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Our understanding of cholera transmission and burden largely relies on clinic-based surveillance, which can obscure trends, bias burden estimates and limit the impact of targeted cholera-prevention measures. Serological surveillance provides a complementary approach to monitoring infections, although the link between serologically derived infections and medically attended disease incidence-shaped by immunological, behavioral and clinical factors-remains poorly understood. We unravel this cascade in a cholera-endemic Bangladeshi community by integrating clinic-based surveillance, healthcare-seeking and longitudinal serological data through statistical modeling. Combining the serological trajectories with a reconstructed incidence timeline of symptomatic cholera, we estimated an annual Vibrio cholerae O1 infection incidence rate of 535 per 1,000 population (95% credible interval 514-556), with incidence increasing by age group. Clinic-based surveillance alone underestimated the number of infections and reported cases were not consistently correlated with infection timing. Of the infections, 4 in 3,280 resulted in symptoms, only 1 of which was reported through the surveillance system. These results impart insights into cholera transmission dynamics and burden in the epicenter of the seventh cholera pandemic, where >50% of our study population had an annual V. cholerae O1 infection, and emphasize the potential for a biased view of disease burden and infection risk when depending solely on clinical surveillance data., (© 2024. The Author(s).)

Background: Cholera 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., Methods and Findings: We conducted a systematic review of studies that tested ≥10 suspected cholera cases for V. cholerae O1/O139 using culture, PCR, and/or a rapid diagnostic test. We searched PubMed, Embase, Scopus, and Google Scholar for studies that sampled at least one suspected case between January 1, 2000 and April 19, 2023, to reflect contemporary patterns in V. cholerae positivity. We estimated diagnostic test sensitivity and specificity using a latent class meta-analysis. We estimated V. cholerae positivity using a random-effects meta-analysis, adjusting for test performance. We included 119 studies from 30 countries. V. cholerae positivity was lower in studies with representative sampling and in studies that set minimum ages in suspected case definitions. After adjusting for test performance, on average, 52% (95% credible interval (CrI): 24%, 80%) of suspected cases represented true V. cholerae infections. After adjusting for test performance and study methodology, the odds of a suspected case having a true infection were 5.71 (odds ratio 95% CrI: 1.53, 15.43) times higher when surveillance was initiated in response to an outbreak than in non-outbreak settings. Variation across studies was high, and a limitation of our approach was that we were unable to explain all the heterogeneity with study-level attributes, including diagnostic test used, setting, and case definitions., Conclusions: In this study, we found that burden estimates based on suspected cases alone may overestimate the incidence of medically attended cholera by 2-fold. However, accounting for cases missed by traditional clinical surveillance is key to unbiased cholera burden estimates. Given the substantial variability in positivity between settings, extrapolations from suspected to confirmed cases, which is necessary to estimate cholera incidence rates without exhaustive testing, should be based on local data., Competing Interests: JL is a paid statistical advisor for PLOS Medicine., (Copyright: © 2023 Wiens et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Cholera is an acute diarrheal disease caused by the bacteria Vibrio cholerae. Each year, 100'000 people die from cholera. The links between cholera, weather and climate are visible in the seasonality of cholera globally, but evidence to date illustrates that the relationships between them are highly heterogeneous across settings, with differences in both the direction and strength of the associations. Before we can devise evidence-based scenarios on how climate change may influence cholera burden in the future, more detailed case studies, using more robust climate and epidemiological data from across the globe, are needed. In the meantime, provision of sustainable water and sanitation is of the highest priority to offset potential impacts of climate change on cholera., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Background: Vibriocidal antibodies are currently the best characterised correlate of protection against cholera and are used to gauge immunogenicity in vaccine trials. Although other circulating antibody responses have been associated with a decreased risk of infection, the correlates of protection against cholera have not been comprehensively compared. We aimed to analyse antibody-mediated correlates of protection from both V cholerae infection and cholera-related diarrhoea., Methods: We conducted a systems serology study that analysed 58 serum antibody biomarkers as correlates of protection against V cholerae O1 infection or diarrhoea. We used serum samples from two cohorts: household contacts of people with confirmed cholera in Dhaka, Bangladesh, and cholera-naive volunteers who were recruited at three centres in the USA, vaccinated with a single dose of CVD 103-HgR live oral cholera vaccine, and then challenged with V cholerae O1 El Tor Inaba strain N16961. We measured antigen-specific immunoglobulin responses against antigens using a customised Luminex assay and used conditional random forest models to examine which baseline biomarkers were most important for classifying individuals who went on to develop infection versus those who remained uninfected or asymptomatic. V cholerae infection was defined as having a positive stool culture result on days 2-7 or day 30 