Comparing Physician and Artificial Intelligence Chatbot Responses to Patient Questions Posted to a Public Social Media Forum.

Importance: The rapid expansion of virtual health care has caused a surge in patient messages concomitant with more work and burnout among health care professionals. Artificial intelligence (AI) assistants could potentially aid in creating answers to patient questions by drafting responses that could be reviewed by clinicians. Objective: To evaluate the ability of an AI chatbot assistant (ChatGPT), released in November 2022, to provide quality and empathetic responses to patient questions. Design, Setting, and Participants: In this cross-sectional study, a public and nonidentifiable database of questions from a public social media forum (Reddit's r/AskDocs) was used to randomly draw 195 exchanges from October 2022 where a verified physician responded to a public question. Chatbot responses were generated by entering the original question into a fresh session (without prior questions having been asked in the session) on December 22 and 23, 2022. The original question along with anonymized and randomly ordered physician and chatbot responses were evaluated in triplicate by a team of licensed health care professionals. Evaluators chose "which response was better" and judged both "the quality of information provided" (very poor, poor, acceptable, good, or very good) and "the empathy or bedside manner provided" (not empathetic, slightly empathetic, moderately empathetic, empathetic, and very empathetic). Mean outcomes were ordered on a 1 to 5 scale and compared between chatbot and physicians. Results: Of the 195 questions and responses, evaluators preferred chatbot responses to physician responses in 78.6% (95% CI, 75.0%-81.8%) of the 585 evaluations. Mean (IQR) physician responses were significantly shorter than chatbot responses (52 [17-62] words vs 211 [168-245] words; t = 25.4; P < .001). Chatbot responses were rated of significantly higher quality than physician responses (t = 13.3; P < .001). The proportion of responses rated as good or very good quality (≥ 4), for instance, was higher for chatbot than physicians (chatbot: 78.5%, 95% CI, 72.3%-84.1%; physicians: 22.1%, 95% CI, 16.4%-28.2%;). This amounted to 3.6 times higher prevalence of good or very good quality responses for the chatbot. Chatbot responses were also rated significantly more empathetic than physician responses (t = 18.9; P < .001). The proportion of responses rated empathetic or very empathetic (≥4) was higher for chatbot than for physicians (physicians: 4.6%, 95% CI, 2.1%-7.7%; chatbot: 45.1%, 95% CI, 38.5%-51.8%; physicians: 4.6%, 95% CI, 2.1%-7.7%). This amounted to 9.8 times higher prevalence of empathetic or very empathetic responses for the chatbot. Conclusions: In this cross-sectional study, a chatbot generated quality and empathetic responses to patient questions posed in an online forum. Further exploration of this technology is warranted in clinical settings, such as using chatbot to draft responses that physicians could then edit. Randomized trials could assess further if using AI assistants might improve responses, lower clinician burnout, and improve patient outcomes.

Clinical evaluation of the BioFire Global Fever Panel for the identification of malaria, leptospirosis, chikungunya, and dengue from whole blood: a prospective, multicentre, cross-sectional diagnostic accuracy study.

