Search

Background Household transmission studies inform how viruses spread among close contacts, but few characterize household transmission of endemic coronaviruses. Methods We used data collected from 223 households with school-age children participating in weekly disease surveillance over 2 respiratory virus seasons (December 2015 to May 2017), to describe clinical characteristics of endemic human coronaviruses (HCoV-229E, HcoV-HKU1, HcoV-NL63, HcoV-OC43) infections, and community and household transmission probabilities using a chain-binomial model correcting for missing data from untested households. Results Among 947 participants in 223 households, we observed 121 infections during the study, most commonly subtype HCoV-OC43. Higher proportions of infected children ( Conclusions Our study highlights the need for large household studies to inform household transmission, the challenges in estimating household transmission probabilities from asymptomatic individuals, and implications for controlling endemic CoVs.

Cholera remains a major threat in sub-Saharan Africa (SSA), where some of the highest case-fatality rates are reported. Knowing in what months and where cholera tends to occur across the continent could aid in improving efforts to eliminate cholera as a public health concern. However, largely due to the absence of unified large-scale datasets, no continent-wide estimates exist. In this study, we aimed to estimate cholera seasonality across SSA and explore the correlation between hydroclimatic variables and cholera seasonality.Using the global cholera database of the Global Task Force on Cholera Control, we developed statistical models to synthesise data across spatial and temporal scales to infer the seasonality of excess (defined as incidence higher than the 2010-16 mean incidence rate) suspected cholera occurrence in SSA. We developed a Bayesian statistical model to infer the monthly risk of excess cholera at the first and second administrative levels. Seasonality patterns were then grouped into spatial clusters. Finally, we studied the association between seasonality estimates and hydroclimatic variables (mean monthly fraction of area flooded, mean monthly air temperature, and cumulative monthly precipitation).24 (71%) of the 34 countries studied had seasonal patterns of excess cholera risk, corresponding to approximately 86% of the SSA population. 12 (50%) of these 24 countries also had subnational differences in seasonality patterns, with strong differences in seasonality strength between regions. Seasonality patterns clustered into two macroregions (west Africa and the Sahel vs eastern and southern Africa), which were composed of subregional clusters with varying degrees of seasonality. Exploratory association analysis found most consistent and positive correlations between cholera seasonality and precipitation and, to a lesser extent, between cholera seasonality and temperature and flooding.Widespread cholera seasonality in SSA offers opportunities for intervention planning. Further studies are needed to study the association between cholera and climate.US National Aeronautics and Space Administration Applied Sciences Program and the BillMelinda Gates Foundation.

Genomic surveillance has shaped our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. We performed a global landscape analysis on SARS-CoV-2 genomic surveillance and genomic data using a collection of country-specific data. Here, we characterize increasing circulation of the Alpha variant in early 2021, subsequently replaced by the Delta variant around May 2021. SARS-CoV-2 genomic surveillance and sequencing availability varied markedly across countries, with 45 countries performing a high level of routine genomic surveillance and 96 countries with a high availability of SARS-CoV-2 sequencing. We also observed a marked heterogeneity of sequencing percentage, sequencing technologies, turnaround time and completeness of released metadata across regions and income groups. A total of 37% of countries with explicit reporting on variants shared less than half of their sequences of variants of concern (VOCs) in public repositories. Our findings indicate an urgent need to increase timely and full sharing of sequences, the standardization of metadata files and support for countries with limited sequencing and bioinformatics capacity.

Improvements in water and sanitation should reduce cholera risk. But it is unclear which water and sanitation access are associated with cholera risk. We estimated the association between eight water and sanitation measures and annual cholera incidence access across sub-Saharan Africa (2010-2016) for data aggregated at the country and district-level. We fit random forest regression and classification models to understand how well these measures combined might be able to predict cholera incidence rates and identify high cholera incidence areas. Across spatial scales, piped or “other improved” water access was inversely associated with cholera incidence. Access to piped water, piped sanitation, and piped or “other improved” sanitation were associated with decreased district-level cholera incidence. The classification model had moderate skill in identifying high cholera incidence areas (cross-validated-AUC 0.81 95%CI 0.78–0.83) with high negative predictive values (92.5–100.0%) indicating the utility of water and sanitation measures for screening out areas that are unlikely to be cholera hotspots. While comprehensive cholera risk assessments must incorporate other data sources (e.g., historical incidence), our results suggest that water and sanitation measures could alone be useful in narrowing the geographic focus for detailed risk assessments.SynopsisWe quantified the relationship between high-resolution estimates of water and sanitation access and cholera incidence and assessed the utility of water and sanitation measures in identifying high risk geographic areas in sub-Saharan Africa.

