Risk Map of Cholera Infection for Vaccine Deployment: The Eastern Kolkata Case

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You, Young Ae; Ali, Mohammad; Kanungo, Suman; Sah, Binod; Manna, Byomkesh; Puri, Mahesh; Nair, G. Balakrish; Bhattacharya, Sujit Kumar; Convertino, Matteo; Deen, Jacqueline L.; Lopez, Anna Lena; Wierzba, Thomas F.; Clemens, John; Sur, Dipika

2013-01-01

Background Despite advancement of our knowledge, cholera remains a public health concern. During March-April 2010, a large cholera outbreak afflicted the eastern part of Kolkata, India. The quantification of importance of socio-environmental factors in the risk of cholera, and the calculation of the risk is fundamental for deploying vaccination strategies. Here we investigate socio-environmental characteristics between high and low risk areas as well as the potential impact of vaccination on the spatial occurrence of the disease. Methods and Findings The study area comprised three wards of Kolkata Municipal Corporation. A mass cholera vaccination campaign was conducted in mid-2006 as the part of a clinical trial. Cholera cases and data of the trial to identify high risk areas for cholera were analyzed. We used a generalized additive model (GAM) to detect risk areas, and to evaluate the importance of socio-environmental characteristics between high and low risk areas. During the one-year pre-vaccination and two-year post-vaccination periods, 95 and 183 cholera cases were detected in 111,882 and 121,827 study participants, respectively. The GAM model predicts that high risk areas in the west part of the study area where the outbreak largely occurred. High risk areas in both periods were characterized by poor people, use of unsafe water, and proximity to canals used as the main drainage for rain and waste water. Cholera vaccine uptake was significantly lower in the high risk areas compared to low risk areas. Conclusion The study shows that even a parsimonious model like GAM predicts high risk areas where cholera outbreaks largely occurred. This is useful for indicating where interventions would be effective in controlling the disease risk. Data showed that vaccination decreased the risk of infection. Overall, the GAM-based risk map is useful for policymakers, especially those from countries where cholera remains to be endemic with periodic outbreaks. PMID:23936491

An Estimation of Private Household Costs to Receive Free Oral Cholera Vaccine in Odisha, India

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Mogasale, Vittal; Kar, Shantanu K.; Kim, Jong-Hoon; Mogasale, Vijayalaxmi V.; Kerketta, Anna S.; Patnaik, Bikash; Rath, Shyam Bandhu; Puri, Mahesh K.; You, Young Ae; Khuntia, Hemant K.; Maskery, Brian; Wierzba, Thomas F.; Sah, Binod

2015-01-01

Background Service provider costs for vaccine delivery have been well documented; however, vaccine recipients’ costs have drawn less attention. This research explores the private household out-of-pocket and opportunity costs incurred to receive free oral cholera vaccine during a mass vaccination campaign in rural Odisha, India. Methods Following a government-driven oral cholera mass vaccination campaign targeting population over one year of age, a questionnaire-based cross-sectional survey was conducted to estimate private household costs among vaccine recipients. The questionnaire captured travel costs as well as time and wage loss for self and accompanying persons. The productivity loss was estimated using three methods: self-reported, government defined minimum daily wages and gross domestic product per capita in Odisha. Findings On average, families were located 282.7 (SD = 254.5) meters from the nearest vaccination booths. Most family members either walked or bicycled to the vaccination sites and spent on average 26.5 minutes on travel and 15.7 minutes on waiting. Depending upon the methodology, the estimated productivity loss due to potential foregone income ranged from $0.15 to $0.29 per dose of cholera vaccine received. The private household cost of receiving oral cholera vaccine constituted 24.6% to 38.0% of overall vaccine delivery costs. Interpretation The private household costs resulting from productivity loss for receiving a free oral cholera vaccine is a substantial proportion of overall vaccine delivery cost and may influence vaccine uptake. Policy makers and program managers need to recognize the importance of private costs and consider how to balance programmatic delivery costs with private household costs to receive vaccines. PMID:26352143

An Estimation of Private Household Costs to Receive Free Oral Cholera Vaccine in Odisha, India.

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Vittal Mogasale

Full Text Available Service provider costs for vaccine delivery have been well documented; however, vaccine recipients' costs have drawn less attention. This research explores the private household out-of-pocket and opportunity costs incurred to receive free oral cholera vaccine during a mass vaccination campaign in rural Odisha, India.Following a government-driven oral cholera mass vaccination campaign targeting population over one year of age, a questionnaire-based cross-sectional survey was conducted to estimate private household costs among vaccine recipients. The questionnaire captured travel costs as well as time and wage loss for self and accompanying persons. The productivity loss was estimated using three methods: self-reported, government defined minimum daily wages and gross domestic product per capita in Odisha.On average, families were located 282.7 (SD = 254.5 meters from the nearest vaccination booths. Most family members either walked or bicycled to the vaccination sites and spent on average 26.5 minutes on travel and 15.7 minutes on waiting. Depending upon the methodology, the estimated productivity loss due to potential foregone income ranged from $0.15 to $0.29 per dose of cholera vaccine received. The private household cost of receiving oral cholera vaccine constituted 24.6% to 38.0% of overall vaccine delivery costs.The private household costs resulting from productivity loss for receiving a free oral cholera vaccine is a substantial proportion of overall vaccine delivery cost and may influence vaccine uptake. Policy makers and program managers need to recognize the importance of private costs and consider how to balance programmatic delivery costs with private household costs to receive vaccines.

Knowledge of, attitudes toward, and preventive practices relating to cholera and oral cholera vaccine among urban high-risk groups: findings of a cross-sectional study in Dhaka, Bangladesh

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2013-01-01

Background In endemic countries such as Bangladesh, consequences of cholera place an enormous financial and social burden on patients and their families. Cholera vaccines not only provide health benefits to susceptible populations but also have effects on the earning capabilities and financial stability of the family. Community-based research and evaluations are necessary to understand perceptions about and practices of the community relating to cholera and oral cholera vaccines. This may help identify the ways in which such vaccines may be successfully introduced, and other preventive measures can be implemented. The present study assessed the knowledge of, attitudes toward, and preventive practices relating to cholera and oral cholera vaccine among an urban population residing in a high cholera-prone setting in Dhaka, Bangladesh. Methods This cross-sectional study was conducted in an area of high cholera prevalence in 15 randomly-selected clusters in Mirpur, Dhaka city. A study team collected data through a survey and in-depth interviews during December 2010–February 2011. Results Of 2,830 families included in the final analysis, 23% could recognize cholera as acute watery diarrhea and 16% had ever heard of oral cholera vaccine. About 54% of the respondents had poor knowledge about cholera-related issues while 97% had a positive attitude toward cholera and oral cholera vaccine. One-third showed poor practice relating to the prevention of cholera. The findings showed a significant (p cholera were the significant predictors to having poor knowledge. Conclusions The findings suggest the strengthening of health education activities to improve knowledge on cholera, its prevention and treatment and information on cholera vaccination among high-risk populations. The data also underscore the potential of mass cholera vaccination to prevent and control cholera. PMID:23509860

Cost-effectiveness of oral cholera vaccine in a stable refugee population at risk for epidemic cholera and in a population with endemic cholera.

OpenAIRE

Murray, J.; McFarland, D. A.; Waldman, R. J.

1998-01-01

Recent large epidemics of cholera with high incidence and associated mortality among refugees have raised the question of whether oral cholera vaccines should be considered as an additional preventive measure in high-risk populations. The potential impact of oral cholera vaccines on populations prone to seasonal endemic cholera has also been questioned. This article reviews the potential cost-effectiveness of B-subunit, killed whole-cell (BS-WC) oral cholera vaccine in a stable refugee popula...

Mass vaccination with a two-dose oral cholera vaccine in a long-standing refugee camp, Thailand.

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Phares, Christina R; Date, Kashmira; Travers, Philippe; Déglise, Carole; Wongjindanon, Nuttapong; Ortega, Luis; Bhuket, Ponchanok Rattanadilok Na

2016-01-02

During 2005-2012, surveillance in Maela refugee camp, Thailand, identified four cholera outbreaks, with rates up to 10.7 cases per 1000 refugees. In 2013, the Thailand Ministry of Public Health sponsored a two-dose oral cholera vaccine (OCV) campaign for the approximately 46,000 refugees living in Maela. We enumerated the target population (refugees living in Maela who are ≥1 year old and not pregnant) in a census three months before the campaign and issued barcoded OCV cards to each individual. We conducted the campaign using a fixed-post strategy during two eight-day rounds plus one two-day round for persons who had missed their second dose and recorded vaccine status for each individual. To identify factors associated with no vaccination (versus at least one dose) and those associated with adverse events following immunization (AEFI), we used separate marginal log-binomial regression models with robust variance estimates to account for household clustering. A total of 63,057 OCV doses were administered to a target population of 43,485 refugees. An estimated 35,399 (81%) refugees received at least one dose and 27,658 (64%) received two doses. A total of 993 additional doses (1.5%) were wasted including 297 that were spat out. Only 0.05% of refugees, mostly children, could not be vaccinated due to repeated spitting. Characteristics associated with no vaccination (versus at least one dose) included age ≥15 years (versus 1-14 years), Karen ethnicity (versus any other ethnicity) and, only among adults 15-64 years old, male sex. Passive surveillance identified 84 refugees who experienced 108 AEFI including three serious but coincidental events. The most frequent AEFI were nausea (49%), dizziness (38%), and fever (30%). Overall, AEFI were more prevalent among young children and older adults. Our results suggest that mass vaccination in refugee camps with a two-dose OCV is readily achievable and AEFI are few. Published by Elsevier Ltd.

Estimating the cost of cholera-vaccine delivery from the societal point of view: A case of introduction of cholera vaccine in Bangladesh.

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Sarker, Abdur Razzaque; Islam, Ziaul; Khan, Iqbal Ansary; Saha, Amit; Chowdhury, Fahima; Khan, Ashraful Islam; Cravioto, Alejandro; Clemens, John David; Qadri, Firdausi; Khan, Jahangir A M

2015-09-11

Cholera is a major global public health problem that causes both epidemic and endemic disease. The World Health Organization recommends oral cholera vaccines as a public health tool in addition to traditional prevention practices and treatments in both epidemic and endemic settings. In many developing countries like Bangladesh, the major issue concerns the affordability of this vaccine. In February 2011, a feasibility study entitled, "Introduction of Cholera Vaccine in Bangladesh (ICVB)", was conducted for a vaccination campaign using inactivated whole-cell cholera vaccine (Shanchol) in a high risk area of Mirpur, Dhaka. Empirical data obtained from this trial was used to determine the vaccination cost for a fully immunized person from the societal perspective. A total of 123,661 people were fully vaccinated receiving two doses of the vaccine, while 18,178 people received one dose of the same vaccine. The total cost for vaccine delivery was US$ 492,238 giving a total vaccination cost per fully-vaccinated individual of US$ 3.98. The purchase cost of the vaccine accounted for 58% of the overall cost of vaccination. Attempts to reduce the per-dose cost of the vaccine are likely to have a large impact on the cost of similar vaccination campaigns in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

Oral cholera vaccine use in Zanzibar: socioeconomic and behavioural features affecting demand and acceptance

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Chaignat Claire-Lise

2009-04-01

Full Text Available Abstract Background Cholera remains a serious public health problem in low-income countries despite efforts in the past to promote oral rehydration therapy as major treatment. In 2007, the majority of worldwide cases (94% and deaths (99% were reported from Africa. To improve cholera control efforts in addition to maintaining and improving existing water supply, sanitation and hygiene behaviour measures, the World Health Organization has recently started to consider the use of vaccines as an additional public health tool. To assess this new approach in endemic settings, a project was launched in Zanzibar to vaccinate 50,000 individuals living in communities at high risk of cholera with an oral two-dose vaccine (Dukoral®. Immunisation programmes in low-income countries have suffered a reduced coverage or were even brought to a halt because of an ignorance of local realities. To ensure the success of vaccination campaigns, implementers have to consider community-held perceptions and behaviours regarding the infectious disease and the vaccine of interest. The main aim of this study is to provide advice to the Ministry of Health and Social Welfare of Zanzibar regarding routine introduction of an oral cholera vaccine from a socioeconomic and behavioural perspective as part of a long-term development for a sustained cholera prevention strategy. Methods and design Qualitative and quantitative methods of health social science research will be applied on four stakeholder levels before and after the mass vaccination campaign. Rapid assessment individual interviews and focus groups will be used to describe cholera- and vaccine-related views of policy makers, health care professionals and community representatives. The cultural epidemiological approach will be employed on the individual household resident level in a repeated cross-sectional design to estimate determinants of anticipated and actual oral cholera vaccine acceptance. Discussion The study

Oral cholera vaccine use in Zanzibar: socioeconomic and behavioural features affecting demand and acceptance

Science.gov (United States)

Schaetti, Christian; Hutubessy, Raymond; Ali, Said M; Pach, Al; Weiss, Mitchell G; Chaignat, Claire-Lise; Khatib, Ahmed M

2009-01-01

Background Cholera remains a serious public health problem in low-income countries despite efforts in the past to promote oral rehydration therapy as major treatment. In 2007, the majority of worldwide cases (94%) and deaths (99%) were reported from Africa. To improve cholera control efforts in addition to maintaining and improving existing water supply, sanitation and hygiene behaviour measures, the World Health Organization has recently started to consider the use of vaccines as an additional public health tool. To assess this new approach in endemic settings, a project was launched in Zanzibar to vaccinate 50,000 individuals living in communities at high risk of cholera with an oral two-dose vaccine (Dukoral®). Immunisation programmes in low-income countries have suffered a reduced coverage or were even brought to a halt because of an ignorance of local realities. To ensure the success of vaccination campaigns, implementers have to consider community-held perceptions and behaviours regarding the infectious disease and the vaccine of interest. The main aim of this study is to provide advice to the Ministry of Health and Social Welfare of Zanzibar regarding routine introduction of an oral cholera vaccine from a socioeconomic and behavioural perspective as part of a long-term development for a sustained cholera prevention strategy. Methods and design Qualitative and quantitative methods of health social science research will be applied on four stakeholder levels before and after the mass vaccination campaign. Rapid assessment individual interviews and focus groups will be used to describe cholera- and vaccine-related views of policy makers, health care professionals and community representatives. The cultural epidemiological approach will be employed on the individual household resident level in a repeated cross-sectional design to estimate determinants of anticipated and actual oral cholera vaccine acceptance. Discussion The study presented here is designed to

Use of oral cholera vaccine as a vaccine probe to define the geographical dimensions of person-to-person transmission of cholera.

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Ali, Mohammad; Kim, Deok Ryun; Kanungo, Suman; Sur, Dipika; Manna, Byomkesh; Digilio, Laura; Dutta, Shanta; Marks, Florian; Bhattacharya, Sujit K; Clemens, John

2018-01-01

Cholera is known to be transmitted from person to person, and inactivated oral cholera vaccines (OCVs) have been shown to confer herd protection via interruption of this transmission. However, the geographic dimensions of chains of person-to-person transmission of cholera are uncertain. The ability of OCVs to confer herd protection was used to define these dimensions in two cholera-endemic settings, one in rural Bangladesh and the other in urban India. Two large randomized, placebo-controlled trials of inactivated OCVs, one in rural Matlab, Bangladesh and the other in urban Kolkata, India, were reanalyzed. Vaccine herd protection was evaluated by relating the risk of cholera in placebo recipients to vaccine coverage of surrounding residents residing within concentric rings. In Matlab, concentric rings in 100-m increments up to 700m were evaluated; in Kolkata, 50-m increments up to 350m were evaluated. One hundred and eight cholera cases among 24667 placebo recipients were detected during 1year of post-vaccination follow-up at Matlab; 128 cholera cases among 34968 placebo recipients were detected during 3 years of follow-up in Kolkata. Consistent inverse relationships were observed between vaccine coverage of the ring and the risk of cholera in the central placebo recipient for rings with radii up to 500m in Matlab and up to 150m in Kolkata. These results suggest that the dimensions of chains of person-to-person transmission in endemic settings can be quite large and may differ substantially from setting to setting. Using OCVs as 'probes' to define these dimensions can inform geographical targeting strategies for the deployment of these vaccines in endemic settings. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Antibody Secreting Cell Responses following Vaccination with Bivalent Oral Cholera Vaccine among Haitian Adults.

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Wilfredo R Matias

2016-06-01

Full Text Available The bivalent whole-cell (BivWC oral cholera vaccine (Shanchol is effective in preventing cholera. However, evaluations of immune responses following vaccination with BivWC have been limited. To determine whether BivWC induces significant mucosal immune responses, we measured V. cholerae O1 antigen-specific antibody secreting cell (ASC responses following vaccination.We enrolled 24 Haitian adults in this study, and administered doses of oral BivWC vaccine 14 days apart (day 0 and day 14. We drew blood at baseline, and 7 days following each vaccine dose (day 7 and 21. Peripheral blood mononuclear cells (PBMCs were isolated, and ASCs were enumerated using an ELISPOT assay. Significant increases in Ogawa (6.9 cells per million PBMCs and Inaba (9.5 cells per million PBMCs OSP-specific IgA ASCs were detected 7 days following the first dose (P < 0.001, but not the second dose. The magnitude of V. cholerae-specific ASC responses did not appear to be associated with recent exposure to cholera. ASC responses measured against the whole lipolysaccharide (LPS antigen and the OSP moiety of LPS were equivalent, suggesting that all or nearly all of the LPS response targets the OSP moiety.Immunization with the BivWC oral cholera vaccine induced ASC responses among a cohort of healthy adults in Haiti after a single dose. The second dose of vaccine resulted in minimal ASC responses over baseline, suggesting that the current dosing schedule may not be optimal for boosting mucosal immune responses to V. cholerae antigens for adults in a cholera-endemic area.

Potential impact of reactive vaccination in controlling cholera ...

African Journals Online (AJOL)

Background. To contain ongoing cholera outbreaks, the World Health Organization has suggested that reactive vaccination should be considered in addition to its previous control measures. Objectives. To explore the potential impact of a hypothetical reactive oral cholera vaccination using the example of the recent ...

Effectiveness of Oral Cholera Vaccine in Haiti: 37-Month Follow-Up.

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Sévère, Karine; Rouzier, Vanessa; Anglade, Stravinsky Benedict; Bertil, Claudin; Joseph, Patrice; Deroncelay, Alexandra; Mabou, Marie Marcelle; Wright, Peter F; Guillaume, Florence Duperval; Pape, Jean William

2016-05-04

The first oral cholera vaccine (OCV) campaign, since its prequalification by the World Health Organization, in response to an ongoing cholera epidemic (reactive vaccination) was successfully conducted in a poor urban slum of approximately 70,000 inhabitants in Port-au-Prince, Haiti, in 2012. Vaccine coverage was 75% of the target population. This report documents the impact of OCV in reducing the number of culture-confirmed cases of cholera admitted to the Groupe Haïtien d'Etude du Sarcome de Kaposi et des Infections Opportunistes (GHESKIO) cholera treatment center from that community in the 37 months postvaccination (April 2012-April 30, 2015). Of 1,788 patients with culture-confirmed cholera, 1,770 (99%) were either from outside the vaccine area (1,400 cases) or from the vaccinated community who had not received OCV (370 cases). Of the 388 people from the catchment area who developed culture-confirmed cholera, 370 occurred among the 17,643 people who had not been vaccinated (2.1%) and the remaining 18 occurred among the 52,357 people (0.034%) who had been vaccinated (P cholera in outbreak settings. © The American Society of Tropical Medicine and Hygiene.

Effectiveness of an oral cholera vaccine campaign to prevent clinically-significant cholera in Odisha State, India.

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Wierzba, Thomas F; Kar, Shantanu K; Mogasale, Vijayalaxmi V; Kerketta, Anna S; You, Young Ae; Baral, Prameela; Khuntia, Hemant K; Ali, Mohammad; Kim, Yang Hee; Rath, Shyam Bandhu; Bhattachan, Anuj; Sah, Binod

2015-05-15

A clinical trial conducted in India suggests that the oral cholera vaccine, Shanchol, provides 65% protection over five years against clinically-significant cholera. Although the vaccine is efficacious when tested in an experimental setting, policymakers are more likely to use this vaccine after receiving evidence demonstrating protection when delivered to communities using local health department staff, cold chain equipment, and logistics. We used a test-negative, case-control design to evaluate the effectiveness of a vaccination campaign using Shanchol and validated the results using a cohort approach that addressed disparities in healthcare seeking behavior. The campaign was conducted by the local health department using existing resources in a cholera-endemic area of Puri District, Odisha State, India. All non-pregnant residents one year of age and older were offered vaccine. Over the next two years, residents seeking care for diarrhea at one of five health facilities were asked to enroll following informed consent. Cases were patients seeking treatment for laboratory-confirmed V. cholera-associated diarrhea. Controls were patients seeking treatment for V. cholerae negative diarrhea. Of 51,488 eligible residents, 31,552 individuals received one dose and 23,751 residents received two vaccine doses. We identified 44 V. cholerae O1-associated cases and 366 non V. cholerae diarrhea controls. The adjusted protective effectiveness for persons receiving two doses was 69.0% (95% CI: 14.5% to 88.8%), which is similar to the adjusted estimates obtained from the cohort approach. A statistical trend test suggested a single dose provided a modicum of protection (33%, test for trend, p=0.0091). This vaccine was found to be as efficacious as the results reported from a clinical trial when administered to a rural population using local health personnel and resources. This study provides evidence that this vaccine should be widely deployed by public health departments in

Cholera in Haiti: Reproductive numbers and vaccination coverage estimates

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Mukandavire, Zindoga; Smith, David L.; Morris, J. Glenn, Jr.

2013-01-01

Cholera reappeared in Haiti in October, 2010 after decades of absence. Cases were first detected in Artibonite region and in the ensuing months the disease spread to every department in the country. The rate of increase in the number of cases at the start of epidemics provides valuable information about the basic reproductive number (). Quantitative analysis of such data gives useful information for planning and evaluating disease control interventions, including vaccination. Using a mathematical model, we fitted data on the cumulative number of reported hospitalized cholera cases in Haiti. varied by department, ranging from 1.06 to 2.63. At a national level, 46% vaccination coverage would result in an () cholera vaccines in endemic and non-endemic regions, our results suggest that moderate cholera vaccine coverage would be an important element of disease control in Haiti.

Lipopolysaccharide-specific memory B cell responses to an attenuated live cholera vaccine are associated with protection against Vibrio cholerae infection.

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Haney, Douglas J; Lock, Michael D; Gurwith, Marc; Simon, Jakub K; Ishioka, Glenn; Cohen, Mitchell B; Kirkpatrick, Beth D; Lyon, Caroline E; Chen, Wilbur H; Sztein, Marcelo B; Levine, Myron M; Harris, Jason B

2018-05-11

The single-dose live attenuated vaccine CVD 103-HgR protects against experimental Vibrio cholerae infection in cholera-naïve adults for at least 6 months after vaccination. While vaccine-induced vibriocidal seroconversion is associated with protection, vibriocidal titers decline rapidly from their peak 1-2 weeks after vaccination. Although vaccine-induced memory B cells (MBCs) might mediate sustained protection in individuals without detectable circulating antibodies, it is unknown whether oral cholera vaccination induces a MBC response. In a study that enrolled North American adults, we measured lipopolysaccharide (LPS)- and cholera toxin (CtxB)-specific MBC responses to PXVX0200 (derived from the CVD 103-HgR strain) and assessed stool volumes following experimental Vibrio cholerae infection. We then evaluated the association between vaccine-induced MBC responses and protection against cholera. There was a significant increase in % CT-specific IgG, % LPS-specific IgG, and % LPS-specific IgA MBCs which persisted 180 days after vaccination as well as a significant association between vaccine-induced increase in % LPS-specific IgA MBCs and lower post-challenge stool volume (r = -0.56, p < 0.001). Oral cholera vaccination induces antigen-specific MBC responses, and the anamnestic LPS-specific responses may contribute to long-term protection and provide correlates of the duration of vaccine-induced protection. NCT01895855. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Oral cholera vaccine--for whom, when, and why?

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Topps, Maureen H

2006-01-01

The search for a safe, effective, well tolerated, low cost vaccine against the ancient cholera enemy has been ongoing since the 19th century and has been revitalized in the past two decades since the advent of recombinant technology. Large-scale field trials have readily demonstrated the tolerability and safety of oral cholera vaccine in various forms. Variable levels of protection have been shown and one challenge has been to demonstrate whether this is a cost effective treatment in differing environments including its use in endemic and epidemic areas as well as for travelers. A review of recent literature was undertaken to assess the effectiveness and uses of currently available oral cholera vaccine. While the evidence does not support the creation of formal guidelines, some clear recommendations can be made. There is undoubtedly the potential to reduce the burden of illness both in endemic and epidemic situations. For travelers, certain higher risk groups may benefit from protection against cholera. More significantly, the short term cross-protection afforded by whole cell, B subunit (WC BS) oral cholera vaccine formulations against enterotoxigenic E. coli, (ETEC), the commonest causative agent of traveler's diarrhoea, may prove to be the most important raison d'être.

Spatial and environmental connectivity analysis in a cholera vaccine trial.

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Emch, Michael; Ali, Mohammad; Root, Elisabeth D; Yunus, Mohammad

2009-02-01

This paper develops theory and methods for vaccine trials that utilize spatial and environmental information. Satellite imagery is used to identify whether households are connected to one another via water bodies in a study area in rural Bangladesh. Then relationships between neighborhood-level cholera vaccine coverage and placebo incidence and neighborhood-level spatial variables are measured. The study hypothesis is that unvaccinated people who are environmentally connected to people who have been vaccinated will be at lower risk compared to unvaccinated people who are environmentally connected to people who have not been vaccinated. We use four datasets including: a cholera vaccine trial database, a longitudinal demographic database of the rural population from which the vaccine trial participants were selected, a household-level geographic information system (GIS) database of the same study area, and high resolution Quickbird satellite imagery. An environmental connectivity metric was constructed by integrating the satellite imagery with the vaccine and demographic databases linked with GIS. The results show that there is a relationship between neighborhood rates of cholera vaccination and placebo incidence. Thus, people are indirectly protected when more people in their environmentally connected neighborhood are vaccinated. This result is similar to our previous work that used a simpler Euclidean distance neighborhood to measure neighborhood vaccine coverage [Ali, M., Emch, M., von Seidlein, L., Yunus, M., Sack, D. A., Holmgren, J., et al. (2005). Herd immunity conferred by killed oral cholera vaccines in Bangladesh. Lancet, 366(9479), 44-49]. Our new method of measuring environmental connectivity is more precise since it takes into account the transmission mode of cholera and therefore this study validates our assertion that the oral cholera vaccine provides indirect protection in addition to direct protection.

Knowledge, Attitudes, and Practices regarding Diarrhea and Cholera following an Oral Cholera Vaccination Campaign in the Solomon Islands

OpenAIRE

Burnett, Eleanor; Dalipanda, Tenneth; Ogaoga, Divi; Gaiofa, Jenny; Jilini, Gregory; Halpin, Alison; Dietz, Vance; Date, Kashmira; Mintz, Eric; Hyde, Terri; Wannemuehler, Kathleen; Yen, Catherine

2016-01-01

Background In response to a 2011 cholera outbreak in Papua New Guinea, the Government of the Solomon Islands initiated a cholera prevention program which included cholera disease prevention and treatment messaging, community meetings, and a pre-emptive cholera vaccination campaign targeting 11,000 children aged 1?15 years in selected communities in Choiseul and Western Provinces. Methodology and Principal Findings We conducted a post-vaccination campaign, household-level survey about knowledg...

Cost-benefit comparisons of investments in improved water supply and cholera vaccination programs.

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Jeuland, Marc; Whittington, Dale

2009-05-18

This paper presents the first cost-benefit comparison of improved water supply investments and cholera vaccination programs. Specifically, we compare two water supply interventions -- deep wells with public hand pumps and biosand filters (an in-house, point-of-use water treatment technology) -- with two types of cholera immunization programs with new-generation vaccines -- general community-based and targeted and school-based programs. In addition to these four stand-alone investments, we also analyze five combinations of water and vaccine interventions: (1) borehole+hand pump and community-based cholera vaccination, (2) borehole+hand pump and school-based cholera vaccination, (3) biosand filter and community-based cholera vaccination, (4) biosand filter and school-based cholera vaccination, and (5) biosand filter and borehole+hand pump. Using recent data applicable to developing country locations for parameters such as disease incidence, the effectiveness of vaccine and water supply interventions against diarrheal diseases, and the value of a statistical life, we construct cost-benefit models for evaluating these interventions. We then employ probabilistic sensitivity analysis to estimate a frequency distribution of benefit-cost ratios for all four interventions, given a wide variety of possible parameter combinations. Our results demonstrate that there are many plausible conditions in developing countries under which these interventions will be attractive, but that the two improved water supply interventions and the targeted cholera vaccination program are much more likely to yield attractive cost-benefit outcomes than a community-based vaccination program. We show that implementing community-based cholera vaccination programs after borehole+hand pump or biosand filters have already been installed will rarely be justified. This is especially true when the biosand filters are already in place, because these achieve substantial cholera risk reductions on their own

Local perceptions of cholera and anticipated vaccine acceptance in Katanga province, Democratic Republic of Congo

Science.gov (United States)

2013-01-01

Background In regions where access to clean water and the provision of a sanitary infrastructure has not been sustainable, cholera continues to pose an important public health burden. Although oral cholera vaccines (OCV) are effective means to complement classical cholera control efforts, still relatively little is known about their acceptability in targeted communities. Clarification of vaccine acceptability prior to the introduction of a new vaccine provides important information for future policy and planning. Methods In a cross-sectional study in Katanga province, Democratic Republic of Congo (DRC), local perceptions of cholera and anticipated acceptance of an OCV were investigated. A random sample of 360 unaffected adults from a rural town and a remote fishing island was interviewed in 2010. In-depth interviews with a purposive sample of key informants and focus-group discussions provided contextual information. Socio-cultural determinants of anticipated OCV acceptance were assessed with logistic regression. Results Most respondents perceived contaminated water (63%) and food (61%) as main causes of cholera. Vaccines (28%), health education (18%) and the provision of clean water (15%) were considered the most effective measures of cholera control. Anticipated vaccine acceptance reached 97% if an OCV would be provided for free. Cholera-specific knowledge of hygiene and self-help in form of praying for healing were positively associated with anticipated OCV acceptance if costs of USD 5 were assumed. Conversely, respondents who feared negative social implications of cholera were less likely to anticipate acceptance of OCVs. These fears were especially prominent among respondents who generated their income through fishing. With an increase of assumed costs to USD 10.5, fear of financial constraints was negatively associated with anticipated vaccine acceptance as well. Conclusions Results suggest a high motivation to use an OCV as long as it seems affordable. The

Feasibility and acceptability of oral cholera vaccine mass ...

African Journals Online (AJOL)

... acceptable by the community to conduct a largescale mass OCV campaign in Malawi within five weeks. Of 320,000 OCV doses received, Malawi managed to administer at least 294,221 (91.9%) of the doses. OCV could therefore be considered to be introduced as additional measure in cholera hot spot areas in Malawi.

Critical Analysis of Compositions and Protective Efficacies of Oral Killed Cholera Vaccines

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2014-01-01

Two cholera vaccines, sold as Shanchol and Dukoral, are currently available. This review presents a critical analysis of the protective efficacies of these vaccines. Children under 5 years of age are very vulnerable to cholera and account for the highest incidence of cholera cases and more than half of the resulting deaths. Both Shanchol and Dukoral are two-spaced-dose oral vaccines comprising large numbers of killed cholera bacteria. The former contains Vibrio cholerae O1 and O139 cells, and the latter contains V. cholerae O1 cells with the recombinant B subunit of cholera toxin. In a field trial in Kolkata (India), Shanchol, the preferred vaccine, protected 45% of the test subjects in all of the age groups and only 17% of the children under 5 years of age during the first year of surveillance. In a field trial in Peru, two spaced doses of Dukoral offered negative protection in children under 5 years of age and little protection (15%) in vaccinees over 6 years of age during the first year of surveillance. Little is known about Dukoral's long-term protective efficacy. Both of these vaccines have questionable compositions, using V. cholerae O1 strains isolated in 1947 that have been inactivated by heat and formalin treatments that may denature protein. Immunological studies revealed Dukoral's reduced and short-lived efficacy, as measured by several immunological endpoints. Various factors, such as the necessity for multiple doses, poor protection of children under 5 years of age, the requirement of a cold supply chain, production costs, and complex logistics of vaccine delivery, greatly reduce the suitability of either of these vaccines for endemic or epidemic cholera control in resource-poor settings. PMID:25056361

Dynamics of cholera epidemics with impulsive vaccination and disinfection.

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Sisodiya, Omprakash Singh; Misra, O P; Dhar, Joydip

2018-04-01

Waterborne diseases have a tremendous influence on human life. The contaminated drinking water causes water-borne disease like cholera. Pulse vaccination is an important and effective strategy for the elimination of infectious diseases. A waterborne disease like cholera can also be controlled by using impulse technique. In this paper, we have proposed a delayed SEIRB epidemic model with impulsive vaccination and disinfection. We have studied the pulse vaccination strategy and sanitation to control the cholera disease. The existence and stability of the disease-free and endemic periodic solution are investigated both analytically and numerically. It is shown that there exists an infection-free periodic solution, using the impulsive dynamical system defined by the stroboscopic map. It is observed that the infection-free periodic solution is globally attractive when the impulse period is less than some critical value. From the analysis of the model, we have obtained a sufficient condition for the permanence of the epidemic with pulse vaccination. The main highlight of this paper is to introduce impulse technique along with latent period into the SEIRB epidemic model to investigate the role of pulse vaccination and disinfection on the dynamics of the cholera epidemics. Copyright © 2018 Elsevier Inc. All rights reserved.

Sociocultural determinants of anticipated oral cholera vaccine acceptance in three African settings: a meta-analytic approach.

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Sundaram, Neisha; Schaetti, Christian; Merten, Sonja; Schindler, Christian; Ali, Said M; Nyambedha, Erick O; Lapika, Bruno; Chaignat, Claire-Lise; Hutubessy, Raymond; Weiss, Mitchell G

2016-01-14

likely in Zanzibar. Prayer as a form of self-treatment was associated with vaccine acceptance in SE-DRC and W-Kenya, but not in Zanzibar. These cholera-endemic African communities are especially interested in no-cost OCVs. Health education and attention to local social and cultural features of cholera and vaccines would likely increase vaccine coverage. High demand and absence of insurmountable sociocultural barriers to vaccination with OCVs indicate potential for mass vaccination in planning for comprehensive control or elimination.

Assessing effects of cholera vaccination in the presence of interference.

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Perez-Heydrich, Carolina; Hudgens, Michael G; Halloran, M Elizabeth; Clemens, John D; Ali, Mohammad; Emch, Michael E

2014-09-01

Interference occurs when the treatment of one person affects the outcome of another. For example, in infectious diseases, whether one individual is vaccinated may affect whether another individual becomes infected or develops disease. Quantifying such indirect (or spillover) effects of vaccination could have important public health or policy implications. In this article we use recently developed inverse-probability weighted (IPW) estimators of treatment effects in the presence of interference to analyze an individually-randomized, placebo-controlled trial of cholera vaccination that targeted 121,982 individuals in Matlab, Bangladesh. Because these IPW estimators have not been employed previously, a simulation study was also conducted to assess the empirical behavior of the estimators in settings similar to the cholera vaccine trial. Simulation study results demonstrate the IPW estimators can yield unbiased estimates of the direct, indirect, total, and overall effects of vaccination when there is interference provided the untestable no unmeasured confounders assumption holds and the group-level propensity score model is correctly specified. Application of the IPW estimators to the cholera vaccine trial indicates the presence of interference. For example, the IPW estimates suggest on average 5.29 fewer cases of cholera per 1000 person-years (95% confidence interval 2.61, 7.96) will occur among unvaccinated individuals within neighborhoods with 60% vaccine coverage compared to neighborhoods with 32% coverage. Our analysis also demonstrates how not accounting for interference can render misleading conclusions about the public health utility of vaccination. © 2014, The International Biometric Society.

Single-dose Live Oral Cholera Vaccine CVD 103-HgR Protects Against Human Experimental Infection With Vibrio cholerae O1 El Tor.

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Chen, Wilbur H; Cohen, Mitchell B; Kirkpatrick, Beth D; Brady, Rebecca C; Galloway, David; Gurwith, Marc; Hall, Robert H; Kessler, Robert A; Lock, Michael; Haney, Douglas; Lyon, Caroline E; Pasetti, Marcela F; Simon, Jakub K; Szabo, Flora; Tennant, Sharon; Levine, Myron M

2016-06-01

No licensed cholera vaccine is presently available in the United States. Cholera vaccines available in other countries require 2 spaced doses. A single-dose cholera vaccine that can rapidly protect short-notice travelers to high-risk areas and help control explosive outbreaks where logistics render 2-dose immunization regimens impractical would be a major advance.PXVX0200, based on live attenuated Vibrio cholerae O1 classical Inaba vaccine strain CVD 103-HgR, elicits seroconversion of vibriocidal antibodies (a correlate of protection) within 10 days of a single oral dose. We investigated the protection conferred by this vaccine in a human cholera challenge model. Consenting healthy adult volunteers, 18-45 years old, were randomly allocated 1:1 to receive 1 oral dose of vaccine (approximately 5 × 10(8) colony-forming units [CFU]) or placebo in double-blind fashion. Volunteers ingested approximately 1 × 10(5) CFU of wild-type V. cholerae O1 El Tor Inaba strain N16961 10 days or 3 months after vaccination and were observed on an inpatient research ward for stool output measurement and management of hydration. The vaccine was well tolerated, with no difference in adverse event frequency among 95 vaccinees vs 102 placebo recipients. The primary endpoint, moderate (≥3.0 L) to severe (≥5.0 L) diarrheal purge, occurred in 39 of 66 (59.1%) placebo controls but only 2 of 35 (5.7%) vaccinees at 10 days (vaccine efficacy, 90.3%; P < .0001) and 4 of 33 (12.1%) vaccinees at 3 months (vaccine efficacy, 79.5%; P < .0001). The significant vaccine efficacy documented 10 days and 3 months after 1 oral dose of PXVX0200 supports further development as a single-dose cholera vaccine. NCT01895855. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Urban cholera transmission hotspots and their implications for reactive vaccination: evidence from Bissau city, Guinea bissau.

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Andrew S Azman

Full Text Available Use of cholera vaccines in response to epidemics (reactive vaccination may provide an effective supplement to traditional control measures. In Haiti, reactive vaccination was considered but, until recently, rejected in part due to limited global supply of vaccine. Using Bissau City, Guinea-Bissau as a case study, we explore neighborhood-level transmission dynamics to understand if, with limited vaccine and likely delays, reactive vaccination can significantly change the course of a cholera epidemic.We fit a spatially explicit meta-population model of cholera transmission within Bissau City to data from 7,551 suspected cholera cases from a 2008 epidemic. We estimated the effect reactive vaccination campaigns would have had on the epidemic under different levels of vaccine coverage and campaign start dates. We compared highly focused and diffuse strategies for distributing vaccine throughout the city. We found wide variation in the efficiency of cholera transmission both within and between areas of the city. "Hotspots", where transmission was most efficient, appear to drive the epidemic. In particular one area, Bandim, was a necessary driver of the 2008 epidemic in Bissau City. If vaccine supply were limited but could have been distributed within the first 80 days of the epidemic, targeting vaccination at Bandim would have averted the most cases both within this area and throughout the city. Regardless of the distribution strategy used, timely distribution of vaccine in response to an ongoing cholera epidemic can prevent cases and save lives.Reactive vaccination can be a useful tool for controlling cholera epidemics, especially in urban areas like Bissau City. Particular neighborhoods may be responsible for driving a city's cholera epidemic; timely and targeted reactive vaccination at such neighborhoods may be the most effective way to prevent cholera cases both within that neighborhood and throughout the city.

Use of oral cholera vaccines in an outbreak in Vietnam: a case control study.

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Dang Duc Anh

Full Text Available BACKGROUND: Killed oral cholera vaccines (OCVs are available but not used routinely for cholera control except in Vietnam, which produces its own vaccine. In 2007-2008, unprecedented cholera outbreaks occurred in the capital, Hanoi, prompting immunization in two districts. In an outbreak investigation, we assessed the effectiveness of killed OCV use after a cholera outbreak began. METHODOLOGY/PRINCIPAL FINDINGS: From 16 to 28 January 2008, vaccination campaigns with the Vietnamese killed OCV were held in two districts of Hanoi. No cholera cases were detected from 5 February to 4 March 2008, after which cases were again identified. Beginning 8 April 2008, residents of four districts of Hanoi admitted to one of five hospitals for acute diarrhea with onset after 5 March 2008 were recruited for a matched, hospital-based, case-control outbreak investigation. Cases were matched by hospital, admission date, district, gender, and age to controls admitted for non-diarrheal conditions. Subjects from the two vaccinated districts were evaluated to determine vaccine effectiveness. 54 case-control pairs from the vaccinated districts were included in the analysis. There were 8 (15% and 16 (30% vaccine recipients among cases and controls, respectively. The vaccine was 76% protective against cholera in this setting (95% CI 5% to 94%, P = 0.042 after adjusting for intake of dog meat or raw vegetables and not drinking boiled or bottled water most of the time. CONCLUSIONS/SIGNIFICANCE: This is the first study to explore the effectiveness of the reactive use of killed OCVs during a cholera outbreak. Our findings suggest that killed OCVs may have a role in controlling cholera outbreaks.

Successful comeback of the single-dose live oral cholera vaccine CVD 103-HgR.

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Herzog, Christian

2016-01-01

Effective and easy to administer cholera vaccines are in need more than ever, for at risk populations and travellers alike. In many parts of the world cholera is still endemic, causing outbreaks and constituting repeatedly serious public health problems. The oral live cholera vaccine CVD 103-HgR (Orochol, Mutachol), the first genetically modified organism (GMO) used as vaccine, was in its time (launched 1993, Switzerland) the ideal cholera vaccine: single-dose, protective efficacy of 80-100% against moderate to severe cholera, acting within 8 days and exhibiting excellent safety, indiscernible from placebo. However, there were strong headwinds: In the 1990s the indication for cholera vaccines was generally downplayed by experts and in 1997 the European Commission called for a moratorium of GMOs which blocked the registration in the European Union. Thus, demand for this vaccine remained low and in 2003 it was taken off the market for economic reasons. After a decade in obscurity it (Vaxchora) has resurfaced again, now produced in the U.S. and equipped with a U.S. FDA license (June 10, 2016). What had happened? This commentary gives a critical account of an almost unbelievable string of misadventures, emerging adverse circumstances and man-made failures which nearly killed this single-dose live oral cholera vaccine. The good news is that patience and persistence lead to success in the end, allowing good science to prevail for the benefit of those in need. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cholera Vaccination Campaign Contributes to Improved Knowledge Regarding Cholera and Improved Practice Relevant to Waterborne Disease in Rural Haiti

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Aibana, Omowunmi; Franke, Molly; Teng, Jessica; Hilaire, Johanne; Raymond, Max; Ivers, Louise C.

2013-01-01

Background Haiti's cholera epidemic has been devastating partly due to underlying weak infrastructure and limited clean water and sanitation. A comprehensive approach to cholera control is crucial, yet some have argued that oral cholera vaccination (OCV) might result in reduced hygiene practice among recipients. We evaluated the impact of an OCV campaign on knowledge and health practice in rural Haiti. Methodology/Principal Findings We administered baseline surveys on knowledge and practice relevant to cholera and waterborne disease to every 10th household during a census in rural Haiti in February 2012 (N = 811). An OCV campaign occurred from May–June 2012 after which we administered identical surveys to 518 households randomly chosen from the same region in September 2012. We compared responses pre- and post-OCV campaign. Post-vaccination, there was improved knowledge with significant increase in percentage of respondents with ≥3 correct responses on cholera transmission mechanisms (odds ratio[OR] 1.91; 95% confidence interval[CI] 1.52–2.40), preventive methods (OR 1.83; 95% CI 1.46–2.30), and water treatment modalities (OR 2.75; 95% CI 2.16–3.50). Relative to pre-vaccination, participants were more likely post-OCV to report always treating water (OR 1.62; 95% CI 1.28–2.05). Respondents were also more likely to report hand washing with soap and water >4 times daily post-vaccine (OR 1.30; 95% CI 1.03–1.64). Knowledge of treating water as a cholera prevention measure was associated with practice of always treating water (OR 1.47; 95% CI 1.14–1.89). Post-vaccination, knowledge was associated with frequent hand washing (OR 2.47; 95% CI 1.35–4.51). Conclusion An OCV campaign in rural Haiti was associated with significant improvement in cholera knowledge and practices related to waterborne disease. OCV can be part of comprehensive cholera control and reinforce, not detract from, other control efforts in Haiti. PMID:24278498

Cholera vaccination campaign contributes to improved knowledge regarding cholera and improved practice relevant to waterborne disease in rural Haiti.

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Omowunmi Aibana

2013-11-01

Full Text Available Haiti's cholera epidemic has been devastating partly due to underlying weak infrastructure and limited clean water and sanitation. A comprehensive approach to cholera control is crucial, yet some have argued that oral cholera vaccination (OCV might result in reduced hygiene practice among recipients. We evaluated the impact of an OCV campaign on knowledge and health practice in rural Haiti.We administered baseline surveys on knowledge and practice relevant to cholera and waterborne disease to every 10th household during a census in rural Haiti in February 2012 (N = 811. An OCV campaign occurred from May-June 2012 after which we administered identical surveys to 518 households randomly chosen from the same region in September 2012. We compared responses pre- and post-OCV campaign. Post-vaccination, there was improved knowledge with significant increase in percentage of respondents with ≥ 3 correct responses on cholera transmission mechanisms (odds ratio[OR] 1.91; 95% confidence interval[CI] 1.52-2.40, preventive methods (OR 1.83; 95% CI 1.46-2.30, and water treatment modalities (OR 2.75; 95% CI 2.16-3.50. Relative to pre-vaccination, participants were more likely post-OCV to report always treating water (OR 1.62; 95% CI 1.28-2.05. Respondents were also more likely to report hand washing with soap and water >4 times daily post-vaccine (OR 1.30; 95% CI 1.03-1.64. Knowledge of treating water as a cholera prevention measure was associated with practice of always treating water (OR 1.47; 95% CI 1.14-1.89. Post-vaccination, knowledge was associated with frequent hand washing (OR 2.47; 95% CI 1.35-4.51.An OCV campaign in rural Haiti was associated with significant improvement in cholera knowledge and practices related to waterborne disease. OCV can be part of comprehensive cholera control and reinforce, not detract from, other control efforts in Haiti.

Maximizing protection from use of oral cholera vaccines in developing country settings

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Desai, Sachin N; Cravioto, Alejandro; Sur, Dipika; Kanungo, Suman

2014-01-01

When oral vaccines are administered to children in lower- and middle-income countries, they do not induce the same immune responses as they do in developed countries. Although not completely understood, reasons for this finding include maternal antibody interference, mucosal pathology secondary to infection, malnutrition, enteropathy, and previous exposure to the organism (or related organisms). Young children experience a high burden of cholera infection, which can lead to severe acute dehydrating diarrhea and substantial mortality and morbidity. Oral cholera vaccines show variations in their duration of protection and efficacy between children and adults. Evaluating innate and memory immune response is necessary to understand V. cholerae immunity and to improve current cholera vaccine candidates, especially in young children. Further research on the benefits of supplementary interventions and delivery schedules may also improve immunization strategies. PMID:24861554

A retrospective analysis of oral cholera vaccine use, disease severity and deaths during an outbreak in South Sudan.

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Bekolo, Cavin Epie; van Loenhout, Joris Adriaan Frank; Rodriguez-Llanes, Jose Manuel; Rumunu, John; Ramadan, Otim Patrick; Guha-Sapir, Debarati

2016-09-01

To determine whether pre-emptive oral cholera vaccination reduces disease severity and mortality in people who develop cholera disease during an outbreak. The study involved a retrospective analysis of demographic and clinical data from 41 cholera treatment facilities in South Sudan on patients who developed cholera disease between 23 April and 20 July 2014 during a large outbreak, a few months after a pre-emptive oral vaccination campaign. Patients who developed severe dehydration were regarded as having a severe cholera infection. Vaccinated and unvaccinated patients were compared and multivariate logistic regression analysis was used to identify factors associated with developing severe disease or death. In total, 4115 cholera patients were treated at the 41 facilities: 1946 (47.3%) had severe disease and 62 (1.5%) deaths occurred. Multivariate analysis showed that patients who received two doses of oral cholera vaccine were 4.5-fold less likely to develop severe disease than unvaccinated patients (adjusted odds ratio, aOR: 0.22; 95% confidence interval, CI: 0.11-0.44). Moreover, those with severe cholera were significantly more likely to die than those without (aOR: 4.76; 95% CI: 2.33-9.77). Pre-emptive vaccination with two doses of oral cholera vaccine was associated with a significant reduction in the likelihood of developing severe cholera disease during an outbreak in South Sudan. Moreover, severe disease was the strongest predictor of death. Two doses of oral cholera vaccine should be used in emergencies to reduce the disease burden.

Effectiveness of one dose of oral cholera vaccine in response to an outbreak: a case-cohort study.

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Azman, Andrew S; Parker, Lucy A; Rumunu, John; Tadesse, Fisseha; Grandesso, Francesco; Deng, Lul L; Lino, Richard Laku; Bior, Bior K; Lasuba, Michael; Page, Anne-Laure; Ontweka, Lameck; Llosa, Augusto E; Cohuet, Sandra; Pezzoli, Lorenzo; Sodjinou, Dossou Vincent; Abubakar, Abdinasir; Debes, Amanda K; Mpairwe, Allan M; Wamala, Joseph F; Jamet, Christine; Lessler, Justin; Sack, David A; Quilici, Marie-Laure; Ciglenecki, Iza; Luquero, Francisco J

2016-11-01

Oral cholera vaccines represent a new effective tool to fight cholera and are licensed as two-dose regimens with 2-4 weeks between doses. Evidence from previous studies suggests that a single dose of oral cholera vaccine might provide substantial direct protection against cholera. During a cholera outbreak in May, 2015, in Juba, South Sudan, the Ministry of Health, Médecins Sans Frontières, and partners engaged in the first field deployment of a single dose of oral cholera vaccine to enhance the outbreak response. We did a vaccine effectiveness study in conjunction with this large public health intervention. We did a case-cohort study, combining information on the vaccination status and disease outcomes from a random cohort recruited from throughout the city of Juba with that from all the cases detected. Eligible cases were those aged 1 year or older on the first day of the vaccination campaign who sought care for diarrhoea at all three cholera treatment centres and seven rehydration posts throughout Juba. Confirmed cases were suspected cases who tested positive to PCR for Vibrio cholerae O1. We estimated the short-term protection (direct and indirect) conferred by one dose of cholera vaccine (Shanchol, Shantha Biotechnics, Hyderabad, India). Between Aug 9, 2015, and Sept 29, 2015, we enrolled 87 individuals with suspected cholera, and an 898-person cohort from throughout Juba. Of the 87 individuals with suspected cholera, 34 were classified as cholera positive, 52 as cholera negative, and one had indeterminate results. Of the 858 cohort members who completed a follow-up visit, none developed clinical cholera during follow-up. The unadjusted single-dose vaccine effectiveness was 80·2% (95% CI 61·5-100·0) and after adjusting for potential confounders was 87·3% (70·2-100·0). One dose of Shanchol was effective in preventing medically attended cholera in this study. These results support the use of a single-dose strategy in outbreaks in similar epidemiological

Effectiveness of reactive oral cholera vaccination in rural Haiti: a case-control study and bias-indicator analysis.

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Ivers, Louise C; Hilaire, Isabelle J; Teng, Jessica E; Almazor, Charles P; Jerome, J Gregory; Ternier, Ralph; Boncy, Jacques; Buteau, Josiane; Murray, Megan B; Harris, Jason B; Franke, Molly F

2015-03-01

Between April and June, 2012, a reactive cholera vaccination campaign was done in Haiti with an oral inactivated bivalent whole-cell vaccine. We aimed to assess the effectiveness of the vaccine in a case-control study and to assess the likelihood of bias in that study in a bias-indicator study. Residents of Bocozel or Grand Saline who were eligible for the vaccination campaign (ie, age ≥12 months, not pregnant, and living in the region at the time of the vaccine campaign) were included. In the primary case-control study, cases had acute watery diarrhoea, sought treatment at one of three participating cholera treatment units, and had a stool sample positive for cholera by culture. For each case, four control individuals who did not seek treatment for acute watery diarrhoea were matched by location of residence, enrolment time (within 2 weeks of the case), and age (1-4 years, 5-15 years, and >15 years). Cases in the bias-indicator study were individuals with acute watery diarrhoea with a negative stool sample for cholera. Controls were selected in the same manner as in the primary case-control study. Trained staff used standard laboratory procedures to do rapid tests and stool cultures from study cases. Participants were interviewed to collect data on sociodemographic characteristics, risk factors for cholera, and self-reported vaccination. Data were analysed by conditional logistic regression, adjusting for matching factors. From Oct 24, 2012, to March 9, 2014, 114 eligible individuals presented with acute watery diarrhoea and were enrolled, 25 of whom were subsequently excluded. 47 participants were analysed as cases in the vaccine effectiveness case-control study and 42 as cases in the bias-indicator study. 33 (70%) of 47 cholera cases self-reported vaccination versus 167 (89%) of 188 controls (vaccine effectiveness 63%, 95% CI 8-85). 27 (57%) of 47 cases had certified vaccination versus 147 (78%) of 188 controls (vaccine effectiveness 58%, 13-80). Neither self

First outbreak response using an oral cholera vaccine in Africa: vaccine coverage, acceptability and surveillance of adverse events, Guinea, 2012.

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Francisco J Luquero

Full Text Available BACKGROUND: Despite World Health Organization (WHO prequalification of two safe and effective oral cholera vaccines (OCV, concerns about the acceptability, potential diversion of resources, cost and feasibility of implementing timely campaigns has discouraged their use. In 2012, the Ministry of Health of Guinea, with the support of Médecins Sans Frontières organized the first mass vaccination campaign using a two-dose OCV (Shanchol as an additional control measure to respond to the on-going nationwide epidemic. Overall, 316,250 vaccines were delivered. Here, we present the results of vaccination coverage, acceptability and surveillance of adverse events. METHODOLOGY/PRINCIPAL FINDINGS: We performed a cross-sectional cluster survey and implemented adverse event surveillance. The study population included individuals older than 12 months, eligible for vaccination, and residing in the areas targeted for vaccination (Forécariah and Boffa, Guinea. Data sources were household interviews with verification by vaccination card and notifications of adverse events from surveillance at vaccination posts and health centres. In total 5,248 people were included in the survey, 3,993 in Boffa and 1,255 in Forécariah. Overall, 89.4% [95%CI:86.4-91.8%] and 87.7% [95%CI:84.2-90.6%] were vaccinated during the first round and 79.8% [95%CI:75.6-83.4%] and 82.9% [95%CI:76.6-87.7%] during the second round in Boffa and Forécariah respectively. The two dose vaccine coverage (including card and oral reporting was 75.8% [95%CI: 71.2-75.9%] in Boffa and 75.9% [95%CI: 69.8-80.9%] in Forécariah respectively. Vaccination coverage was higher in children. The main reason for non-vaccination was absence. No severe adverse events were notified. CONCLUSIONS/SIGNIFICANCE: The well-accepted mass vaccination campaign reached high coverage in a remote area with a mobile population. Although OCV should not be foreseen as the long-term solution for global cholera control, they

Neighborhood-targeted and case-triggered use of a single dose of oral cholera vaccine in an urban setting: Feasibility and vaccine coverage.

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Parker, Lucy A; Rumunu, John; Jamet, Christine; Kenyi, Yona; Lino, Richard Laku; Wamala, Joseph F; Mpairwe, Allan M; Muller, Vincent; Llosa, Augusto E; Uzzeni, Florent; Luquero, Francisco J; Ciglenecki, Iza; Azman, Andrew S

2017-06-01

In June 2015, a cholera outbreak was declared in Juba, South Sudan. In addition to standard outbreak control measures, oral cholera vaccine (OCV) was proposed. As sufficient doses to cover the at-risk population were unavailable, a campaign using half the standard dosing regimen (one-dose) targeted high-risk neighborhoods and groups including neighbors of suspected cases. Here we report the operational details of this first public health use of a single-dose regimen of OCV and illustrate the feasibility of conducting highly targeted vaccination campaigns in an urban area. Neighborhoods of the city were prioritized for vaccination based on cumulative attack rates, active transmission and local knowledge of known cholera risk factors. OCV was offered to all persons older than 12 months at 20 fixed sites and to select groups, including neighbors of cholera cases after the main campaign ('case-triggered' interventions), through mobile teams. Vaccination coverage was estimated by multi-stage surveys using spatial sampling techniques. 162,377 individuals received a single-dose of OCV in the targeted neighborhoods. In these neighborhoods vaccine coverage was 68.8% (95% Confidence Interval (CI), 64.0-73.7) and was highest among children ages 5-14 years (90.0%, 95% CI 85.7-94.3), with adult men being less likely to be vaccinated than adult women (Relative Risk 0.81, 95% CI: 0.68-0.96). In the case-triggered interventions, each lasting 1-2 days, coverage varied (range: 30-87%) with an average of 51.0% (95% CI 41.7-60.3). Vaccine supply constraints and the complex realities where cholera outbreaks occur may warrant the use of flexible alternative vaccination strategies, including highly-targeted vaccination campaigns and single-dose regimens. We showed that such campaigns are feasible. Additional work is needed to understand how and when to use different strategies to best protect populations against epidemic cholera.

Protection against cholera from killed whole-cell oral cholera vaccines: a systematic review and meta-analysis.