BACKGROUND: Acute febrile illness is a common presentation for patients at hospitals globally. Assays that can diagnose a variety of common pathogens in blood could help to establish a diagnosis for targeted disease management. We aimed to evaluate the performance of the BioFire Global Fever Panel (GF Panel), a multiplex nucleic acid amplification test performed on whole blood specimens run on the BioFire FilmArray System, in the diagnosis of several pathogens that cause acute febrile illness. METHODS: We did a prospective, multicentre, cross-sectional diagnostic accuracy study to evaluate the GF Panel. Consenting adults and children older than 6 months presenting with fever in the previous 2 days were enrolled consecutively in sub-Saharan Africa (Ghana, Kenya, Tanzania, Uganda), southeast Asia (Cambodia, Thailand), central and South America (Honduras, Peru), and the USA (Washington, DC; St Louis, MO). We assessed the performance of six analytes (chikungunya virus, dengue virus [serotypes 1-4], Leptospira spp, Plasmodium spp, Plasmodium falciparum, and Plasmodium vivax or Plasmodium ovale) on the GF Panel. The performance of the GF Panel was assessed using comparator PCR assays with different primers followed by bidirectional sequencing on nucleic acid extracts from the same specimen. We calculated the positive percent agreement and negative percent agreement of the GF Panel with respect to the comparator assays. This study is registered with ClinicalTrials.gov, NCT02968355. FINDINGS: From March 26, 2018, to Sept 30, 2019, 1965 participants were enrolled at ten sites worldwide. Of the 1875 participants with analysable results, 980 (52·3%) were female and the median age was 22 years (range 0-100). At least one analyte was detected in 657 (35·0%) of 1875 specimens. The GF Panel had a positive percent agreement for the six analytes evaluated as follows: chikungunya virus 100% (95% CI 86·3-100), dengue virus 94·0% (90·6-96·5), Leptospira spp 93·8% (69·8-99·8), Plasmodium spp 98·3% (96·3-99·4), P falciparum 92·7% (88·8-95·6), and P vivax or P ovale 92·7% (86·7-96·6). The GF Panel had a negative percent agreement equal to or greater than 99·2% (98·6-99·6) for all analytes. INTERPRETATION: This 1 h sample-to-answer, molecular device can detect common causative agents of acute febrile illness with excellent positive percent agreement and negative percent agreement directly in whole blood. The targets of the assay are prevalent in tropical and subtropical regions globally, and the assay could help to provide both public health surveillance and individual diagnoses. FUNDING: BioFire Defense, Joint Project Manager for Medical Countermeasure Systems and US Army Medical Materiel Development Activity, and National Institute of Allergy and Infectious Diseases.

Behavioral health and sleep problems among US Army veterinarians and veterinary technicians participating in the Millennium Cohort Study.

OBJECTIVE: To determine the prevalences and relative odds of mental health problems, suicidal ideation, psychotropic medication use, problem drinking, trouble sleeping, and lack of social support among veterinarians and veterinary technicians, compared with other medical professionals, in the US Army. SAMPLE: 7,744 US Army personnel (957 officers [101 veterinarians and 856 physicians and dentists] and 6,787 enlisted personnel [334 veterinary technicians and 6,453 medics]) participating in the Millennium Cohort Study. PROCEDURES: Eligible participants completed ≥ 1 survey while serving as an Army veterinarian, veterinary technician, physician, general dentist, or medic. Analysis methods including multivariable logistic regression adjusted for covariates and stratified by pay grade were used to investigate associations between each health-care occupation and outcomes of interest. RESULTS: Veterinarians had higher reported prevalences of mental health problems, trouble sleeping, and lack of social support than did nontrauma physicians, trauma physicians, or dentists. On multivariable analysis, veterinarians had higher odds of mental health problems, trouble sleeping, and lack of social support, compared with physicians and dentists combined; odds for these outcomes were also higher for veterinarians, compared with various individual reference groups. Veterinary technicians had lower reported prevalence and lower odds of psychotropic medication use, compared with medics. CONCLUSIONS AND CLINICAL RELEVANCE: Further examination of Army policies and organizational structures related to veterinarians may be warranted, along with the development of policies and interventions designed to improve mental health, sleep quality, and social support among military veterinarians.

Prospective safety surveillance study of ACAM2000 smallpox vaccine in deploying military personnel.

