Suchergebnisse

BACKGROUND: Coccidioidomycosis ranges clinically from a self-limited respiratory illness to multi-organ dissemination. Based largely on skin testing from the 1940s, 60% of infections are thought to be asymptomatic. Limited Coccidioides seroincidence data support our understanding of the epidemiology and pathogenicity of this disease. METHODS: This retrospective cohort study tested 2000 U.S. military personnel for Coccidioides exposure after transfer to an endemic region of California between 2011 and 2017. The presence of IgG and IgM anti-Coccidioides antibodies were tested on pre- and post-transfer serum samples from the DoD Serum Repository to establish rates of seroconversion. Medical histories and participant demographics including race/ethnicity and military occupational specialty codes were collected from the electronic medical record and participants were stratified by a history of Coccidioides-specific or general respiratory illness based on ICD9/ICD10 coding. RESULTS: Thirty of 2000 participants tested newly positive for anti-Coccidioides antibodies after 12 months on station. Seroconversion incidence varied from 0.0-1.32 annually and overall 0.5 per 100 person years. Seroconverters were more frequently diagnosed with coccidioidomycosis or pneumonia than non-converters (p=0.027). No statistically significant association between demographic characteristics and seroconversion or disease was observed. Clinical disease was detected in only three seroconverters (10%). Incidence Rate of Coccidioidomycosis Infection among Active Duty Stationed at NAS Lemoore, 2011-2017 [Image: see text] Seroconversion Status by Cocci/Pneumonia Diagnosis Status [Image: see text] CONCLUSION: In this study Coccidioides seroincidence was similar to that observed by others, adding longitudinal evidence to epidemiologic assumptions about coccidioidomycosis. A trend toward increasing incidence over the course of the study is consistent with the classification of coccidioidomycosis as an emerging infectious disease. While transmission ...

BACKGROUND: Bloodstream infections (BSI) are associated with both inpatient mortality and substantial morbidity in the United States. We sought to characterize the epidemiology of BSIs with ESKAPE pathogens on patients served by the United States Military Healthcare System (MHS), which actively prospectively captures clinical and microbiological data from US service members and their beneficiaries. METHODS: We performed a retrospective analysis of MHS patients with blood cultures positive for ESKAPE pathogens (E. faecium, S. aureus, K. pneumoniae, A. baumannii, P. aeruginosa, and Enterobacter spp.), as well as Neisseria gonorrhoeae and Raoultella spp. between January 2010 and December 2015. Microbiological data from the Navy and Marine Core Public Health Center was retrospectively collated with clinical and demographic data from the MHS Data Repository. RESULTS: We identified 7,404 patients who experienced 8,791 episodes of ESKAPE (including N. gonorrhoeae and Raoultella spp.) BSI. The patients were predominately active duty (N=688) or retired (N=2,517) Armed Forces service members and their dependents (N=2,361). Further, 59.4% were male and 47.5% were >65 years old. A total of 5,594 (75.5%) of BSI episodes were associated with hospital admission, with an average length of stay of 14.9 days (SD of 27.5 days) and 47.4% (N=2,650) of those admissions were associated with an ICU stay averaging 8.6 days (SD of 18.0 days). The most common pathogens detected were E. coli (34.6%, N= 3,042) followed by S. aureus (28.0%,N=2,464), with 7.6% and 40.7% of isolates resistant to ceftriaxone and methicillin, respectively. We found a larger proportion of E. coli BSI in females (47.4% versus 26.2%) and S. aureus BSI in males (32% versus 21.9%). The frequency of A. baumannii BSI in younger patients, ages 18-30, was an average 4.5 fold higher than in older age groups (30-50, 50-65 and >65). CONCLUSION: We noted epidemiological differences in the burden of ESKAPE pathogen BSIs, in various populations including sex and age ...