After three years with no confirmed cholera cases in Haiti, an outbreak ofVibrio choleraeO1 emerged in October 2022. Levels of pre-existing antibodies provide an estimate of prior immunologic exposure, reveal potentially relevant immune responses, and set a baseline for future serosurveillance. We analyzed dried blood spots collected in 2021 from a population-weighted representative cross-sectional serosurvey in two communes in the Ouest Department of Haiti. We found lower levels of circulating IgG and IgA antibodies againstV. choleraelipopolysaccharide (LPS, IgG and IgA pV. choleraeLPS IgG, suggest that populations in Haiti may be highly susceptible to cholera disease, especially among young children.

ObjectivesThis cohort study including essential workers, assessed the□risk and incidence of SARS-CoV-2□infection during the second surge of COVID-19 according to baseline serostatus and occupational sector.MethodsEssential workers were selected from a seroprevalence survey cohort in Geneva, Switzerland and were linked to a state centralized registry compiling SARS-CoV-2 infections. Primary outcome was the number of virologically-confirmed infections from serological assessment (between May and September 2020) to January 25, 2021, according to baseline antibody status and stratified by three pre-defined occupational groups (occupations requiring sustained physical proximity, involving brief regular contact or others). Secondary outcomes included the incidence of infection.Results10457 essential workers were included (occupations requiring sustained physical proximity accounted for 3057 individuals, those involving regular brief contact, 3645, and 3755 workers were classified under “Other essential occupations”). After a follow-up period of over 27 weeks, 5 (0.6%) seropositive and 830 (8.5%) seronegative individuals had a positive SARS-CoV-2 test, with an incidence rate of 0.2 (95% CI 0.1 to 0.6) and 3.2 (95% CI 2.9 to 3.4) cases per person-week, respectively. Incidences were similar across occupational groups. Seropositive essential workers had a 93% reduction in the hazard (HR of 0.07, 95% CI 0.03 to 0.17) of having a positive test during follow-up with no significant between-occupational group difference.ConclusionsA ten-fold reduction in the hazard of being virologically tested positive was observed among anti-SARS-CoV-2 seropositive essential workers regardless of their sector of occupation, confirming the seroprotective effect of a previous SARS-CoV2 exposure at least six months after infection.Key messagesWhat is already known about this subject?Risk of SARS-CoV-2 reinfection is low in the general population and among healthcare workers.What are the new findings?A ten-fold reduction of risk of being virologically tested positive reinfection is observed among anti-SARS-CoV-2 seropositive essential workers of different activity sectors, regardless of their occupation-related risk of exposure.How might this impact on policy or clinical practice in the foreseeable future?Vaccination could be delayed in individuals with previous history of SARS-CoV-2 infection with serologic confirmation, regardless of their occupational exposure. These observations need to be confirmed for new SARS-CoV-2 variants.

Binding antibody levels against SARS-CoV-2 have shown to be correlates of protection against infection with pre-Omicron lineages. This has been challenged by the emergence of immune-evasive variants, notably the Omicron sublineages, in an evolving immune landscape with high levels of cumulative incidence and vaccination coverage. This in turn limits the use of commercially available high-throughput methods to quantify binding antibodies as a tool to monitor protection at the population-level. In this work, we leverage repeated serological measurements between April 2020 and December 2021 on 1’083 participants of a population-based cohort in Geneva, Switzerland, to evaluate anti-Spike RBD antibody levels as a correlate of protection against Omicron BA.1/BA.2 infections during the December 2021-March 2022 epidemic wave. We do so by first modeling antibody dynamics in time with kinetic models. We then use these models to predict antibody trajectories into the time period where Omicron BA.1/BA.2 were the predominant circulating sub-lineages and use survival analyses to compare the hazard of having a positive SARS-CoV-2 test by antibody level, vaccination status and infection history. We find that antibody kinetics in our sample are mainly determined by infection and vaccination history, and to a lesser extent by demographics. After controlling for age and previous infections (based on anti-nucleocapsid serology), survival analyses reveal a significant reduction in the hazard of having a documented positive SARS-CoV-2 infection during the Omicron BA.1/BA.2 wave with increasing antibody levels, reaching up to a three-fold reduction for anti-S antibody levels above 800 IU/mL (HR 0.30, 95% CI 0.22-0.41). However, we did not detect a reduction in hazard among uninfected participants. Taken together these results indicate that anti-Spike RBD antibody levels, as quantified by the immunoassay used in this study, are an indirect correlate of protection against Omicron BA.1/BA.2 for individuals with a history of previous SARS-CoV-2 infection. Despite the uncertainty in what SARS-COV-2 variant will come next, these results provide reassuring insights into the continued interpretation of SARS-CoV-2 binding antibody measurements as an independent marker of protection at both the individual and population levels.