OBJECTIVES: To compare rates of myopericarditis, severe and serious dermatological or neurological events, and other adverse events in deploying US military personnel who received or did not receive ACAM2000® (Smallpox [Vaccinia] Vaccine, Live) vaccine and to evaluate potential risk factors for development of myopericarditis. METHODS: Prospective observational cohort study enrolling up to 15,000 ACAM2000 recipients (Cohort 1) and up to 5000 persons otherwise eligible for ACAM2000 vaccination but not vaccinated due to recency of vaccination or characteristics of their contacts (Cohort 2). Data and specimens were collected initially and 10 (6-17) days later. Those with clinical or laboratory evidence of possible myopericarditis were referred for further evaluation and adjudication by a blinded independent review committee. The adjusted odds ratio for myopericarditis was determined by a logistic regression model controlling for age, race, gender, and exercise regimen. RESULTS: 14,667 subjects provided initial data and specimens (Cohort 1, 10,825; Cohort 2, 3842); 12,110 (Cohort 1, 8945; Cohort 2, 3165) completed Visit 2 per-protocol. A total of 125 (Cohort 1, 111; Cohort 2, 14) were referred for myopericarditis adjudication, yielding 54 (Cohort 1, 44, Cohort 2, 10) subclinical myopericarditis, 5 suspected myocarditis, 1 confirmed myocarditis, and 1 suspected pericarditis. Unadjusted myopericarditis rates were: Cohort 1, 5.7/1000 (95% CI, 4.3-7.5); Cohort 2, 3.2/1000 (95% CI, 1.7-5.8). Unadjusted and adjusted odds ratios for myopericarditis were 1.8 (95% CI: 0.9-3.6) and 1.3 (95% CI: 0.6-2.6), respectively. One hundred seventeen subjects (1.1%) in Cohort 1 and 13 (0.3%) in Cohort 2 experienced at least 1 serious adverse event. No instances of serious and severe neurological or dermatological adverse events were reported. CONCLUSIONS: In this carefully screened, generally young and healthy service-member population, ACAM2000 vaccination was associated with modest non-significant increases in the risk of myopericarditis (adjusted OR, 1.3; unadjusted OR, 1.8); all but seven cases were subclinical. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT00928577.

Mental health, physical health, and health-related behaviors of U.S. Army Special Forces.

OBJECTIVES: To prospectively examine the health and health-related behaviors of Army Special Forces personnel in comparison with two distinct, but functionally similar Army groups. METHODS: Special Forces, Ranger Qualified, and General Purposes Forces enrolled in the Millennium Cohort Study were identified using data from the Defense Manpower Data Center. Using prospective survey data (2001-2014), we estimated the association of Army specialization with mental health, social support, physical health, and health-related behaviors with multivariable regression models. RESULTS: Among the 5,392 eligible participants (84.4% General Purposes Forces, 10.0% Special Forces, 5.6% Ranger Qualified), Special Forces personnel reported the lowest prevalence of mental disorders, physical health problems, and unhealthy behaviors. In the multivariable models, Special Forces personnel were less likely to report mental health problems, multiple somatic symptoms, and unhealthy behaviors compared with General Purpose Forces infantrymen (odds ratios [OR]: 0.20-0.54, p-values < .01). Overall, Special Forces personnel were similar in terms of mental and physical health compared with Ranger Qualified infantrymen, but were less likely to sleep < 5 hours/night (OR: 0.60, 95% confidence intervals: 0.40, 0.92) and have 5 or more multiple somatic symptoms (OR: 0.69, 95% CI: 0.49, 0.98). Both Special Forces personnel and Ranger Qualified infantrymen engaged in more healthy behaviors compared with General Purpose Forces infantrymen (OR: 2.57-6.22, p-values<0.05). Engagement in more healthy behaviors reduced the odds of subsequent adverse health outcomes, regardless of specialization. CONCLUSIONS: Army Special Forces personnel were found to be mentally and physically healthier than General Purpose Forces infantrymen, which may in part be due to their tendency to engage in healthy behaviors. Findings indicate that engagement in a greater number of healthy behaviors may reduce odds for subsequent adverse outcomes.

Postpartum Fitness and Body Mass Index Changes in Active Duty Navy Women.

