.3 years). Antinuclear antibodies were present in 78 percent (at a dilution of 1:120 or more), anti–double-stranded DNA antibodies in 55 percent, anti-Ro antibodies in 47 percent, anti-La antibodies in 34 percent, anti-Sm antibodies in 32 percent, anti–nuclear ribonucleoprotein antibodies in 26 percent, and antiphospholipid antibodies in 18 percent. Antinuclear, antiphospholipid antibodies, anti-Ro, and anti-La antibodies were present earlier than anti-Sm and anti–nuclear ribonucleoprotein antibodies (a mean of 3.4 years before the diagnosis vs. 1.2 years, P=0.005). Anti–double-stranded DNA antibodies, with a mean onset 2.2 years before the diagnosis, were found later than antinuclear antibodies (P=0.06) and earlier than anti–nuclear ribonucleoprotein antibodies (P=0.005). For many patients, the earliest available serum sample was positive; therefore, these measures of the average time from the first positive antibody test to the diagnosis are underestimates of the time from the development of antibodies to the diagnosis. Of the 130 initial matched controls, 3.8 percent were positive for one or more autoantibodies. Conclusions Autoantibodies are typically present many years before the diagnosis of SLE. Furthermore, the appearance of autoantibodies in patients with SLE tends to follow a predictable course, with a progressive accumulation of specific autoantibodies before the onset of SLE, while patients are still asymptomatic.
Severe acute pneumonitis among deployed U.S. military personnel—Southwest Asia, March--August 2003. MMWR. 2003 Sep 12:52(36);857-9.7-

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Hoge CW, Brundage JF, Engel CC Jr, Messer SC, Orman DT. Reply to letter to the editor. Am J Psychiatry. 2003 Jun 1;160(6):1191-1192.
Halsell JS, Riddle JR, Atwood JE, Gardner P, Shope R, Poland GA, Gray GC, Ostroff S, Eckart RE, Hospenthal DR, Gibson RL, Grabenstein JD, Arness MK, Tornberg DN, and the Department of Defense Smallpox Vaccination Clinical Evaluation Team. Myopericarditis following smallpox vaccination among U.S. military personnel. JAMA. 2003 Jun 25:289(24):3283-9.
Context.In the United States, the annual incidence of myocarditis is estimated at 1 to 10 per 100,000 population with as many as 1 to 5 percent of patients with acute viral infections having involvement of the myocardium. Although many viruses have been reported to cause myopericarditis, it has been a rare or unrecognized event after vaccination with the currently utilized strain of vaccinia virus (New York City Board of Health; DryvaxÒ, Wyeth Laboratories, Marietta, PA). Objective. To describe a series of probable post-vaccination myopericarditis cases among U.S. military service members reported since the reintroduction of vaccinia vaccine as a countermeasure against possible use of smallpox virus as an agent of biological warfare or bioterrorism. Design. Surveillance case definitions are presented. The cases were identified either through sentinel reporting to U.S. military headquarters, surveillance using the Defense Medical Surveillance System or reports to the Vaccine Adverse Event Reporting System. The cases occurred among individuals vaccinated from mid-December 2002 through 14 March 2003. Results. Among 230,734 primary vaccinees, there were 18 cases of probable post-smallpox vaccination myopericarditis (an incidence of 7.8 per 100,000 over 30 days). There were no cases among 95,622 previously vaccinated. All were white males aged 21 to 33 years, who presented with acute myopericarditis 7 to 19 days following vaccination. A causal relationship is supported by the close temporal clustering (7 to 19 days; mean 10.5 days post-vaccination), wide geographic and temporal distribution, occurrence in only primary vaccinees, and lack of evidence for alternative etiologies or other diseases associated with myopericarditis. Additional supporting evidence is the observation that the observed rate of myopericarditis among primary vaccinees is 3.6-fold higher than the expected rate among non-vaccinated personnel. Conclusion.Among U.S. military personnel vaccinated against smallpox, myopericarditis occurred at a rate of 1 per 12,819 primary vaccinees. Myopericarditis should be considered an expected adverse event associated with smallpox vaccination. Clinicians should consider myopericarditis in the differential diagnosis of patients presenting with chest pain 4 to 30 days following smallpox vaccination and be aware of the implications as well as the need to report this potential adverse advent.
Lange J, Lesikar S, Rubertone MV, Brundage JF. Comprehensive systematic surveillance for adverse effects of Anthrax Vaccine Adsorbed, 1998-2000. Vaccine. 2003;21(15): 1620-8.
Routine vaccinations of U.S. military personnel with Anthrax Vaccine Adsorbed began in 1998. To systematically identify clinical diagnoses reported more frequently after vaccination than before, all military personnel were retrospectively assigned to pre- or post-vaccination cohorts. Cohort assignments were based on vaccination statuses each day of a 3-year surveillance period. For each cohort, rates of hospitalizations and ambulatory visits for 843 specific diagnoses were calculated using data in a public health surveillance system. Compared to the pre-vaccination cohort, the post-vaccination cohort had statistically higher rates of hospitalizations for 17 diagnoses, of ambulatory visits for 34 diagnoses, and in both clinical settings for one diagnosis (malaria). After accounting for systematic differences in coding/reporting and residual confounding, the number and nature of clinical diagnoses more frequent after anthrax vaccination than before were consistent with expectations due to random variation. This surveillance suggests that Anthrax Vaccine Adsorbed has few, if any, clinically significant adverse effects.