BackgroundHepatitis E virus, typically genotypes 1 and 2, is a major cause of avoidable morbidity and mortality in South Asia. Although case fatality risk among pregnant women can reach as high as 25%, a lack of population-level disease burden data has been cited as a primary factor in key global policy recommendations against the routine use of licensed hepatitis E vaccines, one of the only effective tools available for preventing disease and death.MethodsWe tested serum from a nationally-representative serosurvey in Bangladesh for anti-HEV IgG. We estimated the proportion of the population with evidence of historical HEV infection and used Bayesian geostatistical models to generate high-resolution national maps of seropositivity. We examined variability in seropositivity by individual-level, household-level, and community-level risk factors using spatial logistic regression.ResultsWe tested serum samples from 2924 individuals from 70 communities representing all divisions of Bangladesh and estimated a national seroprevalence of hepatitis E of 20% (95% CI 17-24%). Seropositivity increased with age and male sex (OR: 2.2, 95% CI: 1.8–2.8). Community-level seroprevalence ranged from 0-78% with the seroprevalence in urban areas being higher, including Dhaka, the capital, with 3-fold (95%CrI 2.3-3.7) higher seroprevalence than the rest of the country.ConclusionHepatitis E infections are common throughout Bangladesh, though 90% of women reach reproductive age without any evidence of previous exposure to the virus, thus likely susceptible to infection and disease. Strengthening clinical surveillance for hepatitis E, especially in urban areas may help generate additional evidence needed to appropriately target interventions like vaccines to the populations most likely to benefit.

IntroductionOral cholera vaccines (OCVs), though in short supply globally, can effectively reduce the risk of cholera caused by pandemicVibrio choleraeO1, which is highly variable in space and time. Few cholera surveillance systems perform systematic confirmatory testing forV. cholerae, which limits the efficient selection of vaccination campaign targets and public health impact of OCV.MethodsWe developed a spatial modeling framework that simulates vaccine targeting and changing cholera susceptibility and burden for 35 countries in Africa from 2022-2035. We explored the relative gains in efficiency across 18 vaccination scenarios that varied by their vaccination targeting approach and confirmatory testing capacity. Efficiency was calculated as the number of true cholera cases averted per 1,000 fully vaccinated persons.ResultsScenarios with more restrictive targeting-defined by greater bacteriological confirmation capacity, smaller geographic targeting scale, and higher incidence rate thresholds-were associated with higher vaccination campaign efficiency. The most restrictive scenario averted 9.41 (95% PI: 7.76-11.88) cases per 1,000 fully vaccinated persons. This was 10 times more efficient than the least restrictive scenario, which vaccinated roughly 20 times as many people and only averted about 2 times as many cases. Scenarios that based targeting according to clinical surveillance averted the most cases, at the cost of using many more vaccines. Across modeled countries, scenarios with national laboratory confirmation at the national level had substantially improved efficiency compared to clinical surveillance alone, while district-level laboratory capacity yielded only minor additional gains.ConclusionLess restrictive targeting of vaccination campaigns averts the most cholera cases, while district-level bacteriological confirmation capacity that enables targeting of districts with the highest burden of true cholera represents the most efficient use of vaccine. Nevertheless, these modeling scenarios represent simplified versions of complex logistical and decision-making challenges in cholera surveillance and vaccine distribution. In reality, building testing capacity at levels in-between the national and district-levels is likely to best balance surveillance data quality with feasibility.

