Viral coinfections and their impact on long-term immunity represent an understudied area in disease ecology and infectious disease research. Coinfections can influence the host's susceptibility to future infections, alter host and pathogen population dynamics, modify infection and shedding patterns, impose evolutionary pressures, and affect the risk of zoonotic spillover. Egyptian rousette bats (ERB; Rousettus aegyptiacus; common name: Egyptian rousettes) are a natural reservoir host for Marburg virus (MARV) and Ravn virus (RAVV), as well as a vertebrate reservoir for Kasokero virus (KASV) and a putative reservoir for Sosuga virus (SOSV). Viral coinfections have been documented in numerous free-ranging bat species as well as ERBs, raising questions about how these interactions influence immune responses, viral shedding, and pathogen maintenance within the natural host population. This is particularly critical given the genetic diversity among co-circulating viral species (e.g., MARV and RAVV) and the potential implications for the development of protective immunity and subsequent viral inoculation outcomes. In this study, ERBs previously infected with MARV alone or KASV + MARV were inoculated approximately 8 months later with homotypic (MARV) or heterotypic (RAVV) orthomarburgvirus isolates. The results demonstrated no viral replication or shedding post-inoculation, and all bats displayed strong secondary immune responses consistent with sterilizing immunity. These findings suggest that both MARV monoinfection and KASV + MARV coinfection confer robust protection against reinfection, regardless of the viral isolate. This research enhances our understanding of immune responses during viral coinfections in bats and their potential role in mitigating zoonotic pathogen spillover.IMPORTANCELong-term immunity elicited in bats during coinfection (i.e., simultaneous infection) with viruses they naturally host is not well understood. These interactions could affect susceptibility to subsequent reinfection and pathogen spread. Egyptian rousette bats, natural hosts for several pathogenic zoonotic viruses, including Marburg and Kasokero viruses, can be found multiply infected in the wild, but the immune consequences of being coinfected remain unclear. Here, bats previously infected with either Marburg virus alone or with both Kasokero and Marburg viruses were later challenged with Marburg virus or the related Ravn virus. No reinoculated bats showed signs of virus replication, and all mounted strong immune responses. These results suggest that this coinfection combination still provides robust protection against reinfection, even with diverse orthomarburgviruses. This study helps improve our understanding of how bats manage viral coinfections and may inform how these interactions influence zoonotic spillover risk.

BACKGROUND: Phthalates are endocrine-disrupting chemicals that can dysregulate hormonal systems supporting female sexual function (eg, estrogen interference). Female sexual function is important for positive sexual expression, fertility, and well-being but remains understudied in the context of environmental toxicants to which females are ubiquitously exposed. Identifying environmental determinants of female sexual dysfunction can inform exposure-reduction strategies and clinical practice to improve sexual health. AIM: We investigated associations between phthalate exposure and sexual function in a cohort of North American females. METHODS: We leveraged cross-sectional data from a subset of 21-45-year-old females trying to conceive enrolled in Pregnancy Study Online (n = 347) to assess associations between phthalate and phthalate alternative exposure and sexual function, measured on a modified version of the Female Sexual Function Index-6 (FSFI-6). We summed FSFI-6 responses (range = 2-30); lower scores reflected poorer function. We measured urinary concentrations of 18 phthalate and alternative metabolites using online solid phase extraction coupled with high-performance liquid chromatography isotope dilution tandem mass spectrometry. Given that the biomarkers were nonlinearly associated with FSFI-6 scores, we categorized creatinine-corrected biomarker concentrations in tertiles. We used multivariable linear regression to estimate mean differences (beta) with 95% confidence intervals (CIs) in FSFI-6 scores per tertile increase in biomarker concentrations, adjusting for hypothesized confounders. In secondary analyses, we considered individual FSFI-6 items (range = 1-5) as outcome variables. OUTCOMES: Female sexual function measured on the FSFI-6. RESULTS: Most biomarkers were not associated with FSFI-6 scores. Mono-n-butyl phthalate concentrations were weakly and non-monotonically associated with lower summed FSFI-6 scores (beta = -0.8, 95% CI = -1.8, 0.2) and orgasm scores (beta = -0.3, 95% CI = -0.7, 0.1) at the second (vs first) tertile, reflecting poorer sexual function. Mono-2-ethyl-5-carboxypentyl terephthalate concentrations were weakly associated with poorer scores for orgasm, while other biomarkers (notably, mono-carboxyisononyl phthalate) were associated with higher summed FSFI-6 and FSFI-6 item scores. CLINICAL IMPLICATIONS: Exposure to phthalates should be considered in clinical settings, particularly for females experiencing issues with sexual function. STRENGTHS AND LIMITATIONS: This study represents one of the first to assess associations of phthalate exposure and female sexual function, and we investigated associations in an established cohort with a validated measure of sexual function. We were limited by our sample size and cross-sectional study design. CONCLUSION: Although associations for most phthalate biomarkers were null, some were weakly associated with female sexual function, suggesting exposure to certain chemicals may affect female sexual function with implications for clinical practice and exposure reduction strategies.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are persistent, widespread environmental contaminants and some are endocrine-disrupting. Studies of gynecologic cancers are limited; we evaluated ovarian cancer, a rare, often fatal malignancy. METHODS: This nested case-control study included 318 ovarian cancer cases and 472 individually matched female controls in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, which recruited participants aged 55-74 years from 10 U.S. study centers (1993-2001). We ascertained cases through 2016 and quantitated eight PFAS in prediagnostic serum samples. We estimated ORs and 95% CIs for continuous (log2-transformed) and categorized PFAS concentrations via conditional logistic regression models implicitly adjusting for matching factors (age, center, randomization year, year of blood draw, race and ethnicity) and adjusted for smoking, body mass index, family history of cancer, menopausal hormone therapy and oral contraceptive use, parity, and number of freeze-thaws. RESULTS: We found a positive association with ovarian cancer for a doubling in 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (MeFOSAA) concentrations (ORperlog2=1.24, CI = 1.03-1.49) and 62% greater risk among those in the highest quartile (ORQ4vsQ1=1.62, CI = 1.03-2.54; p-trend = 0.02). Perfluorooctane sulfonic acid (PFOS) was associated with increased risk (ORperlog2=1.47, CI = 1.05-2.06) with no quartile trend (p-trend = 0.79). Associations with perfluorononanoic (ORperlog2=1.36, CI = 0.95-1.95) and perfluorodecanoic acid (ORperlog2=1.35, CI = 0.94-1.95) were suggested, with non-monotonic quartile trends (p-trend = 0.12-0.21). MeFOSAA associations were strongest in women aged 55-59 (ORperlog2=1.60, CI = 1.13-2.27), more moderate in those 60-64 (ORperlog2=1.31, CI = 0.90-1.90) and null among women 65 + (ORperlog2=1.02, CI = 0.73-1.43; p-heterogeneity = 0.22). Associations persisted in cases diagnosed ≥8 years after blood collection. CONCLUSIONS: These findings offer novel evidence for PFAS as ovarian cancer risk factors, particularly PFOS and MeFOSAA, a PFOS precursor.

