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Since 1971, Cameroon has been facing an ever-growing series of cholera epidemics; despite all the efforts made by the government to address this substantial public health problem. In 2020, in addition to the COVID-19 pandemic, Cameroon recorded a high cholera case fatality rate of 5.3% following epidemics noted in the South, Littoral, and South-West regions which is far higher than the 1% World Health Organization acceptable rate.The Ministry of Public Health organized a reactive vaccination campaign against cholera to address the high mortality rate in the affected health districts. The first round was in August 2020 and the second in March 2021. We conducted a cross-sectional study and reviewed this vaccination campaign's challenges, best practices, and lessons. The vaccination coverage for the two doses of the oral cholera vaccine was 80.4%, with a refusal rate as high as 67%. People 20 years and above recorded the lowest vaccination coverage. The main challenge was misinformation about the cholera vaccine. The best practice was thorough population sensitization through community actors.Proper communication will always brave the odds of hesitancy and favor mass population vaccination to thwart hesitancy and consolidate herd immunity.

The non-O1/non-O139 Vibrio cholerae caused outbreaks or sporadic cases of gastroenteritis that was rarely seen in good sanitary condition. It was described a case of systemic multiple organ lesions that worsened because of non-O1/non-O139 V. cholerae, suggesting that serogroups have a potential virulence in enhancing pathogenicity with patients with underlying diseases compared with a healthy population.Samples are identified by strain culture, polymerase chain reaction (PCR) virulence identification, and whole genome sequencing.A middle-aged man was diagnosed with cytotoxin-producing and nontoxin V. cholerae non-O1/non-O139 serogroups. Although lacking the CT toxin encoded by ctxAB gene, the pathogenesis of cholera relies on the synergistic action of many other genes, especially virulence genes.This case suggested that the laborers engaging in agricultural production are at potential risk of V. cholerae infection by exposure of open wounds to contaminated water . However, epidemiological investigation should focus on the objective cause of the change of working environment. Furthermore, common diseases can possibly enhance the virulence of non-O1/non-O139 serogroups by attacking the tight junction of small intestinal epithelial cells, further triggering bacteremia, a process that may lead to death within 48-72 hours, which requires great attention.

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.

Bangladesh remains cholera endemic with biannual seasonal peaks causing epidemics. At least 300,000 severe cases and over 4,500 deaths occur each year. The available oral cholera vaccineshave not yet been adopted for cholera control in Bangladesh due to insufficient number of doses available for endemic control. With a public private partnership, icddr,b initiated a collaboration between vaccine manufacturers in Bangladesh and abroad. A locally manufactured Oral Cholera Vaccine (OCV) named Cholvax became available for testing in Bangladesh. We evaluated the safety and immunogenicity of this locally produced Cholvax (Incepta Vaccine Ltd) inexpensive OCV comparatively to Shanchol (Shantha Biotechnics-Sanofi Pasteur) which is licensed in several countries. We conducted a randomized non-inferiority clinical trial of bivalent, killed oral whole-cell cholera vaccine Cholvax vs. Shanchol in the cholera-endemic area of Mirpur, Dhaka, among three different age cohorts (1-5, 6-17 and 18-45 years) between April 2016 and April 2017. Two vaccine doses were given at 14 days apart to 2,052 healthy participants. No vaccine-related serious adverse events were reported. There were no significant differences in the frequency of solicited (7.31% vs. 6.73%) and unsolicited (1.46% vs. 1.07%) adverse events reported between the Cholvax and Shanchol groups. Vibriocidal antibody responses among the overall population for O1 Ogawa (81% vs. 77%) and O1 Inaba (83% vs. 84%) serotypes showed that Cholvax was non-inferior to Shanchol, with the non-inferiority margin of -10%. For O1 Inaba, GMT was 462.60 (Test group), 450.84 (Comparator group) with GMR 1.02(95% CI: 0.92, 1.13). For O1 Ogawa, GMT was 419.64 (Test group), 387.22 (Comparator group) with GMR 1.12 (95% CI: 1.02, 1.23). Cholvax was safe and non-inferior to Shanchol in terms of immunogenicity in the different age groups. These results support public use of Cholvax to contribute for reduction of the cholera burden in Bangladesh. ClinicalTrials.gov number: NCT027425581.

Bacterial pathogens must maintain a delicate balance between acquiring novel genetic material and preserving their well-engrained cell physiology. In the recent study by Jaskólska et al., an astonishing example of this sophisticated phenomenon was found in Vibrio cholerae,with the pandemic strain encoding systems within two horizontally acquired pathogenicity islands that degrade incoming DNA.

Summary Background There are an estimated 1·3–4·0 million cases of cholera and 20 000–140 000 cholera-related deaths worldwide each year. The rice-based cholera toxin B subunit (CTB) vaccine, MucoRice-CTB, is an oral candidate vaccine that does not require a cold chain, has shown efficacy in animal models, and could be of benefit in places where there is a paucity of medical infrastructure. We aim to assess the safety, tolerability, and immunogenicity of MucoRice-CTB in humans. Methods We did a double-blind, randomised, placebo-controlled, dose-escalation, phase 1 study at one centre in Tokyo, Japan. Eligible participants were healthy adult men with measurable serum and faecal antibodies against CTB at screening. Participants were excluded if they had allergy to rice; history of cholera or travellers' diarrhoea; poorly controlled constipation; abnormal results on hepatic, renal, or haematological screening tests; use of any over-the-counter drugs within 7 days before first administration; inability to use a medically acceptable means of contraception; or other reasons by medical judgment of the investigator. Three dose cohorts of participants were randomly assigned by block to receive oral MucoRice-CTB (1 g, 3 g, or 6 g) or placebo (1 g, 3 g, or 6 g), once every 2 weeks for 8 weeks (for a total of 4 doses). The dose groups were performed sequentially, and each dose cohort was completed before the higher dose cohort began. All medical staff, participants, and most trial staff were masked to treatment allocation. The primary outcomes were safety and tolerability, measured by 12-lead electrocardiogram; vital signs; haematology, biochemistry, and urinalysis; rice protein-specific serum IgE antibody concentration; and monitoring of adverse events. Participants were assessed at baseline and at 1, 2, 4, 6, 8, and 16 weeks after the first administration of vaccine or placebo. The safety analysis set included all participants enrolled in the trial who received at least one dose of the study drug or placebo and were compliant with good clinical practice. The full analysis population included all participants enrolled in the trial who received at least one dose of the study drug and for whom any data were obtained after the start of study drug administration. Meta-genomic analysis of study participants was performed using bacterial DNA from faecal samples before vaccination. This trial is registered with UMIN.ac.jp, UMIN000018001. Findings Between June 23, 2015, and May 31, 2016, 226 participants were recruited and assessed for eligibility. 166 participants were excluded based on health condition or schedule. We then randomly selected 60 male volunteers aged 20–40 years who were enrolled and assigned to MucoRice-CTB (10 participants assigned to 1 g, 10 participants assigned to 3 g, and 10 participants assigned to 6 g), or placebo (10 participants assigned to 1 g, 10 participants assigned to 3 g, and 10 participants assigned to 6 g). All participants received at least one dose of study drug or placebo and were included in the safety analyses. Two participants given MucoRice-CTB 3 g and one participant given MucoRice-CTB 6 g were lost to follow-up and excluded from the efficacy analysis. Serum CTB-specific IgG and IgA antibody concentrations in participants who received 6 g MucoRice-CTB increased significantly in both a time-dependent and dose-dependent manner compared with those in the placebo groups (p for interaction=0·002 for IgG, p=0·004 for IgA). Genome analysis of subjects' faeces before vaccination revealed that compared to non-responders, responders had a gut microbiota of higher diversity with the presence of Escherichia coli and Shigella spp. 28 (93%) of 30 participants who received MucoRice-CTB at any dose had at least one adverse event during the study period, compared with 30 (100%) of 30 participants given placebo. Grade 3 or higher adverse events were reported in four participants in the MucoRice-CTB group (5 events) and four participants in the placebo group (10 events). The most common serious adverse event was haemoglobin decreased (2 events in 2 participants in the pooled MucoRice-CTB group, 2 events in 2 participants in the placebo group; all grade 3). Interpretation Participants given MucoRice-CTB showed increased CTB-specific serum IgG and IgA antibody concentrations without inducing serious adverse events, indicating that MucoRice-CTB could be a safe and potent vaccine to prevent diarrhoeal disease. MucoRice-CTB induced neutralising antibodies against diarrhoeal toxins in a gut microbiota-dependent manner. A similar phase 1 trial will be done with participants of other ethnicities to substantiate our findings. Funding Translational Research Acceleration Network Program of Japan Agency for Medical Research and Development; Ministry of Education, Culture, Sports, Science and Technology, Japan; Science and Technology Research Partnership for Sustainable Development; Grant-in-Aid for Scientific Research (S) (18H05280) (to H K) from the Japan Society for the Promotion of Science (JSPS); Grant-in-Aid for Young Scientists (B) (16K16144) (to Y K) from JSPS; Grant-in-Aid for Young Scientists (18K18148) (to Y K) from JSPS; Grant from International Joint Usage/Research Center (K3002), the Institute of Medical Science, University of Tokyo