Levin LI, Munger KL, Rubertone MV, Peck CA, Lennette ET, Spiegelman D, Ascherio A. Multiple sclerosis and Epstein-Barr virus. JAMA. 2003;289:1533-1536.
Context Infection with Epstein-Barr virus (EBV) has been associated with an increased risk of multiple sclerosis (MS), but the temporal relationship remains unclear. Objective To determine whether antibodies to EBV are elevated before the onset of MS. Design, Setting, and Population Nested case-control study conducted among more than 3 million U.S. military personnel with blood samples collected between 1988 and 2000 and stored in the Department of Defense Serum Repository. Cases were identified as individuals granted temporary or permanent disability because of MS. For each case (n = 83), 2 controls matched by age, sex, race/ethnicity, and dates of blood sample collection were selected. Main Outcome Measures Antibodies including IgA against EBV viral capsid antigen (VCA) and IgG against VCA, nuclear antigens (EBNA complex, EBNA-1, and EBNA-2), diffuse and restricted early antigens, and cytomegalovirus. Results The average time between blood collection and MS onset was 4 years. The strongest predictors of MS were serum levels of IgG antibodies to VCA or EBNA complex. The risk of MS increased monotonically with these antibody titers; relative risk (RR) in persons in the highest category of VCA (2560) compared with those in the lowest (160) was 19.7 (95% confidence interval [CI], 2.2-174; P for trend = .004). For EBNA complex titers, the RR for those in the highest category (1280) was 33.9 (95% CI, 4.1-283; P for trend <.001) vs those in the lowest category (40). Similarly strong positive associations between EBV antibodies and risk of MS were already present in samples collected 5 or more years before MS onset. No association was found between cytomegalovirus antibodies and MS. Conclusion These results suggest a relationship between EBV infection and development of MS.
Wasserman GM, Grabenstein JD, Pittman PR, Rubertone MV, Gibbs PP, Wang LZ, Golder LG. Analysis of adverse events after anthrax immunization in U.S. Army medical personnel. J Occup Environ Med. 2003 Mar;45(3):222-33.
A broad range of health effects in a cohort of 601 health care personnel, immunized with anthrax vaccine adsorbed (AVA) as a military occupational health requirement, were assessed to evaluate adverse events both qualitatively and quantitatively. Active surveillance showed that localized reactions were common and occurred more often in women than men. Five patients were reported to the Vaccine Adverse Event Reporting System, but only one event could be definitively attributed to immunization, a large localized reaction. Two separate cohort studies, one using nested data from a standardized health risk appraisal instrument and the other comparing rates of outpatient visits and hospitalizations, did not reveal significant differences between AVA-immunized and unimmunized individuals. Our findings suggest that AVA is relatively reactogenic but do not indicate serious adverse health effects due to immunization.
Silverberg MJ, Brundage JF, Rubertone MV. Timing and completeness of routine testing for antibodies to human immunodeficiency virus, type 1, among active duty members of the U.S. Armed Forces. Mil Med. 2003 Feb;168(2):160-4.
Since October 1985, the U.S. Armed Forces has conducted routine testing of all personnel for antibodies to human immunodeficiency virus, type-1. Sera that remain after HIV-1 testing are archived in the DoD Serum Repository for potential uses in medical surveillance, clinical, and research activities. The goal of this study was to document the timing and completeness of routine HIV-1 testing among active duty military personnel and to identify factors associated with more recent testing. The date of the most recent HIV-1 test and demographic characteristics of each active duty servicemember were obtained from the Defense Medical Surveillance System. Of all individuals on active duty on 31 August 2001 (N=1,370,367), 98.6% had ever been tested. In the two years prior to the index date, 86.5%, 89.8%, 78.3% and 92.8% of Army, Navy, Air Force and Marine Corps personnel, respectively, had been tested. Older personnel, those with postgraduate degrees, and those who were married had the longest time intervals since their most recent tests. The results of this analysis may inform the planning and conduct of HIV-1 prevention programs as well as deployment-related and other surveillance activities and seroepidemiologic studies that use specimens stored in the DoD Serum Repository.
Wilson ALG, Lange JL, Brundage JF, Frommelt RA. Risk factors for accidental death among male soldiers. Prev Med. 2003 Jan;36:124-30.
Background. In the United States, the leading cause of deaths for young men is unintentional injury. The experience of the U.S. Army, because it is comprised of mostly young men, provides insights into factors associated with risk of accidental death. Between 1990 and 1998, accidents accounted for more than half of all deaths of men on active duty in the U.S. Army. Methods. All men on active duty in the U.S. Army who died in an accident between 1990 and 1998 were included in the study. For each accidental death case, four randomly selected controls were also included, matched on gender and contemporaneous military service. Results. In multivariate analyses, accidental death victims were more likely to be unmarried, limited to a high school education, in combat-specific occupations, veterans of a recent deployment, and previously hospitalized for an "injury/poisoning," "mental disorder," or "sign/symptom/ill-defined condition." Of behaviors reported on routine health risk assessments, the strongest predictor of a subsequent fatal accident was motorcycle use while the most excess deaths were attributable to consuming more than five alcoholic drinks per week. Conclusions. There are characteristics, experiences, and behaviors that predict accidental death risk. The findings may inform safety and health promotion programs aimed at young adults.