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Bi, Qifang; Ferreras, Eva; Pezzoli, Lorenzo; Legros, Dominique; Ivers, Louise C; Date, Kashmira; Qadri, Firdausi; Digilio, Laura; Sack, David A; Ali, Mohammad; Lessler, Justin; Luquero, Francisco J; Azman, Andrew S

2017-10-01

Killed whole-cell oral cholera vaccines (kOCVs) are becoming a standard cholera control and prevention tool. However, vaccine efficacy and direct effectiveness estimates have varied, with differences in study design, location, follow-up duration, and vaccine composition posing challenges for public health decision making. We did a systematic review and meta-analysis to generate average estimates of kOCV efficacy and direct effectiveness from the available literature. For this systematic review and meta-analysis, we searched PubMed, Embase, Scopus, and the Cochrane Review Library on July 9, 2016, and ISI Web of Science on July 11, 2016, for randomised controlled trials and observational studies that reported estimates of direct protection against medically attended confirmed cholera conferred by kOCVs. We included studies published on any date in English, Spanish, French, or Chinese. We extracted from the published reports the primary efficacy and effectiveness estimates from each study and also estimates according to number of vaccine doses, duration, and age group. The main study outcome was average efficacy and direct effectiveness of two kOCV doses, which we estimated with random-effect models. This study is registered with PROSPERO, number CRD42016048232. Seven trials (with 695 patients with cholera) and six observational studies (217 patients with cholera) met the inclusion criteria, with an average two-dose efficacy of 58% (95% CI 42-69, I 2 =58%) and effectiveness of 76% (62-85, I 2 =0). Average two-dose efficacy in children younger than 5 years (30% [95% CI 15-42], I 2 =0%) was lower than in those 5 years or older (64% [58-70], I 2 =0%; pcholera for at least 3 years. One kOCV dose provides at least short-term protection, which has important implications for outbreak management. kOCVs are effective tools for cholera control. The Bill & Melinda Gates Foundation. Copyright This is an Open Access article published under the CC BY 3.0 IGO license which permits

Reduction of travellers' diarrhoea by WC/rBS oral cholera vaccine in young, high-risk travellers.

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Torrell, Josep Ma Ramon; Aumatell, Cristina Masuet; Ramos, Sergi Morchon; Mestre, Laura Gavaldà; Salas, Carme Micheo

2009-06-19

A bidirectional cohort study investigates whether pre-travel vaccination with whole cell/recombinant B subunit inactivated, killed oral cholera vaccine reduces the incidence of diarrhoea in young adult travellers to high-risk areas. Risk of travellers' diarrhoea was assessed according to destination and reason for travel in high-risk travellers of a travel clinic in Barcelona, Spain. Those at high-risk between January and December 2005 were advised on water/food safety and hygiene. High-risk travellers between January and December 2006 were additionally vaccinated with WC/rBS oral cholera vaccine. Data regarding diarrhoea were gathered by structured telephone interview or e-mailed questionnaire following the travellers' return. The incidence of diarrhoea in the group vaccinated with WC/rBS oral cholera vaccine (n=321) was 17.4%, compared with 39.7% in the non-vaccinated group (n=337) (adjusted risk ratio 0.40). The first episode was significantly shorter in the vaccinated group (mean 2.3 days) than in the non-vaccinated group (mean 3.8 days) (pyoung, high-risk travellers. Vaccination with the WC/rBS oral cholera vaccine as well as food safety and hygiene advice could offer effective means of reducing the risk of diarrhoea while abroad.

Cost Evaluation of a Government-Conducted Oral Cholera Vaccination Campaign-Haiti, 2013.

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Routh, Janell A; Sreenivasan, Nandini; Adhikari, Bishwa B; Andrecy, Lesly L; Bernateau, Margarette; Abimbola, Taiwo; Njau, Joseph; Jackson, Ernsley; Juin, Stanley; Francois, Jeannot; Tohme, Rania A; Meltzer, Martin I; Katz, Mark A; Mintz, Eric D

2017-10-01

The devastating 2010 cholera epidemic in Haiti prompted the government to introduce oral cholera vaccine (OCV) in two high-risk areas of Haiti. We evaluated the direct costs associated with the government's first vaccine campaign implemented in August-September 2013. We analyzed data for major cost categories and assessed the efficiency of available campaign resources to vaccinate the target population. For a target population of 107,906 persons, campaign costs totaled $624,000 and 215,295 OCV doses were dispensed. The total vaccine and operational cost was $2.90 per dose; vaccine alone cost $1.85 per dose, vaccine delivery and administration $0.70 per dose, and vaccine storage and transport $0.35 per dose. Resources were greater than needed-our analyses suggested that approximately 2.5-6 times as many persons could have been vaccinated during this campaign without increasing the resources allocated for vaccine delivery and administration. These results can inform future OCV campaigns in Haiti.

Knowledge of, attitudes toward, and preventive practices relating to cholera and oral cholera vaccine among urban high-risk groups: findings of a cross-sectional study in Dhaka, Bangladesh

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Wahed, Tasnuva; Kaukab, Sheikh Shah Tanvir; Saha, Nirod Chandra; Khan, Iqbal Ansary; Khanam, Farhana; Chowdhury, Fahima; Saha, Amit; Khan, Ashraful Islam; Siddik, Ashraf Uddin; Cravioto, Alejandro; Qadri, Firdausi; Uddin, Jasim

2013-01-01

Background In endemic countries such as Bangladesh, consequences of cholera place an enormous financial and social burden on patients and their families. Cholera vaccines not only provide health benefits to susceptible populations but also have effects on the earning capabilities and financial stability of the family. Community-based research and evaluations are necessary to understand perceptions about and practices of the community relating to cholera and oral cholera vaccines. This may hel...

Potential impact of reactive vaccination in controlling cholera outbreaks: an exploratory analysis using a Zimbabwean experience.

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Kim, Sun-Young; Choi, Yeongchull; Mason, Peter R; Rusakaniko, Simbarashe; Goldie, Sue J

2011-09-05

To contain ongoing cholera outbreaks, the World Health Organization has suggested that reactive vaccination should be considered in addition to its previous control measures. To explore the potential impact of a hypothetical reactive oral cholera vaccination using the example of the recent large-scale cholera outbreak in Zimbabwe. This was a retrospective cost-effectiveness analysis calculating the health and economic burden of the cholera outbreak in Zimbabwe with and without reactive vaccination. The primary outcome measure was incremental cost per disability-adjusted life year (DALY) averted. Under the base-case assumptions (assuming 50% coverage among individuals aged ≥2 years), reactive vaccination could have averted 1 320 deaths and 23 650 DALYs. Considering herd immunity, the corresponding values would have been 2 920 deaths and 52 360 DALYs averted. The total vaccination costs would have been ~$74 million and ~$21 million, respectively, with per-dose vaccine price of US$5 and $1. The incremental costs per DALY averted of reactive vaccination were $2 770 and $370, respectively, for vaccine price set at $5 and $1. Assuming herd immunity, the corresponding cost was $980 with vaccine price of $5, and the programme was cost-saving with a vaccine price of $1. Results were most sensitive to case-fatality rate, per-dose vaccine price, and the size of the outbreak. Reactive vaccination has the potential to be a cost-effective measure to contain cholera outbreaks in countries at high risk. However, the feasibility of implementation should be further evaluated, and caution is warranted in extrapolating the findings to different settings in the absence of other in-depth studies.

Potential for Controlling Cholera Using a Ring Vaccination Strategy: Re-analysis of Data from a Cluster-Randomized Clinical Trial.

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Mohammad Ali

2016-09-01

Full Text Available Vaccinating a buffer of individuals around a case (ring vaccination has the potential to target those who are at highest risk of infection, reducing the number of doses needed to control a disease. We explored the potential vaccine effectiveness (VE of oral cholera vaccines (OCVs for such a strategy.This analysis uses existing data from a cluster-randomized clinical trial in which OCV or placebo was given to 71,900 participants in Kolkata, India, from 27 July to 10 September 2006. Cholera surveillance was then conducted on 144,106 individuals living in the study area, including trial participants, for 5 y following vaccination. First, we explored the risk of cholera among contacts of cholera patients, and, second, we measured VE among individuals living within 25 m of cholera cases between 8 and 28 d after onset of the index case. For the first analysis, individuals living around each index case identified during the 5-y period were assembled using a ring to define cohorts of individuals exposed to cholera index cases. An index control without cholera was randomly selected for each index case from the same population, matched by age group, and individuals living around each index control were assembled using a ring to define cohorts not exposed to cholera cases. Cholera attack rates among the exposed and non-exposed cohorts were compared using different distances from the index case/control to define the rings and different time frames to define the period at risk. For the VE analysis, the exposed cohorts were further stratified according to the level of vaccine coverage into high and low coverage strata. Overall VE was assessed by comparing the attack rates between high and low vaccine coverage strata irrespective of individuals' vaccination status, and indirect VE was assessed by comparing the attack rates among unvaccinated members between high and low vaccine coverage strata. Cholera risk among the cohort exposed to cholera cases was 5

Oral cholera vaccine coverage in hard-to-reach fishermen communities after two mass Campaigns, Malawi, 2016.

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Sauvageot, Delphine; Saussier, Christel; Gobeze, Abebe; Chipeta, Sikhona; Mhango, Innocent; Kawalazira, Gift; Mengel, Martin A; Legros, Dominique; Cavailler, Philippe; M'bang'ombe, Maurice

2017-09-12

From December 2015 to August 2016, a large epidemic of cholera affected the fishermen of Lake Chilwa in Malawi. A first reactive Oral Cholera Vaccines (OCV) campaign was organized, in February, in a 2km radius of the lake followed by a preemptive one, conducted in November, in a 25km radius. We present the vaccine coverage reached in hard-to-reach population using simplified delivery strategies. We conducted two-stage random-sampling cross-sectional surveys among individuals living in a 2km and 25km radius of Lake Chilwa (islands and floating homes included). Individuals aged 12months and older from Machinga and Zomba districts were sampled: 43 clusters of 14 households were surveyed. Simplified strategies were used for those living in islands and floating homes: self- delivery and community-supervised delivery of the second dose. Vaccine coverage (VC) for at-least-two-doses was estimated taking into account sampling weights and design effects. A total of 1176 households were surveyed (2.7% of non-response). Among the 2833 individuals living in the 2km radius of Lake and the 2915 in the 25km radius: 457 (16.1%) and 239 (8.2%) lived in floating homes or on islands at some point in the year, respectively. For the overall population, VC was 75.6% and 54.2%, respectively. In the 2km radius, VC was 92.2% for those living on the lake at some point of the year: 271 (64.8%) used the simplified strategies. The main reasons for non-vaccination were absence during the campaign and vaccine shortage. Few adverse events occurring in the 24h following vaccination was reported. We reached a high two-dose coverage of the most at-risk population using simplified delivery strategies. Because of the high fishermen mobility, regular catch-up campaigns or another strategy specifically targeting fishermen need to be assessed for more efficient vaccines use. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

First Outbreak Response Using an Oral Cholera Vaccine in Africa: Vaccine Coverage, Acceptability and Surveillance of Adverse Events, Guinea, 2012

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Luquero, Francisco J.; Grout, Lise; Ciglenecki, Iza; Sakoba, Keita; Traore, Bala; Heile, Melat; Dialo, Alpha Amadou; Itama, Christian; Serafini, Micaela; Legros, Dominique; Grais, Rebecca F.

2013-01-01

Background Despite World Health Organization (WHO) prequalification of two safe and effective oral cholera vaccines (OCV), concerns about the acceptability, potential diversion of resources, cost and feasibility of implementing timely campaigns has discouraged their use. In 2012, the Ministry of Health of Guinea, with the support of Médecins Sans Frontières organized the first mass vaccination campaign using a two-dose OCV (Shanchol) as an additional control measure to respond to the on-going nationwide epidemic. Overall, 316,250 vaccines were delivered. Here, we present the results of vaccination coverage, acceptability and surveillance of adverse events. Methodology/Principal Findings We performed a cross-sectional cluster survey and implemented adverse event surveillance. The study population included individuals older than 12 months, eligible for vaccination, and residing in the areas targeted for vaccination (Forécariah and Boffa, Guinea). Data sources were household interviews with verification by vaccination card and notifications of adverse events from surveillance at vaccination posts and health centres. In total 5,248 people were included in the survey, 3,993 in Boffa and 1,255 in Forécariah. Overall, 89.4% [95%CI:86.4–91.8%] and 87.7% [95%CI:84.2–90.6%] were vaccinated during the first round and 79.8% [95%CI:75.6–83.4%] and 82.9% [95%CI:76.6–87.7%] during the second round in Boffa and Forécariah respectively. The two dose vaccine coverage (including card and oral reporting) was 75.8% [95%CI: 71.2–75.9%] in Boffa and 75.9% [95%CI: 69.8–80.9%] in Forécariah respectively. Vaccination coverage was higher in children. The main reason for non-vaccination was absence. No severe adverse events were notified. Conclusions/Significance The well-accepted mass vaccination campaign reached high coverage in a remote area with a mobile population. Although OCV should not be foreseen as the long-term solution for global cholera control, they should be

Improving immunization approaches to cholera.

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Saha, Amit; Rosewell, Alexander; Hayen, Andrew; MacIntyre, C Raina; Qadri, Firdausi

2017-03-01

Cholera's impact is greatest in resource-limited countries. In the last decade several large epidemics have led to a global push to improve and implement the tools for cholera prevention and control. Areas covered: PubMed, Google Scholar and the WHO website were searched to review the literature and summarize the current status of cholera vaccines to make recommendations on improving immunization approaches to cholera. Oral cholera vaccines (OCVs) have demonstrated their effectiveness in endemic, outbreak response and emergency settings, highlighting their potential for wider adoption. While two doses of the currently available OCVs are recommended by manufacturers, a single dose would be easier to implement. Encouragingly, recent studies have shown that cold chain requirements may no longer be essential. The establishment of the global OCV stockpile in 2013 has been a major advance in cholera preparedness. New killed and live-attenuated vaccines are being actively explored as candidate vaccines for endemic settings and/or as a traveller's vaccine. The recent advances in cholera vaccination approaches should be considered in the global cholera control strategy. Expert commentary: The development of affordable cholera vaccines is a major success to improve cholera control. New vaccines and country specific interventions will further reduce the burden of this disease globally.

Immunogenicity of a killed bivalent (O1 and O139 whole cell oral cholera vaccine, Shanchol, in Haiti.

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Richelle C Charles

2014-05-01

Full Text Available Studies of the immunogenicity of the killed bivalent whole cell oral cholera vaccine, Shanchol, have been performed in historically cholera-endemic areas of Asia. There is a need to assess the immunogenicity of the vaccine in Haiti and other populations without historical exposure to Vibrio cholerae.We measured immune responses after administration of Shanchol, in 25 adults, 51 older children (6-17 years, and 47 younger children (1-5 years in Haiti, where cholera was introduced in 2010. A≥4-fold increase in vibriocidal antibody titer against V. cholerae O1 Ogawa was observed in 91% of adults, 74% of older children, and 73% of younger children after two doses of Shanchol; similar responses were observed against the Inaba serotype. A≥2-fold increase in serum O-antigen specific polysaccharide IgA antibody levels against V. cholerae O1 Ogawa was observed in 59% of adults, 45% of older children, and 61% of younger children; similar responses were observed against the Inaba serotype. We compared immune responses in Haitian individuals with age- and blood group-matched individuals from Bangladesh, a historically cholera-endemic area. The geometric mean vibriocidal titers after the first dose of vaccine were lower in Haitian than in Bangladeshi vaccinees. However, the mean vibriocidal titers did not differ between the two groups after the second dose of the vaccine.A killed bivalent whole cell oral cholera vaccine, Shanchol, is highly immunogenic in Haitian adults and children. A two-dose regimen may be important in Haiti, and other populations lacking previous repeated exposures to V. cholerae.

Using Mobile Health (mHealth) and geospatial mapping technology in a mass campaign for reactive oral cholera vaccination in rural Haiti.

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Teng, Jessica E; Thomson, Dana R; Lascher, Jonathan S; Raymond, Max; Ivers, Louise C

2014-01-01

In mass vaccination campaigns, large volumes of data must be managed efficiently and accurately. In a reactive oral cholera vaccination (OCV) campaign in rural Haiti during an ongoing epidemic, we used a mobile health (mHealth) system to manage data on 50,000 participants in two isolated communities. Data were collected using 7-inch tablets. Teams pre-registered and distributed vaccine cards with unique barcodes to vaccine-eligible residents during a census in February 2012. First stored on devices, data were uploaded nightly via Wi-fi to a web-hosted database. During the vaccination campaign between April and June 2012, residents presented their cards at vaccination posts and their barcodes were scanned. Vaccinee data from the census were pre-loaded on tablets to autopopulate the electronic form. Nightly analysis of the day's community coverage informed the following day's vaccination strategy. We generated case-finding reports allowing us to identify those who had not yet been vaccinated. During 40 days of vaccination, we collected approximately 1.9 million pieces of data. A total of 45,417 people received at least one OCV dose; of those, 90.8% were documented to have received 2 doses. Though mHealth required up-front financial investment and training, it reduced the need for paper registries and manual data entry, which would have been costly, time-consuming, and is known to increase error. Using Global Positioning System coordinates, we mapped vaccine posts, population size, and vaccine coverage to understand the reach of the campaign. The hardware and software were usable by high school-educated staff. The use of mHealth technology in an OCV campaign in rural Haiti allowed timely creation of an electronic registry with population-level census data, and a targeted vaccination strategy in a dispersed rural population receiving a two-dose vaccine regimen. The use of mHealth should be strongly considered in mass vaccination campaigns in future initiatives.

Socio-cultural determinants of anticipated acceptance of an oral cholera vaccine in Western Kenya.

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Sundaram, N; Schaetti, C; Chaignat, C-L; Hutubessy, R; Nyambedha, E O; Mbonga, L A; Weiss, M G

2013-03-01

Determinants of anticipated acceptance of an oral cholera vaccine (OCV) were studied in urban and rural communities of Western Kenya. An explanatory model interview administered to 379 community residents assessed anticipated vaccine acceptance at various prices from no cost to full-cost recovery, socio-cultural features of cholera and social characteristics. Nearly all (99%) residents indicated willingness to accept a no-cost OCV, 95% at a price of US$ 0·8, 73% at US$ 4·2 and 59% at US$ 8·4. Logistic regression models analysed socio-cultural determinants of anticipated OCV acceptance. Prominence of non-specific symptoms for cholera was negatively associated with acceptance. A cholera-specific symptom (thirst), self-help referring to prayer, income and education were positively associated. In the high-cost model, education was no longer significant and reliance on herbal treatment was a significant determinant of vaccine non-acceptance. Findings suggest high motivation for OCVs, if affordable. Socio-cultural determinants are better predictors of anticipated acceptance than socio-demographic factors alone.

Oral Cholera Vaccination Delivery Cost in Low- and Middle-Income Countries: An Analysis Based on Systematic Review.

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Mogasale, Vittal; Ramani, Enusa; Wee, Hyeseung; Kim, Jerome H

2016-12-01

Use of the oral cholera vaccine (OCV) is a vital short-term strategy to control cholera in endemic areas with poor water and sanitation infrastructure. Identifying, estimating, and categorizing the delivery costs of OCV campaigns are useful in analyzing cost-effectiveness, understanding vaccine affordability, and in planning and decision making by program managers and policy makers. To review and re-estimate oral cholera vaccination program costs and propose a new standardized categorization that can help in collation, analysis, and comparison of delivery costs across countries. Peer reviewed publications listed in PubMed database, Google Scholar and World Health Organization (WHO) websites and unpublished data from organizations involved in oral cholera vaccination. The publications and reports containing oral cholera vaccination delivery costs, conducted in low- and middle-income countries based on World Bank Classification. Limits are humans and publication date before December 31st, 2014. No participants are involved, only costs are collected. Oral cholera vaccination and cost estimation. A systematic review was conducted using pre-defined inclusion and exclusion criteria. Cost items were categorized into four main cost groups: vaccination program preparation, vaccine administration, adverse events following immunization and vaccine procurement; the first three groups constituting the vaccine delivery costs. The costs were re-estimated in 2014 US dollars (US$) and in international dollar (I$). Ten studies were identified and included in the analysis. The vaccine delivery costs ranged from US$0.36 to US$ 6.32 (in US$2014) which was equivalent to I$ 0.99 to I$ 16.81 (in I$2014). The vaccine procurement costs ranged from US$ 0.29 to US$ 29.70 (in US$2014), which was equivalent to I$ 0.72 to I$ 78.96 (in I$2014). The delivery costs in routine immunization systems were lowest from US$ 0.36 (in US$2014) equivalent to I$ 0.99 (in I$2014). The reported cost categories

A single-dose antihelminthic treatment does not influence immunogenicity of a meningococcal and a cholera vaccine in Gabonese school children.

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Brückner, Sina; Agnandji, Selidji Todagbe; Elias, Johannes; Berberich, Stefan; Bache, Emmanuel; Fernandes, José; Loembe, Marguerite Massinga; Hass, Johanna; Lell, Bertrand; Mordmüller, Benjamin; Adegnika, Ayola Akim; Kremsner, Peter; Esen, Meral

2016-10-17

We recently described the effect of a single-dose antihelminthic treatment on vaccine immunogenicity to a seasonal influenza vaccine. Here we report the effect of antihelminthics on the immunogenicity of a meningococcal vaccine and a cholera vaccine in primary school children living in Lambaréné, Gabon. Since infection with helminths remains a major public health problem and the influence on cognitive and physical development as well as the immunomodulatory effects are well established, we investigated if a single-dose antihelminthic treatment prior to immunization positively influences antibody titers and vaccine-specific memory B-cells. In this placebo-controlled, double-blind trial the effect of a single-dose antihelminthic treatment prior to immunization with a meningococcal as well as with a cholera vaccine was investigated. Anti-meningococcal antibodies were assessed by serum bactericidal assay, cholera vaccine-specific antibody titers by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Day 0; vaccination), four weeks (Day 28) and 12weeks (Day 84) following vaccination. Meningococcal and cholera vaccine-specific memory B-cells were measured at Day 0 and 84 by vaccine-specific Enzyme-linked Immunospot (ELISpot) assay. The helminth burden of the participants was assessed four weeks before vaccination (Day -28) and at Day 84 by the Merthiolate-Iodine-Formaldehyde technique. Out of 280 screened school children, 96 received a meningococcal vaccine and 89 a cholera vaccine following allocation to either the single-dose antihelminthic treatment group or the placebo group. Bactericidal antibody titers increased following immunization with the meningococcal vaccine at Day 28 and Day 84 in 68 participants for serogroup A, and in 80 participants for serogroup C. The cholera vaccine titers increased in all participants with a peak at Day 28. The number of memory B-cells increased following vaccination compared to baseline. There was no statistically significant

Socio-cultural determinants of anticipated acceptance of an oral cholera vaccine in Western Kenya

OpenAIRE

SUNDARAM, N.; SCHAETTI, C.; CHAIGNAT, C.-L.; HUTUBESSY, R.; NYAMBEDHA, E. O.; MBONGA, L. A.; WEISS, M. G.

2012-01-01

SUMMARY Determinants of anticipated acceptance of an oral cholera vaccine (OCV) were studied in urban and rural communities of Western Kenya. An explanatory model interview administered to 379 community residents assessed anticipated vaccine acceptance at various prices from no cost to full-cost recovery, socio-cultural features of cholera and social characteristics. Nearly all (99%) residents indicated willingness to accept a no-cost OCV, 95% at a price of US$ 0?8, 73% at US$ 4?2 and 59% at ...

Oral Cholera Vaccination Delivery Cost in Low- and Middle-Income Countries: An Analysis Based on Systematic Review

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Ramani, Enusa; Wee, Hyeseung; Kim, Jerome H.

2016-01-01

Background Use of the oral cholera vaccine (OCV) is a vital short-term strategy to control cholera in endemic areas with poor water and sanitation infrastructure. Identifying, estimating, and categorizing the delivery costs of OCV campaigns are useful in analyzing cost-effectiveness, understanding vaccine affordability, and in planning and decision making by program managers and policy makers. Objectives To review and re-estimate oral cholera vaccination program costs and propose a new standardized categorization that can help in collation, analysis, and comparison of delivery costs across countries. Data sources Peer reviewed publications listed in PubMed database, Google Scholar and World Health Organization (WHO) websites and unpublished data from organizations involved in oral cholera vaccination. Study eligibility criteria The publications and reports containing oral cholera vaccination delivery costs, conducted in low- and middle-income countries based on World Bank Classification. Limits are humans and publication date before December 31st, 2014. Participants No participants are involved, only costs are collected. Intervention Oral cholera vaccination and cost estimation. Study appraisal and synthesis method A systematic review was conducted using pre-defined inclusion and exclusion criteria. Cost items were categorized into four main cost groups: vaccination program preparation, vaccine administration, adverse events following immunization and vaccine procurement; the first three groups constituting the vaccine delivery costs. The costs were re-estimated in 2014 US dollars (US$) and in international dollar (I$). Results Ten studies were identified and included in the analysis. The vaccine delivery costs ranged from US$0.36 to US$ 6.32 (in US$2014) which was equivalent to I$ 0.99 to I$ 16.81 (in I$2014). The vaccine procurement costs ranged from US$ 0.29 to US$ 29.70 (in US$2014), which was equivalent to I$ 0.72 to I$ 78.96 (in I$2014). The delivery costs in

Oral Cholera Vaccine Coverage during an Outbreak and Humanitarian Crisis, Iraq, 2015.

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Lam, Eugene; Al-Tamimi, Wasan; Russell, Steven Paul; Butt, Muhammad Obaid-Ul Islam; Blanton, Curtis; Musani, Altaf Sadrudin; Date, Kashmira

2017-01-01

During November-December 2015, as part of the 2015 cholera outbreak response in Iraq, the Iraqi Ministry of Health targeted ≈255,000 displaced persons >1 year of age with 2 doses of oral cholera vaccine (OCV). All persons who received vaccines were living in selected refugee camps, internally displaced persons camps, and collective centers. We conducted a multistage cluster survey to obtain OCV coverage estimates in 10 governorates that were targeted during the campaign. In total, 1,226 household and 5,007 individual interviews were conducted. Overall, 2-dose OCV coverage in the targeted camps was 87% (95% CI 85%-89%). Two-dose OCV coverage in the 3 northern governorates (91%; 95% CI 87%-94%) was higher than that in the 7 southern and central governorates (80%; 95% CI 77%-82%). The experience in Iraq demonstrates that OCV campaigns can be successfully implemented as part of a comprehensive response to cholera outbreaks among high-risk populations in conflict settings.

A cost-benefit analysis of programmatic use of CVD 103-HgR live oral cholera vaccine in a high-risk population.

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Cookson, S T; Stamboulian, D; Demonte, J; Quero, L; Martinez de Arquiza, C; Aleman, A; Lepetic, A; Levine, M M

1997-02-01

Cholera spread to Latin America in 1991; subsequently, cholera vaccination was considered as an interim intervention until long-term solutions involving improved water supplies and sanitation could be introduced. Three successive summer cholera outbreaks in northern Argentina and the licensing of the new single-dose oral cholera vaccine, CVD 103-HgR, raised questions of the cost and benefit of using this new vaccine. This study explored the potential benefits to the Argentine Ministry of Health of treatment costs averted, versus the costs of vaccination with CVD 103-HgR in the relatively confined population of northern Argentina affected by the cholera outbreaks. Water supplies and sanitation in this area are poor but a credible infrastructure for vaccine delivery exists. In our cost-benefit model of a 3-year period (1992-1994) with an annual incidence of 2.5 case-patients per 1000 population and assumptions of vaccine efficacy of 75% and coverage of 75%, vaccination of targeted high risk groups would prevent 1265 cases. Assuming a cost of US$602 per treated case and of US$1.50 per dose of vaccine, the total discounted savings from use of vaccine in the targeted groups would be US$132,100. The projected savings would be altered less by vaccine coverage (range 75-90%) or efficacy (60-85%) changes than by disease incidence changes. Our analysis underestimated the true costs of cholera in Argentina because we included only medical expenditures; Indirect losses to trade and tourism had the greatest economic impact. However, vaccination with CVD 103-HgR was still cost-beneficial in the base case.

A retrospective analysis of oral cholera vaccine use, disease severity and deaths during an outbreak in South Sudan

NARCIS (Netherlands)

Bekolo, C.E.; Loenhout, J.A. van; Rodriguez-Llanes, J.M.; Rumunu, J.; Ramadan, O.P.; Guha-Sapir, D.

2016-01-01

OBJECTIVE: To determine whether pre-emptive oral cholera vaccination reduces disease severity and mortality in people who develop cholera disease during an outbreak. METHODS: The study involved a retrospective analysis of demographic and clinical data from 41 cholera treatment facilities in South

Traffic of antibody-secreting cells after immunization with a liposome-associated, CpG-ODN-adjuvanted oral cholera vaccine.

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Somroop, Srinuan; Tongtawe, Pongsri; Chaisri, Urai; Tapchaisri, Pramuan; Chongsa-nguan, Manas; Srimanote, Potjanee; Chaicumpa, Wanpen

2006-12-01

An oral cholera vaccine made up of heat-treated recombinant cholera toxin (rCT), V. cholerae lipopolysaccharide (LPS), and recombinant toxin-co-regulated pili subunit A (rTcpA), entrapped in liposomes in the presence of unmethylated bacterial CpG-DNA (ODN#1826) was used to orally immunize a group of eight week old rats. A booster dose was given 14 days later. Control rats received placebo (vaccine diluent). The kinetics of the immune response were investigated by enumerating the antigen specific-antibody secreting cells (ASC) in the blood circulation and intestinal lamina propria using the ELISPOT assay and a histo-immunofluorescence assay (IFA), respectively. ASC of all antigenic specificities were detected in the blood of the vaccinated rats as early as two days after the booster dose. The numbers of LPS-ASC and TcpA-ASC in the blood were at their peak at day 3 post booster while the number of CT-ASC was highest at day 4 after the booster immunization. At day 13 post immunization, no ASC were detected in the blood. A several fold increase in the number of ASC of all antigenic specificities in the lamina propria above the background numbers of the control animals were found in all vaccinated rats at days 6 and 13 post booster (earlier and later time points were not studied). Vibriocidal antibody and specific antibodies to CT, LPS and TcpA were detected in 57.1% and 52.4%, 14.3%, and 19.0% of the orally vaccinated rats, respectively. The data indicated that rats orally primed with the vaccine could produce a rapid anamnestic response after re-exposure to the V. cholerae antigens. Thus, a single dose of the vaccine is expected to elicit a similar anamnestic immune response in people from cholera endemic areas who have been naturally primed to V. cholerae antigens, while two doses at a 14 day interval should be adequate for a traveler to a disease endemicarea.

Chloroplast-derived vaccine antigens confer dual immunity against cholera and malaria by oral or injectable delivery.

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Davoodi-Semiromi, Abdoreza; Schreiber, Melissa; Nalapalli, Samson; Verma, Dheeraj; Singh, Nameirakpam D; Banks, Robert K; Chakrabarti, Debopam; Daniell, Henry

2010-02-01

Cholera and malaria are major diseases causing high mortality. The only licensed cholera vaccine is expensive; immunity is lost in children within 3 years and adults are not fully protected. No vaccine is yet available for malaria. Therefore, in this study, the cholera toxin-B subunit (CTB) of Vibrio cholerae fused to malarial vaccine antigens apical membrane antigen-1 (AMA1) and merozoite surface protein-1 (MSP1) was expressed in lettuce and tobacco chloroplasts. Southern blot analysis confirmed homoplasmy and stable integration of transgenes. CTB-AMA1 and CTB-MSP1 fusion proteins accumulated up to 13.17% and 10.11% (total soluble protein, TSP) in tobacco and up to 7.3% and 6.1% (TSP) in lettuce, respectively. Nine groups of mice (n = 10/group) were immunized subcutaneously (SQV) or orally (ORV) with purified antigens or transplastomic tobacco leaves. Significant levels of antigen-specific antibody titres of immunized mice completely inhibited proliferation of the malarial parasite and cross-reacted with the native parasite proteins in immunoblots and immunofluorescence studies. Protection against cholera toxin challenge in both ORV (100%) and SQV (89%) mice correlated with CTB-specific titres of intestinal, serum IgA and IgG1 in ORV and only IgG1 in SQV mice, but no other immunoglobulin. Increasing numbers of interleukin-10(+) T cell but not Foxp3(+) regulatory T cells, suppression of interferon-gamma and absence of interleukin-17 were observed in protected mice, suggesting that immunity is conferred via the Tr1/Th2 immune response. Dual immunity against two major infectious diseases provided by chloroplast-derived vaccine antigens for long-term (>300 days, 50% of mouse life span) offers a realistic platform for low cost vaccines and insight into mucosal and systemic immunity.

A Cholera Conjugate Vaccine Containing O-specific Polysaccharide (OSP of V. cholerae O1 Inaba and Recombinant Fragment of Tetanus Toxin Heavy Chain (OSP:rTTHc Induces Serum, Memory and Lamina Proprial Responses against OSP and Is Protective in Mice.

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Md Abu Sayeed

Full Text Available Vibrio cholerae is the cause of cholera, a severe watery diarrhea. Protection against cholera is serogroup specific. Serogroup specificity is defined by the O-specific polysaccharide (OSP component of lipopolysaccharide (LPS.Here we describe a conjugate vaccine for cholera prepared via squaric acid chemistry from the OSP of V. cholerae O1 Inaba strain PIC018 and a recombinant heavy chain fragment of tetanus toxin (OSP:rTTHc. We assessed a range of vaccine doses based on the OSP content of the vaccine (10-50 μg, vaccine compositions varying by molar loading ratio of OSP to rTTHc (3:1, 5:1, 10:1, effect of an adjuvant, and route of immunization.Immunized mice developed prominent anti-OSP and anti-TT serum IgG responses, as well as vibriocidal antibody and memory B cell responses following intramuscular or intradermal vaccination. Mice did not develop anti-squarate responses. Intestinal lamina proprial IgA responses targeting OSP occurred following intradermal vaccination. In general, we found comparable immune responses in mice immunized with these variations, although memory B cell and vibriocidal responses were blunted in mice receiving the highest dose of vaccine (50 μg. We found no appreciable change in immune responses when the conjugate vaccine was administered in the presence or absence of immunoadjuvant alum. Administration of OSP:rTTHc resulted in 55% protective efficacy in a mouse survival cholera challenge model.We report development of an Inaba OSP:rTTHc conjugate vaccine that induces memory responses and protection against cholera in mice. Development of an effective cholera conjugate vaccine that induces high level and long-term immune responses against OSP would be beneficial, especially in young children who respond poorly to polysaccharide antigens.

5 year efficacy of a bivalent killed whole-cell oral cholera vaccine in Kolkata, India: a cluster-randomised, double-blind, placebo-controlled trial.

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Bhattacharya, Sujit K; Sur, Dipika; Ali, Mohammad; Kanungo, Suman; You, Young Ae; Manna, Byomkesh; Sah, Binod; Niyogi, Swapan K; Park, Jin Kyung; Sarkar, Banwarilal; Puri, Mahesh K; Kim, Deok Ryun; Deen, Jacqueline L; Holmgren, Jan; Carbis, Rodney; Dhingra, Mandeep Singh; Donner, Allan; Nair, G Balakrish; Lopez, Anna Lena; Wierzba, Thomas F; Clemens, John D

2013-12-01

Efficacy and safety of a two-dose regimen of bivalent killed whole-cell oral cholera vaccine (Shantha Biotechnics, Hyderabad, India) to 3 years is established, but long-term efficacy is not. We aimed to assess protective efficacy up to 5 years in a slum area of Kolkata, India. In our double-blind, cluster-randomised, placebo-controlled trial, we assessed incidence of cholera in non-pregnant individuals older than 1 year residing in 3933 dwellings (clusters) in Kolkata, India. We randomly allocated participants, by dwelling, to receive two oral doses of modified killed bivalent whole-cell cholera vaccine or heat-killed Escherichia coli K12 placebo, 14 days apart. Randomisation was done by use of a computer-generated sequence in blocks of four. The primary endpoint was prevention of episodes of culture-confirmed Vibrio cholerae O1 diarrhoea severe enough for patients to seek treatment in a health-care facility. We identified culture-confirmed cholera cases among participants seeking treatment for diarrhoea at a study clinic or government hospital between 14 days and 1825 days after receipt of the second dose. We assessed vaccine protection in a per-protocol population of participants who had completely ingested two doses of assigned study treatment. 69 of 31 932 recipients of vaccine and 219 of 34 968 recipients of placebo developed cholera during 5 year follow-up (incidence 2·2 per 1000 in the vaccine group and 6·3 per 1000 in the placebo group). Cumulative protective efficacy of the vaccine at 5 years was 65% (95% CI 52-74; pcholera vaccines. Established long-term efficacy of this vaccine could assist policy makers formulate rational vaccination strategies to reduce overall cholera burden in endemic settings. Bill & Melinda Gates Foundation and the governments of South Korea and Sweden. Copyright © 2013 Elsevier Ltd. All rights reserved.

Alga-Produced Cholera Toxin-Pfs25 Fusion Proteins as Oral Vaccines

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Gregory, James A.; Topol, Aaron B.; Doerner, David Z.

2013-01-01

Infectious diseases disproportionately affect indigent regions and are the greatest cause of childhood mortality in developing countries. Practical, low-cost vaccines for use in these countries are paramount to reducing disease burdens and concomitant poverty. Algae are a promising low-cost system for producing vaccines that can be orally delivered, thereby avoiding expensive purification and injectable delivery. We engineered the chloroplast of the eukaryotic alga Chlamydomonas reinhardtii to produce a chimeric protein consisting of the 25-kDa Plasmodium falciparum surface protein (Pfs25) fused to the β subunit of the cholera toxin (CtxB) to investigate an alga-based whole-cell oral vaccine. Pfs25 is a promising malaria transmission-blocking vaccine candidate that has been difficult to produce in traditional recombinant systems due to its structurally complex tandem repeats of epidermal growth factor-like domains. The noncatalytic CtxB domain of the cholera holotoxin assembles into a pentameric structure and acts as a mucosal adjuvant by binding GM1 ganglioside receptors on gut epithelial cells. We demonstrate that CtxB-Pfs25 accumulates as a soluble, properly folded and functional protein within algal chloroplasts, and it is stable in freeze-dried alga cells at ambient temperatures. In mice, oral vaccination using freeze-dried algae that produce CtxB-Pfs25 elicited CtxB-specific serum IgG antibodies and both CtxB- and Pfs25-specific secretory IgA antibodies. These data suggest that algae are a promising system for production and oral delivery of vaccine antigens, but as an orally delivered adjuvant, CtxB is best suited for eliciting secretory IgA antibodies for vaccine antigens against pathogens that invade mucosal surfaces using this strategy. PMID:23603678

Evaluation of Knowledge and Practices Regarding Cholera, Water Treatment, Hygiene, and Sanitation Before and After an Oral Cholera Vaccination Campaign-Haiti, 2013-2014.

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Childs, Lana; François, Jeannot; Choudhury, Alina; Wannemuehler, Kathleen; Dismer, Amber; Hyde, Terri B; Yen, Catherine Y; Date, Kashmira A; Juin, Stanley; Katz, Mark A; Kantor, Erica Felker; Routh, Janell; Etheart, Melissa; Wright, Tracie; Adrien, Paul; Tohme, Rania A

2016-12-07

In 2013, the Government of Haiti implemented its first oral cholera vaccine (OCV) campaign in Petite Anse, an urban setting, and Cerca Carvajal, a rural commune. We conducted and compared responses to two independent cross-sectional knowledge and practices household surveys pre- (N = 297) and post- (N = 302) OCV campaign in Petite Anse. No significant differences in knowledge about causes, symptoms, and prevention of cholera were noted. Compared with precampaign respondents, fewer postcampaign respondents reported treating (66% versus 27%, P treatment practices necessary for cholera and other diarrheal diseases prevention were noted in the postcampaign survey. Future OCV campaigns in Haiti should be used as an opportunity to emphasize the importance of maintaining good water, sanitation, and hygiene practices, and include a comprehensive, integrated approach for cholera control. © The American Society of Tropical Medicine and Hygiene.

Cholera: an overview with reference to the Yemen epidemic.

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Rabaan, Ali A

2018-06-22

Cholera is a secretory diarrhoeal disease caused by infection with Vibrio cholerae, primarily the V. cholerae O1 El Tor biotype. There are approximately 2.9 million cases in 69 endemic countries annually, resulting in 95 000 deaths. Cholera is associated with poor infrastructure and lack of access to sanitation and clean drinking water. The current cholera epidemic in Yemen, linked to spread of V. cholerae O1 (Ogawa serotype), is associated with the ongoing war. This has devastated infrastructure and health services. The World Health Organization had estimated that 172 286 suspected cases arose between 27th April and 19th June 2017, including 1170 deaths. While there are three oral cholera vaccines prequalified by the World Health Organization, there are issues surrounding vaccination campaigns in conflict situations, exacerbated by external factors such as a global vaccine shortage. Major movements of people complicates surveillance and administration of double doses of vaccines. Cholera therapy mainly depends on rehydration, with use of antibiotics in more severe infections. Concerns have arisen about the rise of antibiotic resistance in cholera, due to mobile genetic elements. In this review, we give an overview of cholera epidemiology, virulence, antibiotic resistance, therapy and vaccines, in the light of the ongoing epidemic in Yemen.

Evaluation of Knowledge and Practices Regarding Cholera, Water Treatment, Hygiene, and Sanitation before and after an Oral Cholera Vaccination Campaign—Haiti, 2013–2014

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Childs, Lana; François, Jeannot; Choudhury, Alina; Wannemuehler, Kathleen; Dismer, Amber; Hyde, Terri B.; Yen, Catherine Y.; Date, Kashmira A.; Juin, Stanley; Katz, Mark A.; Kantor, Erica Felker; Routh, Janell; Etheart, Melissa; Wright, Tracie; Adrien, Paul; Tohme, Rania A.

2016-01-01

In 2013, the Government of Haiti implemented its first oral cholera vaccine (OCV) campaign in Petite Anse, an urban setting, and Cerca Carvajal, a rural commune. We conducted and compared responses to two independent cross-sectional knowledge and practices household surveys pre- (N = 297) and post- (N = 302) OCV campaign in Petite Anse. No significant differences in knowledge about causes, symptoms, and prevention of cholera were noted. Compared with precampaign respondents, fewer postcampaign respondents reported treating (66% versus 27%, P treatment practices necessary for cholera and other diarrheal diseases prevention were noted in the postcampaign survey. Future OCV campaigns in Haiti should be used as an opportunity to emphasize the importance of maintaining good water, sanitation, and hygiene practices, and include a comprehensive, integrated approach for cholera control. PMID:27799642

Comparison of immune responses to a killed bivalent whole cell oral cholera vaccine between endemic and less endemic settings.

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Desai, Sachin N; Akalu, Zenebe; Teferi, Mekonnen; Manna, Byomkesh; Teshome, Samuel; Park, Ju Yeon; Yang, Jae Seung; Kim, Deok Ryun; Kanungo, Suman; Digilio, Laura

2016-02-01

Studies on safety, immunogenicity and efficacy of the killed, bivalent whole cell oral cholera vaccine (Shanchol) have been conducted in historically endemic settings of Asia. Recent cholera vaccination campaigns in Haiti and Guinea have also demonstrated favourable immunogenicity and effectiveness in nonendemic outbreak settings. We performed a secondary analysis, comparing immune responses of Shanchol from two randomised controlled trials performed in an endemic and a less endemic area (Addis Ababa) during a nonoutbreak setting. While Shanchol may offer some degree of immediate protection in primed populations living in cholera endemic areas, as well as being highly immunogenic in less endemic settings, understanding the characteristics of immune responses in each of these areas is vital in determining ideal dosing strategies that offer the greatest public health impact to populations from areas with varying degrees of cholera endemicity. © 2015 John Wiley & Sons Ltd.

A single dose of live-attenuated 638 Vibrio cholerae oral vaccine is safe and immunogenic in adult volunteers in Mozambique

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Hilda María García

2011-12-01

Full Text Available A placebo-controlled randomized, double-blind, clinical trial was carried out to assess the safety, reactogenicity, and immunogenicity of the lyophilized vaccine candidate against cholera derived from the live attenuated 638 Vibrio cholerae O1 El Tor Ogawa strain. One hundred and twenty presumably healthy female and male adult volunteers aged between 18 and 50 years were included. They were from Maputo, Mozambique a cholera endemic area, where, in addition, human immunodeficiency virus (HIV seroprevalence is from 20 to 30%. A dose of 2 x 10 9 colony forming units (CFU was given to 80 subjects and other 40 received only vaccine lyoprotectors as a placebo control. Out-patient follow-up of adverse events was carried out during the following 30 days after vaccination. The immune response was evaluated by the estimation of seroconversion rate and the geometric mean titer (GMT of vibriocidal antibodies in the sera from volunteers that was collected previously, and at days 14 and 21 after immunization. No serious adverse events were reported. The adverse events found in the vaccine group were similar to those of the placebo groups. They were independent from the detection of antibodies against HIV-1, HIV-2, hepatitis (H A; HC and hepatitis B surface antigen. The presence of helminthes did not modify the incidence of adverse events. The 638 vaccine strain was isolated in 37 (46.25% vaccinated volunteer's feces. The peak of the GMT of vibriocidal antibodies in the vaccine group was 9056 versus 39 in the placebo group at 14 days with a total seroconversion of 97.4% at 21 days. The 638 vaccine candidate is safe and immunogenic in a cholera endemic region.

Optimal allocation of the limited oral cholera vaccine supply between endemic and epidemic settings.

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Moore, Sean M; Lessler, Justin

2015-10-06

The World Health Organization (WHO) recently established a global stockpile of oral cholera vaccine (OCV) to be preferentially used in epidemic response (reactive campaigns) with any vaccine remaining after 1 year allocated to endemic settings. Hence, the number of cholera cases or deaths prevented in an endemic setting represents the minimum utility of these doses, and the optimal risk-averse response to any reactive vaccination request (i.e. the minimax strategy) is one that allocates the remaining doses between the requested epidemic response and endemic use in order to ensure that at least this minimum utility is achieved. Using mathematical models, we find that the best minimax strategy is to allocate the majority of doses to reactive campaigns, unless the request came late in the targeted epidemic. As vaccine supplies dwindle, the case for reactive use of the remaining doses grows stronger. Our analysis provides a lower bound for the amount of OCV to keep in reserve when responding to any request. These results provide a strategic context for the fulfilment of requests to the stockpile, and define allocation strategies that minimize the number of OCV doses that are allocated to suboptimal situations. © 2015 The Authors.

The health economics of cholera: A systematic review.

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Hsiao, Amber; Hall, Angela H; Mogasale, Vittal; Quentin, Wilm

2018-06-12

Vibrio cholera is a major contributor of diarrheal illness that causes significant morbidity and mortality globally. While there is literature on the health economics of diarrheal illnesses more generally, few studies have quantified the cost-of-illness and cost-effectiveness of cholera-specific prevention and control interventions. The present systematic review provides a comprehensive overview of the literature specific to cholera as it pertains to key health economic measures. A systematic review was performed with no date restrictions up through February 2017 in PubMed, Econlit, Embase, Web of Science, and Cochrane Review to identify relevant health economics of cholera literature. After removing duplicates, a total of 1993 studies were screened and coded independently by two reviewers, resulting in 22 relevant studies. Data on population, methods, and results (cost-of-illness and cost-effectiveness of vaccination) were compared by country/region. All costs were adjusted to 2017 USD for comparability. Costs per cholera case were found to be rather low: $1000/case. There is adequate evidence to support the economic value of vaccination for the prevention and control of cholera when vaccination is targeted at high-incidence populations and/or areas with high case fatality rates due to cholera. When herd immunity is considered, vaccination also becomes a cost-effective option for the general population and is comparable in cost-effectiveness to other routine immunizations. Cholera vaccination is a viable short-to-medium term option, especially as the upfront costs of building water, sanitation, and hygiene (WASH) infrastructure are considerably higher for countries that face a significant burden of cholera. While WASH may be the more cost-effective solution in the long-term when implemented properly, cholera vaccination can still be a feasible, cost-effective strategy. Copyright © 2018 Elsevier Ltd. All rights reserved.

Vibriocidal antibody responses to a bivalent killed whole-cell oral cholera vaccine in a phase III trial in Kolkata, India.

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Suman Kanungo

Full Text Available BACKGROUND: During the development of a vaccine, identification of the correlates of protection is of paramount importance for establishing an objective criterion for the protective performance of the vaccine. However, the ascertainment of correlates of immunity conferred by any vaccine is a difficult task. METHODS: While conducting a phase three double-blind, cluster-randomized, placebo-controlled trial of a bivalent killed whole-cell oral cholera vaccine in Kolkata, we evaluated the immunogenicity of the vaccine in a subset of participants. Randomly chosen participants (recipients of vaccine or placebo were invited to provide blood samples at baseline, 14 days after the second dose and one year after the first dose. At these time points, serum geometric mean titers (GMT of vibriocidal antibodies and seroconversion rates for vaccine and placebo arms were calculated and compared across the age strata (1 to 5 years, 5 to 15 years and more than 15 years as well as for all age groups. RESULTS: Out of 137 subjects included in analysis, 69 were vaccinees and 68 received placebo. There were 5•7 and 5•8 geometric mean fold (GMF rises in titers to Vibrio cholerae Inaba and Ogawa, respectively at 14 days after the second dose, with 57% and 61% of vaccinees showing a four-fold or greater titer rise, respectively. After one year, the titers to Inaba and Ogawa remained 1•7 and 2•8 fold higher, respectively, compared to baseline. Serum vibriocidal antibody response to V. cholerae O139 was much lower than that to Inaba or Ogawa. No significant differences in the GMF-rises were observed among the age groups. CONCLUSIONS: The reformulated oral cholera vaccine induced a statistically significant anti-O1 Inaba and O1 Ogawa vibriocidal antibody response 14 days after vaccination, which although declined after one year remained significantly higher than baseline. Despite this decline, the vaccine remained protective five years after vaccination.

Exoproteome and Secretome Derived Broad Spectrum Novel Drug and Vaccine Candidates in Vibrio cholerae Targeted by Piper betel Derived Compounds

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Barh, Debmalya; Barve, Neha; Gupta, Krishnakant; Chandra, Sudha; Jain, Neha; Tiwari, Sandeep; Leon-Sicairos, Nidia; Canizalez-Roman, Adrian; Rodrigues dos Santos, Anderson; Hassan, Syed Shah; Almeida, Síntia; Thiago Jucá Ramos, Rommel; Augusto Carvalho de Abreu, Vinicius; Ribeiro Carneiro, Adriana; de Castro Soares, Siomar; Luiz de Paula Castro, Thiago; Miyoshi, Anderson; Silva, Artur; Kumar, Anil; Narayan Misra, Amarendra; Blum, Kenneth; Braverman, Eric R.; Azevedo, Vasco

2013-01-01

Vibrio cholerae is the causal organism of the cholera epidemic, which is mostly prevalent in developing and underdeveloped countries. However, incidences of cholera in developed countries are also alarming. Because of the emergence of new drug-resistant strains, even though several generic drugs and vaccines have been developed over time, Vibrio infections remain a global health problem that appeals for the development of novel drugs and vaccines against the pathogen. Here, applying comparative proteomic and reverse vaccinology approaches to the exoproteome and secretome of the pathogen, we have identified three candidate targets (ompU, uppP and yajC) for most of the pathogenic Vibrio strains. Two targets (uppP and yajC) are novel to Vibrio, and two targets (uppP and ompU) can be used to develop both drugs and vaccines (dual targets) against broad spectrum Vibrio serotypes. Using our novel computational approach, we have identified three peptide vaccine candidates that have high potential to induce both B- and T-cell-mediated immune responses from our identified two dual targets. These two targets were modeled and subjected to virtual screening against natural compounds derived from Piper betel. Seven compounds were identified first time from Piper betel to be highly effective to render the function of these targets to identify them as emerging potential drugs against Vibrio. Our preliminary validation suggests that these identified peptide vaccines and betel compounds are highly effective against Vibrio cholerae. Currently we are exhaustively validating these targets, candidate peptide vaccines, and betel derived lead compounds against a number of Vibrio species. PMID:23382822

Exoproteome and secretome derived broad spectrum novel drug and vaccine candidates in Vibrio cholerae targeted by Piper betel derived compounds.

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Debmalya Barh

Full Text Available Vibrio cholerae is the causal organism of the cholera epidemic, which is mostly prevalent in developing and underdeveloped countries. However, incidences of cholera in developed countries are also alarming. Because of the emergence of new drug-resistant strains, even though several generic drugs and vaccines have been developed over time, Vibrio infections remain a global health problem that appeals for the development of novel drugs and vaccines against the pathogen. Here, applying comparative proteomic and reverse vaccinology approaches to the exoproteome and secretome of the pathogen, we have identified three candidate targets (ompU, uppP and yajC for most of the pathogenic Vibrio strains. Two targets (uppP and yajC are novel to Vibrio, and two targets (uppP and ompU can be used to develop both drugs and vaccines (dual targets against broad spectrum Vibrio serotypes. Using our novel computational approach, we have identified three peptide vaccine candidates that have high potential to induce both B- and T-cell-mediated immune responses from our identified two dual targets. These two targets were modeled and subjected to virtual screening against natural compounds derived from Piper betel. Seven compounds were identified first time from Piper betel to be highly effective to render the function of these targets to identify them as emerging potential drugs against Vibrio. Our preliminary validation suggests that these identified peptide vaccines and betel compounds are highly effective against Vibrio cholerae. Currently we are exhaustively validating these targets, candidate peptide vaccines, and betel derived lead compounds against a number of Vibrio species.

The Burden of Cholera in Uganda

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Bwire, Godfrey; Malimbo, Mugagga; Maskery, Brian; Kim, Young Eun; Mogasale, Vittal; Levin, Ann

2013-01-01

Introduction In 2010, the World Health Organization released a new cholera vaccine position paper, which recommended the use of cholera vaccines in high-risk endemic areas. However, there is a paucity of data on the burden of cholera in endemic countries. This article reviewed available cholera surveillance data from Uganda and assessed the sufficiency of these data to inform country-specific strategies for cholera vaccination. Methods The Uganda Ministry of Health conducts cholera surveillance to guide cholera outbreak control activities. This includes reporting the number of cases based on a standardized clinical definition plus systematic laboratory testing of stool samples from suspected cases at the outset and conclusion of outbreaks. This retrospective study analyzes available data by district and by age to estimate incidence rates. Since surveillance activities focus on more severe hospitalized cases and deaths, a sensitivity analysis was conducted to estimate the number of non-severe cases and unrecognized deaths that may not have been captured. Results Cholera affected all ages, but the geographic distribution of the disease was very heterogeneous in Uganda. We estimated that an average of about 11,000 cholera cases occurred in Uganda each year, which led to approximately 61–182 deaths. The majority of these cases (81%) occurred in a relatively small number of districts comprising just 24% of Uganda's total population. These districts included rural areas bordering the Democratic Republic of Congo, South Sudan, and Kenya as well as the slums of Kampala city. When outbreaks occurred, the average duration was about 15 weeks with a range of 4–44 weeks. Discussion There is a clear subdivision between high-risk and low-risk districts in Uganda. Vaccination efforts should be focused on the high-risk population. However, enhanced or sentinel surveillance activities should be undertaken to better quantify the endemic disease burden and high-risk populations

Peru-15 (Choleragarde(®)), a live attenuated oral cholera vaccine, is safe and immunogenic in human immunodeficiency virus (HIV)-seropositive adults in Thailand.

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Ratanasuwan, W; Kim, Y H; Sah, B K; Suwanagool, S; Kim, D R; Anekthananon, A; Lopez, A L; Techasathit, W; Grahek, S L; Clemens, J D; Wierzba, T F

2015-09-11

Many areas with endemic and epidemic cholera report significant levels of HIV transmission. According to the World Health Organization (WHO), over 95% of reported cholera cases occur in Africa, which also accounts for nearly 70% of people living with HIV/AIDS globally. Peru-15, a promising single dose live attenuated oral cholera vaccine (LA-OCV), was previously found to be safe and immunogenic in cholera endemic areas. However, no data on the vaccine's safety among HIV-seropositive adults had been collected. This study was a double-blinded, individually randomized, placebo-controlled trial enrolling HIV-seropositive adults, 18-45 years of age, conducted in Bangkok, Thailand, to assess the safety of Peru-15 in a HIV-seropositive cohort. 32 HIV infected subjects were randomized to receive either a single oral dose of the Peru-15 vaccine with a buffer or a placebo (buffer only). No serious adverse events were reported during the follow-up period in either group. The geometric mean fold (GMF) rise in V. cholerae O1 El Tor specific antibody titers between baseline and 7 days after dosing was 32.0 (pcholerae was isolated from the stool of one vaccinee, and found to be genetically identical to the Peru-15 vaccine strain. There were no significant changes in HIV viral load or CD4 T-cell counts between vaccine and placebo groups. Peru-15 was shown to be safe and immunogenic in HIV-seropositive Thai adults. Copyright © 2015 Elsevier Ltd. All rights reserved.

Optimized oral cholera vaccine distribution strategies to minimize disease incidence: A mixed integer programming model and analysis of a Bangladesh scenario.

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Smalley, Hannah K; Keskinocak, Pinar; Swann, Julie; Hinman, Alan

2015-11-17

In addition to improved sanitation, hygiene, and better access to safe water, oral cholera vaccines can help to control the spread of cholera in the short term. However, there is currently no systematic method for determining the best allocation of oral cholera vaccines to minimize disease incidence in a population where the disease is endemic and resources are limited. We present a mathematical model for optimally allocating vaccines in a region under varying levels of demographic and incidence data availability. The model addresses the questions of where, when, and how many doses of vaccines to send. Considering vaccine efficacies (which may vary based on age and the number of years since vaccination), we analyze distribution strategies which allocate vaccines over multiple years. Results indicate that, given appropriate surveillance data, targeting age groups and regions with the highest disease incidence should be the first priority, followed by other groups primarily in order of disease incidence, as this approach is the most life-saving and cost-effective. A lack of detailed incidence data results in distribution strategies which are not cost-effective and can lead to thousands more deaths from the disease. The mathematical model allows for what-if analysis for various vaccine distribution strategies by providing the ability to easily vary parameters such as numbers and sizes of regions and age groups, risk levels, vaccine price, vaccine efficacy, production capacity and budget. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effectiveness and economic analysis of the whole cell/recombinant B subunit (WC/rbs inactivated oral cholera vaccine in the prevention of traveller's diarrhoea

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Diez-Diaz Rosa

2009-05-01

Full Text Available Abstract Background Nowadays there is a debate about the indication of the oral whole-cell/recombinant B-subunit cholera vaccine (WC/rBS in traveller's diarrhoea. However, a cost-benefit analysis based on real data has not been published. Methods A cost-effectiveness and cost-benefit study of the oral cholera vaccine (WC/rBS, Dukoral® for the prevention of traveller's diarrhoea (TD was performed in subjects travelling to cholera risk areas. The effectiveness of WC/rBS vaccine in the prevention of TD was analyzed in 362 travellers attending two International Vaccination Centres in Spain between May and September 2005. Results The overall vaccine efficacy against TD was 42,6%. Direct healthcare-related costs as well as indirect costs (lost vacation days subsequent to the disease were considered. Preventive vaccination against TD resulted in a mean saving of 79.26 € per traveller. Conclusion According to the cost-benefit analysis performed, the recommendation for WC/rBS vaccination in subjects travelling to zones at risk of TD is beneficial for the traveller, regardless of trip duration and visited continent.

