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Dengue virus (DENV) transmission from humans to mosquitoes is a poorly documented, but critical component of DENV epidemiology. Magnitude of viremia is the primary determinant of successful human-to-mosquito DENV transmission. People with the same level of viremia, however, can vary in their infectiousness to mosquitoes as a function of other factors that remain to be elucidated. Here, we report on a field-based study in the city of Iquitos, Peru, where we conducted direct mosquito feedings on people naturally infected with DENV and that experienced mild illness. We also enrolled people naturally infected with Zika virus (ZIKV) after the introduction of ZIKV in Iquitos during the study period. Of the 54 study participants involved in direct mosquito feedings, 43 were infected with DENV-2, two with DENV-3, and nine with ZIKV. Our analysis excluded participants whose viremia was detectable at enrollment but undetectable at the time of mosquito feeding, which was the case for all participants with DENV-3 and ZIKV infections. We analyzed the probability of onward transmission during 50 feeding events involving 27 participants infected with DENV-2 based on the presence of infectious virus in mosquito saliva 7-16 days post blood meal. Transmission probability was positively associated with the level of viremia and duration of extrinsic incubation in the mosquito. In addition, transmission probability was influenced by the day of illness in a non-monotonic fashion; i.e., transmission probability increased until 2 days after symptom onset and decreased thereafter. We conclude that mildly ill DENV-infected humans with similar levels of viremia during the first two days after symptom onset will be most infectious to mosquitoes on the second day of their illness. Quantifying variation within and between people in their contribution to DENV transmission is essential to better understand the biological determinants of human infectiousness, parametrize epidemiological models, and improve disease surveillance and prevention strategies.

Over half the world's population is at risk for viruses transmitted by Aedes mosquitoes, such as dengue and Zika. The primary vector, Aedes aegypti, thrives in urban environments. Despite decades of effort, cases and geographic range of Aedes-borne viruses (ABVs) continue to expand. Rigorously proven vector control interventions that measure protective efficacy against ABV diseases are limited to Wolbachia in a single trial in Indonesia and do not include any chemical intervention. Spatial repellents, a new option for efficient deployment, are designed to decrease human exposure to ABVs by releasing active ingredients into the air that disrupt mosquito-human contact. A parallel, cluster-randomized controlled trial was conducted in Iquitos, Peru, to quantify the impact of a transfluthrin-based spatial repellent on human ABV infection. From 2,907 households across 26 clusters (13 per arm), 1,578 participants were assessed for seroconversion (primary endpoint) by survival analysis. Incidence of acute disease was calculated among 16,683 participants (secondary endpoint). Adult mosquito collections were conducted to compare Ae. aegypti abundance, blood-fed rate, and parity status through mixed-effect difference-in-difference analyses. The spatial repellent significantly reduced ABV infection by 34.1% (one-sided 95% CI lower limit, 6.9%; one-sided P value = 0.0236, z = 1.98). Aedes aegypti abundance and blood-fed rates were significantly reduced by 28.6 (95% CI 24.1%, ∞); z = -9.11) and 12.4% (95% CI 4.2%, ∞); z = -2.43), respectively. Our trial provides conclusive statistical evidence from an appropriately powered, preplanned cluster-randomized controlled clinical trial of the impact of a chemical intervention, in this case a spatial repellent, to reduce the risk of ABV transmission compared to a placebo.

Background Among combat injured, invasive fungal infections (IFIs) result in significant morbidity. Cultures and histopathology are the primary diagnostic methods for IFIs, but they have limitations. We previously evaluated a panfungal polymerase chain reaction assay, which was 83% sensitive and 99% specific for angioinvasive IFIs. Here, we evaluated 3 less resource-intensive seminested assays targeting clinically relevant fungi in the order Mucorales and genera Aspergillus and Fusarium. Methods Formalin-fixed paraffin-embedded tissue specimens from a multicenter trauma IFI cohort (2009-2014) were used. Cases were US military personnel injured in Afghanistan with histopathologic IFI evidence. Controls were patients with similar injury patterns and no laboratory IFI evidence (negative culture and histopathology). Seminested assays specific to Mucorales (V4/V5 regions of 18S rDNA), Aspergillus (mitochondrial tRNA), and Fusarium (internal transcribed spacer [ITS]/28A regions of DNA) were compared with a panfungal assay amplifying the internal transcribed spacer 2 region of rDNA and to histopathology. Results Specimens from 92 injury sites (62 subjects) were compared with control specimens from 117 injuries (101 subjects). We observed substantial agreement between the seminested and panfungal assays overall, especially for the order Mucorales. Moderate agreement was observed at the genus level for Aspergillus and Fusarium. When compared with histopathology, sensitivity and specificity of seminested assays were 67.4% and 96.6%, respectively (sensitivity increased to 91.7% when restricted to sites with angioinvasion). Conclusions Prior studies of seminested molecular diagnostics have focused on culture-negative samples from immunocompromised patients. Our findings underscore the utility of the seminested approach in diagnosing soft-tissue IFIs using formalin-fixed paraffin-embedded tissue samples, especially with angioinvasion. [ABSTRACT FROM AUTHOR]

