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The role that inhaled particulate matter plays in the development of post-deployment lung disease among US service members deployed to Southwest Asia during the Global War on Terrorism has been difficult to define. There is a persistent gap in data addressing the relationship between relatively short-term (months to a few years) exposures to high levels of particulate matter during deployment and the subsequent development of adverse pulmonary outcomes. Surgical lung biopsies from deployed service members and veterans (DSMs) and non-deployed service members and veterans (NDSMs) who develop lung diseases can be analyzed to potentially identify residual deployment-specific particles and develop associations with pulmonary pathological diagnoses. We examined 52 surgical lung biopsies from 25 DSMs and 27 NDSMs using field emission scanning electron microscopy (FE-SEM) with energy dispersive x-ray spectroscopy (EDS) to identify any between-group differences in the number and composition of retained inorganic particles, then compared the particle analysis results with the original histopathologic diagnoses. We recorded a higher number of total particles in biopsies from DSMs than from NDSMs, and this difference was mainly accounted for by geologic clays (illite, kaolinite), feldspars, quartz/silica, and titanium-rich silicate mixtures. Biopsies from DSMs deployed to other Southwest Asia regions (SWA-Other) had higher particle counts than those from DSMs primarily deployed to Iraq or Afghanistan, due mainly to illite. Distinct deployment-specific particles were not identified. Particles did not qualitatively associate with country of deployment. The individual diagnoses of the DSMs and NDSMs were not associated with elevated levels of total particles, metals, cerium oxide, or titanium dioxide particles. These results support the examination of particle-related lung disease in DSMs in the context of comparison groups, such as NDSMs, to assist in determining the strength of associations between specific pulmonary pathology diagnoses and deployment-specific inorganic particulate matter exposure.

Evidence suggests excess head and neck adipose tissue contributes to OSA, particularly in obese patients. Surgical treatments are often ineffective in this subset of the population. We sought to investigate the role of tongue fat in the normal and overweight populations. In this prospective cohort study, patients underwent overnight polysomnography and MRI using a Dixon sequence. Volumetric reconstruction evaluated the size and distribution of tongue fat deposits in subjects with and without sleep apnea. The study included 86 patients; mean age of 42.2 (SD 11.2) years, 16% female. Average BMI 27.5 kg/m 2 (SD 2.9), with 18.6% ( n  = 16) normal BMI, 61.6% ( n  = 53) overweight, 19.8% ( n  = 17) obese. Logistic regression lines showed positive associations for BMI and age with AHI. No significant correlation was found between tongue fat volume or fraction and increased AHI nor presence of OSA. Although tongue volume and fat fraction were higher in patients with AHI ≥ 5 events per hour, the difference was not statistically significant. This study suggests that tongue fat does not play a significant role in the pathophysiology of OSA in the non-obese (BMI < 30) patient population. Therefore, selective treatments targeting tongue fat should focus on obese and morbidly obese patients.

Pneumococcal colonization prevalence and colonization density, which has been associated with invasive disease, can offer insight into local pneumococcal ecology and help inform vaccine policy discussions. The Pneumonia Etiology Research for Child Health Project (PERCH), a multi-country case-control study, evaluated the etiology of hospitalized cases of severe and very severe pneumonia among children aged 1-59 months. The PERCH Thailand site enrolled children during January 2012-February 2014. We determined pneumococcal colonization prevalence and density, and serotype distribution of colonizing isolates. We enrolled 224 severe/very severe pneumonia cases and 659 community controls in Thailand. Compared to controls, cases had lower colonization prevalence (54.5% vs. 62.5%, p = 0.12) and lower median colonization density (42.1 vs. 210.2 x 103 copies/mL, p <0.0001); 42% of cases had documented antibiotic pretreatment vs. 0.8% of controls. In no sub-group of assessed cases did pneumococcal colonization density exceed the median for controls, including cases with no prior antibiotics (63.9x103 copies/mL), with consolidation on chest x-ray (76.5x103 copies/mL) or with pneumococcus detected in whole blood by PCR (9.3x103 copies/mL). Serotype distribution was similar among cases and controls, and a high percentage of colonizing isolates from cases and controls were serotypes included in PCV10 (70.0% and 61.8%, respectively) and PCV13 (76.7% and 67.9%, respectively). Pneumococcal colonization is common among children aged <5 years in Thailand. However, colonization density was not higher among children with severe pneumonia compared to controls. These results can inform discussions about PCV introduction and provide baseline data to monitor PCV impact after introduction in Thailand.