BackgroundCholera surveillance relies on clinical diagnosis of acute watery diarrhea. Suspected cholera case definitions have high sensitivity but low specificity, challenging our ability to characterize cholera burden and epidemiology. Our objective was to estimate the proportion of clinically suspected cholera that are true Vibrio cholerae infections and identify factors that explain variation in positivity.MethodsWe conducted a systematic review of studies from 2000-2021 that tested ≥10 suspected cholera cases for V. cholerae O1/O139 using culture, PCR and/or a rapid diagnostic test. We estimated diagnostic test sensitivity and specificity using a latent class meta-analysis. We estimated positivity using a random-effects meta-analysis, adjusting for test performance and study methodology.ResultsWe included 113 studies from 28 countries. V. cholerae positivity was lower in studies with representative sampling and lower minimum ages in suspected case definitions. After adjusting for sampling methods, case definitions, and tests, on average half (49%, 95% Credible Interval: 43%-54%) of suspected cases represented true V. cholerae infections, although variation across studies was high. Odds of a suspected case having a true infection were 1.64 (95% Credible Interval: 1.06-2.52) times higher when surveillance was initiated in response to an outbreak than in non-outbreak settings.ConclusionsBurden estimates based on suspected cases alone may overestimate the incidence of medically attended cholera about twofold. However, accounting for cases missed by traditional clinical surveillance is key to unbiased overall cholera burden estimates. Given variability between settings, assumptions about positivity, which are necessary without exhaustive testing, should be based on local data.Key pointsBy pooling results from 113 studies and adjusting for diagnostic tests and study methods, we find that approximately half of suspected cholera cases represent true Vibrio cholerae infections, though this fraction varies widely across epidemiological settings.

More than two years into the COVID-19 pandemic, most of the population has developed anti-SARS-CoV-2 antibodies from infection and/or vaccination. However, public health decision-making is hindered by the lack of up-to-date and precise characterization of the immune landscape in the population. Here, we estimated anti-SARS-CoV-2 antibodies seroprevalence and cross-variant neutralization capacity after Omicron became dominant in Geneva, Switzerland.We conducted a population-based serosurvey between April 29 and June 9, 2022, recruiting children and adults of all ages from age-stratified random samples of the general population of Geneva, Switzerland. We tested for anti-SARS-CoV-2 antibodies using commercial immunoassays targeting either the spike (S) or nucleocapsid (N) protein, and for antibody neutralization capacity against different SARS-CoV-2 variants using a cell-free Spike trimer-ACE2 binding-based surrogate neutralization assay. We estimated seroprevalence and neutralization capacity using a Bayesian modeling framework accounting for the demographics, vaccination, and infection statuses of the Geneva population.Among the 2521 individuals included in the analysis, the estimated total antibodies seroprevalence was 93.8% (95% CrI 93.1-94.5), including 72.4% (70.0-74.7) for infection-induced antibodies. Estimates of neutralizing antibodies in a representative subsample (N = 1160) ranged from 79.5% (77.1-81.8) against the Alpha variant to 46.7% (43.0-50.4) against the Omicron BA.4/BA.5 subvariants. Despite having high seroprevalence of infection-induced antibodies (76.7% [69.7-83.0] for ages 0-5 years, 90.5% [86.5-94.1] for ages 6-11 years), children aged12 years had substantially lower neutralizing activity than older participants, particularly against Omicron subvariants. Overall, vaccination was associated with higher neutralizing activity against pre-Omicron variants. Vaccine booster alongside recent infection was associated with higher neutralizing activity against Omicron subvariants.While most of the Geneva population has developed anti-SARS-CoV-2 antibodies through vaccination and/or infection, less than half has neutralizing activity against the currently circulating Omicron BA.5 subvariant. Hybrid immunity obtained through booster vaccination and infection confers the greatest neutralization capacity, including against Omicron.General Directorate of Health in Geneva canton, Private Foundation of the Geneva University Hospitals, European Commission ("CoVICIS" grant), and a private foundation advised by CARIGEST SA.

