Research Projects : Export

Background

Cholera epidemics occur frequently in low-income countries affected by concurrent humanitarian crises. Evaluations of these epidemic response remains largely unpublished and there is a need to generate evidence on response efforts to inform future programmes. This review of MSF cholera epidemic responses aimed to describe the main characteristics of the cholera epidemics and related responses in these three countries, to identify challenges to the effectiveness and feasibility of different intervention strategies based on available data; and to make recommendations for epidemic prevention and control practice and policy.

Methods

Case studies from the Democratic Republic of Congo, Malawi and Mozambique were purposively selected by MSF for this review due to the documented burden of cholera in each of the countries, frequency of cholera outbreaks, and risk of concurrent humanitarian crises. Data were extracted on the characteristics of the epidemics; time between alert and response; and, the delivery of health and water, sanitation and hygiene (WASH) interventions. A Theory of Change for cholera response programmes was built to assess factors that affected implementation of the responses.

Results and conclusions

A total of 20 epidemic response reports were identified, 15 in DRC, one in Malawi and four in Mozambique. All contexts experienced concurrent humanitarian crises, either armed conflict or natural disasters. Across the three countries, median time between the date of alert and date of the start of the response by MSF was 23 days (IQR 14-41). Almost all responses targeted interventions community-wide, and all responses implemented in-patient treatment of suspected cholera cases in either established HCFs or temporary cholera treatment units (CTUs). In three responses, interventions were delivered as case-area targeted interventions (CATI) and four responses targeted households of admitted suspected cholera cases. CATI or delivery of interventions to households of admitted suspected cases occurred from 2017 onwards only. Overall, 74 factors affecting implementation were identified across reports including delayed supplies of materials, insufficient quantities of materials were delivered for effective programme delivery and limited or lack of coordination with local government or other agencies. Based on this review, the following recommendations are made to improve cholera prevention and control efforts: conduct rigorous and structured evaluations of cholera response programmes; explore improved models for epidemic preparedness, including rapid mobilisation of supplies and deployment of trained staff; invest in and strengthen partnerships with national and local government and other agencies as part of epidemic preparedness activities; and to standardise reporting templates within and across countries to provide consistent and accessible data by internal and external staff and collate learnings.

Based on this review, the following recommendations are made to improve cholera prevention and control efforts: conduct rigorous and structured evaluations of cholera response programmes; explore improved models for epidemic preparedness, including rapid mobilisation of supplies and deployment of trained staff; invest in and strengthen partnerships with national and local government and other agencies as part of epidemic preparedness activities; and to standardise reporting templates within and across countries to provide consistent and accessible data by internal and external staff and collate learnings.

In this project, we evaluated a program where Red Crescent volunteers staffed ORPs locally in conflict-affected areas. It was found volunteers could effectively staff the ORPs, provide ORS to minor cases, and refer moderate/sever cases. However, the mobile phone based monitoring system was not effectively established.

It is recommended to continue using volunteers to staff ORP.

Objective

Evaluate the effectiveness of the Case Area Targeted Intervention (CATI) approach in reducing the incidence of new cases during cholera outbreaks.  And in so doing, to determine factors that support optimal delivery and interventions for CATIs towards cholera reduction in humanitarian settings and fragile states.

Aim

The primary aim is to characterize the relationship between CATI activation time (time between case presentation at a cholera treatment facility and the start of the CATI intervention) and cholera incidence in the area covered by CATI interventions. Secondary aims include:

• Document procedures of implementing CATIs and develop recommendations to maximize their impact in future cholera outbreaks.
• Describe the integration of water, sanitation, and hygiene (WASH) and health activities delivered via CATI.
• Characterize the relationship between CATI completeness (in terms of coverage within the specified geographic area and activities implemented within households) and incidence of new cholera cases.
• Estimate CATI effectiveness using secondary parameters (e.g. reported diarrheal incidence, free chlorine residual (FCR) in the drinking water sample, and knowledge and practices to prevent cholera transmission).
• Document coordination mechanisms between Ministries, United Nations (UN) agencies, Clusters, and non-governmental organizations (NGOs) and develop recommendations for coordination in future responses.

Study Design

The proposed research will be conducted in future cholera outbreaks that take place in recognized humanitarian contexts in at least two different countries; locations will be selected based on where cholera outbreaks occur and the presence of a CATI implementing partner.  Organizations that frequently implement CATI interventions during cholera response that have agreed to partner with JHSPH include Action Against Hunger, Solidarités International, and Medair. Countries with humanitarian emergencies that are at high risk of cholera outbreaks include Democratic Republic of the Congo, Nigeria, Ethiopia, Mozambique and Yemen, though it is possible that other humanitarian contexts may serve as a research location if a cholera outbreak occurs and one of the aforementioned implementing partners responds with a CATI intervention.

The JHSPH IRB approval has classified this study as Non-Human Subjects Research.   Government or IRB approval will be attained prior to conducting the research.

The research team will be present at the site as soon as possible after the first cholera case has been documented and begin data collection as soon as feasible. If travel to the study location is not feasible for security reasons, the JHSPH research team will conduct the study remotely through the partner organization that is providing on-the-ground CATI response to the cholera outbreak.

Because the aim of the research is to evaluate CATIs as delivered by NGOs in response to a cholera outbreak, a randomized design is not possible. Thus, we will rely on comparison groups that will occur naturally, according to the outbreak size and capacity of the response organization. This will necessitate a flexible sampling approach.

We anticipate the primary comparison will be rapid vs. delayed CATI implementation (e.g. end stage of outbreak); however, it is also possible that areas with no CATI implementation could be used as a comparison group [in outbreaks where there is insufficient capacity to respond to all cases].  Additional points of comparison may include the delay between case presentation and CATI implementation:  e.g. CATI implemented within 24h, in 2 days, in 3 days, in 4 days, etc.

The proposed research is an observational study of cholera interventions implemented by NGOs in response to cholera outbreaks (i.e. no intervention is proposed).  The study will include the following components:

• Observation of CATI delivery
• Key informant interviews: 1) NGO staff members delivering the CATI intervention to characterize perceived strengths and weakness of the intervention, household selection, logistical processes and implementation challenges; 2) Humanitarian response managers from the partner NGO, UN agencies, national governments and other organizations engaged in the cholera response to ascertain perceptions of the response, coordination and CATI delivery and implementation
• Cholera treatment facility line lists: Information from cholera line lists is used to plan CATI interventions, where each individual on the line list (i.e. a cholera case) receives a household visit from a CATI team. The JHSPH study team will request line lists from health facilities [which may be augmented by the study team] to evaluate coverage of CATI interventions.
• Follow up survey: The household follow up survey will be conducted approximately 14 days after the presentation of the suspected cholera case at a cholera treatment facility. The exact sampling approach will depend on the density of housing in the community and the CATI implementation strategy. Household surveys will enquire about receipt of the CATI intervention, household composition, incidence of diarrhea and diarrhea care seeking among household members in the period since CATI implementation (or case presentation if there was no CATI), knowledge and practices of hygiene behaviors and observation of free chlorine level (FCR) in stored drinking water.

Cholera continues to pose a major global public health threat and is a marker of inequality and poverty as it reflects the lack of access to basic water and sanitation infrastructures. The risk of the spread of cholera is particularly high in humanitarian settings and fragile contexts.

Cholera transmission risk is higher for cholera case household members and nearby households. Mass interventions to contain cholera outbreaks are not resource efficient.  Preventive interventions targeting cholera case-households and neighbors have been found effective in past outbreaks. These interventions are often referred to as case area targeted interventions (CATIs). CATIs predominantly include water, sanitation, and hygiene (WASH) activities but can also include epidemiological surveillance, and health (clinical) services, primarily oral vaccination and antibiotic chemoprophylaxis.

There are limited studies on the best practices and effectiveness of CATIs in humanitarian settings.   This study aims to identify those factors that support optimal delivery and interventions of these CATIs for cholera reduction in humanitarian settings and fragile states.  The study design centers around observing the CATI activities of partner organizations as they respond to a cholera outbreaks in known humanitarian or fragile settings.

There is limited evidence studying the mechanisms, composition, interventions, timing, effectiveness of CATIs in humanitarian settings. This proposed research for CATI in humanitarian settings will focus on variations in CATI implementation and timing, monitoring and evaluation, and coordination and integration with the aim of expanding available evidence that can be used to inform the development of operational guidance for CATI interventions in cholera response.

Burden

Diarrhea is the second most leading causes of deaths in children under 5 years of age globally, with an estimated 800,000 deaths annually. On an average, a child in Bangladesh suffers from 3-5 episodes of diarrhea per year. Children suffering from frequent and recurrent diarrhea suffer from food wasting, and the ultimate result is severe malnutrition and growth stunting. Once stunted, its effects typically become permanent, and children may never regain the height lost as a result of stunting. Previous studies have identified lack of caregiver hand washing with soap and treatment of household drinking water, poor water storage practices, and lack of caregivers knowledge about diarrhea prevention as important risk factors for diarrheal disease in paediatric populations. Water, sanitation, and hygiene (WASH) interventions promoting household chlorination of drinking water and hand washing with soap have the potential to reduce diarrheal disease incidence in children less than five years of age an estimated 30 to 40%. Furthermore, Community Based WASH interventions are expensive and often difficult to implement in an urban context in low resource settings. Our team has recently developed a Hospital Based WASH intervention which is entitled CHoBI7 (Cholera Hospital-Based Intervention for 7 days). The CHoBI7 intervention was initially designed to reduce cholera infection among family members of hospitalized cholera cases during the one week high risk period after the case presents at the hospital. This low cost Hospital Based WASH intervention resulted in a significant reduction in the incidence of symptomatic cholera, and a 47% percent reduction in the incidence of cholera infection among household members of hospitalized cholera cases. Furthermore, we observed sustained uptake of the promoted hand washing with soap and water treatment behaviours among intervention households 6 to 12 months after the intervention was delivered.

