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Disability after childhood diarrhea is an important burden on global productivity. Recent studies suggest that gut bacterial communities influence how humans recover from infectious diarrhea, but we still lack extensive data and mechanistic hypotheses for how these bacterial communities respond to diarrheal disease and its treatment. Here, we report that after Vibrio cholerae infection, the human gut microbiota undergoes an orderly and reproducible succession that features transient reversals in relative levels of enteric Bacteroides and Prevotella . Elements of this succession may be a common feature in microbiota recovery from acute secretory diarrhea, as we observed similar successional dynamics after enterotoxigenic Escherichia coli (ETEC) infection. Our metagenomic analyses suggest that multiple mechanisms drive microbial succession after cholera, including bacterial dispersal properties, changing enteric oxygen and carbohydrate levels, and phage dynamics. Thus, gut microbiota recovery after cholera may be predictable at the level of community structure but is driven by a complex set of temporally varying ecological processes. Our findings suggest opportunities for diagnostics and therapies targeting the gut microbiota in humans recovering from infectious diarrhea. IMPORTANCE Disability after diarrhea is a major burden on public health in the developing world. Gut bacteria may affect this recovery, but it remains incompletely understood how resident microbes in the digestive tract respond to diarrheal illness. Here, we observed an orderly and reproducible succession of gut bacterial groups after cholera in humans. Genomic analyses associated the succession with bacterial dispersal in food, an altered microbial environment, and changing phage levels. Our findings suggest that it may one day be feasible to manage resident bacterial populations in the gut after infectious diarrhea. Disability after diarrhea is a major burden on public health in the developing world. Gut bacteria may affect this recovery, but it remains incompletely understood how resident microbes in the digestive tract respond to diarrheal illness. Here, we observed an orderly and reproducible succession of gut bacterial groups after cholera in humans. Genomic analyses associated the succession with bacterial dispersal in food, an altered microbial environment, and changing phage levels. Our findings suggest that it may one day be feasible to manage resident bacterial populations in the gut after infectious diarrhea.

The degree of protection conferred after receiving an oral cholera vaccine (OCV) varies based on age, prior exposure to Vibrio cholerae , and unknown factors. Recent evidence suggests that the microbiota may mediate some of the unexplained differences in oral vaccine responses. Here, we use metagenomic sequencing of the fecal microbiota at the time of vaccination and relate microbial features to immune responses after OCV using a reference-independent gene-level method. We find that the presence of sphingolipid-producing bacteria is associated with the development of protective immune responses after OCV. We test these associations by stimulating human macrophages with Bacteroides xylanisolvens metabolites and find that sphingolipid-containing extracts increase innate immune responses to OCV antigens. Our findings demonstrate a new analytic method for translating metagenomic sequencing data into strain-specific results associated with a biological outcome, and in validating this tool, we identify that microbe-derived sphingolipids impact immune responses to OCV antigens. The microbiota may mediate the differential responses to oral cholera vaccine (OCV). Here, the authors reveal that the presence of sphingolipid-producing bacteria is associated with the development of protective immune responses after OCV.

Two circular chromosomes are a defining feature of the bacterial family Vibrionaceae , including the pathogen Vibrio cholerae , with rare reports of isolates with a single, fused chromosome. Here, we use long-read sequencing to analyse 467  V. cholerae O1 isolates from 47 cholera patients and household contacts in Bangladesh. We identify several independent chromosome fusion events that are likely transmissible within a household. Fusions occur in a 12 kilobase-pair homologous sequence shared between the two chromosomes and are stable for at least 200 generations under laboratory conditions. We find no detectable effect of fusion on V. cholerae growth, virulence factor expression, or biofilm formation. The factors promoting fusion, affecting chromosome stability, and subtle phenotypic or clinical consequences merit further investigation. The pathogenic bacterium Vibrio cholerae typically has two circular chromosomes. Here, Cuénod et al. analyse 467 clinical isolates and identify several independent chromosome fusion events that are likely transmissible within a household, can be stable for 200 generations under laboratory conditions, and do not substantively affect bacterial growth, virulence factor expression, or biofilm formation.

