Vaccination and risk of type 1 diabetes mellitus in active component U.S. Military, 2002-2008.

AIMS/HYPOTHESIS: To evaluate whether vaccination increases the risk of type 1 diabetes mellitus in active component U.S. military personnel. METHODS: We conducted a retrospective cohort study among active component U.S. military personnel age 17-35 years. Individuals with first time diagnoses of type 1 diabetes between January 1, 2002 and December 31, 2008 were identified using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. We used Poisson regression to estimate risk ratios between individual vaccine exposures and type 1 diabetes. Secondary analyses were performed controlling for receipt of multiple vaccines and available demographic variables. RESULTS: Our study population consisted of 2,385,102 individuals followed for approximately 7,644,098 person-years of service. This included 1074 incident type 1 diabetes cases. We observed no significant increased risk of type 1 diabetes after vaccination with anthrax vaccine adsorbed (AVA) [RR=1.00; 95% CI (0.85, 1.17)], smallpox vaccine [RR=0.84; 95% (CI 0.70, 1.01)], typhoid vaccine [RR=1.03; 95% CI (0.87, 1.22)], hepatitis B vaccine [RR=0.83; 95% CI (0.72, 0.95)], measles mumps rubella vaccine (MMR) [RR=0.71, 95% CI (0.61, 0.83)], or yellow fever vaccine [RR=0.70; 95% CI (0.59, 0.82)]. CONCLUSIONS: We did not find an increased risk of diagnosed type 1 diabetes and any of the study vaccines. We recommend that follow-up studies using medical record review to confirm case status should be considered to corroborate these findings.

Serosurvey of bacterial and viral respiratory pathogens among deployed U.S. service members.

BACKGROUND: Respiratory illnesses can cause substantial morbidity during military deployments. Bordetella pertussis, Chlamydia pneumoniae, Mycoplasma pneumoniae, adenovirus, parainfluenza, and respiratory syncytial virus (RSV) are hypothesized causes. PURPOSE: To determine pathogen-specific seroprevalence prior to and after deployment in support of Operation Enduring Freedom (OEF). METHODS: A retrospective cohort study of 1000 service members deployed between June 30, 2004, and June 30, 2007, was conducted from 2008 through 2009. Pre- and post-deployment sera were tested for the presence of antibody to each pathogen. RESULTS: Pre-deployment IgG seropositivity was high for adenovirus, RSV, and parainfluenza (98.7%, 97.8%, and 81.6%, respectively), whereas seropositivity for B. pertussis, M. pneumoniae, and C. pneumoniae was 14.2%, 21.9%, and 65.1%, respectively. As defined by seroconversion in 1000 subjects, the following were identified: 43 new parainfluenza infections (24% of susceptibles); 37 new pertussis infections (4% of susceptibles); 33 new C. pneumoniae infections (10% of susceptibles); and 29 new M. pneumoniae infections (4% of susceptibles). B. pertussis seroconversion was two to four times higher than reports for the general U.S. population. Overall, 14.2% of the service members seroconverted to at least one of these six pathogens; this increased to 30.1% seroconversion when influenza was included. However, serologic testing was not clearly associated with clinical illness in this report. CONCLUSIONS: Serologic evidence for respiratory infections was common among the 2004-2007 OEF-deployed military, sometimes at a higher rate than the general U.S. population. Awareness of this risk and implementation of preventive measures should be emphasized by leadership prior to and during deployment.

Department of Defense influenza and other respiratory disease surveillance during the 2009 pandemic.

The Armed Forces Health Surveillance Center's Division of Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) supports and oversees surveillance for emerging infectious diseases, including respiratory diseases, of importance to the U.S. Department of Defense (DoD). AFHSC-GEIS accomplishes this mission by providing funding and oversight to a global network of partners for respiratory disease surveillance. This report details the system's surveillance activities during 2009, with a focus on efforts in responding to the novel H1N1 Influenza A (A/H1N1) pandemic and contributions to global public health. Active surveillance networks established by AFHSC-GEIS partners resulted in the initial detection of novel A/H1N1 influenza in the U.S. and several other countries, and viruses isolated from these activities were used as seed strains for the 2009 pandemic influenza vaccine. Partners also provided diagnostic laboratory training and capacity building to host nations to assist with the novel A/H1N1 pandemic global response, adapted a Food and Drug Administration-approved assay for use on a ruggedized polymerase chain reaction platform for diagnosing novel A/H1N1 in remote settings, and provided estimates of seasonal vaccine effectiveness against novel A/H1N1 illness. Regular reporting of the system's worldwide surveillance findings to the global public health community enabled leaders to make informed decisions on disease mitigation measures and controls for the 2009 A/H1N1 influenza pandemic. AFHSC-GEIS's support of a global network contributes to DoD's force health protection, while supporting global public health.