Two-dose killed oral cholera vaccines (OCV) are currently being used widely to control cholera. The standard dose-interval for OCV is 2 weeks; however, during emergency use of the vaccine, it may be more appropriate to use the available doses to quickly give a single dose to more people and give a delayed second dose when more vaccine becomes available. This study is an open label, randomized, phase 2 clinical trial of the vibriocidal response induced by OCV, comparing the responses when the second dose was given either 2 weeks (standard dose interval) or 6 months (extended dose interval) after the first dose. Vaccine was administered to healthy participants 1 year of age living in the Lukanga Swamps area of Zambia. Three age cohorts (5 years, 5-14 years, and ≥ 15 years) were randomized to the either dose-interval. The primary outcome was the vibriocidal GMT 14 days after the second dose. 156 of 172 subjects enrolled in the study were included in this analysis. The Inaba vibriocidal titers were not significantly different 14 days post dose two for a standard dose-interval GMT: 45.6 (32-64.9), as compared to the GMT 47.6 (32.6-69.3), for the extended dose-interval, (p = 0.87). However, the Ogawa vibriocidal GMTs were significantly higher 14 days post dose two for the extended-dose interval at 87.6 (58.9-130.4) compared to the standard dose-interval group at 49.7 (34.1-72.3), p = 0.04. Vibriocidal seroconversion rates (a 4-fold rise in vibriocidal titer) were not significantly different between dose-interval groups. This study demonstrated that vibriocidal titers 14 days after a second dose when given at an extended\ dose interval were similar to the standard dose-interval. The findings suggest that a flexible dosing schedule may be considered when epidemiologically appropriate. The trial was registered at Clinical Trials.gov (NCT03373669).

The World Health Organization (WHO) recommends the use of oral cholera vaccines (OCVs) as part of an integrated control program, both in highly endemic settings and during cholera epidemics. The available and internationally recommended WHO-prequalified OCVs (Dukoral, Shanchol, Euvichol) contain multiple heat and formalin-killed V. cholerae strains of Inaba and Ogawa serotypes. MSD Wellcome Trust Hilleman Laboratories Pvt. Ltd. in technical collaboration with University of Gothenburg, Sweden has developed a new single strain OCV, Hillchol. This vaccine consists of formaldehyde-inactivated whole cell El Tor V. cholerae O1 bacteria engineered into the Hikojima serotype for stable expression of both the Ogawa (AB) and Inaba (AC) LPS antigens on the bacterial surface. We evaluated the safety and immunogenicity of this novel and potentially much less expensive OCV in comparison with Shanchol.We conducted a randomized, non-inferiority, age-descending clinical trial of OCV (Hillchol vs. Shanchol) in the Mirpur area of Dhaka city from July 2016 to May 2017. This study was carried out in three different age cohorts (1-5, 5-17 and ≥18 years old). Two doses of vaccine were given at 14 days intervals to 560 healthy participants.No serious adverse events were reported. There were no significant differences in the rates of adverse events between the test vaccine (Hillchol) and the comparator (Shanchol) group. Serum vibriocidal antibody responses in all age groups combined were comparable for all the O1 Ogawa (59% vs. 67%; 90% CI of difference: -14.55, -0.84) and Inaba (70% vs. 71%; 90% CI of difference: -7.24, 5.77) serotypes, showing that the Hillchol vaccine was non-inferior to Shanchol. This new vaccine was also non-inferior to Shanchol in the different age strata.The safety and immunogenicity profile of the new OCV Hillchol is comparable to Shanchol in persons residing in a cholera-endemic setting. ClinicalTrials.gov number: NCT02823899.

Cholera, a water-borne bacteria infectious disease, shows clear spatial variation in its transmission pattern. It is thus important to incorporate understanding on the spatial variability of its transmission when making transmission prediction and intervention decisions. However, for an emerging cholera outbreak, transmission dynamics models are often uncertain as model parameters are indeterminate and epidemic state can only be partially observed. Hence, ensuing intervention decisions have to be made under uncertainty and thus the resultant optimization problem is challenging. In this paper, we study a multi-period location-specific resource allocation problem for cholera outbreak intervention with periodically acquired state information from different locations and increasingly understood transmission parameters over time. We formulate the problem as a nonlinear optimization model on a set of ordinary-differential-equations governing location-specific disease transmission dynamics. We propose a data-driven optimization approach to determine the optimal strategy of intervention resource allocation at each period and each community in a rolling-horizon manner. At each period, we integrate single-period model parameter fitting and scenario-based stochastic programming to make decisions under uncertainty with newly acquired system understanding. We conduct comparative studies to assess the performance of our data-driven optimization approach and offer insights into intervention resource allocation policy development. We conclude that our data-driven optimization approach is effective to multi-period decision problems under system dynamics with indeterminate parameters.

Objective Detecting traces of ancient DNA of Vibrio cholerae to provide genetic information associated with the fifth cholera pandemic. Materials Sediment samples from the sacral foramina of four individuals were analyzed, recovered from a mass grave near an institution dedicated exclusively to the isolation and treatment of citizens infected with cholera in the late 19th century in the city of Cordoba, Argentina. Methods Paleogenetic techniques (ancient DNA extraction, PCR amplification, and Sanger sequencing) were applied. Specific primers for Vibrio cholerae (VCR, ctxA, ctxB, and tcpA) were designed. Results By amplifying and sequencing the Vibrio cholerae repeats fragment, the infection in at least one individual was confirmed. Conclusions The synthesis of the paleogenetic results with the archaeological and historical evidence strongly supports that at least one individual from the mass grave in Cordoba, Argentina, was a victim of the fifth cholera pandemic. Significance Confirming the presence of the disease through multiple lines of evidence, including genetic, archaeological, and historical analyses, strengthens and affirms our understanding of the presence, effects, and potential evolutionary paths of the disease in the past. Limitations Vibrio cholerae repeats were sequenced in one individual, while the remaining genes could not be amplified, which is likely related to gene copy number. Suggestions for future research Paleogenetic examination of ancient samples from different locations will broaden our understanding of the origin, evolution, and past dissemination of Vibrio cholerae epidemic strains.

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.