Knowledge gap

Despite successful intervention in our just concluded hospital based study we still do not understand if all the procedures involved can be integrated into the services provided for hospitalized diarrhea patients at health facilities of Bangladesh and the promoted hand washing with soap and water and water treatment behaviour would be a long lasting practice in the community.

Hypothesis

Based on what we have learned from our just concluded Hospital Based WASH intervention study entitled “Cholera Hospital-Based Intervention for 7 day” (CHoBI7), we hypothesize that developing and evaluating scalable approaches might help this innovative and low cost CHoBI7 intervention to be integrated into the services provided for hospitalized diarrhea patients at the health facilities of Bangladesh. We also hypothesize that evaluating the ability of the CHoBI7 intervention, which could lead to a sustained uptake of the promoted hand washing with soap and water treatment behaviours might reduce the burden of diarrheal diseases over time.

Objective 1

To Develop scalable approaches to integrate the CHoBI7 intervention in urban health facilities through formative research and engagement of key stakeholders.

Objective 3

Investigate the effectiveness of the developed scalable approaches for program delivery of CHoBI7 in terms of: (1) reductions in diarrheal disease prevalence during the 12 months period after the index diarrhea patient in the health facility receives the intervention; and (2) sustained high uptake of hand washing with soap and water treatment practices at 1 week, 1 month, 3 months, 6 months, 9 months, and 12 months post intervention.

Objective 3

Calculate the cost effectiveness of upscaling the CHoBI7 intervention in terms of cost per Disability Adjusted Life Year (DALY) averted and case and death averted for cholera and moderate to severe diarrhea episodes.

Objective 4

Investigate the feasibility of implementing the proposed low cost approaches for program delivery of CHoBI7 as part of the National Emerging and Re-emerging Diseases Program through identification of potential barriers to successful implementation, and engagement with key government stakeholders.

Objective 5

Disseminate the findings of CHoBI7 intervention implementation and evaluation activities and our recent CHoBI7 efficacy trial at the household, health facility, and national and local government levels through the creation of a website, policy planning workshops with government leaders, development of policy briefs, publishing finding in peer reviewed scientific journals, and presentations at international scientific meetings.

Methods

Diarrheal patients admitted to icddr,b Dhaka Hospital or Mugda General Hospital would be screened and enrolled according to inclusion criteria. Diarrhea patients will be recruited after they received ORS or intravenous rehydration. Household members would be recruited those accompanying the diarrhea patient to the hospital and reside in the home of the enrolled diarrhea patient. Written informed consent would be taken from the patients and their HHC before enrolment. A baseline questionnaire will then be administered to each enrolled diarrhea patient and enrolled accompanying household members (adult and child), stool sample will be collected, and anthropometric measurements will be performed. After the baseline questionnaire is administered to the index diarrhea patient and accompanying household members, they will then be randomized to their respective study arm (Control Arm/Health Facility Based Dissemination Arm / Health Facility Based Dissemination and Home Visits Arm) based on the day they arrive to the hospital. The first arm will receive the standard message given to hospitalized diarrhea patients in health facilities in Bangladesh on the use of oral rehydration solution (ORS) (Control Arm). The second arm will receive the standard message plus Health Facility Based Dissemination of CHoBI 7 (Health Facility Based Dissemination-Only Arm) and bi-weekly (every two weeks) follow-up phone calls or text messaging. The third arm will receive the standard message plus Health Facility Based Dissemination of CHoBI 7 plus two home visits (Health Facility Based Dissemination and Home Visits Arm) and biweekly follow-up phone calls or text messaging. These Randomized Control Trial activities would be 12 Months in duration in each enrolled household. Stool samples would be collected from the HHC on different time period, household drinking water would also be collected and direct observation (5 hr long) would also be performed.

Outcome measures/variables

Develop low cost effective strategies for delivering CHoBI7 in urban health facilities which can be integrated into the National Emerging and Re-emerging Diseases Program.

Cholera remains a persistent global health problem that can be controlled by appropriate water and sanitation and oral cholera vaccination. Our project aims to support the geographic targeting of cholera control interventions with four key objectives:

• maintenance of a global database of cholera surveillance data which can be used by countries and GTFCC stakeholders to access centralized data sources and understand the country and regional cholera epidemiology;
• development of a statistical mapping pipeline, which produces high resolution global maps of cholera burden;
• provision of technical epidemiological and modeling support to countries and NGOs in cholera control;
• participation in GTFCC working groups to develop evidence-driven guidance related to cholera surveillance and elimination, targeting OCV campaigns, and identifying cholera burden hotspots.

This project supports efforts to map the global burden of cholera through the maintenance of a global database of cholera incidence and mortality and the development of statistical modeling methods to produce high resolution maps of cholera burden. The study team is working to develop a user-friendly web interface to the cholera database to support country and GTFCC stakeholder access to centralized data sources, and the global burden maps serve as the foundation for many planning and intervention targeting activities such as strategic demand forecasts for OCV and hotspot identification.

Effective targeting of OCV campaigns and WASH interventions for cholera control requires knowledge of the highest burden areas worldwide. The global cholera database and mapping efforts resulting from this project support countries and GTFCC stakeholders in characterizing cholera epidemiology and targeting their cholera control efforts.

Cholera outbreaks caused by Vibrio cholerae are endemic in Kenya and the East Africa region accounting for nearly 10% of all cases reported from sub-Saharan Africa and the case-fatality rates remain above 2.5%, which is unacceptably high. Cholera is spread through consumption of fecally contaminated water or food. Investigating the relationship between cholera occurrence in terms of dominant hotspots and various environmental and human factors associated with the hotspots is important for managing cases and preventing future outbreaks. Whereas WASH interventions have been recommended by various studies as a control strategy for Cholera, the critical intervention pathways that have the most significant public health impact are not known.

The current research aims to study hotspots identified from previous outbreaks and from ongoing outbreaks in Kenya using drone technology to map areas for immediate sampling, exposure risks and most critical transmission pathways surveillance. Using SANIPATH techniques in identifying critical environmental and human factors associated with hotspots, we are deploying novel techniques including Whole Genome Sequencing (WGS) and bioinformatics partnering with relevant governmental agencies that will deploy our rapid detection and tracking techniques of these hotspots in a bid to innovatively establish preventive measures for infection emergence and spread. Data analysis will be done using basic descriptive statistics (percentages, means, standard deviations, modes) and the latest version of SAS software suite (SAS Institute Inc.) Ethical approval has been sought from Scientific Ethics Review Unit (SERU) in Kenya Medical Research Institute

Cholera is a disease caused and spread by germs that you get by eating or drinking contaminated food or water.

We are investigating areas in Mukuru slums that may harbor high concentration of these germs, e.g. sewers, open drainages, homesteads and water supply chains etc. We are using satellite imaging technologies to map areas of high risk for cholera, then get samples to investigate presence of these germs in the lab at KEMRI. This will help manage those with the disease as well as prevent future occurrence of the disease.

Work with local governments and communities to make evidence-based intervention decisions and co-design and implement WASH and/or OCV campaigns as appropriate for the local context; and

Build capacity in regional academic institutions and health ministries for applied public health research to strengthen cholera prevention and control programs.

Bangladesh remains endemic for cholera, which experiences biannual outbreaks with additional epidemics seen during times of floods, cyclones or any natural disaster [1, 2]. It affects all age groups with the majority of fatal cases occurring in children [3-6]. Therefore, immunization against cholera remains an important public health component in the prevention and control of the disease [6]. A problem that may be a stumbling block in the path is that the oral cholera vaccine (OCV) is in short supply globally and only about 2-3 million doses are produced each year. In Bangladesh alone we anticipate that 170 million doses will be needed in a 5 year time frame if only high risk populations are targeted. Globally for the rest of Asia and Africa as well as for Haiti, millions of doses of vaccine is needed for control of endemic and epidemic cholera. The global demand for the vaccine is therefore high and the good news is that, there is now provision for local production of over 50 million doses in Bangladesh. With this prospect in view, planning for prevention of cholera by use of OCV, it may be possible to decrease the burden of the disease in Bangladesh.

Knowledge gap

More evidence is needed to address uncertainties around the cholera disease burden, as well as the impact, feasibility, and cost-effectiveness of various vaccination strategies against cholera, to add to the existing knowledge base. A special need for acquiring field evidence of these vaccine attributes in settings with endemic cholera, which account for a very large fraction of the global cholera disease burden, is also recognized [7].

There is a great need for identify financing mechanisms for introduction of vaccination against cholera. All these efforts will hopefully decrease the burden due to cholera which has both health and financial burden on the country. Studies have shown that the cost of hospitalization and illness to the patient and the family is around ten times higher than the cost of vaccine [8, 9].

A countrywide surveillance is needed which will help to identify the disease burden in the country, so as to plan appropriate treatment and preventive measures.

Relevance

Bangladesh needs to plan strategies for introduction of a locally produced oral cholera vaccine in Bangladesh. Thus clear information from national stakeholders on the cholera investment strategy for Bangladesh is needed based on which future plans can be made. In addition, information i s needed on the strategies for vaccination and areas which need to come under coverage. With the availability of a locally produced vaccine in Bangladesh, financing plans and funders will be needed to materialize the immunization plans for people with OCV.

Objectives

The objectives of the proposal are as follows:

• Build a plan (including surveillance of high risk areas) and identify strategies for the introduction of OCV in Bangladesh by developing the cholera investment case based on the present scenario.
• Identify a financing plan for the introduction of the locally produced vaccine in Bangladesh in the short term.