Maternal influenza vaccination and effect on influenza virus infection in young infants.

OBJECTIVE: To assess the effect of seasonal influenza vaccination during pregnancy on laboratory-confirmed influenza in infants to 6 months of age. DESIGN: Nonrandomized, prospective, observational cohort study. SETTING: Navajo and White Mountain Apache Indian reservations, including 6 hospitals on the Navajo reservation and 1 on the White Mountain Apache reservation. PARTICIPANTS: A total of 1169 mother-infant pairs with mothers who delivered an infant during 1 of 3 influenza seasons. MAIN EXPOSURE: Maternal seasonal influenza vaccination. MAIN OUTCOME MEASURES: In infants, laboratory-confirmed influenza, influenza-like illness (ILI), ILI hospitalization, and influenza hemagglutinin inhibition antibody titers. RESULTS: A total of 1160 mother-infant pairs had serum collected and were included in the analysis. Among infants, 193 (17%) had an ILI hospitalization, 412 (36%) had only an ILI outpatient visit, and 555 (48%) had no ILI episodes. The ILI incidence rate was 7.2 and 6.7 per 1000 person-days for infants born to unvaccinated and vaccinated women, respectively. There was a 41% reduction in the risk of laboratory-confirmed influenza virus infection (relative risk, 0.59; 95% confidence interval, 0.37-0.93) and a 39% reduction in the risk of ILI hospitalization (relative risk, 0.61; 95% confidence interval, 0.45-0.84) for infants born to influenza-vaccinated women compared with infants born to unvaccinated mothers. Infants born to influenza-vaccinated women had significantly higher hemagglutinin inhibition antibody titers at birth and at 2 to 3 months of age than infants of unvaccinated mothers for all 8 influenza virus strains investigated. CONCLUSIONS: Maternal influenza vaccination was significantly associated with reduced risk of influenza virus infection and hospitalization for an ILI up to 6 months of age and increased influenza antibody titers in infants through 2 to 3 months of age.

Hepatitis E seroprevalence and seroconversion among US military service members deployed to Afghanistan.

BACKGROUND: Hepatitis E virus (HEV) has been recognized as a threat to military forces since its discovery. Although HEV seroprevalence in Afghanistan is not known, HEV infection is thought to be highly endemic in that country. This study determined the incidence of HEV seroconversion among United States (US) service members who were deployed to Afghanistan, as well as the prevalence of antibodies to HEV prior to the deployment. METHODS: A random sample of 1500 subjects was selected from the cohort of service members who were deployed to Afghanistan between 2002 and 2006. Predeployment and postdeployment serum samples from these subjects were tested by enzyme immunoassay for total antibodies to HEV. Results. The seroprevalence of antibodies to HEV in US service members prior to deployment was 1.1%. The seroconversion rate among service members deployed to Afghanistan was 0.13%. CONCLUSIONS: Although subpopulations may be at higher risk for HEV exposure during deployment, the risk among US service members deployed to Afghanistan in this study was low. Previously implemented and current preventive measures in theater appear to have been adequate. With future deployments to new areas or changes in military operations in areas of risk, continued surveillance for HEV infection in the military will be warranted.

Active tuberculosis and recent overseas deployment in the U.S. military.

BACKGROUND: The risk of active TB resulting from military deployment to endemic areas is unknown. It has typically been assumed that the risk of TB approximates the risk among local nationals in that country. PURPOSE: This nested case-control study assesses the putative association of overseas deployment with active tuberculosis among active-component U.S. military service members. METHODS: Deployment histories and other exposures among 578 active TB cases and 2312 controls matched on year of entry into service and length of service between 1990 and 2006 were compared in 2009 using multivariate conditional logistic regression. Multiple imputation methods were used to account for missing data. RESULTS: The matched OR of active TB for military deployers as compared to nondeployers was 1.18 (95% CI=0.91, 1.52). A significant association of deployments of 90-179 days was found, but this was inconsistent with the overall negative result. Significant associations were seen with foreign birth and nonwhite racial or ethnic groups. Overseas stationing in Korea was also found to be associated with active TB. CONCLUSIONS: No strong or consistent association was found between active TB and deployment, but an association was seen with long-term residence in TB-endemic countries (Korea). The strongest risk factors for active TB in the U.S. military population were found to exist prior to accession into military service. These conclusions were robust in sensitivity analysis.