Background Cameroon chose Oral Cholera Vaccine (OCV) mass vaccination campaign in addition to other interventions to respond to outbreaks since 2015. There is still a persistent controversy on the effectiveness of reactive OCV mass vaccination campaign. Objective This article aimed to share evidence-based observations on the effect of a reactive single-dose OCV mass vaccination campaign on cholera cases in Cameroon. Methods Health area centered risk analysis was used to identify nine high risk health areas among four health districts in the |North Region as hotspots. About 537,274 people at risk of cholera transmission one year of age and above including pregnant women were eligible to receive OCV. A total of 537,279 doses of OCV was deployed for vaccination from August 1–5, 2019 through door-to-door strategy for urban health districts, and fixed/ temporary fixed posts strategies for rural health districts. Results The overall vaccination coverage was 99.9%. Vaccine wastage rate was less than 0.5% (0.0011%). Independent monitoring showed vaccination coverage at 97.2%. The 2019 epidemic curve went down after OCV intervention on the contrary to that in the year 2018 at the same period. After OCV intervention, cholera cases dropped from about 10.5 to 9.3 cases per week at the regional level while at the district level, they dropped from 5.3 to 2.1, 2.2 to 1.7, 0.6 to 0 and 1.7 to 1.5 cases per week respectively for Garoua, Garoua II, Tchollire and Pitoa. Though not statistically significant (p = 1.4, α = 0.05), cases per 1000 population seemed to remain unchanged among OCV zones (0.32/1000) and non-OCV zones (0.31/1000) in 2018 while they increased from 0.37 (OCV zones) to 0.53 (non-0CV zones) cases per 1000 population in 2019. Conclusion There might have been a general trend in the reduction of the number of new cases after a reactive single-dose OCV campaign.

Availability of clean, safe drinking water is one of the primary needs of human beings. The present study focused on the quality of drinking water in Alappuzha district, in the state of Kerala, India. The harmful concentrations of water-soluble chemicals in drinking water can adversely affect human health. This investigation probed the influence of toxic chemical pollutants on human health. Although concentrations of chemical parameters in the water samples were found to be within the permissible limits, cases of humans infected by waterborne disease such as Leptospirosis, Hepatitis A, and Hepatitis E, Cholera, Shigellosis, and Amoebic meningoencephalitis were reported in the district, in the year 2016. This suggests that microorganisms play a vital role in contaminating water and spreading disease. As many of these diseases are lethal, expedient remedial measures must be undertaken to alleviate their incidence and severity.

The bacterial enhancer-binding protein (bEBP) FlrC, controls motility and colonization of Vibrio cholerae by regulating the transcription of class-III flagellar genes in σ(54)-dependent manner. However, the mechanism by which FlrC regulates transcription is not fully elucidated. Although, most bEBPs require nucleotides to stimulate the oligomerization necessary for function, our previous study showed that the central domain of FlrC (FlrC(C)) forms heptamer in a nucleotide-independent manner. Furthermore, heptameric FlrC(C) binds ATP in “cis-mediated” style without any contribution from sensor I motif (285)REDXXYR(291) of the trans protomer. This atypical ATP binding raises the question of whether heptamerization of FlrC is solely required for transcription regulation, or if it is also critical for ATPase activity. ATPase assays and size exclusion chromatography of the trans-variants FlrC(C)-Y290A and FlrC(C)-R291A showed destabilization of heptameric assembly with concomitant abrogation of ATPase activity. Crystal structures showed that in the cis-variant FlrC(C)-R349A drastic shift of Walker A encroached ATP-binding site, whereas the site remained occupied by ADP in FlrC(C)-Y290A. We postulated that FlrC(C) heptamerizes through concentration-dependent cooperativity for maximal ATPase activity and upon heptamerization, packing of trans-acting Tyr(290) against cis-acting Arg(349) compels Arg(349) to maintain proper conformation of Walker A. Finally, a Trp quenching study revealed binding of cyclic-di-GMP with FlrC(C). Excess cyclic-di-GMP repressed ATPase activity of FlrC(C) through destabilization of heptameric assembly, especially at low concentration of protein. Systematic phylogenetic analysis allowed us to propose similar regulatory mechanisms for FlrCs of several Vibrio species and a set of monotrichous Gram-negative bacteria.

The sub-Saharan region of Africa is rapidly urbanizing, that has consequently spurred the development of specific challenges in terms of access to basic services and sanitation. Thus, exposure to waterborne diseases, including cholera, has been a recurrent problem for the people residing in these urban locations. It is important to understand the different risks faced by people in urban areas as it might aid in preventing and controlling the spread of the disease. A review of literature was conducted, using specific selection criteria to obtain relevant publications that described the risk factors for cholera outbreak in urban areas of sub-Saharan Africa. A perusal of available literature indicated that despite the heterogeneity in the urban areas of Africa, there are similarities with respect to the risk factors associated with the incidence of cholera epidemics. These risk factors include geographical location, hydroclimatic parameters, urban environment, genomics of the Vibrio cholerae virulence, sanitation, and human behavior. A succinct comprehension of the possible relationship between the different risk factors might prove to be helpful in managing the cholera epidemic.

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.

Nous allons confronter la description scientifique du choléra et les mesures pour le prévenir et le guérir, avec celles qu’en écrit Giono dans son roman. Giono enrichit par la psychologie de ses personnages l’approche psychodynamique des réactions humaines face à une épidémie. Les affects déployés, la peur de la mort, la pulsion et le désir de vivre, les réactions de groupe, trouvent leur origine dans cette peur de l’inconnu, comme une réminiscence du trauma de la naissance où le désir suit la pulsion.

Background In 2018, Zimbabwe declared another major cholera outbreak a decade after recording one of the worst cholera outbreaks in Africa. Methods A mathematical model for cholera was used to estimate the magnitude of the cholera outbreak and vaccination coverage using cholera cases reported data. A Markov chain Monte Carlo method based on a Bayesian framework was used to fit the model in order to estimate the basic reproductive number and required vaccination coverage for cholera control. Results The results showed that the outbreak had a basic reproductive number of 1.82 (95% credible interval [CrI] 1.53–2.11) and required vaccination coverage of at least 58% (95% Crl 45–68%) to be contained using an oral cholera vaccine of 78% efficacy. Sensitivity analysis demonstrated that a vaccine with at least 55% efficacy was sufficient to contain the outbreak but at higher coverage of 75% (95% Crl 58–88%). However, high-efficacy vaccines would greatly reduce the required coverage, with 100% efficacy vaccine reducing coverage to 45% (95% Crl 35–53%). Conclusions These findings reinforce the crucial need for oral cholera vaccines to control cholera in Zimbabwe, considering that the decay of water reticulation and sewerage infrastructure is unlikely to be effectively addressed in the coming years.

The unique genetic makeup and remarkable competency of Vibrio cholerae are the key factors that help the cholera pathogen adapt rapidly to adverse environmental conditions and resist the detrimental effect of antimicrobial agents. In the last few decades, V. cholerae that causes acute watery diarrhoeal disease cholera has emerged as a notorious multidrug resistant (MDR) enteric pathogen. Although chromosomal mutations can contribute to antimicrobial resistance (AMR), the frequent acquisition of extrachromosomal mobile genetic elements (MGEs) from closely/distantly related bacterial species are major players in V. cholerae drug resistance. Whole genome sequence analysis of clinical and environmental V. cholerae strains revealed that the genome of most of the recent isolates harbour integrating conjugative elements (ICEs), plasmids, superintegron, transposable elements and insertion sequences, which are the key carriers of genetic traits encoding antimicrobial resistance function. Different antimicrobial resistance genes identified in V. cholerae can contribute in antibiotic resistance by facilitating one of the following three mechanisms; (i) reduced permeability or active efflux of the antibiotics, (ii) alteration of the antibiotic targets by introducing post-transcriptional/translational modifications and (iii) hydrolysis or chemical modification of antibiotics. Here, we present an overview of the present insights on the emergence and mechanisms of AMR in V. cholerae.