Brundage JF, Ryan MAK, Feighner BH, Erdtmann FJ. Meningococcal disease among U.S. military servicemembers in relation to routine uses of vaccines with different serogroup-specific components, 1964-1998. Clin Infect Dis. 2002 Dec 1;35(11):1376-81.
Historically, military recruits have been at high risk of meningococcal disease. Beginning in the 1940s, the U.S. military relied on mass treatment with sulfadiazine to control outbreaks in training camps. In the 1960s, a vaccine was developed in response to the emergence of sulfadiazine resistant strains. Since 1971, all new recruits in the U.S. military have been immunized against Neisseria meningitidis during their first days of service. Serogroups represented in vaccines given to servicemembers have changed over time: the quadrivalent (A,C,Y,W135) vaccine has been given since 1982. In the U.S. military, meningococcal disease rates declined by approximately 94% from 1964 to 1998. After initiating routine immunizations in 1971, crude rates declined sharply and remained low; in addition, there were few cases of disease caused by serogroups represented in contemporaneously administered vaccines. In the U.S. military, immunizations have been effective in preventing disease caused by vaccine-homologous serogroups of N. meningitidis.
Rubertone MV, Brundage JF. The Defense Medical Surveillance System and the Department of Defense Serum Repository: glimpses of the future of comprehensive public health surveillance. Am J Pub Hlth. 2002 Dec;92(12):1900-4.
The Defense Medical Surveillance System (DMSS) is the central repository of medical surveillance data for the U.S. Armed Forces. The DMSS integrates data from sources worldwide in a continuously expanding relational database that documents military and medical experiences of servicemembers throughout their careers. The Department of Defense Serum Repository (DoDSR) is a central archive of sera drawn from servicemembers for medical surveillance purposes. Currently, the DMSS contains data relevant to more than 7 million individuals who have served in the Armed Forces since 1990; and the DoDSR contains more than 27 million specimens that are linkable to data in the DMSS. Recent applications of the DMSS and DoDSR provide glimpses of capabilities and uses of comprehensive public health surveillance systems.
Silverberg M, Frommelt A, Lange J, Brundage J, Rubertone M, Winterton BS. Lightning-associated injuries and deaths -- United States Armed Forces, 1998-2001. MMWR. 2002 Sep 27;51(38):859-62.

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Hoge CW, Lesikar SE, Guevara R, Lange J, Brundage J, Engel CC, Messer SC, Orman DT. Mental disorder diagnoses among U.S. military personnel in the 1990s: association with high health care utilization and early military attrition. Am J Psychiatry. 2002 Sep;159(9):1576-83.
Background/ Objective. Epidemiological studies have shown that mental disorders are associated with reduced health-related quality of life, high health care utilization, and work absenteeism. However, there have been limited measures of the burden of mental disorders in large working populations, such as the U.S. military, using population-based methods. Methods. Analysis was conducted of hospitalizations among all active duty military personnel (16.4 million person-years) from 1990-1999 and ambulatory visits from 1996-1999 using the Defense Medical Surveillance System. Rates of hospitalization, ambulatory visits, and attrition from military service were compared for persons diagnosed with mental disorders and those diagnosed with 15 other ICD-9 disease categories. Results. Mental disorders was the leading category of discharge diagnoses among men and the second leading category among women; 13% of all hospitalizations and 23% of all inpatient bed days were attributed to mental disorders. Six percent of the military population received ambulatory services for mental disorders annually in 1998 and 1999. Among a one-year cohort of personnel, forty-seven percent of those hospitalized for the first time for a mental disorder left military service within six months. This compared with an attrition rate of only 12% (range 11-18%) following hospitalization for any of the 15 other disease categories (relative risk= 4.04; 95% CI 3.91-4.17). This remained significant after controlling for age, gender, and duration of service. Conclusions. Mental disorders appear to represent the most important source of medical and occupational morbidity among active duty U.S. military personnel. These findings provide new population-based evidence that mental disorders are common, disabling, and costly to society.
Campbell KE, Brundage JF. Effects of climate, latitude, and season on the incidence of Bell's palsy, U.S. Armed Forces, October 1997-September 1999. Am J Epidemiol. 2002 Jul 1;158(1):32-9.
Bell's palsy is a relatively common disease characterized by the sudden onset of unilateral facial paralysis. Using a centralized surveillance system that contains demographic, military assignment, and medical encounter data of U.S. military service members, the authors estimated rates, trends, and demographic correlates of risk of Bell's palsy during a 2-year period. Poisson regression was used to estimate the independent effects of climate, season, and latitude. From October 1997 to September 1999, there were 1,181 incident cases of Bell's palsy among U.S. service members. The crude incidence rate was 42.77 per 100,000 person-years. Incidence rates increased with age and were higher among females, Blacks, Hispanics, married persons, and enlisted service members. Both climate (adjusted rate ratio for arid vs. nonarid climate = 1.34) and season (adjusted rate ratio for cold vs. warm months = 1.31) were independent predictors of risk of Bell's palsy. Latitude was not a statistically significant predictor when demographic, climate, and season effects were taken into account. The results are consistent with hypotheses regarding viral etiologies (e.g., reactivation of herpes simplex) of Bell's palsy.
Brundage JF, Kohlhase KF, Gambel JM. Hospitalization experiences of U.S. servicemembers before, during, and after participation in peacekeeping operations in Bosnia-Herzegovina. Am J Ind Med. 2002 Apr;41(4):279-84.