after enrolment of the household's index cholera case and, in the vaccine challenge cohort, was the development of symptomatic diarrhoea (defined as two or more loose stools of ≥200 mL each, or a single loose stool of ≥300 mL over a 48-h period)., Findings: In the household contact cohort (261 participants from 180 households), 20 (34%) of the 58 studied biomarkers were associated with protection against V cholerae infection. We identified serum antibody-dependent complement deposition targeting the O1 antigen as the most predictive correlate of protection from infection in the household contacts, whereas vibriocidal antibody titres ranked lower. A five-biomarker model predicted protection from V cholerae infection with a cross-validated area under the curve (cvAUC) of 79% (95% CI 73-85). This model also predicted protection against diarrhoea in unvaccinated volunteers challenged with V cholerae O1 after vaccination (n=67; area under the curve [AUC] 77%, 95% CI 64-90). Although a different five-biomarker model best predicted protection from the development of cholera diarrhoea in the challenged vaccinees (cvAUC 78%, 95% CI 66-91), this model did poorly at predicting protection against infection in the household contacts (AUC 60%, 52-67)., Interpretation: Several biomarkers predict protection better than vibriocidal titres. A model based on protection against infection among household contacts was predictive of protection against both infection and diarrhoeal illness in challenged vaccinees, suggesting that models based on observed conditions in a cholera-endemic population might be more likely to identify broadly applicable correlates of protection than models trained on single experimental settings., Funding: National Institute of Allergy and Infectious Diseases and National Institute of Child Health and Human Development, National Institutes of Health., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Cholera was first described in the areas around the Bay of Bengal and spread globally, resulting in seven pandemics during the past two centuries. It is caused by toxigenic Vibrio cholerae O1 or O139 bacteria. Cholera is characterised by mild to potentially fatal acute watery diarrhoeal disease. Prompt rehydration therapy is the cornerstone of management. We present an overview of cholera and its pathogenesis, natural history, bacteriology, and epidemiology, while highlighting advances over the past 10 years in molecular epidemiology, immunology, and vaccine development and deployment. Since 2014, the Global Task Force on Cholera Control, a WHO coordinated network of partners, has been working with several countries to develop national cholera control strategies. The global roadmap for cholera control focuses on stopping transmission in cholera hotspots through vaccination and improved water, sanitation, and hygiene, with the aim to reduce cholera deaths by 90% and eliminate local transmission in at least 20 countries by 2030., Competing Interests: Declaration of interests ASA is supported by grants from the National Institutes of Health (R01 AI135115) and grants from the Bill & Melinda Gates Foundation (INV-021879 and INV-002667). ASA and SD serve on the Global Task Force for Cholera Control working groups for Oral Cholera Vaccines and Surveillance and Epidemiology of Cholera. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: A surveillance system that is sensitive to detecting high burden areas is critical for achieving widespread disease control. In 2014, Bangladesh established a nationwide, facility-based cholera surveillance system for Vibrio cholerae infection. We sought to measure the sensitivity of this surveillance system to detect cases to assess whether cholera elimination targets outlined by the Bangladesh national control plan can be adequately measured., Methods: We overlaid maps of nationally representative annual V cholerae seroincidence onto maps of the catchment areas of facilities where confirmatory laboratory testing for cholera was conducted, and we identified its spatial complement as surveillance greyspots, areas where cases likely occur but go undetected. We assessed surveillance system sensitivity and changes to sensitivity given alternate surveillance site selection strategies., Results: We estimated that 69% of Bangladeshis (111.7 million individuals) live in surveillance greyspots and that 23% (25.5 million) of these individuals live in areas with the highest V cholerae infection rates., Conclusions: The cholera surveillance system in Bangladesh has the ability to monitor progress towards cholera elimination goals among 31% of the country's population, which may be insufficient for accurately measuring progress. Increasing surveillance coverage, particularly in the highest risk areas, should be considered., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Cholera remains a significant public health burden worldwide, and better methods for monitoring cholera incidence would enhance the effectiveness of public health interventions. The serum bactericidal assay (SBA) has been used extensively for Vibrio cholerae vaccine assessments and serosurveillance. Current SBA approaches for V. cholerae rely on colony enumeration or optical density (OD600nm) readings to measure viable bacteria following complement-mediated lysis. These methods provide titer values that are constrained to discrete dilution values and rely on bacterial outgrowth, which is time consuming and prone to variation. Detection of bacterial proteins following complement-mediated lysis presents a faster and potentially less variable alternative approach independent of bacterial outgrowth. Here, we present an SBA that measures luciferase luminescence driven by lysis-released adenylate kinase. This approach is faster and less variable than growth-dependent SBAs and directly measures continuous titer values. This novel SBA method can potentially be applied to other bacteria of interest.