Cholera continues to be poorly controlled in multiple epidemic and endemic areas across the globe, with estimated annual incidence of 1.3–4.0 million cases, resulting in 21,000 to 143,000 deaths worldwide in 2015. The usual approach for patient diagnosis and cholera surveillance is clinical examination of cases of acute watery diarrhea (AWD), confirmed by positive culture or polymerase chain reaction tests. Rapid diagnostic tests (RDTs) are used in regions with limited laboratory capacities but have been found to demonstrate large variations in performance, ranging in sensitivity from 58% to 100% and in specificity from 60% to 100%. Most countries rely on hospital-based surveillance of diarrheal disease to compute the cholera burden. The World Health Organization (WHO) recommends that countries assess public health events involving cholera against the International Health Regulations 2005 criteria and determine need for official notification using the standard case definition. Cholera is an often under-recognized and under reported problem because of differences in case definitions, reluctance by authorities to acknowledge and report cholera, inadequacies in hospital surveillance systems, lack of effective diagnostic tests and commonalities in clinical presentation of cholera with other AWD etiologies. The resulting gap in burden data impairs economic analysis of disease impact and identification of areas for targeted control interventions. There is an urgent need to strengthen surveillance data by supplementing reported numbers with estimates from literature reviews and data from modelling studies, developing better-performing RDTs, enhancing monitoring and evaluation processes of in-country surveillance systems, and encouraging countries to report cholera cases by “rewarding” better reporting with technical support and improved access to vaccines. It is imperative that immediate steps are taken towards strengthening surveillance and reporting systems globally, especially in cholera-prone and resource-limited areas, where it will enable countries to articulate their demand for resources more accurately.

Cholera still affects about three million people a year and kills approximately 100,000. Cholera can be effectively managed in the majority of cases with oral rehydration solution alone. Up to one third of patients present with severe dehydration, which can be diagnosed clinically, and will require rapid intravenous rehydration with Ringers Lactate or other appropriate fluid before being managed with oral rehydration solution. Antibiotics reduce the duration of illness and should be used in patients with severe dehydration. Resistance is common and local sensitivities should guide the choice of antibiotic. All children between six months and five years should receive zinc supplements. Effective case management with strict attention to detail including infection control and the use of protocolized approaches can reduce the mortality to around 1% even in resource poor settings.

Cholera remains a major global public health problem that is primarily linked to insufficient access to safe water and proper sanitation. Oral Cholera Vaccine (OCV) has been recommended as an additional public health tool along with WASH in cholera endemic countries and in areas at risk for outbreaks. The new generation OCV is safe and offers good protection in older children and adults while limited protection in younger children less than five years of age has been observed. The combination of direct vaccine protection and vaccine herd immunity effects makes OCV highly cost-effective and, therefore, attractive for use in developing countries. Additionally, in recent studies OCV was safe in pregnant women, supporting its use in pregnant women in cholera endemic countries. However, knowledge need to be developed for current vaccines for their prolonged duration of protection and vaccines need improvements for better immune response in younger children. A single dose vaccination regimen would be more cost-effective and easier to deliver. Recent approaches have focused on designing genetically attenuated cholera strains for use in single-dose cholera vaccines. The global demand for OCV has been boosted by the WHO recommendation to use OCV and is driven largely by epidemics and outbreaks and has been increasing due to the availability of cheaper easy-to-use vaccines, feasibility of mass OCV vaccination campaigns, demonstration of protection to underserved population in precarious situations, and vaccine costs being borne by Gavi (Vaccine Alliance). For rapid access in emergency and equitable distribution of OCV in cholera-endemic low-income countries, a global OCV stockpile was established in 2013 with support from the Global Alliance for Vaccines and Immunization. The three WHO-prequalified vaccines are Dukoral®, Shanchol™, Euvichol® (and Euvichol® Plus presentation), the latter two being included in the stockpile.

Background The economic burden data can provide a basis to inform investments in cholera control and prevention activities. However, treatment costs and productivity loss due to cholera are not well studied. Methods We included Asian countries that either reported cholera cases to the World Health Organization (WHO) in 2015 or were considered cholera endemic in 2015 global burden of disease study. Public health service delivery costs for hospitalization and outpatient costs, out-of-pocket costs to patients and households, and lost productivity were extracted from literature. A probabilistic multivariate sensitivity analysis was conducted for key outputs using Monte Carlo simulation. Scenario analyses were conducted using data from the WHO cholera reports and conservative and liberal disease burden estimates. Results Our analysis included 14 Asian countries that were estimated to have a total of 850,000 cholera cases and 25,500 deaths in 2015 While, the WHO cholera report documented around 60,000 cholera cases and 28 deaths. We estimated around $20.2 million (I$74.4 million) in out-of-pocket expenditures, $8.5 million (I$30.1 million) in public sector costs, and $12.1 million (I$43.7 million) in lost productivity in 2015. Lost productivity due to premature deaths was estimated to be $985.7 million (I$3,638.6 million). Our scenario analyses excluding mortality costs showed that the economic burden ranged from 20.3% ($8.3 million) to 139.3% ($57.1 million) in high and low scenarios when compared to the base case scenario ($41 million) and was least at 10.1% ($4.1 million) when estimated based on cholera cases reported to WHO. Conclusion The economic burden of cholera in Asia provides a better understanding of financial offsets that can be achieved, and the value of investments on cholera control measures. With a clear understanding of the limitations of the underlying assumptions, the information may be used in economic evaluations and policy decisions.

Cholera-endemic Eastern India has played an important role in the development of oral cholera vaccines (OCV) through conduct of pivotal trials in Kolkata which led to the registration of the first low-cost bivalent killed whole cell OCV in India in 2009, and subsequent prequalification by the World Health Organization prequalification in 2011. Odisha hosted an influential early demonstration project for use of the vaccine in a high-risk population and provided data and lessons that were crucial input in the Vaccine Investment Strategy developed by Gavi, the Vaccine Alliance in 2013. With Gavi's decision to finance an OCV stockpile, the demand for OCV surged and vaccine has been deployed with great success worldwide in areas of need in response to outbreaks and disasters, most notably in Africa. However, although India is considered one of the highest burden countries, no further use of OCV has occurred since the demonstration project in Odisha in 2011. In this paper we will summarize the important contributions of India to the development and use of OCV and discuss the possible barriers to OCV introduction as a public health tool to control cholera.

Vaccination is a key intervention to prevent and control cholera in conjunction with water, sanitation and hygiene activities. An oral cholera vaccine (OCV) stockpile was established by the World Health Organization (WHO) in 2013. We reviewed its use from July 2013 to all of 2018 in order to assess its role in cholera control. We computed information related to OCV deployments and campaigns conducted including setting, target population, timelines, delivery strategy, reported adverse events, coverage achieved, and costs. In 2013–2018, a total of 83,509,941 OCV doses have been requested by 24 countries, of which 55,409,160 were approved and 36,066,010 eventually shipped in 83 deployments, resulting in 104 vaccination campaigns in 22 countries. OCVs had in general high uptake (mean administrative coverage 1st dose campaign at 90.3%; 2nd dose campaign at 88.2%; mean survey-estimated two-dose coverage at 69.9%, at least one dose at 84.6%) No serious adverse events were reported. Campaigns were organized quickly (five days median duration). In emergency settings, the longest delay was from the occurrence of the emergency to requesting OCV (median: 26 days). The mean cost of administering one dose of vaccine was 2.98 USD. The OCV stockpile is an important public health resource. OCVs were generally well accepted by the population and their use demonstrated to be safe and feasible in all settings. OCV was an inexpensive intervention, although timing was a limiting factor for emergency use. The dynamic created by the establishment of the OCV stockpile has played a role in the increased use of the vaccine by setting in motion a virtuous cycle by which better monitoring and evaluation leads to better campaign organization, better cholera control, and more requests being generated. Further work is needed to improve timeliness of response and contextualize strategies for OCV delivery in the various settings.

