Duration of seropositivity following yellow fever vaccination in U.S. military service members.

BACKGROUND: The United States military regularly deploys thousands of service members throughout areas of South America and Africa that are endemic for yellow fever (YF) virus. To determine if booster doses might be needed for service members who are repetitively or continually deployed to YF endemic areas, we evaluated seropositivity among US military personnel receiving a single dose of YF vaccine based on time post-vaccination. METHODS: Serum antibodies were measured using a plaque reduction neutralization test with 50% cutoff in 682 military personnel at 5-39 years post-vaccination. We determined noninferiority of immune response by comparing the proportion seropositive among those vaccinated 10-14 years previously with those vaccinated 5-9 years previously. Noninferiority was supported if the lower-bound of the 2-tailed 95% CI for p10-14years - p5-9years was ≥-0.10. Additionally, the geometric mean antibody titer (GMT) at various timepoints following vaccination were compared to the GMT at 5-9 years. RESULTS: The proportion of military service members with detectable neutralizing antibodies 10-14 years after a single dose of YF vaccine (95.8%, 95% CI 91.2-98.1%) was non-inferior to the proportion 5-9 years after vaccination (97.8%, 95% CI 93.7-99.3%). Additionally, GMT among vaccine recipients at 10-14 years post vaccination (99, 95% CI 82-121) was non-inferior to GMT in YF vaccine recipients at 5-9 years post vaccination (115, 95% CI 96-139). The proportion of vaccinees with neutralizing antibodies remained high, and non-inferior, among those vaccinated 15-19 years prior (98.5%, 95%CI 95.5-99.7%). Although the proportion seropositive decreased among vaccinees ≥ 20 years post vaccination, >90% remained seropositive. CONCLUSIONS: Neutralizing antibodies were present in > 95% of vaccine recipients for at least 19 years after vaccination, suggesting that booster doses every 10 years are not essential for most U.S. military personnel.

Immune response at 12-23 months following a single dose of Vero cell culture-derived Japanese encephalitis (JE) vaccine in adults previously vaccinated with mouse brain-derived JE vaccine.

BACKGROUND: Japanese encephalitis (JE) virus is an important cause of neurological disease in Asia. JE vaccine is recommended for travelers with higher JE risk itineraries. Inactivated Vero cell culture-derived JE vaccine (JE-VC) is the only JE vaccine currently available in the United States. An inactivated mouse brain-derived JE vaccine (JE-MB) previously was available but production was discontinued. One JE-VC dose administered to adults previously vaccinated with ≥3 doses of JE-MB provides good short-term protection for at least one month, but data on longer-term protection are limited. We evaluated non-inferiority of the JE virus neutralizing antibody response at 12-23 months in JE-MB-vaccinated adults administered one JE-VC dose compared with JE vaccine-naïve adults administered a JE-VC two-dose primary series. METHODS: We obtained archived sera from U.S. military personnel and performed a 50% plaque reduction neutralization test for anti-JE virus neutralizing antibodies. We compared the geometric mean titer (GMT) and seroprotection rate at 12-23 months after one JE-VC dose in previously JE-MB-vaccinated personnel and after the second JE-VC dose in previously JE vaccine-naïve personnel. Non-inferiority was concluded if the lower bound of the two-sided 95% confidence interval (CI) of the GMT ratio in previously vaccinated to vaccine-naïve personnel was >1/1.5. RESULTS: The GMT in previously JE-MB-vaccinated persons was 75 (95% CI 63-90) and in previously JE vaccine-naïve persons was 12 (95% CI 11-14), and seroprotection rates were 94% (235/250) and 54% (135/250), respectively. The ratio of GMTs was 6.3 (95% CI: 5.0-7.7), satisfying the criterion for non-inferiority. CONCLUSIONS: One JE-VC dose in previously JE-MB-vaccinated military personnel provides good protection for at least 1-2 years. The benefits of administration of a single JE-VC dose in previously JE-MB-vaccinated adults include a shorter time to completion of re-vaccination before travel, a decrease in the risk of adverse events, and reduced costs.

Health-related behaviors and effectiveness of trivalent inactivated versus live attenuated influenza vaccine in preventing influenza-like illness among young adults.

BACKGROUND: Vaccination is the preferred preventive strategy against influenza. Though health behaviors are known to affect immunity and vaccine delivery modes utilize different immune processes, data regarding the preferred influenza vaccine type among adults endorsing specific health-related behaviors (alcohol use, tobacco use, and exercise level) are limited. METHODS: The relative effectiveness of two currently available influenza vaccines were compared for prevention of influenza-like illness during 2 well-matched influenza seasons (2006/2007, 2008/2009) among US military personnel aged 18-49 years. Relative vaccine effectiveness was compared between those self-reporting and not reporting recent smoking history and potential alcohol problem, and by exercise level using Cox proportional hazard modeling adjusted for sociodemographic and military factors, geographic area, and other health behaviors. RESULTS: 28,929 vaccination events and 3936 influenza-like illness events over both influenza seasons were studied. Of subjects, 27.5% were smokers, 7.7% had a potential alcohol-related problem, 10.5% reported minimal exercise, and 4.4% reported high exercise levels. Overall, the risk of influenza-like illness did not significantly differ between live attenuated and trivalent inactivated influenza vaccine recipients (hazard ratio, 0.98; 95% confidence interval, 0.90-1.06). In the final adjusted model, the relative effectiveness of the 2 vaccine types did not differ by smoking status (p = 0.10), alcohol status (p = 0.21), or activity level (p = 0.11). CONCLUSIONS: Live attenuated and trivalent inactivated influenza vaccines were similarly effective in preventing influenza-like illness among young adults and did not differ by health-related behavior status. Influenza vaccine efforts should continue to focus simply on delivering vaccine.