Background: Despite advances in prevention, detection, and treatment, cholera remains a major public health problem in Bangladesh and little is known about cholera outside of limited historical sentinel surveillance sites. In Bangladesh, a comprehensive national cholera control plan is essential, although national data are needed to better understand the magnitude and geographic distribution of cholera., Methods: We conducted systematic hospital-based cholera surveillance among diarrhea patients in 22 sites throughout Bangladesh from 2014 to 2018. Stool specimens were collected and tested for Vibrio cholerae by microbiological culture. Participants' socioeconomic status and clinical, sanitation, and food history were recorded. We used generalized estimating equations to identify the factors associated with cholera among diarrhea patients., Results: Among 26 221 diarrhea patients enrolled, 6.2% (n = 1604) cases were V. cholerae O1. The proportion of diarrhea patients positive for cholera in children <5 years was 2.1% and in patients ≥5 years was 9.5%. The proportion of cholera in Dhaka and Chittagong Division was consistently high. We observed biannual seasonal peaks (pre- and postmonsoon) for cholera across the country, with higher cholera positivity during the postmonsoon in western regions and during the pre-monsoon season in eastern regions. Cholera risk increased with age, occupation, and recent history of diarrhea among household members., Conclusions: Cholera occurs throughout a large part of Bangladesh. Cholera-prone areas should be prioritized to control the disease by implementation of targeted interventions. These findings can help strengthen the cholera-control program and serve as the basis for future studies for tracking the impact of cholera-control interventions in Bangladesh., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Yemen is currently experiencing, to our knowledge, the largest cholera epidemic in recent history. The first cases were declared in September 2016, and over 1.1 million cases and 2,300 deaths have since been reported 1 . Here we investigate the phylogenetic relationships, pathogenesis and determinants of antimicrobial resistance by sequencing the genomes of Vibrio cholerae isolates from the epidemic in Yemen and recent isolates from neighbouring regions. These 116 genomic sequences were placed within the phylogenetic context of a global collection of 1,087 isolates of the seventh pandemic V. cholerae serogroups O1 and O139 biotype El Tor 2-4 . We show that the isolates from Yemen that were collected during the two epidemiological waves of the epidemic 1 -the first between 28 September 2016 and 23 April 2017 (25,839 suspected cases) and the second beginning on 24 April 2017 (more than 1 million suspected cases)-are V. cholerae serotype Ogawa isolates from a single sublineage of the seventh pandemic V. cholerae O1 El Tor (7PET) lineage. Using genomic approaches, we link the epidemic in Yemen to global radiations of pandemic V. cholerae and show that this sublineage originated from South Asia and that it caused outbreaks in East Africa before appearing in Yemen. Furthermore, we show that the isolates from Yemen are susceptible to several antibiotics that are commonly used to treat cholera and to polymyxin B, resistance to which is used as a marker of the El Tor biotype.

Targeted interventions have been delivered to neighbors of cholera cases in major epidemic responses globally despite limited evidence for the impact of such targeting. Using data from urban epidemics in Chad and Democratic Republic of the Congo, we estimate the extent of spatiotemporal zones of increased cholera risk around cases. In both cities, we found zones of increased risk of at least 200 meters during the 5 days immediately after case presentation to a clinic. Risk was highest for those living closest to cases and diminished in time and space similarly across settings. These results provide a rational basis for rapidly delivering targeting interventions.