Background Non-battle related musculoskeletal injuries (MSKI) are one of the primary medical issues diminishing Service member medical readiness. The MSKI problem is challenging because it is difficult to assess all of the factors that increase MSKI risk and influence post-MSKI outcomes. Currently, there are no high-throughput, clinically-feasible, and comprehensive assessments to generate patient-centric data for informing pre- and post-MSKI risk assessment and mitigation strategies. The objective of the “Pre-neuromusculoskeletal injury Risk factor Evaluation and Post-neuromusculoskeletal injury Assessment for Return-to-duty/activity Enhancement (PREPARE)” study is to develop a comprehensive suite of clinical assessments to identify the patient-specific factors contributing to MSKI risks and undesired post-MSKI outcomes. Methods This is a phased approach, multi-center prospective, observational study (ClinicalTrials.gov number: NCT05111925) to identify physical and psychosocial factors contributing to greater MSKI risk and undesired post-MSKI outcomes, and to identify and validate a minimal set of assessments to personalize risk mitigation and rehabilitation strategies. In Phase I, one cohort (n = 560) will identify the physical and psychosocial factors contributing to greater MSKI risks (single assessment), while a second cohort (n = 780) will identify the post-MSKI physical and psychosocial factors contributing to undesired post-MSKI outcomes (serial assessments at enrollment, 4 weeks post-enrollment, 12 weeks post-enrollment). All participants will complete comprehensive movement assessments captured via a semi-automated markerless motion capture system and instrumented walkway, joint range of motion assessments, psychosocial measures, and self-reported physical fitness performance and MSKI history. We will follow participants for 6 months. We will identify the minimum set of clinical assessments that provide requisite data to personalize MSKI risk mitigation and rehabilitation strategies, and in Phase II validate our optimized assessments in new cohorts. Discussion The results of this investigation will provide clinically relevant data to efficiently inform MSKI risk mitigation and rehabilitation programs, thereby helping to advance medical care and retain Service members on active duty status. Trial Registration : PREPARE was prospectively registered on ClinicalTrials.gov (NCT05111925) on 5 NOV 2021, prior to study commencement.

Malariometric parameters are often primary endpoints of efficacy trials of malaria vaccine candidates. This study aims to describe the epidemiology of malaria prior to the conduct of a series of drug and vaccine trials in a rural area of Burkina Faso. Malaria incidence was prospectively evaluated over one year follow-up among two cohorts of children aged 0-5 years living in the Saponé health district. The parents of 1089 children comprising a passive case detection cohort were encouraged to seek care from the local health clinic at any time their child felt sick. Among this cohort, 555 children were randomly selected for inclusion in an active surveillance sub-cohort evaluated for clinical malaria during twice weekly home visits. Malaria prevalence was evaluated by cross-sectional survey during the low and high transmission seasons. Number of episodes per child ranged from 0 to 6 per year. Cumulative incidence was 67.4% in the passive and 86.2% in the active cohort and was highest among children 0-1 years. Clinical malaria prevalence was 9.8% in the low and 13.0% in the high season (p>0.05). Median days to first malaria episode ranged from 187 (95% CI 180-193) among children 0-1 years to 228 (95% CI 212, 242) among children 4-5 years. The alternative parasite thresholds for the malaria case definition that achieved optimal sensitivity and specificity (70-80%) were 3150 parasites/µl in the high and 1350 parasites/µl in the low season. Clinical malaria burden was highest among the youngest age group children, who may represent the most appropriate target population for malaria vaccine candidate development. The pyrogenic threshold of parasitaemia varied markedly by season, suggesting a value for alternative parasitaemia levels in the malaria case defintion. Regional epidemiology of malaria described, Sapone area field centers are positioned for future conduct of malaria vaccine trials.

Objective The objective of this study is to evaluate patient and provider satisfaction with telemedicine encounters across 3 otolaryngology practices. Study Design Cross-sectional survey. Setting A military community hospital, an academic military hospital, and a nonmilitary academic center. Methods A telephone-based survey of patients undergoing telemedicine encounters for routine otolaryngology appointments was performed between April and July 2020. Patients were asked about their satisfaction, the factors affecting care, and demographic information. A provider survey was emailed to staff otolaryngologists. The survey asked about satisfaction, concerns for reimbursement or liability, encounters best suited for telemedicine, and demographic information. The results were analyzed with descriptive statistics and a multivariable logistic linear regression model to determine odds ratios. Results A total of 325 patients were surveyed, demonstrating high satisfaction with telemedicine (average score, 4.49 of 5 [best possible answer]). Patients perceived “no negative impact” or “minor negative impact” on the encounter due to the lack of a physical examination or face-to-face interaction (1.86 and 1.95 of 5, respectively). High satisfaction was consistent across groups for distance to travel, age, and reason for referral. A total of 25 providers were surveyed, with an average satisfaction score of 3.44 of 5. Providers reported “slight” to “somewhat” concern about reimbursement (40%) and liability (32%). Conclusion Given patients’ and providers’ levels of satisfaction, there is likely a role for telemedicine in otolaryngology practice that may benefit patient care independent of the COVID-19 pandemic.