Background Recently World Health Organization’s Global Task Force on Cholera Control (GTFCC) has published a global roadmap for prevention and control of cholera. We review preparedness of existing governmental non-vaccine programs and strategies for cholera prevention and control in India. We also describe strengths and gaps in the context of implementation of the global roadmap. Methods We reviewed published literature on non-vaccine based strategies for prevention and control of cholera in India and analyzed strengths and weaknesses of Government of India’s major anti-cholera and ante-diarrhea initiatives under Integrated Disease Surveillance Program (IDSP), National Rural Health Mission (NRHM), and other disease surveillance platforms. Results The first strategy of the WHO global roadmap, namely, preparedness for early detection and outbreak containment, has been addressed by the IDSP. NRHM complements IDSP activities by focusing on sanitation, hygiene, nutrition, and safe drinking water. We identified the need to adopt stricter case definitions and data validation protocols. Multi-sectoral approach to prevent cholera occurrences and re-occurrences [the second suggested strategy in the global roadmap], highlights identification of hotspots and implementing strategies based on transmission dynamics. We recommend development of comprehensive models by integrating data sources beyond the national programs to eliminate cholera hotspots in India. Implementing the third proposed strategy in the global roadmap, coordinated technical support, resource mobilization, and partnerships at local and global levels, has major challenges in India due to structural issues related to health systems and health programs. Conclusion Even with a robust public health infrastructure, absence of a national cholera program might have resulted in lack of specific focus and concerted efforts for cholera prevention and control in India. A National Taskforce for Cholera Control must develop India-specific ‘National Cholera Prevention and Response Road Map’ with an appropriate administrative and financially viable framework for its implementation.

Development of oral cholera vaccines (OCVs) experienced exciting times over the last two decades. A two-dose OCV, found efficacious through field trials, has obtained license for use in India. However, the current policy discussion revolves around 'to use or not to use' this vaccine covering entire population in the country, which has its own cost implications. We conducted a systematic review to address this conundrum. The disease burden and distribution, potential impact, programmatic issues, and competing priorities were kept in consideration. Peer reviewed articles and 'Integrated Disease Surveillance Program' data, generated by Government of India, were accessed. Our synthesis highlights that cholera burden estimates for India have been hamstrung by their extrapolation from a single incidence study conducted in Kolkata. Heterogeneity of 685 Indian districts regarding vulnerability to cholera is also obvious. Analysis of outbreak reports indicated that some settlements and sub-populations were more vulnerable to diarrhea/cholera than others. Infrastructure failure leading to contamination of drinking water and behavioral issues were of concern. Investment in safe water, sanitation and hygiene (WASH) and addressing inequity of health services pertaining to vulnerable population groups are the needs of the hour. OCV could play an important role as one of the elements in such multi-component cholera prevention effort. OCV administration through public health system in Odisha identified logistic challenges, with low uptake of the second dose at 46%, while 61% of the target population received the first dose. We identified accumulating global evidence on the advantage and efficacy of single-dose based approach, where the same OCV, as licensed in India, was used. The short-lasting nature of cholera outbreaks in India also argue in favor of such pragmatism. Failure to implement multi-component prevention strategy today runs the risk of perpetuating inequity, recurring cholera outbreaks in future, and its retinue of costs.

We have earlier reported that a single dose of oral cholera vaccine (OCV) is protective in adults and children ≥5 years of age and sustained for 2 years. We enrolled participants (n = 240) from this study, between March-September 2017, over 3 years after receiving a primary single dose. Immune responses were measured in placebo group (Primary Immunization group: PI) and compared with those who received a single dose (Booster Immunization group: BI). The children were 4 to 18 years. Blood was collected at day 0 (before vaccination) and after receiving 1st and 2nd doses of OCV. Overall, the BI and PI groups showed vibriocidal antibody response after 1st and 2nd dose of vaccination in all age groups to V. cholerae O1 and O139. Young children in the BI group showed significantly higher vibriocidal antibody response two weeks after receiving the first dose as compared to PI group to LPS. Elevated plasma IgA responses to LPS after the first dose were observed among the BI group compared to the PI group among the young children. Mucosal antibody responses measured in fecal extracts showed similar increases as that of vibriocidal and LPS responses in the BI group. These results suggest a single boosting dose of OCV generated immune response in primed population >5 years of age who had earlier received OCV. However, young children who had received OCV earlier, boosting after a single dose, resulted in increased immune responses compared to the PI group. Further studies are needed to assess protection obtained from different strategies, especially for young children and to determine the numbers of primary and booster doses needed. In addition, more information is needed regarding the optimum interval between primary and booster doses to plan future interventions for cholera control. ClinicalTrials.gov Identifier: NCT 02027207.

In the freshwater environment of north India, cholera appears seasonally in form of clusters as well as sporadically, accounting for a significant piece of the puzzle of cholera epidemiology. We describe a number of cholera outbreaks with an average attack rate of 96.5/1000 but an overall low case fatality (0.17). Clinical cholera cases coincided with high rainfall and elevated temperatures, whereas isolation of V. cholerae non-O1 non-O139 from water was dependent on temperature (p 0.05) but was independent of rainfall and pH (p 0.05). However, isolation from plankton samples correlated with increased temperature and pH (p 0.05). A lag period of almost a month was observed between rising temperature and increased isolation of V. cholerae from the environment, which in succession was followed by an appearance of cholera cases in the community a month later. Our results suggested that the aquatic environment can harbor highly divergent V. cholerae strains and serve as a reservoir for multiple V. cholera virulence-associated genes that may be exchanged via mobile genetic elements. In agreement with PFGE, AFLP data also proved that the V. cholerae O1 population was not clonal but was closely related. Our investigation did not support the concept that seasonal cholera outbreaks occur by movement of a single clonal strain across the region, as the clinical isolates from the same years were clearly different, implying that continuous evolution of V. cholerae O1 strains occurs in the cholera endemic area. Interestingly, the viable but non-culturable (VBNC) V. cholerae O1 cells were demonstrated in 2.21% samples from natural water bodies in addition to 40.69% samples from cholera-affected areas respectively. This suggests that aquatic environs do harbor the pathogenic O1 strain, though the isolation of culturable V. cholerae O1 is a rare event in the presence of relatively abundant non-O1 non-O139 isolates.

Seafood has frequently been associated with foodborne illness because pathogens are easily introduced during seafood cultivation, handling, and processing. Vibrio parahaemolyticus and Vibrio cholerae are human pathogens that cause gastroenteritis and cholera, respectively, and Vibrio vulnificus can cause fatal wound infections and septicemia. However, information about the occurrence of these pathogens in oysters from the Pacific coast of Mexico is limited to V. parahaemolyticus. In the present study, we evaluated the presence and abundance of these three Vibrio species in 68 raw oysters (Crassostrea corteziensis) obtained from retail seafood markets in Sinaloa, Mexico. The most probable number (MPN)-PCR assay was used for amplification of the tlh (thermolabile hemolysin), ompW (outer membrane protein), and vvhA (hemolytic cytolysin) genes that are specific to V. parahaemolyticus, V. cholerae, and V. vulnificus, respectively. All oyster samples were positive for at least one Vibrio species. V. parahaemolyticus, V. cholerae, and V. vulnificus prevalences were 77.9, 8.8, and 32.3% overall, respectively, and most species were present in all sample periods with increased prevalence in period 3. The tdh (thermostable direct hemolysin) gene was detected in 30.1%, trh (TDH-related hemolysin) was detected in 3.7%, and tdh/trh was detected in 7.5% of the total tlh-positive samples (53 of 68), whereas the pandemic serotype O3:K6 (orf8 positive) was detected in only 1 sample (1.8%). The total prevalence of tdh and/or trh was 41.5%. In none of the samples positive for V. cholerae were the cholera toxin (ctxA) and cholix (chxA) toxigenic genes or the rfb gene encoding the O1 and O139 antigens amplified, suggesting the presence of non-O1 non-O139 V. cholerae strains. Our results clearly indicated a high prevalence of pathogenic Vibrio species in raw oysters from retail seafood markets in Mexico. Consumption of these raw oysters carries the potential risk of foodborne illness, which can be limited by cooking.