Objective: To assess the performance of the SD Bioline Cholera Ag O1/O139 rapid diagnostic test (RDT) compared to a reference standard combining culture and PCR for the diagnosis of cholera cases during an outbreak., Methods: RDT and bacterial culture were performed on site using fresh stools collected from cholera suspected cases, and from stools enriched in alkaline peptone water. Dried stool samples on filter paper were tested for V. cholerae by PCR in Lusaka (as part of a laboratory technology transfer project) and at a reference laboratory in Paris, France. A sample was considered positive for cholera by the reference standard if any of the culture or PCR tests was positive for V. cholerae O1 or O139., Results: Among the 170 samples tested with SD Bioline and compared to the reference standard, the RDT showed a sensitivity of 90.9% (95% CI: 81.3-96.6) and specificity of 95.2% (95% CI: 89.1-98.4). After enrichment, the sensitivity was 95.5% (95% CI: 87.3-99.1) and specificity 100% (95% CI: 96.5-100)., Conclusion: The observed sensitivity and specificity were within recommendations set by the Global Task Force for Cholera Control on the use of cholera RDT (sensitivity = 90%; specificity = 85%). Although the sample size was small, our findings suggest that the SD Bioline RDT could be used in the field to rapidly alert public health officials to the likely presence of cholera cases when an outbreak is suspected., (© 2018 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Background: Vibrio cholerae causes over 2 million cases of cholera and 90,000 deaths each year. Serosurveillance can be a useful tool for estimating the intensity of cholera transmission and prioritizing populations for cholera control interventions. Current methods involving venous blood draws and downstream specimen storage and transport methods pose logistical challenges in most settings where cholera strikes. To overcome these challenges, we developed methods for determining cholera-specific immune responses from dried blood spots (DBS)., Methodology/principal Findings: As conventional vibriocidal assay methods were unsuitable for DBS eluates from filter paper, we adopted a drop-plate culture method. We show that DBS collected from volunteers in South Sudan, and stored for prolonged periods in field conditions, retained functional vibriocidal antibodies, the titers of which correlated with paired serum titers determined by conventional spectrophotometric methods (r = 0.94, p = 0.00012). We also showed that eluates from DBS Serum Separator cards could be used with conventional spectrophotometric vibriocidal methods, and that they correlated with paired serum at a wide range of titers (r = 0.96, p<0.0001). Similarly, we used ELISA methods to show that V. cholerae O-specific polysaccharide antibody responses from DBS eluates correlated with results from paired serum for IgG (r = 0.85, p = 0.00006), IgM (r = 0.79, p = 0.00049) and IgA (r = 0.73, p = 0.0019), highlighting its potential for use in determination of isotype-specific responses. Storage of DBS cards at a range of temperatures did not change antibody responses., Conclusion: In conclusion, we have developed and demonstrated a proof-of-concept for assays utilizing DBS for assessing cholera-specific immune responses.

Cholera rapid diagnostic tests (RDT) could play a central role in outbreak detection and surveillance in low-resource settings, but their modest performance has hindered their broad adoption. The addition of an enrichment step may improve test specificity. We describe the results of a prospective diagnostic evaluation of the Crystal VC RDT (Span Diagnostics, India) with enrichment step and of culture, each compared to polymerase chain reaction (PCR), during a cholera outbreak in South Sudan. RDTs were performed on alkaline peptone water inoculated with stool and incubated for 4-6 hours at ambient temperature. Cholera culture was performed from wet filter paper inoculated with stool. Molecular detection of Vibrio cholerae O1 by PCR was done from dry Whatman 903 filter papers inoculated with stool, and from wet filter paper supernatant. In August and September 2015, 101 consecutive suspected cholera cases were enrolled, of which 36 were confirmed by PCR. The enriched RDT had 86.1% (95% CI: 70.5-95.3) sensitivity and 100% (95% CI: 94.4-100) specificity compared to PCR as the reference standard. The sensitivity of culture versus PCR was 83.3% (95% CI: 67.2-93.6) for culture performed on site and 72.2% (95% CI: 54.8-85.8) at the international reference laboratory, where samples were tested after an average delay of two months after sample collection, and specificity was 98.5% (95% CI: 91.7-100) and 100% (95% CI: 94.5-100), respectively. The RDT with enrichment showed performance comparable to that of culture and could be a sustainable alternative to culture confirmation where laboratory capacity is limited., Competing Interests: The authors have declared that no competing interests exist.