ObjectivesTo examine outcomes from respiratory pathogens containment strategies focused on international travellers.DesignWe developed a compartmental model generalisable to respiratory infectious diseases, in which international travellers interact with each other and airline/airport workers during transit. We used SARS-CoV-2 Omicron surge data (basic reproduction number (R0): 9.5) as a case example and performed sensitivity and scenario analyses, including varying the R0 for different respiratory pathogens.SettingsA US high-volume airport.ParticipantsSimulated international travellers and airline/airport workers.InterventionsProjection of new and imported SARS-CoV-2 infections without intervention (No Intervention); pre-travel screening for travellers who intend to travel (intended travellers) with PCR (Pre-travel PCR); or antigen testing (Pre-travel Ag); mask-wearing guidance for travellers and workers (Mask-wearing); and a Combined strategy (Pre-travel PCR & Mask-wearing).Outcome measuresThe number of new and imported respiratory disease infections over the 90-day simulation period.ResultsOver the 90-day simulation, the number of infected travellers entering the USA would be: 1 155 580 (27.2% of 4.2 million (M) intended travellers) with No Intervention; 709 560/4.2M (16.7%) with Pre-travel PCR; 862 330/4.2M (20.3%) with Pre-travel Ag; 1033 820/4.2M (24.4%) with Mask-wearing; and 650 480/4.2M (15.3%) with Combined. The number of new infections among airline/airport workers would be: 25 670 (73.3% of 35 000 workers) with No Intervention; 25 260 (72.2%) in Pre-travel PCR; 25 590 (73.1%) in Pre-travel Ag; 24 630 (70.4%) in Mask-wearing; and 18 770 (53.6%) in Combined. In scenario analyses, the most impactful parameters were R0 of the respiratory pathogen and population immunity level.ConclusionsA Combined strategy of pre-travel PCR testing and mask-wearing would most effectively reduce respiratory infection among international travellers and airline/airport workers, but would still allow a substantial number of infections to enter the USA, especially when the pathogen is highly transmissible.

Interventional studies targeting environment enteropathy (EE) are impeded by the lack of appropriate, validated, non-invasive biomarkers of EE. Thus, we aimed to validate the association of potential biomarkers for EE with enteric infections and nutritional status in a longitudinal birth cohort study. We measured endotoxin core antibody (EndoCab) and soluble CD14 (sCD14) in serum, and myeloperoxidase (MPO) in feces using commercially available enzyme-linked immunosorbent assay (ELISA) kits. We found that levels of serum EndoCab and sCD14 increase with the cumulative incidence of enteric infections. We observed a significant correlation between the fecal MPO level in the children at 24 months of age with the total number of bacterial and viral infections, the total number of parasitic infections, and the total number of diarrheal episodes and diarrheal duration. We observed that the levels of serum EndoCab, sCD14, and fecal MPO at 3 months of age were significantly associated with whether children were malnourished at 18 months of age or not. Biomarkers such as fecal MPO, serum EndoCab and sCD14 in children at an early age may be useful as a measure of cumulative burden of preceding enteric infections, which are predictive of subsequent malnutrition status and may be useful non-invasive biomarkers for EE.

Understanding the characteristics of the humoral immune responses following COVID-19 vaccinations is crucial for refining vaccination strategies and predicting immune responses to emerging SARS-CoV-2 variants. A longitudinal analysis of SARS-CoV-2 spike receptor binding domain (RBD) specific IgG antibody responses, encompassing IgG subclasses IgG1, IgG2, IgG3, and IgG4 was performed. Participants received four mRNA vaccine doses (group 1; n=10) or two ChAdOx1 nCoV-19 and two mRNA booster doses (group 2; n=19) in Bangladesh over two years. Findings demonstrate robust IgG responses after primary Covishield or mRNA doses; declining to baseline within six months. First mRNA booster restored and surpassed primary IgG responses but waned after six months. Surprisingly, a second mRNA booster did not increase IgG levels further. Comprehensive IgG subclass analysis showed primary Covishield/mRNA vaccination generated predominantly IgG1 responses with limited IgG2/IgG3, Remarkably, IgG4 responses exhibited a distinct pattern. IgG4 remained undetectable initially but increased extensively six months after the second mRNA dose, eventually replacing IgG1 after the 3rd/4th mRNA doses. Conversely, initial Covishield recipients lack IgG4, surged post-second mRNA booster. Notably, mRNA-vaccinated individuals displayed earlier, robust IgG4 levels post first mRNA booster versus Covishield counterparts. IgG1 to IgG4 ratios decreased with increasing doses, most pronounced with four mRNA doses. This study highlights IgG response kinetics, influenced by vaccine type and doses, impacting immunological tolerance and IgG4 induction, shaping future vaccination strategies. This study highlights the dynamics of IgG responses dependent on vaccine type and number of doses, leading to immunological tolerance and IgG4 induction, and shaping future vaccination strategies.