Biomarkers of Environmental Enteropathy are Positively Associated with Immune Responses to an Oral Cholera Vaccine in Bangladeshi Children.

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Muhammad Ikhtear Uddin

2016-11-01

Full Text Available Environmental enteropathy (EE is a poorly understood condition that refers to chronic alterations in intestinal permeability, absorption, and inflammation, which mainly affects young children in resource-limited settings. Recently, EE has been linked to suboptimal oral vaccine responses in children, although immunological mechanisms are poorly defined. The objective of this study was to determine host factors associated with immune responses to an oral cholera vaccine (OCV. We measured antibody and memory T cell immune responses to cholera antigens, micronutrient markers in blood, and EE markers in blood and stool from 40 Bangladeshi children aged 3-14 years who received two doses of OCV given 14 days apart. EE markers included stool myeloperoxidase (MPO and alpha anti-trypsin (AAT, and plasma endotoxin core antibody (EndoCab, intestinal fatty acid binding protein (i-FABP, and soluble CD14 (sCD14. We used multiple linear regression analysis with LASSO regularization to identify host factors, including EE markers, micronutrient (nutritional status, age, and HAZ score, predictive for each response of interest. We found stool MPO to be positively associated with IgG antibody responses to the B subunit of cholera toxin (P = 0.03 and IgA responses to LPS (P = 0.02; plasma sCD14 to be positively associated with LPS IgG responses (P = 0.07; plasma i-FABP to be positively associated with LPS IgG responses (P = 0.01 and with memory T cell responses specific to cholera toxin (P = 0.01; stool AAT to be negatively associated with IL-10 (regulatory T cell responses specific to cholera toxin (P = 0.02, and plasma EndoCab to be negatively associated with cholera toxin-specific memory T cell responses (P = 0.02. In summary, in a cohort of children 3-14 years old, we demonstrated that the majority of biomarkers of environmental enteropathy were positively associated with immune responses after vaccination with an OCV.

Comparison of two control groups for estimation of oral cholera vaccine effectiveness using a case-control study design.

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Franke, Molly F; Jerome, J Gregory; Matias, Wilfredo R; Ternier, Ralph; Hilaire, Isabelle J; Harris, Jason B; Ivers, Louise C

2017-10-13

Case-control studies to quantify oral cholera vaccine effectiveness (VE) often rely on neighbors without diarrhea as community controls. Test-negative controls can be easily recruited and may minimize bias due to differential health-seeking behavior and recall. We compared VE estimates derived from community and test-negative controls and conducted bias-indicator analyses to assess potential bias with community controls. From October 2012 through November 2016, patients with acute watery diarrhea were recruited from cholera treatment centers in rural Haiti. Cholera cases had a positive stool culture. Non-cholera diarrhea cases (test-negative controls and non-cholera diarrhea cases for bias-indicator analyses) had a negative culture and rapid test. Up to four community controls were matched to diarrhea cases by age group, time, and neighborhood. Primary analyses included 181 cholera cases, 157 non-cholera diarrhea cases, 716 VE community controls and 625 bias-indicator community controls. VE for self-reported vaccination with two doses was consistent across the two control groups, with statistically significant VE estimates ranging from 72 to 74%. Sensitivity analyses revealed similar, though somewhat attenuated estimates for self-reported two dose VE. Bias-indicator estimates were consistently less than one, with VE estimates ranging from 19 to 43%, some of which were statistically significant. OCV estimates from case-control analyses using community and test-negative controls were similar. While bias-indicator analyses suggested possible over-estimation of VE estimates using community controls, test-negative analyses suggested this bias, if present, was minimal. Test-negative controls can be a valid low-cost and time-efficient alternative to community controls for OCV effectiveness estimation and may be especially relevant in emergency situations. Copyright © 2017. Published by Elsevier Ltd.

Mechanisms Underlying the Immune Response Generated by an Oral Vibrio cholerae Vaccine

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Danylo Sirskyj

2016-07-01

Full Text Available Mechanistic details underlying the resulting protective immune response generated by mucosal vaccines remain largely unknown. We investigated the involvement of Toll-like receptor signaling in the induction of humoral immune responses following oral immunization with Dukoral, comparing wild type mice with TLR-2-, TLR-4-, MyD88- and Trif-deficient mice. Although all groups generated similar levels of IgG antibodies, the proliferation of CD4+ T-cells in response to V. cholerae was shown to be mediated via MyD88/TLR signaling, and independently of Trif signaling. The results demonstrate differential requirements for generation of immune responses. These results also suggest that TLR pathways may be modulators of the quality of immune response elicited by the Dukoral vaccine. Determining the critical signaling pathways involved in the induction of immune response to this vaccine would be beneficial, and could contribute to more precisely-designed versions of other oral vaccines in the future.

Cholera in travelers: shifting tides in epidemiology, management, and prevention.

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Fillion, Katie; Mileno, Maria D

2015-01-01

The distribution of cholera's devastating effects has changed. While cholera is endemic in 50 countries mostly in Asia and Africa, more than half of the cases reported in 2012 were in the Western Hemisphere, predominantly Haiti. Since the current epidemic began in Haiti in 2010, there has been spread to the Dominican Republic, Cuba, and most recently Mexico. Several recent case reports document individuals returning home from affected areas with diarrhea from cholera, in some cases severe. Hopeful news reported the containment of an outbreak through the use of a Vibrio cholera vaccine. There are safe and effective oral cholera vaccines available and recommended in outbreaks and endemic areas, although they are not currently available in the USA or to travelers. This review aims to discuss the latest data to aid our current recommendations for the prevention of cholera in travelers beyond standard personal and food hygiene precautions for the prevention of travelers' diarrhea and to offer insights on the most current data available about cholera vaccine progress and potential use.

Good manufacturing practices production of a purification-free oral cholera vaccine expressed in transgenic rice plants.

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Kashima, Koji; Yuki, Yoshikazu; Mejima, Mio; Kurokawa, Shiho; Suzuki, Yuji; Minakawa, Satomi; Takeyama, Natsumi; Fukuyama, Yoshiko; Azegami, Tatsuhiko; Tanimoto, Takeshi; Kuroda, Masaharu; Tamura, Minoru; Gomi, Yasuyuki; Kiyono, Hiroshi

2016-03-01

The first Good Manufacturing Practices production of a purification-free rice-based oral cholera vaccine (MucoRice-CTB) from transgenic plants in a closed cultivation system yielded a product meeting regulatory requirements. Despite our knowledge of their advantages, plant-based vaccines remain unavailable for human use in both developing and industrialized countries. A leading, practical obstacle to their widespread use is producing plant-based vaccines that meet governmental regulatory requirements. Here, we report the first production according to current Good Manufacturing Practices of a rice-based vaccine, the cholera vaccine MucoRice-CTB, at an academic institution. To this end, we established specifications and methods for the master seed bank (MSB) of MucoRice-CTB, which was previously generated as a selection-marker-free line, evaluated its propagation, and given that the stored seeds must be renewed periodically. The production of MucoRice-CTB incorporated a closed hydroponic system for cultivating the transgenic plants, to minimize variations in expression and quality during vaccine manufacture. This type of molecular farming factory can be operated year-round, generating three harvests annually, and is cost- and production-effective. Rice was polished to a ratio of 95 % and then powdered to produce the MucoRice-CTB drug substance, and the identity, potency, and safety of the MucoRice-CTB product met pre-established release requirements. The formulation of MucoRice-CTB made by fine-powdering of drug substance and packaged in an aluminum pouch is being evaluated in a physician-initiated phase I study.

N-Glycosylation of cholera toxin B subunit: serendipity for novel plant-made vaccines?

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Nobuyuki eMatoba

2015-12-01

Full Text Available The non-toxic B subunit of cholera toxin (CTB has attracted considerable interests from vaccinologists due to strong mucosal immunomodulatory effects and potential utility as a vaccine scaffold for heterologous antigens. Along with other conventional protein expression systems, various plant species have been used as recombinant production hosts for CTB and its fusion proteins. However, it has recently become clear that the protein is N-glycosylated within the endoplasmic reticulum of plant cells – a eukaryotic post-translational modification that is not present in native CTB. While functionally active aglycosylated variants have been successfully engineered to circumvent potential safety and regulatory issues related to glycosylation, this modification may actually provide advantageous characteristics to the protein as a vaccine platform. Based on data from our recent studies, I discuss the unique features of N-glycosylated CTB produced in plants for the development of novel vaccines.

Immunization with cholera toxin B subunit induces high-level protection in the suckling mouse model of cholera.

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Gregory A Price

Full Text Available Cholera toxin (CT is the primary virulence factor responsible for severe cholera. Vibrio cholerae strains unable to produce CT show severe attenuation of virulence in animals and humans. The pentameric B subunit of CT (CTB contains the immunodominant epitopes recognized by antibodies that neutralize CT. Although CTB is a potent immunogen and a promising protective vaccine antigen in animal models, immunization of humans with detoxified CT failed to protect against cholera. We recently demonstrated however that pups reared from mice immunized intraperitoneally (IP with 3 doses of recombinant CTB were well protected against a highly lethal challenge dose of V. cholerae N16961. The present study investigated how the route and number of immunizations with CTB could influence protective efficacy in the suckling mouse model of cholera. To this end female mice were immunized with CTB intranasally (IN, IP, and subcutaneously (SC. Serum and fecal extracts were analyzed for anti-CTB antibodies by quantitative ELISA, and pups born to immunized mothers were challenged orogastrically with a lethal dose of V. cholerae. Pups from all immunized groups were highly protected from death by 48 hours (64-100% survival. Cox regression showed that percent body weight loss at 24 hours predicted death by 48 hours, but we were unable to validate a specific amount of weight loss as a surrogate marker for protection. Although CTB was highly protective in all regimens, three parenteral immunizations showed trends toward higher survival and less weight loss at 24 hours post infection. These results demonstrate that immunization with CTB by any of several routes and dosing regimens can provide protection against live V. cholerae challenge in the suckling mouse model of cholera. Our data extend the results of previous studies and provide additional support for the inclusion of CTB in the development of a subunit vaccine against V. cholerae.

Guinea pig complement potently measures vibriocidal activity of human antibodies in response to cholera vaccines.

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Kim, Kyoung Whun; Jeong, Soyoung; Ahn, Ki Bum; Yang, Jae Seung; Yun, Cheol-Heui; Han, Seung Hyun

2017-12-01

The vibriocidal assay using guinea pig complement is widely used for the evaluation of immune responses to cholera vaccines in human clinical trials. However, it is unclear why guinea pig complement has been used over human complement in the measurement of vibriocidal activity of human sera and there have not been comparison studies for the use of guinea pig complement over those from other species. Therefore, we comparatively investigated the effects of complements derived from human, guinea pig, rabbit, and sheep on vibriocidal activity. Complements from guinea pig, rabbit, and human showed concentration-dependent vibriocidal activity in the presence of quality control serum antibodies. Of these complements, guinea pig complement was the most sensitive and effective over a wide concentration range. When the vibriocidal activity of complements was measured in the absence of serum antibodies, human, sheep, and guinea pig complements showed vibriocidal activity up to 40-fold, 20-fold, and 1-fold dilution, respectively. For human pre- and post-vaccination sera, the most potent vibriocidal activity was observed when guinea pig complement was used. In addition, the highest fold-increases between pre- and post- vaccinated sera were obtained with guinea pig complement. Furthermore, human complement contained a higher amount of V. cholerae- and its lipopolysaccharide-specific antibodies than guinea pig complement. Collectively, these results suggest that guinea pig complements are suitable for vibriocidal assays due to their high sensitivity and effectiveness to human sera.

[Synthesis of protective antigens during submerged cultivation of Vibrio cholerae].

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Fedorova, V A; Syrova, N A; Gromova, O V; Tershkina, N E; Devdariani, Z L; Dzhaparidze, M N; Meleshchenko, M V; Dobrova, G V; Beliakova, N I; Ermakov, N M; Eliseev, Iu Iu

2000-01-01

The effectiveness of dot immunoanalysis for evaluating the dynamics of the synthesis of O-antigen, cholera toxin, neuraminidase, adhesin CFA1 in the process of the reactor cultivation of V. cholerae used for the production of oral chemical cholera vaccine is shown. The established regularities of the synthesis of the protective antigens of V. cholerae in the process of scaled-up cultivation are discussed.

Cost-benefit of WC/rBS oral cholera vaccine for vaccination against ETEC-caused travelers' diarrhea.

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Lundkvist, Jonas; Steffen, Robert; Jönsson, Bengt

2009-01-01

The most common infectious health problem encountered by travelers to countries in the developing region is travelers' diarrhea (TD), with enterotoxigenic Escherichia coli (ETEC) being the most common pathogen isolated. Although mild in most cases, the disease still leads to the loss of a significant part of a vacation or business trip. There is currently a lack of knowledge about the costs in relation to the benefits of vaccination against TD caused by ETEC, and the purposes of this study were to estimate and develop a cost-benefit analysis of vaccination using whole-cell/recombinant-B-subunit oral cholera vaccine. The consequences of the vaccination were identified and quantified in monetary terms. The cost-benefits for leisure and business travelers were assessed separately. The value of the travel was separated into the cost of the trip and of lost leisure time/business opportunities. A person with TD was in base case estimated to lose on average 3.5 days of a 7-day leisure trip and 2.5 days of a 4-day business trip. Results are presented for a Canadian traveler to endemic areas in year 2007 in US$. The average cost of a TD event was estimated at $1,460 and $1,996 for leisure and business travelers, respectively. The net value of the vaccination, however, varied with the risk of the disease. Through extensive literature searches, an updated ETEC map illustrating the proportion of ETEC-caused TD was created. The analysis indicated that vaccination would be considered cost-effective at incidence rates of ETEC-caused TD above about 13 and 9% for leisure and business travelers, respectively. It is, however, important to keep in mind that it is the value of the travel for the individual traveler that will decide if the vaccination provides good value for money.

Cholera - management and prevention.

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Davies, Hannah G; Bowman, Conor; Luby, Stephen P

2017-06-01

Cholera is an acute secretory diarrhoeal infection caused by the bacterium Vibrio cholerae. It is likely to have originated in the Indian sub-continent; however, it spread to cause six worldwide pandemics between 1817-1923. The ongoing seventh worldwide pandemic of cholera began in 1961. The intensity, duration and severity of cholera epidemics have been increasing, signaling the need for more effective control and prevention measures. The response to the cholera pandemics of the 19th century led to the development of safe and effective sanitation and water systems which have effectively removed the risk of cholera in many settings. However, such systems are not in place to protect billions of people worldwide. Although some progress has been made in expanding access to water in recent years, achieving optimal infrastructure will, in the most optimistic scenario, take decades. Climate change, extreme weather events and rapid urbanisation suggests that alternatives to the current paradigm of providing large centralised water and sanitation systems should be considered, including smaller decentralised systems. The aim of this review paper is to provide an overview of current knowledge regarding management of cholera with a focus on prevention measures including vaccination and water and sanitation interventions. © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Innovative vaccine delivery strategies in response to a cholera outbreak in the challenging context of Lake Chilwa. A rapid qualitative assessment.

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Heyerdahl, Leonard W; Ngwira, Bagrey; Demolis, Rachel; Nyirenda, Gabriel; Mwesawina, Maurice; Rafael, Florentina; Cavailler, Philippe; Bernard Le Gargasson, Jean; Mengel, Martin A; Gessner, Bradford D; Guillermet, Elise

2017-11-07

A reactive campaign using two doses of Shanchol Oral Cholera Vaccine (OCV) was implemented in 2016 in the Lake Chilwa Region (Malawi) targeting fish dependent communities. Three strategies for the second vaccine dose delivery (including delivery by a community leader and self-administration) were used to facilitate vaccine access. This assessment collected vaccine perceptions and opinions about the OCV campaign of 313 study participants, including: fishermen, fish traders, farmers, community leaders, and one health and one NGO officer. Socio-demographic surveys were conducted, In Depth Interviews and Focus Group Discussions were conducted before and during the campaign. Some fishermen perceived the traditional delivery strategy as reliable but less practical. Delivery by traditional leaders was acceptable for some participants while others worried about traditional leaders not being trained to deliver vaccines or beneficiaries taking doses on their own. A slight majority of beneficiaries considered the self-administration strategy practical while some beneficiaries worried about storing vials outside of the cold chain or losing vials. During the campaign, a majority of participants preferred receiving oral vaccines instead of injections given ease of intake and lack of pain. OCV was perceived as efficacious and safe. However, a lack of information on how sero-protection may be delayed and the degree of sero-protection led to loss of trust in vaccine potency among some participants who witnessed cholera cases among vaccinated individuals. OCV campaign implementation requires accompanying communication on protective levels, less than 100% vaccine efficacy, delays in onset of sero-protection, and out of cold chain storage. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Socioeconomic risk factors for cholera in different transmission settings: An analysis of the data of a cluster randomized trial in Bangladesh.

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Saha, Amit; Hayen, Andrew; Ali, Mohammad; Rosewell, Alexander; Clemens, John D; Raina MacIntyre, C; Qadri, Firdausi

2017-09-05

Cholera remains a threat globally, and socioeconomic factors play an important role in transmission of the disease. We assessed socioeconomic risk factors for cholera in vaccinated and non-vaccinated communities to understand whether the socioeconomic risk factors differ by transmission patterns for cholera. We used data from a cluster randomized control trial conducted in Dhaka, Bangladesh. There were 90 geographic clusters; 30 in each of the three arms of the study: vaccine (VAC), vaccine plus behavioural change (VBC), and non-intervention. The data were analysed for the three populations: (1) vaccinees in the vaccinated communities (VAC and VBC arms), (2) non-vaccinated individuals in the vaccinated communities and (3) all individuals in the non-vaccinated communities (non-intervention arm). A generalized estimating equation with logit link function was used to evaluate the risk factors for cholera among these different populations adjusting for household level correlation in the data. A total of 528 cholera and 226 cholera with severe dehydration (CSD) in 268,896 persons were observed during the two-year follow-up. For population 1, the cholera risk was not associated with any socioeconomic factors; however CSD was less likely to occur among individuals living in a household having ≤4 members (aOR=0.55, 95% CI=0.32-0.96). Among population 2, younger participants and individuals reporting diarrhoea during registration were more likely to have cholera. Females and individuals reporting diarrhoea during registration were at increased risk of CSD. Among population 3, individuals living in a household without a concrete floor, in an area with high population density, closer to the study hospital, or not treating drinking water were at significantly higher risk for both cholera and CSD. The profile of socioeconomic factors associated with cholera varies by individuals' vaccination status as well as the transmission setting. In a vaccinated community where

[Study on the immunogenicity and safety of recombinant B-subunit/whole cell cholera vaccine infused with antacids in healthy population at ages of 2-6 years].

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Huang, T; Li, R C; Liu, D P

2017-09-06

Objective: To assess the immunogenicity and safety of recombinant B-subunit/whole cell cholera vaccine (rBS/WC) oral cholera vaccine (Ora Vacs) infused with antacids in healthy population at ages of 2-6 years. Methods: Between December 2009 and January 2010, we recruited 900 volunteers aged 2-6 years od through giving out recruitment notice for the eligible children's parents from different vaccination clinics of Chongzuo city in Guangxi Zhuang Autonomous Region. This study was a randomized, double-blind, placebo-controlled trial, and subjects were randomly (2∶1) assigned to receive Cholera vaccine infused with antacids or placebo, and observed for safety. Serum samples of 300 subjects in immunogenicity subgroups (200 for vaccine groups, 100 for control groups) before the 1st dose and 49 d (±3 d) after immunization were collected, and determined for antibody levels against the cholera toxin (anti-CT) and cholera vibriocidal (anti-Vab) with Enzyme-linked immunosorbent assays (ELISA), based on which the GMT was calculated. There were 266 cases paired with the serum samples before and after immunization (177 for vaccine groups, 89 for control groups). The comparison of subjects' age at enrollment and the level of GMT before and after immunization between groups were analyzed by t test. The superiority test for the difference between seroconversion rates of vaccine groups and control groups were analyzed by χ(2) test. Results: Of 900 subjects enrolled, the number of males and females were 503 and 397 respectively (vaccine groups 335 vs . 265, control groups 168 vs . 132), the average ages of vaccine groups and control groups at enrollment were (4.8±1.2) years and (4.9±1.2) years respectively. There were no significant differences between groups in terms of gender and age (χ(2)=0.00, P= 1.000; t= 0.55, P= 0.585). The 2 times increase rates of anti-CT and anti-Vab in vaccine groups after inoculation were 90.96% and 57.63% respectively, which were superiority to

Cholera cases cluster in time and space in Matlab, Bangladesh: implications for targeted preventive interventions.

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Debes, Amanda K; Ali, Mohammad; Azman, Andrew S; Yunus, Mohammad; Sack, David A

2016-12-01

: Cholera remains a serious public health threat in Asia, Africa and in parts of the Americas. Three World health Organization (WHO) pre-qualified oral cholera vaccines are now available but their supply is limited, so current supplies must be administered strategically. This requires an improved understanding of disease transmission and control strategies. : We used demographics and disease surveillance data collected from 1991 to 2000 in Matlab, Bangladesh, to estimate the spatial and temporal extent of the zone of increased risk around cholera cases. Specifically, we compare the cholera incidence among individuals living close to cholera cases with that among individuals living close to those without medically-attended cholera in this rural endemic setting. : Those living within 50 m of a confirmed cholera case had 36 times (95% confidence interval: 23-56) the risk of becoming a cholera case in the first 3 days (after case presentation) compared with risk elsewhere in the community. The relative risk gradually declined in space and time, but remained significantly high up to 450 me away within 3 days of case presentation, and up to 150 m away within 23 days from the date of presentation of the case. : These findings suggest that, if conducted rapidly, vaccinating individuals living close to a case (ring vaccination) could be an efficient and effective strategy to target vaccine to a high-risk population in an endemic setting. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

Cholera Epidemic - Lusaka, Zambia, October 2017-May 2018.

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Sinyange, Nyambe; Brunkard, Joan M; Kapata, Nathan; Mazaba, Mazyanga Lucy; Musonda, Kunda G; Hamoonga, Raymond; Kapina, Muzala; Kapaya, Fred; Mutale, Lwito; Kateule, Ernest; Nanzaluka, Francis; Zulu, James; Musyani, Chileshe Lukwesa; Winstead, Alison V; Davis, William W; N'cho, Hammad S; Mulambya, Nelia L; Sakubita, Patrick; Chewe, Orbie; Nyimbili, Sulani; Onwuekwe, Ezinne V C; Adrien, Nedghie; Blackstock, Anna J; Brown, Travis W; Derado, Gordana; Garrett, Nancy; Kim, Sunkyung; Hubbard, Sydney; Kahler, Amy M; Malambo, Warren; Mintz, Eric; Murphy, Jennifer; Narra, Rupa; Rao, Gouthami G; Riggs, Margaret A; Weber, Nicole; Yard, Ellen; Zyambo, Khozya D; Bakyaita, Nathan; Monze, Namani; Malama, Kennedy; Mulwanda, Jabbin; Mukonka, Victor M

2018-05-18

On October 6, 2017, an outbreak of cholera was declared in Zambia after laboratory confirmation of Vibrio cholerae O1, biotype El Tor, serotype Ogawa, from stool specimens from two patients with acute watery diarrhea. The two patients had gone to a clinic in Lusaka, the capital city, on October 4. Cholera cases increased rapidly, from several hundred cases in early December 2017 to approximately 2,000 by early January 2018 (Figure). In collaboration with partners, the Zambia Ministry of Health (MoH) launched a multifaceted public health response that included increased chlorination of the Lusaka municipal water supply, provision of emergency water supplies, water quality monitoring and testing, enhanced surveillance, epidemiologic investigations, a cholera vaccination campaign, aggressive case management and health care worker training, and laboratory testing of clinical samples. In late December 2017, a number of water-related preventive actions were initiated, including increasing chlorine levels throughout the city's water distribution system and placing emergency tanks of chlorinated water in the most affected neighborhoods; cholera cases declined sharply in January 2018. During January 10-February 14, 2018, approximately 2 million doses of oral cholera vaccine were administered to Lusaka residents aged ≥1 year. However, in mid-March, heavy flooding and widespread water shortages occurred, leading to a resurgence of cholera. As of May 12, 2018, the outbreak had affected seven of the 10 provinces in Zambia, with 5,905 suspected cases and a case fatality rate (CFR) of 1.9%. Among the suspected cases, 5,414 (91.7%), including 98 deaths (CFR = 1.8%), occurred in Lusaka residents.

Environmental Monitoring of Endemic Cholera

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ElNemr, W.; Jutla, A. S.; Constantin de Magny, G.; Hasan, N. A.; Islam, M.; Sack, R.; Huq, A.; Hashem, F.; Colwell, R.

2012-12-01

Cholera remains a major public health threat. Since Vibrio cholerae, the causative agent of the disease, is autochthonous to riverine, estuarine, and coastal waters, it is unlikely the bacteria can be eradicated from its natural habitat. Prediction of disease, in conjunction with preventive vaccination can reduce the prevalence rate of a disease. Understanding the influence of environmental parameters on growth and proliferation of bacteria is an essential first step in developing prediction methods for outbreaks. Large scale geophysical variables, such as SST and coastal chlorophyll, are often associated with conditions favoring growth of V. cholerae. However, local environmental factors, meaning biological activity in ponds from where the bulk of populations in endemic regions derive water for daily usage, are either neglected or oversimplified. Using data collected from several sites in two geographically distinct locations in South Asia, we have identified critical local environmental factors associated with cholera outbreak. Of 18 environmental variables monitored for water sources in Mathbaria (a coastal site near the Bay of Bengal) and Bakergonj (an inland site) of Bangladesh, water depth and chlorophyll were found to be important factors associated with initiation of cholera outbreaks. Cholera in coastal regions appears to be related to intrusion. However, monsoonal flooding creates conditions for cholera epidemics in inland regions. This may be one of the first attempts to relate in-situ environmental observations with cholera. We anticipate that it will be useful for further development of prediction models in the resource constrained regions.

Cost-of-illness of cholera to households and health facilities in rural Malawi.

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Patrick G Ilboudo

Full Text Available Cholera remains an important public health problem in many low- and middle-income countries. Vaccination has been recommended as a possible intervention for the prevention and control of cholera. Evidence, especially data on disease burden, cost-of-illness, delivery costs and cost-effectiveness to support a wider use of vaccine is still weak. This study aims at estimating the cost-of-illness of cholera to households and health facilities in Machinga and Zomba Districts, Malawi. A cross-sectional study using retrospectively collected cost data was undertaken in this investigation. One hundred patients were purposefully selected for the assessment of the household cost-of-illness and four cholera treatment centres and one health facility were selected for the assessment conducted in health facilities. Data collected for the assessment in households included direct and indirect costs borne by cholera patients and their families while only direct costs were considered for the assessment conducted in health facilities. Whenever possible, descriptive and regression analysis were used to assess difference in mean costs between groups of patients. The average costs to patients' households and health facilities for treating an episode of cholera amounted to US$65.6 and US$59.7 in 2016 for households and health facilities, respectively equivalent to international dollars (I$ 249.9 and 227.5 the same year. Costs incurred in treating a cholera episode were proportional to duration of hospital stay. Moreover, 52% of households used coping strategies to compensate for direct and indirect costs imposed by the disease. Both households and health facilities could avert significant treatment expenditures through a broader use of pre-emptive cholera vaccination. These findings have direct policy implications regarding priority investments for the prevention and control of cholera.

Cost-of-illness of cholera to households and health facilities in rural Malawi.

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Ilboudo, Patrick G; Huang, Xiao Xian; Ngwira, Bagrey; Mwanyungwe, Abel; Mogasale, Vittal; Mengel, Martin A; Cavailler, Philippe; Gessner, Bradford D; Le Gargasson, Jean-Bernard

2017-01-01

Cholera remains an important public health problem in many low- and middle-income countries. Vaccination has been recommended as a possible intervention for the prevention and control of cholera. Evidence, especially data on disease burden, cost-of-illness, delivery costs and cost-effectiveness to support a wider use of vaccine is still weak. This study aims at estimating the cost-of-illness of cholera to households and health facilities in Machinga and Zomba Districts, Malawi. A cross-sectional study using retrospectively collected cost data was undertaken in this investigation. One hundred patients were purposefully selected for the assessment of the household cost-of-illness and four cholera treatment centres and one health facility were selected for the assessment conducted in health facilities. Data collected for the assessment in households included direct and indirect costs borne by cholera patients and their families while only direct costs were considered for the assessment conducted in health facilities. Whenever possible, descriptive and regression analysis were used to assess difference in mean costs between groups of patients. The average costs to patients' households and health facilities for treating an episode of cholera amounted to US$65.6 and US$59.7 in 2016 for households and health facilities, respectively equivalent to international dollars (I$) 249.9 and 227.5 the same year. Costs incurred in treating a cholera episode were proportional to duration of hospital stay. Moreover, 52% of households used coping strategies to compensate for direct and indirect costs imposed by the disease. Both households and health facilities could avert significant treatment expenditures through a broader use of pre-emptive cholera vaccination. These findings have direct policy implications regarding priority investments for the prevention and control of cholera.

Strategies to Prevent Cholera Introduction during International Personnel Deployments: A Computational Modeling Analysis Based on the 2010 Haiti Outbreak

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Lewnard, Joseph A.; Antillón, Marina; Gonsalves, Gregg; Miller, Alice M.; Ko, Albert I.; Pitzer, Virginia E.

2016-01-01

Background Introduction of Vibrio cholerae to Haiti during the deployment of United Nations (UN) peacekeepers in 2010 resulted in one of the largest cholera epidemics of the modern era. Following the outbreak, a UN-commissioned independent panel recommended three pre-deployment intervention strategies to minimize the risk of cholera introduction in future peacekeeping operations: screening for V. cholerae carriage, administering prophylactic antimicrobial chemotherapies, or immunizing with oral cholera vaccines. However, uncertainty regarding the effectiveness of these approaches has forestalled their implementation by the UN. We assessed how the interventions would have impacted the likelihood of the Haiti cholera epidemic. Methods and Findings We developed a stochastic model for cholera importation and transmission, fitted to reported cases during the first weeks of the 2010 outbreak in Haiti. Using this model, we estimated that diagnostic screening reduces the probability of cases occurring by 82% (95% credible interval: 75%, 85%); however, false-positive test outcomes may hamper this approach. Antimicrobial chemoprophylaxis at time of departure and oral cholera vaccination reduce the probability of cases by 50% (41%, 57%) and by up to 61% (58%, 63%), respectively. Chemoprophylaxis beginning 1 wk before departure confers a 91% (78%, 96%) reduction independently, and up to a 98% reduction (94%, 99%) if coupled with vaccination. These results are not sensitive to assumptions about the background cholera incidence rate in the endemic troop-sending country. Further research is needed to (1) validate the sensitivity and specificity of rapid test approaches for detecting asymptomatic carriage, (2) compare prophylactic efficacy across antimicrobial regimens, and (3) quantify the impact of oral cholera vaccine on transmission from asymptomatic carriers. Conclusions Screening, chemoprophylaxis, and vaccination are all effective strategies to prevent cholera introduction

Multi-site cholera surveillance within the African Cholera Surveillance Network shows endemicity in Mozambique, 2011-2015.

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Semá Baltazar, Cynthia; Langa, José Paulo; Dengo Baloi, Liliana; Wood, Richard; Ouedraogo, Issaka; Njanpop-Lafourcade, Berthe-Marie; Inguane, Dorteia; Elias Chitio, Jucunu; Mhlanga, Themba; Gujral, Lorna; D Gessner, Bradford; Munier, Aline; A Mengel, Martin

2017-10-01

Mozambique suffers recurrent annual cholera outbreaks especially during the rainy season between October to March. The African Cholera Surveillance Network (Africhol) was implemented in Mozambique in 2011 to generate accurate detailed surveillance data to support appropriate interventions for cholera control and prevention in the country. Africhol was implemented in enhanced surveillance zones located in the provinces of Sofala (Beira), Zambézia (District Mocuba), and Cabo Delgado (Pemba City). Data were also analyzed from the three outbreak areas that experienced the greatest number of cases during the time period under observation (in the districts of Cuamba, Montepuez, and Nampula). Rectal swabs were collected from suspected cases for identification of Vibrio cholerae, as well as clinical, behavioral, and socio-demographic variables. We analyzed factors associated with confirmed, hospitalized, and fatal cholera using multivariate logistic regression models. A total of 1,863 suspected cases and 23 deaths (case fatality ratio (CFR), 1.2%) were reported from October 2011 to December 2015. Among these suspected cases, 52.2% were tested of which 23.5% were positive for Vibrio cholerae O1 Ogawa. Risk factors independently associated with the occurrence of confirmed cholera were living in Nampula city district, the year 2014, human immunodeficiency virus infection, and the primary water source for drinking. Cholera was endemic in Mozambique during the study period with a high CFR and identifiable risk factors. The study reinforces the importance of continued cholera surveillance, including a strong laboratory component. The results enhanced our understanding of the need to target priority areas and at-risk populations for interventions including oral cholera vaccine (OCV) use, and assess the impact of prevention and control strategies. Our data were instrumental in informing integrated prevention and control efforts during major cholera outbreaks in recent years.

Recommendations of the Advisory Committee on Immunization Practices for Use of Cholera Vaccine.

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Wong, Karen K; Burdette, Erin; Mahon, Barbara E; Mintz, Eric D; Ryan, Edward T; Reingold, Arthur L

2017-05-12

Cholera, caused by infection with toxigenic Vibrio cholerae bacteria of serogroup O1 (>99% of global cases) or O139, is characterized by watery diarrhea that can be severe and rapidly fatal without prompt rehydration. Cholera is endemic in approximately 60 countries and causes epidemics as well. Globally, cholera results in an estimated 2.9 million cases of disease and 95,000 deaths annually (1). Cholera is rare in the United States, and most U.S. cases occur among travelers to countries where cholera is endemic or epidemic. Forty-two U.S. cases were reported in 2011 after a cholera epidemic began in Haiti (2); however, <25 cases per year have been reported in the United States since 2012.

Multi-site cholera surveillance within the African Cholera Surveillance Network shows endemicity in Mozambique, 2011–2015

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Langa, José Paulo; Dengo Baloi, Liliana; Wood, Richard; Ouedraogo, Issaka; Njanpop-Lafourcade, Berthe-Marie; Inguane, Dorteia; Elias Chitio, Jucunu; Mhlanga, Themba; Gujral, Lorna; D. Gessner, Bradford; Munier, Aline; A. Mengel, Martin

2017-01-01

Background Mozambique suffers recurrent annual cholera outbreaks especially during the rainy season between October to March. The African Cholera Surveillance Network (Africhol) was implemented in Mozambique in 2011 to generate accurate detailed surveillance data to support appropriate interventions for cholera control and prevention in the country. Methodology/Principal findings Africhol was implemented in enhanced surveillance zones located in the provinces of Sofala (Beira), Zambézia (District Mocuba), and Cabo Delgado (Pemba City). Data were also analyzed from the three outbreak areas that experienced the greatest number of cases during the time period under observation (in the districts of Cuamba, Montepuez, and Nampula). Rectal swabs were collected from suspected cases for identification of Vibrio cholerae, as well as clinical, behavioral, and socio-demographic variables. We analyzed factors associated with confirmed, hospitalized, and fatal cholera using multivariate logistic regression models. A total of 1,863 suspected cases and 23 deaths (case fatality ratio (CFR), 1.2%) were reported from October 2011 to December 2015. Among these suspected cases, 52.2% were tested of which 23.5% were positive for Vibrio cholerae O1 Ogawa. Risk factors independently associated with the occurrence of confirmed cholera were living in Nampula city district, the year 2014, human immunodeficiency virus infection, and the primary water source for drinking. Conclusions/Significance Cholera was endemic in Mozambique during the study period with a high CFR and identifiable risk factors. The study reinforces the importance of continued cholera surveillance, including a strong laboratory component. The results enhanced our understanding of the need to target priority areas and at-risk populations for interventions including oral cholera vaccine (OCV) use, and assess the impact of prevention and control strategies. Our data were instrumental in informing integrated prevention and

Social and cultural features of cholera and shigellosis in peri-urban and rural communities of Zanzibar

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Hutubessy Raymond

2010-11-01

Full Text Available Abstract Background Responding to the high burden of cholera in developing countries, the WHO now considers vaccination as a supplement to the provision of safe drinking water and improved sanitation in the strategy for cholera control in endemic settings. Cultural concepts of illness affect many aspects of public health. In the first step of a two-step strategy to examine determinants of cholera vaccine acceptance, this study identified social and cultural features of diarrhoeal illness for cholera control in endemic communities. Methods A cultural epidemiological study with locally adapted vignette-based interviews was conducted in two cholera-endemic communities of Zanzibar. A random sample of unaffected peri-urban (n = 179 and rural (n = 177 adults was interviewed to study community ideas of cholera and shigellosis, considering categories of distress, perceived causes, and help-seeking behaviour. Results Cholera was recognised by 88%. Symptoms of dehydration were most prominent in reports at the peri-urban site. Interference with work leading to strain on household finances was frequently emphasised. Dirty environment was the most prominent perceived cause, followed by unsafe drinking water and germ-carrying flies. Causes unrelated to the biomedical basis of cholera were reported more often by rural respondents. Rural women had more difficulty (20% to identify a cause than men (7.1%, p = 0.016. Peri-urban self treatment emphasised rehydration; the rural community preferred herbal treatment and antibiotics. Shigellosis was recognised by 70%. Fewer regarded it as very serious compared with cholera (76% vs. 97%, p Conclusions This study clarified local views of cholera and shigellosis relevant for diarrhoeal disease control in Zanzibar. The finding that rural women were less likely than men to specify causes of cholera suggests more attention to them is required. Better health education is needed for cholera in rural areas and for shigellosis

Development of fowl cholera vaccine: I. Protection of Pasteurella multocida local isolate vaccine against challenge of homologous and heterologous strains.

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Supar

2001-03-01

vaccinated chicken showed the presence of antibody responses againsted the extract cell and whole cell antigens of either P. multocida BCC 2331 or DY2 local isolate as detected by ELISA. The antibody responses from vaccinated chicken against extra cellular antigens prepared from broth cultures of BCC 2331 and DY2 were detected only from vaccinated chicken with vaccine containing killed antigen of BCC 2331 and/or DY2 isolate. It is likely, the local isolate of P. multocida BCC 2331 and DY2 would be benefit for producing inactive fowl cholera vaccine use in Indonesia, but the protective antigen that enhances immune protection should be determined by means of immunoblotting techniques.

Plasma and Mucosal Immunoglobulin M, Immunoglobulin A, and Immunoglobulin G Responses to the Vibrio cholerae O1 Protein Immunome in Adults With Cholera in Bangladesh.

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Charles, Richelle C; Nakajima, Rie; Liang, Li; Jasinskas, Al; Berger, Amanda; Leung, Daniel T; Kelly, Meagan; Xu, Peng; Kovác, Pavol; Giffen, Samantha R; Harbison, James D; Chowdhury, Fahima; Khan, Ashraful I; Calderwood, Stephen B; Bhuiyan, Taufiqur Rahman; Harris, Jason B; Felgner, Philip L; Qadri, Firdausi; Ryan, Edward T

2017-07-01

Cholera is a severe dehydrating illness of humans caused by toxigenic strains of Vibrio cholerae O1 or O139. Identification of immunogenic V. cholerae antigens could lead to a better understanding of protective immunity in human cholera. We probed microarrays containing 3652 V. cholerae antigens with plasma and antibody-in-lymphocyte supernatant (ALS, a surrogate marker of mucosal immune responses) from patients with severe cholera caused by V. cholerae O1 in Bangladesh and age-, sex-, and ABO-matched Bangladeshi controls. We validated a subset of identified antigens using enzyme-linked immunosorbent assay. Overall, we identified 608 immunoreactive V. cholerae antigens in our screening, 59 of which had higher immunoreactivity in convalescent compared with acute-stage or healthy control samples (34 in plasma, 39 in mucosal ALS; 13 in both sample sets). Identified antigens included cholera toxin B and A subunits, V. cholerae O-specific polysaccharide and lipopolysaccharide, toxin coregulated pilus A, sialidase, hemolysin A, flagellins (FlaB, FlaC, and FlaD), phosphoenolpyruvate-protein phosphotransferase, and diaminobutyrate-2-oxoglutarate aminotransferase. This study is the first antibody profiling of the mucosal and systemic antibody responses to the nearly complete V. cholerae O1 protein immunome; it has identified antigens that may aid in the development of an improved cholera vaccine. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Development of stable Vibrio cholerae O1 Hikojima type vaccine strains co-expressing the Inaba and Ogawa lipopolysaccharide antigens.

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Stefan L Karlsson

Full Text Available We describe here the development of stable classical and El Tor V. cholerae O1 strains of the Hikojima serotype that co-express the Inaba and Ogawa antigens of O1 lipopolysaccharide (LPS. Mutation of the wbeT gene reduced LPS perosamine methylation and thereby gave only partial transformation into Ogawa LPS on the cell surface. The strains express approximately equal amounts of Inaba- and Ogawa-LPS antigens which are preserved after formalin-inactivation of the bacteria. Oral immunizations of both inbred and outbred mice with formalin-inactivated whole-cell vaccine preparations of these strains elicited strong intestinal IgA anti-LPS as well as serum vibriocidal antibody responses against both Inaba and Ogawa that were fully comparable to the responses induced by the licensed Dukoral vaccine. Passive protection studies in infant mice showed that immune sera raised against either of the novel Hikojima vaccine strains protected baby mice against infection with virulent strains of both serotypes. This study illustrates the power of using genetic manipulation to improve the properties of bacteria strains for use in killed whole-cell vaccines.

Generation of transgenic corn-derived Actinobacillus pleuropneumoniae ApxIIA fused with the cholera toxin B subunit as a vaccine candidate

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Shin, Min-Kyoung; Jung, Myung Hwan; Lee, Won-Jung; Choi, Pil Son; Jang, Yong-Suk

2011-01-01

Corn, one of the most important forage crops worldwide, has proven to be a useful expression vehicle due to the availability of established transformation procedures for this well-studied plant. The exotoxin Apx, a major virulence factor, is recognized as a common antigen of Actinobacillus (A.) pleuropneumoniae, the causative agent of porcine pleuropneumonia. In this study, a cholera toxin B (CTB)-ApxIIA#5 fusion protein and full-size ApxIIA expressed in corn seed, as a subunit vaccine candidate, were observed to induce Apx-specific immune responses in mice. These results suggest that transgenic corn-derived ApxIIA and CTB-ApxIIA#5 proteins are potential vaccine candidates against A. pleuropneumoniae infection. PMID:22122907

Mass psychogenic illness after vaccination.

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Clements, C John

2003-01-01

When vaccines are administered to groups, the physical reactions of the recipients may be similar, causing a form of mass reaction, the mechanism for which is the same as that for mass reactions from other causes. These phenomena have been categorised as mass psychogenic illness (MPI), and have been defined as the collective occurrence of a constellation of symptoms suggestive of organic illness but without an identified cause in a group of people with shared beliefs about the cause of the symptom(s). A review of the literature shows that such outbreaks have been reported in differing cultural and environmental settings including developing and industrialised countries, in the work place, on public transport, in schools, and the military. The perceived threats have been against agents such as food poisoning, fire and toxic gases. Whatever the place or perceived threat, the response seems to be similar. The symptoms generally included headache, dizziness, weakness, and loss of consciousness. Once under way, MPIs are not easy to stop. Incidents reported in the literature show that they can quickly gather momentum and can be amplified by the press who disseminate information rapidly, escalating the events. Management of such mass events can be extremely difficult. Should the public health official in charge continue to try and determine the cause, or should this person call off the entire investigation? It is suggested here that once vaccines are identified as a probable cause of the phenomenon, a dismissive approach may actually be harmful. Unless the spokesperson has already earned a high level of trust, the public are not likely to be convinced easily that nothing was wrong with the vaccine until it has been tested. An increased awareness of MPIs on the part of organisers of future mass vaccination campaigns seems appropriate. Immunisation managers should be aware that mass immunisation campaigns could generate such mass reactions. It is therefore essential that

Induction of indoleamine 2, 3-dioxygenase in human dendritic cells by a cholera toxin B subunit-proinsulin vaccine.

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Jacques C Mbongue

Full Text Available Dendritic cells (DC interact with naïve T cells to regulate the delicate balance between immunity and tolerance required to maintain immunological homeostasis. In this study, immature human dendritic cells (iDC were inoculated with a chimeric fusion protein vaccine containing the pancreatic β-cell auto-antigen proinsulin linked to a mucosal adjuvant the cholera toxin B subunit (CTB-INS. Proteomic analysis of vaccine inoculated DCs revealed strong up-regulation of the tryptophan catabolic enzyme indoleamine 2, 3-dioxygenase (IDO1. Increased biosynthesis of the immunosuppressive enzyme was detected in DCs inoculated with the CTB-INS fusion protein but not in DCs inoculated with proinsulin, CTB, or an unlinked combination of the two proteins. Immunoblot and PCR analyses of vaccine treated DCs detected IDO1mRNA by 3 hours and IDO1 protein synthesis by 6 hours after vaccine inoculation. Determination of IDO1 activity in vaccinated DCs by measurement of tryptophan degradation products (kynurenines showed increased tryptophan cleavage into N-formyl kynurenine. Vaccination did not interfere with monocytes differentiation into DC, suggesting the vaccine can function safely in the human immune system. Treatment of vaccinated DCs with pharmacological NF-κB inhibitors ACHP or DHMEQ significantly inhibited IDO1 biosynthesis, suggesting a role for NF-κB signaling in vaccine up-regulation of dendritic cell IDO1. Heat map analysis of the proteomic data revealed an overall down-regulation of vaccinated DC functions, suggesting vaccine suppression of DC maturation. Together, our experimental data indicate that CTB-INS vaccine induction of IDO1 biosynthesis in human DCs may result in the inhibition of DC maturation generating a durable state of immunological tolerance. Understanding how CTB-INS modulates IDO1 activity in human DCs will facilitate vaccine efficacy and safety, moving this immunosuppressive strategy closer to clinical applications for prevention

The Impact of a One-Dose versus Two-Dose Oral Cholera Vaccine Regimen in Outbreak Settings: A Modeling Study

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Azman, Andrew S.; Luquero, Francisco J.; Ciglenecki, Iza; Grais, Rebecca F.; Sack, David A.; Lessler, Justin

2015-01-01

Background In 2013, a stockpile of oral cholera vaccine (OCV) was created for use in outbreak response, but vaccine availability remains severely limited. Innovative strategies are needed to maximize the health impact and minimize the logistical barriers to using available vaccine. Here we ask under what conditions the use of one dose rather than the internationally licensed two-dose protocol may do both. Methods and Findings Using mathematical models we determined the minimum relative single-dose efficacy (MRSE) at which single-dose reactive campaigns are expected to be as or more effective than two-dose campaigns with the same amount of vaccine. Average one- and two-dose OCV effectiveness was estimated from published literature and compared to the MRSE. Results were applied to recent outbreaks in Haiti, Zimbabwe, and Guinea using stochastic simulations to illustrate the potential impact of one- and two-dose campaigns. At the start of an epidemic, a single dose must be 35%–56% as efficacious as two doses to avert the same number of cases with a fixed amount of vaccine (i.e., MRSE between 35% and 56%). This threshold decreases as vaccination is delayed. Short-term OCV effectiveness is estimated to be 77% (95% CI 57%–88%) for two doses and 44% (95% CI −27% to 76%) for one dose. This results in a one-dose relative efficacy estimate of 57% (interquartile range 13%–88%), which is above conservative MRSE estimates. Using our best estimates of one- and two-dose efficacy, we projected that a single-dose reactive campaign could have prevented 70,584 (95% prediction interval [PI] 55,943–86,205) cases in Zimbabwe, 78,317 (95% PI 57,435–100,150) in Port-au-Prince, Haiti, and 2,826 (95% PI 2,490–3,170) cases in Conakry, Guinea: 1.1 to 1.2 times as many as a two-dose campaign. While extensive sensitivity analyses were performed, our projections of cases averted in past epidemics are based on severely limited single-dose efficacy data and may not fully capture

The Impact of a One-Dose versus Two-Dose Oral Cholera Vaccine Regimen in Outbreak Settings: A Modeling Study.

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Andrew S Azman

2015-08-01

Full Text Available In 2013, a stockpile of oral cholera vaccine (OCV was created for use in outbreak response, but vaccine availability remains severely limited. Innovative strategies are needed to maximize the health impact and minimize the logistical barriers to using available vaccine. Here we ask under what conditions the use of one dose rather than the internationally licensed two-dose protocol may do both.Using mathematical models we determined the minimum relative single-dose efficacy (MRSE at which single-dose reactive campaigns are expected to be as or more effective than two-dose campaigns with the same amount of vaccine. Average one- and two-dose OCV effectiveness was estimated from published literature and compared to the MRSE. Results were applied to recent outbreaks in Haiti, Zimbabwe, and Guinea using stochastic simulations to illustrate the potential impact of one- and two-dose campaigns. At the start of an epidemic, a single dose must be 35%-56% as efficacious as two doses to avert the same number of cases with a fixed amount of vaccine (i.e., MRSE between 35% and 56%. This threshold decreases as vaccination is delayed. Short-term OCV effectiveness is estimated to be 77% (95% CI 57%-88% for two doses and 44% (95% CI -27% to 76% for one dose. This results in a one-dose relative efficacy estimate of 57% (interquartile range 13%-88%, which is above conservative MRSE estimates. Using our best estimates of one- and two-dose efficacy, we projected that a single-dose reactive campaign could have prevented 70,584 (95% prediction interval [PI] 55,943-86,205 cases in Zimbabwe, 78,317 (95% PI 57,435-100,150 in Port-au-Prince, Haiti, and 2,826 (95% PI 2,490-3,170 cases in Conakry, Guinea: 1.1 to 1.2 times as many as a two-dose campaign. While extensive sensitivity analyses were performed, our projections of cases averted in past epidemics are based on severely limited single-dose efficacy data and may not fully capture uncertainty due to imperfect

Near real-time forecasting for cholera decision making in Haiti after Hurricane Matthew.

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Pasetto, Damiano; Finger, Flavio; Camacho, Anton; Grandesso, Francesco; Cohuet, Sandra; Lemaitre, Joseph C; Azman, Andrew S; Luquero, Francisco J; Bertuzzo, Enrico; Rinaldo, Andrea

2018-05-01

Computational models of cholera transmission can provide objective insights into the course of an ongoing epidemic and aid decision making on allocation of health care resources. However, models are typically designed, calibrated and interpreted post-hoc. Here, we report the efforts of a team from academia, field research and humanitarian organizations to model in near real-time the Haitian cholera outbreak after Hurricane Matthew in October 2016, to assess risk and to quantitatively estimate the efficacy of a then ongoing vaccination campaign. A rainfall-driven, spatially-explicit meta-community model of cholera transmission was coupled to a data assimilation scheme for computing short-term projections of the epidemic in near real-time. The model was used to forecast cholera incidence for the months after the passage of the hurricane (October-December 2016) and to predict the impact of a planned oral cholera vaccination campaign. Our first projection, from October 29 to December 31, predicted the highest incidence in the departments of Grande Anse and Sud, accounting for about 45% of the total cases in Haiti. The projection included a second peak in cholera incidence in early December largely driven by heavy rainfall forecasts, confirming the urgency for rapid intervention. A second projection (from November 12 to December 31) used updated rainfall forecasts to estimate that 835 cases would be averted by vaccinations in Grande Anse (90% Prediction Interval [PI] 476-1284) and 995 in Sud (90% PI 508-2043). The experience gained by this modeling effort shows that state-of-the-art computational modeling and data-assimilation methods can produce informative near real-time projections of cholera incidence. Collaboration among modelers and field epidemiologists is indispensable to gain fast access to field data and to translate model results into operational recommendations for emergency management during an outbreak. Future efforts should thus draw together multi

Vaccines for preventing enterotoxigenic Escherichia coli (ETEC) diarrhoea.

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Ahmed, Tanvir; Bhuiyan, Taufiqur R; Zaman, K; Sinclair, David; Qadri, Firdausi

2013-07-05

Infection with enterotoxigenic Escherichia coli (ETEC) bacteria is a common cause of diarrhoea in adults and children in developing countries and is a major cause of 'travellers' diarrhoea' in people visiting or returning from endemic regions. A killed whole cell vaccine (Dukoral®), primarily designed and licensed to prevent cholera, has been recommended by some groups to prevent travellers' diarrhoea in people visiting endemic regions. This vaccine contains a recombinant B subunit of the cholera toxin that is antigenically similar to the heat labile toxin of ETEC. This review aims to evaluate the clinical efficacy of this vaccine and other vaccines designed specifically to protect people against diarrhoea caused by ETEC infection. To evaluate the efficacy, safety, and immunogenicity of vaccines for preventing ETEC diarrhoea. We searched the Cochrane Infectious Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, and http://clinicaltrials.gov up to December 2012. Randomized controlled trials (RCTs) and quasi-RCTs comparing use of vaccines to prevent ETEC with use of no intervention, a control vaccine (either an inert vaccine or a vaccine normally given to prevent an unrelated infection), an alternative ETEC vaccine, or a different dose or schedule of the same ETEC vaccine in healthy adults and children living in endemic regions, intending to travel to endemic regions, or volunteering to receive an artificial challenge of ETEC bacteria. Two authors independently assessed each trial for eligibility and risk of bias. Two independent reviewers extracted data from the included studies and analyzed the data using Review Manager (RevMan) software. We reported outcomes as risk ratios (RR) with 95% confidence intervals (CI). We assessed the quality of the evidence using the GRADE approach. Twenty-four RCTs, including 53,247 participants, met the inclusion criteria. Four studies assessed the protective

Novel mucosal DNA-MVA HIV vaccination in which DNA-IL-12 plus Cholera Toxin B subunit (CTB) cooperates to enhance cellular systemic and mucosal genital tract immunity

OpenAIRE

Maeto, Cynthia Alejandra; Rodríguez, Ana María; Holgado, María Pía; Falivene, Juliana; Gherardi, Maria Magdalena

2017-01-01

Induction of local antiviral immune responses at the mucosal portal surfaces where HIV-1 and other viral pathogens are usually first encountered remains a primary goal for most vaccines against mucosally acquired viral infections. Exploring mucosal immunization regimes in order to find optimal vector combinations and also appropriate mucosal adjuvants in the HIV vaccine development is decisive. In this study we analyzed the interaction of DNA-IL-12 and cholera toxin B subunit (CTB) after thei...

Cholera Toxin B: One Subunit with Many Pharmaceutical Applications

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Keegan J. Baldauf

2015-03-01

Full Text Available Cholera, a waterborne acute diarrheal disease caused by Vibrio cholerae, remains prevalent in underdeveloped countries and is a serious health threat to those living in unsanitary conditions. The major virulence factor is cholera toxin (CT, which consists of two subunits: the A subunit (CTA and the B subunit (CTB. CTB is a 55 kD homopentameric, non-toxic protein binding to the GM1 ganglioside on mammalian cells with high affinity. Currently, recombinantly produced CTB is used as a component of an internationally licensed oral cholera vaccine, as the protein induces potent humoral immunity that can neutralize CT in the gut. Additionally, recent studies have revealed that CTB administration leads to the induction of anti-inflammatory mechanisms in vivo. This review will cover the potential of CTB as an immunomodulatory and anti-inflammatory agent. We will also summarize various recombinant expression systems available for recombinant CTB bioproduction.

Cholera in pregnancy: Clinical and immunological aspects.

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Khan, Ashraful I; Chowdhury, Fahima; Leung, Daniel T; Larocque, Regina C; Harris, Jason B; Ryan, Edward T; Calderwood, Stephen B; Qadri, Firdausi

2015-10-01

The objective of this study was to examine the clinical and immunological features of cholera in pregnancy. Women of reproductive age presenting to the icddr,b Dhaka hospital with cholera, and enrolled as part of a larger cohort study, were tested for pregnancy on admission. We compared initial clinical features and immune responses of pregnant patients with non-pregnant female patients at days 2, 7 and 21 after infection. Among reproductive age women enrolled between January 2001 and May 2006, 9.7% (14/144) were pregnant. The duration of diarrhoea prior to admission tended to be higher in pregnant compared to non-pregnant patients (p=0.08), but other clinical characteristics did not differ. Antibody responses to cholera toxin B subunit (CtxB), toxin-coregulated pilus A (TcpA), Vibrio cholerae lipopolysaccharide (LPS), and serum vibriocidal antibody responses, were comparable between pregnant and non-pregnant patients. There were no deaths among the pregnant cases or non-pregnant controls, and no adverse foetal outcomes, including stillbirths, during 21 days of follow up of pregnant cases. To our knowledge, this is the first report of immune responses in pregnant women with cholera. We found that pregnant woman early in pregnancy has comparable clinical illness and subsequent immune responses compared to non-pregnant women. These findings suggest that the evaluation of safety and immunogenicity of oral cholera vaccines in pregnancy should be an area of future investigations. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Cholera Incidence and Mortality in Sub-Saharan African Sites during Multi-country Surveillance.