Vibrio cholerae causes cholera, a severe diarrheal disease. Understanding the local genetic diversity and transmission of V. cholerae will improve our ability to control cholera. Vibrio cholerae isolates clustered in genetically related groups (clonal complexes, CC) by multilocus variable tandem-repeat analysis (MLVA) were compared by whole genome sequencing (WGS). Isolates in CC1 had been isolated from two geographical locations. Isolates in a second genetically distinct group, CC2, were isolated only at one location. Using WGS, CC1 isolates from both locations revealed, on average, 43.8 nucleotide differences, while those strains comprising CC2 averaged 19.7 differences. Strains from both MLVA-CCs had an average difference of 106.6. Thus, isolates comprising CC1 were more closely related (P < 10(-6)) to each other than to isolates in CC2. Within a MLVA-CC, after removing all paralogs, alternative alleles were found in all possible combinations on separate chromosomes indicative of recombination within the core genome. Including recombination did not affect the distinctiveness of the MLVA-CCs when measured by WGS. We found that WGS generally reflected the same genetic relatedness of isolates as MLVA, indicating that isolates from the same MLVA-CC shared a more recent common ancestor than isolates from the same location that clustered in a distinct MLVA-CC., (© FEMS 2016.)

Following mass population displacements in South Sudan, preventive cholera vaccination campaigns were conducted in displaced persons camps before a 2014 cholera outbreak. We compare cholera transmission in vaccinated and unvaccinated areas and show vaccination likely halted transmission within vaccinated areas, illustrating the potential for oral cholera vaccine to stop cholera transmission in vulnerable populations.

Background: To evaluate the specificity of the Crystal VC dipstick test for detecting cholera., Methods: We compared direct testing using the Crystal VC dipstick test and testing after enrichment for 6 h in alkaline peptone water (APW) to bacterial culture as the gold standard. Samples positive by dipstick but negative by culture were also tested using PCR., Results: Stool was collected from 125 patients. The overall specificities of the direct testing and testing after 6-h enrichment in APW compared to bacterial culture were 91.8% and 98.4% (P = 0.125), respectively, and the sensitivities were 65.6% and 75.0% (P = 0.07), respectively., Conclusion: The increase in the sensitivity of the Crystal VC kit with the use of the 6-h enrichment step in APW compared to direct testing was marginally significant. The Crystal VC dipstick had a much higher specificity than previously reported (91-98%). Therefore, this method might be a promising screening tool for cholera outbreak surveillance in resource-limited settings where elimination of false-positive results is critical., (© 2014 John Wiley & Sons Ltd.)

Cholera remains a major public health problem. To compare the relative contribution of strains from the environment with strains isolated from patients during outbreaks, we performed multilocus variable tandem repeat analyses on samples collected during the 2010 and 2011 outbreak seasons in 2 geographically distinct areas of Bangladesh. A total of 222 environmental and clinical isolates of V. cholerae O1 were systematically collected from Chhatak and Mathbaria. In Chhatak, 75 of 79 isolates were from the same clonal complex, in which extensive differentiation was found in a temporally consistent pattern of successive mutations at single loci. A total of 59 isolates were collected from 6 persons; most isolates from 1 person differed by sequential single-locus mutations. In Mathbaria, 60 of 84 isolates represented 2 separate clonal complexes. The small number of genetic lineages in isolates from patients, compared with those from the environment, is consistent with accelerated transmission of some strains among humans during an outbreak.