BACKGROUND: While the majority of illness due to COVID-19 does not require hospitalization, little has been described about the host inflammatory response in the ambulatory setting. Differences in the levels of inflammatory signaling proteins between outpatient and hospitalized populations could identify key maladaptive immune responses during COVID-19. METHODS: Samples were collected from 76 participants (41% female, mean 46.8 years of age) enrolled at five military treatment facilities between March 20, 2020 and June 17, 2020 in an ongoing prospective COVID-19 cohort. This analysis was restricted to those with positive SARS-CoV-2 (severe acute respiratory syndrome–coronavirus 2) RT-PCR testing and included hospitalized (N=29; 10 requiring an ICU stay) and non-hospitalized (N=43) participants. Severity markers (IL6, D-dimer, procalcitonin, ferritin, ICAM-1, IL5, lipocalin, RAGE, TNFR, VEGFA, IFNγ, IL1β) were measured in plasma (mg/dL) using the Ella immunoassay and natural log transformed. Univariate negative binomial regression was performed to determine relative risk of hospitalization. Using the full marker panel, we performed a Principal Component Analysis (PCA) to determine directions of maximal variance in the data. Pearson's correlation coefficient was determined between analytes and each axis. RESULTS: Participants requiring ambulatory-, hospital-, and ICU-level care had samples collected at 44.0 (IQR: 35.0–51.0), 40.0 (13.0–51.0), and 47.5 (21.0–54.0) days, respectively. Higher unadjusted levels of IL6, D-dimer, procalcitonin, or ferritin were each associated with hospitalization (Table 1). The PCA showed a separation along axes between level of care and duration of symptoms (Fig 1). While significant correlations were noted with a number of biomarkers, PC1 most correlated with TNFR1 (r=0.88) and PC2 most correlated with IL6Ra (r=0.95). PC1 axis variation accounted for 36.5% of variance and the PC2 axis accounted for 20.0% of variance. Figure 1. Principal Component Analysis (PCA) of biomarkers by level ...

With growing concern of persistent or multiple waves of SARS-CoV-2 in the United States, sensitive and specific SARS-CoV-2 antibody assays remain critical for community and hospital-based SARS-CoV-2 surveillance. Here, we describe the development and application of a multiplex microsphere-based immunoassay (MMIA) for COVD-19 antibody studies, utilizing serum samples from non-human primate SARS-CoV-2 infection models, an archived human sera bank and subjects enrolled at five U.S. military hospitals. The MMIA incorporates prefusion stabilized spike glycoprotein trimers of SARS-CoV-2, SARS-CoV-1, MERS-CoV, and the seasonal human coronaviruses HCoV-HKU1 and HCoV-OC43, into a multiplexing system that enables simultaneous measurement of off-target pre-existing cross-reactive antibodies. We report the sensitivity and specificity performances for this assay strategy at 98% sensitivity and 100% specificity for subject samples collected as early as 10 days after the onset of symptoms. In archival sera collected prior to 2019 and serum samples from subjects PCR negative for SARS-CoV-2, we detected seroprevalence of 72% and 98% for HCoV-HKU1 and HCoV-0C43, respectively. Requiring only 1.25 μL of sera, this approach permitted the simultaneous identification of SARS-CoV-2 seroconversion and polyclonal SARS-CoV-2 IgG antibody responses to SARS-CoV-1 and MERS-CoV, further demonstrating the presence of conserved epitopes in the spike glycoprotein of zoonotic betacoronaviruses. Application of this serology assay in observational studies with serum samples collected from subjects before and after SARS-CoV-2 infection will permit an investigation of the influences of HCoV-induced antibodies on COVID-19 clinical outcomes.