INTRODUCTION: Active duty Navy women participate in biannual Physical Fitness Assessments (PFAs), which include height and weight measurements and a Physical Readiness Test (PRT). PFAs are waived during pregnancy and resume the cycle after 6 months following maternity leave. The purpose of this study was to compare changes in PFA results over time between women who had or did not have a live birth during the follow-up period, and identify characteristics of women with lower PFA results postpartum. MATERIALS AND METHODS: This longitudinal study included 14,142 active duty Navy women, aged 19-40 years, with PFA results during July 2011-June 2015. Multivariable logistic regression, Stuart-Maxwell tests, and mixed effects modeling were used to examine changes in PRT scores and body mass index over time between women with and without a live birth during follow-up. All data were analyzed in 2017. This study was approved by the institutional review boards at the Uniformed Services University Office of Research and the Naval Health Research Center, and informed consent was waived in accordance with 32 CFR § 219.116(d). RESULTS: Postpartum women had increased odds of PRT failures (AOR = 3.88, 95% CI: 1.44-10.40) and lower PRT scores (AOR = 1.47, 95% CI: 1.12-1.92) up to 2.5 years postpartum, versus women without a live birth. Being enlisted, obese/overweight prepregnancy, and younger were risk factors for suboptimal PFA outcomes. Mean core strength and cardiovascular endurance, but not upper body strength, scores were significantly lower in postpartum women at 1 year postpartum versus women without a live birth. CONCLUSIONS: Our findings show that additional interventions may be needed to assist women in returning to prepregnancy fitness up to 1 year postpartum. Future studies should examine additional factors that may improve postpartum fitness in addition to enhancing maternity leave policies.

Seasonal Influenza Vaccine Impact on Pandemic H1N1 Vaccine Efficacy.

BACKGROUND: In 2009, a novel influenza A (pH1N1) was identified, resulting in a pandemic with significant morbidity and mortality. A monovalent pH1N1 vaccine was separately produced in addition to the seasonal trivalent influenza vaccine. Formulation of the seasonal influenza vaccine (injectable trivalent inactivated influenza vaccine [TIV] vs. intranasal live, attenuated influenza vaccine [LAIV]) was postulated to have impacted the efficacy of the pH1N1 vaccination. METHODS: We reviewed electronic health and databases, which included vaccination records, and healthcare encounters for influenza-like illness (ILI), influenza, and pneumonia among US military members. We examined rates by vaccination type to identify factors associated with the risk for study outcomes. RESULTS: Compared with those receiving the seasonal influenza vaccine alone, subjects receiving the pH1N1 vaccine, either alone (RR, 0.49) or in addition to the seasonal vaccine (RR, 0.51), had an approximately 50% reduction in ILI, 88% reduction in influenza (RR, 0.11 and 0.12, respectively), and 63% reduction in pneumonia (RR, 0.37 and 0.35, respectively). There was no clinically significant difference in ILI, influenza, or pneumonia attack rates among those receiving the pH1N1 vaccine with or without presence of the seasonal vaccine. Similarly, there was no clinically relevant difference in pH1N1 effectiveness between seasonal TIV and LAIV recipients. CONCLUSIONS: During the 2009-2010 pandemic, the pH1N1 vaccination was effective in reducing rates of ILI, influenza, and pneumonia. Administration of the seasonal vaccine should continue without concern of potential interference with a novel pandemic vaccine, though more studies are needed to determine if this is applicable to other influenza seasons.

New-Onset Asthma and Combat Deployment: Findings From the Millennium Cohort Study.

Recent reports suggest US military service members who deployed in support of the recent conflicts in Iraq and Afghanistan have higher rates of new-onset asthma than those who did not deploy. However, it is unknown whether combat experiences, in addition to deployment, contribute to new-onset asthma risk. This study aimed to longitudinally determine the risk factors for developing asthma, including combat deployment (categorized as deployed with combat experience, deployed without combat experience, or nondeployed), among participants in the Millennium Cohort Study from 2001 to 2013. A total of 75,770 participants completed a baseline survey and at least 1 triennial follow-up survey on deployment experiences, lifestyle characteristics, and health outcomes. Complementary log-log models stratified by sex were used to estimate the relative risk of developing asthma among participants who reported no history of asthma at baseline. In models with adjustments, those who deployed with combat experience were 24%-30% more likely to develop asthma than those who did not deploy. Deployed personnel without combat experience were not at a higher risk for new-onset asthma compared with nondeployers. Further research is needed to identify specific features of combat that are associated with greater asthma risk to inform prevention strategies.

Department of Defense Birth and Infant Health Registry: select reproductive health outcomes, 2003-2014.