Objectives: Recent large cholera outbreaks highlight the need for improved understanding of the pathogenesis and epidemiology of cholera. The incubation period of cholera has important implications for clinical and public health decision-making, yet statements of the incubation period of cholera are often imprecise. Here we characterize the distribution of cholera's incubation period., Methods: We conducted a systematic review of the literature for statements of the incubation period of cholera and data that might aid in its estimation. We extracted individual-level data, parametrically estimated the distribution of toxigenic cholera's incubation period, and evaluated evidence for differences between strains., Results: The incubation period did not differ by a clinically significant margin between strains (except O1 El Tor Ogawa). We estimate the median incubation period of toxigenic cholera to be 1.4 days (95% CI, 1.3-1.6). Five percent of cholera cases will develop symptoms by 0.5 days (95% CI 0.4-0.5), and 95% by 4.4 days (95% CI 3.9-5.0) after infection., Conclusions: We recommend that cholera investigations use a recall period of at least five days to capture relevant exposures; significantly longer than recent risk factor studies from the Haitian epidemic. This characterization of cholera's incubation period can help improve clinical and public health practice and advance epidemiologic research., (Copyright © 2012 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Background: Indian subcontinent being an important region in the fight to eliminate cholera needs better cholera surveillance. Current methods miss most infections, skewing disease burden estimates. Triangulating serosurvey data, clinical cases, and risk factors could reveal India's true cholera risk. Methods: We synthesized data from a nationally representative serosurvey, outbreak reports and risk factors like water, sanitation and the Multidimensional Poverty Index, to create a composite vulnerability index for assessing state-wise cholera risk in India. We tested 7,882 stored sera samples collected during 2017–18 from individuals aged 9–45 years, for vibriocidal antibodies to Vibrio cholerae O1 using a cut-off titre ≥320 defining as elevated titre. We also extracted data from the 2015–19 Integrated Disease Surveillance Programme and published cholera reports. Results: Overall, 11.7% (CI: 10.4–13.3%) of the sampled population had an elevated titre of cholera vibriocidal antibodies (≥320). The Southern region experienced the highest incidence (16.8%, CI: 12.1–22.8), followed by the West (13.2%, CI: 10.0–17.3) and North (10.7%, CI: 9.3–12.3). Proportion of samples with an elevated vibriocidal titre (≥320) was significantly higher among individuals aged 18–45 years (13.0% CI: 11.2–15.1) compared to children 9–17 years (8.6%, CI 7.3–10.0, p<0.05); we found no differences between sex or urbanicity. Between 2015–2019, the Integrated Disease Surveillance Program (IDSP) reported 29,400 cases of cholera across the country. Using the composite vulnerability index, we found Karnataka, Madhya Pradesh, and West Bengal were the most vulnerable states in India in terms of risk of cholera. Conclusion: The present study showed that cholera infection is present in all five regions across India. The states with high cholera vulnerability could be prioritized for targeted prevention interventions. Author summary: Cholera remains a significant public health threat in areas with inadequate water, sanitation, and hygiene (WASH). The World Health Organization's Global Task Force on Cholera Control (GTFCC) launched "Ending Cholera: A Global Roadmap to 2030" to reduce cholera deaths and eliminate the disease in 20 countries by 2030 through targeted interventions, including improved WASH practices and disease surveillance. cholera surveillance, especially in developing countries seldom poses difficulty in terms of the need for laboratory infrastructure, and other resource constraints. Thereby, in this study, we utilized a viable approach with serosurvey data from 2017, cholera outbreak data, WASH indicators, and the Multidimensional Poverty Index (MPI) to create a composite vulnerability index for cholera risk in India. Overall, 11.7% of the sampled population had detectable levels of cholera antibodies reflecting previous infection. The Southern region of India experienced the highest incidence, followed by the West and North. the study showed that cholera infection is present in all five regions across India. Further, the vulnerability index which we built could be utilized in other settings so that effective tailored interventions could be applied in identified priority areas. [ABSTRACT FROM AUTHOR]

A Vibrio cholerae O1 outbreak emerged in Haiti in October 2022 after years of cholera absence. In samples from a 2021 serosurvey, we found lower circulating antibodies against V. cholerae lipopolysaccharide in children <5 years of age and no vibriocidal antibodies, suggesting high susceptibility to cholera, especially among young children. [ABSTRACT FROM AUTHOR]

Cholera remains a significant public health problem worldwide. In settings of declining incidence, serosurveillance may be used to augment clinical surveillance. We utilized dried blood spot sampling and cholera-specific antibody testing to examine the serologic profiles of vaccinated and unvaccinated children in southern Vietnam, where cholera was recently eliminated. [ABSTRACT FROM AUTHOR]