Methods

We will update the current cholera investment case study on cholera vaccination for Bangladesh which was previously prepared by International Vaccine Institute (IVI) in 2009. This will provide a useful evidence based guide to policy makers in Bangladesh in making decisions about the use of OCV as well as to the global health community in considering technical and financial support for cholera vaccine introduction. The information on where and whom to vaccinate will also be obtained to accumulate information by working on nationwide cholera surveillance from all over Bangladesh. Surveillance will be conducted in different government and non government hospitals and medical colleges in sites already known to have diarrheal disease burden.

Bangladesh remains endemic for cholera, which experiences biannual outbreaks with additional epidemics seen during times of floods, cyclones or any natural disaster. It affects all age groups with the majority of fatal cases occurring in children. Therefore, immunization against cholera remains an important public health component in the prevention and control of the disease. In Bangladesh alone we anticipate that 170 million doses will be needed in a 5 year time frame if only high risk populations are targeted. The global demand for the vaccine is high and the good news is that, there is now provision for local production of over 50 million doses in Bangladesh. With this prospect in view, planning for prevention of cholera by use of OCV, it may be possible to decrease the burden of the disease in Bangladesh.

Bangladesh needs to plan strategies for introduction of a locally produced oral cholera vaccine in Bangladesh. Thus clear information from national stakeholders on the cholera investment strategy for Bangladesh is needed based on which future plans can be made. In addition, information is needed on the strategies for vaccination and areas which need to come under coverage. With the availability of a locally produced vaccine in Bangladesh, financing plans and funders will be needed to materialize the immunization plans for people with OCV.

Therefore, the objectives of the current study are as follows:

• Build a plan (including surveillance of high risk areas) and identify strategies for the introduction of OCV in Bangladesh by developing the cholera investment case based on the present scenario.
• Identify a financing plan for the introduction of the locally produced vaccine in Bangladesh in the short term.

Different data will be used to develop and recommend up to 3 optimal strategies for introduction of Oral Cholera vaccine (OCV) with associated vaccine demand, budget and health impact. For this recommendation we will communicate with different level of Government of Bangladesh (GoB) and other internal and external stakeholders with our preferred feasible strategy for introduction of vaccine.

The objective of this study is to test the safety and immunogenicity of HaitiV – a novel live-attenuated cholera vaccine. Pre-clinical data suggest that HaitiV can provide rapid (within a day), single-dose, long-lived protection from cholera. The key goals of the study are 1) creation of a GMP lot of HaitiV for use in human studies and development and approval of an investigator sponsored Investigational New Drug application to conduct a first-inhuman Phase I trial of HaitiV; 2) determination of the maximum tolerated dose and safety profile of HaitiV; and 3) identification of the most immunogenic HaitiV dose. These studies will provide the pivotal data required for future development of this vaccine, including human challenge studies and field trials in cholera endemic regions.

Cholera remains an important challenge to global public health. Killed cholera vaccines have shown promise as tools for cholera control, but these vaccines have limitations, including minimal activity in children and delay in eliciting protection. In contrast to killed cholera vaccines, HaitiV, our novel highly engineered live-attenuated cholera vaccine, leverages the unusual capacity of the cholera pathogen to replicate in and colonize the human small intestine. Our pre-clinical studies in animal models have shown that administration of this live vaccine confers rapid protection to animals prior to engendering protective immune responses to a range of Vibrio cholerae antigens. Such rapid protection could have major impact on reactive cholera vaccine campaigns, curtailing epidemic spread. The vaccine also has great promise to provide single-dose long-lived protection in children as well as adults. Thus, completion of the proposed first-in-human trial of HaitiV could propel the development of a transformative new tool for global cholera control.

This study will yield critical data about a new agent for cholera control.

In this project, we are working to complete a systematic review (stratifying cholera WASH evidence by context), and to convene a working group to inform WASH components of National Cholera Control Plan development.

The project aims to inform National Cholera Control Plan Development.

This project will compare the vibriocidal titers in subjects who receive a second dose of oral cholera vaccine (Shanchol), two weeks, 6 months or 11.5 months after the first dose. The primary outcome is the geometric mean vibriocidal titer two weeks after the second dose. Additional follow-up serum samples will determine the persistence of the vibriocidal titers.

This will provide guidance when the second dose of OCV is delayed.

Prospective cohort study

Household contacts of cholera cases are at a greater risk of Vibrio cholerae infection than the general population. There is currently no agreed standard of care for household contacts, despite their high risk of infection, in cholera response strategies such as case-area targeted interventions (CATI). In 2018, hygiene kit distribution and health promotion was recommended by Médecins Sans Frontières for admitted patients and accompanying household members upon admission to the health care facilities, as part of an overall response to a cholera outbreak in the Democratic Republic of Congo (DRC).

To investigate the effectiveness of the intervention and risk factors for cholera infection, we conducted a prospective cohort study and followed household contacts of cholera patients for 7-days after the patient sought care. Clinical surveillance was based on reported symptoms of cholera and diarrhoea, and environmental surveillance was conducted through the collection of food and water samples. All analyses were stratified by the receipt of the hygiene kit and compliance of use.

Multivariate analysis suggested evidence of a dose-response relationship with increased kit use associated with decreased risk of suspected cholera: household contacts in the high kit-use group had a 66% lower incidence of suspected cholera, the mid-use group had a 53% lower incidence and low-use group had 22% lower incidence, compared to household contacts without a kit. Drinking water contamination was significantly reduced among households in receipt of a kit. There was no significant effect on self-reported diarrhoea or food contamination.

The integration of a hygiene kit intervention to case-households, may be effective in reducing cholera transmission among household contacts and environmental contamination within the household. Further work is required to evaluate other proactive localised distribution among patients and case-households or to households surrounding those case-households to optimise future cholera response programmes in emergency contexts.

Process evaluation

Cholera remains a leading cause of infectious disease outbreaks globally, and a major public health threat in complex emergencies. Hygiene kits distributed to cholera case-households have previously shown an effect in reducing cholera incidence and are recommended by Médecins Sans Frontières (MSF) for distribution to admitted patients and accompanying household members upon admission to health care facilities (HCFs).

This process evaluation documented the implementation, participant response and context of hygiene kit distribution by MSF during a 2018 cholera outbreak in Kasaï-Oriental, Democratic Republic of Congo (DRC). The study population comprised key informant interviews with seven MSF staff, 17 staff from other organisations and a random sample of 27 hygiene kit recipients. Structured observations were conducted of hygiene kit demonstrations and health promotion, and programme reports were analysed to triangulate data.

Between Week (W) 28-48 of the 2018 cholera outbreak in Kasaï-Oriental, there were 667 suspected cholera cases with a 5% case fatality rate (CFR). Across seven HCFs supported by MSF, 196 patients were admitted with suspected cholera between W43-W47 and hygiene kit were provided to patients upon admission and health promotion at the HCF was conducted to accompanying household contacts 5-6 times per day. Distribution of hygiene kits was limited and only 52% of admitted suspected cholera cases received a hygiene kit. The delay of the overall response, delayed supply and insufficient quantities of hygiene kits available limited the coverage and utility of the hygiene kits, and may have diminished the effectiveness of the intervention. The integration of a WASH intervention for cholera control at the point of patient admission is a growing trend and promising intervention for case-targeted cholera responses.

These two complimentary studies in the Democratic Republic of Congo (DRC) evaluated the effectiveness of hygiene kit distribution to admitted cholera patients and their households at health care facilities, and the implementation and receipt of the overall cholera response.

The study followed household contacts of cholera patients for 7-days after the cholera patient sought care and received the intervention, collected data on reported symptoms of cholera and diarrhoea, and collected environmental samples of food and water to test for contamination. One of the studies examined the effectiveness of the hygiene kit distribution on the incidence of cholera and diarrhoeal disease and on food and water contamination. The other study collected quantitative data on intervention reach and distribution and qualitative data on receipt of the intervention by the study population. This study examined the challenges and successes to intervention delivery and receipt by the population.

Integration of the hygiene kits at the point of admission of suspected cases is possible, and both an effective and promising intervention for case-targeted cholera control. There was a 66% lower incidence of cholera among the population who received and frequently used the hygiene kit. There was positive response, use and adherence to hygiene kits by households. However, there were barriers to the timely supply, inadequate availability and consequent limited coverage of the hygiene kits. Further work is required to identify ways to improve implementation and delivery of this promising intervention.

The research may help responding agencies decide what types of intervention to include in their emergency cholera response programmes.

This collaborative project between Johns Hopkins University; University of Maryland; University of Florida, Ministry of Health, United Republic of Tanzania, M.A. Sante, Yaoundé, Cameroon, and the Nigeria Centre for Disease Control will describe the molecular epidemiology of cholera in Tanzania and Cameroon to determine the degree to which cholera in these countries originates locally or is introduced from outside and is
transmitted widely.

This study is attempting to characterize the epidemiology in these cholera endemic countries in Africa.

This study attempts to provide a more complete understanding of cholera epidemiology in Africa.

In 2018, the World Health Organization (WHO) Global Task Force on Cholera Control (GTFCC) declared an objective to reduce global cholera mortality by 90% and eliminate cholera in 20 priority countries by 2030. Despite years of cholera research, however, the burden and geographic variability of cholera across India is poorly understood due to underreporting, limited laboratory capacity, inconsistent case definitions, and apprehensions of negative impacts on travel, trade and commerce.