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Sauvageot, Delphine; Njanpop-Lafourcade, Berthe-Marie; Akilimali, Laurent; Anne, Jean-Claude; Bidjada, Pawou; Bompangue, Didier; Bwire, Godfrey; Coulibaly, Daouda; Dengo-Baloi, Liliana; Dosso, Mireille; Orach, Christopher Garimoi; Inguane, Dorteia; Kagirita, Atek; Kacou-N'Douba, Adele; Keita, Sakoba; Kere Banla, Abiba; Kouame, Yao Jean-Pierre; Landoh, Dadja Essoya; Langa, Jose Paulo; Makumbi, Issa; Miwanda, Berthe; Malimbo, Muggaga; Mutombo, Guy; Mutombo, Annie; NGuetta, Emilienne Niamke; Saliou, Mamadou; Sarr, Veronique; Senga, Raphael Kakongo; Sory, Fode; Sema, Cynthia; Tante, Ouyi Valentin; Gessner, Bradford D; Mengel, Martin A

2016-05-01

Cholera burden in Africa remains unknown, often because of weak national surveillance systems. We analyzed data from the African Cholera Surveillance Network (www.africhol.org). During June 2011-December 2013, we conducted enhanced surveillance in seven zones and four outbreak sites in Togo, the Democratic Republic of Congo (DRC), Guinea, Uganda, Mozambique and Cote d'Ivoire. All health facilities treating cholera cases were included. Cholera incidences were calculated using culture-confirmed cholera cases and culture-confirmed cholera cases corrected for lack of culture testing usually due to overwhelmed health systems and imperfect test sensitivity. Of 13,377 reported suspected cases, 34% occurred in Conakry, Guinea, 47% in Goma, DRC, and 19% in the remaining sites. From 0-40% of suspected cases were aged under five years and from 0.3-86% had rice water stools. Within surveillance zones, 0-37% of suspected cases had confirmed cholera compared to 27-38% during outbreaks. Annual confirmed incidence per 10,000 population was cholera incidence, age distribution, clinical presentation, culture confirmation, and testing frequency. These results can help guide preventive activities, including vaccine use.

Killed Whole-Cell Oral Cholera Vaccine Induces CCL20 Secretion by Human Intestinal Epithelial Cells in the Presence of the Short-Chain Fatty Acid, Butyrate

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Ju-Ri Sim

2018-01-01

Full Text Available Short-chain fatty acids (SCFAs, such as acetate, butyrate, and propionate, modulate immune responses in the gut. However, the effect of SCFAs on mucosal vaccine-induced immune cell migration is poorly understood. Here, we investigated whether SCFAs modulate chemokine expression induced by the killed whole-cell oral cholera vaccine, Shanchol™, in human intestinal epithelial cells. Shanchol™ induced expression of CCL2, CCL5, CCL20, and CXCL10 at the mRNA level, but not at the protein level. Interestingly, CCL20 secretion was substantially increased by co-stimulation with Shanchol™ and butyrate, while neither acetate nor propionate showed such effect. Enhanced CCL20 secretion was associated with GPR109A activation, and histone deacetylase (HDAC inhibition. In addition, co-treatment with Shanchol™ and butyrate synergistically increased the secretion of adenosine triphosphate (ATP. Moreover, CCL20 secretion was decreased by inhibiting the extracellular ATP receptor P2X7. However, neither inflammasomes nor caspases were involved in CCL20 production. The culture supernatant of cells treated with Shanchol™ and butyrate augmented human immature dendritic cell migration. Collectively, these results suggest that butyrate enhances Shanchol™-induced CCL20 production in human intestinal epithelial cells via HDAC inhibition and ATP-P2X7 signaling by activating GPR109A. These effects potentially enhance the mucosal immune responses in the gut induced by this oral cholera vaccine.

Stimulation of mucosal immune response following oral administration of enterotoxigenic Escherichia coli fimbriae (CFA/I) entrapped in liposomes in conjunction with inactivated whole-cell Vibrio cholerae vaccine.

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Dima, V F; Ionescu, M D; Palade, R; Balotescu, C; Becheanu, G; Dima, S V

2001-01-01

In this study, we have searched for an effective mucosal vaccine. An oral enterotoxigenic E. coli vaccine containing colonization factor antigen (CFA/I) associated with inactivated whole-cell V. cholerae vaccine (WCV) has been tested for safety and immunogenicity in animals. Five groups of animals were used. The results showed the following: (a) vaccine containing CFA/I antigen entrapped in liposomes and associated with WCV (batch C) had increased titers of specific antibodies to CFA/I antigen in 15 to 18 (83.3%) animals; (b) specific Peyer's patches (PP), lymph nodes (LN) and spleen (SPL) lymphocytes proliferation was detected following in vitro restimulation with CFA/I antigen or WCV. This response gradually increased to the highest value by the 35th postimmunization day. Moreover, lower PP, LN and spleen (SPL) proliferation was observed in rabbits receiving soluble CFA/I antigen (S-CFA/I) or free liposomes (F-L) alone; (c) adhesion of E. coli H10407 strain labelled with 3H-leucine in immunized and control animals revealed the following local effects: (i) protection of rabbit intestinal mucosa against virulent E. coli cells; (ii) inhibition of adhesion of ETEC bacteria to intestinal mucosa and (iii) significantly faster release of E. coli H 10407 strain labelled with 3H-leucine from the intestinal tract of immunized animals. The histopathological and electron microscope findings confirmed the above results. The experimental results point out an efficient protection against infection with E. coli strains (ETEC), after mucosal vaccination with CFA/I antigen entrapped in liposomes associated with inactivated whole-cell Vibrio cholerae as immunological adjuvant.

SAFETY AND EFFICIENCY OF INACTIVATED OF SUBUNIT INFLUENZA VACCINE AT MASS VACCINATION OF CHILDREN

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Yu.Z. Gendon

2007-01-01

Full Text Available The article considers the results of infantile mass vaccination with inactivated subunit influenza vaccine (Influvac. It shows that vaccination of 57–72% of children aged 3–17 from organized collectives residing in Mytishchi and Orekhovoczuevo districts of Moscow region was accompanied with nearly triple reduce of flu rates vs. Narofominsk and Odintsovo districts where vaccination was occasional (< 1% of children. The efficiency of the vaccination made 63,7%. Low reactogenicity of the influenza vaccine was recorded. Its convenient packing allows vaccination of large number of children in a short time. The article justifies the necessity of yearly vaccinations even in case of similarity of flu virus strain.Key words: children, mass vaccination, subunit flu vaccine, safety.

Spatially explicit modelling of cholera epidemics

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Finger, F.; Bertuzzo, E.; Mari, L.; Knox, A. C.; Gatto, M.; Rinaldo, A.

2013-12-01

Epidemiological models can provide crucial understanding about the dynamics of infectious diseases. Possible applications range from real-time forecasting and allocation of health care resources to testing alternative intervention mechanisms such as vaccines, antibiotics or the improvement of sanitary conditions. We apply a spatially explicit model to the cholera epidemic that struck Haiti in October 2010 and is still ongoing. The dynamics of susceptibles as well as symptomatic and asymptomatic infectives are modelled at the scale of local human communities. Dissemination of Vibrio cholerae through hydrological transport and human mobility along the road network is explicitly taken into account, as well as the effect of rainfall as a driver of increasing disease incidence. The model is calibrated using a dataset of reported cholera cases. We further model the long term impact of several types of interventions on the disease dynamics by varying parameters appropriately. Key epidemiological mechanisms and parameters which affect the efficiency of treatments such as antibiotics are identified. Our results lead to conclusions about the influence of different intervention strategies on the overall epidemiological dynamics.

Rainfall mediations in the spreading of epidemic cholera

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Righetto, L.; Bertuzzo, E.; Mari, L.; Schild, E.; Casagrandi, R.; Gatto, M.; Rodriguez-Iturbe, I.; Rinaldo, A.

2013-10-01

Following the empirical evidence of a clear correlation between rainfall events and cholera resurgence that was observed in particular during the recent outbreak in Haiti, a spatially explicit model of epidemic cholera is re-examined. Specifically, we test a multivariate Poisson rainfall generator, with parameters varying in space and time, as a driver of enhanced disease transmission. The relevance of the issue relates to the key insight that predictive mathematical models may provide into the course of an ongoing cholera epidemic aiding emergency management (say, in allocating life-saving supplies or health care staff) or in evaluating alternative management strategies. Our model consists of a set of dynamical equations (SIRB-like i.e. subdivided into the compartments of Susceptible, Infected and Recovered individuals, and including a balance of Bacterial concentrations in the water reservoir) describing a connected network of human communities where the infection results from the exposure to excess concentrations of pathogens in the water. These, in turn, are driven by rainfall washout of open-air defecation sites or cesspool overflows, hydrologic transport through waterways and by mobility of susceptible and infected individuals. We perform an a posteriori analysis (from the beginning of the epidemic in October 2010 until December 2011) to test the model reliability in predicting cholera cases and in testing control measures, involving vaccination and sanitation campaigns, for the ongoing epidemic. Even though predicting reliably the timing of the epidemic resurgence proves difficult due to rainfall inter-annual variability, we find that the model can reasonably quantify the total number of reported infection cases in the selected time-span. We then run a multi-seasonal prediction of the course of the epidemic until December 2015, to investigate conditions for further resurgences and endemicity of cholera in the region with a view to policies which may bring to

Assessment of Risk of Cholera in Haiti following Hurricane Matthew.

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Khan, Rakib; Anwar, Rifat; Akanda, Shafqat; McDonald, Michael D; Huq, Anwar; Jutla, Antarpreet; Colwell, Rita

2017-09-01

Damage to the inferior and fragile water and sanitation infrastructure of Haiti after Hurricane Matthew has created an urgent public health emergency in terms of likelihood of cholera occurring in the human population. Using satellite-derived data on precipitation, gridded air temperature, and hurricane path and with information on water and sanitation (WASH) infrastructure, we tracked changing environmental conditions conducive for growth of pathogenic vibrios. Based on these data, we predicted and validated the likelihood of cholera cases occurring past hurricane. The risk of cholera in the southwestern part of Haiti remained relatively high since November 2016 to the present. Findings of this study provide a contemporary process for monitoring ground conditions that can guide public health intervention to control cholera in human population by providing access to vaccines, safe WASH facilities. Assuming current social and behavioral patterns remain constant, it is recommended that WASH infrastructure should be improved and considered a priority especially before 2017 rainy season.

The increased severity in patients presenting to hospital with diarrhea in Dhaka, Bangladesh since the emergence of the hybrid strain of Vibrio cholerae O1 is not unique to cholera patients.

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Chowdhury, Fahima; Kuchta, Alison; Khan, Ashraful Islam; Faruque, A S G; Calderwood, Stephen B; Ryan, Edward T; Qadri, Firdausi

2015-11-01

A hybrid strain of Vibrio cholerae O1 El Tor that expresses a classical cholera toxin (CT) emerged in 2001. This hybrid variant rapidly replaced the previous El Tor strain around the world. The global emergence of this variant coincided with anecdotal reports that cholera patients were presenting with more severe dehydration and disease in many locations. A comparison was made of the severity of disease before and after the emergence of the hybrid strain in cholera patients attending an icddr,b hospital in Dhaka, Bangladesh. It was found that cholera patients presented with more severe dehydration and severe disease in the later period. However, this was also true for all non-cholera patients as well. In addition, in sub-analyses of patients who presented with rotavirus and enterotoxigenic Escherichia coli (ETEC), similar results were found. Comparing the two periods for differences in patient characteristics, nutritional status, vaccination status, and income, no plausible cause for patients presenting with more severe disease was identified in the later period. As a shift in severity for both cholera and non-cholera was observed, these results indicate that the altered El Tor strain cannot fully explain the difference in cholera severity before and after 2001. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

High-resolution spatial analysis of cholera patients reported in Artibonite department, Haiti in 2010–2011

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Maya Allan

2016-03-01

Conclusion/significance: These findings demonstrate the value of high-resolution mapping for pinpointing locations most affected by cholera, and in the future could help prioritize the places in need of interventions such as improvement of sanitation and vaccination. The findings also describe spatio-temporal transmission patterns of the epidemic in a cholera-naïve country such as Haiti. By identifying transmission hubs, it is possible to target prevention strategies that, over time, could reduce transmission of the disease and eventually eliminate cholera in Haiti.

Linking Satellite Derived Land Surface Temperature with Cholera: A Case Study for South Sudan

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Aldaach, H. S. V.; Jutla, A.; Akanda, A. S.; Colwell, R. R.

2014-12-01

A sudden onset of cholera in South Sudan, in April 2014 in Northern Bari in Juba town resulted in more than 400 cholera cases after four weeks of initial outbreak with a case of fatality rate of CFR 5.4%. The total number of reported cholera cases for the period of April to July, 2014 were 5,141 including 114 deaths. With the limited efficacy of cholera vaccines, it is necessary to develop mechanisms to predict cholera occurrence and thereafter devise intervention strategies for mitigating impacts of the disease. Hydroclimatic processes, primarily precipitation and air temperature are related to epidemic and episodic outbreak of cholera. However, due to coarse resolution of both datasets, it is not possible to precisely locate the geographical location of disease. Here, using Land Surface Temperature (LST) from MODIS sensors, we have developed an algorithm to identify regions susceptible for cholera. Conditions for occurrence of cholera were detectable at least one month in advance in South Sudan and were statistically sensitive to hydroclimatic anomalies of land surface and air temperature, and precipitation. Our results indicate significant spatial and temporal averaging required to infer usable information from LST over South Sudan. Preliminary results that geographically location of cholera outbreak was identifiable within 1km resolution of the LST data.

Therapeutic Potential of Cholera Toxin B Subunit for the Treatment of Inflammatory Diseases of the Mucosa

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Joshua M. Royal

2017-11-01

Full Text Available Cholera toxin B subunit (CTB is a mucosal immunomodulatory protein that induces robust mucosal and systemic antibody responses. This well-known biological activity has been exploited in cholera prevention (as a component of Dukoral® vaccine and vaccine development for decades. On the other hand, several studies have investigated CTB’s immunotherapeutic potential in the treatment of inflammatory diseases such as Crohn’s disease and asthma. Furthermore, we recently found that a variant of CTB could induce colon epithelial wound healing in mouse colitis models. This review summarizes the possible mechanisms behind CTB’s anti-inflammatory activity and discuss how the protein could impact mucosal inflammatory disease treatment.

Cholera

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... causes a large amount of watery diarrhea. Causes Cholera is caused by the bacterium Vibrio cholerae . These bacteria release a toxin that causes an ... include: Africa Some parts of Asia India Bangladesh Mexico South and Central America ... Symptoms of cholera can be mild to severe. They include: Abdominal ...

Vibrio cholerae Infection of Drosophilamelanogaster Mimics the Human Disease Cholera.

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2005-09-01

Full Text Available Cholera, the pandemic diarrheal disease caused by the gram-negative bacterium Vibrio cholerae, continues to be a major public health challenge in the developing world. Cholera toxin, which is responsible for the voluminous stools of cholera, causes constitutive activation of adenylyl cyclase, resulting in the export of ions into the intestinal lumen. Environmental studies have demonstrated a close association between V. cholerae and many species of arthropods including insects. Here we report the susceptibility of the fruit fly, Drosophila melanogaster, to oral V. cholerae infection through a process that exhibits many of the hallmarks of human disease: (i death of the fly is dependent on the presence of cholera toxin and is preceded by rapid weight loss; (ii flies harboring mutant alleles of either adenylyl cyclase, Gsalpha, or the Gardos K channel homolog SK are resistant to V. cholerae infection; and (iii ingestion of a K channel blocker along with V. cholerae protects wild-type flies against death. In mammals, ingestion of as little as 25 mug of cholera toxin results in massive diarrhea. In contrast, we found that ingestion of cholera toxin was not lethal to the fly. However, when cholera toxin was co-administered with a pathogenic strain of V. cholerae carrying a chromosomal deletion of the genes encoding cholera toxin, death of the fly ensued. These findings suggest that additional virulence factors are required for intoxication of the fly that may not be essential for intoxication of mammals. Furthermore, we demonstrate for the first time the mechanism of action of cholera toxin in a whole organism and the utility of D. melanogaster as an accurate, inexpensive model for elucidation of host susceptibility to cholera.

The potential impact of case-area targeted interventions in response to cholera outbreaks: A modeling study.

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Finger, Flavio; Bertuzzo, Enrico; Luquero, Francisco J; Naibei, Nathan; Touré, Brahima; Allan, Maya; Porten, Klaudia; Lessler, Justin; Rinaldo, Andrea; Azman, Andrew S

2018-02-01

Cholera prevention and control interventions targeted to neighbors of cholera cases (case-area targeted interventions [CATIs]), including improved water, sanitation, and hygiene, oral cholera vaccine (OCV), and prophylactic antibiotics, may be able to efficiently avert cholera cases and deaths while saving scarce resources during epidemics. Efforts to quickly target interventions to neighbors of cases have been made in recent outbreaks, but little empirical evidence related to the effectiveness, efficiency, or ideal design of this approach exists. Here, we aim to provide practical guidance on how CATIs might be used by exploring key determinants of intervention impact, including the mix of interventions, "ring" size, and timing, in simulated cholera epidemics fit to data from an urban cholera epidemic in Africa. We developed a micro-simulation model and calibrated it to both the epidemic curve and the small-scale spatiotemporal clustering pattern of case households from a large 2011 cholera outbreak in N'Djamena, Chad (4,352 reported cases over 232 days), and explored the potential impact of CATIs in simulated epidemics. CATIs were implemented with realistic logistical delays after cases presented for care using different combinations of prophylactic antibiotics, OCV, and/or point-of-use water treatment (POUWT) starting at different points during the epidemics and targeting rings of various radii around incident case households. Our findings suggest that CATIs shorten the duration of epidemics and are more resource-efficient than mass campaigns. OCV was predicted to be the most effective single intervention, followed by POUWT and antibiotics. CATIs with OCV started early in an epidemic focusing on a 100-m radius around case households were estimated to shorten epidemics by 68% (IQR 62% to 72%), with an 81% (IQR 69% to 87%) reduction in cases compared to uncontrolled epidemics. These same targeted interventions with OCV led to a 44-fold (IQR 27 to 78) reduction in

[An oral chemical vaccine from the hypertoxigenic strains of the causative agent of cholera KM-76 Inaba and KM-68 Ogawa].

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Dzhaparidze, M N; Naumov, A V; Nikitina, G P; Meleshchenko, M V; Dobrova, G V; Zavorotnykh, V I; Gracheva, V P; Zakharova, T L

1991-04-01

The material on the development of chemical vaccine, prepared from two newly formed strains (KM-76 Inaba and KM-68 Ogawa) and intended for oral administration, is presented. The conditions for the submerged cultivation of these strains have been established, which makes it possible to increase the production of choleragen 8- to 10-fold and O-antigen 3- to 4-fold in comparison with V. cholerae natural strain 569B. The maximum accumulation of neuraminidase, protease, phospholipase, along with choleragen, has been registered in the logarithmic phase and that of O-antigen, in the stationary phase of growth. The use of strains KM-76 and KM-68 has led to the fourfold increase of the specific activity of the main immunogens, thus permitting the respective increase of the yield of the oral vaccine without changes in its high capacity for the formation of specific antibodies and its low residual toxigenicity.

Cholera Treatment

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... Diagnosis and Detection Laboratory Testing for Cholera Treatment Rehydration Therapy Antibiotic Treatment Zinc Treatment Prevention & Control Five ... page for current cholera treatment recommendations. Cholera Treatments Rehydration therapy , meaning prompt restoration of lost fluids and ...

Cholera Incidence and Mortality in Sub-Saharan African Sites during Multi-country Surveillance

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Sauvageot, Delphine; Njanpop-Lafourcade, Berthe-Marie; Akilimali, Laurent; Anne, Jean-Claude; Bidjada, Pawou; Bompangue, Didier; Bwire, Godfrey; Coulibaly, Daouda; Dengo-Baloi, Liliana; Dosso, Mireille; Orach, Christopher Garimoi; Inguane, Dorteia; Kagirita, Atek; Kacou-N’Douba, Adele; Keita, Sakoba; Kere Banla, Abiba; Kouame, Yao Jean-Pierre; Landoh, Dadja Essoya; Langa, Jose Paulo; Makumbi, Issa; Miwanda, Berthe; Malimbo, Muggaga; Mutombo, Guy; Mutombo, Annie; NGuetta, Emilienne Niamke; Saliou, Mamadou; Sarr, Veronique; Senga, Raphael Kakongo; Sory, Fode; Sema, Cynthia; Tante, Ouyi Valentin; Gessner, Bradford D.; Mengel, Martin A.

2016-01-01

Background Cholera burden in Africa remains unknown, often because of weak national surveillance systems. We analyzed data from the African Cholera Surveillance Network (www.africhol.org). Methods/ Principal findings During June 2011–December 2013, we conducted enhanced surveillance in seven zones and four outbreak sites in Togo, the Democratic Republic of Congo (DRC), Guinea, Uganda, Mozambique and Cote d’Ivoire. All health facilities treating cholera cases were included. Cholera incidences were calculated using culture-confirmed cholera cases and culture-confirmed cholera cases corrected for lack of culture testing usually due to overwhelmed health systems and imperfect test sensitivity. Of 13,377 reported suspected cases, 34% occurred in Conakry, Guinea, 47% in Goma, DRC, and 19% in the remaining sites. From 0–40% of suspected cases were aged under five years and from 0.3–86% had rice water stools. Within surveillance zones, 0–37% of suspected cases had confirmed cholera compared to 27–38% during outbreaks. Annual confirmed incidence per 10,000 population was Conakry had corrected incidences of 20.2 and 5.8 respectively, while the other zones a median of 0.3. During outbreaks, corrected incidence varied from 2.6 to 13.0. Case fatality ratios ranged from 0–10% (median, 1%) by country. Conclusions/Significance Across different African epidemiological contexts, substantial variation occurred in cholera incidence, age distribution, clinical presentation, culture confirmation, and testing frequency. These results can help guide preventive activities, including vaccine use. PMID:27186885

An Optimal Cost Effectiveness Study on Zimbabwe Cholera Seasonal Data from 2008–2011

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Sardar, Tridip; Mukhopadhyay, Soumalya; Bhowmick, Amiya Ranjan; Chattopadhyay, Joydev

2013-01-01

Incidence of cholera outbreak is a serious issue in underdeveloped and developing countries. In Zimbabwe, after the massive outbreak in 2008–09, cholera cases and deaths are reported every year from some provinces. Substantial number of reported cholera cases in some provinces during and after the epidemic in 2008–09 indicates a plausible presence of seasonality in cholera incidence in those regions. We formulate a compartmental mathematical model with periodic slow-fast transmission rate to study such recurrent occurrences and fitted the model to cumulative cholera cases and deaths for different provinces of Zimbabwe from the beginning of cholera outbreak in 2008–09 to June 2011. Daily and weekly reported cholera incidence data were collected from Zimbabwe epidemiological bulletin, Zimbabwe Daily cholera updates and Office for the Coordination of Humanitarian Affairs Zimbabwe (OCHA, Zimbabwe). For each province, the basic reproduction number () in periodic environment is estimated. To the best of our knowledge, this is probably a pioneering attempt to estimate in periodic environment using real-life data set of cholera epidemic for Zimbabwe. Our estimates of agree with the previous estimate for some provinces but differ significantly for Bulawayo, Mashonaland West, Manicaland, Matabeleland South and Matabeleland North. Seasonal trend in cholera incidence is observed in Harare, Mashonaland West, Mashonaland East, Manicaland and Matabeleland South. Our result suggests that, slow transmission is a dominating factor for cholera transmission in most of these provinces. Our model projects cholera cases and cholera deaths during the end of the epidemic in 2008–09 to January 1, 2012. We also determine an optimal cost-effective control strategy among the four government undertaken interventions namely promoting hand-hygiene & clean water distribution, vaccination, treatment and sanitation for each province. PMID:24312540

Update: cholera--Western Hemisphere, and recommendations for treatment of cholera.

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1991-08-16

Epidemic cholera appeared in Peru in January 1991 and subsequently spread to Ecuador, Colombia, Chile, Brazil, Mexico, and Guatemala. Cholera can be a severe, life-threatening illness but is highly preventable and easily treated; however, few health-care practitioners in the United States have experience identifying and treating cholera. This report provides an update on cholera in the Western Hemisphere and provides recommendations on the clinical diagnosis and treatment of cholera in the United States.

The high burden of cholera in children: comparison of incidence from endemic areas in Asia and Africa.

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Jacqueline L Deen

Full Text Available BACKGROUND: Cholera remains an important public health problem. Yet there are few reliable population-based estimates of laboratory-confirmed cholera incidence in endemic areas around the world. METHODS: We established treatment facility-based cholera surveillance in three sites in Jakarta (Indonesia, Kolkata (India, and Beira (Mozambique. The annual incidence of cholera was estimated using the population census as the denominator and the age-specific number of cholera cases among the study cohort as the numerator. FINDINGS: The lowest overall rate was found in Jakarta, where the estimated incidence was 0.5/1000 population/year. The incidence was three times higher in Kolkata (1.6/1000/year and eight times higher in Beira (4.0/1000/year. In all study sites, the greatest burden was in children under 5 years of age. CONCLUSION: There are considerable differences in cholera incidence across these endemic areas but in all sites, children are the most affected. The study site in Africa had the highest cholera incidence consistent with a growing impression of the large cholera burden in Africa. Burden estimates are useful when considering where and among whom interventions such as vaccination would be most needed.

Comparing sociocultural features of cholera in three endemic African settings

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2013-01-01

Background Cholera mainly affects developing countries where safe water supply and sanitation infrastructure are often rudimentary. Sub-Saharan Africa is a cholera hotspot. Effective cholera control requires not only a professional assessment, but also consideration of community-based priorities. The present work compares local sociocultural features of endemic cholera in urban and rural sites from three field studies in southeastern Democratic Republic of Congo (SE-DRC), western Kenya and Zanzibar. Methods A vignette-based semistructured interview was used in 2008 in Zanzibar to study sociocultural features of cholera-related illness among 356 men and women from urban and rural communities. Similar cross-sectional surveys were performed in western Kenya (n = 379) and in SE-DRC (n = 360) in 2010. Systematic comparison across all settings considered the following domains: illness identification; perceived seriousness, potential fatality and past household episodes; illness-related experience; meaning; knowledge of prevention; help-seeking behavior; and perceived vulnerability. Results Cholera is well known in all three settings and is understood to have a significant impact on people’s lives. Its social impact was mainly characterized by financial concerns. Problems with unsafe water, sanitation and dirty environments were the most common perceived causes across settings; nonetheless, non-biomedical explanations were widespread in rural areas of SE-DRC and Zanzibar. Safe food and water and vaccines were prioritized for prevention in SE-DRC. Safe water was prioritized in western Kenya along with sanitation and health education. The latter two were also prioritized in Zanzibar. Use of oral rehydration solutions and rehydration was a top priority everywhere; healthcare facilities were universally reported as a primary source of help. Respondents in SE-DRC and Zanzibar reported cholera as affecting almost everybody without differentiating much for gender, age

Mapping the burden of cholera in sub-Saharan Africa and implications for control: an analysis of data across geographical scales.

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Lessler, Justin; Moore, Sean M; Luquero, Francisco J; McKay, Heather S; Grais, Rebecca; Henkens, Myriam; Mengel, Martin; Dunoyer, Jessica; M'bangombe, Maurice; Lee, Elizabeth C; Djingarey, Mamoudou Harouna; Sudre, Bertrand; Bompangue, Didier; Fraser, Robert S M; Abubakar, Abdinasir; Perea, William; Legros, Dominique; Azman, Andrew S

2018-03-01

Cholera remains a persistent health problem in sub-Saharan Africa and worldwide. Cholera can be controlled through appropriate water and sanitation, or by oral cholera vaccination, which provides transient (∼3 years) protection, although vaccine supplies remain scarce. We aimed to map cholera burden in sub-Saharan Africa and assess how geographical targeting could lead to more efficient interventions. We combined information on cholera incidence in sub-Saharan Africa (excluding Djibouti and Eritrea) from 2010 to 2016 from datasets from WHO, Médecins Sans Frontières, ProMED, ReliefWeb, ministries of health, and the scientific literature. We divided the study region into 20 km × 20 km grid cells and modelled annual cholera incidence in each grid cell assuming a Poisson process adjusted for covariates and spatially correlated random effects. We combined these findings with data on population distribution to estimate the number of people living in areas of high cholera incidence (>1 case per 1000 people per year). We further estimated the reduction in cholera incidence that could be achieved by targeting cholera prevention and control interventions at areas of high cholera incidence. We included 279 datasets covering 2283 locations in our analyses. In sub-Saharan Africa (excluding Djibouti and Eritrea), a mean of 141 918 cholera cases (95% credible interval [CrI] 141 538-146 505) were reported per year. 4·0% (95% CrI 1·7-16·8) of districts, home to 87·2 million people (95% CrI 60·3 million to 118·9 million), have high cholera incidence. By focusing on the highest incidence districts first, effective targeted interventions could eliminate 50% of the region's cholera by covering 35·3 million people (95% CrI 26·3 million to 62·0 million), which is less than 4% of the total population. Although cholera occurs throughout sub-Saharan Africa, its highest incidence is concentrated in a small proportion of the continent. Prioritising high-risk areas

Cholera Incidence and Mortality in Sub-Saharan African Sites during Multi-country Surveillance.

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Delphine Sauvageot

2016-05-01

Full Text Available Cholera burden in Africa remains unknown, often because of weak national surveillance systems. We analyzed data from the African Cholera Surveillance Network (www.africhol.org.During June 2011-December 2013, we conducted enhanced surveillance in seven zones and four outbreak sites in Togo, the Democratic Republic of Congo (DRC, Guinea, Uganda, Mozambique and Cote d'Ivoire. All health facilities treating cholera cases were included. Cholera incidences were calculated using culture-confirmed cholera cases and culture-confirmed cholera cases corrected for lack of culture testing usually due to overwhelmed health systems and imperfect test sensitivity. Of 13,377 reported suspected cases, 34% occurred in Conakry, Guinea, 47% in Goma, DRC, and 19% in the remaining sites. From 0-40% of suspected cases were aged under five years and from 0.3-86% had rice water stools. Within surveillance zones, 0-37% of suspected cases had confirmed cholera compared to 27-38% during outbreaks. Annual confirmed incidence per 10,000 population was <0.5 in surveillance zones, except Goma where it was 4.6. Goma and Conakry had corrected incidences of 20.2 and 5.8 respectively, while the other zones a median of 0.3. During outbreaks, corrected incidence varied from 2.6 to 13.0. Case fatality ratios ranged from 0-10% (median, 1% by country.Across different African epidemiological contexts, substantial variation occurred in cholera incidence, age distribution, clinical presentation, culture confirmation, and testing frequency. These results can help guide preventive activities, including vaccine use.

The repertoire of glycosphingolipids recognized by Vibrio cholerae.

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John Benktander

Full Text Available The binding of cholera toxin to the ganglioside GM1 as the initial step in the process leading to diarrhea is nowadays textbook knowledge. In contrast, the knowledge about the mechanisms for attachment of Vibrio cholerae bacterial cells to the intestinal epithelium is limited. In order to clarify this issue, a large number of glycosphingolipid mixtures were screened for binding of El Tor V. cholerae. Several specific interactions with minor complex non-acid glycosphingolipids were thereby detected. After isolation of binding-active glycosphingolipids, characterization by mass spectrometry and proton NMR, and comparative binding studies, three distinct glycosphingolipid binding patterns were defined. Firstly, V. cholerae bound to complex lacto/neolacto glycosphingolipids with the GlcNAcβ3Galβ4GlcNAc sequence as the minimal binding epitope. Secondly, glycosphingolipids with a terminal Galα3Galα3Gal moiety were recognized, and the third specificity was the binding to lactosylceramide and related compounds. V. cholerae binding to lacto/neolacto glycosphingolipids, and to the other classes of binding-active compounds, remained after deletion of the chitin binding protein GbpA. Thus, the binding of V. cholerae to chitin and to lacto/neolacto containing glycosphingolipids represents two separate binding specificities.

Analyzing transmission dynamics of cholera with public health interventions.

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Posny, Drew; Wang, Jin; Mukandavire, Zindoga; Modnak, Chairat

2015-06-01

Cholera continues to be a serious public health concern in developing countries and the global increase in the number of reported outbreaks suggests that activities to control the diseases and surveillance programs to identify or predict the occurrence of the next outbreaks are not adequate. These outbreaks have increased in frequency, severity, duration and endemicity in recent years. Mathematical models for infectious diseases play a critical role in predicting and understanding disease mechanisms, and have long provided basic insights in the possible ways to control infectious diseases. In this paper, we present a new deterministic cholera epidemiological model with three types of control measures incorporated into a cholera epidemic setting: treatment, vaccination and sanitation. Essential dynamical properties of the model with constant intervention controls which include local and global stabilities for the equilibria are carefully analyzed. Further, using optimal control techniques, we perform a study to investigate cost-effective solutions for time-dependent public health interventions in order to curb disease transmission in epidemic settings. Our results show that the basic reproductive number (R0) remains the model's epidemic threshold despite the inclusion of a package of cholera interventions. For time-dependent controls, the results suggest that these interventions closely interplay with each other, and the costs of controls directly affect the length and strength of each control in an optimal strategy. Copyright © 2015 Elsevier Inc. All rights reserved.

Emergency Preparedness in the Workplace: The Flulapalooza Model for Mass Vaccination.

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Swift, Melanie D; Aliyu, Muktar H; Byrne, Daniel W; Qian, Keqin; McGown, Paula; Kinman, Patricia O; Hanson, Katherine Louise; Culpepper, Demoyne; Cooley, Tamara J; Yarbrough, Mary I

2017-09-01

To explore whether an emergency preparedness structure is a feasible, efficient, and sustainable way for health care organizations to manage mass vaccination events. We used the Hospital Incident Command System to conduct a 1-day annual mass influenza vaccination event at Vanderbilt University Medical Center over 5 successive years (2011-2015). Using continuous quality improvement principles, we assessed whether changes in layout, supply management, staffing, and documentation systems improved efficiency. A total of 66 591 influenza vaccines were administered at 5 annual Flulapalooza events; 13 318 vaccines per event on average. Changes to the physical layout, staffing mix, and documentation processes improved vaccination efficiency 74%, from approximately 38 to 67 vaccines per hour per vaccinator, while reducing overall staffing needs by 38%. An unexpected finding was the role of social media in facilitating active engagement. Health care organizations can use a closed point-of-dispensing model and Hospital Incident Command System to conduct mass vaccination events, and can adopt the "Flulapalooza method" as a best practice model to enhance efficiency.

A spatially explicit model for the future progression of the current Haiti cholera epidemic

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Bertuzzo, E.; Mari, L.; Righetto, L.; Gatto, M.; Casagrandi, R.; Rodriguez-Iturbe, I.; Rinaldo, A.

2011-12-01

As a major cholera epidemic progresses in Haiti, and the figures of the infection, up to July 2011, climb to 385,000 cases and 5,800 deaths, the development of general models to track and predict the evolution of the outbreak, so as to guide the allocation of medical supplies and staff, is gaining notable urgency. We propose here a spatially explicit epidemic model that accounts for the dynamics of susceptible and infected individuals as well as the redistribution of textit{Vibrio cholera}, the causative agent of the disease, among different human communities. In particular, we model two spreading pathways: the advection of pathogens through hydrologic connections and the dissemination due to human mobility described by means of a gravity-like model. To this end the country has been divided into hydrologic units based on drainage directions derived from a digital terrain model. Moreover the population of each unit has been estimated from census data downscaled to 1 km x 1 km resolution via remotely sensed geomorphological information (LandScan texttrademark project). The model directly account for the role of rainfall patterns in driving the seasonality of cholera outbreaks. The two main outbreaks in fact occurred during the rainy seasons (October and May) when extensive floodings severely worsened the sanitation conditions and, in turn, raised the risk of infection. The model capability to reproduce the spatiotemporal features of the epidemic up to date grants robustness to the foreseen future development. In this context, the duration of acquired immunity, a hotly debated topic in the scientific community, emerges as a controlling factor for progression of the epidemic in the near future. The framework presented here can straightforwardly be used to evaluate the effectiveness of alternative intervention strategies like mass vaccinations, clean water supply and educational campaigns, thus emerging as an essential component of the control of future cholera

Vaccines for viral and bacterial pathogens causing acute gastroenteritis: Part II: Vaccines for Shigella, Salmonella, enterotoxigenic E. coli (ETEC) enterohemorragic E. coli (EHEC) and Campylobacter jejuni

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O’Ryan, Miguel; Vidal, Roberto; del Canto, Felipe; Carlos Salazar, Juan; Montero, David

2015-01-01

In Part II we discuss the following bacterial pathogens: Shigella, Salmonella (non-typhoidal), diarrheogenic E. coli (enterotoxigenic and enterohemorragic) and Campylobacter jejuni. In contrast to the enteric viruses and Vibrio cholerae discussed in Part I of this series, for the bacterial pathogens described here there is only one licensed vaccine, developed primarily for Vibrio cholerae and which provides moderate protection against enterotoxigenic E. coli (ETEC) (Dukoral®), as well as a few additional candidates in advanced stages of development for ETEC and one candidate for Shigella spp. Numerous vaccine candidates in earlier stages of development are discussed. PMID:25715096

Oral administration of a recombinant cholera toxin B subunit promotes mucosal healing in the colon.

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Baldauf, K J; Royal, J M; Kouokam, J C; Haribabu, B; Jala, V R; Yaddanapudi, K; Hamorsky, K T; Dryden, G W; Matoba, N

2017-07-01

Cholera toxin B subunit (CTB) is a component of a licensed oral cholera vaccine. However, CTB has pleiotropic immunomodulatory effects whose impacts on the gut are not fully understood. Here, we found that oral administration in mice of a plant-made recombinant CTB (CTBp) significantly increased several immune cell populations in the colon lamina propria. Global gene expression analysis revealed that CTBp had more pronounced impacts on the colon than the small intestine, with significant activation of TGFβ-mediated pathways in the colon epithelium. The clinical relevance of CTBp-induced impacts on colonic mucosa was examined. In a human colon epithelial model using Caco2 cells, CTBp, but not the non-GM1-binding mutant G33D-CTBp, induced TGFβ-mediated wound healing. In a dextran sodium sulfate (DSS) acute colitis mouse model, oral administration of CTBp protected against colon mucosal damage as manifested by mitigated body weight loss, decreased histopathological scores, and blunted escalation of inflammatory cytokine levels while inducing wound healing-related genes. Furthermore, biweekly oral administration of CTBp significantly reduced disease severity and tumorigenesis in the azoxymethane/DSS model of ulcerative colitis and colon cancer. Altogether, these results demonstrate CTBp's ability to enhance mucosal healing in the colon, highlighting its potential application in ulcerative colitis therapy besides cholera vaccination.

The risk of aseptic meningitis associated with the Leningrad-Zagreb mumps vaccine strain following mass vaccination with measles-mumps-rubella vaccine, Rio Grande do Sul, Brazil, 1997.

Science.gov (United States)

da Silveira, Claudio Marcos; Kmetzsch, Claudete Iris; Mohrdieck, Renate; Sperb, Alethea Fagundes; Prevots, D Rebecca

2002-10-01

Few data are available on the risk of aseptic meningitis following vaccination with the Leningrad-Zagreb (L-Z) strain of mumps vaccine. In 1997 the mumps vaccine was introduced into the state of Rio Grande do Sul in Brazil through mass vaccination with mumps-measles-rubella (MMR), targeting children aged 1-11 years. Five municipalities used exclusively MMR vaccine containing the L-Z strain of mumps. An outbreak of aseptic meningitis was observed shortly after the mass campaign. To estimate the risk of aseptic meningitis associated with this strain, we analysed vaccination and meningitis case surveillance data from the selected municipalities. A case of vaccine-associated aseptic meningitis was defined as one with a pleocytosis of 10-1,500 leukocytes/ml and occurring within 15-35 days after vaccine receipt. We estimated a risk of 2.9 cases per 10,000 doses of L-Z administered, equivalent to 1 case per 3,390 doses administered. The overall risk of aseptic meningitis following the campaign was increased 12.2-fold (95% CI: 6.0-24.7) compared with the same period in 1995-1996. Following the mass campaign, the incidence of mumps declined 93% during 1998-2000. Vaccination with the L-Z strain of mumps vaccine as part of a mass campaign was associated with a significantly increased risk of aseptic meningitis. Decisions about type of mumps vaccine and mumps vaccination strategies must consider vaccine safety issues in addition to other criteria.

Cholera in Zimbabwe

NARCIS (Netherlands)

Pruyt, E.

2009-01-01

By the end of December 2008, alarming reports and articles concerning the cholera outbreak in Zimbabwe received plenty of international media coverage. By that time nearly 30000 cases of cholera infections and 1600 cholera deaths had been reported. In the first week of January 2009, a System

Vaccines today, vaccines tomorrow: a perspective.

Science.gov (United States)

Loucq, Christian

2013-01-01

Vaccines are considered as one of the major contributions of the 20th century and one of the most cost effective public health interventions. The International Vaccine Institute has as a mission to discover, develop and deliver new and improved vaccines against infectious diseases that affects developing nations. If Louis Pasteur is known across the globe, vaccinologists like Maurice Hilleman, Jonas Salk and Charles Mérieux are known among experts only despite their contribution to global health. Thanks to a vaccine, smallpox has been eradicated, polio has nearly disappeared, Haemophilus influenzae B, measles and more recently meningitis A are controlled in many countries. While a malaria vaccine is undergoing phase 3, International Vaccine Institute, in collaboration with an Indian manufacturer has brought an oral inactivated cholera vaccine to pre-qualification. The field of vaccinology has undergone major changes thanks to philanthropists such as Bill and Melinda Gates, initiatives like the Decade of Vaccines and public private partnerships. Current researches on vaccines have more challenging targets like the dengue viruses, malaria, human immunodeficiency virus, the respiratory syncytial virus and nosocomial diseases. Exciting research is taking place on new adjuvants, nanoparticles, virus like particles and new route of administration. An overcrowded infant immunization program, anti-vaccine groups, immunizing a growing number of elderlies and delivering vaccines to difficult places are among challenges faced by vaccinologists and global health experts.

The global burden of cholera

Science.gov (United States)

Lopez, Anna Lena; You, Young Ae; Kim, Young Eun; Sah, Binod; Maskery, Brian; Clemens, John

2012-01-01

Abstract Objective To estimate the global burden of cholera using population-based incidence data and reports. Methods Countries with a recent history of cholera were classified as endemic or non-endemic, depending on whether they had reported cholera cases in at least three of the five most recent years. The percentages of the population in each country that lacked access to improved sanitation were used to compute the populations at risk for cholera, and incidence rates from published studies were applied to groups of countries to estimate the annual number of cholera cases in endemic countries. The estimates of cholera cases in non-endemic countries were based on the average numbers of cases reported from 2000 to 2008. Literature-based estimates of cholera case-fatality rates (CFRs) were used to compute the variance-weighted average cholera CFRs for estimating the number of cholera deaths. Findings About 1.4 billion people are at risk for cholera in endemic countries. An estimated 2.8 million cholera cases occur annually in such countries (uncertainty range: 1.4–4.3) and an estimated 87 000 cholera cases occur in non-endemic countries. The incidence is estimated to be greatest in children less than 5 years of age. Every year about 91 000 people (uncertainty range: 28 000 to 142 000) die of cholera in endemic countries and 2500 people die of the disease in non-endemic countries. Conclusion The global burden of cholera, as determined through a systematic review with clearly stated assumptions, is high. The findings of this study provide a contemporary basis for planning public health interventions to control cholera. PMID:22461716

Spatio-temporal epidemiology of the cholera outbreak in Papua New Guinea, 2009-2011.

Science.gov (United States)

Horwood, Paul F; Karl, Stephan; Mueller, Ivo; Jonduo, Marinjho H; Pavlin, Boris I; Dagina, Rosheila; Ropa, Berry; Bieb, Sibauk; Rosewell, Alexander; Umezaki, Masahiro; Siba, Peter M; Greenhill, Andrew R

2014-08-20

Cholera continues to be a devastating disease in many developing countries where inadequate safe water supply and poor sanitation facilitate spread. From July 2009 until late 2011 Papua New Guinea experienced the first outbreak of cholera recorded in the country, resulting in >15,500 cases and >500 deaths. Using the national cholera database, we analysed the spatio-temporal distribution and clustering of the Papua New Guinea cholera outbreak. The Kulldorff space-time permutation scan statistic, contained in the software package SatScan v9.2 was used to describe the first 8 weeks of the outbreak in Morobe Province before cholera cases spread throughout other regions of the country. Data were aggregated at the provincial level to describe the spread of the disease to other affected provinces. Spatio-temporal and cluster analyses revealed that the outbreak was characterized by three distinct phases punctuated by explosive propagation of cases when the outbreak spread to a new region. The lack of road networks across most of Papua New Guinea is likely to have had a major influence on the slow spread of the disease during this outbreak. Identification of high risk areas and the likely mode of spread can guide government health authorities to formulate public health strategies to mitigate the spread of the disease through education campaigns, vaccination, increased surveillance in targeted areas and interventions to improve water, sanitation and hygiene.

[Cholera in pediatrics].

Science.gov (United States)

Lezama-Basulto, L A; Mota-Hernández, F

1993-09-01

Cholerae is a grave and acute bacterial intestine infection which is caused by a bacilo, V. cholerae 01, that produces toxic products. Its clinical symptoms range from abundant liquid diarrhoea combined with vomiting and rapid dehydration. It is highly lethal when right treatment is not applied. There are also cases of cholera where victims do not show any symptoms of it, that is asymptomatic carriers. Any clinical suspicion of cholerae has to be corroborated by epidemiological data and its diagnostic confirmation should be done by isolating the bacteria, V. cholerae. When beginning the treatment, it is not necessary to confirm the diagnostic and this is based on the restitution of the liquids lost through vomiting and facing using any methods that are recommended for any other type of diarrhoea. The antimicrobial treatment is used only for grave cases. This present revision includes recent knowledge about cholerae emphasising on the effective management of cases through an adequate use of right treatment methods and also using the principal prevention measures against dissemination of this disease.

An epidemic model for the future progression of the current Haiti cholera epidemic

Science.gov (United States)

Bertuzzo, E.; Mari, L.; Righetto, L.; Casagrandi, R.; Gatto, M.; Rodriguez-Iturbe, I.; Rinaldo, A.

2012-04-01

As a major cholera epidemic progresses in Haiti, and the figures of the infection, up to December 2011, climb to 522,000 cases and 7,000 deaths, the development of general models to track and predict the evolution of the outbreak, so as to guide the allocation of medical supplies and staff, is gaining notable urgency. We propose here a spatially explicit epidemic model that accounts for the dynamics of susceptible and infected individuals as well as the redistribution of Vibrio cholera, the causative agent of the disease, among different human communities. In particular, we model two spreading pathways: the advection of pathogens through hydrologic connections and the dissemination due to human mobility described by means of a gravity-like model. To this end the country has been divided into hydrologic units based on drainage directions derived from a digital terrain model. Moreover the population of each unit has been estimated from census data downscaled to 1 km x 1 km resolution via remotely sensed geomorphological information (LandScan project). The model directly accounts for the role of rainfall patterns in driving the seasonality of cholera outbreaks. The two main outbreaks in fact occurred during the rainy seasons (October and May) when extensive floodings severely worsened the sanitation conditions and, in turn, raised the risk of infection. The model capability to reproduce the spatiotemporal features of the epidemic up to date grants robustness to the foreseen future development. To this end, we generate realistic scenario of future precipitation in order to forecast possible epidemic paths up to the end of the 2013. In this context, the duration of acquired immunity, a hotly debated topic in the scientific community, emerges as a controlling factor for progression of the epidemic in the near future. The framework presented here can straightforwardly be used to evaluate the effectiveness of alternative intervention strategies like mass vaccinations

Identifying cholera "hotspots" in Uganda: An analysis of cholera surveillance data from 2011 to 2016.

Science.gov (United States)

Bwire, Godfrey; Ali, Mohammad; Sack, David A; Nakinsige, Anne; Naigaga, Martha; Debes, Amanda K; Ngwa, Moise C; Brooks, W Abdullah; Garimoi Orach, Christopher

2017-12-01

Despite advance in science and technology for prevention, detection and treatment of cholera, this infectious disease remains a major public health problem in many countries in sub-Saharan Africa, Uganda inclusive. The aim of this study was to identify cholera hotspots in Uganda to guide the development of a roadmap for prevention, control and elimination of cholera in the country. We obtained district level confirmed cholera outbreak data from 2011 to 2016 from the Ministry of Health, Uganda. Population and rainfall data were obtained from the Uganda Bureau of Statistics, and water, sanitation and hygiene data from the Ministry of Water and Environment. A spatial scan test was performed to identify the significantly high risk clusters. Cholera hotspots were defined as districts whose center fell within a significantly high risk cluster or where a significantly high risk cluster was completely superimposed onto a district. A zero-inflated negative binomial regression model was employed to identify the district level risk factors for cholera. In total 11,030 cases of cholera were reported during the 6-year period. 37(33%) of 112 districts reported cholera outbreaks in one of the six years, and 20 (18%) districts experienced cholera at least twice in those years. We identified 22 districts as high risk for cholera, of which 13 were near a border of Democratic Republic of Congo (DRC), while 9 districts were near a border of Kenya. The relative risk of having cholera inside the high-risk districts (hotspots) were 2 to 22 times higher than elsewhere in the country. In total, 7 million people were within cholera hotspots. The negative binomial component of the ZINB model shows people living near a lake or the Nile river were at increased risk for cholera (incidence rate ratio, IRR = 0.98, 95% CI: 0.97 to 0.99, p cholera in a district (IRR = 0.99, 95% CI: 0.98 to 1.00, p = .02 and IRR = 1.02, 95% CI: 1.01 to 1.03, p cholera in the district. The study identified cholera

Actions of cholera toxin and the prevention and treatment of cholera

Science.gov (United States)

Holmgren, Jan

1981-07-01

The drastic intestinal secretion of fluid and electrolytes that is characteristic of cholera is the result of reasonably well understood cellular and biochemical actions of the toxin secreted by Vibrio cholerae. Based on this understanding it is possible to devise new techniques for the treatment and prophylaxis of cholera to complement those based on fluid replacement therapy and sanitation.

Phylogenetic Diversity of Vibrio cholerae Associated with Endemic Cholera in Mexico from 1991 to 2008

OpenAIRE

Choi, Seon Young; Rashed, Shah M.; Hasan, Nur A.; Alam, Munirul; Islam, Tarequl; Sadique, Abdus; Johura, Fatema-Tuz; Eppinger, Mark; Ravel, Jacques; Huq, Anwar; Cravioto, Alejandro; Colwell, Rita R.

2016-01-01

ABSTRACT An outbreak of cholera occurred in 1991 in Mexico, where it had not been reported for more than a century and is now endemic. Vibrio cholerae O1 prototype El Tor and classical strains coexist with altered El Tor strains (1991 to 1997). Nontoxigenic (CTX?) V.?cholerae El Tor dominated toxigenic (CTX+) strains (2001 to 2003), but V.?cholerae CTX+ variant El Tor was isolated during 2004 to 2008, outcompeting CTX? V.?cholerae. Genomes of six Mexican V.?cholerae O1 strains isolated during...

Radiolabelling of cholera toxin

International Nuclear Information System (INIS)

Santos, R.G.; Neves, Nicoli M.J.; Abdalla, L.F.; Brandao, R.L.; Etchehebehere, L.; Lima, M.E. de; Nicoli, J.R.

1999-01-01

Binding of cholera toxin to ganglioside receptors of enterocyte microvilli catalyzes the activation of adenylate cyclase causing a rise in cAMP which final result is a copious diarrhea. Saccharomyces boulardii, a nonpathogenic yeast has been used to prevent diarrhea. Although the antidiarrheic properties of S. boulardii are widely recognized, this yeast has been used on empirical basis, and the mechanism of this protective effect is unknown. The addition of cholera toxin to S. boulardii induces the raising of cAMP that triggers the activation of neutral trehalase. This suggests that toxin specifically binding to cells, is internalized and active the protein phosphorylation cascade. Our objective is labeling the cholera toxin to verify the presence of binding sites on yeast cell surfaces for the cholera toxin. Cholera toxin was radiolabelled with Na 125 I by a chloramine-T method modified from Cuatrecasas and Griffiths et alii. The 125 I-Cholera toxin showed a specific radioactivity at about 1000 cpm/fmol toxin. Biological activity of labeled cholera toxin measured by trehalase activation was similar to the native toxin. (author)

Rainfall-driven epidemic cholera: hydrologic controls on water-borne disease and multi-season projections

Science.gov (United States)

Righetto, L.; Bertuzzo, E.; Mari, L.; Casagrandi, R.; Gatto, M.; Rodriguez-Iturbe, I.; Rinaldo, A.

2012-12-01

Following the acknowledgement of a clear correlation between rainfall events and cholera resurgence, that was observed in Haiti starting from May 2011, we use a multi-variate Poisson generator to produce rainfall inputs, with which we force spatially explicit models of cholera spreading. Our models consist of ODE systems of equations, describing a network of human communities (divided in Susceptible, Infected and Recovered individuals) connected by river transport of pathogens and human mobility. We perform an a posteriori analysis -- from the beginning of the epidemic until December 2011 -- to assess the model reliability in predicting cholera cases and in testing control measures -- involving vaccination and sanitation campaigns. We then run a multi-seasonal prediction of the course of the epidemic until December 2015, to investigate further resurgences of cholera in the region and to evaluate, again, the effect of policies which may bring to the eradication of the disease in Haiti. We conclude that mathematical models may represent a key information tool for policy makers, as a way to preliminarly assess the possible future course of an epidemic and to test intervention policies to be deployed. Effect of intervention policies on the predicted course of the epidemic between 28/05-31/12/2011 (blue lines: simulations with the observed rainfall pattern; red lines/shaded range: median/25th-75th percentile range of simulations with generated rainfall). A) Effect of a reduction of the 20% of the contact rate , applied in one month starting from the 1st of June (dashed blue/red lines) or the 1st of July (dotted blue/red lines). B) A) Effect of a vaccination of 4 million individuals, implemented in one month starting from the 1st of June (dashed blue/red lines) or the 1st of July (dotted blue/red lines). C) Number of new cases in the period 28/05-31/12/2011 as a function of the reduction of the contact rate . D) Number of new cases in the period 28/05-31/12/2011 as a

Novel type of specialized transduction for CTX phi or its satellite phage RS1 mediated by filamentous phage VGJ phi in Vibrio cholerae.

Science.gov (United States)

Campos, Javier; Martínez, Eriel; Marrero, Karen; Silva, Yussuan; Rodríguez, Boris L; Suzarte, Edith; Ledón, Talena; Fando, Rafael

2003-12-01

The main virulence factor of Vibrio cholerae, the cholera toxin, is encoded by the ctxAB operon, which is contained in the genome of the lysogenic filamentous phage CTX phi. This phage transmits ctxAB genes between V. cholerae bacterial populations that express toxin-coregulated pilus (TCP), the CTX phi receptor. In investigating new forms of ctxAB transmission, we found that V. cholerae filamentous phage VGJ phi, which uses the mannose-sensitive hemagglutinin (MSHA) pilus as a receptor, transmits CTX phi or its satellite phage RS1 by an efficient and highly specific TCP-independent mechanism. This is a novel type of specialized transduction consisting in the site-specific cointegration of VGJ phi and CTX phi (or RS1) replicative forms to produce a single hybrid molecule, which generates a single-stranded DNA hybrid genome that is packaged into hybrid viral particles designated HybP phi (for the VGJ phi/CTX phi hybrid) and HybRS phi (for the VGJ phi/RS1 hybrid). The hybrid phages replicate by using the VGJ phi replicating functions and use the VGJ phi capsid, retaining the ability to infect via MSHA. The hybrid phages infect most tested strains more efficiently than CTX phi, even under in vitro optimal conditions for TCP expression. Infection and lysogenization with HybP phi revert the V. cholerae live attenuated vaccine strain 1333 to virulence. Our results reinforce that TCP is not indispensable for the acquisition of CTX phi. Thus, we discuss an alternative to the current accepted evolutionary model for the emergence of new toxigenic strains of V. cholerae and the importance of our findings for the development of an environmentally safer live attenuated cholera vaccine.

Radiolabelling of cholera toxin

Energy Technology Data Exchange (ETDEWEB)

Santos, R.G.; Neves, Nicoli M.J. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN), Belo Horizonte, MG (Brazil); Abdalla, L.F.; Brandao, R.L.; Etchehebehere, L. [Ouro Preto Univ., MG (Brazil). Escola de Farmacia. Lab. de Fisiologia e Bioquimica de Microorganismos; Lima, M.E. de [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Inst. de Ciencias Biologicas. Dept. de Bioquimica e Imunologia; Nicoli, J.R. [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Inst. de Ciencias Biologicas. Dept. de Microbiologia

1999-11-01

Binding of cholera toxin to ganglioside receptors of enterocyte microvilli catalyzes the activation of adenylate cyclase causing a rise in cAMP which final result is a copious diarrhea. Saccharomyces boulardii, a nonpathogenic yeast has been used to prevent diarrhea. Although the antidiarrheic properties of S. boulardii are widely recognized, this yeast has been used on empirical basis, and the mechanism of this protective effect is unknown. The addition of cholera toxin to S. boulardii induces the raising of cAMP that triggers the activation of neutral trehalase. This suggests that toxin specifically binding to cells, is internalized and active the protein phosphorylation cascade. Our objective is labeling the cholera toxin to verify the presence of binding sites on yeast cell surfaces for the cholera toxin. Cholera toxin was radiolabelled with Na {sup 125} I by a chloramine-T method modified from Cuatrecasas and Griffiths et alii. The {sup 125} I-Cholera toxin showed a specific radioactivity at about 1000 cpm/fmol toxin. Biological activity of labeled cholera toxin measured by trehalase activation was similar to the native toxin. (author) 5 refs., 3 figs.; e-mail: nevesmj at urano.cdtn.br

Yemen in a Time of Cholera: Current Situation and Challenges.