Background: Antibodies targeting O-specific polysaccharide (OSP) of Vibrio cholerae may protect against cholera; however, little is known about this immune response in infected immunologically naïve humans. Methodology: We measured serum anti-OSP antibodies in adult North American volunteers experimentally infected with V. cholerae O1 Inaba El Tor N16961. We also measured vibriocidal and anti-cholera toxin B subunit (CtxB) antibodies and compared responses to those in matched cholera patients in Dhaka, Bangladesh, an area endemic for cholera. Principal findings: We found prominent anti-OSP antibody responses following initial cholera infection: these responses were largely IgM and IgA, and highest to infecting serotype with significant cross-serotype reactivity. The anti-OSP responses peaked 10 days after infection and remained elevated over baseline for ≥ 6 months, correlated with vibriocidal responses, and may have been blunted in blood group O individuals (IgA anti-OSP). We found significant differences in immune responses between naïve and endemic zone cohorts, presumably reflecting previous exposure in the latter. Conclusions: Our results define immune responses to O-specific polysaccharide in immunologically naive humans with cholera, find that they are largely IgM and IgA, may be blunted in blood group O individuals, and differ in a number of significant ways from responses in previously humans. These differences may explain in part varying degrees of protective efficacy afforded by cholera vaccination between these two populations. Trial registration number: ClinicalTrials.gov NCT01895855. Author summary: Cholera is an acute, secretory diarrheal disease caused by Vibrio cholerae O1. There is a growing body of evidence that immune responses targetting the O-specific polysaccharide (OSP) of V. cholerae are associated with protecton against cholera. Despite this, little is known about immune responses targeting OSP in immunologically naive individals. Cholera affects populations in severely resource-limited areas. To address this, we assessed anti-OSP immune responses in North American volunteers experimentally infected with wild type V. cholerae O1 El Tor Inaba strain N16961. We found that antibody responses were largely IgM and IgA, cross-reacted to both Inaba and Ogawa serotypes, and correlated with vibriocidal responses. We found no association of responses to severity of disease, but did find that blood group O individuals mounted lower IgA fold-changes to OSP than did non-blood group O individuals. Individuals with blood group O are at particular risk for severe cholera, and are less well protected against cholera following oral vaccination. We also compared anti-OSP responses in previously unexposed individuals to responses in matched endemic zone patients, and found a number of significant differences. Such differences may explain in part the varying degrees of protective efficacy afforded by cholera vaccination between these two populations. [ABSTRACT FROM AUTHOR]

Rapid diagnostic tests (RDTs) for cholera are an important emerging tool for surveillance, yet the currently available tests have several limitations. We assess the performance of a new RDT, Cholkit, during a cholera outbreak in Malawi compared with culture and find a sensitivity of 93.0% (95% CI, 83.0%–98.1%) and a specificity of 95.7% (95% CI, 78.1%–100.0%). [ABSTRACT FROM AUTHOR]

Combining the official cholera line list data and outbreak investigation reports from the ministries of health in Uganda and South Sudan with molecular analysis of Vibrio cholerae strains revealed the interrelatedness of the epidemics in both countries in 2014. These results highlight the need for collaboration to control cross-border outbreaks. [ABSTRACT FROM AUTHOR]

Background: Cholera prevention and control interventions targeted to neighbors of cholera cases (case-area targeted interventions [CATIs]), including improved water, sanitation, and hygiene, oral cholera vaccine (OCV), and prophylactic antibiotics, may be able to efficiently avert cholera cases and deaths while saving scarce resources during epidemics. Efforts to quickly target interventions to neighbors of cases have been made in recent outbreaks, but little empirical evidence related to the effectiveness, efficiency, or ideal design of this approach exists. Here, we aim to provide practical guidance on how CATIs might be used by exploring key determinants of intervention impact, including the mix of interventions, "ring" size, and timing, in simulated cholera epidemics fit to data from an urban cholera epidemic in Africa.Methods and Findings: We developed a micro-simulation model and calibrated it to both the epidemic curve and the small-scale spatiotemporal clustering pattern of case households from a large 2011 cholera outbreak in N'Djamena, Chad (4,352 reported cases over 232 days), and explored the potential impact of CATIs in simulated epidemics. CATIs were implemented with realistic logistical delays after cases presented for care using different combinations of prophylactic antibiotics, OCV, and/or point-of-use water treatment (POUWT) starting at different points during the epidemics and targeting rings of various radii around incident case households. Our findings suggest that CATIs shorten the duration of epidemics and are more resource-efficient than mass campaigns. OCV was predicted to be the most effective single intervention, followed by POUWT and antibiotics. CATIs with OCV started early in an epidemic focusing on a 100-m radius around case households were estimated to shorten epidemics by 68% (IQR 62% to 72%), with an 81% (IQR 69% to 87%) reduction in cases compared to uncontrolled epidemics. These same targeted interventions with OCV led to a 44-fold (IQR 27 to 78) reduction in the number of people needed to target to avert a single case of cholera, compared to mass campaigns in high-cholera-risk neighborhoods. The optimal radius to target around incident case households differed by intervention type, with antibiotics having an optimal radius of 30 m to 45 m compared to 70 m to 100 m for OCV and POUWT. Adding POUWT or antibiotics to OCV provided only marginal impact and efficiency improvements. Starting CATIs early in an epidemic with OCV and POUWT targeting those within 100 m of an incident case household reduced epidemic durations by 70% (IQR 65% to 75%) and the number of cases by 82% (IQR 71% to 88%) compared to uncontrolled epidemics. CATIs used late in epidemics, even after the peak, were estimated to avert relatively few cases but substantially reduced the number of epidemic days (e.g., by 28% [IQR 15% to 45%] for OCV in a 100-m radius). While this study is based on a rigorous, data-driven approach, the relatively high uncertainty about the ways in which POUWT and antibiotic interventions reduce cholera risk, as well as the heterogeneity in outbreak dynamics from place to place, limits the precision and generalizability of our quantitative estimates.Conclusions: In this study, we found that CATIs using OCV, antibiotics, and water treatment interventions at an appropriate radius around cases could be an effective and efficient way to fight cholera epidemics. They can provide a complementary and efficient approach to mass intervention campaigns and may prove particularly useful during the initial phase of an outbreak, when there are few cases and few available resources, or in order to shorten the often protracted tails of cholera epidemics. [ABSTRACT FROM AUTHOR]