In-person schooling has proved contentious and difficult to study throughout the SARS-CoV-2 pandemic. Data from a massive online survey in the United States indicates an increased risk of COVID-19-related outcomes among respondents living with a child attending school in-person. School-based mitigation measures are associated with significant reductions in risk, particularly daily symptoms screens, teacher masking, and closure of extra-curricular activities. With seven or more mitigation measures, the association between in-person schooling and COVID-19-related outcomes all but disappears. Teachers working outside the home were more likely to report COVID-19-related outcomes, but this association is similar to other occupations (e.g., healthcare, office work). In-person schooling is associated with household COVID-19 risk, but this risk can likely be controlled with properly implemented school-based mitigation measures.One sentence summaryLiving with children attending in-person school is linked to a higher risk of COVID-19 outcomes, which school-based interventions can mitigate.

Understanding the risk of infection from household- and community-exposures and the transmissibility of asymptomatic infections is critical to SARS-CoV-2 control. Limited previous evidence is based primarily on virologic testing, which disproportionately misses mild and asymptomatic infections. Serologic measures are more likely to capture all previously infected individuals. We apply household transmission models to data from a cross-sectional, household-based population serosurvey of 4,534 people ≥5 years from 2,267 households enrolled April-June 2020 in Geneva, Switzerland. We found that the risk of infection from exposure to a single infected household member aged ≥5 years (17.3%,13.7-21.7) was more than three-times that of extra-household exposures over the first pandemic wave (5.1%,4.5-5.8). Young children had a lower risk of infection from household members. Working-age adults had the highest extra-household infection risk. Seropositive asymptomatic household members had 69.4% lower odds (95%CrI,31.8-88.8%) of infecting another household member compared to those reporting symptoms, accounting for 14.5% (95%CrI, 7.2-22.7%) of all household infections., Household-based studies can provide insights into SARS-CoV-2 transmission. Here, the authors fit transmission models to serological data from Geneva, Switzerland, and estimate that the risk of infection from single household exposure (17.3%) was higher than for extra-household exposure (5.1%).

Vibriocidal antibodies are the best characterized correlate of protection against cholera and are used to gauge immunogenicity in vaccine trials. However, there is no vibriocidal titer threshold associated with absolute protection against infection with Vibrio cholerae or with symptomatic disease in infected individuals. While other circulating antibody responses have also been associated with a decreased risk of V. cholerae infection, there has been no comprehensive comparison of correlates of protection against cholera. To address this, we analyzed 58 serum antibody biomarkers as correlates of protection against both V. cholerae infection and against cholera diarrhea in infected individuals. The study was performed in two cohorts: (1) household contacts of patients with cholera in Bangladesh, and (2) North American volunteers who were vaccinated with a single dose of CVD 103-HgR live oral cholera vaccine and then challenged with virulent V. cholerae O1 El Tor Inaba. In household contacts, we identified 20 antibody markers that were correlated with protection against V. cholerae infection, though there was overlap between distributions. Conditional random forest models identified serum antibody-dependent complement deposition, targeting the V. cholerae O1 antigen, as the most predictive individual correlate of protection from infection, while vibriocidal antibody titers were less predictive. The model that most accurately predicted protection from infection included five biomarkers, with a cross-validated area under the curve (cvAUC) of 79% (95% CI 73-85). Similarly, in North American volunteers who were challenged with V. cholerae after vaccination, a different five-biomarker model predicted protection from the development of cholera diarrhea with a cvAUC of 78% (95% CI 66-91). Thus, while several new biomarkers predict protection better than vibriocidal titers, it remains difficult to consistently predict whether an individual will be protected from future mucosal infection or symptoms using current serologic markers.

Background A rapidly increasing number of serological surveys for antibodies to SARS-CoV-2 have been reported worldwide. We aimed to synthesise, combine, and assess this large corpus of data. Methods In this systematic review and meta-analysis, we searched PubMed, Embase, Web of Science, and five preprint servers for articles published in English between Dec 1, 2019, and Dec 22, 2020. Studies evaluating SARS-CoV-2 seroprevalence in humans after the first identified case in the area were included. Studies that only reported serological responses among patients with COVID-19, those using known infection status samples, or any animal experiments were all excluded. All data used for analysis were extracted from included papers. Study quality was assessed using a standardised scale. We estimated age-specific, sex-specific, and race-specific seroprevalence by WHO regions and subpopulations with different levels of exposures, and the ratio of serology-identified infections to virologically confirmed cases. This study is registered with PROSPERO, CRD42020198253. Findings 16 506 studies were identified in the initial search, 2523 were assessed for eligibility after removal of duplicates and inappropriate titles and abstracts, and 404 serological studies (representing tests in 5 168 360 individuals) were included in the meta-analysis. In the 82 studies of higher quality, close contacts (18·0%, 95% CI 15·7–20·3) and high-risk health-care workers (17·1%, 9·9–24·4) had higher seroprevalence than did low-risk health-care workers (4·2%, 1·5–6·9) and the general population (8·0%, 6·8–9·2). The heterogeneity between included studies was high, with an overall I2 of 99·9% (p