Vibrio cholera (V. cholera) is a facultative pathogen that colonizes the small intestine and produces cholerae toxin as the primary virulence factor that causes cholera and fatal diarrhea in humans. In recent decades, V. cholera has emerged as a notorious multidrug-resistant enteric pathogen. This meta-analysis estimated the pooled proportion of V. cholera antimicrobial resistance against RNA and DNA effective antibiotics.A systematic search was performed for relevant literature until 05 June 2021 in PubMed, Scopus, Embase, and Web of Science databases. Freeman-Tukey double arcsine transformation was performed to estimate weighted pooled resistance (WPR).The meta-analysis were included 164 articles. The WPR of V. cholera were as follows 76% [67,84] to furazolidone, 65% [29,94] to nitrofurantoin, 55% [44,66] to nalidixic acid, 10% [2,23] to rifampicin, 4%(0, 12) to novobiocin, 4% [2,6] to norfloxacin, 3% [1,4] to ciprofloxacin, 1%(0, 3) to sparofloxacin, 0%(0, 3) to levofloxacin, 0%(0, 2) to ofloxacin, 0%(0, 0) to gatifloxacin.V. cholera is a severe problem in Asia and Africa, especially in South Asian countries. The resistance patterns are various in geographical regions. novobiocin 0% (0, 0), and ofloxacin 0% (0, 1) in Africa, gatifloxacin 0% (0, 0), and levofloxacin 0% (0, 6) in Asia and ciprofloxacin 0% (0, 2) in North America are most effective antibiotis. The resistance rate to furazolidone, nalidixic acid, nitrofurantoin, and cephalothin has increased over the years. Monitoring antibiotic resistance and prescribing an appropriate antibiotic is vital to control resistance.

In this issue of Cell, Alavi et al. report that infection by Vibrio cholerae is blocked by gut microbiome-mediated hydrolysis of bile acids. Cholera therefore joins amebic dysentery and Clostridioides difficile colitis as enteric infections profoundly influenced by the microbiome's impact on bile acid metabolism.

Ogawa and Inaba are two main serotypes of O1 V. cholerae and alternate among cholera epidemics. The rfbT gene encodes a methyltransferase and is required for Ogawa serotype. The Inaba serotype is the consequence of genetic alterations in rfbT gene which results in loss-of-function enzyme product. However, the expression and regulation of rfbT has not been understood yet. Here we demonstrated that a global regulator, cAMP receptor protein (CRP), positively regulates rfbT transcription through a non-canonical CRP binding site (CBS) in its promoter region. This finding is supported by the analyses of rfbT mRNA abundance, rfbT–lacZ fusions and electrophoretic mobility shift assay (EMSA). The analyses of rfbT mRNA level in wild type (WT), Δcrp, and lower or higher level of cAMP backgrounds revealed that CRP is required for rfbT expression in response to intracellular cAMP level. Subsequent rfbT–lacZ fusions and EMSA collectively displayed that cAMP-CRP complex transcriptionally activates rfbT through directly binding to CBS in rfbT promoter region. Consistently, serological microagglutination test showed that crp deletion resulted in at least 4-fold decrease in titer of Ogawa serum compared to its WT. These results expanded our knowledge of understanding the genetic determinants and probable regulatory mechanism of V. cholerae O1 serotype shift between Ogawa and Inaba.

Cholera is an infectious disease caused by the bacterium vibrio cholerae, which can lead to widespread epidemics in the deterioration of public health systems or the associated infrastructure. Vaccination and water sanitation are two well-known methods for the prevention and intervention of cholera epidemics. In this paper, we propose an age-structured cholera model that incorporates both the environment-to-human and human-to-human transmission pathways and that includes host vaccination and water sanitation as disease control measures. We rigorously investigate the threshold dynamics of this model using the basic reproduction number derived from our analysis. Meanwhile, we perform an optimal control study to explore cost-effective intervention strategies for cholera. Our numerical simulation results show that the outcome of the optimal control is shaped by the complex interactions among the age structure of the hosts, the costs of the control measures, the transmission modes of the disease, and the different approaches of cholera intervention.

Multiple diarrheagenic enteric bacterial infections cause global morbidity and mortality. A combination vaccine is needed to combat different diarrhea-causing organisms. In our present work, we formulated a combination of antigens from three different diarrheagenic Escherichia coli strains and three different Vibrio cholerae strains. We demonstrated that our newly formulated combination immunogen was able to raise species-specific immunogenicity. This formulation also gave protection against different diarrheagenic E. coli strains in the removable intestinal tie-adult rabbit diarrhea model. However, protective efficacy was not found against the V. cholerae El Tor Ogawa Haitian variant, but challenged with V. cholerae El Tor Inaba or O139 showed protection in rabbits. This is the first report of a single formulated nonliving heat-killed combination immunogen from different diarrheagenic E. coli and V. cholerae that could bestow protection against different bacteria in an animal model.

Introduction In 2014, an oral cholera vaccine (OCV) campaign targeting 185,314 persons aged ≥1 years was conducted in 3 departments via fixed post and door-to-door strategies. This was the first use of the global OCV stockpile in Haiti. Methods We conducted a multi-stage cluster survey to assess departmental OCV coverage. Target population estimates were projected from the 2003 Haiti population census with adjustments for population growth and estimated proportion of pregnant women. In the three departments, we sampled 30/106 enumeration areas (EAs) in Artibonite, 30/244 EAs in Centre, and 20/29 EAs in Ouest; 20 households were systematically sampled in each EA. Household and individual interviews using a standard questionnaire were conducted in each selected household; data on OCV receipt were obtained from vaccination card or verbal report. We calculated OCV campaign coverage estimates and 95% confidence intervals (CIs) accounting for survey design. Results Overall two-dose OCV coverage was 70% (95% CI: 60, 79), 63% (95% CI: 55, 71), and 44% (95% CI: 35, 53) in Artibonite, Centre, and Ouest, respectively. Two-dose coverage was higher in the 1–4 years age group than among those ≥ 15 years in Artibonite (difference: 11%; 95% CI: 5%, 17%) and Ouest (difference: 12%; 95% CI: 3, 20). A higher percentage of children aged 5–14 years received both recommended doses than did those ≥ 15 years (Artibonite: 14% (95% CI: 8%, 19%) difference; Centre: 11% difference (95% CI: 5%, 17%); Ouest: 10% difference (95% CI: 2%, 17%). The most common reason for not receiving any OCV dose was being absent during the campaign or not having heard about vaccination activities. Conclusions While coverage estimates in Artibonite and Centre were comparable with other OCV campaigns in Haiti and elsewhere, inadequate social mobilization and outdated population estimates might have contributed to lower coverage in Ouest.