The Chatbot Assessment Reporting Tool (CHART) is a reporting guideline developed to provide reporting recommendations for studies evaluating the performance of generative artificial intelligence (AI)-driven chatbots when summarizing clinical evidence and providing health advice, referred to as Chatbot Health Advice (CHA) studies. CHART was developed in several phases after performing a comprehensive systematic review to identify variation in the conduct, reporting and methodology in CHA studies. Findings from the review were used to develop a draft checklist that was revised through an international, multidisciplinary modified asynchronous Delphi consensus process of 531 stakeholders, three synchronous panel consensus meetings of 48 stakeholders, and subsequent pilot testing of the checklist. CHART includes 12 items and 39 subitems to promote transparent and comprehensive reporting of CHA studies. These include Title (subitem 1a), Abstract/Summary (subitem 1b), Background (subitems 2ab), Model Identifiers (subitem 3ab), Model Details (subitems 4abc), Prompt Engineering (subitems 5ab), Query Strategy (subitems 6abcd), Performance Evaluation (subitems 7ab), Sample Size (subitem 8), Data Analysis (subitem 9a), Results (subitems 10abc), Discussion (subitems 11abc), Disclosures (subitem 12a), Funding (subitem 12b), Ethics (subitem 12c), Protocol (subitem 12d), and Data Availability (subitem 12e). The CHART checklist and corresponding methodological diagram were designed to support key stakeholders including clinicians, researchers, editors, peer reviewers, and readers in reporting, understanding, and interpreting the findings of CHA studies.

IMPORTANCE: The rise in chatbot health advice (CHA) studies is accompanied by heterogeneity in reporting standards, impacting their interpretability. OBJECTIVE: To provide reporting recommendations for studies evaluating the performance of generative artificial intelligence (AI)-driven chatbots when summarizing clinical evidence and providing health advice. DESIGN, SETTING, AND PARTICIPANTS: CHART was developed in several phases after performing a comprehensive systematic review to identify variation in the conduct, reporting, and methodology in CHA studies. Findings from the review were used to develop a draft checklist that was revised through an international, multidisciplinary modified asynchronous Delphi consensus process of 531 stakeholders, 3 synchronous panel consensus meetings of 48 stakeholders, and subsequent pilot testing of the checklist. RESULTS: CHART includes 12 items and 39 subitems to promote transparent and comprehensive reporting of CHA studies. These include title (subitem 1a), abstract or summary (subitem 1b), background (subitems 2ab), model identifiers (subitem 3ab), model details (subitems 4abc), prompt engineering (subitems 5ab), query strategy (subitems 6abcd), performance evaluation (subitems 7ab), sample size (subitem 8), data analysis (subitem 9a), results (subitems 10abc), discussion (subitems 11abc), disclosures (subitem 12a), funding (subitem 12b), ethics (subitem 12c), protocol (subitem 12d), and data availability (subitem 12e). CONCLUSIONS AND RELEVANCE: The CHART checklist and corresponding methodological diagram were designed to support key stakeholders including clinicians, researchers, editors, peer reviewers, and readers in reporting, understanding, and interpreting the findings of CHA studies.

BACKGROUND: The Chatbot Assessment Reporting Tool (CHART) is a reporting guideline developed to provide reporting recommendations for studies evaluating the performance of generative artificial intelligence (AI)-driven chatbots when summarizing clinical evidence and providing health advice, referred to as Chatbot Health Advice (CHA) studies. METHODS: CHART was developed in several phases after performing a comprehensive systematic review to identify variation in the conduct, reporting, and methodology in CHA studies. Findings from the review were used to develop a draft checklist that was revised through an international, multidisciplinary modified asynchronous Delphi consensus process of 531 stakeholders, three synchronous panel consensus meetings of 48 stakeholders, and subsequent pilot testing of the checklist. RESULTS: CHART includes 12 items and 39 subitems to promote transparent and comprehensive reporting of CHA studies. These include Title (subitem 1a), Abstract/Summary (subitem 1b), Background (subitems 2ab), Model Identifiers (subitems 3ab), Model Details (subitems 4abc), Prompt Engineering (subitems 5ab), Query Strategy (subitems 6abcd), Performance Evaluation (subitems 7ab), Sample Size (subitem 8), Data Analysis (subitem 9a), Results (subitems 10abc), Discussion (subitems 11abc), Disclosures (subitem 12a), Funding (subitem 12b), Ethics (subitem 12c), Protocol (subitem 12d), and Data Availability (subitem 12e). CONCLUSION: The CHART checklist and corresponding methodological diagram were designed to support key stakeholders including clinicians, researchers, editors, peer reviewers, and readers in reporting, understanding, and interpreting the findings of CHA studies.