Established following a 1998 directive, the Department of Defense Birth and Infant Health Registry (Registry) team conducts surveillance of select reproductive health outcomes among military families. Data are compiled from the Military Health System Data Repository and Defense Manpower Data Center to define the Registry cohort and outcomes of interest. Outcomes are defined using ICD-9/ICD-10 and Current Procedural Terminology codes, and include: pregnancy outcomes (e.g., live births, losses), birth defects, preterm births, and male:female infant sex ratio. This report includes data from 2003-2014 on 1,304,406 infants among military families and 258,332 pregnancies among active duty women. Rates of common adverse infant and pregnancy outcomes were comparable to or lower than those in the general US population. These observations, along with prior Registry analyses, provide reassurance that military service is not independently associated with increased risks for select adverse reproductive health outcomes. The Registry's diverse research portfolio demonstrates its unique capabilities to answer a wide range of questions related to reproductive health. These data provide the military community with information to identify successes and areas for improvement in prevention and care.

Immune Responses in U.S. Military Personnel Who Received Meningococcal Conjugate Vaccine (MenACWY) Concomitantly with Other Vaccines Were Higher than in Personnel Who Received MenACWY Alone.

Immunological responses to vaccination can differ depending on whether the vaccine is given alone or with other vaccines. This study was a retrospective evaluation of the immunogenicity of a tetravalent meningococcal conjugate vaccine for serogroups A, C, W, and Y (MenACWY) administered alone (n = 41) or concomitantly with other vaccines (n = 279) to U.S. military personnel (mean age, 21.6 years) entering the military between 2006 and 2008. Concomitant vaccines included tetanus/diphtheria (Td), inactivated polio vaccine (IPV), hepatitis vaccines, and various influenza vaccines, among others; two vaccine groups excluded Tdap and IPV. Immune responses were evaluated in baseline and postvaccination sera for Neisseria meningitidis serogroups C and Y 1 to 12 months (mean, 4.96 months) following vaccination. Functional antibodies were measured by using a serum bactericidal antibody assay with rabbit complement (rSBA) and by measurement of serogroup-specific immunoglobulin G (IgG) antibodies. The percentage of vaccinees reaching threshold levels (IgG concentration in serum, ≥2 µg/ml; rSBA titer, ≥8) corresponding to an immunologic response was higher postvaccination than at baseline (P < 0.001). Administration of MenACWY along with other vaccines was associated with higher geometric means of IgG concentrations and rSBA titers than those measured 4.60 months after a single dose of MenACWY. In addition, higher percentages of vaccinees reached the immunological threshold (range of odds ratios [ORs], 1.5 to 21.7) and more of them seroconverted (OR range, 1.8 to 4.8) when MenACWY was administered with any other vaccine than when administered alone. Additional prospective randomized clinical trials are needed to confirm the observed differences among groups in the immune response to MenACWY when given concomitantly with other vaccines to U.S. military personnel.

Effect of multiple, simultaneous vaccines on polio seroresponse and associated health outcomes.

BACKGROUND: Administration of multiple simultaneous vaccines to infants, children, and military recruits is not uncommon. However, little research exists to examine associated serological and health effects, especially in adults. METHOD: We retrospectively examined 416 paired serum specimens from U.S. military subjects who had received the inactivated polio vaccine (IPV) alone or in combination with either 1 other vaccine (<3 group) or 4 other vaccines (>4 group). Each of the 2 groups was subdivided into 2 subgroups in which Tdap was present or absent. RESULTS: The >4 group was associated with a higher proportion of polio seroconversions than the <3 group (95% vs. 58%, respectively, p<0.01). Analysis of the <3 subgroup that excluded Tdap vs. the >4 subgroup that excluded Tdap showed no difference between them (p>0.1). However, the >4 subgroup that included Tdap had significantly more seroconversions than either the <3 subgroup that excluded Tdap or the >4 subgroup that excluded Tdap (p<0.01). Overall, at least 98% of subjects were at or above the putative level of seroprotection both pre- and post-vaccination, yet at least 81% of subjects seroconverted. In an analysis of 400 of the subjects in which clinic in- and outpatient encounters were counted over the course of 1 year following vaccinations, there was no significant difference between the 2 groups (p>0.1). CONCLUSION: A combination of >4 vaccines including IPV appeared to have an immunopotentiation effect on polio seroconversion, and Tdap in particular was a strong candidate for an important role. The dose of IPV we studied in our subjects, who already had a high level of seroprotection, acted as a booster. In addition, there appear to be no negative health consequences from receiving few versus more multiple simultaneous vaccinations.