COVID-19 caused by SARS-CoV-2 ranges from asymptomatic to severe disease and can cause fatal and devastating outcome in many cases. In this study, we have compared the clinical, biochemical and immunological parameters across the different disease spectrum of COVID-19 in Bangladeshi patients. This longitudinal study was conducted in two COVID-19 hospitals and also around the community in Dhaka city in Bangladesh between November 2020 to March 2021. A total of 100 patients with COVID-19 infection were enrolled and classified into asymptomatic, mild, moderate and severe cases (n = 25/group). In addition, thirty age and sex matched healthy participants were enrolled and 21 were analyzed as controls based on exclusion criteria. After enrollment (study day1), follow-up visits were conducted on day 7, 14 and 28 for the cases. Older age, male gender and co-morbid conditions were the risk factors for severe COVID-19 disease. Those with moderate and severe cases of infection had low lymphocyte counts, high neutrophil counts along with a higher neutrophil-lymphocyte ratio (NLR) at enrollment; this decreased to normal range within 42 days after the onset of symptom. At enrollment, D-dimer, CRP and ferritin levels were elevated among moderate and severe cases. The mild, moderate, and severe cases were seropositive for IgG antibody by day 14 after enrollment. Moderate and severe cases showed significantly higher IgM and IgG levels of antibodies to SARS-CoV-2 compared to mild and asymptomatic cases. We report on the clinical, biochemical, and hematological parameters associated with the different severity of COVID-19 infection. We also show different profile of antibody response against SARS-CoV-2 in relation to disease severity, especially in those with moderate and severe disease manifestations compared to the mild and asymptomatic infection.

Global travel plays a role in the spread of infectious diseases. Existing travel surveillance programs collect data before and after trips, resulting in data incompleteness and recall bias. We developed the Travel Healthy mobile app to address these gaps, by enabling U.S. travelers to report daily symptom surveys including GPS location. The app offers traveler tools, including outbreak notices, a travel wallet, and a malaria medication reminder. We developed Travel Healthy following a user-centric approach. We recruited study participants through an online platform and at the Travelers’ Advice and Immunization Center at Massachusetts General Hospital, between July 2023 and August 2024. We analyzed demographic, GPS, and self-reported symptom data from the first 50 participants. Data were collected starting one day before the trip and ending three days after. A post-travel feedback survey was performed. Participants visited 204 locations in Asia, Africa, the Americas, and Europe. Mean age was 33 years and 66 % were female. The most common purposes of travel were leisure and/or business, with 46 (92 %) of participants listing these as traveling reasons. A total of 755 daily symptom surveys were entered, with 105 reporting symptoms, corresponding to 29 of the 50 (58 %) participants. Among all symptoms with GPS data, 58 % were upper respiratory symptoms, 25 % were gastrointestinal (clustered in South Asia), and 17 % were other. Post-travel questionnaires showed that participants found the application easy to use. This pilot study underscores the potential of participatory surveillance tools to complement traditional public health surveillance methods for travel-related illness. •The Travel Healthy app enables U.S. travelers to report daily symptom surveys, including GIS location.•Travel Healthy generates high-resolution disease surveillance during travel that would be hard to obtain otherwise.•We applied a user-centric approach to make the app easy to use and to provide useful features to travelers.•We report demographics and symptoms of the first 50 users, who visited 204 locations in Asia, Africa, the Americas, and Europe.

The effects of climate disruption are fundamentally health issues. As physicians, we have a special responsibility to safeguard health and alleviate suffering, and individual actions are far from enough to address the challenge we collectively face.