BACKGROUND: The National Blood Collection and Utilization Survey (NBCUS) is conducted biennially to estimate US blood collection and utilization. Supplemental data from the 2023 NBCUS not presented elsewhere are described here. METHODS: Data on blood donor characteristics, donation deferrals, component costs, transfusion-associated adverse reactions, and use of pathogen-reduced platelets during 2023 were collected from US blood collecting and transfusing facilities. National estimates were produced using weighting and imputation methods. RESULTS: Compared with 2021, successful blood donations from donors aged 45-64 decreased (11%) in 2023 but still accounted for most donations overall (39%). Donations from donors aged 16-18 years, Black or African American, and Hispanic donors increased by 66%, 38%, and 9%, respectively, since 2021. Donation deferrals for travel increased since 2021 (+162%). From 2021 to 2023, the median price hospitals paid per unit of leukoreduced red blood cells, fresh frozen plasma, and leukoreduced and pathogen-reduced apheresis platelets increased. Apheresis platelets experienced the largest price increase per unit (+$65). Compared with 2021, the proportion of transfusing facilities using pathogen-reduced platelets increased in 2023 (60% vs. 64%). The overall rate of transfusion-associated adverse reactions per 100,000 components transfused was higher in 2023 than in 2021 (312.3 vs. 273.8), although the rate of transfusion-transmitted infections (bacterial, viral, and parasitic) declined in 2023 (0.25 vs. 0.43). CONCLUSION: From 2021 to 2023, blood donations among older donors decreased, while donations from younger and Black or African American donors increased. Adoption of pathogen-reduced platelets and cost of all blood products increased.

OBJECTIVE: To examine participants' motivations and their experiences throughout a decentralized, longitudinal COVID-19 study in the U.S. METHODS: We recruited 355 participants from the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE) between November 2022 - March 2023 to answer five qualitative survey questions anonymously. We used an inductive content analysis approach to analyze the data. RESULTS: We identified five key themes from the analysis, which reflected participants' a) motivations to join the study, b) study benefits, c) perceptions of survey questions, d) experiences with the research process, and e) preferences for disseminating research findings. Participants were motivated to learn with researchers about COVID-19. They expressed divided opinions about the relevance of INSPIRE research questions. They reported difficulties navigating the virtual research platform and the need for making survey participation less cognitively demanding. They sought more regular feedback on study findings. CONCLUSIONS: Our findings offered insights into incorporating decentralized participatory methods in longitudinal research, strengthening reciprocal research communications, making virtual research platforms user-friendly, and employing strategies to reduce participants' cognitive burden in research. POLICY IMPLICATIONS: Longitudinal studies should focus on optimizing these aspects of participant engagement to produce rigorous findings that inform policy and practice on lasting effects of COVID-19 including Long COVID.

BACKGROUND: The clinical and genomic epidemiology of human metapneumovirus (hMPV) infections in community settings is not well understood. METHODS: From 2018 to 2022, individuals with respiratory symptoms were recruited and enrolled from the greater Seattle, Washington community in the United States. Residual clinical specimens from individuals presenting with respiratory symptoms were additionally collected. Specimens were tested for hMPV by reverse-transcription polymerase chain reaction, with whole genome sequencing performed on a subset (209/1002). RESULTS: hMPV positivity was higher among clinical specimens (835/21 539 [3.9%]) compared to community specimens (167/28 348 [0.6%]). Children aged 0-4 years had the highest percent positivity across both clinical and community settings (497/10 213 [4.9%] and 28/1640 [1.7%], respectively). In multivariate analysis, a household income of ≤US$100 000 (adjusted odds ratio [aOR], 1.72 [95% confidence interval {CI}, 1.07-2.85]), and recent international travel (aOR, 6.51 [95% CI, 3.11-12.22]) were associated with hMPV positivity. A subset of 209 of 1002 samples (21%) was sequenced; the distribution of subtypes A2b, A2c, B1, and B2 were similar across both community and clinical settings, with an increase in the proportion of subtype B1 after the start of the pandemic. CONCLUSIONS: Risk factors of testing positive for hMPV in a community setting included lower household income and recent international travel. Co-circulation of hMPV subtypes was observed across community and clinical settings.

BACKGROUND: Understanding the population dynamics and geographical range of Aedes aegypti is critically important for arbovirus vector surveillance and control. Little is known about the current distribution and seasonality of Ae. aegypti in Grand Lomé, Togo. We developed an investigation to determine whether Ae. aegypti was present across Lomé communes during a 1-year collection period. METHODS: Mosquito ovitraps (n = 70) were deployed across the 13 communes in the Grand Lomé health region and were examined between May 2022 and April 2023. Generalized linear mixed models (GLMMs) were applied to investigate the relationship between larval collections and seasonality. The European Space Agency (ESA) WorldCover 10 m 2020 product was used to represent different land cover classes and to determine whether sites with higher larval numbers differed from sites with lower numbers. RESULTS: A total of 52,768 Ae. aegypti larvae were collected across the 13 communes of Grand Lomé. The highest incidence of Ae. aegypti larvae was observed in the commune of Bè-Ouest (= 122.74 per 1000 population). Agoè-Nyivé was the commune with the lowest incidence over the entire study period. There was a statistically significant difference in Ae. aegypti larval counts between the rainy and dry seasons. Eight land-use classes were represented by the ESA 10 m product in Grand Lomé, with the built-up category being the most common. We found a significant relationship between larval abundance categories and land cover classes. CONCLUSIONS: This study shows that Ae. aegypti larvae can be found across all communes of the Grand Lomé region in both the rainy and dry seasons, especially in ovitraps surrounded by built-up land cover category. The results of this study could be useful in guiding disease vector surveillance and control efforts due to the potential imminent risk of upcoming dengue outbreaks.