A population pharmacokinetic modeling approach shows that serum penicillin G concentrations are below inhibitory concentrations by two weeks after benzathine penicillin G injection in the majority of young adults.

Serum penicillin G falls to low levels 2 weeks after injection as benzathine penicillin G (BPG) in young adults. Using Pmetrics and previously reported penicillin G pharmacokinetic data after 1.2 million units were given as BPG to 329 male military recruits, here we develop the first reported population pharmacokinetic model of penicillin G after BPG injection. We simulated time-concentration profiles over a broad range of pediatric and adult weights after alternative doses and dose frequencies to predict the probability of maintaining serum penicillin G concentrations of >0.02 mg/liter, a proposed protective threshold against group A Streptococcus pyogenes (GAS). The final population model included linear absorption into a central compartment, distribution to and from a peripheral compartment, and linear elimination from the central compartment, with allometrically scaled volumes and rate constants. With 1.2 million units of BPG given intramuscularly every 4 weeks in four total doses, only 23.2% of 5,000 simulated patients maintained serum penicillin G trough concentrations of >0.02 mg/liter 4 weeks after the last dose. When the doses were 1.8 million units and 2.4 million units, the percentages were 30.2% and 40.7%, respectively. With repeated dosing of 1.2 million units every 3 weeks and every 2 weeks for 4 doses, the percentages of simulated patients with a penicillin G trough concentration of >0.02 mg/liter were 37.8% and 65.2%, respectively. Our simulations support recommendations for more frequent rather than higher BPG doses to prevent recurrent rheumatic heart disease in areas of high GAS prevalence or during outbreaks.

Dramatic decline of respiratory illness among US military recruits after the renewed use of adenovirus vaccines.

BACKGROUND: In late 2011, after a 12-year hiatus, oral vaccines against adenovirus types 4 (Ad4) and 7 (Ad7) were again produced and administered to US military recruits. This study examined the impact of the new adenovirus vaccines on febrile respiratory illness (FRI) and adenovirus rates and investigated if new serotypes emerged. FRI rates and their associated hospitalizations had markedly risen since vaccine production ceased in 1999. METHODS: From 1996 to 2013, the Naval Health Research Center conducted FRI surveillance at 8 military recruit training centers in the United States. During this period, 58 103 FRI pharyngeal swab specimens were studied, yielding 37 048 adenovirus-positive cases, among which 64% were typed. RESULTS: During the 2 years after reintroduction of the vaccines, military trainees experienced a 100-fold decline in adenovirus disease burden (from 5.8 to 0.02 cases per 1000 person-weeks, P < .0001), without evidence that vaccine pressure had increased the impact of adenovirus types other than Ad4 and Ad7. Although the percentage of type 14 increased following reintroduction of the vaccination, the actual number of cases decreased. We estimate that the vaccines prevent approximately 1 death, 1100-2700 hospitalizations, and 13 000 febrile adenovirus cases each year among the trainees. CONCLUSIONS: These data strongly support the continued production and use of Ad4 and Ad7 vaccines in controlling FRI among US military trainees. Continued surveillance for emerging adenovirus subtypes is warranted.

Persistence of serogroup C antibody responses following quadrivalent meningococcal conjugate vaccination in United States military personnel.