Seasonal influenza vaccine and protection against pandemic (H1N1) 2009-associated illness among US military personnel.

INTRODUCTION: A novel A/H1N1 virus is the cause of the present influenza pandemic; vaccination is a key countermeasure, however, few data assessing prior seasonal vaccine effectiveness (VE) against the pandemic strain of H1N1 (pH1N1) virus are available. MATERIALS AND METHODS: Surveillance of influenza-related medical encounter data of active duty military service members stationed in the United States during the period of April-October 2009 with comparison of pH1N1-confirmed cases and location and date-matched controls. Crude odds ratios (OR) and VE estimates for immunized versus non-immunized were calculated as well as adjusted OR (AOR) controlling for sex, age group, and history of prior influenza vaccination. Separate stratified VE analyses by vaccine type (trivalent inactivated [TIV] or live attenuated [LAIV]), age groups and hospitalization status were also performed. For the period of April 20 to October 15, 2009, a total of 1,205 cases of pH1N1-confirmed cases were reported, 966 (80%) among males and over one-half (58%) under 25 years of age. Overall VE for service members was found to be 45% (95% CI, 33 to 55%). Immunization with prior season's TIV (VE = 44%, 95% CI, 32 to 54%) as well as LAIV (VE = 24%, 95% CI, 6 to 38%) were both found to be associated with protection. Of significance, VE against a severe disease outcome was higher (VE = 62%, 95% CI, 14 to 84%) than against milder outcomes (VE = 42%, 95% CI, 29 to 53%). CONCLUSION: A moderate association with protection against clinically apparent, laboratory-confirmed Pandemic (H1N1) 2009-associated illness was found for immunization with either TIV or LAIV 2008-09 seasonal influenza vaccines. This association with protection was found to be especially apparent for severe disease as compared to milder outcome, as well as in the youngest and older populations. Prior vaccination with seasonal influenza vaccines in 2004-08 was also independently associated with protection.

Influenza and respiratory disease surveillance: the US military's global laboratory-based network.

The US Department of Defense influenza surveillance system now spans nearly 500 sites in 75 countries, including active duty US military and dependent populations as well as host-country civilian and military personnel. This system represents a major part of the US Government's contributions to the World Health Organization's Global Influenza Surveillance Network and addresses Presidential Directive NSTC-7 to expand global surveillance, training, research and response to emerging infectious disease threats. Since 2006, the system has expanded significantly in response to rising pandemic influenza concerns. The expanded system has played a critical role in the detection and monitoring of ongoing H5N1 outbreaks worldwide as well as in the initial detection of, and response to, the current (H1N1) 2009 influenza pandemic. This article describes the system, details its contributions and the critical gaps that it is filling, and discusses future plans.

Comparison of the trivalent live attenuated vs. inactivated influenza vaccines among U.S. military service members.

Limited effectiveness data are available comparing live attenuated influenza vaccine (LAIV) to inactivated influenza vaccine (TIV) among adults. To compare the incidence of influenza-like illness following immunization of adults with LAIV vs. TIV, we conducted a retrospective cohort analysis of active component U.S. military personnel for the 2005-2006 and 2006-2007 influenza seasons. Recruits experienced a much higher burden of disease compared to non-recruits, with crude incidence rates of influenza-like illness 2-16 times higher than non-recruits depending on the season and cohort. For both seasons, a slightly greater protection from influenza-like illness was found for non-recruits who received TIV compared to LAIV (adjusted incidence rate ratio, 1.17 (95% CI, 1.14-1.20) and 1.33 (95% CI, 1.30-1.36), 2005-2006 and 2006-2007 influenza seasons, respectively). However, for Army and Air Force recruits, LAIV was found to provide significantly greater protection from influenza-like illnesses compared to TIV, with adjusted incidence rates of influenza-like illness 22-51% and 18-47% lower among LAIV compared to TIV recipients for the 2005-2006 and 2006-2007 influenza seasons, respectively. Possible reasons for differences in recruit and non-recruit findings include differences in pre-existing influenza antibody levels, differing respiratory disease burden, and/or unmeasured confounding. Consideration of these findings should be made when developing influenza immunization policies.