A nationwide cross-sectional study led by the Agency for Toxic Substances and Disease Registry in collaboration with research and community partners, was designed to investigate health outcomes linked to per- and polyfluoroalkyl substances (PFAS) exposure among residents of communities with contaminated drinking water. The objective was to describe the study design, methods, participant demographics, and PFAS serum concentrations. From 2019 to 2023, adult (18+) and child (ages 4-17) participants were recruited from communities with past or ongoing PFAS contamination of drinking water across eight sites in California, Colorado, Massachusetts, Michigan, New Hampshire, New York, New Jersey, and Pennsylvania. Data on demographics, lifestyle factors, and residential, occupational, and medical history were collected via questionnaires. Extensive clinical tests assessed cardiometabolic, liver, thyroid, kidney, glycemic, and immune parameters. Neurobehavioral tests were administered to children (ages 5-17). PFAS quantified in serum included MeFOSAA, PFHxS, PFOS, PFOA, PFNA, PFDA, and PFUnDA. Serum, whole blood, and urine samples were banked for future analyses. The study enrolled 5826 adults (geometric mean age: 53.6 years; 60.2 % female; 77.2 % non-Hispanic White) and 710 children (geometric mean age: 10.7 years; 48.5 % female; 69 % non-Hispanic White). Compared with NHANES data (2017-2020), adults showed elevated geometric mean concentrations of PFHxS and PFOA; only PFHxS was elevated in children. These serum concentrations reflect a wide range of PFAS exposures in communities affected by contamination from firefighting activities and industrial emissions, and other sources. This large study is a valuable resource for exploring associations between PFAS exposure and health effects in adults and children.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has highlighted the importance of genomic surveillance and whole genome sequencing (WGS) for identifying mutations and supporting epidemiologic investigations. Healthcare workers (HCWs) face unique risks for COVID-19, potentially amplifying outbreaks within healthcare facilities (HCFs). This report details the use of WGS to retrospectively investigate a COVID-19 cluster among HCWs in a tertiary care HCF in the Philippines. METHODS: Epidemiologic investigation was conducted by the HCF infection prevention and control (IPC) staff. The Global Action in Healthcare Network (GAIHN) COVID-19 variant characterization project retrospectively conducted WGS on selected HCW and inpatient respiratory specimens associated with the cluster with reverse-transcription polymerase chain reaction cycle threshold ≤32. Phylogenetic analyses were conducted using Nextstrain. Subclusters were defined by shared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage and epidemiologic data. RESULTS: Investigation by IPC staff identified 19 HCWs with COVID-19 diagnosed during 2-9 September 2022 from a single nursing unit. Specimens for WGS were collected from 8 of these HCWs and from 43 additional HCF staff and inpatients with COVID-19 diagnosed from 1 August through 30 September 2022. Phylogenetic analyses identified 12 unique SARS-CoV-2 lineages and 2 subclusters: subcluster A (BA.5.2 lineage, n = 6) and subcluster B (BA.5.10.1 lineage, n = 7). Pairwise substitution-by-site analyses, combined with epidemiological data, provided support for multiple potential transmission events. CONCLUSIONS: WGS identified SARS-CoV-2 subclusters associated with high-risk exposure settings among HCWs in a tertiary care facility, providing essential insights into transmission pathways and demonstrating its potential to guide targeted IPC interventions and improve outbreak response strategies.

OBJECTIVES: Interfacility patient transfers contribute to the regional spread of multidrug-resistant organisms (MDROs). We evaluated whether transfer patterns of inpatients with similar characteristics to carbapenem-resistant Enterobacterales (CRE) case-patients (CRE surrogates) better reflect hospital-level CRE burden than traditionally used populations. DESIGN: We determined the risk factors for subsequent hospital admission using demographic and clinical information from Tennessee Department of Health tracked CRE case-patients from July 2015 to September 2019. Risk factors were used to identify CRE surrogates among inpatients in the 2018 Tennessee Hospital Discharge Data System (HDDS). Transfer networks of CRE surrogates, Medicare/TennCare beneficiaries, and all-inpatients with ≤365 days of intervening community stays were compared with the transfer networks of CRE case-patients in 2019. The associations between hospital-level CRE prevalence and hospitals' incoming transfer volumes from each network were assessed using negative binomial regression models. RESULTS: Eight risk factors for subsequent hospital admission were identified from 2,518 CRE case-patients, which were used to match CRE case-patients with HDDS inpatients, resulting in 10,069 surrogate patients. CRE surrogate network showed more structural similarities with the CRE case-patient network than with the all-inpatient and Medicare/TennCare networks. A 33% increase in hospitals' CRE prevalence in 2019 was associated with each doubling of incoming transfer of CRE surrogates in 2018 (adjusted Risk Ratio [aRR] 1.33, 95%CI: 1.1, 1.59), higher than all-inpatient (aRR 1.27, 95% CI: 1.08, 1.51) and Medicare/TennCare networks (aRR 1.21, 95% CI: 1.02, 1.44). CONCLUSIONS: Surrogate transfer patterns were associated with hospital-level CRE prevalence, highlighting their value in MDRO containment and prevention.

In April 2024, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was expanded by 1 new order, 1 new family, 6 new subfamilies, 34 new genera and 270 new species. One class, two orders and six species were renamed. Seven families and 12 genera were moved; ten species were renamed and moved; and nine species were abolished. This article presents the updated taxonomy of Negarnaviricota as currently accepted by the ICTV, providing an essential annual update on the classification of members of this phylum that deepen understandings of their evolution, and supports critical public health measures for virus identification and tracking.