Science.gov (United States)

Al-Mekhlafi, Hesham M

2018-03-19

Since early 2015, Yemen has been in the throes of a grueling civil war, which has devastated the health system and public services, and created one of the world's worst humanitarian disasters. The country is currently facing a cholera epidemic the world's largest on record, surpassing one million (1,061,548) suspected cases, with 2,373 related deaths since October 2016. Cases were first confirmed in Sana'a city and then spread to almost all governorates except Socotra Island. Continued efforts are being made by the World Health Organization and international partners to contain the epidemic through improving water, sanitation and hygiene, setting up diarrhea treatment centers, and improving the population's awareness about the disease. The provision of clean water and adequate sanitation is imperative as an effective long-term solution to prevent the further spread of this epidemic. Cholera vaccination campaigns should also be conducted as a preventive measure.

Quality vaccines for all people: Report on the 16th annual general meeting of the Developing Countries Vaccine Manufacturers' Network, 05-07th October 2015, Bangkok, Thailand.

Science.gov (United States)

Pagliusi, Sonia; Ting, Ching-Chia; Khomvilai, Sumana

2016-06-30

The Developing Countries Vaccine Manufacturers Network (DCVMN) assembled high-profile leaders from global health organisations and vaccine manufactures for its 16th Annual General Meeting to work towards a common goal: providing quality vaccines for all people. Vaccines contribute to a healthy community and robust health system; the Ebola outbreak has raised awareness of the threat and damage one single infectious disease can make, and it is clear that the world was not prepared. However, more research to better understand emerging infectious agents might lead to suitable vaccines which help prevent future outbreaks. DCVMN members presented their progress in developing novel vaccines against Dengue, HPV, Chikungunya, Cholera, cell-based influenza and other vaccines, demonstrating the commitment towards eliminating and eradicating preventable diseases worldwide through global collaboration and technology transfer. The successful introduction of novel Sabin-IPV and Oral Cholera vaccine in China and Korea respectively in 2015 was highlighted. In order to achieve global immunisation, local authorities and community leaders play an important role in the decision-making in vaccine introduction and uptake, based on the ability of vaccines to protect vaccinated people and protect non-vaccinated in the community through herd immunity. Reducing the risk of vaccine shortages can also be achieved by increasing regulatory convergence at regional and international levels. Combatting preventable diseases remains challenging, and collective efforts for improving multi-centre clinical trials, creating regional vaccine security strategies, fostering developing vaccine markets and procurement, and building trust in vaccines were discussed. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Drinking cholera

DEFF Research Database (Denmark)

Grant, Stephen Lawrence; Tamason, Charlotte Crim; Hoque, Bilqis Amin

2015-01-01

. cholerae can survive in the river systems in Bangladesh; however,water sources which have been contaminated with river water are avoided as potential drinkingwater sources. Furthermore, there are no physical connecting points between the river system anddrinking water sources among the study population......, indicating that the primary driver for choleracases in Bangladesh is likely not through the contamination of saline-rich river water into drinkingwater sources.......Objectives: To measure the salinity levels of common water sources in coastal Bangladesh andexplore perceptions of water palatability among the local population to investigate the plausibility oflinking cholera outbreaks in Bangladesh with ingestion of saline-rich cholera-infected river water...

Promotion of Cholera Awareness Among Households of Cholera Patients: A Randomized Controlled Trial of the Cholera-Hospital-Based-Intervention-for-7 Days (CHoBI7) Intervention.

Science.gov (United States)

Saif-Ur-Rahman, K M; Parvin, Tahmina; Bhuyian, Sazzadul Islam; Zohura, Fatema; Begum, Farzana; Rashid, Mahamud-Ur; Biswas, Shwapon Kumar; Sack, David; Sack, R Bradley; Monira, Shirajum; Alam, Munirul; Shaly, Nusrat Jahan; George, Christine Marie

2016-12-07

Previous studies have demonstrated that household contacts of cholera patients are highly susceptible to cholera infections for a 7-day period after the presentation of the index patient in the hospital. However, there is no standard of care to prevent cholera transmission in this high-risk population. Furthermore, there is limited information available on awareness of cholera transmission and prevention among cholera patients and their household contacts. To initiate a standard of care for this high-risk population, we developed the Cholera-Hospital-Based-Intervention-for-7-Days (CHoBI7), which delivers a handwashing with soap and water treatment intervention to household contacts during the time they spend with the admitted cholera patient in the hospital and reinforces these messages through home visits. To test CHoBI7, we conducted a randomized controlled trial among 302 intervention cholera patient household members and 302 control cholera patient household members in Dhaka, Bangladesh. In this study, we evaluated the effectiveness of the CHoBI7 intervention in increasing awareness of cholera transmission and prevention, and the key times for handwashing with soap. We observed a significant increase in cholera knowledge score in the intervention arm compared with the control arm at both the 1-week follow-up {score coefficient = 2.34 (95% confidence interval [CI] = 1.96, 2.71)} and 6 to 12-month follow-up period (score coefficient = 1.59 [95% CI = 1.05, 2.13]). This 1-week hospital- and home-based intervention led to a significant increase in knowledge of cholera transmission and prevention which was sustained 6 to 12 months post-intervention. These findings suggest that the CHoBI7 intervention presents a promising approach to increase cholera awareness among this high-risk population. © The American Society of Tropical Medicine and Hygiene.

Phylogenetic Diversity of Vibrio cholerae Associated with Endemic Cholera in Mexico from 1991 to 2008.

Science.gov (United States)

Choi, Seon Young; Rashed, Shah M; Hasan, Nur A; Alam, Munirul; Islam, Tarequl; Sadique, Abdus; Johura, Fatema-Tuz; Eppinger, Mark; Ravel, Jacques; Huq, Anwar; Cravioto, Alejandro; Colwell, Rita R

2016-03-15

An outbreak of cholera occurred in 1991 in Mexico, where it had not been reported for more than a century and is now endemic. Vibrio cholerae O1 prototype El Tor and classical strains coexist with altered El Tor strains (1991 to 1997). Nontoxigenic (CTX(-)) V. cholerae El Tor dominated toxigenic (CTX(+)) strains (2001 to 2003), but V. cholerae CTX(+) variant El Tor was isolated during 2004 to 2008, outcompeting CTX(-) V. cholerae. Genomes of six Mexican V. cholerae O1 strains isolated during 1991 to 2008 were sequenced and compared with both contemporary and archived strains of V. cholerae. Three were CTX(+) El Tor, two were CTX(-) El Tor, and the remaining strain was a CTX(+) classical isolate. Whole-genome sequence analysis showed the six isolates belonged to five distinct phylogenetic clades. One CTX(-) isolate is ancestral to the 6th and 7th pandemic CTX(+) V. cholerae isolates. The other CTX(-) isolate joined with CTX(-) non-O1/O139 isolates from Haiti and seroconverted O1 isolates from Brazil and Amazonia. One CTX(+) isolate was phylogenetically placed with the sixth pandemic classical clade and the V. cholerae O395 classical reference strain. Two CTX(+) El Tor isolates possessing intact Vibrio seventh pandemic island II (VSP-II) are related to hybrid El Tor isolates from Mozambique and Bangladesh. The third CTX(+) El Tor isolate contained West African-South American (WASA) recombination in VSP-II and showed relatedness to isolates from Peru and Brazil. Except for one isolate, all Mexican isolates lack SXT/R391 integrative conjugative elements (ICEs) and sensitivity to selected antibiotics, with one isolate resistant to streptomycin. No isolates were related to contemporary isolates from Asia, Africa, or Haiti, indicating phylogenetic diversity. Sequencing of genomes of V. cholerae is critical if genetic changes occurring over time in the circulating population of an area of endemicity are to be understood. Although cholera outbreaks occurred rarely

A brief history of vaccines & vaccination in India

Directory of Open Access Journals (Sweden)

Chandrakant Lahariya

2014-01-01

Full Text Available The challenges faced in delivering lifesaving vaccines to the targeted beneficiaries need to be addressed from the existing knowledge and learning from the past. This review documents the history of vaccines and vaccination in India with an objective to derive lessons for policy direction to expand the benefits of vaccination in the country. A brief historical perspective on smallpox disease and preventive efforts since antiquity is followed by an overview of 19 th century efforts to replace variolation by vaccination, setting up of a few vaccine institutes, cholera vaccine trial and the discovery of plague vaccine. The early twentieth century witnessed the challenges in expansion of smallpox vaccination, typhoid vaccine trial in Indian army personnel, and setting up of vaccine institutes in almost each of the then Indian States. In the post-independence period, the BCG vaccine laboratory and other national institutes were established; a number of private vaccine manufacturers came up, besides the continuation of smallpox eradication effort till the country became smallpox free in 1977. The Expanded Programme of Immunization (EPI (1978 and then Universal Immunization Programme (UIP (1985 were launched in India. The intervening events since UIP till India being declared non-endemic for poliomyelitis in 2012 have been described. Though the preventive efforts from diseases were practiced in India, the reluctance, opposition and a slow acceptance of vaccination have been the characteristic of vaccination history in the country. The operational challenges keep the coverage inequitable in the country. The lessons from the past events have been analysed and interpreted to guide immunization efforts.

A brief history of vaccines & vaccination in India.

Science.gov (United States)

Lahariya, Chandrakant

2014-04-01

The challenges faced in delivering lifesaving vaccines to the targeted beneficiaries need to be addressed from the existing knowledge and learning from the past. This review documents the history of vaccines and vaccination in India with an objective to derive lessons for policy direction to expand the benefits of vaccination in the country. A brief historical perspective on smallpox disease and preventive efforts since antiquity is followed by an overview of 19 th century efforts to replace variolation by vaccination, setting up of a few vaccine institutes, cholera vaccine trial and the discovery of plague vaccine. The early twentieth century witnessed the challenges in expansion of smallpox vaccination, typhoid vaccine trial in Indian army personnel, and setting up of vaccine institutes in almost each of the then Indian States. In the post-independence period, the BCG vaccine laboratory and other national institutes were established; a number of private vaccine manufacturers came up, besides the continuation of smallpox eradication effort till the country became smallpox free in 1977. The Expanded Programme of Immunization (EPI) (1978) and then Universal Immunization Programme (UIP) (1985) were launched in India. The intervening events since UIP till India being declared non-endemic for poliomyelitis in 2012 have been described. Though the preventive efforts from diseases were practiced in India, the reluctance, opposition and a slow acceptance of vaccination have been the characteristic of vaccination history in the country. The operational challenges keep the coverage inequitable in the country. The lessons from the past events have been analysed and interpreted to guide immunization efforts.

The burden of diarrhoea, shigellosis, and cholera in North Jakarta, Indonesia: findings from 24 months surveillance

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Lee Hyejon

2005-10-01

Full Text Available Abstract Background In preparation of vaccines trials to estimate protection against shigellosis and cholera we conducted a two-year community-based surveillance study in an impoverished area of North Jakarta which provided updated information on the disease burden in the area. Methods We conducted a two-year community-based surveillance study from August 2001 to July 2003 in an impoverished area of North Jakarta to assess the burden of diarrhoea, shigellosis, and cholera. At participating health care providers, a case report form was completed and stool sample collected from cases presenting with diarrhoea. Results Infants had the highest incidences of diarrhoea (759/1 000/year and cholera (4/1 000/year. Diarrhea incidence was significantly higher in boys under 5 years (387/1 000/year than girls under 5 years (309/1 000/year; p Shigella flexneri was the most common Shigella species isolated and 73% to 95% of these isolates were resistant to ampicillin, trimethoprim-sulfamethoxazole, chloramphenicol and tetracycline but remain susceptible to nalidixic acid, ciprofloxacin, and ceftriaxone. We found an overall incidence of cholera of 0.5/1 000/year. Cholera was most common in children, with the highest incidence at 4/1 000/year in those less than 1 year of age. Of the 154 V. cholerae O1 isolates, 89 (58% were of the El Tor Ogawa serotype and 65 (42% were El Tor Inaba. Thirty-four percent of patients with cholera were intravenously rehydrated and 22% required hospitalization. V. parahaemolyticus infections were detected sporadically but increased from July 2002 onwards. Conclusion Diarrhoea causes a heavy public health burden in Jakarta particularly in young children. The impact of shigellosis is exacerbated by the threat of antimicrobial resistance, whereas that of cholera is aggravated by its severe manifestations.

An evaluation of the 2012 measles mass vaccination campaign in ...

African Journals Online (AJOL)

Introduction: To estimate the post-campaign level of measles vaccination coverage in Guinea. Method: Interview of parents and observation of measles vaccination cards of children aged 9 to 59 months during the mass measles campaign. A nationwide cluster randomized sample under health District stratification. Results: ...

Cholera in Azov area

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O. N. Domashenko

2015-01-01

Full Text Available The purpose of research is analysis of clinical course and treatment results of patients with cholera in the Azov area. Materials and methods. During the period from 29.05.2011 to 19.08.2011 33 cases of cholera (32 adults and 1 child and 25 vibrio carriers (22 adults and 3 children, which were caused by toxigenic strains of Vibrio cholera El Tor serogroup O1 Ogawa. Results. Likely factors of disease transmission in Mariupol are sea and river water, and the fish that were caught in the waters of the city. Typical and watery diarrhoea, vomiting, abdominal pain and lack of normal body temperature, dehydration syndrome, characterized clinical cholera for adults in most cases. The mean duration of diarrhoea was 6,6 days. At 46.9% observed atypical symptoms in 10 (31,3% – abdominal pain (1 patient cramping in 7 cases, localized in the epigastria region, at 2-over stomach. In 5 patients (15,6% had an increase in body temperature to 37,2–37,7 degrees Celsius. In 15 (46,9% patients had severe nausea accompanied by vomiting. Easy for cholera was observed in 1 (3.1%, moderate – in 14 (43,8%, heavy – in 17 (53,1% patients. Dehydration I level is set at 4 (12,5%, II – from 6 (18,7%, III – in 18 (56,3%, IV – 4 (12,5% patients. Cholera outbreak was characterized by a predominance of severe disease and severe dehydration (III and IV, which was observed in 68.8% of patients. The decisive factor in the treatment of cholera patients was initiated in a timely manner rehydration therapy, in particular the introduction of the solution «Trisol». Against the background of rehydration therapy hyperkalaemia was observed in 9,4% of cases, vascular rehydration at 9,4%, the cell rehydration in 3,1% of patients. Fatal accidents cholera outbreaks have not been observed. Conclusion. Clinical diagnosis of cholera and the provision of medical care in the prehospital phase were poor, indicating the need for systematic conducting training seminars among experts

Purification and characterization of Yersinia enterocolitica and Yersinia pestis LcrV-cholera toxin A(2)/B chimeras.

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Tinker, Juliette K; Davis, Chadwick T; Arlian, Britni M

2010-11-01

Yersinia pestis is a virulent human pathogen and potential biological weapon. Despite a long history of research on this organism, there is no licensed vaccine to protect against pneumonic forms of Y. pestis disease. In the present study, plasmids were constructed to express cholera toxin A(2)/B chimeric molecules containing the LcrV protective antigen from Yersinia enterocolitica and Y. pestis. These chimeras were expressed and purified to high yields from the supernatant of transformed Escherichia coli. Western and GM(1) ELISA assays were used to characterize the composition, receptor-binding and relative stability of the LcrV-CTA(2)/B chimera in comparison to cholera toxin. In addition, we investigated the ability of the Y. pestis LcrV-CTA(2)/B chimera to bind to and internalize into cultured epithelial cells and macrophages by confocal microscopy. These studies indicate that the uptake and trafficking of the LcrV antigen from the chimera is comparable to the trafficking of native toxin. Together these findings report that stable, receptor-binding, non-toxic LcrV-cholera toxin A(2)/B chimeras can be expressed at high levels in E. coli and purified from the supernatant. In addition, the internalization of antigen in vitro reported here supports the development of these molecules as novel mucosal vaccine candidates. Copyright 2010 Elsevier Inc. All rights reserved.

In a time of cholera.

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Grace, P A

2014-03-01

Dr. Nathaniel Alcock in his book A treatise on cholera described 22 cases of cholera that he treated in 1832. Blood-letting, either by leeches or venesection, was an essential part of the treatment. The belief was that reducing the blood volume would relieve stress on the heart and lungs allowing for better function. The receipts of the Townsend Street Cholera Hospital where Dr. Alcock worked show how extensive the practice was. Outside Dublin, local Boards of Health dealt with the cholera epidemic. Various public measures such as street cleaning and removal of patients to temporary hospitals were undertaken and various cures were tried. The overall mortality rate from cholera in Ireland during the epidemic was 38 %, but in some areas much higher. Even as cholera was spreading in the 1830s, a number of doctors were showing that intravenous fluids could dramatically alter the course of the disease. Unfortunately, their work was ignored and blood-letting continued to be a major component of the treatment of cholera for another 55 years.

Cost of illness for cholera in a high risk urban area in Bangladesh: an analysis from household perspective

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2013-01-01

Background Cholera poses a substantial health burden to developing countries such as Bangladesh. In this study, the objective is to estimate the economic burden of cholera treatments incurred by households. The study was carried out in the context of a large vaccine trial in an urban area of Bangladesh. Methods The study used a combination of prospective and retrospective incidence-based cost analyses of cholera illness per episode per household. A total of 394 confirmed cholera hospitalized cases were identified and treated in the study area during June–October 2011. Households with cholera patients were interviewed within 15 days after discharge from hospitals or clinics. To estimate the total cost of cholera illness a structured questionnaire was used, which included questions on direct medical costs, non-medical costs, and the indirect costs of patients and caregivers. Results The average total household cost of treatment for an episode of cholera was US$30.40. Total direct and indirect costs constituted 24.6% (US$7.40) and 75.4% (US$23.00) of the average total cost, respectively. The cost for children under 5 years of age (US$21.50) was higher than that of children aged 5–14 years (US$17.50). The direct cost of treatment was similar for male and female patients, but the indirect cost was higher for males. Conclusion Our study suggests that by preventing one cholera episode (3 days on an average), we can avert a total cost of 2,278.50 BDT (US$30.40) per household. Among medical components, medicines are the largest cost driver. No clear socioeconomic gradient emerged from our study, but limited demographic patterns were observed in the cost of illness. By preventing cholera cases, large production losses can be reduced. PMID:24188717

Clinical, epidemiological, and spatial characteristics of Vibrio parahaemolyticus diarrhea and cholera in the urban slums of Kolkata, India

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Kanungo Suman

2012-09-01

Full Text Available Abstract Background There is not much information on the differences in clinical, epidemiological and spatial characteristics of diarrhea due to V. cholerae and V. parahaemolyticus from non-coastal areas. We investigated the differences in clinical, epidemiological and spatial characteristics of the two Vibrio species in the urban slums of Kolkata, India. Methods The data of a cluster randomized cholera vaccine trial were used. We restricted the analysis to clusters assigned to placebo. Survival analysis of the time to the first episode was used to analyze risk factors for V. parahaemolyticus diarrhea or cholera. A spatial scan test was used to identify high risk areas for cholera and for V. parahaemolyticus diarrhea. Results In total, 54,519 people from the placebo clusters were assembled. The incidence of cholera (1.30/1000/year was significantly higher than that of V. parahaemolyticus diarrhea (0.63/1000/year. Cholera incidence was inversely related to age, whereas the risk of V. parahaemolyticus diarrhea was age-independent. The seasonality of diarrhea due to the two Vibrio species was similar. Cholera was distinguished by a higher frequency of severe dehydration, and V. parahaemolyticus diarrhea was by abdominal pain. Hindus and those who live in household not using boiled or treated water were more likely to have V. parahaemolyticus diarrhea. Young age, low socioeconomic status, and living closer to a project healthcare facility were associated with an increased risk for cholera. The high risk area for cholera differed from the high risk area for V. parahaemolyticus diarrhea. Conclusion We report coexistence of the two vibrios in the slums of Kolkata. The two etiologies of diarrhea had a similar seasonality but had distinguishing clinical features. The risk factors and the high risk areas for the two diseases differ from one another suggesting different modes of transmission of these two pathogens.

Identifying cholera "hotspots" in Uganda: An analysis of cholera surveillance data from 2011 to 2016

OpenAIRE

Bwire, Godfrey; Ali, Mohammad; Sack, David A.; Nakinsige, Anne; Naigaga, Martha; Debes, Amanda K.; Ngwa, Moise C.; Brooks, W. Abdullah; Garimoi Orach, Christopher

2017-01-01

Background Despite advance in science and technology for prevention, detection and treatment of cholera, this infectious disease remains a major public health problem in many countries in sub-Saharan Africa, Uganda inclusive. The aim of this study was to identify cholera hotspots in Uganda to guide the development of a roadmap for prevention, control and elimination of cholera in the country. Methodology/Principle findings We obtained district level confirmed cholera outbreak data from 2011 t...

What is cholera?

DEFF Research Database (Denmark)

Tamason, Charlotte Crim; Tulsiani, Suhella; Siddique, A.

2016-01-01

more commonly described than death (47%) as negative effects of cholera. Conclusions: The results from this study are suggestive of a need for reformulation of cholera and diarrhea communication. Messaging should be based on signs of dehydration, foregoing the use of medical terminology....

The importance of thinking beyond the water-supply in cholera epidemics: A historical urban case-study.

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Phelps, Matthew D; Azman, Andrew S; Lewnard, Joseph A; Antillón, Marina; Simonsen, Lone; Andreasen, Viggo; Jensen, Peter K M; Pitzer, Virginia E

2017-11-01

Planning interventions to respond to cholera epidemics requires an understanding of the major transmission routes. Interrupting short-cycle (household, foodborne) transmission may require different approaches as compared long-cycle (environmentally-mediated/waterborne) transmission. However, differentiating the relative contribution of short- and long-cycle routes has remained difficult, and most cholera outbreak control efforts focus on interrupting long-cycle transmission. Here we use high-resolution epidemiological and municipal infrastructure data from a cholera outbreak in 1853 Copenhagen to explore the relative contribution of short- and long-cycle transmission routes during a major urban epidemic. We fit a spatially explicit time-series meta-population model to 6,552 physician-reported cholera cases from Copenhagen in 1853. We estimated the contribution of long-cycle waterborne transmission between neighborhoods using historical municipal water infrastructure data, fitting the force of infection from hydraulic flow, then comparing model performance. We found the epidemic was characterized by considerable transmission heterogeneity. Some neighborhoods acted as localized transmission hotspots, while other neighborhoods were less affected or important in driving the epidemic. We found little evidence to support long-cycle transmission between hydrologically-connected neighborhoods. Collectively, these findings suggest short-cycle transmission was significant. Spatially targeted cholera interventions, such as reactive vaccination or sanitation/hygiene campaigns in hotspot neighborhoods, would likely have been more effective in this epidemic than control measures aimed at interrupting long-cycle transmission, such as improving municipal water quality. We recommend public health planners consider programs aimed at interrupting short-cycle transmission as essential tools in the cholera control arsenal.

Non-toxigenic environmental Vibrio cholerae O1 strain from Haiti provides evidence of pre-pandemic cholera in Hispaniola

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Azarian, Taj; Ali, Afsar; Johnson, Judith A.; Jubair, Mohammad; Cella, Eleonora; Ciccozzi, Massimo; Nolan, David J.; Farmerie, William; Rashid, Mohammad H.; Sinha-Ray, Shrestha; Alam, Meer T.; Morris, J. Glenn; Salemi, Marco

2016-01-01

Vibrio cholerae is ubiquitous in aquatic environments, with environmental toxigenic V. cholerae O1 strains serving as a source for recurrent cholera epidemics and pandemic disease. However, a number of questions remain about long-term survival and evolution of V. cholerae strains within these aquatic environmental reservoirs. Through monitoring of the Haitian aquatic environment following the 2010 cholera epidemic, we isolated two novel non-toxigenic (ctxA/B-negative) Vibrio cholerae O1. These two isolates underwent whole-genome sequencing and were investigated through comparative genomics and Bayesian coalescent analysis. These isolates cluster in the evolutionary tree with strains responsible for clinical cholera, possessing genomic components of 6th and 7th pandemic lineages, and diverge from “modern” cholera strains around 1548 C.E. [95% HPD: 1532–1555]. Vibrio Pathogenicity Island (VPI)-1 was present; however, SXT/R391-family ICE and VPI-2 were absent. Rugose phenotype conversion and vibriophage resistance evidenced adaption for persistence in aquatic environments. The identification of V. cholerae O1 strains in the Haitian environment, which predate the first reported cholera pandemic in 1817, broadens our understanding of the history of pandemics. It also raises the possibility that these and similar environmental strains could acquire virulence genes from the 2010 Haitian epidemic clone, including the cholera toxin producing CTXϕ. PMID:27786291

Epidemiology of cholera outbreaks and socio-economic characteristics of the communities in the fishing villages of Uganda: 2011-2015.

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Godfrey Bwire

2017-03-01

Full Text Available The communities in fishing villages in the Great Lakes Region of Africa and particularly in Uganda experience recurrent cholera outbreaks that lead to considerable mortality and morbidity. We evaluated cholera epidemiology and population characteristics in the fishing villages of Uganda to better target prevention and control interventions of cholera and contribute to its elimination from those communities.We conducted a prospective study between 2011-15 in fishing villages in Uganda. We collected, reviewed and documented epidemiological and socioeconomic data for 10 cholera outbreaks that occurred in fishing communities located along the African Great Lakes and River Nile in Uganda. These outbreaks caused 1,827 suspected cholera cases and 43 deaths, with a Case-Fatality Ratio (CFR of 2.4%. Though the communities in the fishing villages make up only 5-10% of the Ugandan population, they bear the biggest burden of cholera contributing 58% and 55% of all reported cases and deaths in Uganda during the study period. The CFR was significantly higher among males than females (3.2% vs. 1.3%, p = 0.02. The outbreaks were seasonal with most cases occurring during the months of April-May. Male children under age of 5 years, and 5-9 years had increased risk. Cholera was endemic in some villages with well-defined "hotspots". Practices predisposing communities to cholera outbreaks included: the use of contaminated lake water, poor sanitation and hygiene. Additional factors were: ignorance, illiteracy, and poverty.Cholera outbreaks were a major cause of morbidity and mortality among the fishing communities in Uganda. In addition to improvements in water, sanitation, and hygiene, oral cholera vaccines could play an important role in the prevention and control of these outbreaks, particularly when targeted to high-risk areas and populations. Promotion and facilitation of access to social services including education and reduction in poverty should contribute to

Antibiotics resistance in El Tor Vibrio cholerae 01 isolated during cholera outbreaks in Mozambique from 2012 to 2015.

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Liliana Candida Dengo-Baloi

Full Text Available Mozambique has recorded cyclically epidemic outbreaks of cholera. Antibiotic therapy is recommended in specific situations for management and control of cholera outbreaks. However, an increase in resistance rates to antibiotics by Vibrio cholerae has been reported in several epidemic outbreaks worldwide. On the other hand, there are few recent records of continuous surveillance of antibiotics susceptibility pattern of V. cholerae in Mozambique.The purpose of this study was to evaluate antibiotics resistance pattern of Vibrio cholerae O1 Ogawa isolated during Cholera outbreaks in Mozambique to commonly used antibiotics.We analyzed data from samples received in the context of surveillance and response to Cholera outbreaks in the National Reference Laboratory of Microbiology from the National Institute of Health of Mozambique, 159 samples suspected of cholera from cholera treatment centers of, Metangula (09, Memba (01, Tete City (08, Moatize (01, Morrumbala (01 districts, City of Quelimane (01, Lichinga (06 and Nampula (86 districts, from 2012 to 2015. Laboratory culture and standard biochemical tests were employed to isolate and identify Vibrio cholerae; serotypes were determined by antisera agglutination reaction in blade. Biotype and presence of important virulence factors analysis was done by PCR. Antibiotics susceptibility pattern was detected by disk diffusion method Kirby Bauer. Antibiotic susceptibility and results were interpreted by following as per recommendations of CLSI (Clinical and Laboratory Standards Institute 2014. All samples were collected and tested in the context of Africhol Project, approved by the National Bioethics Committee for Health.Among isolates from of Vibrio cholerae O1 El Tor Ogawa resistance to Sulphamethoxazole-trimethropim was 100% (53/53 to Trimethoprim-, being 100% (54/54 for Ampicillin, 99% (72/74 for Nalidixic Acid, 97% (64/66 to Chloramphenicol, 95% (42/44 for Nitrofurantoin and (19/20 Cotrimoxazole, 83% (80

Antibiotics resistance in El Tor Vibrio cholerae 01 isolated during cholera outbreaks in Mozambique from 2012 to 2015.

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Dengo-Baloi, Liliana Candida; Semá-Baltazar, Cynthia Amino; Manhique, Lena Vania; Chitio, Jucunu Elias; Inguane, Dorteia Luísa; Langa, José Paulo

2017-01-01

Mozambique has recorded cyclically epidemic outbreaks of cholera. Antibiotic therapy is recommended in specific situations for management and control of cholera outbreaks. However, an increase in resistance rates to antibiotics by Vibrio cholerae has been reported in several epidemic outbreaks worldwide. On the other hand, there are few recent records of continuous surveillance of antibiotics susceptibility pattern of V. cholerae in Mozambique. The purpose of this study was to evaluate antibiotics resistance pattern of Vibrio cholerae O1 Ogawa isolated during Cholera outbreaks in Mozambique to commonly used antibiotics. We analyzed data from samples received in the context of surveillance and response to Cholera outbreaks in the National Reference Laboratory of Microbiology from the National Institute of Health of Mozambique, 159 samples suspected of cholera from cholera treatment centers of, Metangula (09), Memba (01), Tete City (08), Moatize (01), Morrumbala (01) districts, City of Quelimane (01), Lichinga (06) and Nampula (86) districts, from 2012 to 2015. Laboratory culture and standard biochemical tests were employed to isolate and identify Vibrio cholerae; serotypes were determined by antisera agglutination reaction in blade. Biotype and presence of important virulence factors analysis was done by PCR. Antibiotics susceptibility pattern was detected by disk diffusion method Kirby Bauer. Antibiotic susceptibility and results were interpreted by following as per recommendations of CLSI (Clinical and Laboratory Standards Institute) 2014. All samples were collected and tested in the context of Africhol Project, approved by the National Bioethics Committee for Health. Among isolates from of Vibrio cholerae O1 El Tor Ogawa resistance to Sulphamethoxazole-trimethropim was 100% (53/53) to Trimethoprim-, being 100% (54/54) for Ampicillin, 99% (72/74) for Nalidixic Acid, 97% (64/66) to Chloramphenicol, 95% (42/44) for Nitrofurantoin and (19/20) Cotrimoxazole, 83% (80

Cholera Fact Sheet

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... news-room/fact-sheets/detail/cholera","@context":"http://schema.org","@type":"Article"}; العربية 中文 français русский español ... that includes feedback at the local level and information-sharing at the global level. Cholera cases are ...

Elevation and cholera: an epidemiological spatial analysis of the cholera epidemic in Harare, Zimbabwe, 2008-2009

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Luque Fernandez Miguel A

2012-06-01

Full Text Available Abstract Background In highly populated African urban areas where access to clean water is a challenge, water source contamination is one of the most cited risk factors in a cholera epidemic. During the rainy season, where there is either no sewage disposal or working sewer system, runoff of rains follows the slopes and gets into the lower parts of towns where shallow wells could easily become contaminated by excretes. In cholera endemic areas, spatial information about topographical elevation could help to guide preventive interventions. This study aims to analyze the association between topographic elevation and the distribution of cholera cases in Harare during the cholera epidemic in 2008 and 2009. Methods We developed an ecological study using secondary data. First, we described attack rates by suburb and then calculated rate ratios using whole Harare as reference. We illustrated the average elevation and cholera cases by suburbs using geographical information. Finally, we estimated a generalized linear mixed model (under the assumption of a Poisson distribution with an Empirical Bayesian approach to model the relation between the risk of cholera and the elevation in meters in Harare. We used a random intercept to allow for spatial correlation of neighboring suburbs. Results This study identifies a spatial pattern of the distribution of cholera cases in the Harare epidemic, characterized by a lower cholera risk in the highest elevation suburbs of Harare. The generalized linear mixed model showed that for each 100 meters of increase in the topographical elevation, the cholera risk was 30% lower with a rate ratio of 0.70 (95% confidence interval=0.66-0.76. Sensitivity analysis confirmed the risk reduction with an overall estimate of the rate ratio between 20% and 40%. Conclusion This study highlights the importance of considering topographical elevation as a geographical and environmental risk factor in order to plan cholera preventive

Cholera in the Americas.

Science.gov (United States)

1991-01-01

The cholera epidemic 1st hit South America in January 1991 in the coastal town of Chancay, Peru. In 2 weeks, it spread over 2000 km of the Pacific coast. By the end of the 1st month, it had already reached the mountains and tropical forests. By August 1991, cholera cases were reported in order of appearances in Ecuador, Colombia, Chile, Brazil, the US, Mexico, Guatemala, Bolivia, and El Salvador. Health authorities still do not know how it was introduced into South America. The case fatality rate has remained at a low of 1%, probably due to the prompt actions of health authorities in informing the public of the epidemic and what preventive cautions should be taken. This epidemic is part of the 7th pandemic which originated in Celebes, Indonesia in 1961. Cholera can spread relatively unchecked in Latin America because sewage in urban areas is not treated even though they do have sewage collection systems. The untreated wastewater enters rivers and the ocean. Consumption of raw seafood is not unusual and has been responsible for cholera infection in some cases. In fact, many countries placed import restrictions on marine products from Peru following the outbreak at a loss of $US10-$US40 million. Municipal sewage treatment facilities, especially stabilization ponds, would prevent the spread of cholera and other pathogens. In rural areas, pit latrines located away from wells can effectively dispose of human wastes. Most water supplies in Latin America are not disinfected. Disinfection drinking water with adequate levels of chlorine would effectively destroy V. cholera. If this is not possible, boiling the water for 2-3 minutes would destroy the pathogen. Any cases of cholera must be reported to PAHO. PAHO has responded to the outbreak by forming a Cholera Task Force and arranged transport of oral rehydration salts, intravenous fluids, antibiotics, and other essential medical supplies.

Phylogenetic Diversity of Vibrio cholerae Associated with Endemic Cholera in Mexico from 1991 to 2008

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Seon Young Choi

2016-03-01

Full Text Available An outbreak of cholera occurred in 1991 in Mexico, where it had not been reported for more than a century and is now endemic. Vibrio cholerae O1 prototype El Tor and classical strains coexist with altered El Tor strains (1991 to 1997. Nontoxigenic (CTX− V. cholerae El Tor dominated toxigenic (CTX+ strains (2001 to 2003, but V. cholerae CTX+ variant El Tor was isolated during 2004 to 2008, outcompeting CTX−V. cholerae. Genomes of six Mexican V. cholerae O1 strains isolated during 1991 to 2008 were sequenced and compared with both contemporary and archived strains of V. cholerae. Three were CTX+ El Tor, two were CTX− El Tor, and the remaining strain was a CTX+ classical isolate. Whole-genome sequence analysis showed the six isolates belonged to five distinct phylogenetic clades. One CTX− isolate is ancestral to the 6th and 7th pandemic CTX+V. cholerae isolates. The other CTX− isolate joined with CTX− non-O1/O139 isolates from Haiti and seroconverted O1 isolates from Brazil and Amazonia. One CTX+ isolate was phylogenetically placed with the sixth pandemic classical clade and the V. cholerae O395 classical reference strain. Two CTX+ El Tor isolates possessing intact Vibrio seventh pandemic island II (VSP-II are related to hybrid El Tor isolates from Mozambique and Bangladesh. The third CTX+ El Tor isolate contained West African-South American (WASA recombination in VSP-II and showed relatedness to isolates from Peru and Brazil. Except for one isolate, all Mexican isolates lack SXT/R391 integrative conjugative elements (ICEs and sensitivity to selected antibiotics, with one isolate resistant to streptomycin. No isolates were related to contemporary isolates from Asia, Africa, or Haiti, indicating phylogenetic diversity.

The cholera

International Nuclear Information System (INIS)

Castaneda, Elizabeth; De la Hoz, Fernando

1996-01-01

The cholera is a sharp intestinal infection, characterized by the abrupt appearance of abundant watery diarrhea and vomit, severe dehydration, metabolic imbalance and circulatory collapse; although it can study a symptomatic or to cause light symptomatology. In the cases serious non-treaties the death can take place in the 24 later hours to its appearance; the lethality in these cases can exceed 50 percent. However. With the treatment of re-hydration appropriate. This decreases to less ten percent. The cholera is related in direct form with the poverty; it is presented where accumulation and lack of measures of hygiene exist and of drinkable water. It is for it that the best strategy to prevent the illness is to eliminate the factors that favor its transmission: to improve the quality of the water and to implement elementary measures of hygiene. When the environmental conditions are favorable, the cholera has been absent

Improving polio vaccination during supplementary campaigns at areas of mass transit in India

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Bahl Sunil

2010-05-01

Full Text Available Abstract Background In India, children who are traveling during mass immunization campaigns for polio represent a substantial component of the total target population. These children are not easily accessible to health workers and may thus not receive vaccine. Vaccination activities at mass transit sites (such as major intersections, bus depots and train stations, can increase the proportion of children vaccinated but the effectiveness of these activities, and factors associated with their success, have not been rigorously evaluated. Methods We assessed data from polio vaccination activities in Jyotiba Phule Nagar district, Uttar Pradesh, India, conducted in June 2006. We used trends in the vaccination results from the June activities to plan the timing, locations, and human resource requirements for transit vaccination activities in two out of the seven blocks in the district for the July 2006 supplementary immunization activity (SIA. In July, similar data was collected and for the first time vaccination teams also recorded the proportion of children encountered each day who were vaccinated (a new monitoring system. Results In June, out of the 360,937 total children vaccinated, 34,643 (9.6% received vaccinations at mass transit sites. In the July SIA, after implementation of a number of changes based on the June monitoring data, 36,475 children were vaccinated at transit sites (a 5.3% increase. Transit site vaccinations in July increased in the two intervention blocks from 18,194 to 21,588 (18.7% and decreased from 16,449 to 14,887 (9.5% in the five other blocks. The new monitoring system showed the proportion of unvaccinated children at street intersection transit sites in the July campaign decreased from 24% (1,784/7,405 at the start of the campaign to 3% (143/5,057 by the end of the SIA, consistent with findings from the more labor-intensive post-vaccination coverage surveys routinely performed by the program. Conclusions Analysis of

Cholera Prevention and Control

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... name=”commit” type=”submit” value=”Submit” /> Prevention & Control Recommend on Facebook Tweet Share Compartir Prevention of ... of cholera and other diarrheal disease prevention. Prevention & Control Topics Ending Cholera: The Global Roadmap to 2030 ...

Phylodynamic analysis of clinical and environmental Vibrio cholerae isolates from Haiti reveals diversification driven by positive selection.

Science.gov (United States)

Azarian, Taj; Ali, Afsar; Johnson, Judith A; Mohr, David; Prosperi, Mattia; Veras, Nazle M; Jubair, Mohammed; Strickland, Samantha L; Rashid, Mohammad H; Alam, Meer T; Weppelmann, Thomas A; Katz, Lee S; Tarr, Cheryl L; Colwell, Rita R; Morris, J Glenn; Salemi, Marco

2014-12-23

Phylodynamic analysis of genome-wide single-nucleotide polymorphism (SNP) data is a powerful tool to investigate underlying evolutionary processes of bacterial epidemics. The method was applied to investigate a collection of 65 clinical and environmental isolates of Vibrio cholerae from Haiti collected between 2010 and 2012. Characterization of isolates recovered from environmental samples identified a total of four toxigenic V. cholerae O1 isolates, four non-O1/O139 isolates, and a novel nontoxigenic V. cholerae O1 isolate with the classical tcpA gene. Phylogenies of strains were inferred from genome-wide SNPs using coalescent-based demographic models within a Bayesian framework. A close phylogenetic relationship between clinical and environmental toxigenic V. cholerae O1 strains was observed. As cholera spread throughout Haiti between October 2010 and August 2012, the population size initially increased and then fluctuated over time. Selection analysis along internal branches of the phylogeny showed a steady accumulation of synonymous substitutions and a progressive increase of nonsynonymous substitutions over time, suggesting diversification likely was driven by positive selection. Short-term accumulation of nonsynonymous substitutions driven by selection may have significant implications for virulence, transmission dynamics, and even vaccine efficacy. Cholera, a dehydrating diarrheal disease caused by toxigenic strains of the bacterium Vibrio cholerae, emerged in 2010 in Haiti, a country where there were no available records on cholera over the past 100 years. While devastating in terms of morbidity and mortality, the outbreak provided a unique opportunity to study the evolutionary dynamics of V. cholerae and its environmental presence. The present study expands on previous work and provides an in-depth phylodynamic analysis inferred from genome-wide single nucleotide polymorphisms of clinical and environmental strains from dispersed geographic settings in

Cholera Illness and Symptoms

Science.gov (United States)

... Share Compartir Cholera is an acute, diarrheal illness caused by infection of the intestine with the bacterium Vibrio cholerae and is spread by ingestion of contaminated food or water. The infection is often mild or without symptoms, ...

Vibrio cholerae Colonization of Soft-Shelled Turtles.

Science.gov (United States)

Wang, Jiazheng; Yan, Meiying; Gao, He; Lu, Xin; Kan, Biao

2017-07-15

Vibrio cholerae is an important human pathogen and environmental microflora species that can both propagate in the human intestine and proliferate in zooplankton and aquatic organisms. Cholera is transmitted through food and water. In recent years, outbreaks caused by V. cholerae -contaminated soft-shelled turtles, contaminated mainly with toxigenic serogroup O139, have been frequently reported, posing a new foodborne disease public health problem. In this study, the colonization by toxigenic V. cholerae on the body surfaces and intestines of soft-shelled turtles was explored. Preferred colonization sites on the turtle body surfaces, mainly the carapace and calipash of the dorsal side, were observed for the O139 and O1 strains. Intestinal colonization was also found. The colonization factors of V. cholerae played different roles in the colonization of the soft-shelled turtle's body surface and intestine. Mannose-sensitive hemagglutinin (MSHA) of V. cholerae was necessary for body surface colonization, but no roles were found for toxin-coregulated pili (TCP) or N -acetylglucosamine-binding protein A (GBPA). Both TCP and GBPA play important roles for colonization in the intestine, whereas the deletion of MSHA revealed only a minor colonization-promoting role for this factor. Our study demonstrated that V. cholerae can colonize the surfaces and the intestines of soft-shelled turtles and indicated that the soft-shelled turtles played a role in the transmission of cholera. In addition, this study showed that the soft-shelled turtle has potential value as an animal model in studies of the colonization and environmental adaption mechanisms of V. cholerae in aquatic organisms. IMPORTANCE Cholera is transmitted through water and food. Soft-shelled turtles contaminated with Vibrio cholerae (commonly the serogroup O139 strains) have caused many foodborne infections and outbreaks in recent years, and they have become a foodborne disease problem. Except for epidemiological

Agent-based modelling of cholera diffusion

NARCIS (Netherlands)

Augustijn-Beckers, Petronella; Doldersum, Tom; Useya, Juliana; Augustijn, Dionysius C.M.

2016-01-01

This paper introduces a spatially explicit agent-based simulation model for micro-scale cholera diffusion. The model simulates both an environmental reservoir of naturally occurring V.cholerae bacteria and hyperinfectious V. cholerae. Objective of the research is to test if runoff from open refuse

Epidemic cholera spreads like wildfire

Science.gov (United States)

Roy, Manojit; Zinck, Richard D.; Bouma, Menno J.; Pascual, Mercedes

2014-01-01

Cholera is on the rise globally, especially epidemic cholera which is characterized by intermittent and unpredictable outbreaks that punctuate periods of regional disease fade-out. These epidemic dynamics remain however poorly understood. Here we examine records for epidemic cholera over both contemporary and historical timelines, from Africa (1990-2006) and former British India (1882-1939). We find that the frequency distribution of outbreak size is fat-tailed, scaling approximately as a power-law. This pattern which shows strong parallels with wildfires is incompatible with existing cholera models developed for endemic regions, as it implies a fundamental role for stochastic transmission and local depletion of susceptible hosts. Application of a recently developed forest-fire model indicates that epidemic cholera dynamics are located above a critical phase transition and propagate in similar ways to aggressive wildfires. These findings have implications for the effectiveness of control measures and the mechanisms that ultimately limit the size of outbreaks.

Environmental Factors Influencing Epidemic Cholera

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Jutla, Antarpreet; Whitcombe, Elizabeth; Hasan, Nur; Haley, Bradd; Akanda, Ali; Huq, Anwar; Alam, Munir; Sack, R. Bradley; Colwell, Rita

2013-01-01

Cholera outbreak following the earthquake of 2010 in Haiti has reaffirmed that the disease is a major public health threat. Vibrio cholerae is autochthonous to aquatic environment, hence, it cannot be eradicated but hydroclimatology-based prediction and prevention is an achievable goal. Using data from the 1800s, we describe uniqueness in seasonality and mechanism of occurrence of cholera in the epidemic regions of Asia and Latin America. Epidemic regions are located near regional rivers and are characterized by sporadic outbreaks, which are likely to be initiated during episodes of prevailing warm air temperature with low river flows, creating favorable environmental conditions for growth of cholera bacteria. Heavy rainfall, through inundation or breakdown of sanitary infrastructure, accelerates interaction between contaminated water and human activities, resulting in an epidemic. This causal mechanism is markedly different from endemic cholera where tidal intrusion of seawater carrying bacteria from estuary to inland regions, results in outbreaks. PMID:23897993

Sustained Local Diversity of Vibrio cholerae O1 Biotypes in a Previously Cholera-Free Country.

Science.gov (United States)

Boucher, Yan

2016-05-03

Although the current cholera pandemic can trace its origin to a specific time and place, many variants of Vibrio cholerae have caused this disease over the last 50 years. The relative clinical importance and geographical distribution of these variants have changed with time, but most remain in circulation. Some countries, such as Mexico and Haiti, had escaped the current pandemic, until large epidemics struck them in 1991 and 2010, respectively. Cholera has been endemic in these countries ever since. A recent retrospective study in mBio presents the results of more than 3 decades of V. cholerae monitoring from environmental and clinical sources in Mexico (S. Y. Choi et al., mBio 7:e02160-15, 2016, http://dx.doi.org/10.1128/mBio.02160-15). It reveals that multiple V. cholerae variants, including classical strains from the previous pandemic, as well as completely novel biotypes, have been circulating in Mexico. This discovery has important implications for the epidemiology and evolution of V. cholerae. Copyright © 2016 Boucher.

Sustained Local Diversity of Vibrio cholerae O1 Biotypes in a Previously Cholera-Free Country

Directory of Open Access Journals (Sweden)

Yan Boucher

2016-07-01

Full Text Available Although the current cholera pandemic can trace its origin to a specific time and place, many variants of Vibrio cholerae have caused this disease over the last 50 years. The relative clinical importance and geographical distribution of these variants have changed with time, but most remain in circulation. Some countries, such as Mexico and Haiti, had escaped the current pandemic, until large epidemics struck them in 1991 and 2010, respectively. Cholera has been endemic in these countries ever since. A recent retrospective study in mBio presents the results of more than 3 decades of V. cholerae monitoring from environmental and clinical sources in Mexico (S. Y. Choi et al., mBio 7:e02160-15, 2016, http://dx.doi.org/10.1128/mBio.02160-15. It reveals that multiple V. cholerae variants, including classical strains from the previous pandemic, as well as completely novel biotypes, have been circulating in Mexico. This discovery has important implications for the epidemiology and evolution of V. cholerae.

How Will Climate Change Impact Cholera Outbreaks?

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Nasr Azadani, F.; Jutla, A.; Rahimikolu, J.; Akanda, A. S.; Huq, A.; Colwell, R. R.

2014-12-01

Environmental parameters associated with cholera are well documented. However, cholera continues to be a global public health threat. Uncertainty in defining environmental processes affecting growth and multiplication of the cholera bacteria can be affected significantly by changing climate at different temporal and spatial scales, either through amplification of the hydroclimatic cycle or by enhanced variability of large scale geophysical processes. Endemic cholera in the Bengal Delta region of South Asia has a unique pattern of two seasonal peaks and there are associated with asymmetric and episodic variability in river discharge. The first cholera outbreak in spring is related with intrusion of bacteria laden coastal seawater during low river discharge. Cholera occurring during the fall season is hypothesized to be associated with high river discharge related to a cross-contamination of water resources and, therefore, a second wave of disease, a phenomenon characteristic primarily in the inland regions. Because of difficulties in establishing linkage between coarse resolutions of the Global Climate Model (GCM) output and localized disease outbreaks, the impact of climate change on diarrheal disease has not been explored. Here using the downscaling method of Support Vector Machines from HADCM3 and ECHAM models, we show how cholera outbreak patterns are changing in the Bengal Delta. Our preliminary results indicate statistically significant changes in both seasonality and magnitude in the occurrence of cholera over the next century. Endemic cholera is likely to transform into epidemic forms and new geographical areas will be at risk for cholera outbreaks.

[Complications and treatment of cholera during pregnancy].

Science.gov (United States)

Figueroa Damian, R; Villagrana Zesati, R; Kasis Ariceaga, D

1994-07-01

Since 1961 cholera has spread in many countries reaching a pandemic form. Since 1991 Mexico has been involved in this pandemia. Near 20% of all cases of cholera in our country happen in fertile women, so the possibility of the association between cholera and pregnancy is high. We present the case of a pregnant woman, who during her third trimester presented a episode of cholera, developing premature labor. Furthermore is revised the medical literature about the general principles of the management of cholera, and the association between pregnancy and the intestinal infection.

Impact of universal mass vaccination with monovalent inactivated hepatitis A vaccines – A systematic review

Science.gov (United States)

Stuurman, Anke L.; Marano, Cinzia; Bunge, Eveline M.; De Moerlooze, Laurence; Shouval, Daniel

2017-01-01

ABSTRACT The WHO recommends integration of universal mass vaccination (UMV) against hepatitis A virus (HAV) in national immunization schedules for children aged ≥1 year, if justified on the basis of acute HAV incidence, declining endemicity from high to intermediate and cost-effectiveness. This recommendation has been implemented in several countries. Our aim was to assess the impact of UMV using monovalent inactivated hepatitis A vaccines on incidence and persistence of anti-HAV (IgG) antibodies in pediatric populations. We conducted a systematic review of literature published between 2000 and 2015 in PubMed, Cochrane Library, LILACS, IBECS identifying a total of 27 studies (Argentina, Belgium, China, Greece, Israel, Panama, the United States and Uruguay). All except one study showed a marked decline in the incidence of hepatitis A post introduction of UMV. The incidence in non-vaccinated age groups decreased as well, suggesting herd immunity but also rising susceptibility. Long-term anti-HAV antibody persistence was documented up to 17 y after a 2-dose primary vaccination. In conclusion, introduction of UMV in countries with intermediate endemicity for HAV infection led to a considerable decrease in the incidence of hepatitis A in vaccinated and in non-vaccinated age groups alike. PMID:27786671

A localized outbreak of cholera due to vibrio cholerae, ogawa resistant to tetracyclines

International Nuclear Information System (INIS)

Ahmed, S.

2015-01-01

To study the clinical and laboratory parameters of a localized Cholera outbreak and determine the sensitivity pattern of the subtype involved. Study Design: A descriptive study. Place and Duration of Study: Combined Military Hospital, Lahore. Duration of Study: Two weeks. Patients and Methods: The study is about a localized outbreak of cholera in a group of soldiers, who consumed water from a single contaminated source of water. We are presenting here an account of the clinical and laboratory parameters of 39 hospitalized cases of cholera, who presented with profuse watery diarrhoea and vomiting. There vital signs, hydration status and systemic examination findings were recorded. Stool samples were sent for routine and microscopic examination and bacteriological culture. Blood samples were taken for complete blood count, serum sodium, potassium, urea and creatinine examination. SPSS 18 was used for statistical analysis of the results. Results: The average age of thirty nine men studied in this outbreak was 24.9 ± 6.9 years. There was no statistically significant difference between confirmed and suspected cholera cases on descriptive analysis of the clinical and laboratory parameters. Majority of patients showed pre-renal azotemia which improved within 48 to 72 hours of hospitalization. Stool cultures isolated Vibrio cholerae, subtype Ogawa, which was resistant to tetracyclines, cotrimoxazole and nalidixic acid but sensitive to fluoroquinolones and third generation cephalosporins. The outbreak was controlled when the contaminated water source was sealed and rectified. Conclusion: Multiple drug resistance strains of Vibrio cholera are causing large outbreaks which should be controlled by prevention of the disease and avoiding inappropriate use of antibiotics. (author)

9 CFR 311.3 - Hog cholera.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Hog cholera. 311.3 Section 311.3... CERTIFICATION DISPOSAL OF DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.3 Hog cholera. (a) The carcasses of all hogs affected with hog cholera shall be condemned. (b) Inconclusive but suspicious symptoms...

Successful small intestine colonization of adult mice by Vibrio cholerae requires ketamine anesthesia and accessory toxins.

Directory of Open Access Journals (Sweden)

Verena Olivier

2009-10-01

Full Text Available Vibrio cholerae colonizes the small intestine of adult C57BL/6 mice. In this study, the physical and genetic parameters that facilitate this colonization were investigated. Successful colonization was found to depend upon anesthesia with ketamine-xylazine and neutralization of stomach acid with sodium bicarbonate, but not streptomycin treatment. A variety of common mouse strains were colonized by O1, O139, and non-O1/non-O139 strains. All combinations of mutants in the genes for hemolysin, the multifunctional, autoprocessing RTX toxin (MARTX, and hemagglutinin/protease were assessed, and it was found that hemolysin and MARTX are each sufficient for colonization after a low dose infection. Overall, this study suggests that, after intragastric inoculation, V. cholerae encounters barriers to infection including an acidic environment and an immediate immune response that is circumvented by sodium bicarbonate and the anti-inflammatory effects of ketamine-xylazine. After initial adherence in the small intestine, the bacteria are subjected to additional clearance mechanisms that are evaded by the independent toxic action of hemolysin or MARTX. Once colonization is established, it is suggested that, in humans, these now persisting bacteria initiate synthesis of the major virulence factors to cause cholera disease. This adult mouse model of intestinal V. cholerae infection, now well-characterized and fully optimized, should serve as a valuable tool for studies of pathogenesis and testing vaccine efficacy.

High-resolution spatial analysis of cholera patients reported in Artibonite department, Haiti in 2010-2011.

Science.gov (United States)

Allan, Maya; Grandesso, Francesco; Pierre, Ronald; Magloire, Roc; Coldiron, Matthew; Martinez-Pino, Isabel; Goffeau, Thierry; Gitenet, Romain; François, Gwenola; Olson, David; Porten, Klaudia; Luquero, Francisco J

2016-03-01

for pinpointing locations most affected by cholera, and in the future could help prioritize the places in need of interventions such as improvement of sanitation and vaccination. The findings also describe spatio-temporal transmission patterns of the epidemic in a cholera-naïve country such as Haiti. By identifying transmission hubs, it is possible to target prevention strategies that, over time, could reduce transmission of the disease and eventually eliminate cholera in Haiti. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Global climate and infectious disease: the cholera paradigm.

Science.gov (United States)

Colwell, R R

1996-12-20

The origin of cholera has been elusive, even though scientific evidence clearly shows it is a waterborne disease. However, standard bacteriological procedures for isolation of the cholera vibrio from environmental samples, including water, between epidemics generally were unsuccessful. Vibrio cholerae, a marine vibrio, requiring salt for growth, enters into a dormant, viable but nonculturable stage when conditions are unfavorable for growth and reproduction. The association of Vibrio cholerae with plankton, notably copepods, provides further evidence for the environmental origin of cholera, as well as an explanation for the sporadic and erratic occurrence of cholera epidemics. On a global scale, cholera epidemics can now be related to climate and climatic events, such as El Niño, as well as the global distribution of the plankton host. Remote sensing, with the use of satellite imagery, offers the potential for predicting conditions conducive to cholera outbreaks or epidemics.

Comparative Genomics of Vibrio cholerae O1 Isolated from Cholera Patients in Bangladesh

DEFF Research Database (Denmark)

Hossain, Zenat Zebin; Leekitcharoenphon, Pimlapas; Dalsgaard, Anders

patients was co-infected with two V. cholerae strains (VC-1 and VC-3). Major virulence factors, biotype and antimicrobial resistance genes were identified by WGS. A global phylogenetic tree was inferred using genome wide SNPs (Single Nucleotide Polymorphism) analysis. RESULTS: All the V. cholerae strains...

Cholera in Pregnancy: Outcomes from a Specialized Cholera Treatment Unit for Pregnant Women in L?og?ne, Haiti

OpenAIRE

Ciglenecki, Iza; Bichet, Mathieu; Tena, Javier; Mondesir, Erneau; Bastard, Mathieu; Tran, Nguyen-Toan; Antierens, Annick; Staderini, Nelly

2013-01-01

BACKGROUND: The association between cholera in pregnancy and negative fetal outcome has been described since the 19(th) century. However, there is limited published literature on the subject. We describe pregnancy outcomes from a specialized multidisciplinary hospital unit at the onset of a large cholera outbreak in Haiti in 2010 and 2011. METHODS: Pregnant women with cholera were hospitalized in a specialized unit within the MSF hospital compound in Léogâne and treated using standard cholera...

Detection of cholera (ctx) and zonula occludens (zot) toxin genes in Vibrio cholerae O1, O139 and non-O1 strains.

Science.gov (United States)

Rivera, I G; Chowdhury, M A; Sanchez, P S; Sato, M I; Huq, A; Colwell, R R; Martins, M T

1995-09-01

Vibrio cholerae O1 and V. cholerae non-O1 strains isolated from environmental samples collected in São Paulo, Brazil, during cholera epidemics and pre-epidemic periods were examined for the presence of toxin genes. V. cholerae O1 strains isolated from clinical samples in Peru and Mexico, and V. cholerae O139 strains from India were also examined for the presence of ctx (cholera toxin gene) and zot (zonula occludens toxin gene) by polymerase chain reaction (PCR). A modified DNA-extraction method applied in this study yielded satisfactory recovery of genomic DNA from vibrios. Results showed that strains of V. cholerae O1 isolated during the preepidemic period were ctx (-)/zot (-) whereas strains isolated during the epidemic were ctx (+)/zot (+). All V. cholerae non-O1 strains tested in the study were ctx (-)/zot (-), whereas all V. cholerae O139 strains were ctx (+)/zot (+). Rapid detection of the virulence genes (ctx and zot) can be achieved by PCR and this can serve as an important tool in the epidemiology and surveillance of V. cholerae.