Cholera is a severe diarrheal disease caused by the bacterium Vibrio cholerae (V. cholerae) that results in 3–4 million cases globally with 100,000–150,000 deaths reported annually. Mostly confined to developing nations, current strategies to control the spread of cholera include the provision of safe drinking water and improved sanitation and hygiene, ideally in conjunction with oral vaccination. However, difficulties associated with the costs and logistics of these strategies have hampered their widespread implementation. Specific challenges pertaining to oral cholera vaccines (OCVs) include a lack of safe and effective adjuvants to further enhance gut immune responses, the complex and costly multicomponent vaccine manufacturing, limitations of conventional liquid formulation and the lack of an integrated delivery platform. Herein we describe the use of the orally active adjuvant α-Galactosylceramide (α-GalCer) to strongly enhance intestinal bacterium- and toxin-specific IgA responses to the OCV, Dukoral® in C57BL/6 and BALB/c mice. We further demonstrate the mucosal immunogenicity of a novel multi-antigen, single-component whole-cell killed V. cholerae strain and the enhancement of its immunogenicity by adding α-GalCer. Finally, we report that combining these components and recombinant cholera toxin B subunit in the SmPill® minisphere delivery system induced strong intestinal and systemic antigen-specific antibody responses.

Background The evidence for recommendations regarding vaccination in solid organ transplant recipients is sparse. There is little data comparing vaccine responses between groups on different immunosuppressive drugs. This study was conducted to evaluate the antibody response to Dukoral® oral cholera vaccine in renal transplant recipients (RTR). Methods In a single-center non-randomized controlled clinical trial, healthy volunteers (n = 21) and renal transplant recipients (n = 30) were vaccinated with the oral whole cell/recombinant B subunit cholera vaccine Dukoral® (Valneva Inc., Vienna, Austria). The RTR were stratified according to their maintenance immunosuppressive therapy: either prednisone and a calcineurin inhibitor (cyclosporine A or tacrolimus; P/CNI group; n = 15) or prednisone and mycophenolate (P/MMF group; n = 15). All volunteers ingested Dukoral® at baseline and at day 14. Serum samples were drawn at day 0 and day 21. The primary outcome was seroconversion, defined as either a 3-fold IgA serum titer increase in anti-cholera toxin B antibodies and/or a 4-fold rise in the serum vibriocidal titer. Results Follow-up was complete. Seroconversion after vaccination was 57% (standard error, SE 9%) in RTR and 81% (SE 9%) in healthy controls (Relative Risk, RR 0.70; 95% CI 0.48–1.02). When stratified according to maintenance immunosuppression, the seroconversion rate was 67% (SE 12%) in the P/CNI group (RR compared with controls 0.82; 95% CI 0.55–1.25) and 47% (SE 13%) in the P/MMF group (RR compared with controls 0.58; 95% CI 0.32–1.03). Conclusion Adverse events were mild to moderate and transient. The response to Dukoral was weaker and the seroconversion rate was lower in renal transplant recipients than in healthy controls. In particular, those using mycophenolate had a poor response. Nevertheless, more than half of the transplant recipients seroconverted. Therefore oral vaccines should not be discarded as a potential tool for protection of solid organ transplant recipients. This trial is registered in clinicaltrials.gov under NCT01109914.

Vibrio cholerae O1 can cause life threatening diarrheal disease if left untreated. T cells can play critical roles in inducing B cell mediated immunity. As the mechanism of T cell dependent B cell maturation is not well established, we hypothesized that a specific population of T (follicular helper T, Tfh) cells, are involved in B cell maturation following cholera. We found flowcytometrically that V. cholerae infection induces significant increases in circulating Tfh cells expressing B cell maturation associated protein CD40L early in disease. The increased Tfh cells expressing CD40L recognize cholera toxin most prominently, with lessened responses to V. cholerae membrane preparation (MP) and V. cholerae cytolysin (VCC). We further showed that early induction of Tfh cells and CD40L was associated with later memory B cell responses to same antigens. Lastly, we demonstrated in vitro that Tfh cells isolated after cholera can stimulate class switching of co-cultured, isolated B cells from patients with cholera, leading to production of the more durable IgG antibody isotype colorimetrically. These studies were conducted on circulating Tfh cells; future studies will be directed at examining role of Tfh cells during cholera directly in gut mucosa of biopsied samples, at the single cell level if feasible.

Vibrio cholerae strains producing cholera toxin (CT) and toxin co-regulated pilus (TCP) and belonging to O1 and O139 serogroups are responsible for cholera. However, non-CT producing V. cholerae from non-O1/non-O139 serogroups have been increasingly isolated from diarrheal stools and extra-intestinal infections. In this study, we have developed a multiplex PCR for the simultaneous detection of heat-stable enterotoxin (stn), type three-secretion system (vopF), and cholix toxin (chxA), along with CT (ctx) in V. cholerae strains. As other species from genus Vibrio carries homologous virulence genes, V. cholerae specific ompW was also included to differentiate V. cholerae from other vibrios. This assay was 100% specific and sensitive, and could detect homologous virulence genes like ctxA in V. mimicus and vopF in V. parahaemolyticus. This multiplex PCR assay, which can detect four major virulence genes in V. cholerae, is novel and important for epidemiologic and environmental surveillance of pathogenic V. cholerae.

Spatially specific intervention is proven to be more cost-effective than the “one-fit-all” strategy in controlling infectious disease outbreaks. However, it presents decision challenges due to partially observable epidemic state information and imperfectly determined model parameters. With deployment of mobile sensor, additional information such as geo-tagged bacteria concentration can be acquired, which can help to improve the understanding of the epidemic state and model parameters. Thus, a mobile sensor dispatching problem deciding further sensing spots should be studied considering the surveillance capacity. To solve this problem, we develop a metapopulation model based predictive control approach for making intelligent public health intervention decisions and sensor spatial dispatch decisions for cholera outbreak control. This approach incorporates a mobile sensor deployment scheme considering the improvement on unmeasurable parameter estimation and epidemic state prediction. Then it optimizes spatially specific intervention strengths to mitigate the harm of the infected population with progressively gained understanding of the system via mobile sensing.

The repeated dose toxicity of a prototype cold chain-free, live, attenuated oral cholera vaccine containing 5 × 106 CFU/mL of the VCUSM14P strain was evaluated in Sprague Dawley (SD) rats (single dose administered daily for 30 days) to ascertain its safety for clinical use. Repeated dose toxicity studies for cholera vaccines in the literature have administered 2 or 3 fixed doses at 7, 14, 21 or 69 day intervals. The present study reports an evaluation of 30 repeated doses of cholera vaccine administered at three different concentrations (Group II (1.25 × 106 CFU), Group III (2.5 × 106 CFU) and Group IV (5 × 106 CFU)) in SD rats. The liquid vaccine was administered orally to the rats with the respective dose every day, and normal saline was administered to the control group (Group I). No significant difference (P > 0.05) was observed in the body weights and biochemical parameters of the rats after 15 and 30 repeated doses compared to those of the control group. However, compared to those of Group I, a significant increase (P < 0.05) in the organ to body weight ratios of the lungs, ureter, liver, kidney, heart and spleen was found in G-II, G-III and G-IV. In the haematological analysis, a significant increase in the WBC was observed in G-II and G-IV compared to that in G-I. The histopathological findings indicated mild to moderate degeneration in the liver, kidney, heart and spleen in the treated rats. Mild to moderate lymphocytic infiltration in the lungs was observed in the G-II and G-III rats, and severe infiltration was observed in the G-IV rats. These histopathological findings may be attributed to the 30 doses of vaccine given in daily succession without an interval. In the acute toxicity study, a single dose of vaccine up to 10 × 106 CFU did not cause any adverse effects and lethality in SD rats.

The transmission of cholera, a water- and food-borne intestinal infection, involves complex interactions among human hosts, pathogens, and the environment, and is impacted by the spatial variation and seasonal fluctuation. In this paper, we propose a new deterministic model to investigate the spatiotemporal dynamics of cholera transmission. The model employs a reaction–convection–diffusion system to represent the spatial movement of the hosts and pathogens, and incorporates time-periodic parameters to describe the seasonality of the disease transmission and bacterial growth rates. Using the theory of principle eigenvalues, we define and analyze the basic reproduction number of this model, based on which we establish the threshold type results for cholera transmission in a spatiotemporally heterogeneous environment.