Background: There are relationships among morbidity experiences before, during, and after participation in overseas military operations. Methods: U.S. servicemembers who deployed to Bosnia-Herzegovina during a 4-year period were classified based on their last hospitalizations prior to deploying. Hospitalization rates during and following deployment were calculated in relation to the timing and causes of pre-deployment hospitalizations. Results: Deployers ever hospitalized pre-deployment were 120% and 50% more likely to be hospitalized during and following deployment, respectively. For nearly every category of diagnoses, hospitalization rates during and following deployment were highest among those hospitalized for the same category, intermediate among those hospitalized for other categories, and lowest among those not hospitalized prior to deploying. Deployers hospitalized within 1 month, 2-3 months, or > 3 months of deploying were 3.8, 2.6, and 1.4-times more likely to be hospitalized during deployment. Conclusions: The nature and recency of prior hospitalizations significantly determine during and post-deployment hospitalization risks.
Sanchez JL, Binn LN, Innis BL, Reynolds RD, Lee T, Mitchell-Raymundo F, Craig SC, Marquez JP, Shepherd GA, Polyak CS, Conolly J, Kohlhase KF. Epidemic of adenovirus-induced respiratory illness among U.S. military recruits: epidemiologic and immunologic risk factors in healthy, young adults. J Med Virol. 2001 Dec;65(4):710-8.
Adenovirus (Ad)-induced acute respiratory illnesses resurged among civilian adults and selected military training populations in the United States during the late 1990s. We examined the epidemiologic and immunologic correlates of Ad-induced respiratory illnesses during a large outbreak at an Army basic training installation in southeast United States during a 9-day period in November 1997. A total of 79 recruits hospitalized with acute respiratory illnesses were evaluated during the outbreak period; confirmation of Ad infection by isolation of Ad-like cytopathic agents from throat cultures was detected in 71 (90%) of these patients. Serotyping of 19 (27%) of these 71 isolates identified the etiologic agent to be Ad type 4 (Ad4). In addition, 30 (81%) of 37 patients in whom paired sera were collected demonstrated significant increases (i.e., 4-fold or higher) in serum anti-Ad4 neutralizing antibodies. Anti-Ad4 immunity in new recruits was found to be very low (15 to 22%). A case-control study involving 66 of the 79 hospitalized cases and 189 non-ill controls from the same units was conducted. A lower risk of hospitalization for acute respiratory illnesses was documented for female recruits (odds ratio[OR] = 0.47, P <.05) whereas, a higher risk was noted for smokers (OR = 1.89, P <.05). Unit (training company) attack rates as high as 8 to 10% per week were documented and the outbreak quickly subsided after live, oral Ad types 4 and 7 vaccination was resumed in November 1997. Re-establishment of a military Ad vaccination program is critical for control of Ad-induced acute respiratory illnesses.
Barker TL, Richards AL, Laksono E, Sanchez JL, Feighner BH, McBride WZ, Rubertone MV, Hyams KC. Serosurvey of Borrelia burgdorferi infection among U.S. military personnel: a low risk of infection. Am J Trop Med Hyg. 2001 Dec;65(6):804-9.
A serosurvey of 9,673 United States military personnel was conducted to estimate infection rates with Borrelia burgdorferi sensu stricto, which is the cause of Lyme disease in the United States. Initial screening of sera from 9,673 military personnel on active duty in 1997 was performed by enzyme-linked immunosorbent assay (ELISA); supplemental testing of all ELISA-positive sera was performed by Western blot. Initial screening identified 1,594 (16.5%) ELISA-positive samples, but only 12 (0.12%, 95% confidence interval [CI] = 0.05-0.19%) were confirmed by Western blot. Antecedent serum samples collected from 1988 to 1996 were available for 7,368 (76%) subjects, accounting for 34,020 person-years of observation. Just two of the nine Western blot-positive individuals for whom antecedent samples were available seroconverted during military service for an annual incidence rate of six seroconversions per 100,000 persons (95% CI = 0.7-21.5). The risk of Lyme disease in the U.S. military population was found to be low. Although there may be sub-groups of military personnel who could potentially benefit from vaccination, force-wide use of the Lyme disease vaccine is not warranted.
Paris RM, Bedno SA, Krauss MR, Keep LW, Rubertone MV. Weighing in on type 2 diabetes in the military: characteristics of U.S. military personnel at entry who develop type 2 diabetes. Diabetes Care. 2001 Nov;24(11):1894-8.
Objectives: Current incidence trends in type 2 diabetes portend a significant public health burden and have largely been attributed to similar trends in overweight and physical inactivity. Medical surveillance of the U.S. military indicates that the incidence of all types of diabetes is similar to that in the civilian population (1.9 vs. 1.6 cases per 1,000 person-years) despite weight and fitness standards. Differences in the common determinants of diabetes have not been studied in the military population, which may provide novel clues to the increasing incidence of diabetes in the U.S. Research design and methods: A case-control study, 4-to-1 matched for age, sex, entry date, time in service, and service component (e.g., Army, Navy), was used to describe the association of race/ethnicity, socioeconomic status, and BMI and blood pressure at entry into military service with the subsequent development of type 2 diabetes. Results: Increased BMI (adjusted odds ratio, 3.0 for the > or =30 kg/m(2) vs. < or =20 kg/m(2) categories and 2.0 for the 25.0-29.9 kg/m(2) category, compared with the reference category), African-American (adjusted odds ratio, 2.0) and Hispanic origin (adjusted odds ratio, 1.6) compared with white race and rank (adjusted odds ratio for junior enlisted versus officers, 4.1) were all associated with type 2 diabetes. Conclusions: Individuals with type 2 diabetes in the U.S. military have risk factors similar to the general U.S. population. Because diabetes is a preventable disease, it is of concern that it is occurring in this population of younger and presumably more fit individuals. This has significant implications for the prevention of diabetes in both military and civilian populations.