This survey was conducted with the aim of determining the public health risk of Rocky Mountain spotted fever and murine typhus in the urban and peri-urban areas of El Paso, as well as other areas in Texas, southern New Mexico, and Ciudad Juarez, Mexico. The approach was to assess the diversity of tick and flea species, determine if the ticks and fleas were infected with Rickettsia rickettsii and Rickettsia typhi (R. typhi), respectively, and assess previous human infection with Rickettsia species. Ticks and fleas were collected from domestic and wild animals and tested using a nested polymerase chain reaction assay. Human plasma samples were also tested for antibodies using an indirect fluorescence assay. Among 203 fleas, including Pulex irritans, Echidnophaga gallinacea, and Ctenocephalides felis (C. felis), collected from wild and domestic small mammals, only one pool of four C. felis collected from a dog in the El Paso community was positive for Rickettsia felis. All 194 Rhipicephalus sanguineus ticks collected from stray and domestic dogs in the El Paso community, southern Doña Ana County, and Ciudad Juarez were negative for Rickettsia spp. In Travis County, Texas, a total of 207 ticks collected from white-tailed deer, including 196 Ixodes scapularis and 11 Dermacentor albipictus, were negative for Rickettsia spp. pathogens. Among 375 archived human plasma samples collected in the El Paso community, only two were positive for R. typhi antibodies. These preliminary findings suggested that tick- and flea-borne diseases were not a major health risk in the El Paso community or the other areas included in this survey.

Trichomonas vaginalis is the most common non-viral sexually transmitted infection worldwide. We compared the in vitro activity of the thiazolide nitazoxanide (NTZ) and its metabolite, tizoxanide (TIZ), with the activity of the Food and Drug Administration-approved 5-nitroimidazoles (metronidazole [MTZ], tinidazole [TDZ], and secnidazole [SEC]) against MTZ-susceptible and MTZ-resistant Trichomonas vaginalis clinical isolates. Frozen, stored T. vaginalis clinical isolates (n = 36) were cultured in Diamond's trypticase-yeast-maltose media supplemented with heat-inactivated horse serum and an antibiotic cocktail. Drug-susceptibility assays for the thiazolides (NTZ and TIZ) and the 5-nitroimidazoles (MTZ, TDZ, and SEC) were performed to determine the minimum lethal concentrations (MLCs) for each T. vaginalis isolate and the median MLC for each drug. Of the 36 T. vaginalis isolates cultured, 18 were MTZ resistant and 18 were MTZ susceptible. For the 18 MTZ-resistant strains, the median MLCs for MTZ, TDZ, and SEC were 100, 25, and 50 µg/mL, respectively. By contrast, the median MLCs for NTZ and TIZ were considerably lower at 1.6 and 0.8 µg/mL, respectively. The similarity in thiazolide MLCs in all T. vaginalis strains, regardless of sensitivity to MTZ, suggests that NTZ and TIZ act via a different mechanism than the 5-nitroimidazoles. Future investigations will focus on the in vivo activity of NTZ and TIZ as well as the efficacy of thiazolides used as monotherapy or as combination therapy, particularly in T. vaginalis-infected patients who do not respond to 5-nitroimidazole treatment. IMPORTANCE: Investigating drug resistance and alternative treatment options for Trichomonas vaginalis is crucial due to the increasing prevalence of persistent infections and the potential failure of standard therapies (i.e., 5-nitroimidazoles). Trichomoniasis can lead to significant health complications, including increased susceptibility to sexually transmitted infections and adverse pregnancy outcomes. The rise of 5-nitroimidazole drug-resistant strains poses a challenge to effective treatment, necessitating ongoing research to understand the mechanisms behind this resistance. Exploring alternative treatments, such as novel pharmacological agents like nitazoxanide and tizoxanide, could provide more effective options for managing these persistent infections. Additionally, comprehensive investigations can help inform public health strategies and reduce transmission rates. Ultimately, prioritizing research in this area is essential for improving patient outcomes and safeguarding reproductive health.

BACKGROUND: While electronic cigarettes (ECIG) may have lower toxicant delivery than cigarettes, ECIG-liquids and aerosols still contain toxicants that can potentially disrupt lung lipid homeostasis. METHODS: Participants from two studies underwent bronchoscopy and bronchoalveolar lavage (BAL). Ninety-eight participants (21-44 years old) were included in a cross-sectional study, with 17 ECIG users, 52 non-smokers, and 29 smokers. In the four-week clinical trial, 30 non-smokers were randomly assigned to use nicotine-free, flavorless ECIG or no use. A panel of 75 quantifiable lipid species and 7 lipid classes were assessed in the BAL using two tandem mass spectrometry (MS/MS) platforms. Ten cytokines and lipid-laden macrophages (LLM) were analyzed using the V-PLEX Plus Proinflam Combo 10 panel and Oil Red O staining, respectively. RESULTS: In the cross-sectional study, 43 lipids were associated with smoking status at FDR<0.1, including two between ECIG and non-smokers (PC(14:0/18:1) and PC(18:0/14:0)) in pairwise follow-up analyses (Bonferroni-adjusted p<0.017). Associations between lipid species and cotinine, inflammatory markers, including IL-1β and IL-8, and LLM were also identified, as well as differences in lipid classes between smokers and the other groups. Smokers had higher saturated lipids, including ceramide (CER), sphingomyelin (SM), and diacylglycerol (DAG) than that of non-smokers and ECIG users. No significant associations were identified in the 4-week clinical trial. CONCLUSIONS: Smoking was associated with altered lipid levels, as compared to both non-smokers and ECIG users; the majority were downregulated and ECIG effects tend to be smaller in magnitude than smoking effects, although some were different than those in the smokers group. This is a novel study of healthy individuals examining lipidomic differences between smokers, ECIG users, and non-smokers, indicating potential roles of smoking and ECIG-related lipid alterations in pulmonary disease. TRIAL REGISTRATION: The study was approved by The OSU Institutional Review Board (OSU-2015C0088) in accordance with its ethical standards, the Helsinki declaration, and the Belmont Report, and is registered on Clinicaltrials.gov (NCT02596685; 2015-11-04).