Military medicine has a long history of humanitarian efforts globally, including responses to natural disasters and as planned medical civil action projects. However, ending two decades of war in Afghanistan, Walter Reed National Military Medical Center (WRNMMC) was tasked to receive up to 63 injured patients with less than 96-hour notice on August 27, 2021. As part of Operation Allies Refuge and transition to Operation Allies Welcome, this article highlights the complicated cross-organizational and multidisciplinary response at WRNMMC where ultimately 277 Afghan patients and nonmedical attendants received medical care and other requirements for resettlement. Lessons learned from coordinating the complex short suspense medical, cultural, and logistic efforts are noted as considerations and practical recommendations for future missions. [ABSTRACT FROM AUTHOR]

Background: Multidrug-resistant infections complicating combat-related trauma necessitate the use of broad-spectrum antimicrobials. Recent literature posits an association between vancomycin (VANC) and piperacillin--tazobactam (VPT) combination therapy and acute kidney injury (AKI). We examined whether therapy with VPT was associated with an increased risk of AKI compared to VANC and other broad-spectrum b-lactam antibiotics (VBL) following combat-related injuries. Methods: Patients within the Trauma Infectious Disease Outcomes Study (TIDOS) who received ≥48 hours concomitant VPT or VBL started within 24 hours of each other were assessed. Exclusion criteria were receipt of renal replacement therapy and baseline creatinine >1.5 mg/dL. Acute kidney injury was defined by meeting any of the Risk, Injury, Failure, Loss, End Stage Renal Disease (RIFLE), AKIN, or VANC consensus guidelines criteria 3 to 7 days after therapy initiation. Variables significantly associated with AKI were used in inverse probability treatment weighting to perform univariate and subsequent logistic regression multivariate modeling to determine significant risk factors for AKI. Results: Sixty-one patients who received VPT and 207 who received VBL were included. Both groups had a median age of 24 years and initial median creatinine of 0.7 mg/dL. The VBL patients were more likely to have sustained blast injuries (P = .001) and received nephrotoxic agents (amphotericin [P = .002] and aminoglycosides [P < .001]). In the VBL group, AKI incidence was 9.7% compared to 13.1% in the VPT group (P = .438). Multivariate analysis identified a relative risk of 1.727 (95% CI: 1.027-2.765) for AKI associated with VPT exposure. Acute kidney injury severity generally met RIFLE Risk criteria and was 1 day in duration. Only 1 patient had persistent renal dysfunction 30 days after therapy completion. Conclusion: In this young and previously healthy, severely ill combat-injured population, VPT was associated with nearly twice the risk of AKI compared to VBL. Nevertheless, AKI was of low severity, short duration, and had high rates of renal recovery. [ABSTRACT FROM AUTHOR]