Andreotti G, Lange JL, Brundage JF. The nature, incidence, and impact of eye injuries among U.S. military personnel: implications for prevention. Arch Ophthalmol. 2001 Nov;119(11):1693-7.
Objectives: To assess incidence rates of eye injuries in the U.S. Armed Forces and to identify demographic and occupational correlates of risk. Design: Retrospective population-based study. Setting: U.S. military medical facilities worldwide. Participants: All individuals in the U.S. Armed Forces during 1998. Main outcome measures: Incidence rates of hospitalizations and ambulatory visits for eye injuries. Results: The incidence rate of ambulatory visits (983 per 100 000 person-years) for eye injuries was 58 times higher than the incidence rate of hospitalizations (17 per 100 000 person-years) for eye injuries. Orbital floor fractures, contusions, and open wounds to the ocular adnexa and orbit accounted for 85% of eye injuries resulting in hospitalization, while 80% of ambulatory visits were for superficial wounds and foreign bodies. Hospitalization rates varied widely across demographic subgroups. Men had twice the incidence rate as women, and the youngest age group (17-24 years) had 6 times the incidence rate of the oldest age group (35-65 years). Together, motor vehicle crashes and fights caused nearly half of the hospitalizations. Ambulatory rates varied significantly in relation to occupation but not to demography. Tradespeople (eg, metal body machinist, welder, and metalworker) had incidence rates 3 to 4 times higher than the overall population rate. Conclusions: Hospitalization and ambulatory data provide different views of the morbidity associated with eye injuries. General safety precautions and behavior modification, rather than eye-specific interventions, are indicated to prevent the most serious eye injuries. However, the consistent use of eye protection during known hazardous occupational activities could prevent much of the morbidity associated with the less serious, yet more common, eye injuries.
Arbuckle MR, James JA, Kohlhase KF, Rubertone MV, Dennis GJ, Harley JB. Development of anti-dsDNA autoantibodies prior to clinical diagnosis of systemic lupus erythematosus. Scand J Immunol. 2001 Jul-Aug;54(1-2):211-9.
Anti-double stranded (dsDNA) antibodies are of considerable diagnostic value and are thought to be involved in the pathogenesis of systemic lupus erythematosus (SLE). Fluctuations in anti-dsDNA antibody levels are also used as markers for disease activity and exacerbations. In this study we sought to evaluate the anti-dsDNA antibody level in serum samples collected before the onset of SLE diagnosis. A total of 130 SLE patients were identified with stored serum samples available prior to diagnosis within the U.S. Department of Defense serum repository. All 633 sera available from these patients were screened for anti-dsDNA antibodies using an enzyme linked immunosorbant assay (ELISA). Within this cohort 55% of cases had detectable anti-dsDNA antibodies prior to SLE diagnosis. The onset of anti-dsDNA antibodies ranged from 9.3 years before to within the same month as diagnosis (with a mean onset 2.7 years before diagnosis). In order to assess for fluctuations in anti-dsDNA levels relative to diagnosis, cases were selected with at least two positive samples, one within 6 months and a second greater than 6 months prior to diagnosis (n = 26). Seven of these cases also had samples available shortly after diagnosis (< or = 6 months) for comparison. Fifty-eight percent of the 26 cases developed a significant rise in anti-dsDNA antibody levels within 6 months of diagnosis. A significant decline in anti-dsDNA levels ensued after diagnosis (and following treatment with corticosteroids) in all seven cases with samples available. Patients with a significant rise in anti-dsDNA antibodies at diagnosis were more likely to have renal disease than those who did not (66.7% compared to 27.3%, chi2 =3.94, P<0.05). These data suggest that anti-dsDNA antibodies are present in SLE patient sera much earlier than previously suspected. In addition, the data are consistent with increases in anti-dsDNA levels contributing to the onset of clinical illness in some patients with SLE.
Sanchez JL Jr, Craig SC, Kohlhase K, Polyak C, Ludwig SL, Rumm PD. Health assessment of U.S. military personnel deployed to Bosnia-Herzegovina for Operation Joint Endeavor. Mil Med. 2001 Jun;166(6):470-4.
In anticipation of U.S. forces deploying to Bosnia-Herzegovina, plans were established to conduct medical surveillance of all military service members. This surveillance would provide the Department of Defense with an overview of the hospitalization and outpatient morbidity experience of U.S. forces. Standardized collection of medical data from all U.S. camps using 14 diagnostic categories based on International Classification of Diseases, 9th Revision, codes began in March 1996. Special assessments for hantavirus and tick-borne encephalitis (TBE) infection risk were also conducted. The average disease and nonbattle injury rate for U.S. forces was 7.1 per 100 soldiers per week. Injuries accounted for 28% of medical visits, whereas undefined/other visits accounted for 33%. The majority of remaining visits were for respiratory (14%), dermatologic (10%), and gastrointestinal (6%) complaints. There was one confirmed and one suspected case of hemorrhagic fever with renal syndrome; only 0.1% of individuals (2 of 1,913) tested seroconverted to hantavirus during deployment. No cases of TBE were reported, and the overall low seroconversion rate (0.42%, 4 seroconversions among 959 unimmunized personnel) reflected a very low risk of infection with TBE-related viruses. Operation Joint Endeavor and follow-on Operations Joint Guard and Joint Forge have been extremely healthy deployments.