BACKGROUND: Rotavirus gastroenteritis is one of major causes of death in infants, particularly in sub-Saharan Africa. In the Central African Republic (CAR), sentinel surveillance of rotavirus gastroenteritis was established in 2011. In this study, we assessed the burden of rotavirus gastroenteritis and identified rotavirus strains circulating in CAR during 2011-2021. METHODS: Stool samples were collected from < 5-year-old children with diarrhoea according to WHO criteria, at the sentinel site in Bangui, CAR. Samples were screened for group A rotavirus antigen by EIA. RNA was extracted from all EIA-positive samples which were subjected to genotyping using a semi nested RT-PCR assay. RESULTS: From 2011 to 2021, 1855 stool samples were collected and 854 (46.0%) were positive for rotavirus by EIA. Genotypes were obtained from 77.3% (660/854) EIA positive samples. Of these 660 samples, genotypes funds were: G1 (35.4%) and G2 (26.6%) for VP7, and P[6] (42.7%) and P[8] (35.6%) for the VP4 gene. The most frequent genotype combinations were G1P[8], 19.3% and G1P[6], 15.0%. CONCLUSION: This study reports the prevalence of rotavirus genotypes that circulated for ten years, providing a pre-vaccine baseline data genotype estimate for rotavirus gastroenteritis sentinel surveillance in the Central African Republic. CLINICAL TRIAL NUMBER: Not applicable.

In the United States, Shiga toxin-producing Escherichia coli (STEC) outbreaks cause >265,000 infections and cost $280 million annually. We investigated REPEXH01, a persistent strain of STEC O157:H7 associated with multiple sources, including romaine lettuce and recreational water, that has caused multiple outbreaks since emerging in late 2015. By comparing the genomes of 729 REPEXH01 isolates with those of 2,027 other STEC O157:H7 isolates, we identified a highly conserved, single base pair deletion in espW that was strongly linked to REPEXH01 membership. The biological consequence of that deletion remains unclear; further studies are needed to elucidate its role in REPEXH01. Additional analyses revealed that REPEXH01 isolates belonged to Manning clade 8; possessed the toxins stx2a, stx2c, or both; were predicted to be resistant to several antimicrobial compounds; and possessed a diverse set of plasmids. Those factors underscore the need to continue monitoring REPEXH01 and clarify aspects contributing to its emergence and persistence.

The occupation of firefighting is classified as a Group 1 carcinogen. Increased cancer risk among firefighters may be partly attributable to increased occupational exposure to a range of chemicals, including per- and polyfluoroalkyl substances (PFAS). Some PFAS are known and suspect human carcinogens. Investigating epigenetic response to these PFAS exposures in firefighters may help to identify biological pathways of specific cancers, and previously unidentified health outcomes that are associated with PFAS. We therefore investigated the associations of serum PFAS concentrations with miRNA expression in firefighters. Serum samples collected from 303 firefighters from 6 sites across the USA were analyzed for 9 PFAS along with miRNA expression. Covariate-adjusted linear regression was used to estimate associations between log PFAS and miRNA expression, with false discovery rate (FDR) set to 0.05 for significance, and an exploratory cutoff of FDR q<0.20. Gene set enrichment analysis (GSEA) was performed using miRTarBase's miRWalk pathways. Age, race-ethnicity, BMI, fire department, and sex were controlled for in all models. At FDR<0.05, the linear isomer of perfluorooctane sulfonic acid (PFOS) was inversely associated with miR-128-1-5p expression (Beta = -0.146, 95% CI -0.216, -0.076). At a relaxed FDR of 0.20, we observed inverse associations for the sum of branched isomers of PFOS (Sm-PFOS) with 5 miRNAs (let-7d-5p, let-7a-5p, miR-423-5p, let-7b-5p, miR-629-5p). Several pathways were enriched for multiple PFAS, including those correlated with certain cancers, blood diseases, thyroid disorders, autoimmune disorders, and neurological outcomes. Some PFAS in firefighters were found to be associated with alteration of miRNA consistent with increased risk for a range of chronic diseases.

Exposure to endocrine-disrupting chemicals such as phthalates may increase risk of hypertensive disorders of pregnancy (HDP). Prior studies lack investigation of chemical mixtures, phthalate replacements, or key periods of susceptibility including early pregnancy. In the present study, we used a longitudinal approach to evaluate gestational exposure to phthalates and replacements, as both single-pollutants and mixtures, in association with blood pressure and diagnosis of preeclampsia or any HDP. The Human Placenta and Phthalates prospective pregnancy cohort includes 291 participants recruited from two U.S. clinics. Urinary metabolites of ten phthalates and replacements were quantified at up to 8 time points per individual and averaged to create early (12-15 weeks) and overall (12-38 weeks) pregnancy exposure biomarkers. We collected data on gestational blood pressure (mean = 6.2 measures per participant) and diagnosis of preeclampsia (n = 26 cases) or any HDP (n = 44 cases). Linear mixed effects models estimated associations between exposure biomarkers and repeated blood pressure measures. We estimated exposure biomarker associations with preeclampsia and HDP using Cox proportional hazards or logistic regression models, respectively. Quantile g-computation was used to estimate joint effects of a phthalate or replacement mixture with each outcome. Early pregnancy exposure biomarkers demonstrated greater associations with adverse outcomes compared to overall pregnancy. A one-interquartile range increase in early pregnancy di-isononyl phthalate metabolites (ƩDiNP) was associated with a 1.13 mmHg (95 % confidence interval [CI]: 0.25, 2.37) and 0.90 mmHg (CI: 0.16, 1.65) increase in systolic and diastolic blood pressure, respectively. We also found positive but nonsignificant associations of early pregnancy mono-3-carboxypropyl phthalate, di-2-ethylhexyl terephthalate metabolites, and the high molecular weight phthalate mixture with blood pressure. Early pregnancy ƩDiNP was furthermore associated with increased odds of HDP (odds ratio: 1.37, CI: 1.03, 1.82), but not preeclampsia. In sum, early gestational exposure to DiNP and other high molecular weight phthalates may contribute to HDP.