Background: The contribution of multi-drug-resistant gram-negative bacilli infections (MDRGN-I) in patients with trauma is not well described. We present characteristics of MDRGN-Is among military personnel with deployment-related trauma (2009-2014).Patients and Methods: Data from the Trauma Infectious Disease Outcomes Study were assessed for infectious outcomes and microbial recovery. Infections were classified using standardized definitions. Gram-negative bacilli were defined as multi-drug-resistant if they showed resistance to ≥3 antibiotic classes or were producers of extended-spectrum β-lactamase or carbapenemases.Results: Among 2,699 patients admitted to participating U.S. hospitals, 913 (33.8%) experienced ≥1 infection event, of which 245 (26.8%) had a MDRGN-I. There were 543 MDRGN-I events (24.6% of unique 2,210 infections) with Escherichia coli (48.3%), Acinetobacter spp. (38.6%), and Klebsiella pneumoniae (8.4%) as the most common MDRGN isolates. Incidence of MDRGN-I was 9.1% (95% confidence interval [CI]: 8.0-10.2). Median time to MDRGN-I event was seven days with 75% occurring within 13 days post-trauma. Patients with MDRGN-Is had a greater proportion of blast injuries (84.1% vs. 62.5%; p < 0.0001), traumatic amputations (57.5% vs. 16.3%; p < 0.0001), and higher injury severity (82.0% had injury severity score ≥25 vs. 33.7%; p < 0.0001) compared with patients with either no infections or non-MDRGN-Is. Furthermore, MDRGN-I patients were more frequently admitted to the intensive care unit (90.5% vs. 48.5%; p < 0.0001), colonized with a MDRGN before infection (58.0% vs. 14.7%; p < 0.0001), and required mechanical ventilation (78.0% vs. 28.8% p < 0.0001). Antibiotic exposure before the MDRGN-I event was significantly higher across antibiotic classes except first generation cephalosporins and tetracyclines, which were very commonly used with all patients. Regarding outcomes, patients with MDRGN-Is had a longer length of hospitalization than the comparator group (53 vs. 18 days; p < 0.0001).Conclusions: We found a high rate of MDRGN-I in our population characterized by longer hospitalization and greater injury severity. These findings inform treatment and infection control decisions in the trauma patient population. [ABSTRACT FROM AUTHOR]

Norovirus is the leading cause of acute gastroenteritis (AGE) globally. Few longitudinal studies have assessed norovirus-associated AGE incidence across age groups in community settings in Latin America. During April 2015-April 2019, active surveillance for AGE among community members of all ages was conducted through household visits two to three times per week in San Jeronimo, Cusco, Peru. An asymptomatic control household was selected for every fifth AGE case. Stool specimens were collected from AGE cases, asymptomatic household members, and control household members, and they were tested for norovirus using real-time reverse transcriptase polymerase chain reaction. Data on illness characteristics were collected from AGE cases during a 15-day follow-up period. Annual means of 247 households and 1,555 participants were enrolled during each April-March surveillance year, accounting for 4,176 person-years (PY) of observation. Of 1,099 AGE events reported, 1,014 stool specimens were tested, and 186 (18%) were norovirus positive. Norovirus AGE incidence was 4.4/100 PY (95% CI: 3.9-5.1); incidence was highest among those younger than 2 years old (60.9/100 PY; 95% CI: 46.8-79.4). Among 672 stool specimens from asymptomatic controls, 56 (8%) tested positive for norovirus. Odds of norovirus detection were significantly higher among cases compared with controls (odds ratio: 2.2; 95% CI: 1.6-3.1). Age-stratified norovirus incidence in this periurban community aligns with previously published estimates and was highest among those younger than 2 years old. Establishing baseline norovirus incidence in specific communities is crucial to identify target populations and assess effectiveness of future interventions, such as vaccines.

While costs of norovirus acute gastroenteritis (AGE) to healthcare systems have been estimated, out-of-pocket and indirect costs incurred by households are not well documented in community settings, particularly in developing countries. We conducted active surveillance for AGE in two communities in Peru: Puerto Maldonado (October 2012-August 2015) and San Jeronimo (April 2015-April 2019). Norovirus AGE events with PCR-positive stool specimens were included. Data collected in follow-up interviews included event-related medical resource utilization, associated out-of-pocket costs, and indirect costs. There were 330 norovirus-associated AGE events among 3,438 participants from 685 households. Approximately 49% of norovirus events occurred among children <5 years of age and total cost to the household per episode was highest in this age group. Norovirus events cost a median of US $2.95 (IQR $1.04-7.85) in out-of-pocket costs and $12.58 (IQR $6.39-25.16) in indirect costs. Medication expenses accounted for 53% of out-of-pocket costs, and productivity losses accounted for 59% of the total financial burden on households. The frequency and associated costs of norovirus events to households in Peruvian communities support the need for prevention strategies including vaccines. Norovirus interventions targeting children <5 years of age and their households may have the greatest economic benefit., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)