Ad35.CS.01 is a pre-erythrocytic malaria candidate vaccine. It is a codon optimized nucleotide sequence representing the P. falciparum circumsporozoite (CS) surface antigen inserted in a replication deficient Adenovirus 35 backbone. A Phase 1a trial has been conducted in the USA in naïve adults and showed that the vaccine was safe. The aim of this study is to assess the safety and immunogenicity of ascending dosages in sub Saharan Africa. A double blind, randomized, controlled, dose escalation, phase Ib trial was conducted in a rural area of Balonghin, the Saponé health district (Burkina Faso). Forty-eight healthy adults aged 18-45 years were randomized into 4 cohorts of 12 to receive three vaccine doses (day 0, 28 and 84) of 10(9), 10(10), 5X10(10), 10(11) vp of Ad35.CS.01 or normal saline by intra muscular injection. Subjects were monitored carefully during the 14 days following each vaccination for non serious adverse events. Severe and serious adverse events were collected throughout the participant study duration (12 months from the first vaccination). Humoral and cellular immune responses were measured on study days 0, 28, 56, 84, 112 and 140. Of the forty-eight subjects enrolled, forty-four (91.7%) received all three scheduled vaccine doses. Local reactions, all of mild severity, occurred in thirteen (27.1%) subjects. Severe (grade 3) laboratory abnormalities occurred in five (10.4%) subjects. One serious adverse event was reported and attributed to infection judged unrelated to vaccine. The vaccine induced both antibody titers and CD8 T cells producing IFNγ and TNFα with specificity to CS while eliciting modest neutralizing antibody responses against Ad35. Study vaccine Ad35.CS.01 at four different dose levels was well-tolerated and modestly immunogenic in this population. These results suggest that Ad35.CS.01 should be further investigated for preliminary efficacy in human challenge models and as part of heterologous prime-boost vaccination strategies. ClinicalTrials.gov NCT01018459 http://clinicaltrials.gov/ct2/show/NCT01018459.

Plasmodium falciparum malaria is one of the leading infectious causes of childhood mortality in Africa. EP-1300 is a polyepitope plasmid DNA vaccine expressing 38 cytotoxic T cell epitopes and 16 helper T cell epitopes derived from P. falciparum antigens expressed predominantly in the liver phase of the parasite’s life cycle. We performed a phase 1 randomized, placebo-controlled, dose escalation clinical trial of the EP-1300 DNA vaccine administered via electroporation using the TriGrid Delivery System device (Ichor Medical Systems). Although the delivery of the EP-1300 DNA vaccine via electroporation was safe, tolerability was less than that usually observed with standard needle and syringe intramuscular administration. This was primarily due to acute local discomfort at the administration site during electroporation. Despite the use of electroporation, the vaccine was poorly immunogenic. The reasons for the poor immunogenicity of this polyepitope DNA vaccine remain uncertain. Clinical Trials Registration: ClinicalTrials.gov NCT01169077.

Background High parasite-specific antibody levels are generally associated with low susceptibility to Plasmodium falciparum malaria. This has been supported by several studies in which clinical malaria cases of P. falciparum malaria were reported to be associated with low antibody avidities. This study was conducted to evaluate the role of age, malaria transmission intensity and incidence of clinical malaria in the induction of protective humoral immune response against P. falciparum malaria in children living in Burkina Faso. Methods We combined levels of IgG and IgG subclasses responses to P. falciparum antigens: Merozoite Surface Protein 3 (MSP3), Merozoite Surface Protein 2a (MSP2a), Merozoite Surface Protein 2b (MSP2b), Glutamate Rich Protein R0 (GLURP R0) and Glutamate Rich Protein R2 (GLURP R2) in plasma samples from 325 children under five (05) years with age, malaria transmission season and malaria incidence. Results We notice higher prevalence of P. falciparum infection in low transmission season compared to high malaria transmission season. While, parasite density was lower in low transmission than high transmission season. IgG against all antigens investigated increased with age. High levels of IgG and IgG subclasses to all tested antigens except for GLURP R2 were associated with the intensity of malaria transmission. IgG to MSP3, MSP2b, GLURP R2 and GLURP R0 were associated with low incidence of malaria. All IgG subclasses were associated with low incidence of P. falciparum malaria, but these associations were stronger for cytophilic IgGs. Conclusions On the basis of the data presented in this study, we conclude that the induction of humoral immune response to tested malaria antigens is related to age, transmission season level and incidence of clinical malaria.