Bacterial meningitis is a significant public health concern, with over 1.2 million cases reported globally each year. Rwanda is at increased risk of meningitis outbreaks due to its proximity to countries that lie in the meningitis belt. Rwanda has been conducting surveillance and recording meningitis outbreak cases across the country since 2012. We evaluated the meningitis surveillance system at Kibogora Level Two Teaching hospital, Nyamasheke district of Rwanda to assess whether the surveillance objectives were being met. The study was cross-sectional, using purposive sampling to select healthcare providers participating in the meningitis surveillance. Rwanda's bacterial meningitis data from 2017 to 2021 was collected from clinical registers and Rwanda's electronic integrated disease surveillance system (eIDSR) from Kibogora Level Two Teaching Hospital catchment area, Nyamasheke district, Rwanda. The study area was chosen because a meningitis outbreak was recorded in the area and its bordering country namely Democratic of Republic of Congo (DRC) prior to the current study period. Information on the participant's demographics, occupation, training, professional experience, and their perception on the surveillance system were gathered using a structured questionnaire. Meningitis surveillance systems attributes including usefulness, acceptability, and flexibility were assessed and categorized as poor (< 50% score), reasonable (50-69%), good (70-90%), or excellent (> 90%) in reference to the study conducted on the evaluation of the meningitis surveillance system in Luanda Province, Angola in March 2017. Data collected from clinical registers and eIDSR were used to assess core functions of the meningitis surveillance system including accuracy in detection of cases, laboratory confirmation of cases, and availability of evaluation reports. Descriptive statistics were analyzed using Microsoft Office Excel. Thirty-one healthcare providers working on meningitis surveillance in the Kibogora Level Two Teaching Hospital were interviewed. During the period under evaluation, 48 suspected cases of meningitis were identified; 43 (90%) met the surveillance case definition, and only 10 (21%) were reported to eIDSR (completeness). Attributes such as flexibility scored good while stability and acceptability scored reasonable. Out of 48 suspected meningitis cases, only 2 (4%) samples were collected from patients and sent to the hospital laboratory for analysis. This study found a good knowledge level of the meningitis surveillance system among healthcare workers; however, the system's core functions, such as notification rate and laboratory confirmation were found to have gaps. The notification rate could be improved by conducting regular refresher courses for healthcare workers supporting surveillance system. Moreover, MoH could enhance the implementation of a national policy requiring mandatory CSF sample testing to confirm pathogens for all suspected cases. Future studies should explore performance-based incentives to improve reporting completeness. Rwanda's experience could provide insights for other low-resource settings facing similar surveillance challenges.

BACKGROUND AND OBJECTIVES: In 2023, the Advisory Committee on Immunization Practices recommended either Abrysvo, a vaccine administered during pregnancy, or nirsevimab, a monoclonal antibody administered to infants after birth, to protect infants from respiratory syncytial virus (RSV). Our objective was to assess the proportion of infants immunized against RSV through antenatal RSV vaccination or receipt of nirsevimab among linked pregnancy-infant dyads. METHODS: Using data from 10 Vaccine Safety Datalink health systems and a validated algorithm, we identified pregnant women aged 12 to 55 years with a live birth of 32 weeks' gestation or more from September 22, 2023, through March 31, 2024. We identified RSV vaccination using electronic health records supplemented with immunization information system (registry) data. Among infants from eligible pregnancies, we identified nirsevimab administered through March 31, 2024. We assessed infant RSV immunization, defined as exposure to antenatal RSV vaccination or receipt of nirsevimab, stratified by race and ethnicity, age, and birth month. RESULTS: A total of 36 949 eligible infants were included from 43 722 pregnancies. Overall, 72% of infants were immunized against RSV; estimates were highest among infants born to non-Hispanic (NH) Asian mothers (84%). Disparities were identified by race, with 60% coverage among infants born to NH Black or NH Middle Eastern or North African mothers. Coverage was 59% to 78% by birth month, with nirsevimab more commonly administered to infants born earlier in the season. CONCLUSIONS: In this population of infants, 72% were immunized against RSV. Although overall coverage was high, disparities in immunization by race and ethnicity are a call to action.

OBJECTIVE: To examine the joint associations of plasma concentrations of prenatal per- and polyfluoroalkyl substances (PFAS) mixtures with birth size and postnatal anthropometry measures. MATERIAL AND METHODS: The current study included 641 mother-child dyads from the New Hampshire Birth Cohort Study. PFAS concentrations were quantified in maternal plasma samples collected during pregnancy (median: 28 weeks of gestation). Information on infant weight and length were abstracted from medical records and converted to sex- and age-standardized weight-for-length z-score according to the World Health Organization standard curves. Bayesian kernel machine regression (BKMR) was used to investigate the joint associations of multiple PFAS concentrations during pregnancy with weight-for-length z score at birth, 6-months, and 12-months. To account for longitudinal outcomes, we also fit linear mixed effect models between PFAS exposure burden score, a novel method to quantify total exposure burden to PFAS mixtures, and changes in weight-for-length from birth to 12 months of age. A multiplicative interaction term ("PFAS burden score × time [birth as a reference, 6 months, and 12 months of age]") was included to evaluate a potential time-varying relationship. All models were adjusted for maternal age, education, marital status, parity, smoking, seafood consumption, pre-pregnancy body mass index, and gestational week of blood draw. RESULTS: In BKMR models, all 95 % credible intervals included the null value. In linear mixed effects models, PFAS exposure burden score was associated with a lower weight-for-length z-score (β = -0.20; 95 % confidence interval = -0.35, -0.04). The multiplicative interaction term was significant at both 6 and 12 months of age (P < 0.01 for both time points), particularly among female infants, suggesting a shift toward positive associations between the prenatal PFAS mixtures and weight-for-length z-score during infancy. CONCLUSIONS: Prenatal PFAS mixtures may affect fetal and infant anthropometry measures differently by life stage and biological sex.