Comparison of the effectiveness of trivalent inactivated influenza vaccine and live, attenuated influenza vaccine in preventing influenza-like illness among US military service members, 2006-2009.

BACKGROUND: Influenza is a significant cause of morbidity, and vaccination is the preferred preventive strategy. Data regarding the preferred influenza vaccine type among adults are limited. METHODS: The effectiveness of 2 currently available influenza vaccines LAIV and TIV in preventing influenza-like illness (ILI) was compared among US military members (aged 18-49 years) during 3 consecutive influenza seasons (2006-2009). ILI, influenza, and pneumonia events post-vaccination were compared between vaccine types using Cox proportional hazard models adjusted for sociodemographic factors, occupation, and geographic area. RESULTS: A total of 41 670 vaccination events were evaluated, including 28 929 during 2 "well-matched" seasons (2006-2007 and 2008-2009: LAIV n = 22 734, TIV n = 6195) and 12 741 during a suboptimally matched season due to mild antigenic drift (2007-2008: LAIV n = 9447, TIV n = 3294). ILI crude incidence rates for LAIV and TIV were 139 and 127 cases per 1000 person-seasons for the well-matched seasons, respectively, and 150 and 165 cases per 1000 person-seasons for the suboptimally matched season, respectively. In the multivariable models, there were no differences in ILI events by vaccine type (well-matched seasons: hazard ratio [HR], 0.97; 95% confidence interval [CI], .90-1.06; suboptimally matched season: HR, 1.00; 95% CI, .90-1.11). There were also no differences in influenza and/or pneumonia events by vaccine group. CONCLUSIONS: Between 2006 and 2009, TIV and LAIV had similar effectiveness in preventing ILI and influenza/pneumonia events among healthy adults.

Determination of clinical and demographic predictors of laboratory-confirmed influenza with subtype analysis.

BACKGROUND: Rapid influenza diagnosis is important for early identification of outbreaks, effective management of high-risk contacts, appropriate antiviral use, decreased inappropriate antibiotic use and avoidance of unnecessary laboratory testing. Given the inconsistent performance of many rapid influenza tests, clinical diagnosis remains integral for optimizing influenza management. However, reliable clinical diagnostic methods are not well-established. This study assesses predictors of influenza, and its various subtypes, in a broad population at the point of care, across age groups, then evaluates the performance of clinical case definitions composed of identified predictors. METHODS: Respiratory specimens and demographic and clinical data were obtained from 3- to 80-year-old US military family members presenting for care with influenza-like illness (ILI) from November 2007 to April 2008. Molecular and virus isolation techniques were used to detect and subtype influenza viruses. Associations between influenza diagnosis and demographic/clinical parameters were assessed by logistic regression, including influenza type and subtype analyses. The predictive values of multiple combinations of identified clinical predictors (case definitions), and the Centers for Disease Control and Prevention (CDC) ILI case definition, were estimated. RESULTS: Of 789 subjects, 220 (28%) had laboratory-confirmed influenza (51 A(H1), 46 A(H3), 19 A(unsubtypeable), 67 B, 1 AB coinfection), with the proportion of influenza A to B cases highest among 6- to 17-year-olds (p = 0.019). Independent predictors of influenza included fever, cough, acute onset, body aches, and vaccination status among 6- to 49-year-olds, only vaccination among 3- to 5-year-olds, and only fever among 50- to 80-year-olds. Among 6- to 49-year-olds, some clinical case definitions were highly sensitive (100.0%) or specific (98.6%), but none had both parameters over 60%, though many performed better than the CDC ILI case definition (sensitivity 37.7%, 95% confidence interval 33.6-41.9% in total study population). CONCLUSIONS: Patterns of influenza predictors differed across age groups, with most predictors identified among 6- to 49-year-olds. No combination of clinical and demographic predictors served as a reliable diagnostic case definition in the population and influenza season studied. A standardized clinical case definition combined with a point-of-care laboratory test may be the optimal rapid diagnostic strategy available.

Immunogenicity of one dose of Vero cell culture-derived Japanese encephalitis (JE) vaccine in adults previously vaccinated with mouse brain-derived JE vaccine.

BACKGROUND: There are no data on the use of inactivated Vero cell culture-derived Japanese encephalitis (JE) vaccine (JE-VC) as a booster among individuals who previously received inactivated mouse brain-derived JE vaccine (JE-MB). METHODS: Military personnel who received ≥3 doses of JE-MB or were JE vaccine-naïve were vaccinated with 2 doses of JE-VC on days 0 and 28. Serum neutralizing antibodies were measured pre-vaccination and 28 days after each dose. Non-inferiority was evaluated for seroprotection rate and geometric mean titer (GMT) between previously vaccinated participants post-dose 1 and vaccine-naïve participants post-dose 2. RESULTS: Fifty-three previously vaccinated and 70 JE vaccine-naïve participants were enrolled. Previously vaccinated participants had significantly higher GMTs pre-vaccination, post-dose 1, and post-dose 2. Seroprotection rates among previously vaccinated participants post-dose 1 (44/44, 100%) were noninferior to those achieved in previously naïve participants post-dose 2 (53/57, 93%). The GMT was significantly higher in previously vaccinated participants post-dose 1 (GMT 315; 95% CI 191-520) compared to previously naïve participants post-dose 2 (GMT 79; 95% CI 54-114). CONCLUSIONS: Among military personnel previously vaccinated with ≥3 doses of JE-MB, a single dose of JE-VC adequately boosts neutralizing antibody levels and provides at least short-term protection. Additional studies are needed to confirm these findings in other populations and determine the duration of protection following a single dose of JE-VC in prior recipients of JE-MB.