The green vaccine: A global strategy to combat infectious and autoimmune diseases

Science.gov (United States)

Davoodi-Semiromi, Abdoreza; Samson, Nalapalli; Daniell, Henry

2009-01-01

Plant derived oral green vaccines eliminate expenses associated with fermenters, purification, cold storage/transportation and sterile delivery. Green vaccines are expressed via the plant nuclear or chloroplast genomes. Chloroplast expression has advantages of hyper-expression of therapeutic proteins (10,000 copies of trans-gene per cell), efficient oral delivery and transgene containment via maternal inheritance. To date, 23 vaccine antigens against 16 different bacterial, viral or protozoan pathogens have been expressed in chloroplasts. Mice subcutaneously immunized with the chloroplast derived anthrax protective antigen conferred 100% protection against lethal doses of the anthrax toxin. Oral immunization (ORV) of F1-V antigens without adjuvant conferred greater protection (88%) against 50-fold lethal dose of aerosolized plague (Yersinia pestis) than subcutaneous (SQV) immunization (33%). Oral immunization of malarial vaccine antigens fused to the cholera antigen (CTB-AMA1/CTB-Msp1) conferred prolonged immunity (50% life span), 100% protection against cholera toxin challenge and inhibited proliferation of the malarial parasite. Protection was correlated with antigen-specific titers of intestinal, serum IgA & IgG1 in ORV and only IgG1 in SQV mice, but no other immunoglobulin. High level expression in edible plant chloroplasts ideal for oral delivery and long-term immunity observed should facilitate development of low cost human vaccines for large populations, at times of outbreak. PMID:19430198

Genetic characterization of ØVC8 lytic phage for Vibrio cholerae O1.

Science.gov (United States)

Solís-Sánchez, Alejandro; Hernández-Chiñas, Ulises; Navarro-Ocaña, Armando; De la Mora, Javier; Xicohtencatl-Cortes, Juan; Eslava-Campos, Carlos

2016-03-22

Epidemics and pandemics of cholera, a diarrheal disease, are attributed to Vibrio cholera serogroups O1 and O139. In recent years, specific lytic phages of V. cholera have been proposed to be important factors in the cyclic occurrence of cholera in endemic areas. However, the role and potential participation of lytic phages during long interepidemic periods of cholera in non-endemic regions have not yet been described. The purpose of this study was to isolate and characterize specific lytic phages of V. cholera O1 strains. Sixteen phages were isolated from wastewater samples collected at the Endhó Dam in Hidalgo State, Mexico, concentrated with PEG/NaCl, and purified by density gradient. The lytic activity of the purified phages was tested using different V. cholerae O1 and O139 strains. Phage morphology was visualized by transmission electron microscopy (TEM), and phage genome sequencing was performed using the Genome Analyzer IIx System. Genome assembly and bioinformatics analysis were performed using a set of high-throughput programs. Phage structural proteins were analyzed by mass spectrometry. Sixteen phages with lytic and lysogenic activity were isolated; only phage ØVC8 showed specific lytic activity against V. cholerae O1 strains. TEM images of ØVC8 revealed a phage with a short tail and an isometric head. The ØVC8 genome comprises linear double-stranded DNA of 39,422 bp with 50.8 % G + C. Of the 48 annotated ORFs, 16 exhibit homology with sequences of known function and several conserved domains. Bioinformatics analysis showed multiple conserved domains, including an Ig domain, suggesting that ØVC8 might adhere to different mucus substrates such as the human intestinal epithelium. The results suggest that ØVC8 genome utilize the "single-stranded cohesive ends" packaging strategy of the lambda-like group. The two structural proteins sequenced and analyzed are proteins of known function. ØVC8 is a lytic phage with specific activity against V. cholerae

Epidemic Risk from Cholera Introductions into Mexico

OpenAIRE

Moore, Sean M.; Shannon, Kerry L.; Zelaya, Carla E.; Azman, Andrew S.; Lessler, Justin

2014-01-01

Stemming from the 2010 cholera outbreak in Haiti, cholera transmission in Hispaniola continues with over 40,000 cases in 2013. The presence of an ongoing cholera outbreak in the region poses substantial risks to countries throughout the Americas, particularly in areas with poor infrastructure. Since September 9, 2013 nearly 200 cholera cases have been reported in Mexico, as a result of introductions from Hispaniola or Cuba. There appear to have been multiple introductions into Mexico resultin...

Updated Global Burden of Cholera in Endemic Countries

Science.gov (United States)

Ali, Mohammad; Nelson, Allyson R.; Lopez, Anna Lena; Sack, David A.

2015-01-01

Background The global burden of cholera is largely unknown because the majority of cases are not reported. The low reporting can be attributed to limited capacity of epidemiological surveillance and laboratories, as well as social, political, and economic disincentives for reporting. We previously estimated 2.8 million cases and 91,000 deaths annually due to cholera in 51 endemic countries. A major limitation in our previous estimate was that the endemic and non-endemic countries were defined based on the countries’ reported cholera cases. We overcame the limitation with the use of a spatial modelling technique in defining endemic countries, and accordingly updated the estimates of the global burden of cholera. Methods/Principal Findings Countries were classified as cholera endemic, cholera non-endemic, or cholera-free based on whether a spatial regression model predicted an incidence rate over a certain threshold in at least three of five years (2008-2012). The at-risk populations were calculated for each country based on the percent of the country without sustainable access to improved sanitation facilities. Incidence rates from population-based published studies were used to calculate the estimated annual number of cases in endemic countries. The number of annual cholera deaths was calculated using inverse variance-weighted average case-fatality rate (CFRs) from literature-based CFR estimates. We found that approximately 1.3 billion people are at risk for cholera in endemic countries. An estimated 2.86 million cholera cases (uncertainty range: 1.3m-4.0m) occur annually in endemic countries. Among these cases, there are an estimated 95,000 deaths (uncertainty range: 21,000-143,000). Conclusion/Significance The global burden of cholera remains high. Sub-Saharan Africa accounts for the majority of this burden. Our findings can inform programmatic decision-making for cholera control. PMID:26043000

Epidemic risk from cholera introductions into Mexico.

Science.gov (United States)

Moore, Sean M; Shannon, Kerry L; Zelaya, Carla E; Azman, Andrew S; Lessler, Justin

2014-02-21

Stemming from the 2010 cholera outbreak in Haiti, cholera transmission in Hispaniola continues with over 40,000 cases in 2013. The presence of an ongoing cholera outbreak in the region poses substantial risks to countries throughout the Americas, particularly in areas with poor infrastructure. Since September 9, 2013 nearly 200 cholera cases have been reported in Mexico, as a result of introductions from Hispaniola or Cuba. There appear to have been multiple introductions into Mexico resulting in outbreaks of 2 to over 150 people. Using publicly available data, we attempt to estimate the reproductive number (R) of cholera in Mexico, and thereby assess the potential of continued introductions to establish a sustained epidemic. We estimate R for cholera in Mexico to be between 0.8 to 1.1, depending on the number of introductions, with the confidence intervals for the most plausible estimates crossing 1. These results suggest that the efficiency of cholera transmission in some regions of Mexico is near that necessary for a large epidemic. Intensive surveillance, evaluation of water and sanitation infrastructure, and planning for rapid response are warranted steps to avoid potential large epidemics in the region.

Impact of solar irradiation on cholera toxin secretion by different strains of Vibrio cholerae

CSIR Research Space (South Africa)

Ssemakalu, CC

2013-09-01

Full Text Available , Salomon RN, Garrity K, Reveillaud I, Kopin A, Jackson FR, et al. Vibrio cholerae infection of Drosophila melanogaster mimics the human disease cholera. PLoS Pathog. 2005;1(1):e8. http://dx.doi.org/10.1371/ journal.ppat.0010008 2. World Health...

Costs of Illness Due to Endemic Cholera

Science.gov (United States)

Poulos, C.; Riewpaiboon, A.; Stewart, J.F.; Clemens, J.; Guh, S.; Agtini, M.; Sur, D.; Islam, Z.; Lucas, M.; Whittington, D.

2013-01-01

Summary Economic analyses of cholera immunization programmes require estimates of the costs of cholera. The Diseases of the Most Impoverished programme measured the public, provider, and patient costs of culture-confirmed cholera in four study sites with endemic cholera using a combination of hospital- and community-based studies. Families with culture-proven cases were surveyed at home 7 and 14 days after confirmation of illness. Public costs were measured at local health facilities using a micro-costing methodology. Hospital-based studies found that the costs of severe cholera were USD 32 and 47 in Matlab and Beira. Community-based studies in North Jakarta and Kolkata found that cholera cases cost between USD 28 and USD 206, depending on hospitalization. Patient costs of illness as a percentage of average monthly income were 21% and 65% for hospitalized cases in Kolkata and North Jakarta, respectively. This burden on families is not captured by studies that adopt a provider perspective. PMID:21554781

Persistence of plasmids, cholera toxin genes, and prophage DNA in classical Vibrio cholerae O1.

Science.gov (United States)

Cook, W L; Wachsmuth, K; Johnson, S R; Birkness, K A; Samadi, A R

1984-07-01

Plasmid profiles, the location of cholera toxin subunit A genes, and the presence of the defective VcA1 prophage genome in classical Vibrio cholerae isolated from patients in Bangladesh in 1982 were compared with those in older classical strains isolated during the sixth pandemic and with those in selected eltor and nontoxigenic O1 isolates. Classical strains typically had two plasmids (21 and 3 megadaltons), eltor strains typically had no plasmids, and nontoxigenic O1 strains had zero to three plasmids. The old and new isolates of classical V. cholerae had two HindIII chromosomal digest fragments containing cholera toxin subunit A genes, whereas the eltor strains from Eastern countries had one fragment. The eltor strains from areas surrounding the Gulf of Mexico also had two subunit A gene fragments, which were smaller and easily distinguished from the classical pattern. All classical strains had 8 to 10 HindIII fragments containing the defective VcA1 prophage genome; none of the Eastern eltor strains had these genes, and the Gulf Coast eltor strains contained a different array of weakly hybridizing genes. These data suggest that the recent isolates of classical cholera in Bangladesh are closely related to the bacterial strain(s) which caused classical cholera during the sixth pandemic. These data do not support hypotheses that either the eltor or the nontoxigenic O1 strains are precursors of the new classical strains.

Cholera outbreak caused by drug resistant Vibrio cholerae serogroup O1 biotype ElTor serotype Ogawa in Nepal; a cross-sectional study

Directory of Open Access Journals (Sweden)

Pappu Kumar Gupta

2016-06-01

Full Text Available Abstract Background Cholera is a major cause of mortality and morbidity in underdeveloped countries including Nepal. Recently drug resistance in Vibrio cholerae has become a serious problem mainly in developing countries. The main objectives of our study were to investigate the occurrence of Vibrio cholerae in stool samples from patients with watery diarrhea and to determine the antimicrobial susceptibility patterns of V. cholerae isolates. Methods A total of 116 stool samples from patients suffering from watery diarrhea during July to December 2012 were obtained from outbreak areas from all over Nepal. Alkaline peptone water and thiosulphate citrate bile salt sucrose agar (TCBS were used to isolate the Vibrio cholerae. The isolates were identified with the help of colony morphology, Gram’s staining, conventional biochemical testing, serotyping and biotyping. Antimicrobial susceptibility testing was performed by determining the minimum inhibitory concentration (MIC by agar dilution method. Results Vibrio cholerae was isolated from 26.72 % of total samples. All isolated Vibrio cholerae were confirmed to be Vibrio cholerae serogoup O1 biotype El Tor and serotype Ogawa. All isolates were resistant to ampicillin and cotrimoxazole. Twenty nine isolates were resistant toward two different classes of antibiotics, one strain was resistant to three different classes of antibiotics and one strain was resistant to four different classes of antibiotics. According to the definition of the multidrug resistant bacteria; 6.45 % of the strains of Vibrio cholerae were found to be multidrug resistant. Conclusions Cholera due to multidrug resistant Vibrio cholerae is also possible in Nepal. According to the antimicrobial susceptibility pattern of Vibrio cholerae in our study we recommend to use any antibiotics among tetracycline, doxycycline, levofloxacin, azithromycin, chloramphenicol and ciprofloxacin for preliminary treatment of cholera in Nepal.

Cholera ante portas – The re-emergence of cholera in Kinshasa after a ten-year hiatus

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Bompangue, Didier; Vesenbeckh, Silvan Manuel; Giraudoux, Patrick; Castro, Marcia; Muyembe, Jean-Jacques; Kebela Ilunga, Benoît; Murray, Megan

2012-01-01

Background: Cholera is an endemic disease in certain well-defined areas in the east of the Democratic Republic of Congo (DRC). The west of the country, including the mega-city Kinshasa, has been free of cases since mid 2001 when the last outbreak ended. Methods and Findings: We used routinely collected passive surveillance data to construct epidemic curves of the cholera cases and map the spatio-temporal progress of the disease during the first 47 weeks of 2011. We compared the spatial distribution of disease spread to that which occurred in the last cholera epidemic in Kinshasa between 1996 and 2001. To better understand previous determinants of cholera spread in this region, we conducted a correlation analysis to assess the impact of rainfall on weekly health zone cholera case counts between December 1998 and March 2001 and a Generalized Linear Model (GLM) regression analysis to identify factors that have been associated with the most vulnerable health zones within Kinshasa between October 1998 and June 1999. In February 2011, cholera reemerged in a region surrounding Kisangani and gradually spread westwards following the course of the Congo River to Kinshasa, home to 10 million people. Ten sampled isolates were confirmed to be Vibrio cholerae O1, biotype El Tor, serotype Inaba, resistant to trimethoprim-sulfa, furazolidone, nalidixic acid, sulfisoxaole, and streptomycin, and intermediate resistant to Chloramphenicol. An analysis of a previous outbreak in Kinshasa shows that rainfall was correlated with case counts and that health zone population densities as well as fishing and trade activities were predictors of case counts. Conclusion: Cholera is particularly difficult to tackle in the DRC. Given the duration of the rainy season and increased riverine traffic from the eastern provinces in late 2011, we expect further increases in cholera in the coming months and especially within the mega-city Kinshasa. We urge all partners involved in the response to remain

Crystallization of isoelectrically homogeneous cholera toxin

International Nuclear Information System (INIS)

Spangler, B.D.; Westbrook, E.M.

1989-01-01

Past difficulty in growing good crystals of cholera toxin has prevented the study of the crystal structure of this important protein. The authors have determined that failure of cholera toxin to crystallize well has been due to its heterogeneity. They have now succeeded in overcoming the problem by isolating a single isoelectric variant of this oligomeric protein (one A subunit and five B subunits). Cholera toxin purified by their procedure readily forms large single crystals. The crystal form has been described previously. They have recorded data from native crystals of cholera toxin to 3.0-angstrom resolution with our electronic area detectors. With these data, they have found the orientation of a 5-fold symmetry axis within these crystals, perpendicular to the screw dyad of the crystal. They are now determining the crystal structure of cholera toxin by a combination of multiple heavy-atom isomorphous replacement and density modification techniques, making use of rotational 5-fold averaging of the B subunits

Sustained Local Diversity of Vibrio cholerae O1 Biotypes in a Previously Cholera-Free Country

OpenAIRE

Yan Boucher

2016-01-01

ABSTRACT Although the current cholera pandemic can trace its origin to a specific time and place, many variants of Vibrio cholerae have caused this disease over the last 50?years. The relative clinical importance and geographical distribution of these variants have changed with time, but most remain in circulation. Some countries, such as Mexico and Haiti, had escaped the current pandemic, until large epidemics struck them in 1991 and 2010, respectively. Cholera has been endemic in these coun...

Riverbed Sediments as Reservoirs of Multiple Vibrio cholerae Virulence-Associated Genes: A Potential Trigger for Cholera Outbreaks in Developing Countries.

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Abia, Akebe Luther King; Ubomba-Jaswa, Eunice; Momba, Maggy Ndombo Benteke

2017-01-01

Africa remains the most cholera stricken continent in the world as many people lacking access to safe drinking water rely mostly on polluted rivers as their main water sources. However, studies in these countries investigating the presence of Vibrio cholerae in aquatic environments have paid little attention to bed sediments. Also, information on the presence of virulence-associated genes (VAGs) in environmental ctx -negative V. cholerae strains in this region is lacking. Thus, we investigated the presence of V. cholerae VAGs in water and riverbed sediment of the Apies River, South Africa. Altogether, 120 samples (60 water and 60 sediment samples) collected from ten sites on the river (January and February 2014) were analysed using PCR. Of the 120 samples, 37 sediment and 31 water samples were positive for at least one of the genes investigated. The haemolysin gene (hlyA) was the most isolated gene. The cholera toxin (ctxAB) and non-O1 heat-stable (stn/sto) genes were not detected. Genes were frequently detected at sites influenced by human activities. Thus, identification of V. cholerae VAGs in sediments suggests the possible presence of V. cholerae and identifies sediments of the Apies River as a reservoir for potentially pathogenic V. cholerae with possible public health implications.

Riverbed Sediments as Reservoirs of Multiple Vibrio cholerae Virulence-Associated Genes: A Potential Trigger for Cholera Outbreaks in Developing Countries

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Akebe Luther King Abia

2017-01-01

Full Text Available Africa remains the most cholera stricken continent in the world as many people lacking access to safe drinking water rely mostly on polluted rivers as their main water sources. However, studies in these countries investigating the presence of Vibrio cholerae in aquatic environments have paid little attention to bed sediments. Also, information on the presence of virulence-associated genes (VAGs in environmental ctx-negative V. cholerae strains in this region is lacking. Thus, we investigated the presence of V. cholerae VAGs in water and riverbed sediment of the Apies River, South Africa. Altogether, 120 samples (60 water and 60 sediment samples collected from ten sites on the river (January and February 2014 were analysed using PCR. Of the 120 samples, 37 sediment and 31 water samples were positive for at least one of the genes investigated. The haemolysin gene (hlyA was the most isolated gene. The cholera toxin (ctxAB and non-O1 heat-stable (stn/sto genes were not detected. Genes were frequently detected at sites influenced by human activities. Thus, identification of V. cholerae VAGs in sediments suggests the possible presence of V. cholerae and identifies sediments of the Apies River as a reservoir for potentially pathogenic V. cholerae with possible public health implications.

Parents’ and Adolescents’ Willingness to be Vaccinated Against Serogroup B Meningococcal Disease during a Mass Vaccination in Saguenay–Lac-St-Jean (Quebec

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Eve Dubé

2015-01-01

Full Text Available A mass vaccination campaign with the 4CMenB vaccine (Bexsero®; Novartis Pharmaceutical Canada Inc was launched in a serogroup B endemic area in Quebec. A telephone survey was conducted to assess parental and adolescent opinions about the acceptability of the vaccine. Intent to receive the vaccine or vaccine receipt was reported by the majority of parents (93% and adolescents (75%. Meningitis was perceived as being a dangerous disease by the majority of parents and adolescents. The majority of respondents also considered the 4CMenB vaccine to be safe and effective. The main reason for positive vaccination intention or behaviour was self-protection, while a negative attitude toward vaccination in general was the main reason mentioned by parents who did not intend to have their child vaccinated. Adolescents mainly reported lack of interest, time or information, and low perceived susceptibility and disease severity as the main reasons for not intending to be vaccinated or not being vaccinated.

Human Gut Microbiota Predicts Susceptibility to Vibrio cholerae Infection.

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Midani, Firas S; Weil, Ana A; Chowdhury, Fahima; Begum, Yasmin A; Khan, Ashraful I; Debela, Meti D; Durand, Heather K; Reese, Aspen T; Nimmagadda, Sai N; Silverman, Justin D; Ellis, Crystal N; Ryan, Edward T; Calderwood, Stephen B; Harris, Jason B; Qadri, Firdausi; David, Lawrence A; LaRocque, Regina C

2018-04-12

Cholera is a public health problem worldwide and the risk factors for infection are only partially understood. We prospectively studied household contacts of cholera patients to compare those who were infected with those who were not. We constructed predictive machine learning models of susceptibility using baseline gut microbiota data. We identified bacterial taxa associated with susceptibility to Vibrio cholerae infection and tested these taxa for interactions with V. cholerae in vitro. We found that machine learning models based on gut microbiota predicted V. cholerae infection as well as models based on known clinical and epidemiological risk factors. A 'predictive gut microbiota' of roughly 100 bacterial taxa discriminated between contacts who developed infection and those who did not. Susceptibility to cholera was associated with depleted levels of microbes from the phylum Bacteroidetes. By contrast, a microbe associated with cholera by our modeling framework, Paracoccus aminovorans, promoted the in vitro growth of V. cholerae. Gut microbiota structure, clinical outcome, and age were also linked. These findings support the hypothesis that abnormal gut microbial communities are a host factor related to V. cholerae susceptibility.

The Corn Smut ('Huitlacoche' as a New Platform for Oral Vaccines.

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Margarita Juárez-Montiel

Full Text Available The development of new alternative platforms for subunit vaccine production is a priority in the biomedical field. In this study, Ustilago maydis, the causal agent of common corn smut or 'huitlacoche'has been genetically engineered to assess expression and immunogenicity of the B subunit of the cholera toxin (CTB, a relevant immunomodulatory agent in vaccinology. An oligomeric CTB recombinant protein was expressed in corn smut galls at levels of up to 1.3 mg g-1 dry weight (0.8% of the total soluble protein. Mice orally immunized with 'huitlacoche'-derived CTB showed significant humoral responses that were well-correlated with protection against challenge with the cholera toxin (CT. These findings demonstrate the feasibility of using edible corn smut as a safe, effective, and low-cost platform for production and delivery of a subunit oral vaccine. The implications of this platform in the area of molecular pharming are discussed.

Household Transmission of Vibrio cholerae in Bangladesh.

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Jonathan D Sugimoto

2014-11-01

Full Text Available Vibrio cholerae infections cluster in households. This study's objective was to quantify the relative contribution of direct, within-household exposure (for example, via contamination of household food, water, or surfaces to endemic cholera transmission. Quantifying the relative contribution of direct exposure is important for planning effective prevention and control measures.Symptom histories and multiple blood and fecal specimens were prospectively collected from household members of hospital-ascertained cholera cases in Bangladesh from 2001-2006. We estimated the probabilities of cholera transmission through 1 direct exposure within the household and 2 contact with community-based sources of infection. The natural history of cholera infection and covariate effects on transmission were considered. Significant direct transmission (p-value<0.0001 occurred among 1414 members of 364 households. Fecal shedding of O1 El Tor Ogawa was associated with a 4.9% (95% confidence interval: 0.9%-22.8% risk of infection among household contacts through direct exposure during an 11-day infectious period (mean length. The estimated 11-day risk of O1 El Tor Ogawa infection through exposure to community-based sources was 2.5% (0.8%-8.0%. The corresponding estimated risks for O1 El Tor Inaba and O139 infection were 3.7% (0.7%-16.6% and 8.2% (2.1%-27.1% through direct exposure, and 3.4% (1.7%-6.7% and 2.0% (0.5%-7.3% through community-based exposure. Children under 5 years-old were at elevated risk of infection. Limitations of the study may have led to an underestimation of the true risk of cholera infection. For instance, available covariate data may have incompletely characterized levels of pre-existing immunity to cholera infection. Transmission via direct exposure occurring outside of the household was not considered.Direct exposure contributes substantially to endemic transmission of symptomatic cholera in an urban setting. We provide the first estimate of

Efficacy of Ciprofloxacin for Treatment of Cholera Associated with Diminished Susceptibility to Ciprofloxacin to Vibrio cholerae O1.

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Khan, Wasif Ali; Saha, Debasish; Ahmed, Sabeena; Salam, Mohammed Abdus; Bennish, Michael Louis

2015-01-01

We identified a poor clinical response to treatment of cholera with a single 1 g dose of ciprofloxacin, a standard treatment for cholera. To determine reasons for the poor response and better therapeutic approaches we examined the minimal inhibitor concentration (MIC, n = 275) and disc-diffusion zone sizes (n = 205) for ciprofloxacin and nalidixic acid of V. cholerae O1 strains isolated in Bangladesh from 1994 to 2012, and reexamined data from 161 patients infected with Vibrio cholerae O1 recruited in four clinical trials who received single- or multiple-dose ciprofloxacin for treatment of cholera and compared their clinical response to the V. cholerae O1 susceptibility. Although all 275 isolates of V. cholerae O1 remained susceptible to ciprofloxacin using standard MIC and disc-diffusion thresholds, the MIC90 to ciprofloxacin increased from 0.010 in 1994 to 0.475 μgm/ml in 2012. Isolates became frankly resistant to nalidixic with the MIC90 increasing from 21 μgm/ml in 1994 to >256 μgm/ml and 166 of 205 isolates from 1994 to 2005 being frankly resistant using disc-diffusion testing. Isolates resistant to nalidixic acid by disc-diffusion testing had a median ciprofloxacin MIC of 0.190 μgm/ml (10th-90th centiles 0.022 to 0.380); nalidixic acid-susceptible isolates had a median ciprofloxacin MIC of 0.002 (0.002 to 0.012).The rate of clinical success with single-dose ciprofloxacin treatment for nalidixic acid-susceptible strains was 94% (61 of 65 patients) and bacteriologic success 97% (63/65) compared to 18% (12/67) and 8% (5/67) respectively with nalidixic acid-resistant strains (Ptreatment with ciprofloxacin had 86% and 100% clinical and bacteriologic success rates respectively in patients infected with nalidixic acid-susceptible strains of V. cholerae O1 compared to clinical success 67% and bacteriologic success 60% with nalidixic acid-resistant strains. Single-dose ciprofloxacin is not effective for treating cholera caused by V. cholerae O1 with diminished

Vibrio cholerae as a predator: lessons from evolutionary principles

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Stefan ePukatzki

2013-12-01

Full Text Available Diarrheal diseases are the second-most common cause of death among children under the age of five worldwide. Cholera alone, caused by the marine bacterium Vibrio cholerae, is responsible for several million cases and over 120,000 deaths annually. When contaminated water is ingested, V. cholerae passes through the gastric acid barrier, penetrates the mucin layer of the small intestine, and adheres to the underlying epithelial lining. V. cholerae multiplies rapidly, secretes cholera toxin, and exits the human host in vast numbers during diarrheal purges. How V. cholerae rapidly reaches such high numbers during each purge is not clearly understood. We propose that V. cholerae employs its bactericidal type VI secretion system to engage in intraspecies and intraguild predation for nutrient acquisition to support rapid growth and multiplication.

[The cholera epidemic in Latin America].

Science.gov (United States)

Olsvik, O

1992-05-30

An outbreak of cholera started in Peru in January 1991 and spread through most Latin American countries within a year. This was the first known epidemic of cholera in America for more than a century. In 1991, 321,334 persons were reported to have cholera in Peru, 119,063 were hospitalized, and 2,906 died. Other countries like Ecuador, Colombia, Guatemala, Brazil, Mexico, Bolivia, Chile, El Salvador, Venezuela and Honduras were also affected, but these countries combined accounted for only 20% of the cases registered in Peru. In April 1992, all Latin American countries except Uruguay, Paraguay and French Guyana have reported cholera. The mortality rate for the epidemic in Latin America was only 1%, mainly owing to good oral rehydration treatment provided by Local health services and the Pan American Health Organization. The causative organism was Vibrio cholerae, serogroup O1, serotype Inaba (and Ogawa) of the El Tor biotype. Genetic characterization shows this strain to be unique, and the designation is reserved for the Latin American strain, distinguishing it from the other El Tor isolates from the 7th pandemic.

Vibrio cholerae infection, novel drug targets and phage therapy.

Science.gov (United States)

Fazil, Mobashar Hussain Urf Turabe; Singh, Durg V

2011-10-01

Vibrio cholerae is the causative agent of the diarrheal disease cholera. Although antibiotic therapy shortens the duration of diarrhea, excessive use has contributed to the emergence of antibiotic resistance in V. cholerae. Mobile genetic elements have been shown to be largely responsible for the shift of drug resistance genes in bacteria, including some V. cholerae strains. Quorum sensing communication systems are used for interaction among bacteria and for sensing environmental signals. Sequence analysis of the ctxB gene of toxigenic V. cholerae strains demonstrated its presence in multiple cholera toxin genotypes. Moreover, bacteriophage that lyse the bacterium have been reported to modulate epidemics by decreasing the required infectious dose of the bacterium. In this article, we will briefly discuss the disease, its clinical manifestation, antimicrobial resistance and the novel approaches to locate drug targets to treat cholera.

Genome assortment, not serogroup, defines Vibrio cholerae pandemic strains

Energy Technology Data Exchange (ETDEWEB)

Brettin, Thomas S [Los Alamos National Laboratory; Bruce, David C [Los Alamos National Laboratory; Challacombe, Jean F [Los Alamos National Laboratory; Detter, John C [Los Alamos National Laboratory; Han, Cliff S [Los Alamos National Laboratory; Munik, A C [Los Alamos National Laboratory; Chertkov, Olga [Los Alamos National Laboratory; Meincke, Linda [Los Alamos National Laboratory; Saunders, Elizabeth [Los Alamos National Laboratory; Choi, Seon Y [SEOUL NATL. UNIV.; Haley, Bradd J [U. MARYLAND; Taviani, Elisa [U. MARYLAND; Jeon, Yoon - Seong [INTL. VACCINE INST. SEOUL; Kim, Dong Wook [INTL. VACCINE INST. SEOUL; Lee, Jae - Hak [SEOUL NATL. UNIV.; Walters, Ronald A [PNNL; Hug, Anwar [NATL. INST. CHOLERIC ENTERIC DIS.; Colwell, Rita R [U. MARYLAND

2009-01-01

Vibrio cholerae, the causative agent of cholera, is a bacterium autochthonous to the aquatic environment, and a serious public health threat. V. cholerae serogroup O1 is responsible for the previous two cholera pandemics, in which classical and El Tor biotypes were dominant in the 6th and the current 7th pandemics, respectively. Cholera researchers continually face newly emerging and re-emerging pathogenic clones carrying combinations of new serogroups as well as of phenotypic and genotypic properties. These genotype and phenotype changes have hampered control of the disease. Here we compare the complete genome sequences of 23 strains of V. cholerae isolated from a variety of sources and geographical locations over the past 98 years in an effort to elucidate the evolutionary mechanisms governing genetic diversity and genesis of new pathogenic clones. The genome-based phylogeny revealed 12 distinct V. cholerae phyletic lineages, of which one, designated the V. cholerae core genome (CG), comprises both O1 classical and EI Tor biotypes. All 7th pandemic clones share nearly identical gene content, i.e., the same genome backbone. The transition from 6th to 7th pandemic strains is defined here as a 'shift' between pathogenic clones belonging to the same O1 serogroup, but from significantly different phyletic lineages within the CG clade. In contrast, transition among clones during the present 7th pandemic period can be characterized as a 'drift' between clones, differentiated mainly by varying composition of laterally transferred genomic islands, resulting in emergence of variants, exemplified by V.cholerae serogroup O139 and V.cholerae O1 El Tor hybrid clones that produce cholera toxin of classical biotype. Based on the comprehensive comparative genomics presented in this study it is concluded that V. cholerae undergoes extensive genetic recombination via lateral gene transfer, and, therefore, genome assortment, not serogroup, should be used to

The Corn Smut (‘Huitlacoche’) as a New Platform for Oral Vaccines

Science.gov (United States)

Juárez-Montiel, Margarita; Romero-Maldonado, Andrea; Monreal-Escalante, Elizabeth; Becerra-Flora, Alicia; Korban, Schuyler S.; Rosales-Mendoza, Sergio; Jiménez-Bremont, Juan Francisco

2015-01-01

The development of new alternative platforms for subunit vaccine production is a priority in the biomedical field. In this study, Ustilago maydis, the causal agent of common corn smut or ‘huitlacoche’has been genetically engineered to assess expression and immunogenicity of the B subunit of the cholera toxin (CTB), a relevant immunomodulatory agent in vaccinology. An oligomeric CTB recombinant protein was expressed in corn smut galls at levels of up to 1.3 mg g-1 dry weight (0.8% of the total soluble protein). Mice orally immunized with ‘huitlacoche’-derived CTB showed significant humoral responses that were well-correlated with protection against challenge with the cholera toxin (CT). These findings demonstrate the feasibility of using edible corn smut as a safe, effective, and low-cost platform for production and delivery of a subunit oral vaccine. The implications of this platform in the area of molecular pharming are discussed. PMID:26207365

Dismantling the Taboo against Vaccines in Pregnancy

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Maurizio de Martino

2016-06-01

Full Text Available Vaccinating pregnant women in order to protect them, the fetus, and the child has become universal in no way at all. Prejudice in health professionals add to fears of women and their families. Both these feelings are not supported by even the smallest scientific data. Harmlessness for the mother and the child has been observed for seasonal, pandemic, or quadrivalent influenza, mono, combined polysaccharide or conjugated meningococcal or pneumococcal, tetanus toxoid, acellular pertussis, human papillomavirus, cholera, hepatitis A, Japanese encephalitis, rabies, anthrax, smallpox, yellow fever, mumps, measles and rubella combined, typhoid fever, inactivated or attenuated polio vaccines, and Bacillus Calmétte Guerin vaccines. Instead, the beneficial effects of influenza vaccine for the mother and the child as well as of pertussis vaccine for the child have been demonstrated. Obstetrician-gynecologists, general practitioners, and midwives must incorporate vaccination into their standard clinical care. Strong communication strategies effective at reducing parental vaccine hesitancy and approval of regulatory agencies for use of vaccines during pregnancy are needed. It must be clear that the lack of pre-licensure studies in pregnant women and, consequently, the lack of a statement about the use of the vaccine in pregnant women does not preclude its use in pregnancy.

Combating cholera epidemics by targeting reservoirs of infection ...

African Journals Online (AJOL)

Objectives: To determine the parameters which can be investigated for prevention and effective control of cholera. Data sources: Literature search on compact disk-read only memory (CD-ROM), medline and internet, using the key words: cholera outbreaks, and cholera transmission. A few reviews were manually reviewed.

Avian cholera

Science.gov (United States)

Friend, Milton

1999-01-01

Avian cholera is a contagious disease resulting from infection by the bacterium Pasteurella multocida. Several subspecies of bacteria have been proposed for P. multocida, and at least 16 different P. multocida serotypes or characteristics of antigens in bacterial cells that differentiate bacterial variants from each other have been recognized. The serotypes are further differentiated by other methods, including DNA fingerprinting. These evaluations are useful for studying the ecology of avian cholera (Fig. 7.1), because different serotypes are generally found in poultry and free-ranging migratory birds. These evaluations also show that different P. multocida serotypes are found in wild birds in the eastern United States than those that are found in the birds in the rest of the Nation (Fig. 7.2).

The molecular epidemiology of cholera in Latin America.

Science.gov (United States)

Wachsmuth, I K; Evins, G M; Fields, P I; Olsvik, O; Popovic, T; Bopp, C A; Wells, J G; Carrillo, C; Blake, P A

1993-03-01

To explain the sudden appearance and rapid spread of cholera in Latin America in January 1991, molecular techniques were used to define Vibrio cholerae O1 isolates from around the world. Restriction fragment length polymorphisms of rRNA and ctxA genes, DNA sequence of cholera toxin B subunit gene ctxB, and multilocus enzyme electrophoresis data were used to characterize 197 isolates. Worldwide, there are at least four distinct toxigenic El Tor V. cholerae O1 clones: the seventh pandemic (Eastern Hemisphere), US Gulf Coast, Australian, and Latin American. Nontoxigenic V. cholerae O1 previously isolated in Brazil, Mexico, and Peru are unlike current toxigenic isolates. The Latin American clone probably represents an extension of the seventh pandemic into the Western Hemisphere, while the US Gulf Coast clone most likely evolved separately. These data will be useful in monitoring the spread of cholera, determining the origin of outbreaks in both hemispheres, and implicating specific vehicles of transmission.

A mass campaign too often? results of a vaccination coverage ...

African Journals Online (AJOL)

Objectives. To determine the routine and mass immunisation coverage in children aged between 12 and 23 months in the Dikgale-Soekmekaar district, Northern Province, South Africa. Design. Cross-sectional community-based vaccination prevalence survey using a two-stage cluster sampling technique. Methods. Data on ...

Unique Clones of Vibrio cholerae O1 El Tor with Haitian Type ctxB Allele Implicated in the Recent Cholera Epidemics from Nigeria, Africa.

Science.gov (United States)

Adewale, Akinsinde Kehinde; Pazhani, Gururaja Perumal; Abiodun, Iwalokun Bamidele; Afolabi, Oluwadun; Kolawole, Olukoya Daniel; Mukhopadhyay, Asish K; Ramamurthy, Thanadarayan

2016-01-01

The antimicrobial susceptibility patterns and genetic characteristics of Vibrio cholerae O1, which is responsible for several cholera epidemics in Nigeria, are not reported in detail since 2007. In this study, we screened V. cholerae O1 El Tor biotype isolates from cholera cases and water samples from different states to investigate their phenotypic and genetic attributes with special reference to their clonality. All the V. cholerae O1 biotype El Tor isolates isolated during 2007-2013 were susceptible to fluoroquinolones and tetracycline, the drugs currently used in the treatment of cholera cases in Nigeria. Emergence of CT genotype 7 (Haitian type of ctxB allele) was predominantly seen among Ogawa serotype and the CT genotype 1 (classical ctxB allele) was mostly found in Inaba serotype. Overall, V. cholerae O1 from clinical and water samples were found to be closely related as determined by the pulsed-field gel electrophoresis. V. cholerae isolates from Abia, Kano and Bauchi were found to be genetically distinct from the other states of Nigeria. Fecal contamination of the water sources may be the possible source of the cholera infection. Combined prevalence of Haitian and classical ctxB alleles were detected in Ogawa and Inaba serotypes, respectively. This study further demonstrated that V. cholerae O1 with the ctxB has been emerged similar to the isolates reported in Haiti. Our findings suggest that the use of fluoroquinolones or tetracycline/doxycycline may help in the effective management of acute cholera in the affected Nigerian states. In addition, strengthening the existing surveillance in the hospitals of all the states and supply of clean drinking water may control cholera outbreaks in the future.

[Seroepidemiology of cholera in Mexico].

Science.gov (United States)

González-Bonilla, C; Valle-Valdez, J G; Núñez-León, A; Moguel-Pech, L; Villanueva-Zamudio, A

1994-01-01

Antibodies against Vibrio cholerae were determined in 2352 serum samples obtained from patients with clinical diagnosis of cholera. Samples from their contacts and from healthy people living in the same communities were also analyzed. Vibriocidal antibodies with titers 1:160 or higher were observed in 25% of the samples. An increase of vibriocidal and antitoxin antibody titers were observed in 56 to 60% of the patients in which paired samples were available, one obtained in the acute phase of the disease and the other in the convalescence, confirming the diagnosis of cholera. Differences in the antibody titers were noticed when comparing the serotype according to the geographic area and the season of the year.

Cholera in pregnancy: outcomes from a specialized cholera treatment unit for pregnant women in Léogâne, Haiti.

Science.gov (United States)

Ciglenecki, Iza; Bichet, Mathieu; Tena, Javier; Mondesir, Erneau; Bastard, Mathieu; Tran, Nguyen-Toan; Antierens, Annick; Staderini, Nelly

2013-01-01

The association between cholera in pregnancy and negative fetal outcome has been described since the 19(th) century. However, there is limited published literature on the subject. We describe pregnancy outcomes from a specialized multidisciplinary hospital unit at the onset of a large cholera outbreak in Haiti in 2010 and 2011. Pregnant women with cholera were hospitalized in a specialized unit within the MSF hospital compound in Léogâne and treated using standard cholera treatment guidelines but with earlier, more intense fluid replacement. All women had intravenous access established at admission regardless of their hydration status, and all received antibiotic treatment. Data were collected on patient demographics, pregnancy and cholera status, and pregnancy outcome. In this analysis we calculated risk ratios for fetal death and performed logistic regression analysis to control for confounding factors. 263 pregnant women with cholera were hospitalized between December 2010 and July 2011. None died during hospitalization, 226 (86%) were discharged with a preserved pregnancy and 16 (6%) had live fullterm singleton births, of whom 2 died within the first 5 days postpartum. The remaining 21 pregnancies (8%) resulted in intrauterine fetal death. The risk of fetal death was associated with factors reflecting severity of the cholera episode: after adjusting for confounding factors, the strongest risk factor for fetal death was severe maternal dehydration (adjusted risk ratio for severe vs. mild dehydration was 9.4, 95% CI 2.5-35.3, p = 0.005), followed by severe vomiting (adjusted risk ratio 5.1, 95% 1.1-23.8, p = 0.041). This is the largest cohort of pregnant women with cholera described to date. The main risk factor identified for fetal death was severity of dehydration. Our experience suggests that establishing specialized multidisciplinary units which facilitate close follow-up of both pregnancy and dehydration status due to cholera could be beneficial

Time series analysis of cholera in Matlab, Bangladesh, during 1988-2001.

Science.gov (United States)

Ali, Mohammad; Kim, Deok Ryun; Yunus, Mohammad; Emch, Michael

2013-03-01

The study examined the impact of in-situ climatic and marine environmental variability on cholera incidence in an endemic area of Bangladesh and developed a forecasting model for understanding the magnitude of incidence. Diarrhoea surveillance data collected between 1988 and 2001 were obtained from a field research site in Matlab, Bangladesh. Cholera cases were defined as Vibrio cholerae O1 isolated from faecal specimens of patients who sought care at treatment centres serving the Matlab population. Cholera incidence for 168 months was correlated with remotely-sensed sea-surface temperature (SST) and in-situ environmental data, including rainfall and ambient temperature. A seasonal autoregressive integrated moving average (SARIMA) model was used for determining the impact of climatic and environmental variability on cholera incidence and evaluating the ability of the model to forecast the magnitude of cholera. There were 4,157 cholera cases during the study period, with an average of 1.4 cases per 1,000 people. Since monthly cholera cases varied significantly by month, it was necessary to stabilize the variance of cholera incidence by computing the natural logarithm to conduct the analysis. The SARIMA model shows temporal clustering of cholera at one- and 12-month lags. There was a 6% increase in cholera incidence with a minimum temperature increase of one degree celsius in the current month. For increase of SST by one degree celsius, there was a 25% increase in the cholera incidence at currrent month and 18% increase in the cholera incidence at two months. Rainfall did not influenc to cause variation in cholera incidence during the study period. The model forecast the fluctuation of cholera incidence in Matlab reasonably well (Root mean square error, RMSE: 0.108). Thus, the ambient and sea-surface temperature-based model could be used in forecasting cholera outbreaks in Matlab.

Geographical patterns of cholera in Mexico, 1991-1996.

Science.gov (United States)

Borroto, R J; Martinez-Piedra, R

2000-08-01

The seventh cholera pandemic has been ongoing in Mexico since 1991 and threatens to become endemic. This paper aims to determine the geographical pattern of cholera in Mexico to define areas at high risk of endemic cholera. Ecologic research was conducted based upon the cartography of disease incidence. The 32 Mexican states were grouped into five strata according to the value of the 1991-1996 cumulative incidence rate of cholera. Rate ratios were computed for strata of states classified by geographical situation, urbanization, and poverty level. Cholera incidence was 2.47 times higher in coastal states than in the interior (95% CI : 2.42-2.52). The disease was negatively associated with urbanization. Incidence in the least urbanized stratum was four times as high as in the most urban stratum (95% CI : 3.9-4.12). The poorest stratum showed the most remarkable incidence, i.e. 5.9 times higher than the rate in the least poor stratum (95% CI : 5.73-6.04). This ecologic research suggests that high poverty level, low urbanization, and southern location are the most important predictors of endemic cholera in Mexican states. It is hypothesized that the natural environment of the coastal plains in southern states may also play a significant role in cholera incidence. Poor communities residing in the southern, predominantly rural, coastal states should be prioritized when it comes to investing in safe water supply facilities, adequate excreta disposal systems and cholera surveillance.

Investigation of household contamination of Vibrio cholerae in Bangladesh

DEFF Research Database (Denmark)

Hossain, Zenat Zebin; Farhana, Israt; Mohan Tulsiani, Suhella

. cholerae El Tor strain N16961, showed hemolysis and proteolysis activity but none of them exhibited any hemagglutinin activity on human erythrocytes. The study findings indicate that V. cholerae contamination is mostly originated in and around kitchen area rather than latrine area. Contaminated food...... and water supply may be the reason behind this relatively high presence of virulence factors in food plates and water pots. Direct exposure routes of disease transmission should be a major consideration in cholera prevention policies. Investigation of household contamination of Vibrio cholerae in Bangladesh......The role of in-house transmission on the incidence of Vibrio cholerae, the deadly waterborne pathogen, is still not developed. The aim of the current study was to investigate possible contamination routes in household domain for effective cholera control in Bangladesh. To examine the prevalence...

Microsurgeon Hirudo medicinalis as a Natural Bioshuttle for Spontaneous Mass Vaccination against Influenza A Virus

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Sajjad Khani

2011-09-01

Full Text Available Introduction: Recent report on existence of a stem region of hemagglutinin has arisen new hopes for vaccination of influenza A as it consist of a conserve fusion peptide shared across several influenza subtypes and can be targeted by human immune system. Methods: Given that traditional vaccination based on live attenuated viruses often fails to surpass such viral infection, a great deal of attention has been devoted to develop a safe yet efficient system for vaccination influenza A. We believe that a natural bioshuttle can be recruited for spontaneous mass vaccination. Results: Thus, here, we hypothesize that a bioengineered transgenic Hirudo medicinalis can be considered as an alive bioshuttle for in-situ vaccination against influenza A virus. By introducing the designated gene(s encoding the target fragment (i.e., stem region of hemagglutinin, this microsurgeon can act as a rapid microproducer of viral proteins for in-house mass vaccination through imparting the necessary proteins such as those, naturally presented in leech's saliva. Conclusion: This peculiar bioshuttle can be easily exploited as a medical modality choice at home resulting in greater patient compliance.

Cholera Epidemiology in Nigeria: an overview | Adagbada | Pan ...

African Journals Online (AJOL)

Cholera is an acute diarrhoeal infection caused by ingestion of food or water contaminated with the bacterium, Vibrio cholera. Choleragenic V. cholera O1 and O139 are the only causative agents of the disease. The two most distinguishing epidemiologic features of the disease are its tendency to appear in explosive ...

Flagella-induced immunity against experimental cholera in adult rabbits.

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Yancey, R J; Willis, D L; Berry, L J

1979-07-01

The adult rabbit ligated ileal loop model was used to evaluate the prophylactic potential of a crude flagellar (CF) vaccine produced from the classical. Inaba strain CA401. A greater than 1,000-fold increase in the challenge inoculum was required to induce an intestinal fluid response in actively immunized adult rabbits equivalent to that produced in unimmunized animals. Similar protection was afforded against challenge with classical and El Tor biotypes of both Inaba and Ogawa serotypes. Highly virulent 35S-labeled vibrios were inhibited in their ability to associated with the intestinal mucosa of CF-immunized rabbits. The protection conferred by CF immunization was found to be superior to that of a commercial bivalent vaccine and also to that of glutaraldehyde-treated cholera toxoid. The critical immunogenic component of CF appears to be a flagella-derived protein. The immunogenicity of CF was destroyed by heat treatment, and absorption of CF-immune serum with aflagellated mutant vibrios did not diminish its ability to confer a high level of passive protection. The intestinal protection of CF-immunized rabbits was completely reversed by the introduction of both goat anti-rabbit immunoglobulins A and G, but by neither alone.

Distribution ofVibrio cholerae in two Florida estuaries.

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Hood, M A; Ness, G E; Rodrick, G E; Blake, N J

1983-04-01

The distribution ofVibrio cholerae was examined in 2 Florida estuaries, Apalachicola and Tampa Bay.Vibrio cholerae serotype non-01 was the most abundant serotype, being isolated from 45% of the oyster samples, 30% of the sediments, 50% of the waters, and 75% of the blue crabs.Vibrio cholerae serotype 01 was isolated from only one oyster sample. Strong linear correlations betweenV. cholerae and temperature, salinity, or the other physical/chemical parameters measured,Escherichia coli, or fecal coliforms were not observed, but a range of temperatures and salinities appeared relevant to the distribution of the organism. The organism was present in the highest concentrations when salinities were 10‰-25‰ and temperatures were 20‡C-35‡C.In vitro growth curves of 95V. cholerae environmental isolates further supported that 10‰-25‰ was an ideal salinity range for the organisms. The results suggest thatV. cholerae is a widely distributed organism in the nutrient-rich warm waters of the Gulf Coast estuaries.

Neurological adverse events temporally associated to mass vaccination against yellow fever in Juiz de Fora, Brazil, 1999-2005.

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Fernandes, Guilherme Côrtes; Camacho, Luiz Antonio Bastos; Sá Carvalho, Marilia; Batista, Maristela; de Almeida, Sonia Maria Rodrigues

2007-04-20

The identification of adverse events following immunization (AEFI) and their prompt investigation are important to allow a timely and scientifically based response to the users of immunization services. This article presents an analysis of notified AEFI cases between 1999 and 2005 and their temporal association with 2001 yellow fever vaccination campaign, AEFI notification attributed to yellow fever vaccination rose from 0.06 to 1.32 per 100,000 vaccinees in Brazil, between 1998 and 2000. During the 2001 yellow fever mass vaccination campaign held in Juiz de Fora, Brazil, 12 cases of aseptic meningitis were temporally associated to yellow fever vaccination, but clinical and laboratory data were not available to confirm nor deny causality. Epidemiological studies associated to enhanced surveillance and standardized protocols should take advantage of public health interventions like mass vaccination campaigns and implementation of new vaccination strategies in order to assess and investigate vaccine safety.

A mass vaccination campaign targeting adults and children to prevent typhoid fever in Hechi; Expanding the use of Vi polysaccharide vaccine in Southeast China: A cluster-randomized trial

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Yang Hong-hui

2005-05-01

Full Text Available Abstract Background One of the goals of this study was to learn the coverage, safety and logistics of a mass vaccination campaign against typhoid fever in children and adults using locally produced typhoid Vi polysaccharide (PS and group A meningococcal PS vaccines in southern China. Methods The vaccination campaign targeted 118,588 persons in Hechi, Guangxi Province, aged between 5 to 60 years, in 2003. The study area was divided into 107 geographic clusters, which were randomly allocated to receive one of the single-dose parenteral vaccines. All aspects regarding vaccination logistics, feasibility and safety were documented and systematically recorded. Results of the logistics, feasibility and safety are reported. Results The campaign lasted 5 weeks and the overall vaccination coverage was 78%. On average, the 30 vaccine teams gave immunizations on 23 days. Vaccine rates were higher in those aged ≤ 15 years (90% than in adolescents and young adults (70%. Planned mop-up activities increased the coverage by 17%. The overall vaccine wastage was 11%. The cold chain was maintained and documented. 66 individuals reported of adverse events out of all vaccinees, where fever (21%, malaise (19% and local redness (19% were the major symptoms; no life-threatening event occurred. Three needle-sharp events were reported. Conclusion The mass immunization proved feasible and safe, and vaccine coverage was high. Emphasis should be placed on: injection safety measures, community involvement and incorporation of mop-up strategies into any vaccination campaign. School-based and all-age Vi mass immunizations programs are potentially important public health strategies for prevention of typhoid fever in high-risk populations in southern China.

High case fatality cholera outbreak in Western Kenya, August 2010

African Journals Online (AJOL)

abp

Abstract. Introduction: Cholera is a disease caused by the bacterium Vibrio cholera and has been an important public health problem since its first pandemic in 1817. Kenya has had numerous outbreaks of cholera ever since it was first detected there during 1971. In August 2010 an outbreak of cholera occurred in Kuria ...

Evaluation of Cholera Toxin Expression in Acidic, Alkaline and Neutral Conditions

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Narges Rahimi

2015-02-01

Full Text Available Background: Cholera is a severe disease which is caused by Vibrio cholerae and it is typically transmitted by either contaminated food or water particularly in developing countries. The most important virulence factor of this bacterium is an enterotoxin called cholera toxin which is a protein complex secreted by the Vibrio cholerae. Objectives: In this project, we determined the production of cholera toxin at different pH values. Materials and Methods: Two standard strain of Vibrio cholerae O1 biovar EL Tor N16961 and Vibrio cholerae O1 biovar Classic ATCC 14035 were used. After overnight cultivation of both the strains the total mRNA extracted and converted to total cDNA. Results: By Relative Real-Time PCR analysis the most cholera toxin production in classical and El Tor strains was at pH 8.5 and 8, respectively. Conclusions: Therefore, We may conclude that use of acidic diet will help in reduction of cholera toxin production.

Antimicrobial drugs for treating cholera

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Leibovici-Weissman, Ya'ara; Neuberger, Ami; Bitterman, Roni; Sinclair, David; Salam, Mohammed Abdus; Paul, Mical

2014-01-01

Background Cholera is an acute watery diarrhoea caused by infection with the bacterium Vibrio cholerae, which if severe can cause rapid dehydration and death. Effective management requires early diagnosis and rehydration using oral rehydration salts or intravenous fluids. In this review, we evaluate the additional benefits of treating cholera with antimicrobial drugs. Objectives To quantify the benefit of antimicrobial treatment for patients with cholera, and determine whether there are differences between classes of antimicrobials or dosing schedules. Search methods We searched the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; African Index Medicus; LILACS; Science Citation Index; metaRegister of Controlled Trials; WHO International Clinical Trials Registry Platform; conference proceedings; and reference lists to March 2014. Selection criteria Randomized and quasi-randomized controlled clinical trials in adults and children with cholera that compared: 1) any antimicrobial treatment with placebo or no treatment; 2) different antimicrobials head-to-head; or 3) different dosing schedules or different durations of treatment with the same antimicrobial. Data collection and analysis Two reviewers independently applied inclusion and exclusion criteria, and extracted data from included trials. Diarrhoea duration and stool volume were defined as primary outcomes. We calculated mean difference (MD) or ratio of means (ROM) for continuous outcomes, with 95% confidence intervals (CI), and pooled data using a random-effects meta-analysis. The quality of evidence was assessed using the GRADE approach. Main results Thirty-nine trials were included in this review with 4623 participants. Antimicrobials versus placebo or no treatment Overall, antimicrobial therapy shortened the mean duration of diarrhoea by about a day and a half compared to placebo or no treatment (MD -36.77 hours, 95% CI -43

High case fatality cholera outbreak in Western Kenya, August 2010 ...

African Journals Online (AJOL)

Introduction: Cholera is a disease caused by the bacterium Vibrio cholera and has been an important public health problem since its first pandemic in 1817. Kenya has had numerous outbreaks of cholera ever since it was first detected there during 1971. In August 2010 an outbreak of cholera occurred in Kuria West District ...

Intestinal Colonization Dynamics of Vibrio cholerae.

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Salvador Almagro-Moreno

2015-05-01

Full Text Available To cause the diarrheal disease cholera, Vibrio cholerae must effectively colonize the small intestine. In order to do so, the bacterium needs to successfully travel through the stomach and withstand the presence of agents such as bile and antimicrobial peptides in the intestinal lumen and mucus. The bacterial cells penetrate the viscous mucus layer covering the epithelium and attach and proliferate on its surface. In this review, we discuss recent developments and known aspects of the early stages of V. cholerae intestinal colonization and highlight areas that remain to be fully understood. We propose mechanisms and postulate a model that covers some of the steps that are required in order for the bacterium to efficiently colonize the human host. A deeper understanding of the colonization dynamics of V. cholerae and other intestinal pathogens will provide us with a variety of novel targets and strategies to avoid the diseases caused by these organisms.

Mass Media Campaign Impacts Influenza Vaccine Obtainment of University Students

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Shropshire, Ali M.; Brent-Hotchkiss, Renee; Andrews, Urkovia K.

2013-01-01

Objective: To describe the effectiveness of a mass media campaign in increasing the rate of college student influenza vaccine obtainment. Participants/Methods: Students ("N" = 721) at a large southern university completed a survey between September 2011 and January 2012 assessing what flu clinic media sources were visualized and if they…

Genotypic and PFGE/MLVA analyses of Vibrio cholerae O1: geographical spread and temporal changes during the 2007-2010 cholera outbreaks in Thailand.

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Kazuhisa Okada

Full Text Available BACKGROUND: Vibrio cholerae O1 El Tor dominated the seventh cholera pandemic which occurred in the 1960s. For two decades, variants of V. cholerae O1 El Tor that produce classical cholera toxin have emerged and spread globally, replacing the prototypic El Tor biotype. This study aims to characterize V. cholerae O1 isolates from outbreaks in Thailand with special reference to genotypic variations over time. METHODS/FINDINGS: A total of 343 isolates of V. cholerae O1 from cholera outbreaks from 2007 to 2010 were investigated, and 99.4% were found to carry the classical cholera toxin B subunit (ctxB and El Tor rstR genes. Pulsed-field gel electrophoresis (PFGE differentiated the isolates into 10 distinct pulsotypes, clustered into two major groups, A and B, with an overall similarity of 88%. Ribotyping, multiple-locus variable-number tandem-repeat analysis (MLVA, and PCR to detect Vibrio seventh pandemic island II (VSP-II related genes of randomly selected isolates from each pulsotype corresponded to the results obtained by PFGE. Epidemiological investigations revealed that MLVA type 2 was strongly associated with a cholera outbreak in northeastern Thailand in 2007, while MLVA type 7 dominated the outbreaks of the southern Gulf areas in 2009 and MLVA type 4 dominated the outbreaks of the central Gulf areas during 2009-2010. Only MLVA type 16 isolates were found in a Thai-Myanmar border area in 2010, whereas those of MLVA types 26, 39, and 41 predominated this border area in 2008. Type 39 then disappeared 1-2 years later as MLVA type 41 became prevalent. Type 41 was also found to infect an outbreak area. CONCLUSIONS: MLVA provided a high-throughput genetic typing tool for understanding the in-depth epidemiology of cholera outbreaks. Our epidemiological surveys suggest that some clones of V. cholerae O1 with similar but distinctive genetic traits circulate in outbreak sites, while others disappear over time.