Dihydroartemisinin-piperaquine, the current first-line drug for uncomplicated malaria caused by Plasmodium falciparum and Plasmodium vivax in Cambodia, was previously shown to be of benefit as malaria chemoprophylaxis when administered as a monthly 3-day regimen. We sought to evaluate the protective efficacy of a compressed monthly 2-day treatment course in the Royal Cambodian Armed Forces. The safety and efficacy of a monthly 2-day dosing regimen of dihydroartemisinin-piperaquine were evaluated in a two-arm, randomized, double-blind, placebo-controlled cohort study with 2:1 treatment allocation. Healthy military volunteers in areas along the Thai-Cambodian border where there is a high risk of malaria were administered two consecutive daily doses of 180 mg dihydroartemisinin and 1,440 mg piperaquine within 30 min to 3 h of a meal once per month for a planned 4-month period with periodic electrocardiographic and pharmacokinetic assessment. The study was halted after only 6 weeks (69 of 231 projected volunteers enrolled) when four volunteers met a prespecified cardiac safety endpoint of QTcF (Fridericia's formula for correct QT interval) prolongation of >500 ms. The pharmacodynamic effect on the surface electrocardiogram (ECG) peaked approximately 4 h after piperaquine dosing and lasted 4 to 8 h. Unblinded review by the data safety monitoring board revealed mean QTcF prolongation of 46 ms over placebo at the maximum concentration of drug in serum (Cmax) on day 2. Given that dihydroartemisinin-piperaquine is one of the few remaining effective antimalarial agents in Cambodia, compressed 2-day treatment courses of dihydroartemisinin-piperaquine are best avoided until the clinical significance of these findings are more thoroughly evaluated. Because ECG monitoring is often unavailable in areas where malaria is endemic, repolarization risk could be mitigated by using conventional 3-day regimens, fasting, and avoidance of repeated dosing or coadministration with other QT-prolonging medications. (This study has been ...

Malaria remains a public health problem in Thailand, especially along its borders where highly mobile populations can contribute to persistent transmission. This study aimed to determine resistant genotypes and phenotypes of 112 Plasmodium falciparum isolates from patients along the Thai-Cambodia border during 2013–2015. The majority of parasites harbored a pfmdr1-Y184F mutation. A single pfmdr1 copy number had CVIET haplotype of amino acids 72–76 of pfcrt and no pfcytb mutations. All isolates had a single pfk13 point mutation (R539T, R539I, or C580Y), and increased % survival in the ring-stage survival assay (except for R539I). Multiple copies of pfpm2 and pfcrt-F145I were detected in 2014 (12.8%) and increased to 30.4% in 2015. Parasites containing either multiple pfpm2 copies with and without pfcrt-F145I or a single pfpm2 copy with pfcrt-F145I exhibited elevated IC(90) values of piperaquine. Collectively, the emergence of these resistance patterns in Thailand near Cambodia border mirrored the reports of dihydroartemisinin-piperaquine treatment failures in the adjacent province of Cambodia, Oddar Meanchey, suggesting a migration of parasites across the border. As malaria elimination efforts ramp up in Southeast Asia, host nations militaries and other groups in border regions need to coordinate the proposed interventions.

BACKGROUND: We evaluated clinical outcomes, functional burden, and complications 1 month after coronavirus disease 2019 (COVID-19) infection in a prospective US Military Health System (MHS) cohort of active duty, retiree, and dependent populations using serial patient-reported outcome surveys and electronic medical record (EMR) review. METHODS: MHS beneficiaries presenting at 9 sites across the United States with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test, a COVID-19-like illness, or a high-risk SARS-CoV-2 exposure were eligible for enrollment. Medical history and clinical outcomes were collected through structured interviews and International Classification of Diseases–based EMR review. Risk factors associated with hospitalization were determined by multivariate logistic regression. RESULTS: A total of 1202 participants were enrolled. There were 1070 laboratory-confirmed SARS-CoV-2 cases and 132 SARS-CoV-2-negative participants. In the first month post–symptom onset among the SARS-CoV-2-positive cases, there were 212 hospitalizations, 80% requiring oxygen, 20 ICU admissions, and 10 deaths. Risk factors for COVID-19-associated hospitalization included race (increased for Asian, Black, and Hispanic compared with non-Hispanic White), age (age 45–64 and 65+ compared with <45), and obesity (BMI≥30 compared with BMI<30). Over 2% of survey respondents reported the need for supplemental oxygen, and 31% had not returned to normal daily activities at 1 month post–symptom onset. CONCLUSIONS: Older age, reporting Asian, Black, or Hispanic race/ethnicity, and obesity are associated with SARS-CoV-2 hospitalization. A proportion of acute SARS-CoV-2 infections require long-term oxygen therapy; the impact of SARS-CoV-2 infection on short-term functional status was substantial. A significant number of MHS beneficiaries had not yet returned to normal activities by 1 month.