To address the issue, we propose to estimate incidence of V. cholerae O1 infections across 5 regions of India using seroepidemiological methods along with triangulation of data on cholera from available multiple sources (a) published literature and grey literature archives (b) program data like Integrated Disease Surveillance Program (IDSP), Field Epidemiology Training Program (FETP) reports, National Health Profile (NHP) maintained by Central Bureau of Health Intelligence (CBHI) and data on Swacch Bharat initiated sanitation drive (c) information from annual reports and (d) serological testing (vibriocidal) for cholera markers on stored samples collected during Dengue National serosurvey. Results from this study will generate robust estimates on risk-prone areas vulnerable to cholera outbreaks in India. Additionally, this will inform the selection of sentinel surveillance sites for the monitoring of culture-positive cholera cases. Given the genetic similarity of V. cholerae strains from other geographical regions, this study will have a profound impact on national and global levels.

This study will identify incidence of cholera in 5 regions of India through measuring the antibody levels in serum. A hotspot mapping of different regions and states in India will be done for Cholera by combining estimates of antibody proportion and magnitude of reported cholera in different types of published literature.

Results from this study will generate robust estimates on risk-prone areas vulnerable to cholera outbreaks in India. Additionally, this will inform the selection of sentinel surveillance sites for the monitoring of culture-positive cholera cases. Given the genetic similarity of V. cholerae strains from other geographical regions, this study will have a profound impact on national and global levels

Background

Cholera is endemic in Bangladesh. The current method for testing samples requires three days and notification of results can take even longer. We hope to evaluate a device that could lessen that time required.

Knowledge gap

We hypothesize that there will be 90% accuracy of the device compared to the gold standard in terms of correct identification and we wish to test that.

Relevance

In order to implement the device to identify dangerous water samples, the device must first be proven to be accurate at a satisfactory level. Therefore the hypothesis will be tested and conclusions drawn to determine the accuracy.

Hypothesis

The accuracy of the device will be 90% compared to the gold standard.

Objectives

Determine sensitivity and specificity of device in field. Discover and address any complications not found in lab that arise in field use. Draw conclusions about the validity of device

Methods

The OmniVis diagnosis process begins with a primer chip. The chip is a one-time-use disposable test kit that contains a freeze-dried biological assay specific for the ctxA gene of Vibrio cholerae. The assay includes six primers for the LAMP technique: F3, B3, FIP, BIP, LF, and LB. The shelf life of the chip with the freeze-dried primer is unknown; it has been proven viable for four months without the need for temperature or humidity regulation when stored with a desiccant. The transportation of the necessary equipment including these primers will be handled by OmniVis via shipment to Bangladesh or direct delivery by OmniVis staff. The chip has a reservoir that will fill when the chip is dipped into the water. The chip will be dipped into the water where it collects between 15 and 25 gl of water. The chip will be dried with a paper towel after which the app analysis will start. All waste products will be transported in biohazard bags and autoclaved before disposal.

Once the water sample is in the chip and the chip is dried, the app is started. The interface shows the user where to insert the chip into the heater. Once the chip is in, the heater works for thirty minutes while a flame moves up the screen to show the progress. During this phase, the LAMP technique is carried out in the housing. Samples containing the ctxA gene will undergo DNA polymerization resulting in the amplification of the strands. This process causes the toxic sample to have a higher viscosity from the saturation of DNA. Samples without the targeted gene will not undergo a significant change in viscosity as no DNA will amplify. The viscosity of the strands of non-amplified samples are significantly different from the polymerized strands — providing the basis for the in-app analytical algorithms measuring the Brownian motion. Once the heating portion is complete, the app prompts for the removal of the chip and the insertion into the camera slot where the microscope lens is used to analyze the sample. There the Brownian motion of the sample is measured via in-app algorithms using the iPhone camera and microscope lens in the apparatus. This analysis can take up to a few minutes after which the app displays the result showing either a cholera-contaminated sample or not. Our application will show us the diffusion coefficient measured by the camera in terms of m/s^2 so that analysis can be carried out on the data. GPS location will be recorded at the time of completion and the diffusion coefficient and location will be stored on the phone. The phone will transfer the data to a cloud server where the data can be accessed.

The previously established conventional sample enrichment technique or “gold standard” of cholera detection will be run in addition to the cellular diagnostic device. The gold standard for cholera detection is a time-intensive lab test to identify the presence of cholera in a sample. Alam’s 2015 study outlined the laboratory test. Water samples of 500 ml were collected from a site and incubated in 2X alk.

Cholera is endemic in Bangladesh. Community water sources contaminated with the bacteria place communities at risk of cholera infection and death.The current method for testing samples requires three days and notification of results can take even longer. We hope to evaluate a device that could lessen that time required.

The rationale behind studying the OmniVis device is the potential to reduce this test-time and reporting to communities. We hypothesize that it will take approximately 30 minutes to complete a water test and determine if the sample is contaminated with cholera. In order to implement the device to identify dangerous water samples contaminated with the cholera germs, the device must first be proven to be accurate at a satisfactory level. The objective of the project is to determine sensitivity and specificity of device in field; Discover and address any complications not found in lab that arise in field use; Draw conclusions about the validity of device.

The research project is designed to compare capability of the Omnivis Technologies rapid cholera detection device and conventional cholera detection method from water by comparing water sample analysis data of both. Based on the comparison, conclusions will be drawn to determine the accuracy.

This research project will generate evidence/data which will be used to improve the accuracy and efficacy of the OmniVis Technologies rapid cholera detection device. Potential use of the OmniVis device to detect dangerous water sample (contaminated with Vibrio cholerae) instantly from water body will lead to proper management, decision-making and control of the cholera epidemic at the initial stage by the government in future.

The icddr,b and IVI have collaborated on multiple research projects addressing the epidemiology of vaccines for cholera. This is in addition to each institution`s individual work on cholera and typhoid fever. To date, papers with significant global health impact been published on these studies, yet, the papers are relatively few in number in relation to the size and richness of the data available from the studies. Computerized datasets from these projects have been cleaned, archived, and documented, and are available for analyses. These datasets thus constitute an important resource for further analyses and publications addressing critical issues related to control of cholera and typhoid by both vaccine and non-vaccine (WASH) measures.

The purpose of this proposal is to:

• To answer scientific questions and publish manuscripts in the international scientific journals using existing computerized and curetted datasets for analyses of the epidemiology of cholera and typhoid, as well as the effectiveness of vaccine and WASH control measures for the control of these disease.
• To form a working group consisting of both senior and junior scientists from each institution, together with selected experts from outside the institutions, to exploit the untapped existing computerized and curetted datasets.

We will achieve the objectives by forming working groups consisting of senior and junior scientists together with a steering committee composed of selected experts from outside the institutions, to analyze the existing datasets and to submit manuscripts based on these analyses for publication in the international scientific literature. We will also present the findings at international scientific meetings and forums. In addition, after completion of the proposal in the 2 year period targeted for the study, the results will be shared with Institute for Health Metrics and Evaluation (IHME), as necessary, to strengthen the cholera and typhoid fever disease burden data.

The vaccine effectiveness will be measured by comparing the ratio of odds of vaccination in the cholera positive patients and odds of vaccination in the cholera negative patients.

Burden

Cholera, a scourge, remains one of the major causes of morbidity and mortality world-wide. The global burden of cholera is estimated to be about 3-5 million cases each year with an estimated deaths of 100,000 to 120,000, majority occurring in the developing countries of Asia and Africa. The causative agent of cholera, Vibrio cholerae, is a genetically versatile bacterial species for which more than 200 serogroups have been identified and for which significant lateral transfer of genes has been demonstrated. Pandemic cholera is generally caused by toxigenic strains of V. cholerae serogroups O1 and O139. V. cholerae O1 has been divided into two biotypes, classical (CL) and El Tor (ET), differing primarily in phenotypic traits and distinct signature genome sequences. Of seven cholera pandemics recorded since 1817, the sixth and presumably the earlier pandemics have been caused by CL biotype, which was replaced in the 1980s by ET biotype initiating the currently ongoing seventh cholera pandemic. The Ganges Delta of the Bay of Bengal has been the traditional home where cholera is endemic for centuries. Although V. cholerae has been an integral part of the bacterial community sharing niche in the estuarine ecosystem of Bay of Bengal, little is known about the aquatic life cycle of V. cholerae, particularly how a pandemic pathogen emerges from the naturally occurring benign population residing this historic ecosystem.

Knowledge gap

Despite intensive research efforts have been made to understand the epidemiology and ecology of V. cholerae, of its physiology and mode of infection in laboratory and in animal model systems, our knowledge is very limited and we still do not fully understand the molecular basis of pathogenicity of the bacterium and why cholera is a seasonal disease, and how a pandemic pathogen takes shape from among the diverse population occurring in the historical niche of the Bay of Bengal estuaries and spread.

Hypothesis

Since cholera has been endemic in the coastal villages of Bay of Bengal (Bangladesh), we hypothesize that the toxigenic V. cholerae responsible for the century-old Asiatic cholera is an integral part of the estuarine vibrio community that are influenced by the local climate, and includes ecological types (ecotypes) unique for this ecosystem.

Objectives

Our primary aim is to:

• Study the population structure (ecotypes) of V. cholerae occurring in the estuarine aquatic ecosystems of the Bay of Bengal

Our secondary aim is to:

• Understand how the naturally occurring toxigenic V. cholerae population (ecotypes) responds to the seasonal change in the regional climate to initiate seasonal cholera.
• Determine virulence potential of epidemiologically significant V. cholerae and related enteric pathogens of environmental and clinical origin by molecular and animal model assays.
• Decipher the transmission of epidemiologically significant V. cholerae regionally, and beyond. For this, we will compare the population structure, virulence and related molecular traits of V. cholerae occurring in the Bay of Bengal estuaries with that of the US east coast (Chesapeake Bay and Falmouth MA), for example.
• Determine antimicrobial resistance (AMR) of environmental and clinical strains of V. cholerae and related enteric pathogens.