Serogroup C meningococcal (MenC) disease accounts for one-third of all meningococcal cases and causes meningococcal outbreaks in the U.S. Quadrivalent meningococcal vaccine conjugated to diphtheria toxoid (MenACYWD) was recommended in 2005 for adolescents and high risk groups such as military recruits. We evaluated anti-MenC antibody persistence in U.S. military personnel vaccinated with either MenACYWD or meningococcal polysaccharide vaccine (MPSV4). Twelve hundred subjects vaccinated with MenACYWD from 2006 to 2008 or MPSV4 from 2002 to 2004 were randomly selected from the Defense Medical Surveillance System. Baseline serologic responses to MenC were assessed in all subjects; 100 subjects per vaccine group were tested during one of the following six post-vaccination time-points: 5-7, 11-13, 17-19, 23-25, 29-31, or 35-37 months. Anti-MenC geometric mean titers (GMT) were measured by rabbit complement serum bactericidal assay (rSBA) and geometric mean concentrations (GMC) by enzyme-linked immunosorbent assay (ELISA). Continuous variables were compared using the Wilcoxon rank sum test and the proportion of subjects with an rSBA titer ≥ 8 by chi-square. Pre-vaccination rSBA GMT was <8 for the MenACWYD group. rSBA GMT increased to 703 at 5-7 months post-vaccination and decreased by 94% to 43 at 3 years post-vaccination. GMT was significantly lower in the MenACWYD group at 5-7 months post-vaccination compared to the MPSV4 group. The percentage of MenACWYD recipients achieving an rSBA titer of ≥ 8 decreased from 87% at 5-7 months to 54% at 3 years. There were no significant differences between vaccine groups in the proportion of subjects with a titer of ≥ 8 at any time-point. GMC for the MenACWYD group was 0.14 µg/mL at baseline, 1.07 µg/mL at 5-7 months, and 0.66 µg/mL at 3 years, and significantly lower than the MPSV4 group at all time-points. Anti-MenC responses wane following vaccination with MenACYWD; a booster dose is needed to maintain protective levels of circulating antibody.

Seroepidemiologic survey for Coxiella burnetii among US military personnel deployed to Southwest and Central Asia in 2005.

We used a seroepidemiologic study to estimate Q fever (Coxiella burnetii) seroprevalence, seroincidence, and risk factors for seroconversion in two deployed military populations in 2005. The first study group resided in an area with a known Q fever outbreak history (Al Asad, Iraq). Of this population, 7.2% seroconverted for an incidence rate of 10.6 seroconversions per 1,000 person-months. The second population included personnel transiting through Qatar on mid-deployment leave from southwest/central Asia. In this group, we found 2.1% prevalence with 0.92 seroconversions per 1,000 person-months. However, no significant risk factors for Q fever seroconversion were found in either population.

A phase 3, randomized, double-blind, placebo-controlled study of the safety and efficacy of the live, oral adenovirus type 4 and type 7 vaccine, in U.S. military recruits.

Adenovirus (ADV) types 4 (ADV-4) and 7 (ADV-7) are presently the major cause of febrile acute respiratory disease (ARD) in U.S. military recruits. We conducted a multi-center, randomized, double-blind, placebo-controlled phase 3 study of the new vaccine to assess its safety and efficacy. Healthy adults at two basic training sites were randomly assigned to receive either vaccine (two enteric-coated tablets consisting of no less than 4.5 log10 TCID50 of live ADV-4 or ADV-7) or placebo in a 3:1 ratio. Volunteers were observed throughout the approximate eight weeks of their basic training and also returned for four scheduled visits. The primary endpoints were prevention of febrile ARD due to ADV-4 and seroconversion of neutralizing serum antibodies to ADV-7, which was not expected to circulate in the study population during the course of the trial. A total of 4151 volunteers were enrolled and 4040 (97%) were randomized and included in the primary analysis (110 were removed prior to randomization and one was removed after randomization due to inability to swallow tablets). A total of 49 ADV-4 febrile ARD cases were identified with 48 in the placebo group and 1 in the vaccine group (attack rates of 4.76% and 0.03%, respectively). Vaccine efficacy was 99.3% (95% CI, 96.0-99.9; P<0.001). Seroconversion rates for vaccine recipients for ADV-4 and ADV-7 were 94.5% (95% CI, 93.4-95.5%) and 93.8% (95% CI: 93.4-95.2%), respectively. The vaccine was well tolerated as compared to placebo. We conclude that the new live, oral ADV-4 and ADV-7 vaccine is safe and effective for use in groups represented by the study population.

Seroepidemiologic investigation of an outbreak of pandemic influenza A H1N1 2009 aboard a US Navy vessel--San Diego, 2009.