Whipple's disease is rarely diagnosed in Latin America. We describe 2 patients with Tropheryma whipplei infection diagnosed in Mexico during 2019-2021. Diagnoses were confirmed by histopathology, electron microscopy, immunohistochemistry, and DNA amplification and sequencing analysis of the 16S rRNA gene. Clinicians should be aware of T. whipplei infection and associated syndromes.

We report 1.3% (19/1,511) of Egyptian rousette bats (ERBs) in Uganda and Sierra Leone were co-infected with different combinations of Marburg, Sosuga, Kasokero, or Yogue viruses. To prevent infection by those viruses, we recommend avoiding ERB-populated areas, avoiding ERBs and ERB-contaminated objects, and thoroughly washing harvested fruits before consumption.

Marburg virus (MARV) and Ravn virus (RAVV), the only two known members of the species Orthomarburgvirus marburgense (family Filoviridae), are causative agents of Marburg virus disease, a severe viral disease that typically emerges in sub-Saharan Africa and is characterized by human-to-human transmission and high case fatalities. Despite the robust characterization of MARV experimental infection in Egyptian rousette bats (ERBs; Rousettus aegyptiacus; common name: Egyptian rousettes), a natural MARV reservoir, experimental infection with RAVV in ERBs has not been completed. Here, we experimentally infect 12 ERBs with RAVV and quantify viral loads in blood, oral swabs, and rectal swabs over a 21-day timeline with serological and cumulative shedding data and baseline clinical parameters. Compared to previously described experimental MARV infection in ERBs, these bats experimentally inoculated with RAVV had significantly higher and prolonged rectal viral shedding loads, as well as significantly prolonged oral shedding and higher peak viremia. All ERBs seroconverted by 21 days post-infection. Additionally, all ERBs demonstrated marked heterogeneity in RAVV viral shedding loads consistent with the Pareto Principle and viral "supershedders." Our results introduce the possibility of variation in transmission dynamics and subsequent spillover differences between RAVV and MARV.IMPORTANCERavn virus, along with Marburg virus, causes severe viral disease in humans with high fatality but little to no clinical disease in its reservoir host, the Egyptian rousette bat. Our findings provide important insights into how Ravn virus behaves in its natural reservoir host, showing that Ravn virus infection followed a similar timeline to Marburg virus infection, with virus detected in blood, saliva, and feces. However, Ravn virus-infected bats had higher levels of viral shedding and shed the virus for a longer period, particularly in feces, compared to Marburg virus. These differences in viral shedding may impact the spread of the virus within bat populations and potentially alter the likelihood of spillover into humans, non-human primates, and other animal species. These insights are crucial for understanding Ravn virus maintenance in its bat reservoir and improving our ability to mitigate or prevent future human outbreaks.

The range of Babesia microti (Franca, 1910)-infected ticks is expanding, resulting in locally acquired human babesiosis cases occurring in new areas: Maryland (2009), the District of Columbia (2013), Virginia (2016), and West Virginia (2017). We collected host-seeking ticks from old fields, ecotones, forested habitats and animal hosts in Delaware, Maryland, and Virginia, 2010 to 2024. Ixodes scapularis Say, the tick vector of babesiosis, was captured in all 3 states. PCR revealed B. microti in 2.7% (36/1310) of I. scapularis, with site prevalence ranging from <1% to 12.5% infected. The first B. microti-positive I. scapularis was collected in Northampton County, Virginia, 2012. Of the B. microti-infected ticks, 50% (18/36) were coinfected with Borrelia burgdorferi and one was triple-infected with B. microti, B. burgdorferi, and Anaplasma phagocytophilum. We collected Ixodes keiransi Beati, Nava, Venzal, and Guglielmone ticks from Delaware and Virginia. We found B. microti and B. burgdorferi in those from Virginia, and B. burgdorferi in ticks from a shrew in Delaware. To our knowledge, this is the first report of B. microti and B. burgdorferi-positive I. keiransi from Virginia, and the first report of B. burgdorferi-positive I. keiransi from Delaware. Ixodes keiransi ticks rarely bite humans but are involved in the maintenance and spread of pathogens when sympatric with I. scapularis. We tested a subset of both tick species for Babesia duncani; none were positive. Jurisdictions in the southern mid-Atlantic region should expect babesiosis cases, and Lyme disease and anaplasmosis coinfections, and healthcare providers should consider these tick-borne infections as part of the differential diagnosis.

Global risk maps are an important tool for assessing the global threat of mosquito and tick-transmitted arboviral diseases. Public health officials increasingly rely on risk maps to understand the drivers of transmission, forecast spread, identify gaps in surveillance, estimate disease burden, and target and evaluate the impact of interventions. Here, we describe how current approaches to mapping arboviral diseases have become unnecessarily siloed, ignoring the strengths and weaknesses of different data types and methods. This places limits on data and model output comparability, uncertainty estimation and generalisation that limit the answers they can provide to some of the most pressing questions in arbovirus control. We argue for a new generation of risk mapping models that jointly infer risk from multiple data types. We outline how this can be achieved conceptually and show how this new framework creates opportunities to better integrate epidemiological understanding and uncertainty quantification. We advocate for more co-development of risk maps among modellers and end-users to better enable risk maps to inform public health decisions. Prospective validation of risk maps for specific applications can inform further targeted data collection and subsequent model refinement in an iterative manner. If the expanding use of arbovirus risk maps for control is to continue, methods must develop and adapt to changing questions, interventions and data availability.