Methodologies

V. cholerae (n=2100) would be isolated by culture method from water samples collected monthly from 8 selected Bay of Bengal estuarine pond and river sites located at the cholera-endemic coastal villages of Potuakhali, Bangladesh. Water samples would be collected aseptically in sterile Nalgene bottle and transferred to icddr,b Dhaka hospital for microbiological analysis. “

We designed this study to monitor and characterizing naturally occurring V. cholerae initiating seasonal (endemic) cholerea in Bangladesh.

Genetic tracking of Vibrio cholerae in its natural aquatic environments to provide insights that will aid prediction and preventive measures against upcoming cholera in Bangladesh

Cholera, an acute watery diarrheal disease, caused by toxigenic strains of the bacterium Vibrio cholerae O1 and O139, causes an estimated over 2.9 million cases and over 95,000 deaths annually in cholera endemic countries alone and frequent epidemics in other settings with poor water and sanitation infrastructure. Global estimates range from 1.4-4.8 million cases and 28,000 – 142,000 deaths every year 1. The disease is characterized by acute onset watery diarrhea leading to rapid dehydration and death, if not promptly treated.

Recently a conflict has been conducted in the Rakhine province of Myanmar. During this conflict over 500,000 Rohingya refugees (URMN) have recently been displaced and entered into Cox’s Bazar district in Bangladesh. Among newly arrived displaced people, 60% are women and children living in conditions where public health facilities are lacking. These people are probably not primed and exposed to cholera and the prevailing conditions are high risk for cholera. In the recent past, e.g in Yemen, South Sudan, Haiti and other countries, lack of WaSH and public health facilities have led to large epidemics with high numbers of cholera cases and death. Considering this risk assessment international co-ordination group (ICG) of WHO allocate 900,000 oral cholera vaccines from WHO stockpile to deploy among the refugees.

The prevention of cholera has become a high priority in the global community. Immunization with OCV is the most effective means of preventing cholera infection and its consequence. The World Health Organization (WHO) has warned of a growing risk of a cholera epidemic at makeshift refugee camps in Bangladesh where hundreds of thousands of Myanmarese Rohingya Muslim refugees are sheltered in dire conditions. The camps did not have safe drinking water and lacked sufficient hygiene; filthy water and feces flowed openly through the camps. Risk of waterborne diseases is high, especially there is very high risk of cholera in these camp. Interventions like vaccination are being scaled-up as the situation remains critical and challenging.

The study of ShanChol OCV on Unregistered Myanmar Nationals (URMN) in children and adults will be able to give information regarding the safety and immunogenicity of the vaccine in URMN subjects. This information will be important for proceeding with the cholera vaccination in the refugee population of same socioeconomic structure in future.

Hypothesis

Oral Cholera vaccine (OCV) is immunogenic in different age groups of Unregistered Myanmar Nationals (URMN).

Objectives

The objective of this study is to evaluate the immunogenicity of OCV among healthy Unregistered Myanmar Nationals (URMN) in Bangladesh.

Methods

This will be cross sectional study on a total of 226 healthy Unregistered Myanmar Nationals (URMN). There will be three age cohort which will consist of 80 participants for age 1-5 yrs, 63 participants for age 6-17 yrs and 83 for age 18 yrs and above, with a total of 226 participants. Blood will be taken before and after OCV administration.

Outcome measures/variables

To evaluate the immunogenicity of OCV among Unregisterd Myanmar Nationals (URMN).
The immunogenicity component will be measured by assessing the sero-conversion rate of vibriocidal antibodies after vaccination with OCV to Vibrio cholerae O1.

Cholera, an acute watery diarrheal disease, caused by toxigenic strains of the bacterium Vibrio cholerae O1 and O139, causes an estimated over 2.9 million cases and over 95,000 deaths annually in cholera endemic countries alone and frequent epidemics in other settings with poor water and sanitation infrastructure. The disease is characterized by acute onset watery diarrhea leading to rapid dehydration and death, if not promptly treated.

Among newly arrived displaced people, 60% are women and children living in conditions where public health facilities are lacking. These people are probably not primed and exposed to cholera and the prevailing conditions are high risk for cholera. In the recent past, e.g in Yemen, South Sudan, Haiti and other countries, lack of WaSH and public health facilities have led to large epidemics with high numbers of cholera cases and death.

The study of ShanChol OCV on FDMN in children and adults will be able to give information regarding the safety and immunogenicity of the vaccine in URMN subjects. This information will be important for proceeding with the cholera vaccination in the refugee population of same socioeconomic structure in future.

Therefore, the objective of this study is to evaluate the immunogenicity of OCV among healthy Forcibly Displaced Myanmar Nationals (FDMN) in Bangladesh.

By evaluating the immune responses of OCV among Forcibly Displaced Myanmar Nationals (FDMN), we can compare the immune responses between Bangladeshi population and FDMN. We can also assess the sero-conversion rate of vibriocidal antibodies after vaccination with OCV to Vibrio cholerae O1.

The cholera burden is concentrated in endemic settings with inadequate water, sanitation and hygiene access. There is limited rigorous evidence for the impact of improved water supply on endemic cholera transmission in low-income urban settings. We propose a pragmatic health impact evaluation of a large-scale water supply intervention in Uvira (South Kivu, Democratic Republic of the Congo), a cholera transmission hotspot. A stepped-wedge cluster randomised trial (SW-CRT) was designed to evaluate the impact of a large-scale drinking water supply intervention on cholera incidence among the 280,000 inhabitants of Uvira. The city was divided into 16 clusters, where new community and household taps will be installed following a randomised sequence over a transition period of up to 8 weeks in each cluster. The primary trial outcomes are the monthly incidence of “confirmed” cholera cases (patients testing positive by rapid detection kit) and of “suspected” cholera cases (patients admitted to the cholera treatment centre). Concurrent process and economic evaluations will provide further information on the context, costs and efficiency of the intervention. Overall, this research has the potential to provide robust evidence to support more effective cholera prevention in challenging, high-burden settings. This trial is registered on clinicaltrials.gov (NCT02928341).

The Uvira research provides a unique opportunity to inform future investments in water supply infrastructure improvements and cholera prevention strategies in endemic transmission hotspots.

Every year cholera affects 1.3 to 4.0 million people worldwide with a particularly high presence in Africa. Based on recent studies, effective targeting interventions in hotspots could eliminate up to 50% of cases in Sub-Saharan Africa (1). Those interventions include Water, Sanitation and Hygiene (WASH) programs whose influence on cholera control, up to present, has been poorly quantified. Considering the limited number of studies on Community-Led Total Sanitation (CLTS) and water coverages related to cholera control, the aim of our work is to determine whether these interventions in cholera hotspots (geographic areas vulnerable to disease transmission) have significant impact on cholera transmission.

In this study, we consider data collected on 125 villages of the Madarounfa district (Niger) during the 2018 cholera outbreak. Using a hurdle model, our findings show that full access to improved sanitation significantly decreases the likelihood of cholera by 91% (P<0.0001) compared to villages no access to sanitation at all. Considering only the villages affected by cholera in the studied area, cholera cases decrease by a factor of 4.3 in those villages where there is partial access to at least quality water sources, while full access to improved water sources decrease the cholera cases by a factor of 6.3 when compared to villages without access to water (P<0.001).

In addition, villages without access to safe water and sanitation are 6.7 times (P<0.0001) more likely to get cholera. Alternatively, villages with full sanitation and water coverage are 9.1 (P < 0.0001) less likely to get cholera.

The findings of our study suggest that significant access to improved water and sanitation at the village level offer a strong barrier against cholera transmission. However, it requires full CLTS coverage of the village to observe strong impact on cholera as partial access only has a limited impact.

Influence on needs for WASH projects in hotspots in prevention of cholera.

To prevent cholera epidemics and empower local public health service for sustainable cholera and other vaccine-preventable disease surveillance and control.The MOCA project was conducted in Cuamba Municipality District where cholera is found to be endemic and period outbreaks occur including the recent cholera epidemic in 2015.

Strengthened local capacity for cholera/diarrheal surveillance and laboratory diagnosis.

Prevention of cholera infection in vulnerable populations in Mozambique. Generation of data on the occurrence of cholera and other vaccine-preventable non-cholera diarrheal infections. Capacity-building of African scientists in the field of public health research collaborations particularly on diarrheal disease and cholera surveillance activities.

This project focuses on defining O-specific polysaccharide (OSP) responses during cholera and development of vaccines protective against cholera and enteric infection.

Immune responses that mediate protection against cholera target the sugar (OSP) that coats the bacteria that causes cholera. Young children in particular do not develop high level or durable immune responses against this sugar after oral cholera vaccination. Understanding and improving these responses will be critical in development of next generation cholera vaccines that can protect young children against cholera, and that can be incorporated in EPI schedules.

Informs development of next generation cholera vaccines for use in children under 5 years of age.

Cholera continues to be a major cause of morbidity and mortality in low-income countries including Bangladesh. It is estimated that over 2.9 million cases and over 95,000 deaths occurs annually in cholera endemic countries alone and frequent epidemics happened in other settings with poor water and sanitation infrastructure. (1) The overall morbidity for cholera remains high. A global stockpile of OCV has been created by WHO in 2013 for epidemic and outbreak settings. (2) The disease is characterized by acute onset of watery diarrhea leading to rapid dehydration and death, if not promptly treated. From August, 2017 Rohingya Myanmar Nationals (RMN) have been influxed to Bangladesh through Cox’s Bazar border of Bangladesh. They are staying at the camps of two different upazilas (Teknaf and Ukhiya) of Cox’s Bazar. According to the latest assessment, more than half (52%) of the total Rakhine state’s population has no access to the improved sanitation facility. Also, around 45% of the population has not access to or is not using improved water supply facility according to the SDG standards.(14) Considering this risk assessment international co-ordination group (ICG) of WHO allocate 900,000 oral cholera vaccines from WHO stockpile to deploy among the RMN.