Live attenuated or inactivated influenza vaccines and medical encounters for respiratory illnesses among US military personnel.

CONTEXT: Since 2004, increasing numbers of military personnel have been immunized with the intranasal live attenuated influenza vaccine (LAIV) while most others received the trivalent inactivated vaccine (TIV). However, data about live virus vaccine effectiveness among healthy adults are limited. OBJECTIVE: To monitor the effectiveness of vaccines to better inform military vaccination policy. DESIGN, SETTING, AND PARTICIPANTS: Surveillance of population-based, propensity-matched, and/or vaccine-naive cohorts of more than a million active-duty, nonrecruit military service members aged 17 to 49 years stationed in the United States during the 2004-2005, 2005-2006, or 2006-2007 influenza season. MAIN OUTCOME MEASURES: Incidence of health care encounters resulting in a primary diagnostic code consistent with pneumonia or influenza. Incident hospitalizations was a secondary outcome. RESULTS: In all 3 seasons, immunization with TIV was associated with lower incidence rates of health care encounters for pneumonia and influenza when compared with no immunization: 8.6 vs 19.4 for 2004-2005, 7.8 vs 10.9 for 2005-2006, and 8.0 vs. 11.7 per 1000 person-years for 2006-2007 (all P < .001). Similar estimates were obtained from propensity-matched and/or vaccine-naive cohorts. Consistently lower vaccine effect following LAIV immunization was only seen during the 2006-2007 influenza season in the total (10.7; 95% confidence interval [CI], 2.72 to 18.1; P = .03) and propensity-matched cohorts (11.8; 95% CI, 0.85 to 21.5; P = .04), and was less than effect from TIV (TIV vs LAIV, 19.8; 95% CI, 13.6 to 25.5; P < .001). Among vaccine-naive service members, however, estimates for LAIV effect were more robust for both the 2005-2006 and 2006-2007 seasons (P = .01) and were comparable with TIV (eg, LAIV, 30.2; 95% CI, 11.2 to 45.2; vs TIV, 35.3; 95% CI, 25.9 to 43.6; in 2005-2006). CONCLUSIONS: Vaccination with TIV was associated with fewer medical encounters related to pneumonia and influenza compared with LAIV or no immunization. In this annually immunized population, this effect was less apparent in those vaccinated with LAIV.

Influenza immunization and subsequent diagnoses of group A streptococcus-illnesses among U.S. Army trainees, 2002-2006.

To assess the association between influenza immunization and subsequent diagnosis of group A streptococcus (GAS)-illness in Army recruits during influenza seasons 2002-2006. A case-control study was employed with cases as trainees with outpatient GAS diagnosis (ICD-9-CM codes: 034.0, 035, 038.0, 041.01, 320.2, 390-392, 482.31) during the influenza season, and controls as trainees with no outpatient GAS diagnosis during the influenza season. Primary exposure was influenza immunization during 1st September to 30th April of each season. Estimated protective effects of influenza immunization against GAS-illness ranged from 50% to 77%. A strong protective effect was suggested for Army trainee influenza immunization on the diagnosis of GAS-illness.

Respiratory disease in Army recruits: surveillance program overview, 1995-2006.

BACKGROUND: Since 1966, the U.S. Army has had in place a comprehensive surveillance system for acute respiratory disease (ARD) because of its continued high incidence in the recruit population. A retrospective review of the program from 1995 to 2006, a continuation of an earlier analysis from 1985-1994, was performed to describe the program and to summarize group A streptococcal (GAS) outbreaks identified through this program. METHODS: Weekly incidence data and daily sentinel case data collected as part of the ARD surveillance program were analyzed in 2007 to report rates of ARD and GAS outbreaks over this 12-year period (1995-2006) for five participating Army sites. RESULTS: Average ARD rates were consistently higher from 2000 to 2006 than from 1995 to 1999. Rate ratios of winter rates to summer rates were greater than 1.0 prior to 2000, but from 2000 to 2006, ratios were consistently near 1.0. Rheumatogenic M types were available for three of five outbreaks. CONCLUSIONS: Continuing high incidence of ARD in the military, re-emerging rheumatogenic M types, and a highly mobile military underscore the need for continued surveillance efforts. The continued employment of interventions with demonstrated effectiveness, such as chemoprophylaxis and basic preventive measures, is essential to reducing the burden of ARD.