Cost-Effectiveness of Mass Dog Vaccination Campaigns against Rabies in Flores Island, Indonesia.

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Wera, E; Mourits, M C M; Siko, M M; Hogeveen, H

2017-12-01

A dynamic deterministic simulation model was developed to determine the cost-effectiveness of different mass dog vaccination strategies against rabies in a dog population representative of a typical village on Flores Island. Cost-effectiveness was measured as public cost per averted dog-rabies case. Simulations started with the introduction of one infectious dog into a susceptible dog population of 399 dogs and subsequently ran for a period of 10 years. The base scenario represented a situation without any control intervention. Evaluated vaccination strategies were as follows: annual vaccination campaigns with short-acting vaccine (immunity duration of 52 weeks) (AV_52), annual campaigns with long-acting vaccine (immunity duration of 156 weeks) (AV_156), biannual campaigns with short-acting vaccine (BV_52) and once-in-2-years campaigns with long-acting vaccine (O2V_156). The effectiveness of the vaccination strategies was simulated for vaccination coverages of 50% and 70%. Cumulative results were reported for the 10-year simulation period. The base scenario resulted in three epidemic waves, with a total of 1274 dog-rabies cases. The public cost of applying AV_52 at a coverage of 50% was US$5342 for a village. This strategy was unfavourable compared to other strategies, as it was costly and ineffective in controlling the epidemic. The costs of AV_52 at a coverage of 70% and AV_156 at a coverage of 70% were, respectively, US$3646 and US$3716, equivalent to US$3.00 and US$3.17 per averted dog-rabies case. Increasing the coverage of AV_156 from 50% to 70% reduced the number of cases by 7% and reduced the cost by US$1452, resulting in a cost-effectiveness ratio of US$1.81 per averted dog-rabies case. This simulation model provides an effective tool to explore the public cost-effectiveness of mass dog vaccination strategies in Flores Island. Insights obtained from the simulation results are useful for animal health authorities to support decision-making in rabies

Controversy and debate on dengue vaccine series-paper 1: review of a licensed dengue vaccine: inappropriate subgroup analyses and selective reporting may cause harm in mass vaccination programs.

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Dans, Antonio L; Dans, Leonila F; Lansang, Mary Ann D; Silvestre, Maria Asuncion A; Guyatt, Gordon H

2018-03-01

Severe life-threatening dengue fever usually occurs when a child is infected by dengue virus a second time. This is caused by a phenomenon called antibody-dependent enhancement (ADE). Since dengue vaccines can mimic a first infection in seronegative children (those with no previous infection), a natural infection later in life could lead to severe disease. The possibility that dengue vaccines can cause severe dengue through ADE has led to serious concern regarding the safety of mass vaccination programs. A published meta-analysis addressed this safety issue for a new vaccine against dengue fever-Dengvaxia. The trials in this meta-analysis have been used to campaign for mass vaccination programs in developing countries. We discuss the results of this paper and point out problems in the analyses. Reporting the findings in an Asian trial (CYD14), the authors show a sevenfold rise in one outcome-hospitalization for dengue fever in children <5 years old. However, they fail to point out two signals of harm for another outcome-hospitalization for severe dengue fever (as confirmed by an independent data monitoring committee): 1. In children younger than 9 years, the relative risk was 8.5 (95% confidence interval [CI]: 0.5, 146.8), and 2. In the overall study group, the relative risk was 5.5 (95% CI: 0.9, 33). The authors conduct a subgroup analysis to support claims that the vaccine is probably safe among children aged 9 years or more. This subgroup analysis has limited credibility because: (1) it was a post hoc analysis; (2) it was one of a large number of subgroup analyses; (3) the test of interaction was not reported, but was insignificant (P = 0.14); and (4) there is no biological basis for a threshold age of 9 years. The more likely explanation for the higher risk in younger children is ADE, that is, more frequent seronegativity, rather than age itself. The selective reporting and inappropriate subgroup claims mask the potential harm of dengue mass vaccination

Evaluation of the mass measles vaccination campaign in Guangdong Province, China.

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Peng, Zhi Qiang; Chen, Wei Shi; He, Qun; Peng, Guo Wen; Wu, Cheng Gang; Xu, Ning; Zhao, Zhan Jie; Shu, Jun; Tan, Qiu; Zheng, Hui Zhen; Lin, Li Feng; Deng, Hui Hong; Lin, Jin Yan; Zhang, Yong Hui

2012-02-01

To evaluate the mass measles vaccination campaign of 2009 in Guangdong Province, China. Data on the campaign implementation, measles surveillance, and serological surveillance were reviewed and analyzed by statistical methods. Rapid coverage surveys showed that 98.09% of children were vaccinated during the campaign. The coverage of migrant children increased significantly from 67.10% to 97.32% (pvaccinated during the campaign. Flyers, notices of information from doctors, and television programs were the best methods to inform parents of the campaign. Awareness of the campaign by residents increased significantly from 91.86% to 97.10% (pvaccination campaign approach for controlling measles in a developing region like Guangdong Province with a vast migrant population has proved effective. Comprehensive mobilization, communication with the mass media, and support from government departments were critical to the success of the campaign. Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Synthesis of protein in intestinal cells exposed to cholera toxin

International Nuclear Information System (INIS)

Peterson, J.W.; Berg, W.D. Jr.; Coppenhaver, D.H.

1987-01-01

The mechanism by which cyclic adenosine monophosphate (AMP), formed by intestinal epithelial cells in response to cholera toxin, ultimately results in alterations in water and electrolyte transport is poorly understood. Several studies have indicated that inhibitors of transcription or translation block much of the transport of ions and water in the intestine and edema formation in tissue elicited by cholera toxin. Data presented in this study confirmed the inhibitory effects of cycloheximide on cholera toxin-induced fluid accumulation in the rabbit intestinal loop model. Neither cycloheximide nor actinomycin D altered the amount of cyclic AMP that accumulated in intestinal cells and Chinese hamster ovary cells exposed to cholera toxin. An increase in [ 3 H] leucine incorporation was readily demonstrable in intestinal epithelial cells from rabbits challenged with Vibrio cholerae. Similarly, intestinal epithelial cells incubated with cholera toxin for 4 hr synthesized substantially more protein than controls as determined by relative incorporation of [ 35 S] methionine. Most of the new protein synthesized in response to cholera toxin was membrane associated and of high molecular weight. The possible significance of the toxin-induced protein relative to cholera pathogenesis was discussed

Cross protection against fowl cholera disease with the use of recombinant Pasteurella multocida FHAB2 peptides vaccine

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It has been demonstrated that fhaB2 (filamentous hemagglutinin) is an important virulence factor for P. multocida in development of fowl cholera disease and that recombinant FHAB2 peptides derived from P. multocida, Pm-1059, protect turkeys against Pm-1059 challenge. To test the hypothesis that rFHA...

Vaccines, inspiring innovation in health.

Science.gov (United States)

Pagliusi, Sonia; Dennehy, Maureen; Kim, Hun

2018-05-19

This report covers the topics of pandemics, epidemics and partnerships, including regulatory convergence initiatives, new technologies and novel vaccines, discussed by leading public and private sector stakeholders at the 18th Annual General Meeting (AGM) of the Developing Countries Vaccine Manufacturers' Network (DCVMN). Contributions of Gavi and the vaccine industry from emerging countries to the growing global vaccine market, by improving the supply base from manufacturers in developing countries and contributing to 58% of doses, were highlighted. The Coalition for Epidemic Preparedness Innovations (CEPI), the International Vaccine Institute (IVI) and others reported on new strategies to ensure speedy progress in preclinical and clinical development of innovative vaccines for future MERS, Zika or other outbreak response. Priorities for vaccine stockpiling, to assure readiness during emergencies and to prevent outbreaks due to re-emerging diseases such as yellow fever, cholera and poliomyelitis, were outlined. The role of partnerships in improving global vaccine access, procurement and immunization coverage, and shared concerns were reviewed. The World Health Organization (WHO) and other international collaborating partners provided updates on the Product, Price and Procurement database, the prequalification of vaccines, the control of neglected tropical diseases, particularly the new rabies elimination initiative, and regulatory convergence proposals to accelerate vaccine registration in developing countries. Updates on supply chain innovations and novel vaccine platforms were presented. The discussions enabled members and partners to reflect on efficiency of research & development, supply chain tools and trends in packaging technologies improving delivery of existing vaccines, and allowing a deeper understanding of the current public-health objectives, industry financing, and global policies, required to ensure optimal investments, alignment and stability of

Local population and regional environmental drivers of cholera in Bangladesh

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Escamilla Veronica

2010-01-01

Full Text Available Abstract Background Regional environmental factors have been shown to be related to cholera. Previous work in Bangladesh found that temporal patterns of cholera are positively related to satellite-derived environmental variables including ocean chlorophyll concentration (OCC. Methods This paper investigates whether local socio-economic status (SES modifies the effect of regional environmental forces. The study area is Matlab, Bangladesh, an area of approximately 200,000 people with an active health and demographic surveillance system. Study data include (1 spatially-referenced demographic and socio-economic characteristics of the population; (2 satellite-derived variables for sea surface temperature (SST, sea surface height (SSH, and OCC; and (3 laboratory confirmed cholera case data for the entire population. Relationships between cholera, the environmental variables, and SES are measured using generalized estimating equations with a logit link function. Additionally two separate seasonal models are built because there are two annual cholera epidemics, one pre-monsoon, and one post-monsoon. Results SES has a significant impact on cholera occurrence: the higher the SES score, the lower the occurrence of cholera. There is a significant negative association between cholera incidence and SSH during the pre-monsoon period but not for the post-monsoon period. OCC is positively associated with cholera during the pre-monsoon period but not for the post-monsoon period. SST is not related to cholera incidence. Conclusions Overall, it appears cholera is influenced by regional environmental variables during the pre-monsoon period and by local-level variables (e.g., water and sanitation during the post-monsoon period. In both pre- and post-monsoon seasons, SES significantly influences these patterns, likely because it is a proxy for poor water quality and sanitation in poorer households.

Cell Vacuolation Caused by Vibrio cholerae Hemolysin

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Figueroa-Arredondo, Paula; Heuser, John E.; Akopyants, Natalia S.; Morisaki, J. Hiroshi; Giono-Cerezo, Silvia; Enríquez-Rincón, Fernando; Berg, Douglas E.

2001-01-01

Non-O1 strains of Vibrio cholerae implicated in gastroenteritis and diarrhea generally lack virulence determinants such as cholera toxin that are characteristic of epidemic strains; the factors that contribute to their virulence are not understood. Here we report that at least one-third of diarrhea-associated nonepidemic V. cholerae strains from Mexico cause vacuolation of cultured Vero cells. Detailed analyses indicated that this vacuolation was related to that caused by aerolysin, a pore-forming toxin of Aeromonas; it involved primarily the endoplasmic reticulum at early times (∼1 to 4 h after exposure), and resulted in formation of large, acidic, endosome-like multivesicular vacuoles (probably autophagosomes) only at late times (∼16 h). In contrast to vacuolation caused by Helicobacter pylori VacA protein, that induced by V. cholerae was exacerbated by agents that block vacuolar proton pumping but not by endosome-targeted weak bases. It caused centripetal redistribution of endosomes, reflecting cytoplasmic alkalinization. The gene for V. cholerae vacuolating activity was cloned and was found to correspond to hlyA, the structural gene for hemolysin. HlyA protein is a pore-forming toxin that causes ion leakage and, ultimately, eukaryotic cell lysis. Thus, a distinct form of cell vacuolation precedes cytolysis at low doses of hemolysin. We propose that this vacuolation, in itself, contributes to the virulence of V. cholerae strains, perhaps by perturbing intracellular membrane trafficking or ion exchange in target cells and thereby affecting local intestinal inflammatory or other defense responses. PMID:11179335

Cell vacuolation caused by Vibrio cholerae hemolysin.

Science.gov (United States)

Figueroa-Arredondo, P; Heuser, J E; Akopyants, N S; Morisaki, J H; Giono-Cerezo, S; Enríquez-Rincón, F; Berg, D E

2001-03-01

Non-O1 strains of Vibrio cholerae implicated in gastroenteritis and diarrhea generally lack virulence determinants such as cholera toxin that are characteristic of epidemic strains; the factors that contribute to their virulence are not understood. Here we report that at least one-third of diarrhea-associated nonepidemic V. cholerae strains from Mexico cause vacuolation of cultured Vero cells. Detailed analyses indicated that this vacuolation was related to that caused by aerolysin, a pore-forming toxin of Aeromonas; it involved primarily the endoplasmic reticulum at early times (approximately 1 to 4 h after exposure), and resulted in formation of large, acidic, endosome-like multivesicular vacuoles (probably autophagosomes) only at late times (approximately 16 h). In contrast to vacuolation caused by Helicobacter pylori VacA protein, that induced by V. cholerae was exacerbated by agents that block vacuolar proton pumping but not by endosome-targeted weak bases. It caused centripetal redistribution of endosomes, reflecting cytoplasmic alkalinization. The gene for V. cholerae vacuolating activity was cloned and was found to correspond to hlyA, the structural gene for hemolysin. HlyA protein is a pore-forming toxin that causes ion leakage and, ultimately, eukaryotic cell lysis. Thus, a distinct form of cell vacuolation precedes cytolysis at low doses of hemolysin. We propose that this vacuolation, in itself, contributes to the virulence of V. cholerae strains, perhaps by perturbing intracellular membrane trafficking or ion exchange in target cells and thereby affecting local intestinal inflammatory or other defense responses.

Characterization of a clinical Vibrio cholerae O139 isolate from Mexico.

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Parveen, Salina; Farrah, Samuel R; Gonzalez-Bonilla, Celia; Zamudio, Altagracia V; Tamplin, Mark L

2003-01-01

Pathogenic strains of Vibrio cholerae O139 possess the cholera toxin A subunit (ctxA) gene as well as the gene for toxin co-regulated pili (tcpA). We report the isolation of a ctxA-negative, tcpA-negative V. cholerae O139 strain (INDREI) from a patient in Mexico diagnosed with gastrointestinal illness. Certain phenotypic characteristics of this strain were identical to those of V. cholerae O1 biotype El Tor. Unlike ctxA-positive V. cholerae O139 strains, this strain was sensitive to a wide panel of antibiotics, including ampicillin, chloramphenicol, ciprofloxacin, gentamicin, furazolidone, nalidixic acid, nitrofurantoin, tetracycline, trimethoprim-sulfamethoxazole, and streptomycin, but was resistant to polymyxin B. Ribotype and pulsed-field gel electrophoresis profiles of INDRE1 differed from those of ctxA-positive V. cholerae O139 and other V. cholerae strains. Phenotypic characteristics of the Mexico strain were similar to those reported for V. cholerae O139 isolates from Argentina and Sri Lanka.

A novel kit for rapid detection of Vibrio cholerae O1.

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Hasan, J A; Huq, A; Tamplin, M L; Siebeling, R J; Colwell, R R

1994-01-01

We report on the development and testing of a novel, rapid, colorimetric immunodiagnostic kit, Cholera SMART, for direct detection of the presence of Vibrio cholerae O1 in clinical specimens. Unlike conventional culture methods requiring several days to complete, the Cholera SMART kit can be used directly in the field by untrained or minimally skilled personnel to detect V. cholerae O1 in less than 15 min, without cumbersome laboratory equipment. A total of 120 clinical and environmental bacterial strains, including both O1 and non-O1 serotypes of V. cholerae isolated from samples collected from a variety of geographical regions, were tested, and positive reactions were observed only with V. cholerae O1. Also, results of a field trial in Bangladesh, employing Cholera SMART, showed 100% specificity and 96% sensitivity compared with conventional culture methods. Another field trial, in Mexico, showed that Cholera SMART was 100% in agreement with a recently described coagglutination test when 108 stool specimens were tested.

The protective activity of tea against infection by Vibrio cholerae O1.

Science.gov (United States)

Toda, M; Okubo, S; Ikigai, H; Suzuki, T; Suzuki, Y; Shimamura, T

1991-02-01

Extracts of black tea exhibited bactericidal activity against Vibrio cholerae O1. The tea extract inhibited the haemolysin activity of V. cholerae O1, El Tor and the morphological changes of Chinese hamster ovary cells induced by cholera toxin. Tea extract also reduced fluid accumulation induced by cholera toxin in sealed adult mice and by V. cholerae O1 in ligated intestinal loops of rabbits. These findings suggest that tea has protective activity against V. cholerae O1.

Conjugated Linoleic Acid Reduces Cholera Toxin Production In Vitro and In Vivo by Inhibiting Vibrio cholerae ToxT Activity.

Science.gov (United States)

Withey, Jeffrey H; Nag, Drubhajyoti; Plecha, Sarah C; Sinha, Ritam; Koley, Hemanta

2015-12-01

The severe diarrheal disease cholera is endemic in over 50 countries. Current therapies for cholera patients involve oral and/or intravenous rehydration, often combined with the use of antibiotics to shorten the duration and intensity of the disease. However, as antibiotic resistance increases, treatment options will become limited. Linoleic acid has been shown to be a potent negative effector of V. cholerae virulence that acts on the major virulence transcription regulator protein, ToxT, to inhibit virulence gene expression. ToxT activates transcription of the two major virulence factors required for disease, cholera toxin (CT) and toxin-coregulated pilus (TCP). A conjugated form of linoleic acid (CLA) is currently sold over the counter as a dietary supplement and is generally recognized as safe by the U.S. Food and Drug Administration. This study examined whether CLA could be used as a new therapy to reduce CT production, which, in turn, would decrease disease duration and intensity in cholera patients. CLA could be used in place of traditional antibiotics and would be very unlikely to generate resistance, as it affects only virulence factor production and not bacterial growth or survival. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Genome-wide study of the defective sucrose fermenter strain of Vibrio cholerae from the Latin American cholera epidemic.

NARCIS (Netherlands)

Garza, D.R.; Thompson, C.C.; Loureiro, E.C.; Dutilh, B.E.; Inada, D.T.; Junior, E.C.; Cardoso, J.F.; Nunes, M.R.; Lima, C.P. de; Silvestre, R.V.; Nunes, K.N.; Santos, E.C.; Edwards, R.A.; Vicente, A.C.; Sa Morais, L.L. de

2012-01-01

The 7th cholera pandemic reached Latin America in 1991, spreading from Peru to virtually all Latin American countries. During the late epidemic period, a strain that failed to ferment sucrose dominated cholera outbreaks in the Northern Brazilian Amazon region. In order to understand the genomic

Protection against Multiple Subtypes of Influenza Viruses by Virus-Like Particle Vaccines Based on a Hemagglutinin Conserved Epitope

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Shaoheng Chen

2015-01-01

Full Text Available We selected the conserved sequence in the stalk region of influenza virus hemagglutinin (HA trimmer, the long alpha helix (LAH, as the vaccine candidate sequence, and inserted it into the major immunodominant region (MIR of hepatitis B virus core protein (HBc, and, by using the E. coli expression system, we prepared a recombinant protein vaccine LAH-HBc in the form of virus-like particles (VLP. Intranasal immunization of mice with this LAH-HBc VLP plus cholera toxin B subunit with 0.2% of cholera toxin (CTB* adjuvant could effectively elicit humoral and cellular immune responses and protect mice against a lethal challenge of homologous influenza viruses (A/Puerto Rico/8/1934 (PR8 (H1N1. In addition, passage of the immune sera containing specific antibodies to naïve mice rendered them resistant against a lethal homologous challenge. Immunization with LAH-HBc VLP vaccine plus CTB* adjuvant could also fully protect mice against a lethal challenge of the 2009 pandemic H1N1 influenza virus or the avian H9N2 virus and could partially protect mice against a lethal challenge of the avian H5N1 influenza virus. This study demonstrated that the LAH-HBc VLP vaccine based on a conserved sequence of the HA trimmer stalk region is a promising candidate vaccine for developing a universal influenza vaccine against multiple influenza viruses infections.

Removal of Cholera Toxin from Aqueous Solution by Probiotic Bacteria

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Jussi A. O. Meriluoto

2012-06-01

Full Text Available Cholera remains a serious health problem, especially in developing countries where basic hygiene standards are not met. The symptoms of cholera are caused by cholera toxin, an enterotoxin, which is produced by the bacterium Vibrio cholerae. We have recently shown that human probiotic bacteria are capable of removing cyanobacterial toxins from aqueous solutions. In the present study we investigate the ability of the human probiotic bacteria, Lactobacillus rhamnosus strain GG (ATCC 53103 and Bifidobacterium longum 46 (DSM 14583, to remove cholera toxin from solution in vitro. Lactobacillus rhamnosus strain GG and Bifidobacterium longum 46 were able to remove 68% and 59% of cholera toxin from aqueous solutions during 18 h of incubation at 37 °C, respectively. The effect was dependent on bacterial concentration and L. rhamnosus GG was more effective at lower bacterial concentrations. No significant effect on cholera toxin concentration was observed when nonviable bacteria or bacterial supernatant was used.

Efficiency of hospital cholera treatment in Ecuador

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Creamer Germán

1999-01-01

Full Text Available This study analyzed the efficiency of cholera treatment in three hospitals representative of the Ecuadorian public health system in order to provide hospital directors and administrators and health service policy-makers with information to plan responses to future epidemics and to reduce the costs of cholera treatment in general. For the study, total and excess cholera treatment costs were calculated using hospital files and statistics and an in-hospital surveillance system of the cholera cases. The type and quantity of each input used for each treatment were analyzed, as well as the number of days hospitalized, according to the severity of the illness. With this process, excess costs were determined in relation to a "treatment norm" that would have been appropriate for each patient. The researchers found that 45% of the cholera treatment costs were excessive. The most important contributor was excess recurrent costs (90%, including extended hospital stays, disproportionate use of intravenous rehydration solutions, and unnecessary laboratory tests. Excess capital costs, from land, buildings, and hospital equipment, represented 10% of the total excess treatment costs. No significant relationship was found between treatment costs and the severity of the illness, nor between costs and a patient's age. A patient's sex appeared to be an important variable, with the cost of treating women being notably higher than for men. An inverse relationship was found between treatment costs and the complexity of the hospital. The researchers concluded there was an inefficient use of resources in the treatment of cholera in the three hospitals where the research was performed.

Requirement for Vibrio cholerae integration host factor in conjugative DNA transfer.

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McLeod, Sarah M; Burrus, Vincent; Waldor, Matthew K

2006-08-01

The requirement for host factors in the transmission of integrative and conjugative elements (ICEs) has not been extensively explored. Here we tested whether integration host factor (IHF) or Fis, two host-encoded nucleoid proteins, are required for transfer of SXT, a Vibrio cholerae-derived ICE that can be transmitted to many gram-negative species. Fis did not influence the transfer of SXT to or from V. cholerae. In contrast, IHF proved to be required for V. cholerae to act as an SXT donor. In the absence of IHF, V. cholerae displayed a modest defect for serving as an SXT recipient. Surprisingly, SXT integration into or excision from the V. cholerae chromosome, which requires an SXT-encoded integrase related to lambda integrase, did not require IHF. Therefore, the defect in SXT transmission in the V. cholerae IHF mutant is probably not related to IHF's ability to promote DNA recombination. The V. cholerae IHF mutant was also highly impaired as a donor of RP4, a broad-host-range conjugative plasmid. Thus, the V. cholerae IHF mutant appears to have a general defect in conjugation. Escherichia coli IHF mutants were not impaired as donors or recipients of SXT or RP4, indicating that IHF is a V. cholerae-specific conjugation factor.

From Cholera to Burns: A Role for Oral Rehydration Therapy

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Green, W.B.; Asuku, M.E.; Feldman, M.; Makam, R.; Noppenberger, D.; Price, L.A.; Prosciak, M.; van Loon, I.N.

2011-01-01

According to the practice guidelines of the American Burn Association on burn shock resuscitation, intravenous (IV) fluid therapy is the standard of care for the replacement of fluid and electrolyte losses in burn injury of ≥20% of the total body surface area. However, in mass burn casualties, IV fluid resuscitation may be delayed or unavailable. Oral rehydration therapy (ORT), which has been shown to be highly effective in the treatment of dehydration in epidemics of cholera, could be an alternate way to replace fluid losses in burns. A prospective case series of three patients was carried out as an initial step to establish whether oral Ceralyte®90 could replace fluid losses requiring IV fluid therapy in thermal injury. The requirement of the continuing IV fluid therapy was reduced by an average of 58% in the first 24 hours after the injury (range 37-78%). ORT may be a feasible alternative to IV fluid therapy in the resuscitation of burns. It could also potentially save many lives in mass casualty situations or in resource-poor settings where IV fluid therapy is not immediately available. Further studies are needed to assess the efficacy of this treatment and to determine whether the present formulations of ORT for cholera need modification. PMID:22283039

Hydroclimatic Extremes and Cholera Dynamics in the 21st Century

Science.gov (United States)

Akanda, A. S.; Jutla, A. S.; Islam, S.

2012-12-01

Cholera, an acute water-borne diarrheal illness, has reemerged as a significant health threat across much of the developing world. Despite major advances in the ecological and the microbiological understanding of the causative agent, V. cholerae, the role of the underlying climatic and environmental processes in propagating transmission is not adequately understood. Recent findings suggest a more prominent role of hydroclimatic extremes - droughts and floods - on the unique dual cholera peaks in the Bengal Delta region of South Asia, the native homeland of cholera. Increasing water scarcity and abundance, and coastal sea-level rise, influenced by changing climate patterns and large-scale climatic phenomena, is likely to adversely impact cholera transmission in South Asia. We focus on understanding how associated changes in macro-scale conditions in this region will impact micro-scale processes related to cholera in coming decades. We use the PRECIS Regional Climate Model over the Ganges-Brahmaputra-Meghna (GBM) basin region to simulate detailed high resolution projections of climate patterns for the 21st century. Precipitation outputs are analyzed for the 1980-2040 period to identify the trends and changes in hydroclimatic extremes and potential impacts on cholera dynamics over the next three decades (2010-2040), in relation to the cholera surveillance operations over the past three decades (1980-2010). We find that an increased number of extreme precipitation events with prolonged dry periods in the Ganges basin region will likely adversely affect dry season cholera outbreaks. Increased monsoon precipitation volumes in the Brahmaputra basin catchments are likely to cause record floods and subsequently trigger large epidemics in downstream areas. Our results provide new insight by identifying the changes in the two distinctly different, pre and post monsoon, cholera transmission mechanisms related to large-scale climatic controls that prevail in the region. A

Molecular characterisation of Vibrio cholerae O1 strains carrying an SXT/R391-like element from cholera outbreaks in Kenya: 1994-2007

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Goddeeris Bruno M

2009-12-01

Full Text Available Abstract Background Over the last decade, cholera outbreaks in parts of Kenya have become common. Although a number of recent studies describe the epidemiology of cholera in Kenya, there is paucity of information concerning the diversity and occurrence of mobile genetic elements in Vibrio cholerae strains implicated in these outbreaks. A total of 65 Vibrio cholerae O1 El Tor serotype Inaba isolated between 1994 and 2007 from various outbreaks in Kenya were investigated for mobile genetic elements including integrons, transposons, the integrating conjugative elements (ICEs, conjugative plasmids and for their genotypic relatedness. Results All the strains were haemolytic on 5% sheep blood and positive for the Vibrio cholerae El Tor-specific haemolysin toxin gene (hylA by PCR. They all contained strB, sulII, floR and the dfrA1 genes encoding resistance to streptomycin, sulfamethoxazole, chloramphenicol and trimethoprim respectively. These genes, together with an ICE belonging to the SXT/R391 family were transferable to the rifampicin-resistant E. coli C600 en bloc. All the strains were negative for integron class 1, 2 and 3 and for transposase gene of transposon Tn7 but were positive for integron class 4 and the trpM gene of transposon Tn21. No plasmids were isolated from any of the 65 strains. All the strains were also positive for all V. cholera El Tor pathogenic genes except the NAG- specific heat-stable toxin (st gene. None of the strains were positive for virulence genes associated with the V. cholerae classical biotype. All the strains were positive for El Tor-specific CTXphi bacteriophage rstrR repressor gene (CTXETΦ but negative for the Classical, Calcutta, and the Environmental repressor types. Pulse Field Gel Electrophoresis (PFGE showed that regardless of the year of isolation, all the strains bearing the SXT element were clonally related. Conclusions This study demonstrates that the V. cholerae O1 strains carrying an SXT/R391-like

Using Inuit traditional ecological knowledge for detecting and monitoring avian cholera among Common Eiders in the eastern Canadian Arctic

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Dominique A. Henri

2018-03-01

knowledge of two past bird mass mortality events that took place about 60 years and a century ago. Those interviewed indicated that that bird mass mortality events potentially caused by avian cholera had not occurred in the study area prior to 2004, supporting the hypothesis that avian cholera emerged only recently in the eastern Canadian Arctic. This study demonstrated that TEK can be a valuable tool for monitoring future avian cholera outbreaks and other wildlife diseases in remote regions.

Haiti's progress in achieving its 10-year plan to eliminate cholera: hidden sickness cannot be cured

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Koski-Karell V

2016-05-01

the three government-sponsored water treatment stations in the research area is still functional and utilized by those who can afford it. Latrines are scarce and often shared by up to 30 people; open defecation remains common. Structural vulnerabilities cut across all sectors – not just water, sanitation, health care, and education, but agriculture, environment, (global and local commerce, transportation, and governance as well. These are among the hidden sicknesses that impede Haiti and its partners' capacity to eliminate cholera. Keywords: water, sanitation, WASH, oral cholera vaccination, elimination 

Estimating effects of improved drinking water and sanitation on cholera.

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Leidner, Andrew J; Adusumilli, Naveen C

2013-12-01

Demand for adequate provision of drinking-water and sanitation facilities to promote public health and economic growth is increasing in the rapidly urbanizing countries of the developing world. With a panel of data on Asia and Africa from 1990 to 2008, associations are estimated between the occurrence of cholera outbreaks, the case rates in given outbreaks, the mortality rates associated with cholera and two disease control mechanisms, drinking-water and sanitation services. A statistically significant and negative effect is found between drinking-water services and both cholera case rates as well as cholera-related mortality rates. A relatively weak statistical relationship is found between the occurrence of cholera outbreaks and sanitation services.

Influence of human behavior on cholera dynamics.

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Wang, Xueying; Gao, Daozhou; Wang, Jin

2015-09-01

This paper is devoted to studying the impact of human behavior on cholera infection. We start with a cholera ordinary differential equation (ODE) model that incorporates human behavior via modeling disease prevalence dependent contact rates for direct and indirect transmissions and infectious host shedding. Local and global dynamics of the model are analyzed with respect to the basic reproduction number. We then extend the ODE model to a reaction-convection-diffusion partial differential equation (PDE) model that accounts for the movement of both human hosts and bacteria. Particularly, we investigate the cholera spreading speed by analyzing the traveling wave solutions of the PDE model, and disease threshold dynamics by numerically evaluating the basic reproduction number of the PDE model. Our results show that human behavior can reduce (a) the endemic and epidemic levels, (b) cholera spreading speeds and (c) the risk of infection (characterized by the basic reproduction number). Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Role of phytoplankton in maintaining endemicity and seasonality of cholera in Bangladesh.

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Islam, M Sirajul; Islam, M Shafiqul; Mahmud, Zahid H; Cairncross, Sandy; Clemens, John D; Collins, Andrew E

2015-09-01

In Bangladesh, cholera is endemic and maintains a regular seasonal pattern. The role of phytoplankton in maintaining endemicity and seasonality of cholera was monitored in Matlab, Bangladesh. Phytoplankton and water samples were collected from two ponds bi-weekly for 1 year. The association of Vibrio cholerae O1 with phytoplankton was studied by culture and direct fluorescent antibody techniques. The bio-physicochemical parameters of water were measured and data for cases of cholera were collected from the records of Matlab hospital. The correlation of cholera cases with levels of phytoplankton, V. cholerae and bio-physicochemical parameters of water was carried out using Pearson's correlation coefficients. V. cholerae O1 survived for 48 days in association with Anabaena variabilis in a culturable state, but survived for a year in a viable but non-culturable (VBNC) state. V. cholerae survived for 12 and 32 days in a culturable state in control water (without algae) and water with algae, respectively. There was a significant correlation between changing levels of cholera cases in the community and the blue green algae and total phytoplankton in the aquatic environment. A significant correlation was also found between the cholera cases and chlorophyll-a and VBNC V. cholerae O1 in the aquatic environment. This study demonstrated the role of phytoplankton in maintaining endemicity and seasonality of cholera in Bangladesh. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Importance of background rates of disease in assessment of vaccine safety during mass immunisation with pandemic H1N1 influenza vaccines

Science.gov (United States)

Black, Steven; Eskola, Juhani; Siegrist, Claire-Anne; Halsey, Neal; MacDonald, Noni; Law, Barbara; Miller, Elizabeth; Andrews, Nick; Stowe, Julia; Salmon, Daniel; Vannice, Kirsten; Izurieta, Hector S; Akhtar, Aysha; Gold, Mike; Oselka, Gabriel; Zuber, Patrick; Pfeifer, Dina; Vellozzi, Claudia

2010-01-01

Because of the advent of a new influenza A H1N1 strain, many countries have begun mass immunisation programmes. Awareness of the background rates of possible adverse events will be a crucial part of assessment of possible vaccine safety concerns and will help to separate legitimate safety concerns from events that are temporally associated with but not caused by vaccination. We identified background rates of selected medical events for several countries. Rates of disease events varied by age, sex, method of ascertainment, and geography. Highly visible health conditions, such as Guillain-Barré syndrome, spontaneous abortion, or even death, will occur in coincident temporal association with novel influenza vaccination. On the basis of the reviewed data, if a cohort of 10 million individuals was vaccinated in the UK, 21·5 cases of Guillain-Barré syndrome and 5·75 cases of sudden death would be expected to occur within 6 weeks of vaccination as coincident background cases. In female vaccinees in the USA, 86·3 cases of optic neuritis per 10 million population would be expected within 6 weeks of vaccination. 397 per 1 million vaccinated pregnant women would be predicted to have a spontaneous abortion within 1 day of vaccination. PMID:19880172

Cholera dynamics with Bacteriophage infection: A mathematical study

International Nuclear Information System (INIS)

Misra, A.K.; Gupta, Alok; Venturino, Ezio

2016-01-01

Highlights: • A mathematical model for the biological control of cholera has been proposed. • The feasibility and stability of all the equilibria have been investigated. • The ODE model is found to exhibit Hopf-bifurcation. • Conditions of global asymptotic stability have been obtained. • The impact of important parameters on cholera spread has been shown. - Abstract: Mathematical modeling of waterborne diseases, such as cholera, including a biological control using Bacteriophage viruses in the aquatic reservoirs is of great relevance in epidemiology. In this paper, our aim is twofold: at first, to understand the cholera dynamics in the region around a water body; secondly, to understand how the spread of Bacteriophage infection in the cholera bacterium V. cholerae controls the disease in the human population. For this purpose, we modify the model proposed by Codeço, for the spread of cholera infection in human population and the one proposed by Beretta and Kuang, for the spread of Bacteriophage infection in the bacteria population [1, 2]. We first discuss the feasibility and local asymptotic stability of all the possible equilibria of the proposed model. Further, in the numerical investigation, we have found that the parameter ϕ, called the phage adsorption rate, plays an important role. There is a critical value, ϕ c , at which the model possess Hopf-bifurcation. For lower values than ϕ c , the equilibrium E * is unstable and periodic solutions are observed, while above ϕ c , the equilibrium E * is locally asymptotically stable, and further shown to be also globally asymptotically stable. We investigate the effect of the various parameters on the dynamics of the infected humans by means of numerical simulations.

The Orphans of Cholera Morbus in Yucatan, 1833

OpenAIRE

Elsa Malvido; Paola Peniche Moreno

2013-01-01

This essay discusses the phenomenon of orphanhood which affected a large number of children after the cholera epidemic that struck Yucatan in July 1833. Moreover, it inquires into the fate of children whose parents died of cholera, the role played by kinship networks to provide them with shelter, and the influence of the Church and the State on the situation. Based on first hand sources, the author suggests that the orphanhood produced by cholera served as a pretext for economically and socia...

Twee Nederlandse reizigers uit Thailand met cholera

NARCIS (Netherlands)

Smit, A. A.; Kuijper, E. J.; Schultz, M. J.; Wieling, W.; Speelman, P.

1994-01-01

Cholera is a disease rarely imported in the Netherlands. Recently a 34-year-old woman who had returned from a trip through Thailand was admitted to our hospital with complaints of vomiting, watery stools and moderate dehydration. Vibrio cholerae OI serotype Ogawa biotype El Tor was isolated from the

[Cytotoxic effect of Vibrio cholerae non-O1 on Vero cells].

Science.gov (United States)

Figueroa-Arredondo, P; García-Lozano, H; Gutiérrez-Cogco, L; Valdespino-Gómez, J L

1994-01-01

At the present time there is still in Mexico a diarrhoeal outbreak due to Vibrio cholerae O1. In INDRE we have isolated from the same outbreak last year (jan-apr), 70 strains of Vibrio cholerae Non-O1. These were isolated from patients with a diarrhoeal illness different from cholera. Patients were of different ages and sex, and from various geographic areas. The isolated strains were confirmed by serological agglutination test with polyclonal antisera, and they neither belong to O1 serogroup or O139. We assayed all the 70 strains in Vero cells, searching for cytotoxic effect, probably attributed to cholera toxin, or any other toxin. The strains were screened by PCR for cholera toxin gene detection, and negative results were obtained. We have found only one CT-producer strain, but it was a rough one so, we are not able to affirm that is not a V. cholerae O1 serotype. Vibrio cholerae Non-O1 strains, tested in Vero cells assay, produced cytotoxic effect within 24 h. It was found that 48/70 strains (66.6%), had cytotoxic activity, showing rounding and then lysis of cells. From our results we concluded that this cytotoxic effect, is not cholera toxin related, instead we propose it could be due to an unknown virulence factor, probably a different toxin in mexican Vibrio cholerae Non-O1 strains.

Persistence of plasmids, cholera toxin genes, and prophage DNA in classical Vibrio cholerae O1.

OpenAIRE

Cook, W L; Wachsmuth, K; Johnson, S R; Birkness, K A; Samadi, A R

1984-01-01

Plasmid profiles, the location of cholera toxin subunit A genes, and the presence of the defective VcA1 prophage genome in classical Vibrio cholerae isolated from patients in Bangladesh in 1982 were compared with those in older classical strains isolated during the sixth pandemic and with those in selected eltor and nontoxigenic O1 isolates. Classical strains typically had two plasmids (21 and 3 megadaltons), eltor strains typically had no plasmids, and nontoxigenic O1 strains had zero to thr...

Epidemic cholera in rural El Salvador: risk factors in a region covered by a cholera prevention campaign.

Science.gov (United States)

Quick, R E; Thompson, B L; Zuniga, A; Dominguez, G; De Brizuela, E L; De Palma, O; Almeida, S; Valencia, A; Ries, A A; Bean, N H

1995-04-01

In response to the Latin American cholera epidemic, El Salvador began a prevention programme in April 1991. The first case was confirmed in August, and 700 cases were reported within 3 months. A matched case-control study was conducted in rural La Libertad Department in November 1991. Illness was associated with eating cold cooked or raw seafood (odds ratio [OR] = 7.0; 95% confidence limits [CL] = 1.4, 35.0) and with drinking water outside the home (OR = 8.8; 95% CL = 1.7, 44.6). Assertion of knowledge about how to prevent cholera (OR = 0.2; 95% CL = 0.1, 0.8) and eating rice (OR = 0.2; 95% CL = 0.1, 0.8) were protective. More controls than patients regularly used soap (OR = 0.3; 95% CL = 0.1, 1.0). This study demonstrated three important points for cholera prevention: (1) seafood should be eaten cooked and hot; (2) populations at risk should be taught to treat household drinking water and to avoid drinking water outside the home unless it is known to be treated; and (3) education about hygiene can be an important tool in preventing cholera.

Vibrio cholerae Classical Biotype Strains Reveal Distinct Signatures in Mexico

OpenAIRE

Alam, Munirul; Islam, M. Tarequl; Rashed, Shah Manzur; Johura, Fatema-tuz; Bhuiyan, Nurul A.; Delgado, Gabriela; Morales, Rosario; Mendez, Jose Luis; Navarro, Armando; Watanabe, Haruo; Hasan, Nur-A; Colwell, Rita R.; Cravioto, Alejandro

2012-01-01

Vibrio cholerae O1 classical (CL) biotype caused the fifth and sixth pandemics, and probably the earlier cholera pandemics, before the El Tor (ET) biotype initiated the seventh pandemic in Asia in the 1970s by completely displacing the CL biotype. Although the CL biotype was thought to be extinct in Asia and although it had never been reported from Latin America, V. cholerae CL and ET biotypes, including a hybrid ET, were found associated with areas of cholera endemicity in Mexico between 199...

Cholera outbreak in Senegal in 2005: was climate a factor?

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Guillaume Constantin de Magny

Full Text Available Cholera is an acute diarrheal illness caused by Vibrio cholerae and occurs as widespread epidemics in Africa. In 2005, there were 31,719 cholera cases, with 458 deaths in the Republic of Senegal. We retrospectively investigated the climate origin of the devastating floods in mid-August 2005, in the Dakar Region of Senegal and the subsequent outbreak of cholera along with the pattern of cholera outbreaks in three other regions of that country. We compared rainfall patterns between 2002 and 2005 and the relationship between the sea surface temperature (SST gradient in the tropical Atlantic Ocean and precipitation over Senegal for 2005. Results showed a specific pattern of rainfall throughout the Dakar region during August, 2005, and the associated rainfall anomaly coincided with an exacerbation of the cholera epidemic. Comparison of rainfall and epidemiological patterns revealed that the temporal dynamics of precipitation, which was abrupt and heavy, was presumably the determining factor. Analysis of the SST gradient showed that the Atlantic Ocean SST variability in 2005 differed from that of 2002 to 2004, a result of a prominent Atlantic meridional mode. The influence of this intense precipitation on cholera transmission over a densely populated and crowded region was detectable for both Dakar and Thiès, Senegal. Thus, high resolution rainfall forecasts at subseasonal time scales should provide a way forward for an early warning system in Africa for cholera and, thereby, trigger epidemic preparedness. Clearly, attention must be paid to both natural and human induced environmental factors to devise appropriate action to prevent cholera and other waterborne disease epidemics in the region.

Cholera toxin expression by El Tor Vibrio cholerae in shallow culture growth conditions.

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Cobaxin, Mayra; Martínez, Haydee; Ayala, Guadalupe; Holmgren, Jan; Sjöling, Asa; Sánchez, Joaquín

2014-01-01

Vibrio cholerae O1 classical, El Tor and O139 are the primary biotypes that cause epidemic cholera, and they also express cholera toxin (CT). Although classical V. cholerae produces CT in various settings, the El Tor and O139 strains require specific growth conditions for CT induction, such as the so-called AKI conditions, which consist of growth in static conditions followed by growth under aerobic shaking conditions. However, our group has demonstrated that CT production may also take place in shallow static cultures. How these type of cultures induce CT production has been unclear, but we now report that in shallow culture growth conditions, there is virtual depletion of dissolved oxygen after 2.5 h of growth. Concurrently, during the first three to 4 h, endogenous CO2 accumulates in the media and the pH decreases. These findings may explain CT expression at the molecular level because CT production relies on a regulatory cascade, in which the key regulator AphB may be activated by anaerobiosis and by low pH. AphB activation stimulates TcpP synthesis, which induces ToxT production, and ToxT directly stimulates ctxAB expression, which encodes CT. Importantly, ToxT activity is enhanced by bicarbonate. Therefore, we suggest that in shallow cultures, AphB is activated by initial decreases in oxygen and pH, and subsequently, ToxT is activated by intracellular bicarbonate that has been generated from endogenous CO2. This working model would explain CT production in shallow cultures and, possibly, also in other growth conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Expression of the Native Cholera Toxin B Subunit Gene and Assembly as Functional Oligomers in Transgenic Tobacco Chloroplasts

Science.gov (United States)

Daniell, Henry; Lee, Seung-Bum; Panchal, Tanvi; Wiebe, Peter O.

2012-01-01

The B subunits of enterotoxigenic Escherichia coli (LTB) and cholera toxin of Vibrio cholerae (CTB) are candidate vaccine antigens. Integration of an unmodified CTB-coding sequence into chloroplast genomes (up to 10,000 copies per cell), resulted in the accumulation of up to 4.1% of total soluble tobacco leaf protein as functional oligomers (410-fold higher expression levels than that of the unmodified LTB gene expressed via the nuclear genome). However, expresssion levels reported are an underestimation of actual accumulation of CTB in transgenic chloroplasts, due to aggregation of the oligomeric forms in unboiled samples similar to the aggregation observed for purified bacterial antigen. PCR and Southern blot analyses confirmed stable integration of the CTB gene into the chloroplast genome. Western blot analysis showed that the chloroplast-synthesized CTB assembled into oligomers and were antigenically identical with purified native CTB. Also, binding assays confirmed that chloroplast- synthesized CTB binds to the intestinal membrane GM1-ganglioside receptor, indicating correct folding and disulfide bond formation of CTB pentamers within transgenic chloroplasts. In contrast to stunted nuclear transgenic plants, chloroplast transgenic plants were morphologically indistinguishable from untransformed plants, when CTB was constitutively expressed in chloroplasts. Introduced genes were inherited stably in subsequent generations, as confirmed by PCR and Southern blot analyses. Increased production of an efficient transmucosal carrier molecule and delivery system, like CTB, in transgenic chloroplasts makes plant-based oral vaccines and fusion proteins with CTB needing oral administration commercially feasible. Successful expression of foreign genes in transgenic chromoplasts and availability of marker-free chloroplast transformation techniques augurs well for development of vaccines in edible parts of transgenic plants. Furthermore, since the quaternary structure of

What is Cholera?

Indian Academy of Sciences (India)

Cholera is a rapidly dehydrating watery diarrheal disease that can lead to death in less than 24 hours if untreated, making it, according to WHO, “one of the most rapidly fatal infectious illnesses known” ...

Genome-wide study of the defective sucrose fermenter strain of Vibrio cholerae from the Latin American cholera epidemic.

Directory of Open Access Journals (Sweden)

Daniel Rios Garza

Full Text Available The 7th cholera pandemic reached Latin America in 1991, spreading from Peru to virtually all Latin American countries. During the late epidemic period, a strain that failed to ferment sucrose dominated cholera outbreaks in the Northern Brazilian Amazon region. In order to understand the genomic characteristics and the determinants of this altered sucrose fermenting phenotype, the genome of the strain IEC224 was sequenced. This paper reports a broad genomic study of this strain, showing its correlation with the major epidemic lineage. The potentially mobile genomic regions are shown to possess GC content deviation, and harbor the main V. cholera virulence genes. A novel bioinformatic approach was applied in order to identify the putative functions of hypothetical proteins, and was compared with the automatic annotation by RAST. The genome of a large bacteriophage was found to be integrated to the IEC224's alanine aminopeptidase gene. The presence of this phage is shown to be a common characteristic of the El Tor strains from the Latin American epidemic, as well as its putative ancestor from Angola. The defective sucrose fermenting phenotype is shown to be due to a single nucleotide insertion in the V. cholerae sucrose-specific transportation gene. This frame-shift mutation truncated a membrane protein, altering its structural pore-like conformation. Further, the identification of a common bacteriophage reinforces both the monophyletic and African-Origin hypotheses for the main causative agent of the 1991 Latin America cholera epidemics.

Non-01 Vibrio cholerae infections in Cancun, Mexico.

Science.gov (United States)

Finch, M J; Valdespino, J L; Wells, J G; Perez-Perez, G; Arjona, F; Sepulveda, A; Bessudo, D; Blake, P A

1987-03-01

To determine the role of Vibrio cholerae as a cause of diarrheal illness in Cancun, Mexico, an investigation was conducted in July and August 1983. Although toxigenic V. cholerae 01 were not found, non-01 V. cholerae were isolated from 22 (16%) of 134 stools from persons with diarrheal illness and none of 22 stools from well persons; 58 (92%) of 63 sewage samples; 12 (86%) of 14 untreated well water samples; a home storage tank for treated water; and 5 (21%) of 24 samples of raw seafood. None of the V. cholerae isolates from patients were toxigenic. The illness occurred mainly in small children, and were characterized principally by diarrhea and abdominal pain. No patient was seriously ill, and all recovered without sequelae. Seven different serotypes of non-01 V. cholerae were isolated from the stool specimens, and Smith serotype 12 accounted for 10 (46%) of the 22 isolates. A matched-pair case-control study found that cases were more likely than controls to have eaten home prepared gelatin (P = 0.03, OR = 5/0) and seafood (P = 0.06, OR = 4/0).

Zinc oxide nanoparticles provide anti-cholera activity by disrupting the interaction of cholera toxin with the human GM1 receptor.

Science.gov (United States)

Sarwar, Shamila; Ali, Asif; Pal, Mahadeb; Chakrabarti, Pinak

2017-11-03

Vibrio cholerae causes cholera and is the leading cause of diarrhea in developing countries, highlighting the need for the development of new treatment strategies to combat this disease agent. While exploring the possibility of using zinc oxide (ZnO) nanoparticles (NPs) in cholera treatment, we previously found that ZnO NPs reduce fluid accumulation in mouse ileum induced by the cholera toxin (CT) protein. To uncover the mechanism of action of ZnO NPs on CT activity, here we used classical (O395) and El Tor (C6706) V. cholerae biotypes in growth and biochemical assays. We found that a ZnO NP concentration of 10 μg/ml did not affect the growth rates of these two strains, nor did we observe that ZnO NPs reduce the expression levels of CT mRNA and protein. It was observed that ZnO NPs form a complex with CT, appear to disrupt the CT secondary structure, and block its interaction with the GM1 ganglioside receptor in the outer leaflet of the plasma membrane in intestinal (HT-29) cells and thereby reduce CT uptake into the cells. In the range of 2.5-10 μg/ml, ZnO NPs exhibited no cytotoxicity on kidney (HEK293) and HT-29 cells. We conclude that ZnO NPs prevent the first step in the translocation of cholera toxin into intestinal epithelial cells without exerting measurable toxic effects on HEK293 and HT-29 cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Seasonality of cholera from 1974 to 2005: a review of global patterns

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Feldacker Caryl

2008-06-01

Full Text Available Abstract Background The seasonality of cholera is described in various study areas throughout the world. However, no study examines how temporal cycles of the disease vary around the world or reviews its hypothesized causes. This paper reviews the literature on the seasonality of cholera and describes its temporal cycles by compiling and analyzing 32 years of global cholera data. This paper also provides a detailed literature review on regional patterns and environmental and climatic drivers of cholera patterns. Data, Methods, and Results Cholera data are compiled from 1974 to 2005 from the World Health Organization Weekly Epidemiological Reports, a database that includes all reported cholera cases in 140 countries. The data are analyzed to measure whether season, latitude, and their interaction are significantly associated with the country-level number of outbreaks in each of the 12 preceding months using separate negative binomial regression models for northern, southern, and combined hemispheres. Likelihood ratios tests are used to determine the model of best fit. The results suggest that cholera outbreaks demonstrate seasonal patterns in higher absolute latitudes, but closer to the equator, cholera outbreaks do not follow a clear seasonal pattern. Conclusion The findings suggest that environmental and climatic factors partially control the temporal variability of cholera. These results also indirectly contribute to the growing debate about the effects of climate change and global warming. As climate change threatens to increase global temperature, resulting rises in sea levels and temperatures may influence the temporal fluctuations of cholera, potentially increasing the frequency and duration of cholera outbreaks.

Vibrio cholerae interactions with Mytilus galloprovincialis hemocytes mediated by serum components.

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Laura eCanesi

2013-12-01

Full Text Available Edible bivalves (e.g., mussels, oysters can accumulate large amount of bacteria in their tissues and act as passive carriers of pathogens to humans. Bacterial persistence inside bivalves depends, at least in part, on hemolymph anti-bacterial activity that is exerted by both serum soluble factors and phagocytic cells (i.e., the hemocytes. It was previously shown that Mytilus galloprovincialis hemolymph serum contains opsonins that mediate D-mannose-sensitive interactions between hemocytes and V. cholerae O1 El Tor bacteria that carry the Mannose–Sensitive Hemagglutinin (MSHA. These opsonins enhance phagocytosis and killing of vibrios by facilitating their binding to hemocytes. Since V. cholerae strains not carrying the MSHA ligand (O1 classical, non O1/O139 are present in coastal water and can be entrapped by mussels, we studied whether in mussel serum, in addition to opsonins directed towards MSHA, other components can mediate opsonization of these bacteria. By comparing interactions of O1 classical and non O1/O139 strains with hemocytes in ASW and serum, it was found that M. galloprovincialis serum contains components that increase by at approximately two fold their adhesion to, association with and killing by hemocytes. Experiments conducted with high and low molecular mass fractions obtained by serum ultrafiltration indicated that these compounds have molecular mass higher than 5000 Da. Serum exposure to high temperature (80°C abolished its opsonizing capability suggesting that the involved serum active components are of protein nature. Further studies are needed to define the chemical properties and specificity of both the involved bacterial ligands and hemolymph opsonins. This information will be central not only to better understand V. cholerae ecology, but also to improve current bivalve depuration practices and properly protect human health.

A simple and convenient microtiter plate assay for the detection of bactericidal antibodies to Vibrio cholerae O1 and Vibrio cholerae O139.

Science.gov (United States)

Boutonnier, Alain; Dassy, Bruno; Duménil, Rémy; Guénolé, Alain; Ratsitorahina, Maherisoa; Migliani, René; Fournier, Jean-Michel

2003-12-01

It is believed that the correlate of protection for cholera can be determined by the serum vibriocidal assay. The currently available vibriocidal assays, based on the conventional agar plating technique, are labor intensive. We developed a simple and convenient microtiter plate assay for the detection of vibriocidal antibodies that is equally as efficient for Vibrio cholerae O1 and for V. cholerae O139. The addition of succinate and neotetrazolium made it possible to measure the growth of surviving bacterial target cells by monitoring a color change. We evaluated assay parameters (target strains, growth of target cells, complement source and concentration) that may affect the reproducibility of the method for V. cholerae O139. The results obtained with the microtiter plate assay were uniformly similar to those obtained with the conventional agar plating assay, when testing both the Inaba and Ogawa serotypes of V. cholerae O1. The microtiter plate assay was also convenient for measuring the activity of animal sera and mouse monoclonal antibodies.

Factors determining water treatment behavior for the prevention of cholera in Chad.

Science.gov (United States)

Lilje, Jonathan; Kessely, Hamit; Mosler, Hans-Joachim

2015-07-01

Cholera is a well-known and feared disease in developing countries, and is linked to high rates of morbidity and mortality. Contaminated drinking water and the lack of sufficient treatment are two of the key causes of high transmission rates. This article presents a representative health survey performed in Chad to inform future intervention strategies in the prevention and control of cholera. To identify critical psychological factors for behavior change, structured household interviews were administered to N = 1,017 primary caregivers, assessing their thoughts and attitudes toward household water treatment according to the Risk, Attitude, Norm, Ability, and Self-regulation model. The intervention potential for each factor was estimated by analyzing differences in means between groups of current performers and nonperformers of water treatment. Personal risk evaluation for diarrheal diseases and particularly for cholera was very low among the study population. Likewise, the perception of social norms was found to be rather unfavorable for water treatment behaviors. In addition, self-reported ability estimates (self-efficacy) revealed some potential for intervention. A mass radio campaign is proposed, using information and normative behavior change techniques, in combination with community meetings focused on targeting abilities and personal commitment to water treatment. © The American Society of Tropical Medicine and Hygiene.

Health impairments arising from drinking water resources contaminated with Vibrio cholerae.

Science.gov (United States)

Ramamurthy, T; Chakraborty, S; Nair, G B; Bhattacharya, S K

2000-01-01

The endemic and seasonal nature of cholera depends upon the survival of toxigenic Vibrio cholerae in various niches of the aquatic environment. To understand the transmission and ecology of V. cholerae, it is necessary to know which component in the aquatic ecosystem can harbor it and thus contribute to the endemic presence. Toxigenic V. cholerae is now recognized as an autochthonous member of the microflora in many aquatic environments based on its protracted survival and proliferation without losing the virulence determinants. This article summarizes knowledge about the ecology, survival strategies and elimination techniques of V. cholerae from natural waters with special reference to drinking water.

9 CFR 309.5 - Swine; disposal because of hog cholera.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Swine; disposal because of hog cholera... INSPECTION AND CERTIFICATION ANTE-MORTEM INSPECTION § 309.5 Swine; disposal because of hog cholera. (a) All swine found by an inspector to be affected with hog cholera shall be identified as U.S. Condemned and...

[The immunology of cholera and the molecular biology of cholera toxin. Recent progress and future perspectives].

Science.gov (United States)

Carrada-Bravo, T

1994-01-01

Vibrio cholerae has recently called the attention of researchers due to its strong immunogenicity and also because it serves as coadjunct immunomodulator of the immune response of the intestinal mucosae for the mixed added antigens as well as for those covalently linked to the toxin. The immunopathogeny of cholera is a complex phenomenon. This article presents the preliminary results of experiments conducted with laboratory rats in order to find the IgA intestinal response of rodents and humans.

Breast milk reduces the risk of illness in children of mothers with cholera

DEFF Research Database (Denmark)

Qureshi, Katja; Mølbak, Kåre; Sandström, Anita

2006-01-01

BACKGROUND: A protective effect of breastfeeding against cholera has been demonstrated in areas endemic of cholera. To assess the protection offered by breast milk from mothers living in an area that had been free from cholera for 7 years, we investigated mothers with cholera and their children...... during an epidemic with Vibrio cholerae El Tor in the capital of Guinea-Bissau. METHODS: Eighty mothers with clinical cholera and their children were identified, and interviewed. Blood samples for vibriocidal and antitoxin antibodies were collected from mother-and-child pairs. Breast milk samples were...... collected from lactating mothers.Cholera was defined as acute watery diarrhea during the epidemic and a vibriocidal reciprocal titer of 20 or above. RESULTS: Three (7%) of 42 breastfed children had cholera as defined above compared with 9 (24%) of 38 nonbreastfed children (RR for breastfed children, 0...