BACKGROUND: During summer 2009, a US Navy ship experienced an influenza-like illness outbreak with 126 laboratory-confirmed cases of pandemic influenza A (H1N1) 2009 virus among the approximately 2000-person crew. METHODS: During September 24-October 9, 2009, a retrospective seroepidemiologic investigation was conducted to characterize the outbreak. We administered questionnaires, reviewed medical records, and collected post-outbreak sera from systematically sampled crewmembers. We used real-time reverse transcription-PCR or microneutralization assays to detect evidence of H1N1 virus infection. RESULTS: Retrospective serologic data demonstrated that the overall H1N1 virus infection attack rate was 32%. Weighted H1N1 virus attack rates were higher among marines (37%), junior-ranking personnel (34%), and persons aged 19-24 years (36%). In multivariable analysis, a higher risk of illness was found for women versus men (odds ratio [OR] = 2.2; 95% confidence interval [CI]: 1.1-4.4), marines versus navy personnel (OR = 1.7; 95% CI, 1.0-2.9), and those aged 19-24 versus ≥ 35 years (OR = 3.9; 95% CI, 1.2-12.8). Fifty-three percent of infected persons did not recall respiratory illness symptoms. Among infected persons, only 35% met criteria for acute respiratory illness and 11% for influenza-like illness. CONCLUSIONS: Approximately half of H1N1 infections were asymptomatic, and thus, the attack rate was higher than estimated by clinical illness alone. Enhanced infection control measures including pre-embarkation illness screening, improved self-reporting of illness, isolation of ill and quarantine of exposed contacts, and prompt antiviral chemoprophylaxis and treatment might be useful in controlling shipboard influenza outbreaks.

Trends in meningococcal disease in the United States military, 1971-2010.

Meningococci have historically caused extensive illness among members of the United States military. Three successive meningococcal vaccine types were used from 1971 through 2010; overall disease incidence dropped by >90% during this period. During 2006-2010, disease incidence of 0.38 (cases per 100,000 person-years) among members of the US military was not significantly different from the incidence of 0.26 among the age-matched US general population. Of the 26 cases in the US military, 5 were fatal, 15 were vaccine failures (e.g., illness in a person who had been vaccinated), and 9 were caused by Neisseria meningitidis serogroup Y. Incidences among 17- to 19-year-old basic trainees and among US Marines were significantly higher than among comparison military populations (p<0.05). No apparent change in epidemiology of meningococcal disease was observed after replacement of quadrivalent polysaccharide vaccine with conjugate vaccine in 2007. The data demonstrate that vaccination with meningococcal vaccine is effective.

Postinfectious gastrointestinal disorders following norovirus outbreaks.

BACKGROUND: The US Centers for Disease Control and Prevention estimates 20.9 million norovirus infections annually in the United States. Although the acute disease burden is sizeable, emerging data suggest norovirus may be associated with chronic gastrointestinal problems. We identified known outbreaks in US military recruits and used the Defense Medical Encounter Database (DMED) to identify the risk of new onset functional gastrointestinal disorders (FGD) and gastroesophageal reflux disease (GERD). METHODS: Subjects reporting for care of acute gastroenteritis (AGE) at a military treatment clinic during 3 known norovirus outbreaks were identified. Each AGE subject was matched with up to 4 subjects with unrelated medical encounters. Medical encounter data were analyzed for the duration of military service time (or a minimum of 1 year) to assess for incident FGD or GERD. Relative risks were calculated using regression models. RESULTS: We identified 1718 subjects from 3 outbreaks. After controlling for important demographic covariates, the incidence of constipation, dyspepsia, and GERD was approximately 1.5-old higher (P < .01) in AGE-exposed subjects than matched subjects. We also noted variability in outcome incidence across outbreaks. CONCLUSIONS: It appears that the risk of dyspepsia, constipation, and GERD are higher among those who have AGE during a confirmed norovirus outbreak. Although these findings need confirmation, they suggest that dysmotility may result subsequent to these infections. If confirmed, the costs and morbidity associated with the chronic consequences of norovirus should be considered.