The prevention of cholera has become a high priority in the global community . Immunization with OCV is the most effective means of preventing cholera infection and its consequence. The World Health Organization (WHO) has warned of a growing risk of a cholera epidemic at the Rohingya camps in Bangladesh where people are sheltered in dire conditions. The camps did not have safe drinking water and lacked sufficient sanitation and hygiene; filthy water and feces flowed openly through the camps. Risk of waterborne diseases is very high, especially there is increasingthe risk of cholera in these camp. Moreover, according to a total number of 782 cases with 11 deaths have been reported in 2016 from Myanmer when the case fatality rate was 1.4%.(9) Interventions like vaccination are being scaled-up as the situation remains critical and challenging. But information related to vaccine effectiveness under this humanitarian condition is lacking

Relevance

The study of Shanchol OCV on Rohingya Myanmar Nationals (RMN) in children and adults will be able to give information regarding the effectiveness of vaccine in RMN subjects. This information will be important for proceeding with the cholera vaccination in the refugee population of same socioeconomic structure in future.

Objectives

The objective of this study is to determine the effectiveness of OCV in a test-negative case control design among Rohingya Myanmar Nationals (RMN) in Bangladesh.

Methods

This study will be conducted in Ukhiya upazila of Cox’s Bazar district. Here we would like to conduct the study through a test-negative case-control design. The participants will be the RMN who will come to the treatment center for seeking management of acute watery diarrhea (AWD). The stool or rectal swab of all participants will be tested. The cholera positive participants will be considered as cases whereas the cholera negative will be considered as control. The vaccine effectiveness will be measured by comparing the ratio of odds of vaccination in the cholera positive patients and odds of vaccination in the cholera negative patients.

Outcome measures/variables

The vaccine effectiveness will be measured by comparing the ratio of odds of vaccination in the cholera positive patients and odds of vaccination in the cholera negative patients.

Cholera continues to be a major cause of morbidity and mortality in low-income countries including Bangladesh. It is estimated that over 2.9 million cases and over 95,000 deaths occurs annually in cholera endemic countries alone and frequent epidemics happened in other settings with poor water and sanitation infrastructure. The overall morbidity for cholera remains high. A global stockpile of OCV has been created by WHO in 2013 for epidemic and outbreak settings. The disease is characterized by acute onset of watery diarrhea leading to rapid dehydration and death, if not promptly treated. From August, 2017 Forcibly Displaced Myanmar Nationals (FDMN) have been influxed to Bangladesh through Cox’s Bazar border of Bangladesh. They are staying at the camps of two different upazilas (Teknaf and Ukhiya) of Cox’s Bazar. According to the latest assessment, more than half (52%) of the total Rakhine state’s population has no access to the improved sanitation facility. Also, around 45% of the population has not access to or is not using improved water supply facility according to the SDG standards. Considering this risk assessment international co-ordination group (ICG) of WHO allocate 900,000 oral cholera vaccines from WHO stockpile to deploy among the FDMN. Therefore the objective of this study is to determine the effectiveness of OCV in a test-negative case control design among Forcibly Displaced Myanmar Nationals (FDMN) in Bangladesh.

“The vaccine effectiveness will be measured by comparing the ratio of odds of vaccination in the cholera positive patients and odds of vaccination in the cholera negative patients.
”

OVERCOME will establish a transnational consortium with multidisciplinary expertise for cross-sectoral collaborative research in creating innovative technological methodologies and applications, including observations/surveillance, Internet of Things, climate/weather forecasting, artificial intelligence, machine learning, and data analytics to strengthen our capacity in predicting the outbreaks of cholera and other water-related diseases. We will engage with stakeholders from academia, industry, governments, NGOs, coming from a wide range of sectors e.g. natural environment, health care, environment-economic, urban planning, utility services, disaster management, policy making, etc., and local communities in co-shaping the research questions and targeted outcomes. One example is that we hope to fill the gap between rainfall and runoff in cholera forecasting, as well as between floods and epidemiology. The team building and methodology defining in the first 12 months will enable the follow-up research in the second phase for delivering an ultimate holistic framework that supports these stakeholders in strategic planning and decision making to enhance societal resilience to climatic hazards. This will strengthen the capacity of vulnerable communities in minimising the negative impact of disasters, such as cholera, and associated health risks, which will improve country progress in addressing Sustainable Development Goals (SDGs).

OVERCOME consortium includes world-leading organisations to develop state-of-the-art research plans that integrate digital innovations in natural hazard and risk predictions in order to develop intervention strategies for strengthening the resilience of vulnerable communities against climate hazards and health impacts, including cholera and other water-related diseases.

The partners from the UK, Malawi, Mozambique, and Zimbabwe will contribute knowledge and skills in climate and meteorology, hydrology and water resources, flood forecasting, droughts, water quality, epidemiology and public health, smart technologies, data science, environmental science, Water, Sanitation and Hygiene (WASH), risk communication, disaster management, social and policy sciences, and socio-economics. The collaboration will combine multidisciplinary knowledge to develop a novel holistic framework to forecast the impact of floods/droughts and associated disease outbreaks. OVERCOME also has strong support from global experts and local major stakeholders. The external partners will steer research direction throughout the project, contribute their complementary knowledge, and engage the team with additional partners through their strong international networking.

OVERCOME consortium will co-design an innovate holistic framework to help governments and local authorities in the partnering countries more accurately identify the timing and locations where the hazards and diseases, including cholera, will hit.

Burden

Cholera is life threatening disease that remains one of the major causes of deaths in the developing countries. Although more than 200 serogroups of V. cholerae reported so far, serogroup O1 and O139 are the major pathogenic strains. Serogroup O1 has two biotypes, classical and El Tor. The classical biotype caused first six cholera pandemics in the Ganges Delta of Bay of Bengal and the other parts of the world. The El Tor biotype of V. cholerae initiated the ongoing 7th pandemic in early 1960s. The El Tor biotype was displaced for a short while in late 1992 when an explosive cholera epidemic occurred by V. cholerae O139 synonym Bengal. O139 however, failed to continue as the predominant epidemic strain and thus V. cholerae El Tor continued to cause the ongoing 7th pandemic.

Knowledge gap

A retrospective study on V. cholerae strains isolated between 1991 and 1997 showed that the biotypes Classical, El Tor, and El Tor variants were involved in endemic cholera in Mexico and ET prototype (wild type) were involved in Peru. We are not aware about the present status of cholera bacteria in different parts of Latin America so; a follow-up study on V. cholerae isolated from 1998 to 2012 was designed.

Hypothesis

The V. cholerae strains causing endemic cholera between 1998 and 2012 in Mexico and other countries of Latin America might not be different in terms of biotype, phenotype, molecular, and phylogenetic properties compared with Asia and Africa.

Objectives

The aim of this study is to determine the prevalent sero-biotypes, molecular status and clonal nature of V. cholerae isolated in Mexico and other Latin American countries and compare those characteristics with the strains isolated from Gangetic Bengal and Africa.

Methods

150 V. cholerae strains (both clinical and environmental) which included 89 strains isolated in Mexico, 45 in Peru, 12 in Brazil, and 6 in Guatemala will be analyzed by culture method, serogrouping and antibiogram. V. cholerae strains will also be subjected to detection of marker genes such as ompW, wbeO1, wbfO139, ctxA and ctxB by PCR. Extensive molecular characterizations using multi-locus genome screening and DNA fingerprinting (phylogeny) by PFGE will also be done.

Outcome measures/variables

This study will generate valuable information on nature (clonal types) of cholera bacteria, their transmission patterns world-wide. This is important because updated information on phenotypic, molecular, and phylogenetic characteristics of V. cholerae associated with cholera in Mexico and other Latin American countries are lacking.

The V. cholerae strains causing endemic cholera between 1998 and 2012 in Mexico and other countries of Latin America might not be different in terms of biotype, phenotype, molecular, and phylogenetic properties compared with Asia and Africa.

Introduction

Cholera remains a frequent cause of outbreaks globally, particularly in areas with inade- quate water, sanitation and hygiene (WASH) services. Cholera is spread through faecal- oral routes, and studies demonstrate that ingestion of Vibrio cholerae occurs from consum- ing contaminated food and water, contact with cholera cases and transmission from contam- inated environmental point sources. WASH guidelines recommending interventions for the prevention and control of cholera are numerous and vary considerably in their recommenda- tions. To date, there has been no review of practice guidelines used in cholera prevention and control programmes.

Methods

We systematically searched international agency websites to identify WASH intervention guidelines used in cholera programmes in endemic and epidemic settings. Recommendations listed in the guidelines were extracted, categorised and analysed. Analysis was based on consistency, concordance and recommendations were classified on the basis of whether the interventions targeted within-household or community-level transmission.

Results

Eight international guidelines were included in this review: three by non-governmental organi- sations (NGOs), one from a non-profit organisation (NPO), three from multilateral organisations and one from a research institution. There were 95 distinct recommendations identified, and concordance among guidelines was poor to fair. All categories of WASH interventions were featured in the guidelines. The majority of recommendations targeted community-level trans- mission (45%), 35% targeted within-household transmission and 20% both.