Cross-sectional Vibrio cholerae–related antibody measures can be used to estimate cholera incidence in a population. Estimating the true prevalence of cholera: Successful development of anti-cholera measures requires accurate estimates of infection incidence. Reporting of cholera cases, however, typically relies on clinical assessment at the time of patient presentation and can be problematized by lack of access to health care and variable, nonspecific symptomatology. Combining a small number of serological markers with machine learning methods, Azman et al. were able to accurately detect individuals who had had cholera infections within the previous year. Simulated serosurveys showed that this simple antibody-based approach could potentially be used as an alternative method to estimate cholera incidence in a population. The development of new approaches to cholera control relies on an accurate understanding of cholera epidemiology. However, most information on cholera incidence lacks laboratory confirmation and instead relies on surveillance systems reporting medically attended acute watery diarrhea. If recent infections could be identified using serological markers, cross-sectional serosurveys would offer an alternative approach to measuring incidence. Here, we used 1569 serologic samples from a cohort of cholera cases and their uninfected contacts in Bangladesh to train machine learning models to identify recent Vibrio cholerae O1 infections. We found that an individual's antibody profile contains information on the timing of V. cholerae O1 infections in the previous year. Our models using six serological markers accurately identified individuals in the Bangladesh cohort infected within the last year [cross-validated area under the curve (AUC), 93.4%; 95% confidence interval (CI), 92.1 to 94.7%], with a marginal performance decrease using models based on two markers (cross-validated AUC, 91.0%; 95% CI, 89.2 to 92.7%). We validated the performance of the two-marker model on data from a cohort of North American volunteers challenged with V. cholerae O1 (AUC range, 88.4 to 98.4%). In simulated serosurveys, our models accurately estimated annual incidence in both endemic and epidemic settings, even with sample sizes as small as 500 and annual incidence as low as two infections per 1000 individuals. Cross-sectional serosurveys may be a viable approach to estimating cholera incidence. [ABSTRACT FROM AUTHOR]

Background: Despite recent insights into cholera transmission patterns in Africa, regional and local dynamics in West Africa--where cholera outbreaks occur every few years--are still poorly understood. Coordinated genomic surveillance of Vibrio cholerae in the areas most affected may reveal transmission patterns important for cholera control. Methods: During a regional sequencing workshop in Nigeria, we sequenced 46 recent V. cholerae isolates from Cameroon, Niger, and Nigeria (37 from 2018 to 2019) to better understand the relationship between the V. cholerae bacterium circulating in these three countries. Results: From these isolates, we generated 44 whole Vibrio cholerae O1 sequences and analyzed them in the context of 1280 published V. cholerae O1 genomes. All sequences belonged to the T12 V. cholerae seventh pandemic lineage. Conclusions: Phylogenetic analysis of newly generated and previously published V. cholerae genomes suggested that the T12 lineage has been continuously transmitted within West Africa since it was first observed in the region in 2009, despite lack of reported cholera in the intervening years. The results from this regional sequencing effort provide a model for future regionally coordinated surveillance efforts. Funding: Funding for this project was provided by Bill and Melinda Gates Foundation OPP1195157. [ABSTRACT FROM AUTHOR]