Hyams KC, Riddle J, Rubertone M, Trump D, Alter MJ, Cruess DF, Han X, Nainam OV, Seeff LB, Mazzuchi JF, Bailey S. Prevalence and incidence of hepatitis C virus infection in the U.S. military: a seroepidemiologic survey of 21,000 troops. Am J Epidemiol. 2001 Apr 15;153(8):764-70.
Because of a high prevalence of hepatitis C virus (HCV) infection (10-20%) among veterans seeking care in Department of Veterans Affairs (VA) hospitals, current U.S. military forces were evaluated for HCV infection. Banked serum samples were randomly selected from military personnel serving in 1997 and were tested for antibody to HCV (anti-HCV). Overall prevalence of anti-HCV among 10,000 active-duty personnel was 0.48% (5/1,000 troops); prevalence increased with age from 0.1% among military recruits and active-duty personnel aged <30 years to 3.0% among troops aged >/=40 years. Prevalence among 2,000 Reservists and active-duty troops was similar. Based on sequential serum samples from 7,368 active-duty personnel (34,020 person-years of observation), annual incidence of infection was 2/10,000. Of 81 HCV RNA-positive troops for whom genotype was determined, genotypes 1a (63%) and 1b (22%) predominated, as in the civilian population. These data indicate that HCV infection risk among current military forces is lower than in VA studies and the general civilian population aged <40 years. The low level of HCV infection may be attributed to infrequent injection drug use in the military due to mandatory testing for illicit drugs prior to induction and throughout military service.

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Barnett SD, Brundage JF. Incidence of recurrent diagnoses of Chlamydia trachomatis genital infections among male and female soldiers of the U.S. Army. Sex Transm Infect. 2001 Feb;77(1):33-6.
Background/objectives: Few studies of Chlamydia trachomatis incidence, especially among men, and most studies of C. trachomatis in U.S. military populations are cross sectional prevalence surveys. A population based retrospective cohort was used to determine risk factors for repeat diagnoses of genital C. trachomatis infections among male and female soldiers with previous C. trachomatis infections. Methods: All active duty soldiers diagnosed with C. trachomatis genital infections between 1994 and 1998. Cohort members were passively followed until repeat diagnoses of C. trachomatis infection, termination of army service, or the end of the study. Results: Among 11,771 soldiers with initial diagnoses of chlamydia, the crude rate of repeat diagnoses was 52.0 per 1000 person years. Women and men aged 20-24 were at greatest unadjusted risk of reinfection. After adjustment, women aged 20-24 and men aged 25-29 were at higher risk than their younger or older counterparts. Conclusions: Results of this study suggest that both male and female soldiers who are diagnosed with chlamydia infections have relatively high risks of reinfection through their 20s.
Preston DM, Levin LI, Jacobson DJ, Jacobsen SJ, Rubertone M, Holmes E, Murphy GP, Moul JW. Prostate-specific antigen levels in young white and black men 20 to 45 years old. Urology. 2000 Nov 1;56(5):812-6.
Objectives: To determine the prostate-specific antigen (PSA) levels and PSA change over time in young white and black men 20 to 45 years old. Methods: The Department of Defense Serum Repository, a serum bank that stores all residual serum from the military human immunodeficiency virus screening program at -25 degrees C, was sampled to obtain a total of 588 black and 588 white subjects 20 to 45 years old. This was a retrospective study with only demographic data available on the studied subjects. The samples used for this study were collected between June 24, 1988 and June 12, 1996. Individuals with a history of prostate disease were excluded by query of a centralized Department of Defense diagnosis database. Three serum specimens evenly distributed over a mean of 6 years were selected for each individual to determine the free and total PSA levels and PSA velocity. The Hybritech Tandem-E PSA assay was used for the total PSA measurement, and the Hybritech Tandem-R assay was used for the free PSA measurement. Results: The baseline serum PSA levels differed by race (P = 0.04). The median (25th, 75th percentile) baseline serum PSA levels for black men 20 to 29, 30 to 39, and 40 to 45 were 0.38 ng/mL (0.26, 0.61), 0.45 ng/mL (0.32, 0. 67), and 0.52 ng/mL (0.37, 0.73), respectively. The median baseline serum PSA levels for the same decade groups in white men were 0.38 ng/mL (0.27, 0.57), 0.45 ng/mL (0.28, 0.68), and 0.40 ng/mL (0.26, 0. 64), respectively. The PSA velocity was higher in white men than in black men (mean 2.8%/yr and 1.6%/yr, respectively, P = 0.032). Conclusions: These results suggest that although black men 20 to 45 years old have higher baseline serum PSA levels than white men of the same age, the PSA velocity is greater in young white than in young black men. Additional work is needed to determine the clinical significance of these findings.
Brundage JF, Kohlhase KF, Rubertone MV. Hospitalizations for all causes of U.S. military service members in relation to participation in Operations Joint Endeavor and Joint Guard, Bosnia-Herzegovina, January 1995 to December 1997. Mil Med. 2000 Jul;165(7):505-11.