Conclusions

Recent evidence suggests that interventions for effective cholera control and response to epidemics should focus on case-centred approaches and within-household transmission. Guidelines did consistently propose interventions targeting transmission within households. However, the majority of recommendations listed in guidelines targeted community-level transmission and tended to be more focused on preventing contamination of the environment by cases or recurrent outbreaks, and the level of service required to interrupt commu- nity-level transmission was often not specified. The guidelines in current use were varied and interpretation may be difficult when conflicting recommendations are provided. Future editions of guidelines should reflect on the inclusion of evidence-based approaches, cholera transmission models and resource-efficient strategies.

Cholera is a diarrhoeal disease caused by ingestion of the pathogenic bacteria Vibrio cholerae. Cholera is spread to susceptible individuals via the faecal-oral routes of transmission from consuming contaminated water and food, contact with cholera cases and from a contaminated environment. Water, sanitation and hygiene (WASH) interventions such as improved water sources, sanitation and hygiene measures can prevent and control the disease. While this is widely accepted, and demonstrated in Europe and the Americas which have been cholera free for decades after sanitary improvements, there is a paucity of evidence to support which WASH interventions are most relevant in cholera-affected populations today.

Guidelines for the implementation of WASH interventions in cholera epidemic and endemic settings have been written by numerous organisations and vary considerably. Whilst appropriate cholera response will be specific to geographical and social context, it is important that the guidelines are informed by the best possible and available evidence.

A total of eight guidelines were identified and 95 recommendations extracted from the guidelines. These were categorised and analysed for their consistency, concordance and according to current cholera transmission models. This paper details the included recommendations from guidelines and recommended actions to improve future guideline development by international organisations.

It may encourage change to guidelines or use of evidence in future cholera WASH guidelines

Diarrheal diseases are one of the most common causes of morbidity and mortality in the world today. It is estimated that a child dies of diarrhea approximately every 15-30 seconds; almost all of these deaths occur in the developing world. One of the, causative organisms, Vibrio cholerae, causes severe secretory diarrhea in humans. A prototypical mucosal infection, V. cholerae does not invade the intestinal epithelium and serves as an excellent model for the study of mucosal immunity and vaccination. The study focuses on defining the mechanisms of protective immunity to infection with V. cholerae so as to understand the requisites for the development of a protective cholera vaccine.

The central hypothesis of this proposal is that V. cholerae expresses specific proteins during early human infection, which generate immune responses that are protective on subsequent exposure; that these proteins may not be adequately expressed during colonization with currently available vaccine strains, and that these differences may explain the generally lessened efficacy of current vaccine approaches. As a result of this study, we hope to assess immune responses following cholera vaccination with the killed oral vaccines (Dukoral and/or Shanchol), and compare with responses to those seen following natural cholera. In order, to assess the duration of immunity to known cholera virulence factors, we will determine antigen-specific memory B cells circulating in human blood, to examine the longevity of B cell immunologic memory. To determine the mucosal immune responses, we will follow the immune responses using duodenal biopsies from patients recovered from cholera and correlate the duration of antigen-specific, antibody-secreting cells over a period of one year.

In addition to cholera patients, we will also study household contacts to assess innate and acquired immune responses early after exposure in household contacts of cholera patients, to determine correlates of subsequent protective immunity to cholera. The study planned is a continuation of investigations of immune responses in cholera (Pr#2005-030).

Yes, that impact the development of immune responses following cholera or that influence the development of clinical illness following exposure to the organism.

The prevention of cholera has become a high priority in the global community. Immunization with OCV is the most effective means of preventing cholera infection and it’s consequences. The World Health Organization (WHO) has warned of a growing risk of a cholera epidemic at the Rohingya camps in Bangladesh where people are sheltered in dire conditions. The camps do not have safe drinking water and lacked sufficient sanitation and hygiene; filthy water and faeces flowed openly through the camps. Risk of waterborne diseases is very high, especially there is increasing the risk of cholera in these camp. Over a million Forcibly Displaced Myanmar Nationals (FDMNs) have been residing in different camps of Ukhia and Teknaf, the two upazilla of Cox’s Bazar. Around the camps, the Bangladeshi host population are also living in close proximity to the FDMNs. The risk of cholera and other diarrhoeal diseases are similarly present for the host community and the fragile population. Moreover, according to WHO, a total number of 782 cases with 11 deaths have been reported in 2016 from Myanmer when the case fatality rate was 1.4%. Interventions like vaccination are being scaled-up as the situation remains critical and challenging. In addition, an impact evaluation of the effectiveness of the mass OCV campaigns carried out between October 2017 to December 2018 is ongoing. This has been carried out in 13 sites in Teknaf (n=2) and Ukhia (n=11). But information related to cholera burden among the FDMNs and host community is necessary to detect epidemics and outbreaks which will leverage cholera containment through vaccination and WASH activities. The objective of this study to carry out cholera surveillance at selected health facilities in Ukhiya and Teknaf Upazila, Cox’sbazar to gather information regarding cholera burden among fragile population (FDMN) and host community.

Burden

Cholera remains a major global health problem, resulting in more than 100,000 deaths and several million cases annually. Bangladesh, which lies in the Ganges River Delta, is a hyper endemic country and has an estimated 300,000 cholera cases and over 4,500 deaths annually. In early 2020, the SARSCoV-2 pandemic shocked the world leading to over 43 million cases and over 1 million deaths globally by October 2020. In Bangladesh, by October 2020, there have been an estimated 400,000 cases and over 5,000 deaths. With the implementation of non-pharmaceutical interventions like social distancing, healthcare seeking behaviors have likely been affected resulting in the likely underestimation of both cholera and COVID-19 cases.

Knowledge gap

To meet the ambitious goals set by the WHO of reducing cholera as a public health threat by 2030 and reduce cholera in the hyper endemic setting of Bangladesh, improving our methods for counting cholera cases and infections is critical for control planning. At present, most cholera burden estimates are derived from passive clinical based surveillance, which only captures a portion of true cases and infections due to barriers to healthcare seeking. While we have recently developed methods to estimate V. cholera infection incidence at the population-level, some fundamental questions still remain on how to interpret this data in relation to clinical incidence. Furthermore, we know little about how the COVID-19 pandemic has affected healthcare seeking for cholera or what the seroprevalence of SARS-CoV-2 is in the population.

Relevance

Results from this study will improve our knowledge of cholera incidence in Bangladesh to aid the distribution of interventions like the oral cholera vaccine. Refining our methods for estimating cholera burden will additionally improve how we estimate cholera burden in other countries and estimate future vaccine demand. This study will also result in the estimation of the seroprevalence of SARSCoV- 2 infection in the study region in Bangladesh which will help inform the implementation of
interventions like vaccination and improve our understanding of how the COVID-19 pandemic has disrupted healthcare seeking behaviours.

Objectives

The primary objective of this study is to improve and refine our methods for estimating correlates of cholera burden from cross-sectional serosurveys though enhanced clinical surveillance of cholera at two healthcare facilities and through serial serosurveys. A secondary objective of this study is to better understand the maturity of the SARS-COV-2 epidemic in this population by measuring the prevalence of SARS-COV-2 antibodies in the population and estimating key individual-, household- and
community-level risk factors for infection.

Study Site

This study will be focused at two healthcare facilities, the Bangladesh Institute of Tropical Infectious Diseases (BITID) and the Sitakunda Upazila Health Complex (UHC), and their catchment population, the Sitakunda Upazila within the Chittagong District in South Eastern Bangladesh. Historical clinical and serologic surveillance from the district suggest that cholera incidence is relatively high compared to other parts of Bangladesh (e.g.,1.15 times the seroincidence than the mean for the country based on a serosurvey conducted in 2015) with two seasonal peaks in cholera admissions, the larger one typically starting in March and the smaller one towards the end of the calendar year. Clinical surveillance data from 2014-2018 illustrate that a greater number of patients with acute watery diarrhea visit BITID from April to June; on average approximately 4,000 individuals seek care at BITID for acute watery diarrhea within a single year. We anticipate that within a 18-month period,
approximately 9,000 patients will seek care at both BITID and the Sitakunda UHC.

Cholera remains a major global health problem, resulting in more than 100,000 deaths and several million cases annually. Bangladesh, which lies in the Ganges River Delta, is a hyper endemic country and has an estimated 300,000 cholera cases and over 4,500 deaths annually. In early 2020, the SARS-CoV-2 pandemic shocked the world leading to over 43 million cases and over 1 million deaths globally by October 2020. In Bangladesh, by October 2020, there have been an estimated 400,000 cases and over 5,000 deaths. With the implementation of non-pharmaceutical interventions like social distancing, healthcare seeking behaviors have likely been affected resulting in the likely underestimation of both cholera and COVID-19 cases.

The primary objective of this study is to improve and refine our methods for estimating correlates of cholera burden from cross-sectional serosurveys though enhanced clinical surveillance of cholera at two healthcare facilities and through serial serosurveys. A secondary objective of this study is to better understand the maturity of the SARS-COV-2 epidemic in this population by measuring the prevalence of SARS-COV-2 antibodies in the population and estimating key individual-, household- and community-level risk factors for infection.

Our primary study outcome is the change in seroincidence between the first and third serosurvey to capture changes in cholera incidence over the course of the typical high and low season at the study site. Our secondary outcome is the prevalence of anti-SARS-CoV-2 antibodies among individuals in the first serosurvey. We will explore the associations between seropositivity (for cholera and SARS-COV-2) and different individual-, household- and community-level risk factors collected in the surveys, including WASH attributes and factors like population density, travel time (to the nearest city), distance to a major water body, community water and sanitation coverage, and poverty.

