Angelia A. Eick

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.