Globally, cholera epidemics continue to challenge disease control. Although mass campaigns covering large populations are commonly used to control cholera, spatial targeting of case households and their radius is emerging as a potentially efficient strategy. We did a Scoping Review to investigate the effectiveness of interventions delivered through case-area targeted intervention, its optimal spatiotemporal scale, and its effectiveness in reducing transmission. 53 articles were retrieved. We found that antibiotic chemoprophylaxis, point-of-use water treatment, and hygiene promotion can rapidly reduce household transmission, and single-dose vaccination can extend the duration of protection within the radius of households. Evidence supports a high-risk spatiotemporal zone of 100 m around case households, for 7 days. Two evaluations separately showed reductions in household transmission when targeting case households, and in size and duration of case clusters when targeting radii. Although case-area targeted intervention shows promise for outbreak control, it is critically dependent on early detection capacity and requires prospective evaluation of intervention packages.

Cholera outbreaks primarily occur in areas lacking adequate water, sanitation, and hygiene (WASH), and infection can cause severe dehydration and death. As individuals living near cholera cases are more likely to contract cholera, case-area targeted interventions (CATI), where a response team visits case and neighbor households and conducts WASH and/or epidemiological interventions, are increasingly implemented to interrupt cholera transmission. As part of a multi-pronged evaluation on whether CATIs reduce cholera transmission, we compared two organizations’ standard operating procedures (SOPs) with information from key informant interviews with 26 staff at national/headquarters and field levels who implemented CATIs in Nigeria in 2021. While organizations generally adhered to SOPs during implementation, deviations related to accessing case household and neighbor household selection were made due to incomplete line lists, high population density, and insufficient staffing and materials. We recommend reducing the CATI radius, providing more explicit context-specific guidance in SOPs, adopting more measures to ensure sufficient staffing and supplies, improving surveillance and data management, and strengthening risk communication and community engagement. The qualitative results herein will inform future quantitative analysis to provide recommendations for overall CATI implementation in future cholera responses in fragile contexts.

Summary Background Between 2014 and 2017, successive cholera epidemics occurred in South Sudan within the context of civil war, population displacement, flooding, and drought. We aim to describe the spatiotemporal and molecular features of the three distinct epidemic waves and explore the role of vaccination campaigns, precipitation, and population movement in shaping cholera spread in this complex setting. Methods In this descriptive epidemiological study, we analysed cholera linelist data to describe the spatiotemporal progression of the epidemics. We placed whole-genome sequence data from pandemic Vibrio cholerae collected throughout these epidemics into the global phylogenetic context. Using whole-genome sequence data in combination with other molecular attributes, we characterise the relatedness of strains circulating in each wave and the region. We investigated the association of rainfall and the instantaneous basic reproduction number using distributed lag non-linear models, compared county-level attack rates between those with early and late reactive vaccination campaigns, and explored the consistency of the spatial patterns of displacement and suspected cholera case reports. Findings The 2014 (6389 cases) and 2015 (1818 cases) cholera epidemics in South Sudan remained spatially limited whereas the 2016–17 epidemic (20 438 cases) spread among settlements along the Nile river. Initial cases of each epidemic were reported in or around Juba soon after the start of the rainy season, but we found no evidence that rainfall modulated transmission during each epidemic. All isolates analysed had similar genotypic and phenotypic characteristics, closely related to sequences from Uganda and Democratic Republic of the Congo. Large-scale population movements between counties of South Sudan with cholera outbreaks were consistent with the spatial distribution of cases. 21 of 26 vaccination campaigns occurred during or after the county-level epidemic peak. Counties vaccinated on or after the peak incidence week had 2·2 times (95% CI 2·1–2·3) higher attack rates than those where vaccination occurred before the peak. Interpretation Pandemic V cholerae of the same clonal origin was isolated throughout the study period despite interepidemic periods of no reported cases. Although the complex emergency in South Sudan probably shaped some of the observed spatial and temporal patterns of cases, the full scope of transmission determinants remains unclear. Timely and well targeted use of vaccines can reduce the burden of cholera; however, rapid vaccine deployment in complex emergencies remains challenging. Funding The Bill & Melinda Gates Foundation.