The role of neutralizing antibodies in protection of American Indian infants against respiratory syncytial virus disease.

BACKGROUND: Navajo and White Mountain Apache infants have respiratory syncytial virus (RSV) hospitalization rates 2-5 times that of the general U.S. infant population. To evaluate whether these high rates can be attributable to low concentrations of maternally derived RSV neutralizing antibodies, we conducted a case-control study. METHODS: Study subjects enrolled in a prospective, hospital-based surveillance study of RSV disease and a group randomized clinical trial of a 7-valent pneumococcal conjugate vaccine. Cord blood specimens were assayed for neutralizing RSV antibody titers. Infants hospitalized with a respiratory illness had a nasal aspirate obtained to determine whether RSV was present. Infants with an RSV respiratory hospitalization were matched by date of birth and geographic location to infants who did not have an RSV hospitalization before 6 months of age. RESULTS: For every 1 log2 increase in titer of cord blood RSV neutralizing antibodies there was a 30% reduced risk of hospitalization with RSV (OR = 0.69, P = 0.003). However, among infants hospitalized with RSV, there was no association between cord blood RSV neutralizing antibody and the severity of the RSV illness. CONCLUSIONS: These findings indicate that American Indian infants with high concentrations of maternally derived RSV neutralizing antibodies are protected from RSV hospitalization before 6 months of age. However, these antibodies do not modify the severity of illness once disease has occurred. The basis for elevated rates of RSV disease among American Indian infants cannot be attributed to a failure of maternal RSV neutralizing antibodies to confer protection.

Incidence of mumps and immunity to measles, mumps and rubella among US military recruits, 2000-2004.

Recent mumps outbreaks have evoked concerns of decreasing mumps immunity among adolescents and adults, including US 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.

Predictors of pneumococcal conjugate vaccine immunogenicity among infants and toddlers in an American Indian PnCRM7 efficacy trial.

BACKGROUND: Pneumococcal conjugate vaccines are important for the prevention of serious illness and death among infants. Factors associated with pneumococcal conjugate vaccine immunogenicity have not been explored. METHODS: Children <24 months of age received 2, 3, or 4 doses of 7-valent pneumococcal conjugate vaccine (PnCRM7) or control vaccine depending on age at enrollment. Serum samples were tested for serotype-specific antibodies by enzyme-linked immunosorbant assay. Multiple linear regression was used to determine predictors of immunogenicity. RESULTS: Among 315 PnCRM7-vaccinated subjects and 295 control subjects enrolled at <7 months of age, geometric mean concentrations (GMCs) of antibodies were significantly higher after dose 3 than after dose 2 for all serotypes except type 4. The proportion of subjects with antibody concentrations > or =5.0 micro g/mL was higher for all serotypes, but the proportion with concentrations > or =0.35 micro g/mL was higher only for types 6B and 23F. Three-dose and 2-dose regimens for those 7-11 and 12-23 months of age, respectively, were highly immunogenic. Increased maternal antibody concentrations were associated with reduced responses to dose 1 and 3 but not to dose 4 of PnCRM7. CONCLUSIONS: Maternal antibody is associated with a reduced infant response to PnCRM7 but does not interfere with immune memory. In infants, a third priming dose increases the antibody GMC and the proportion achieving an antibody concentration > or =5.0 micro g/mL but has little impact on the proportion achieving a concentration > or =0.35 micro g/mL.

Safety and immunogenicity of two octavalent pneumococcal conjugate vaccines in American Indian infants.

We evaluated the safety and immunogenicity of two octavalent pneumococcal polysaccharide vaccines (serotypes 3, 4, 6B, 9V, 14, 18C, 19F, and 23F) conjugated to either diphtheria toxoid (PncD) or tetanus protein (PncT) among White Mountain Apache and Gila River Indian Community infants. This was a prospective, non-randomized, open label, comparative pilot study of PncD and PncT. Since this was a pilot study, a small sample size of 60 infants was enrolled. Enrolled healthy infants received either PncD or PncT at 2, 4, and 6 months of age. Antibody concentrations were measured by enzyme-immunoassay (EIA) prior to each dose and 1 month after the last dose. Local reaction rates were similar between PncD and PncT groups. The geometric mean concentrations (GMCs) were significantly higher for PncD than PncT for serotype 3 whereas GMCs were significantly higher for PncT for serotype 4. For this pilot study, both vaccines appeared to be safe and immunogenic in this group of American Indian infants.