Introduction: Adamawa and Bauchi are cholera endemic states in the north-east region of Nigeria, each with local government areas classified as cholera hotspots. Ineffective implementation of multi-sectoral cholera interventions in both states could make obtaining the global target for cholera control in Nigeria out of reach. A major contributing factor to this challenge is fragility of the region due to persistent Boko Haram insurgency activities, often characterised by the destruction of health infrastruture and displacement of communities to areas with suboptimal living conditions. Given the complexity of disease control in such a fragile setting, this study aims to systematically examine the barriers and/or facilitators influencing the implementation of existing cholera interventions in these states.

Methods: The study will use a systems dynamic approach. First, we will conduct a health facility survey to determine the current health system capacity to support multi-sectoral cholera interventions, and conduct key informant interviews with purposely selected state and national cholera stakeholders to identify the context-specific facilitators and barriers to the implementation of cholera interventions in these states. We will then conduct nine group model building workshops (four in both the Adamawa and Bauchi states and one in Abuja) among cholera stakeholders similar to those recruited for the interviews.

Conclusion: By engaging diverse and relevant cholera stakeholders, including community members, this study has the potential to provide a rich understanding of context-specific factors influencing the implementation of multi-sectoral cholera interventions in a fragile region of Nigeria, with a view to achieve sustainable progress towards cholera control in the country.

Adamawa and Bauchi states are cholera endemic states in the north-east region of Nigeria, each with some local government areas classified as cholera hotspots or high burden areas. However, the prevailing activities of armed conflict, as perpetuated by Boko-Haram, in the region could make the implementation of multi-sectoral cholera interventions ineffective. Moreover, addressing disease burden in such fragile settings is particularly challenging. Thus, this study aims to systematically examine the barriers and/or facilitators influencing the implementation of existing cholera interventions in these states.

To achieve these objectives, the study will use a systems dynamic approach, by first conducting a health facility survey to determine the current health system capacity to support multi-sectoral cholera interventions, as well as conducting key informant interviews with purposely selected cholera stakeholders at various levels of government. These research activities will then be followed by a series of participatory workshops (four in both Adamawa and Bauchi states and one in Abuja) among participants with similar characteristics as those in the key informant interviews. It is worth noting that findings from the first phase of the study will be informing the workshop activities.

Overall, by engaging diverse and relevant cholera stakeholders, including community members, this study has the potential to provide a rich understanding of context-specific factors influencing the implementation of multi-sectoral cholera interventions in a fragile region of Nigeria, with a view to achieve sustainable progress towards cholera control in the country.

Nationally, the study would be providing context-specific findings, generated in collaboration with various cholera stakeholders including policymakers and community representatives. Globally, the study is designed around the GTFCC’s global strategic framework, thereby making the potential findings of direct relevance to cholera global stakeholders.

Surveillance of many human pathogens, including Vibrio cholerae, relies primarily on clinical diagnosis of individuals who seek testing or care. Infections may go unobserved in these passive surveillance systems for a number of reasons, including mild and asymptomatic infections not captured by clinical surveillance as well as symptomatic infections not captured due to factors such as barriers in access to healthcare or limited testing resources. Previous studies in Bangladesh have shown that unobserved infections account for at least half of V. cholerae infections and that individuals with asymptomatic infection shed less V. cholerae in their stool compared to symptomatic cholera. The extent to which this impacts our ability to prevent and control outbreaks, and whether these findings apply to other populations, is unknown. In this study we aim to address this gap in our knowledge by investigating the contribution of unobserved infections to cholera burden and transmission in multiple populations. We will to do this by estimating the magnitude of V. cholerae infections that go unobserved by comparing patterns in clinical and serological data across published studies from various endemic and epidemic locations (aim 1), examining the degree to which individuals with no or mild symptoms shed V. cholerae bacteria that may be transmitted among individuals in Uvira, Democratic Republic of the Congo (aim 2), and estimating the risk of infection following exposure to asymptomatic household contacts of cholera cases in Dhaka, Bangladesh (aim 3). We expect to find high levels of unobserved infections, particularly in areas with barriers to healthcare access. We also anticipate that mild/asymptomatic infections will be associated with bacterial shedding and ongoing transmission, but to a lesser extent than cases with more severe symptoms. Alternatively, since people with mild/asymptomatic infections are less likely to receive antibiotics and often continue to go about their daily routines, we may find increased bacterial shedding and secondary infections in these cases. In either scenario, these results will provide important insights into the degree to which unobserved infections contribute to V. cholerae persistence and spread, as well as their role in our efforts to mitigate outbreaks. Our long-term goal is to better understand the underlying host, microbial, and socio-demographic factors that lead to infections going unobserved so that we can design more effective prevention and control strategies.

Cholera surveillance and control strategies rely primarily on detecting symptomatic cases that seek care; mild infections and infections in individuals with barriers in access to healthcare are often unobserved. This project aims to examine the degree to which unobserved infections contribute to the burden and transmission of Vibrio cholerae. The approaches used in this study will lay the groundwork for addressing critical questions about the host, microbial, and socio-demographic factors that contribute to infections going unobserved, ultimately leading to more effective mitigation strategies.

Results from this study will help us to refine cholera burden estimates and to better understand whether current control strategies, which target symptomatic cholera, are enough to mitigate transmission.

Oral cholera vaccination (OCV) has typically been used in responsive, outbreak response settings, but growing vaccine supply and efforts to promote cholera control planning at national scales have led to more frequent use of preventive vaccination campaigns. The Vaccine Impact Modelling Consortium coordinates a multi-modeling effort to estimate the global impact of vaccines for several vaccine-preventable diseases. This work will expand on an existing OCV modeling framework to project the impact of multiple scenarios of global cholera vaccination campaigns, inform strategic planning for vaccine supply and vaccine demand and underscores the importance of the effective targeting of OCV campaigns. An R package will be developed to make the model more accessible and flexible for other users and policy questions.

This research aims to develop a flexible vaccine impact model that can project the global impact of oral cholera vaccination campaigns under different sets of planning scenarios.

The modeling framework that results from this project can be used to estimate the impact of cholera vaccination campaigns and advocate for increases to OCV campaign funding and supply.

Background

Cholera is a rapidly dehydrating diarrheal illness and remains a global threat to public health. Recently it has been estimated that there are approximately 2.8 million cholera cases and 91,500 cholera deaths in cholera-endemic countries. Till date, no medication exists which can quickly curtail cholera diarrhea.

Knowledge gap

Currently, there have not been studies to understand whether vasoactive intestinal polypeptide (VIP) is a mediator in the pathogenesis of cholera.

Relevance

If VIP is a mediator for cholera diarrhoea, VIP antagonists/blockers could significantly curtail cholera diarrhea. Hopefully this might reduce cholera related morbidity & mortality in endemic countries.

Objectives

To determine VIP levels in cholera ricewater stool and in patients’ plasma obtained simultaneously, both before and after correction of severe dehydration using standard intravenous rehydration and maintenance therapy. Thus to confirm a role of VIP in cholera pathophysiology.

Methods

This would be a descriptive study, patients of either sex, aged 18-64 years attending the Dhaka Hospital of icddr,b with severe dehydration due to cholera will comprise the study population. Rectal catheter stool & venous blood specimen will be obtained just before initiation of IV rehydration therapy, after post rehydration, 24 hours after post rehydration & before discharge.

Outcome measures/variables

Primary outcome measure will be stool & plasma VIP level before & after correction of severe dehydration
Secondary outcome measures will be time to cessation of diarrhoea, the total volume of stool output (ml/kg/hr), the total volume of IVF received, and the total volume of ORS received, development of any severe complications, as decided by treating physician.

Cholera is diarrheal illness and can cause severe dehydration rapidly. Cholera remains a global threat to public health. Recently it has been estimated that there are approximately 2.8 million cholera cases and 91,500 cholera deaths in cholera-endemic countries. Till date, no medication exists which can quickly curtail cholera diarrhea. Currently, there have not been studies to understand whether Vasoactive intestinal peptide (VIP) is a mediator in the pathogenesis of cholera. If VIP is a mediator for cholera diarrhoea, VIP antagonists/blockers could significantly curtail cholera diarrhea. Hopefully this might reduce cholera related morbidity & mortality in endemic countries.

If VIP is a mediator for cholera diarrhoea, VIP antagonists/blockers could significantly curtail cholera diarrhea. Hopefully this might reduce cholera related morbidity & mortality in endemic countries.

This work introduces a promising anti-virulence strategy for cholera control that does not rely on antibiotics. Specifically, we demonstrate that chitosan oligosaccharide (COS)—a naturally derived, FDA-approved, and widely available biopolymer—can significantly reduce intestinal colonization and disease severity in Vibrio cholerae infections.

Through in vivo mouse models, we show that oral administration of COS, particularly when delivered via sodium alginate microspheres (CNMs), effectively suppresses cholera toxin production and bacterial virulence. Importantly, this approach does not inhibit bacterial survival, thereby potentially minimizing the risk of antimicrobial resistance development.

These findings highlight the potential of COS as:

A low-cost, orally administered adjunct therapy to current cholera treatments such as oral rehydration solution;

A preventive intervention in endemic areas, especially during seasonal outbreaks;

A viable candidate for non-antibiotic-based cholera control, aligning with GTFCC’s goals of sustainability and innovation.

We believe this study may offer valuable insight into the development of complementary, accessible, and resistance-sparing strategies for cholera prevention and treatment.

Our recent study published in Nature Microbiology is titled “Vibrio cholerae virulence is blocked by chitosan oligosaccharide-mediated inhibition of ChsR activity” (2024.9(11):2909-2922; DOI: 10.1038/s41564-024-01823-6).

This work reveals the potential application of Chitosan Oligosaccharide in the prevention and treatment of Cholera

In this project, we completed a systematic review of published and gray literature to assess the impact of WASH interventions in disease outbreaks in emergencies.

This work summarized the evidence on WASH and cholera, and identified “commonly implemented but severely under-researched” gaps.