Coliform and Vibrio cholerae Analysis of Drinking Water Collected from Cholera Outbreak Region of Bhaktapur Municipality

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Upendra Thapa Shrestha

2014-09-01

Full Text Available Water borne infections in Nepal, especially in Kathmandu valley is one the major public health problems, causing thousands of deaths every year. Among three cities in the valley, the water borne infection including cholera is most predominant in Bhaktapur district. So the study was carried out to know the microbial drinking water quality in the city and to determine the prevalence of water borne infections in the specified region of the district in 2012. Altogether eighty (two samples from a single site at different interval-2/3 days water samples were collected from Bhaktapur Municipality, one of the most vulnerable regions for water borne diseases, following standard methods as described by APHA, 2010. All samples were transferred to Microbiology laboratory of Khwopa College, Dekocha, Bhaktapur and preceded immediately for Microbial analysis. The coliform density in the water samples were determined by Most Probable Number (MPN method followed by microscopy, colonial morphology and biochemical characterization. Subsequently, the presence of Vibrio cholerae, a causative agent of Cholera was analyzed in the same samples by enrichment in alkaline peptone water followed by culture on Thiosulphate citrate bile-salt sucrose (TCBS agar, a selective media for Vibrio spp. The biochemical tests were then performed to identify V. cholerae. Among eighty water samples, 87.5 percent water samples contained coliforms and half of which (45% contained feacal coliforms, Escherichia coli and remaining 12.5 percent water samples contained no coliforms. Vibrio cholerae were isolated from four water samples (5%. The drinking water quality in the region was found to be very poor. Therefore, the people in the region were suggested to treat the drinking water by using any of physical or chemical disinfection methods prior to drinking. DOI: http://dx.doi.org/10.3126/ije.v3i3.11073 International Journal of Environment Vol.3(3 2014: 139-145

Probiotics, antibiotics and the immune responses to vaccines.

Science.gov (United States)

Praharaj, Ira; John, Sushil M; Bandyopadhyay, Rini; Kang, Gagandeep

2015-06-19

Orally delivered vaccines have been shown to perform poorly in developing countries. There are marked differences in the structure and the luminal environment of the gut in developing countries resulting in changes in immune and barrier function. Recent studies using newly developed technology and analytic methods have made it increasingly clear that the intestinal microbiota activate a multitude of pathways that control innate and adaptive immunity in the gut. Several hypotheses have been proposed for the underperformance of oral vaccines in developing countries, and modulation of the intestinal microbiota is now being tested in human clinical trials. Supplementation with specific strains of probiotics has been shown to have modulatory effects on intestinal and systemic immune responses in animal models and forms the basis for human studies with vaccines. However, most studies published so far that have evaluated the immune response to vaccines in children and adults have been small and results have varied by age, antigen, type of antibody response and probiotic strain. Use of anthelminthic drugs in children has been shown to possibly increase immunogenicity following oral cholera vaccination, lending further support to the rationale for modulation of the immune response to oral vaccination through the intestinal microbiome. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

[A prognostic model of a cholera epidemic].

Science.gov (United States)

Boev, B V; Bondarenko, V M; Prokop'eva, N V; San Román, R T; Raygoza-Anaya, M; García de Alba, R

1994-01-01

A new model for the prognostication of cholera epidemic on the territory of a large city is proposed. This model reflects the characteristic feature of contacting infection by sensitive individuals due to the preservation of Vibrio cholerae in their water habitat. The mathematical model of the epidemic quantitatively reflects the processes of the spread of infection by kinetic equations describing the interaction of the streams of infected persons, the causative agents and susceptible persons. The functions and parameters of the model are linked with the distribution of individuals according to the duration of the incubation period and infectious process, as well as the period of asymptomatic carrier state. The computer realization of the model by means of IBM PC/AT made it possible to study the cholera epidemic which took place in Mexico in 1833. The verified model of the cholera epidemic was used for the prognostication of the possible spread of this infection in Guadalajara, taking into account changes in the epidemiological situation and the size of the population, as well as improvements in sanitary and hygienic conditions, in the city.

El Niño, Rainfall, and the Shifting Geography of Cholera in Africa

Science.gov (United States)

Moore, S.; Azman, A. S.; Zaitchik, B. F.; McKay, H.; Lessler, J.

2017-12-01

The El Niño Southern Oscillation (ENSO) and other climate patterns can have profound impacts on the occurrence of infectious diseases. Because of the key role of water supplies in cholera transmission, a relationship between El Niño events and cholera incidence is highly plausible, and previous research has shown a link between El Niño patterns and cholera in Bangladesh. However, there is little systematic evidence for this link in Africa where many cholera cases and deaths are reported. To understand how ENSO affects the geographic distribution of cholera incidence in Africa, we used a hierarchical Bayesian approach to integrate over 17,000 annual observations of cholera incidence from 2000-2014 in over 3,000 unique locations of varying spatial extent, ranging from entire countries to neighborhoods. The resulting maps reflect modeled cholera incidence at a fine spatial resolution using reported counts of cholera cases, key explanatory variables, and a spatially-dependent covariance term. We then examined the potential mechanistic association between ENSO-related changes in cholera incidence and several environmental variables including rainfall. El Niño profoundly changed the annual geographic distribution of cholera in Africa from 2000-2014, shifting the burden to continental East Africa, where almost 50,000 additional cases occur during El Niño years. Cholera incidence during El Niño years was higher in regions of East Africa with increased rainfall, but incidence was also higher in some areas with decreased rainfall suggesting a complex relationship between rainfall and cholera incidence. Here we show clear evidence for a shift in the distribution of cholera incidence throughout Africa in El Niño and non-El Niño years, likely mediated by El Niño's impact on local climatic factors. Knowledge of this relationship between cholera and climate patterns coupled with El Niño forecasting could be used to notify countries in Africa when they are likely to see

Community health facility preparedness for a cholera surge in Haiti.

Science.gov (United States)

Mobula, Linda Meta; Jacquet, Gabrielle A; Weinhauer, Kristin; Alcidas, Gladys; Thomas, Hans-Muller; Burnham, Gilbert

2013-01-01

With increasing population displacement and worsening water insecurity after the 2010 earthquake, Haiti experienced a large cholera outbreak. Our goal was to evaluate the strengths and weaknesses of seven community health facilities' ability to respond to a surge in cholera cases. Since 2010, Catholic Relief Services (CRS) with a number of public and private donors has been working with seven health facilities in an effort to reduce morbidity and mortality from cholera infection. In November 2012, CRS through the Centers for Disease Control and Prevention (CDC)'s support, asked the Johns Hopkins Center for Refugee and Disaster Response to conduct a cholera surge simulation tabletop exercise at these health facilities to improve each facility's response in the event of a cholera surge. Using simulation development guidelines from the Pan American Health Organization and others, a simulation scenario script was produced that included situations of differing severity, supply chain, as well as a surge of patients. A total of 119 hospital staff from seven sites participated in the simulation exercise including community health workers, clinicians, managers, pharmacists, cleaners, and security guards. Clinics that had challenges during the simulated clinical care of patients were those that did not appropriately treat all cholera patients according to protocol, particularly those that were vulnerable, those that would need additional staff to properly treat patients during a surge of cholera, and those that required a better inventory of supplies. Simulation-based activities have the potential to identify healthcare delivery system vulnerabilities that are amenable to intervention prior to a cholera surge.

Analysis of a cholera toxin B subunit (CTB) and human mucin 1 (MUC1) conjugate protein in a MUC1-tolerant mouse model.

Science.gov (United States)

Pinkhasov, Julia; Alvarez, M Lucrecia; Pathangey, Latha B; Tinder, Teresa L; Mason, Hugh S; Walmsley, Amanda M; Gendler, Sandra J; Mukherjee, Pinku

2010-12-01

Since epithelial mucin 1 (MUC1) is associated with several adenocarcinomas at the mucosal sites, it is pertinent to test the efficacy of a mucosally targeted vaccine formulation. The B subunit of the Vibrio cholerae cholera toxin (CTB) has great potential to act as a mucosal carrier for subunit vaccines. In the present study we evaluated whether a MUC1 tandem repeat (TR) peptide chemically linked to CTB would break self-antigen tolerance in the transgenic MUC1-tolerant mouse model (MUC1.Tg) through oral or parenteral immunizations. We report that oral immunization with the CTB-MUC1 conjugate along with mucosal adjuvant, unmethylated CpG oligodeoxynucleotide (ODN) and interleukin-12 (IL-12) did not break self-antigen tolerance in MUC1.Tg mice, but induced a strong humoral response in wild-type C57BL/6 mice. However, self-antigen tolerance in the MUC1.Tg mouse model was broken after parenteral immunizations with different doses of the CTB-MUC1 conjugate protein and with the adjuvant CpG ODN co-delivered with CTB-MUC1. Importantly, mice immunized systemically with CpG ODN alone and with CTB-MUC1 exhibited decreased tumor burden when challenged with a mammary gland tumor cell line that expresses human MUC1.

Analysis of a Cholera Toxin B Subunit (CTB) and Human Mucin 1 (MUC1) Conjugate Protein in a MUC1 Tolerant Mouse Model

Science.gov (United States)

Pinkhasov, Julia; Alvarez, M. Lucrecia; Pathangey, Latha B.; Tinder, Teresa L.; Mason, Hugh S.; Walmsley, Amanda M.; Gendler, Sandra J.; Mukherjee, Pinku

2011-01-01

Since epithelial mucin 1 (MUC1) is associated with several adenocarcinomas at mucosal sites, it is pertinent to test the efficacy of a mucosally targeted vaccine formulation. The B subunit of the Vibrio cholerae cholera toxin (CTB) has great potential to act as a mucosal carrier for subunit vaccines. In the present study we evaluated whether a MUC1 tandem repeat (TR) peptide chemically linked to CTB would break self-antigen tolerance in the transgenic MUC1 tolerant mouse model (MUC1.Tg) through oral or parenteral immunizations. We report that oral immunization with the CTB-MUC1 conjugate along with mucosal adjuvant, unmethylated CpG oligodeoxynucleotide (ODN) and interleukin-12 (IL-12), did not break self-antigen tolerance in MUC1.Tg mice, but induced a strong humoral response in wild-type C57BL/6 mice. However, self-antigen tolerance in the MUC1.Tg mouse model was broken after parenteral immunizations with different doses of the CTB-MUC1 conjugate protein and with the adjuvant CpG ODN co-delivered with CTB-MUC1. Importantly, mice immunized systemically with CpG ODN alone and with CTB-MUC1 exhibited decreased tumor burden when challenged with a mammary gland tumor cell line that expresses human MUC1. PMID:20824430

Geospatial and temporal patterns of annual cholera outbreaks in Matlab, Bangladesh

Science.gov (United States)

Majumder, M. S.; de Klerk, K.; Meyers, D.

2012-12-01

Cholera is a waterborne diarrheal disease endemic to Bangladesh, resulting in 1 million diagnoses annually. Such disease burden results in incalculable lost wages and treatment expenses, taken from the pockets of an already impoverished society. Two seasonally correlated outbreaks of cholera occur in Bangladesh every year. In the spring and early summer, the Bay of Bengal - which serves as a natural reservoir for the cholera bacteria - flows inland, causing the first outbreak amongst coastal communities. Waste containing the cholera bacteria enters the sewage system and remains untreated due to poor water and sanitation infrastructure. Therefore, during the following monsoon season, flooding of cholera-contaminated sewage into drinking water sources results in a second outbreak. Though considered common knowledge among local populations, this geographic and temporal progression has not been empirically verified in the current literature. The aim of our ongoing study is to systematically analyze the seasonal trajectory of endemic cholera in Bangladesh. This paper discusses the results obtained from a comprehensive survey of available cholera data from the International Centre of Diarrheal Disease Research, Bangladesh (ICDDR,B) in Matlab, Bangladesh. Matlab thana is a near-coastal community that consists of 142 villages. Monsoon season takes place from June through October. Due to its proximity to the Meghna River, which opens into the Bay of Bengal, the area experiences significant flooding during these months. Using 10 years of geographically referenced cholera data, cases were plotted in time and space. Preliminary patterns suggest that villages closer to the Meghna River experience the majority of the area's cholera outbreaks and that case count is highest in late spring and late fall. April/May and November/December represent 25% and 23% of total annual case counts respectively. Moreover, villages further from the coastline demonstrate 57% higher relative

A novel kit for rapid detection of Vibrio cholerae O1.

OpenAIRE

Hasan, J A; Huq, A; Tamplin, M L; Siebeling, R J; Colwell, R R

1994-01-01

We report on the development and testing of a novel, rapid, colorimetric immunodiagnostic kit, Cholera SMART, for direct detection of the presence of Vibrio cholerae O1 in clinical specimens. Unlike conventional culture methods requiring several days to complete, the Cholera SMART kit can be used directly in the field by untrained or minimally skilled personnel to detect V. cholerae O1 in less than 15 min, without cumbersome laboratory equipment. A total of 120 clinical and environmental bact...

antimicrobial susceptibility pattern of vibrio cholerae 01 strains

African Journals Online (AJOL)

hi-tech

East African Medical Journal Vol. 77 No. 7 July 2000. ANTIMICROBIAL SUSCEPTIBILITY PATTERN OF VIBRIO CHOLERAE 01 STRAINS DURING TWO CHOLERA OUTBREAKS IN DAR ES SALAAM,. TANZANIA. W.K. Urassa, MD, MSc, MMed, Lecturer, Department of Microbiology and Immunology, Muhimbili University ...

Human Mobility Patterns and Cholera Epidemics: a Spatially Explicit Modeling Approach

Science.gov (United States)

Mari, L.; Bertuzzo, E.; Righetto, L.; Casagrandi, R.; Gatto, M.; Rodriguez-Iturbe, I.; Rinaldo, A.

2010-12-01

Cholera is an acute enteric disease caused by the ingestion of water or food contaminated by the bacterium Vibrio cholerae. Although most infected individuals do not develop severe symptoms, their stool may contain huge quantities of V.~cholerae cells. Therefore, while traveling or commuting, asymptomatic carriers can be responsible for the long-range dissemination of the disease. As a consequence, human mobility is an alternative and efficient driver for the spread of cholera, whose primary propagation pathway is hydrological transport through river networks. We present a multi-layer network model that accounts for the interplay between epidemiological dynamics, hydrological transport and long-distance dissemination of V.~cholerae due to human movement. In particular, building on top of state-of-the-art spatially explicit models for cholera spread through surface waters, we describe human movement and its effects on the propagation of the disease by means of a gravity-model approach borrowed from transportation theory. Gravity-like contact processes have been widely used in epidemiology, because they can satisfactorily depict human movement when data on actual mobility patterns are not available. We test our model against epidemiological data recorded during the cholera outbreak occurred in the KwaZulu-Natal province of South Africa during years 2000--2001. We show that human mobility does actually play an important role in the formation of the spatiotemporal patterns of cholera epidemics. In particular, long-range human movement may determine inter-catchment dissemination of V.~cholerae cells, thus in turn explaining the emergence of epidemic patterns that cannot be produced by hydrological transport alone. We also show that particular attention has to be devoted to study how heterogeneously distributed drinking water supplies and sanitation conditions may affect cholera transmission.

Acalculous cholecystitis and septicemia caused by non-O1 Vibrio cholerae: first reported case and review of biliary infections with Vibrio cholerae.

Science.gov (United States)

West, B C; Silberman, R; Otterson, W N

1998-03-01

The first case of septicemic acute acalculous cholecystitis caused by non-O1 Vibrio cholerae is described in a healthy traveler, and biliary tract infections from V. cholerae are reviewed. Immediately after a vacation in Cancun, Mexico, a 55-year-old man developed acute cholecystitis. Blood and bile cultures grew non-O1 V. cholerae. At surgery, the gallbladder was acalculous, inflamed, distended, and nearly ruptured. Pathogenetic factors may have included diarrhea prophylaxis with bismuth subsalicylate, distension of the gallbladder from illness-induced fasting, and bacterial toxins in the gallbladder. The patient received i.v. cephapirin, followed by oral cephradine for a total of 10 days, and he made a quick and complete recovery. V. cholerae should be considered in the differential diagnosis of persons from endemic areas who present with cholecystitis or acute jaundice.

Epidemic waves of cholera in the last two decades in Mozambique.

Science.gov (United States)

Langa, José Paulo; Sema, Cynthia; De Deus, Nilsa; Colombo, Mauro Maria; Taviani, Elisa

2015-07-04

Africa is increasingly affected by cholera. In Mozambique, cholera appeared in the early 1970s when the seventh pandemic entered Africa from the Indian subcontinent. In the following decades, several epidemics were registered in the country, the 1997-1999 epidemic being the most extended. Since then, Mozambique has been considered an endemic area for cholera, characterized by yearly outbreaks occurring with a seasonal pattern. At least three pandemic variants are thought to have originated in the Indian subcontinent and spread worldwide at different times. To understand the epidemiology of cholera in Mozambique, whether the disease re-emerges periodically or is imported by different routes of transmission, we investigated clinical V. cholerae O1 isolated during 1997-1999 and 2012-2014 epidemics. By detecting and characterizing seven genetic elements, the mobilome profile of each isolate was obtained. By comparing it to known seventh pandemic reference strains, it was possible to discern among different V. cholerae O1 variants active in the country. During 1997-1999, epidemic strains showed two different genetic profiles, both related to a pandemic clone that originated from India and was reported in other African countries in the 1990s. Isolates from 2012-2014 outbreaks showed a genetic background related to the pandemic strains currently active as the prevalent causative agent of cholera worldwide. Despite cholera being endemic in Mozambique, the epidemiology of the disease in the past 20 years has been strongly influenced by the cholera seventh pandemic waves that originated in the Indian subcontinent.

Phase variable O antigen biosynthetic genes control expression of the major protective antigen and bacteriophage receptor in Vibrio cholerae O1.

Directory of Open Access Journals (Sweden)

Kimberley D Seed

2012-09-01

Full Text Available The Vibrio cholerae lipopolysaccharide O1 antigen is a major target of bacteriophages and the human immune system and is of critical importance for vaccine design. We used an O1-specific lytic bacteriophage as a tool to probe the capacity of V. cholerae to alter its O1 antigen and identified a novel mechanism by which this organism can modulate O antigen expression and exhibit intra-strain heterogeneity. We identified two phase variable genes required for O1 antigen biosynthesis, manA and wbeL. manA resides outside of the previously recognized O1 antigen biosynthetic locus, and encodes for a phosphomannose isomerase critical for the initial step in O1 antigen biosynthesis. We determined that manA and wbeL phase variants are attenuated for virulence, providing functional evidence to further support the critical role of the O1 antigen for infectivity. We provide the first report of phase variation modulating O1 antigen expression in V. cholerae, and show that the maintenance of these phase variable loci is an important means by which this facultative pathogen can generate the diverse subpopulations of cells needed for infecting the host intestinal tract and for escaping predation by an O1-specific phage.

Agglutinating and bactericidal properties of fractions of rabbit anti-Vibrio cholerae serum.

Science.gov (United States)

Pike, R M; Chandler, C H

1969-06-01

The major portion of the agglutinating and bactericidal activity of the sera of rabbits immunized with live Vibrio cholerae or with cholera vaccine was found in the gammaM fractions during the early stages of immunization. After 5 weeks or more, gammaG fractions accounted for more than half of the agglutinating activity. When late antibody was measured as the amount of protein precipitated by somatic antigens, nearly 3 times as much gammaG as gammaM was required for agglutination, and about 30 times as much gammaG as gammaM was required to kill 50% of a standard inoculum in the presence of complement. The ratio of vibriocidal to agglutinin titer of gammaG fractions at different stages of immunization was more variable than that of gammaM fractions. More complement was required for a vibriocidal effect by gammaG than by gammaM. Increasing the amount of complement decreased the amount of both gammaG and gammaM required to kill, but smaller amounts of gammaM required disproportionately larger amounts of complement. Less time was required by gammaM than by gammaG to kill 50% of the inoculum. Removal of the group-reactive antibody from anti-Ogawa serum and serum fractions by absorption with Inaba reduced the vibriocidal titer by more than one-half.

The Orphans of Cholera Morbus in Yucatan, 1833

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Elsa Malvido

2013-07-01

Full Text Available This essay discusses the phenomenon of orphanhood which affected a large number of children after the cholera epidemic that struck Yucatan in July 1833. Moreover, it inquires into the fate of children whose parents died of cholera, the role played by kinship networks to provide them with shelter, and the influence of the Church and the State on the situation. Based on first hand sources, the author suggests that the orphanhood produced by cholera served as a pretext for economically and socially privileged groups to get hold of free labor force both for domestic service and hacienda work.

Mass media effect on vaccines uptake during silent polio outbreak.

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Sagy, Iftach; Novack, Victor; Gdalevich, Michael; Greenberg, Dan

2018-03-14

During 2013, isolation of a wild type 1 poliovirus from routine sewage sample in Israel, led to a national OPV campaign. During this period, there was a constant cover of the outbreak by the mass media. To investigate the association of media exposure and OPV and non-OPV vaccines uptake during the 2013 silent polio outbreak in Israel. We received data on daily immunization rates during the outbreak period from the Ministry of Health (MoH). We conducted a multivariable time trend analysis to assess the association between daily media exposure and vaccines uptake. Analysis was stratified by ethnicity and socio-economic status (SES). During the MoH supplemental immunization activity, 138,799 OPV vaccines were given. There was a significant association between media exposure and OPV uptake, most prominent in a lag of 3-5 days from the exposure among Jews (R.R 1.79C.I 95% 1.32-2.41) and high SES subgroups (R.R 1.71C.I 95% 1.27-2.30). These subgroups also showed increased non-OPV uptake in a lag of 3-5 days from the media exposure, in all vaccines except for MMR. Lower SES and non-Jewish subgroups did not demonstrate the same association. Our findings expand the understanding of public behaviour during outbreaks. The public response shows high variability within specific subgroups. These findings highlight the importance of tailored communication strategies for each subgroup. Copyright © 2018 Elsevier Ltd. All rights reserved.

Public health impact and cost effectiveness of mass vaccination with live attenuated human rotavirus vaccine (RIX4414) in India: model based analysis.

Science.gov (United States)

Rose, Johnie; Hawthorn, Rachael L; Watts, Brook; Singer, Mendel E

2009-09-25

To examine the public health impact of mass vaccination with live attenuated human rotavirus vaccine (RIX4414) in a birth cohort in India, and to estimate the cost effectiveness and affordability of such a programme. Decision analytical Markov model encompassing all direct medical costs. Infection risk and severity depended on age, number of previous infections, and vaccination history; probabilities of use of inpatient and outpatient health services depended on symptom severity. Published clinical, epidemiological, and economic data. When possible, parameter estimates were based on data specific for India. Population Simulated Indian birth cohort followed for five years. Decrease in rotavirus gastroenteritis episodes (non-severe and severe), deaths, outpatient visits, and admission to hospital; incremental cost effectiveness ratio of vaccination expressed as net cost in 2007 rupees per life year saved. In the base case, vaccination prevented 28,943 (29.7%) symptomatic episodes, 6981 (38.2%) severe episodes, 164 deaths (41.0%), 7178 (33.3%) outpatient visits, and 812 (34.3%) admissions to hospital per 100,000 children. Vaccination cost 8023 rupees (about pound100, euro113, $165) per life year saved, less than India's per capita gross domestic product, a common criterion for cost effectiveness. The net programme cost would be equivalent to 11.6% of the 2006-7 budget of the Indian Department of Health and Family Welfare. Model results were most sensitive to variations in access to outpatient care for those with severe symptoms. If this parameter was increased to its upper limit, the incremental cost effectiveness ratio for vaccination still fell between one and three times the per capita gross domestic product, meeting the World Health Organization's criterion for "cost effective" interventions. Uncertainty analysis indicated a 94.7% probability that vaccination would be cost effective according to a criterion of one times per capita gross domestic product per life

Molecular Epidemiology of Cholera Outbreaks during the Rainy Season in Mandalay, Myanmar.

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Roobthaisong, Amonrattana; Okada, Kazuhisa; Htun, Nilar; Aung, Wah Wah; Wongboot, Warawan; Kamjumphol, Watcharaporn; Han, Aye Aye; Yi, Yi; Hamada, Shigeyuki

2017-11-01

Cholera, caused by Vibrio cholerae , remains a global threat to public health. In Myanmar, the availability of published information on the occurrence of the disease is scarce. We report here that cholera incidence in Mandalay generally exhibited a single annual peak, with an annual average of 312 patients with severe dehydration over the past 5 years (since 2011) and was closely associated with the rainy season. We analyzed cholera outbreaks, characterized 67 isolates of V. cholerae serogroup O1 in 2015 from patients from Mandalay, and compared them with 22 V. cholerae O1 isolates (12 from Mandalay and 10 from Yangon) in 2014. The isolates carried the classical cholera toxin B subunit ( ctxB ), the toxin-coregulated pilus A ( tcpA ) of Haitian type, and repeat sequence transcriptional regulator ( rstR ) of El Tor type. Two molecular typing methods, pulsed-field gel electrophoresis and multiple-locus variable-number tandem repeat analysis (MLVA), differentiated the 89 isolates into seven pulsotypes and 15 MLVA profiles. Pulsotype Y15 and one MLVA profile (11, 7, 7, 16, 7) were predominantly found in the isolates from cholera outbreaks in Mandalay, 2015. Pulsotypes Y11, Y12, and Y15 with some MLVA profiles were detected in the isolates from two remote areas, Mandalay and Yangon, with temporal changes. These data suggested that cholera spread from the seaside to the inland area in Myanmar.

Cholera in the United States, 1965-1991. Risks at home and abroad.

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Weber, J T; Levine, W C; Hopkins, D P; Tauxe, R V

1994-03-14

To assess risks for cholera in the United States. Review of published reports of cholera outbreaks and sporadic cases and Centers for Disease Control and Prevention (CDC) memoranda and laboratory reports. Persons with symptomatic laboratory-diagnosed cholera treated in the United States and territories. From 1965 through 1991, 136 cases of cholera were reported. Fifty-three percent of the patients were hospitalized and three persons died (case-fatality rate, 0.02). Ninety-three infections were acquired in the United States and 42 overseas; for one case the source was unknown. Domestically acquired cholera was largely related to the endemic Gulf Coast focus of Vibrio cholerae 01 (56 cases). The major domestic food vehicle was shellfish, particularly crabs harvested from the Gulf of Mexico or nearby estuaries. In 1991, 14 (54%) of 26 domestically acquired cases were caused by food from Ecuador (n = 11) and Thailand (n = 3). During 1991, the first cases of cholera in travelers returning from South America were reported. In 1991, the rate of cholera among air travelers returning from South America was estimated as 0.3 per 100,000; among air travelers returning from Ecuador, 2.6 per 100,000. Cholera remains a small but persistent risk in the United States and for travelers. An endemic focus on the Gulf Coast, the continuing global pandemic, and the epidemic in South America make this likely to continue for years to come. Physicians should know how to diagnose and treat cholera and should report all suspected cases to their state health departments.

Cholera between 1991 and 1997 in Mexico was associated with infection by classical, El Tor, and El Tor variants of Vibrio cholerae.

Science.gov (United States)

Alam, Munirul; Nusrin, Suraia; Islam, Atiqul; Bhuiyan, Nurul A; Rahim, Niaz; Delgado, Gabriela; Morales, Rosario; Mendez, Jose Luis; Navarro, Armando; Gil, Ana I; Watanabe, Haruo; Morita, Masatomo; Nair, G Balakrish; Cravioto, Alejandro

2010-10-01

Vibrio cholerae O1 biotype El Tor (ET), the cause of the current 7th pandemic, has recently been replaced in Asia and Africa by an altered ET biotype possessing cholera toxin (CTX) of the classical (CL) biotype that originally caused the first six pandemics before becoming extinct in the 1980s. Until recently, the ET prototype was the biotype circulating in Peru; a detailed understanding of the evolutionary trend of V. cholerae causing endemic cholera in Latin America is lacking. The present retrospective microbiological, molecular, and phylogenetic study of V. cholerae isolates recovered in Mexico (n = 91; 1983 to 1997) shows the existence of the pre-1991 CL biotype and the ET and CL biotypes together with the altered ET biotype in both epidemic and endemic cholera between 1991 and 1997. According to sero- and biotyping data, the altered ET, which has shown predominance in Mexico since 1991, emerged locally from ET and CL progenitors that were found coexisting until 1997. In Latin America, ET and CL variants shared a variable number of phenotypic markers, while the altered ET strains had genes encoding the CL CTX (CTX(CL)) prophage, ctxB(CL) and rstR(CL), in addition to resident rstR(ET), as the underlying regional signature. The distinct regional fingerprints for ET in Mexico and Peru and their divergence from ET in Asia and Africa, as confirmed by subclustering patterns in a pulsed-field gel electrophoresis (NotI)-based dendrogram, suggest that the Mexico epidemic in 1991 may have been a local event and not an extension of the epidemics occurring in Asia and South America. Finally, the CL biotype reservoir in Mexico is unprecedented and must have contributed to the changing epidemiology of global cholera in ways that need to be understood.

Dealing with cholera: exclusively the domain of environmental ...

African Journals Online (AJOL)

Cholera outbreaks have a profound impact on the health and well-being of communities. Especially young children are vulnerable to the disease and schools report high absenteeism during epidemics. There is both the perception and evidence thereof, that educating communities about cholera (its prevention and ...

Epidemic Cholera and American Reform Movements in the 19th Century

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Seohyung KIM

2015-12-01

Full Text Available The 19th century was the age of great reform in American history. After constructing of the canal and railroads, the industrialization began and American society changed so rapidly. In this period, there were so many social crisis and American people tried to solve these problems within the several reform movements. These reform movements were the driving forces to control cholera during the 19th century. Cholera was the endemic disease in Bengal, India, but after the 19th century it had spread globally by the development of trade networks. The 1832 cholera in the United States was the first epidemic cholera in American history. The mortality of cholera was so high, but it was very hard to find out the cause of this fatal infectious disease. So, different social discourses happened to control epidemic cholera in the 19th century, these can be understood within the similar context of American reform movements during this period. Board of Health in New York States made a new public health act to control cholera in 1832, it was ineffective. Some people insisted that the cause of this infectious disease was the corruption of the United States. They emphasized unjust and immoral system in American society. Moral reform expanded to Nativism, because lots of Irish immigrants were the victims of cholera. So, epidemic cholera was the opportunity to spread the desire for moral reform. To control cholera in 1849, the sanitary reform in Britain had affected. The fact that it was so important to improve and maintain the water quality for the control and prevention of disease spread, the sanitary reform happened. There were two different sphere of the sanitary reform. The former was the private reform to improve sewer or privy, the latter was the public reform to build sewage facilities. The 1849 cholera had an important meaning, because the social discourse, which had emphasized the sanitation of people or home expanded to the public sphere. When cholera

[Epidemic Cholera and American Reform Movements in the 19th Century].

Science.gov (United States)

Kim, Seohyung

2015-12-01

The 19th century was the age of great reform in American history. After constructing of the canal and railroads, the industrialization began and American society changed so rapidly. In this period, there were so many social crisis and American people tried to solve these problems within the several reform movements. These reform movements were the driving forces to control cholera during the 19th century. Cholera was the endemic disease in Bengal, India, but after the 19th century it had spread globally by the development of trade networks. The 1832 cholera in the United States was the first epidemic cholera in American history. The mortality of cholera was so high, but it was very hard to find out the cause of this fatal infectious disease. So, different social discourses happened to control epidemic cholera in the 19th century, these can be understood within the similar context of American reform movements during this period. Board of Health in New York States made a new public health act to control cholera in 1832, it was ineffective. Some people insisted that the cause of this infectious disease was the corruption of the United States. They emphasized unjust and immoral system in American society. Moral reform expanded to Nativism, because lots of Irish immigrants were the victims of cholera. So, epidemic cholera was the opportunity to spread the desire for moral reform. To control cholera in 1849, the sanitary reform in Britain had affected. The fact that it was so important to improve and maintain the water quality for the control and prevention of disease spread, the sanitary reform happened. There were two different sphere of the sanitary reform. The former was the private reform to improve sewer or privy, the latter was the public reform to build sewage facilities. The 1849 cholera had an important meaning, because the social discourse, which had emphasized the sanitation of people or home expanded to the public sphere. When cholera broke out in 1866 again

Epidemiology, determinants and dynamics of cholera in pakistan: gaps and prospects for future research

International Nuclear Information System (INIS)

Naseer, M.; Jamali, T.

2014-01-01

Cholera is one of the notifiable endemic diseases in Pakistan, but the reporting of cholera cases is still unsatisfactory. Most of the diagnosed cases are never reported to the relevant authorities. In the year 1993 - 2005, the country did not report any single case of cholera to the WHO. The objectives of this review were to understand the epidemiology and to identify the possible determinants of cholera infection in Pakistan. Medscape, Medline, PakMedinet and PubMed, was searched, using key words, epidemiology and determinants of cholera infection in Pakistan during 1995 - 2010. Morbidity and mortality due to cholera infection during 1995 - 2010, without any language restriction. Out of 27 articles published between 1995 - 2010, 17 articles were included in the review. Vibrio cholerae O139 identified as a major cause of infection in older age group, while O1 biotype of cholera as a predominant cause of cholera among young individuals. Mainly reported determinants of cholera in Pakistan include poor sanitation and hygiene practices, increased population density in urban areas, leading to rapid and unplanned urbanization of the major cities and climate change due to increased environmental pollution in Pakistan are plausible factors for endemicity of cholera in Pakistan. Cholera reporting as a notifiable disease to the relevant departments and timely action can prevent the risk of outbreaks. There is a need to identify specific behavioral and environmental determinants responsible for outbreaks and epidemics of cholera in Pakistan which can help to design appropriate preventive and control interventions. (author)

Epidemic Cholera in a Crowded Urban Environment, Port-au-Prince, Haiti

OpenAIRE

Dunkle, Stacie E.; Mba-Jonas, Adamma; Loharikar, Anagha; Fouché, Bernadette; Peck, Mireille; Ayers, Tracy; Archer, W. Roodly; De Rochars, Valery M. Beau; Bender, Thomas; Moffett, Daphne B.; Tappero, Jordan W.; Dahourou, George; Roels, Thierry H.; Quick, Robert

2011-01-01

We conducted a case–control study to investigate factors associated with epidemic cholera. Water treatment and handwashing may have been protective, highlighting the need for personal hygiene for cholera prevention in contaminated urban environments. We also found a diverse diet, a possible proxy for improved nutrition, was protective against cholera.

Biochemical and full genome sequence analyses of clinical Vibrio cholerae isolates in Mexico reveals the presence of novel V. cholerae strains.

Science.gov (United States)

Díaz-Quiñonez, José Alberto; Hernández-Monroy, Irma; Montes-Colima, Norma Angélica; Moreno-Pérez, María Asunción; Galicia-Nicolás, Adriana Guadalupe; López-Martínez, Irma; Ruiz-Matus, Cuitláhuac; Kuri-Morales, Pablo; Ortíz-Alcántara, Joanna María; Garcés-Ayala, Fabiola; Ramírez-González, José Ernesto

2016-05-01

The first week of September 2013, the National Epidemiological Surveillance System identified two cases of cholera in Mexico City. The cultures of both samples were confirmed as Vibrio cholerae serogroup O1, serotype Ogawa, biotype El Tor. Initial analyses by PFGE and by PCR-amplification of the virulence genes, suggested that both strains were similar, but different from those previously reported in Mexico. The following week, four more cases were identified in a community in the state of Hidalgo, located 121 km northeast of Mexico City. Thereafter a cholera outbreak started in the region of La Huasteca. Genomic analyses of the four strains obtained in this study confirmed the presence of Pathogenicity Islands VPI-1 and -2, VSP-1 and -2, and of the integrative element SXT. The genomic structure of the 4 isolates was similar to that of V. cholerae strain 2010 EL-1786, identified during the epidemic in Haiti in 2010. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Cholera in Children

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... oral antibiotic will be given. More serious skin infections and bacteria in the blood are treated in the hospital with intravenous antibiotics. In some cases, your child may require surgery to drain pus and damaged tissues. Prevention V cholerae can be killed by boiling, filtering, ...

The population structure of Vibrio cholerae from the Chandigarh Region of Northern India.

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Moataz Abd El Ghany

2014-07-01

Full Text Available Cholera infection continues to be a threat to global public health. The current cholera pandemic associated with Vibrio cholerae El Tor has now been ongoing for over half a century.Thirty-eight V. cholerae El Tor isolates associated with a cholera outbreak in 2009 from the Chandigarh region of India were characterised by a combination of microbiology, molecular typing and whole-genome sequencing. The genomic analysis indicated that two clones of V. cholera circulated in the region and caused disease during this time. These clones fell into two distinct sub-clades that map independently onto wave 3 of the phylogenetic tree of seventh pandemic V. cholerae El Tor. Sequence analyses of the cholera toxin gene, the Vibrio seventh Pandemic Island II (VSPII and SXT element correlated with this phylogenetic position of the two clades on the El Tor tree. The clade 2 isolates, characterized by a drug-resistant profile and the expression of a distinct cholera toxin, are closely related to the recent V. cholerae isolated elsewhere, including Haiti, but fell on a distinct branch of the tree, showing they were independent outbreaks. Multi-Locus Sequence Typing (MLST distinguishes two sequence types among the 38 isolates, that did not correspond to the clades defined by whole-genome sequencing. Multi-Locus Variable-length tandem-nucleotide repeat Analysis (MLVA identified 16 distinct clusters.The use of whole-genome sequencing enabled the identification of two clones of V. cholerae that circulated during the 2009 Chandigarh outbreak. These clones harboured a similar structure of ICEVchHai1 but differed mainly in the structure of CTX phage and VSPII. The limited capacity of MLST and MLVA to discriminate between the clones that circulated in the 2009 Chandigarh outbreak highlights the value of whole-genome sequencing as a route to the identification of further genetic markers to subtype V. cholerae isolates.

Toxigenic Vibrio cholerae O1 in vegetables and fish raised in wastewater irrigated fields and stabilization ponds during a non-cholera outbreak period in Morogoro, Tanzania

DEFF Research Database (Denmark)

Hounmanou, Yaovi M G; Mdegela, Robinson H; Dougnon, Tamègnon V

2016-01-01

gene (tcpA) and the haemolysin gene (hlyA). RESULTS: The prevalence of V. cholerae in wastewater, vegetables and fish was 36.7, 21.7 and 23.3 %, respectively. Two isolates from fish gills were V. cholerae O1 and tested positive for ctx and tcpA. One of these contained in addition the hlyA gene while......BACKGROUND: Cholera, one of the world's deadliest infectious diseases, remains rampant and frequent in Tanzania and thus hinders existing control measures. The present study was undertaken to evaluate the occurrence of toxigenic Vibrio cholerae O1 in wastewater, fish and vegetables during a non......-outbreak period in Morogoro, Tanzania. METHODS: From October 2014 to February 2015, 60 wastewater samples, 60 fish samples from sewage stabilization ponds and 60 wastewater irrigated vegetable samples were collected. Samples were cultured for identification of V. cholerae using conventional bacteriological...

Prevalence of Vibrio cholerae O1 serogroup in Assam, India: A hospital-based study.

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Sharma, Ajanta; Dutta, Bornali Sarmah; Rasul, Elmy Samsun; Barkataki, Dipa; Saikia, Anjanamoyee; Hazarika, Naba Kumar

2017-09-01

Although cholera remains to be an important public health problem, studies on reliable population-based estimates of laboratory confirmed cholera in endemic areas are limited worldwide. The aim of this hospital-based study was to evaluate the prevalence of Vibrio cholerae serogroup in Assam, India, during 2003-2013. Stool samples/rectal swabs were collected from acute watery diarrhoea (AWD) cases during 2003-2013 and processed by standard microbiological procedures. Antibiotic sensitivity test was done following the Clinical and Laboratory Standards Institute guidelines. Year-wise epidemiological trend of cholera was analyzed. Cholera contributed to 3.93 per cent of AWD cases. In Assam, cholera was found to be more prevalent in the rural areas (6.7%) followed by the tea gardens (5.06%), urban slum (1.9%) and urban areas (1.4%). Highest proportion of cholera (13.7%) was observed in 0-10 yr age group. Of them, 11.5 per cent belonged to 0-5 yr age group. V. cholerae O1 El Tor serotype Ogawa was the predominant isolate. Multiple drug-resistant isolates of V. cholerae O1 Ogawa were reported in the study. Emergence of resistance amongst V. cholerae towards many antibiotics is a matter of concern. Hence, continuous surveillance for diarrhoeal disorders is necessary to control the future outbreaks of cholera in this region.

Cholera in Thomas Mann's Death in Venice.

Science.gov (United States)

Rütten, Thomas

2009-01-01

The article sets the cholera motif in Thomas Mann's famous novella Death in Venice against the historical context from which it partially originates. It is shown that this motif, while undoubtedly appropriated to serve Mann's own poetic ends, has a solid grounding in historical and autobiographical fact, thus blurring the boundaries between fact and fiction. The article illustrates the verifiable events of the outbreak of the Venetian cholera epidemic in May 1911, which Mann partly witnessed himself, during a holiday trip to Brioni and Venice, and partly heard and read about. It is established that Thomas Mann's account of the cholera in Venice in his novella is characterised by a rare and almost preternatural insightfulness into an otherwise murky affair that was marked by rumours, speculations and denials.

Modelling cholera epidemics: the role of waterways, human mobility and sanitation.

Science.gov (United States)

Mari, L; Bertuzzo, E; Righetto, L; Casagrandi, R; Gatto, M; Rodriguez-Iturbe, I; Rinaldo, A

2012-02-07

We investigate the role of human mobility as a driver for long-range spreading of cholera infections, which primarily propagate through hydrologically controlled ecological corridors. Our aim is to build a spatially explicit model of a disease epidemic, which is relevant to both social and scientific issues. We present a two-layer network model that accounts for the interplay between epidemiological dynamics, hydrological transport and long-distance dissemination of the pathogen Vibrio cholerae owing to host movement, described here by means of a gravity-model approach. We test our model against epidemiological data recorded during the extensive cholera outbreak occurred in the KwaZulu-Natal province of South Africa during 2000-2001. We show that long-range human movement is fundamental in quantifying otherwise unexplained inter-catchment transport of V. cholerae, thus playing a key role in the formation of regional patterns of cholera epidemics. We also show quantitatively how heterogeneously distributed drinking water supplies and sanitation conditions may affect large-scale cholera transmission, and analyse the effects of different sanitation policies.

Modelling cholera epidemics: the role of waterways, human mobility and sanitation

Science.gov (United States)

Mari, L.; Bertuzzo, E.; Righetto, L.; Casagrandi, R.; Gatto, M.; Rodriguez-Iturbe, I.; Rinaldo, A.

2012-01-01

We investigate the role of human mobility as a driver for long-range spreading of cholera infections, which primarily propagate through hydrologically controlled ecological corridors. Our aim is to build a spatially explicit model of a disease epidemic, which is relevant to both social and scientific issues. We present a two-layer network model that accounts for the interplay between epidemiological dynamics, hydrological transport and long-distance dissemination of the pathogen Vibrio cholerae owing to host movement, described here by means of a gravity-model approach. We test our model against epidemiological data recorded during the extensive cholera outbreak occurred in the KwaZulu-Natal province of South Africa during 2000–2001. We show that long-range human movement is fundamental in quantifying otherwise unexplained inter-catchment transport of V. cholerae, thus playing a key role in the formation of regional patterns of cholera epidemics. We also show quantitatively how heterogeneously distributed drinking water supplies and sanitation conditions may affect large-scale cholera transmission, and analyse the effects of different sanitation policies. PMID:21752809

Antimicrobial Resistance Risks of Cholera Prophylaxis for United Nations Peacekeepers.

Science.gov (United States)

Kunkel, Amber; Lewnard, Joseph A; Pitzer, Virginia E; Cohen, Ted

2017-08-01

More than 5 years after a United Nations peacekeeping battalion introduced cholera to Haiti, over 150,000 peacekeepers continue to be deployed annually from countries where cholera is endemic. The United Nations has thus far declined to provide antimicrobial chemoprophylaxis to peacekeepers, a policy based largely on concerns that the risks of drug resistance generation and spread would outweigh the potential benefits of preventing future cholera importations. In this study, we sought to better understand the relative benefits and risks of cholera chemoprophylaxis for peacekeepers in terms of antibiotic resistance. Using a stochastic model to quantify the potential impact of chemoprophylaxis on importation and transmission of drug-resistant and drug-sensitive Vibrio cholerae , we found that chemoprophylaxis would decrease the probability of cholera importation but would increase the expected number of drug-resistant infections if an importation event were to occur. Despite this potential increase, we found that at least 10 drug-sensitive infections would likely be averted per excess drug-resistant infection under a wide range of assumptions about the underlying prevalence of drug resistance and risk of acquired resistance. Given these findings, policymakers should reconsider whether the potential resistance risks of providing antimicrobial chemoprophylaxis to peacekeepers are sufficient to outweigh the anticipated benefits. Copyright © 2017 American Society for Microbiology.

A brief history of vaccines: smallpox to the present.

Science.gov (United States)

Hsu, Jennifer L

2013-01-01

Modern vaccine history began in the late 18th century with the discovery of smallpox immunization by Edward Jenner. This pivotal step led to substantial progress in prevention of infectious diseases with inactivated vaccines for multiple infectious diseases, including typhoid, plague and cholera. Each advance produced significant decreases in infection-associated morbidity and mortality, thus shaping our modem cultures. As knowledge of microbiology and immunology grew through the 20th century, techniques were developed for cell culture of viruses. This allowed for rapid advances in prevention of polio, varicella, influenza and others. Finally, recent research has led to development of alternative vaccine strategies through use of vectored antigens, pathogen subunits (purified proteins or polysaccharides) or genetically engineered antigens. As the science of vaccinology continues to rapidly evolve, knowledge of the past creates added emphasis on the importance of developing safe and effective strategies for infectious disease prevention in the 21st century.

Satellite Based Assessment of Hydroclimatic Conditions Related to Cholera in Zimbabwe.

Directory of Open Access Journals (Sweden)

Antarpreet Jutla

Full Text Available Cholera, an infectious diarrheal disease, has been shown to be associated with large scale hydroclimatic processes. The sudden and sporadic occurrence of epidemic cholera is linked with high mortality rates, in part, due to uncertainty in timing and location of outbreaks. Improved understanding of the relationship between pathogenic abundance and climatic processes allows prediction of disease outbreak to be an achievable goal. In this study, we show association of large scale hydroclimatic processes with the cholera epidemic in Zimbabwe reported to have begun in Chitungwiza, a city in Mashonaland East province, in August, 2008.Climatic factors in the region were found to be associated with triggering cholera outbreak and are shown to be related to anomalies of temperature and precipitation, validating the hypothesis that poor conditions of sanitation, coupled with elevated temperatures, and followed by heavy rainfall can initiate outbreaks of cholera. Spatial estimation by satellite of precipitation and global gridded air temperature captured sensitivities in hydroclimatic conditions that permitted identification of the location in the region where the disease outbreak began.Satellite derived hydroclimatic processes can be used to capture environmental conditions related to epidemic cholera, as occurred in Zimbabwe, thereby providing an early warning system. Since cholera cannot be eradicated because the causative agent, Vibrio cholerae, is autochthonous to the aquatic environment, prediction of conditions favorable for its growth and estimation of risks of triggering the disease in a given population can be used to alert responders, potentially decreasing infection and saving lives.

[Cholera in 1831. Challenges for science and the federal government].

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Stamm-Kuhlmann, T

1989-01-01

The peak of the first great cholera pandemic in 1831 fomented the controversy among contagionists and non-contagionists. In the following year the public debate centered around the correct interpretation of the recent experiences with cholera. The central government of the bureaucratic-absolutist monarchy in Prussia adhered to a firmly contagionist interpretation of the disease and reacted accordingly. Local authorities in Königsberg and Berlin and the bourgeoisie in the merchant city of Danzig, however, stressed the destructive consequences of the cordon system. They considered the results of an interruption in trade and industry to be worse than the damage inflicted by the epidemic. The summer of 1831 demonstrated that cholera could not be stopped by the cordons, but the King's medical advisors nevertheless remained contagionists. Non-contagionists put forward several hypotheses to explain the origin and the spreading of cholera, mainly "miasma" theory and the Hippocratic paradigm of "epidemic constitution". The correlation between poverty and disease, however, was widely noticed. Physicians in the city of Bremen pointed to the necessity of sanitary precautions to be taken in cholera-free periods. On the other hand, many "honest" citizens believed that individuals with a "dissolute" conduct of life were more at risk to contract cholera than others. Instead of costly sanitary policies, the well-to-do classes preferred to identify the defense against cholera with the segregation of unwelcome elements of society. The article is based on hitherto unpublished sources from the former Prussian State Archives at Merseburg, GDR, and the State Archive of the Hanseatic City of Bremen.

Identification of burden hotspots and risk factors for cholera in India: An observational study.

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Ali, Mohammad; Sen Gupta, Sanjukta; Arora, Nisha; Khasnobis, Pradeep; Venkatesh, Srinivas; Sur, Dipika; Nair, Gopinath B; Sack, David A; Ganguly, Nirmal K

2017-01-01

Even though cholera has existed for centuries and many parts of the country have sporadic, endemic and epidemic cholera, it is still an under-recognized health problem in India. A Cholera Expert Group in the country was established to gather evidence and to prepare a road map for control of cholera in India. This paper identifies cholera burden hotspots and factors associated with an increased risk of the disease. We acquired district level data on cholera case reports of 2010-2015 from the Integrated Disease Surveillance Program. Socioeconomic characteristics and coverage of water and sanitation was obtained from the 2011 census. Spatial analysis was performed to identify cholera hotspots, and a zero-inflated Poisson regression was employed to identify the factors associated with cholera and predicted case count in the district. 27,615 cholera cases were reported during the 6-year period. Twenty-four of 36 states of India reported cholera during these years, and 13 states were classified as endemic. Of 641 districts, 78 districts in 15 states were identified as "hotspots" based on the reported cases. On the other hand, 111 districts in nine states were identified as "hotspots" from model-based predicted number of cases. The risk for cholera in a district was negatively associated with the coverage of literate persons, households using treated water source and owning mobile telephone, and positively associated with the coverage of poor sanitation and drainage conditions and urbanization level in the district. The study reaffirms that cholera continues to occur throughout a large part of India and identifies the burden hotspots and risk factors. Policymakers may use the findings of the article to develop a roadmap for prevention and control of cholera in India.

Molecular Analyses of Vibrio cholerae O1 Clinical Strains, Including New Nontoxigenic Variants Isolated in Mexico during the Cholera Epidemic Years between 1991 and 2000

OpenAIRE

Lizárraga-Partida, Leonardo; Quilici, Marie-Laure

2009-01-01

International audience; We studied the evolution of Vibrio cholerae O1 during the 1991 to 2000 cholera epidemic in Mexico by biochemical, serological, and molecular characterization of strains collected during this period. Strains were divided into toxigenic and nontoxigenic groups according to the presence or absence of genes encoding cholera toxin. As previously reported, we characterized two populations among toxigenic strains, which were present from the first year of the epidemic. BglI r...

Cholera epidemics of the past offer new insights into an old enemy

DEFF Research Database (Denmark)

Phelps, Matthew David; Linnet Perner, Mads; Pitzer, Virginia E

2018-01-01

BACKGROUND: Although cholera is considered the quintessential long-cycle waterborne disease, studies have emphasized the existence of short-cycle (food, household) transmission. We investigated singular Danish cholera epidemics (1853) to elucidate epidemiological parameters and modes of spread...... intervals. RESULTS: Epidemics were seeded by travelers from cholera-affected cities; initial transmission chains involving household members and caretakers ensued. Cholera killed 3.4-8.9% of the populations, with highest mortality among seniors (16%) and lowest in children (2.7%). Transmissibility (R0...

Detection of viable toxigenic Vibrio cholerae and virulent Shigella ...

African Journals Online (AJOL)

. cholerae and the invasion plasmid antigen gene (ipaH) of virulent Shigella spp., was performed and the PCR products were visualised by agarose gel electrophoresis. The assay allowed the detection of as few as 1 cfu/100 ml of V. cholerae ...

Small-molecule inhibitors of toxT expression in Vibrio cholerae.

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Anthouard, Rebecca; DiRita, Victor J

2013-08-06

Vibrio cholerae, a Gram-negative bacterium, infects humans and causes cholera, a severe disease characterized by vomiting and diarrhea. These symptoms are primarily caused by cholera toxin (CT), whose production by V. cholerae is tightly regulated by the virulence cascade. In this study, we designed and carried out a high-throughput chemical genetic screen to identify inhibitors of the virulence cascade. We identified three compounds, which we named toxtazin A and toxtazin B and B', representing two novel classes of toxT transcription inhibitors. All three compounds reduce production of both CT and the toxin-coregulated pilus (TCP), an important colonization factor. We present evidence that toxtazin A works at the level of the toxT promoter and that toxtazins B and B' work at the level of the tcpP promoter. Treatment with toxtazin B results in a 100-fold reduction in colonization in an infant mouse model of infection, though toxtazin A did not reduce colonization at the concentrations tested. These results add to the growing body of literature indicating that small-molecule inhibitors of virulence genes could be developed to treat infections, as alternatives to antibiotics become increasingly needed. V. cholerae caused more than 580,000 infections worldwide in 2011 alone (WHO, Wkly. Epidemiol. Rec. 87:289-304, 2012). Cholera is treated with an oral rehydration therapy consisting of water, glucose, and electrolytes. However, as V. cholerae is transmitted via contaminated water, treatment can be difficult for communities whose water source is contaminated. In this study, we address the need for new therapeutic approaches by targeting the production of the main virulence factor, cholera toxin (CT). The high-throughput screen presented here led to the identification of two novel classes of inhibitors of the virulence cascade in V. cholerae, toxtazin A and toxtazins B and B'. We demonstrate that (i) small-molecule inhibitors of virulence gene production can be

[The role of food in cholera transmission].

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Dobosch, D; Gomez Zavaglia, A; Kuljich, A

1995-01-01

The spreading of cholera, from Peru to other Latinoamerican countries in 1991, raised questions regarding food safety, food transportation and handling. Control, prevention and risks implied in food import-export were also matters of concern. We deemed it interesting to determine the viability of Vibrio cholerae in wide consumption food locally. Selected food had different intrinsic characteristics such as: acidity (pH), water activity (aw), chemical composition, indigenous flora and other biologic and physic parameters. Twenty food products were contaminated with V. cholerae O1, Ogawa, toxigenic and not toxigenic strains: yoghurt, cream cheese, apricot marmelade, hip rose marmelade, mayonnaise, italian pasta for "empanadas", "dulce de leche", meat sausage, meat and spinach ravioli, margarine, milk dessert (made with cocoa, milk confiture, starch and additives), lettuce, tuna fish, ricotta and sterilized milk. Table I shows the viability of V. cholerae in tested foods, its pH and the reasons why the experiments were ended: 75% of the products studied could tolerate the development of the microorganism for a period ranging from one day (pasta for "empanadas") to ninety days (sterilized milk). Foods with acredity higher than pH 5.5 did not favor the growth of Vibrio. When pH was neutral or slightly acid, viability persisted independently from aw, microbial antagonisms and other physic, chemical or biologic parameters. Nevertheless, other factors such as: surface adherence, amino acids, magnesium and environmental influences not yet well determined, could eventually modify the persistence of V. cholerae in food. According to this study, most food products could tolerate growth and persistence of the infectant agent, up for three months in some cases.(ABSTRACT TRUNCATED AT 250 WORDS)

USE OF MODIFIED CAMP TEST FOR PRELIMINARY NONSEROLOGIC IDENTIFICATION OF VIBRIO CHOLERAE IN STOOL SPECIMENS

Directory of Open Access Journals (Sweden)

Murad Lesmana

2012-09-01

Full Text Available Suatu modifikasi uji CAMP digunakan bersama dengan reaksi biokimiawi untuk identifikasi Vibrio cholerae pada sampel klinis. Dari 579 usap dubur penderita diare, 92 (16% memberikan hasil isolasi V. cholerae 01 biotipe El Tor dan 34 (6% V. cholerae non-01. Semua isolat V. cholerae 01 El Tor menunjukkan reaksi CAMP positif kuat dengan gambaran hemolisis sinergistik lengkap berbentuk sosis; sedangkan V. cholerae non-01 memberikan reaksi CAMP yang sempit dengan pola hemolisis menyerupai bulan sabit. Hasil uji CAMP yang dilakukan bersama dengan reaksi biokimiawi sesuai dengan metode biakan konvensional yang menyertakan tes aglutinasi dengan antiserum V. cholerae 01 untuk mengidentifikasi V. cholerae.

[Mexican phenotype and genotype Vibrio cholerae 01].

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Giono, S; Gutiérrez Cogno, L; Rodríguez Angeles, G; del Rio Zolezzi, A; Valdespino González, J L; Sepúlveda Amor, J

1995-01-01

This paper presents the phenotypical and genotypical characterization of 26922 Vibrio cholerae 01 strains isolated in Mexico from 1991 to 1993. All strains isolated were El Tor biovar. Strains were sensitive to antibiotics excluding furazolidone, streptomycin and sulfisoxasole to which we found resistance in 97% and we are using this characteristic as epidemiological markers. We detected a marked change in frequency of Inaba serotype from 1991, when it was dominant, with 99.5%, until 1992 when Ogawa serotype turned to be dominant with 95% of isolates. All Vibrio cholerae 01 strains, except one Ogawa strain, were to igenic, and V. choleraeno 01 were not toxigenic by ELISA, PCR and cell culture tests. Dominant ribotype was 5, but we found some strains with 6a pattern and two with ribotype 12. We are searching for ribotype 2 among hemolytic strains in order to learn if there is any relation to Gulf Coast strains prevalent in the USA, but until now we have not found any V. cholerae ribotype 2 in our isolates. Even if rapid tests are recommended for immediate diagnosis of cholera, it is necessary to continue bacterial isolation in order to have strains for phenotyping and genotyping studies that may support epidemiological analysis.

Top Down Tandem Mass Spectrometric Analysis of a Chemically Modified Rough-Type Lipopolysaccharide Vaccine Candidate

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