Since December 1995, the United States has deployed military forces to Bosnia-Herzegovina to participate for varying periods in peacekeeping operations. Throughout the operations, medical surveillance data have been routinely integrated in the Defense Medical Surveillance System. For this analysis, all individuals who served in the U.S. armed forces between January 1995 and December 1997 were characterized as participants or nonparticipants in the Bosnia-Herzegovina operations. Each participant's service was divided into predeployment, deployment, and postdeployment phases. End points for analyses were hospitalizations (all causes) in military hospitals. The crude hospitalization rate among nonparticipants (80.9 per 1,000 person-years [p-yrs]) exceeded the rate among participants (56.6 per 1,000 p-yrs). Among participants, the crude hospitalization rate during deployment (84.4 per 1,000 p-yrs) exceeded the rates before deployment (54.7 per 1,000 p-yrs) and after deployment (49.9 per 1,000 p-yrs). Proportional hazards regression procedures were used to control for confounding effects in comparisons of participants and nonparticipants, to account for transitions in deployment-phase exposures at appropriate calendar times, and to adjust for changes in hospitalization criteria that were implemented during the study. Although the crude hospitalization rate after deployment was lower than the rate before deployment, adjusted relative risks were elevated during and after deployment (relative to before deployment).
Jones BH, Perrotta DM, Canham-Chervak ML, Nee MA, Brundage JF. Injuries in the military: a review and commentary focused on prevention. Am J Prev Med (suppl). 2000 Apr;18(3S):71-84.
Background: In November 1996, the Armed Forces Epidemiological Board (AFEB) Injury Prevention and Control Work Group issued a report that cited injuries as the leading cause of morbidity and mortality among military service members. This article reviews the types and categories of military morbidity and mortality data examined by the AFEB work group and the companion Department of Defense (DoD) Injury Surveillance and Prevention Work Group. This article further uses the injury data reviewed to illustrate the role of surveillance and research in injury prevention. The review provides the context for discussion of the implications of the AFEB work group's findings for the prevention of injuries in the military. Methods: The AFEB work group consisted of 11 civilian injury epidemiologists, health professionals and scientists from academia, and other non-DoD government agencies, plus six military liaison officers. Injury data from medical databases were provided to the civilian experts on the AFEB work group by the all-military DoD Injury Surveillance and Prevention Work Group. The AFEB work group assessed the value of each database to the process of prevention and made recommendations for improvement and use of each data source. Results: Both work groups found that injuries were the single leading cause of deaths, disabilities, hospitalizations, outpatient visits, and manpower losses among military service members. They also identified numerous data sources useful for determining the causes and risk factors for injuries. Those data sources indicate that training injuries, sports, falls, and motor vehicle crashes are among the most important causes of morbidity for military personnel. Conclusions: While the work group recommends ways to prevent injuries, they felt the top priority for injury prevention must be the formation of a comprehensive medical surveillance system. Data from this surveillance system must be used routinely to prioritize and monitor injury and disease prevention and research programs. The success of injury prevention will depend not just on use of surveillance but also partnerships among the medical, surveillance, and safety agencies of the military services as well as the military commanders, other decision makers, and service members whose direct actions can prevent injuries and disease.
Arness MK, Feighner BH, Canham ML, Taylor DN, Monroe SS, Cieslak TJ, Hoedebecke EL, Polyak CS, Cuthie JC, Fankhauser RL, Humphrey CD, Barker TL, Jenkins CD, Skillman DR. Norwalk-like viral gastroenteritis outbreak in U.S. Army trainees. Emerg Infect Dis. 2000 Mar-Apr;6(2):204-7.
An outbreak of acute gastroenteritis hospitalized 99 (12%) of 835 U. S. Army trainees at Fort Bliss, El Paso, Texas, from August 27 to September 1, 1998. Reverse transcriptase polymerase chain reaction tests for Norwalk-like virus were positive for genogroup 2. Gastroenteritis was associated with one post dining facility and with soft drinks.
Craig SC, Pittman PR, Lewis TE, Rossi CA, Henchal EA, Kuschner RA, Martinez C, Kohlhase KF, Cuthie JC, Welch GE, Sanchez JL. An accelerated schedule for tick-borne encephalitis vaccine: the American Military experience in Bosnia. Am J Trop Med Hyg. 1999 Dec;61(6):874-8.
Tick-borne encephalitis (TBE) is a viral illness endemic to the Balkan region. United States military forces were deployed to Bosnia in early 1996 as part of Operation Joint Endeavor, a U.S.-led multinational peace-keeping operation. To counteract the TBE threat, an inactivated, parenteral vaccine (FSME-Immun Inject; Immuno AG, Vienna, Austria) was offered to soldiers at high risk on a volunteer basis in an accelerated, 3-dose schedule (0, 7, and 28 days). Passive adverse reaction surveillance was conducted on 3,981 vaccinated personnel. Paired sera from a randomly selected group of 1,913 deployed personnel (954 who received vaccine and 959 who were unvaccinated) were tested for antibodies to TBE by an ELISA. Three-dose recipients demonstrated an 80% seroconversion rate (4-fold or greater increase in anti-TBE titers). By comparison, the TBE infection rate in the unvaccinated cohort was found to be only 0.42% (4 of 959). Only 0.18% of vaccinees reported self-limited symptoms. An accelerated immunization schedule appears to be an acceptable option for military personnel or travelers on short-term notice to TBE-endemic areas.