Cholera is an acute, virulent infectious illness caused by the infection of the intestine with the bacterium Vibrio cholerae. In this paper, aMathematical model of the cholera epidemics of the number of susceptible individuals, infected individuals, recovered individuals, concentration of the Vibrio cholerae has been discussed. This model was solved by the methods of the Homotopy Perturbation Method and the New Homotopy Perturbation Method. Our results are compared with the numerical simulation of the problem and a satisfactory agreement of the results is noted.

French Abstract: Au cours de l'histoire, rien n'a tue plus d'etres humains que les maladies infectieuses et la fievre hemorragique. Bien que les taux de mortalite dus aux pandemies aient chute de pres de 1 % par an dans le monde, environ 0,8 % par an, tout au long du XXe siecle, le nombre de nouvelles maladies infectieuses comme le Sars, le VIH et le Covid-19 a presque quadruple par rapport au passe. En Afrique, on a signale un total de 4 522 489 cas confirmes de COVID-19 et 119 816 deces, au 23 avril 2021. La pandemie a eu de graves repercussions sur les secteurs economique et social dans presque tous les pays africains. Il menace de pousser jusqu'a 58 millions de personnes dans l'extreme pauvrete. Cependant, outre les Africains pauvres, la pandemie de Covid affecte egalement la classe moyenne africaine en pleine croissance, c'est-a-dire environ 170 millions sur les 1,3 milliard d'Africains actuellement classes dans la classe moyenne. Pres de huit millions d'entre eux pourraient etre plonges dans la pauvrete a cause du coronavirus et de ses consequences economiques. Ce revers se fera sentir pendant des decennies. En outre, dans l'histoire recente de l'Afrique, d'autres maladies infectieuses comme la trypanosomiase du bassin du Congo de 1896 a 1906 avec un nombre des morts de plus de 500 000 ainsi que l'epidemie de trypanosomose africaine en Ouganda de 1900 a 1920 avec 200 000 a 300 000 deces ont eu un impact negatif considerable sur les societes et economies africaines. En fait, d'autres pandemies, comme la fievre jaune, le cholera, la meningite et la rougeole-sans parler du paludisme-ont contribue a des ralentissements economiques durables et affectent gravement le bien-etre social pendant des decennies. German Abstract: ZUSAMMENFASSUNG : Im Laufe der Geschichte hat nichts mehr Menschen getotet als Infektionskrankheiten. Obwohl die Sterblichkeitsrate durch Pandemien im Laufe des 20. Jahrhunderts weltweit um etwa 0,8% pro Jahr gesunken ist, hat sich die Zahl der neuen Infektionskrankheiten wie Sars, HIV und Covid-19 im vergangenen Jahrhundert fast vervierfacht. In Afrika wurden zum 23. April 2021 insgesamt 4.522.489 bestatigte COVID-19-Falle und 119.816 Todesfalle gemeldet. Die Pandemie hatte schwerwiegende Auswirkungen auf den wirtschaftlichen und sozialen Sektor in fast allen afrikanischen Landern. Sie droht, bis zu 58 Millionen Menschen in extreme Armut zu treiben. Abgesehen von den afrikanischen Armen betrifft die Covid-Pandemie jedoch auch die wachsende afrikanische Mittelschicht, d. h. etwa 170 Millionen der 1,3 Milliarden Menschen in Afrika, die derzeit als Mittelschicht eingestuft sind. Fast acht Millionen von ihnen konnten aufgrund des Coronavirus und seiner wirtschaftlichen Folgen in Armut geraten. Dieser Ruckschlag wird noch Jahrzehnte zu spuren sein. Daruber hinaus hatten in der jungeren afrikanischen Geschichte auch andere Infektionskrankheiten wie die Trypanosomiasis (Schlafkrankheit) im Kongobecken von 1896–1906 mit einer Zahl von uber 500.000 Todesopfern sowie die Trypanosomiasis-Epidemie in Uganda von 1900–1920 mit 200.000–300.000 Todesfallen enorme negative Auswirkungen auf die afrikanischen Gesellschaften und Volkswirtschaften. Tatsachlich haben andere Pandemien wie Gelbfieber, Cholera, Meningitis und Masern - ganz zu schweigen von Malaria - zu lang anhaltenden wirtschaftlichen Abschwungen beigetragen und das soziale Wohlbefinden uber Jahrzehnte hinweg ernsthaft beeintrachtigt. English Abstract: Throughout history, nothing has killed more human beings than infectious diseases. Although, death rates from pandemics dropped globally by about 0.8 % per year, all the way through the 20th century, the number of new infectious diseases like Sars, HIV and Covid-19 increased by nearly fourfold over the past century. In Africa, there were reported a total of 4,522,489 confirmed COVID-19 cases and 119,816 death, as of 23 April 2021. The pandemic impacted seriously on the economic and social sectors in almost all African countries. It is threatening to push up to 58 m people into extreme poverty. However, apart from the African poor, the Covid pandemic also affects the growing African middle class, i.e. about 170 million out of Africa’s 1.3 billion people currently classified as middle class. Nearly eight million of may be thrust into poverty because of the coronavirus and its economic aftermath. This setback will be felt for decades to come. Moreover, in recent African History also other infectouse diseases like the 1896–1906 Congo Basin Trypanosomiasis with a death-toll of over 500.000 as well as the 1900–1920 Uganda African trypanosomiasis epidemic with 200,000–300,000 death had tremendous negative impact on Africa’s societies and economies. Actually, other pandemics, like Yellow Fever, Cholera, Meningitis and Measles – not to mention Malaria - contributed to long-lasting economic downturns and seriously affect the social wellbeing for decades.

Vibrio cholerae is one of the major causes of morbidity and mortality in developing countries. CtxB, responsible for toxin binding to eukaryotic cells, TcpA, involved in bacterial colonization, and OmpW, the highly conserved extracellular protein, are the three of the significant essential virulence factors in V. cholerae with enhanced immunogenic properties. Increasing emergence of antimicrobial-resistant strains (AMR) highlights the urgent need for new therapeutic agents. Uncomplicated high yield production, simple design, inducing either or both humoral and cellular immunity, and long-term immune responsiveness are some of the advantages of IgG antibodies over other immunotherapy agents. Chimeric proteins have the potential of presenting multiple antigens to immune system, simultaneously. Thus, the current study was aimed to evaluate the stability and protective efficacy of DNA and protein-based vaccine candidates of a chimeric gene harboring OTC (OmpW, TcpA and CtxB) against V. cholerae. The immunogenicity and specificity of induced IgGs were confirmed through indirect ELISA and western blot analysis, respectively. The DNA and protein immunized mice sera were able to neutralize the cytotoxicity effects of the cholera toxin (CT) at 5% and 10% dilutions in Y1 cell line, and inhibited 60% and 68% of the bacterial adhesion to HT-29 cells, respectively. The DNA and protein immunized sera provided 99% and 95% viability percent in spleen cell viability assays, and inhibited the bacteria-induced fluid accumulation in ileal loop assay at 1/80 and 1/160 dilutions, respectively. Different groups of passively immunized infant mice and actively immunized adult mice were challenged with V. cholerae. The OTC construct provided high survival rates against lethal infection, and significantly reduced the bacterial loads. Our results highlight the potential therapeutic effect of the recombinant OTC chimeric construct, either as a DNA or protein vaccine, due to its remarkable immunogenicity and protectivity against V. cholerae.

There is debate among researchers regarding the importance of water filtration in reducing mortality during the epidemiological transition. However, there is limited research on how water filtration affected cholera mortality during the second half of the 19th century. Using historical micro-data, this paper provides new evidence on the importance of water filtration in reducing cholera mortality during an outbreak. The results show that access to filtered water protected almost completely against cholera mortality. Water filtration could thereby have contributed more to mortality decline than what has previously been documented.