Summary Background Pandemic Vibrio cholerae from cholera-endemic countries around the Bay of Bengal regularly seed epidemics globally. Without reducing cholera in these countries, including Bangladesh, global cholera control might never be achieved. Little is known about the geographical distribution and magnitude of V cholerae O1 transmission nationally. We aimed to describe infection risk across Bangladesh, making use of advances in cholera seroepidemiology, therefore overcoming many of the limitations of current clinic-based surveillance. Methods We tested serum samples from a nationally representative serosurvey in Bangladesh with eight V cholerae-specific assays. Using these data with a machine-learning model previously validated within a cohort of confirmed cholera cases and their household contacts, we estimated the proportion of the population with evidence of infection by V cholerae O1 in the previous year (annual seroincidence) and used Bayesian geostatistical models to create high-resolution national maps of infection risk. Findings Between Oct 16, 2015, and Jan 24, 2016, we obtained and tested serum samples from 2930 participants (707 households) in 70 communities across Bangladesh. We estimated national annual seroincidence of V cholerae O1 infection of 17·3% (95% CI 10·5–24·1). Our high-resolution maps showed large heterogeneity of infection risk, with community-level annual infection risk within the sampled population ranging from 4·3% to 62·9%. Across Bangladesh, we estimated that 28·1 (95% CI 17·1–39·2) million infections occurred in the year before the survey. Despite having an annual seroincidence of V cholerae O1 infection lower than much of Bangladesh, Dhaka (the capital of Bangladesh and largest city in the country) had 2·0 (95% CI 0·6–3·9) million infections during the same year, primarily because of its large population. Interpretation Serosurveillance provides an avenue for identifying areas with high V cholerae O1 transmission and investigating key risk factors for infection across geographical scales. Serosurveillance could serve as an important method for countries to plan and monitor progress towards 2030 cholera elimination goals. Funding The Bill & Melinda Gates Foundation, National Institutes of Health, and US Centers for Disease Control and Prevention.

Cholera remains a public health threat but is inequitably distributed across sub-Saharan Africa. Lack of standardized reporting and inconsistent outbreak definitions limit our understanding of cholera outbreak epidemiology.From a database of cholera incidence and mortality, we extracted data from sub-Saharan Africa and reconstructed outbreaks of suspected cholera starting in January 2010 to December 2019 based on location-specific average weekly incidence rate thresholds. We then described the distribution of key outbreak metrics.We identified 999 suspected cholera outbreaks in 744 regions across 25 sub-Saharan African countries. The outbreak periods accounted for 1.8 billion person-months (2% of the total during this period) from January 2010 to January 2020. Among 692 outbreaks reported from second-level administrative units (e.g., districts), the median attack rate was 0.8 per 1000 people (interquartile range (IQR), 0.3-2.4 per 1000), the median epidemic duration was 13 weeks (IQR, 8-19), and the median early outbreak reproductive number was 1.8 (range, 1.1-3.5). Larger attack rates were associated with longer times to outbreak peak, longer epidemic durations, and lower case fatality risks.This study provides a baseline from which the progress toward cholera control and essential statistics to inform outbreak management in sub-Saharan Africa can be monitored.

Because of the importance of schools to childhood development, the relationship between in-person schooling and COVID-19 risk has been one of the most important questions of this pandemic. Previous work in the United States during winter 2020–2021 showed that in-person schooling carried some risk for household members and that mitigation measures reduced this risk. Schooling and the COVID-19 landscape changed radically over spring semester 2021. Here, we use data from a massive online survey to characterize changes in in-person schooling behavior and associated risks over that period. We find increases in in-person schooling and reductions in mitigations over time. In-person schooling is associated with increased reporting of COVID-19 outcomes even among vaccinated individuals (although the absolute risk among the vaccinated is greatly reduced). Vaccinated teachers working outside the home were less likely to report COVID-19–related outcomes than unvaccinated teachers working exclusively from home. Adequate mitigation measures appear to eliminate the excess risk associated with in-person schooling.