Barraza EM, Ludwig SL, Gaydos JC, Brundage JF. Reemergence of adenovirus type 4 acute respiratory disease in military trainees: report of an outbreak during a lapse in vaccination. J Infect Dis. 1999 Jun;179(6):1531-3.
From 23 April to 13 May 1995, an outbreak of acute respiratory disease (ARD) hospitalizations occurred in basic training soldiers at Fort Jackson, South Carolina. Weekly hospitalization rates for the most affected military unit reached 11.6%. Virus isolation and serologic studies from a sample of patients identified the agent as adenovirus type 4. Prior to starting vaccinations against adenovirus types 4 and 7 in 1971, these serotypes were the major causes of ARD in basic trainees. No outbreaks were reported when the vaccines were used. A logistical error temporarily interrupted vaccine production, and newly arriving trainees received no adenovirus vaccines from the summer of 1994 through late March 1995. This outbreak occurred in unvaccinated soldiers. The sole manufacturer has permanently stopped adenovirus vaccine production. All type 4 vaccine supplies are now depleted. This outbreak demonstrates continued susceptibility of military recruits to adenovirus type 4 and warns of future outbreaks.
Ludwig SL, Brundage JF, Kelley PW, Nang R, Towle C, Schnurr DP, Crawford-Miksza L, Gaydos J. Prevalence of antibodies to adenovirus, serotypes 4 and 7, among unimmunized U.S. Army trainees: results of a retrospective nationwide seroprevalence survey. J Infect Dis. 1998 Dec;178(6):1776-8.
The 1996 production halt of adenovirus types 4 and 7 vaccines prompted concerns about the resurgence of large respiratory disease outbreaks among U.S. military basic trainees. This serosurvey was conducted to assess the current susceptibility of the trainee population to these viruses. A stratified, random sample (n=303) of trainees' sera was tested using a quantitative colorimetric microneutralization assay to demonstrate antibody titers considered to provide immunologic protection against each adenovirus type. Results were analyzed for relationships between susceptibility and 4 demographic factors-gender, race, prior military service, and age. Results showed that 66% and 73% of trainees were susceptible to serotypes 4 and 7, respectively. Nearly 90% were susceptible to at least one serotype. Susceptibility was significantly (P<.05) related to lack of prior military service and younger age. Consistent with a serosurvey conducted 20 years ago, these results demonstrated significant susceptibility to two vaccine-preventable causes of disease. These findings may have civilian implications.
Brundage JF. Military preventive medicine and medical surveillance in the post-cold war era. Mil Med. 1998 May;163(5):272-7.
In response to the end of the cold war, the United States developed new foreign policy and national security strategies. As a result, many medical support concepts that were operative during the cold war were invalidated. Recently, the Chairman of the Joint Chiefs of Staff provided direction and guidance for long-range strategic planning (Joint Vision 2010). Medical support doctrine that is being developed within the framework of Joint Vision 2010 relies on currently unavailable preventive medicine and medical surveillance capabilities. This report analyzes the relevance and roles of military preventive medicine and medical surveillance in the context of post-cold war resource constraints and military medical support needs, presents the rationale for and objectives of a demand-reduction medical support strategy, and outlines the roles, responsibilities, and characteristics of a defense medical surveillance system.
Brundage JF, Gunzenhauser JD, Longfield JN, Rubertone MV, Ludwig SL, Rubin FA, Kaplan EL. Epidemiology and control of acute respiratory diseases with emphasis on group A beta-hemolytic streptococcus: a decade of U.S. Army experience. Pediatrics. 1996 Jun;97(6 Pt 2):964-70.
Objective. To summarize the experiences of the U.S. Army regarding prevention and control, and frequencies, rates, trends, and determinants of febrile acute respiratory diseases (ARDs), particularly Group A beta-hemolytic streptococcus (GABHS). Methodology. Since 1966, the U.S. Army has conducted routine surveillance of ARDs among basic trainees. Since 1985, all trainees with fever and respiratory tract symptoms have been cultured for GABHS. Field investigations were conducted when outbreaks of acute respiratory or GABHS-associated illnesses were detected. Mass plus tandem benzathine penicillin prophylaxis were used to interdict and control training center GABHS outbreaks. Results. During the period 1985 to 1994, there were 65,184 hospitalizations for acute febrile respiratory illnesses among Army trainees. The crude hospitalization rate was 0.45 per 100 trainees per week. The rate consistently declined over the period. Incremental declines were temporally associated with increased use of adenovirus immunizations and broader use of benzathine penicillin prophylaxis. During the period, 10,789 of 59,818 (18%) pharyngeal cultures were positive for GABHS. GABHS outbreaks were associated with diverse clinical manifestations including streptococcal toxic shock, acute rheumatic fever, and pneumonia. The emergence of mucoid colony morphology in clinical isolates was a consistent indicator of circulating virulent strains with epidemic potential. Outbreak-associated M types were M1, M3, M5, and M18. In response to six GABHS outbreaks, mass plus tandem benzathine penicillin chemoprophylaxis produced rapid and sustained GABHS control. ARD and GABHS recovery rates were lowest when benzathine penicillin prophylaxis was widely used. Conclusions. ARD rates among Army trainees have consistently declined to unprecedented levels. GABHS has reemerged as an important threat to military trainees. Benzathine penicillin chemoprophylaxis is safe and effective for interdicting and preventing GABHS outbreaks in closed, healthy young adult populations.

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