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The authors present a nonparametric method for estimating vaccine efficacy as a smooth function of time from vaccine trials. Use of the method requires a minimum of assumptions. Estimation is based on the smoothed case hazard rate ratio comparing the vaccinated with the unvaccinated. The estimation procedure allows investigators to assess time-varying changes in vaccine-induced protection, such as those produced by waning and boosting. The authors use the method to reanalyze data from a vaccine trial of two cholera vaccines in rural Bangladesh. This analysis reveals the differential protection and waning effects for the vaccines as a function of biotype and age.

The current global initiative to end Cholera by 2030 emphasizes the use of oral cholera vaccine (OCV) combined with feasible household Water-Sanitation-Hygiene (WASH) interventions. However, little is known about how improved WASH practices and behaviors and OCV interact to reduce the risk of cholera. We reanalyzed two arms of a cluster-randomized trial in urban Bangladesh, to evaluate the effectiveness of OCV given as a 2-dose regimen. One arm (30 clusters, n = 94,675) was randomized to vaccination of persons aged one year and older with OCV, and the other arm (30 clusters, n = 80,056) to no intervention. We evaluated the prevention of cholera by household WASH, classified at baseline using a previously validated rule, and OCV over 2 years of follow-up. When analyzed by assignment to OCV clusters rather than receipt of OCV, in comparison to persons living in "Not Better WASH" households in the control clusters, reduction of severe cholera (the primary outcome) was similar for persons in "Not Better WASH" households in vaccine clusters (46%, 95% CI:24,62), for persons in "Better WASH" households in the control clusters (48%, 95% CI:25,64), and for persons in "Better WASH" households in the vaccine clusters (48%, 95% CI:16,67). In contrast, when analyzed by actual receipt of a complete OCV regimen, , in comparison to persons in "Not Better WASH" households in the control clusters, protection against severe cholera increased steadily from 39% (95% CI:13,58) in residents of "Better WASH" households in the control clusters to 57% (95% CI:35,72) in vaccinated persons in "Not Better WASH" households to 63% (95% CI:21,83) in vaccinated persons in "Better WASH" households. This analysis suggests that improved household WASH and OCV received may interact to provide greater protection against cholera. However, the divergence between findings related to intent to vaccinate versus those pertaining to actual receipt of OCV underscores the need for further research on this topic., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Over 700,000 Myanmar nationals known as the 'Rohingyas' fled into Cox's Bazar, Bangladesh, in late 2017. Due to this huge displacement into unhygienic areas, these people became vulnerable to communicable diseases including cholera. Assessing the risk, the Government of Bangladesh (GoB), with the help of the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B) and other international partners, decided to take preventive measures, one of which is the execution of oral cholera vaccination (OCV) campaigns. This paper describes the implementation and delivery of OCV campaigns during humanitarian crises in Bangladesh. Methods: Seven rounds of OCV campaigns were conducted between October 2017 and December 2021. The OCV campaigns were conducted by applying different strategies. Results: Approximately 900,000 Rohingya Myanmar nationals (RMNs) and the host population (amounting to 528,297) received OCV across seven campaigns. In total, 4,661,187 doses of OCVs were administered, which included 765,499 doses for RMNs, and 895,688 doses for the host community. The vaccine was well accepted, and as a result, a high level of coverage was achieved, ranging from 87% to 108% in different campaigns. Conclusions: After successful pre-emptive campaigns in Cox's Bazar humanitarian camps, no cholera outbreaks were detected either in the RMN or host communities. [ABSTRACT FROM AUTHOR]

Bangladesh remains cholera endemic with biannual seasonal peaks causing epidemics. At least 300,000 severe cases and over 4,500 deaths occur each year. The available oral cholera vaccineshave not yet been adopted for cholera control in Bangladesh due to insufficient number of doses available for endemic control. With a public private partnership, icddr,b initiated a collaboration between vaccine manufacturers in Bangladesh and abroad. A locally manufactured Oral Cholera Vaccine (OCV) named Cholvax became available for testing in Bangladesh. We evaluated the safety and immunogenicity of this locally produced Cholvax (Incepta Vaccine Ltd) inexpensive OCV comparatively to Shanchol (Shantha Biotechnics-Sanofi Pasteur) which is licensed in several countries. We conducted a randomized non-inferiority clinical trial of bivalent, killed oral whole-cell cholera vaccine Cholvax vs. Shanchol in the cholera-endemic area of Mirpur, Dhaka, among three different age cohorts (1-5, 6-17 and 18-45 years) between April 2016 and April 2017. Two vaccine doses were given at 14 days apart to 2,052 healthy participants. No vaccine-related serious adverse events were reported. There were no significant differences in the frequency of solicited (7.31% vs. 6.73%) and unsolicited (1.46% vs. 1.07%) adverse events reported between the Cholvax and Shanchol groups. Vibriocidal antibody responses among the overall population for O1 Ogawa (81% vs. 77%) and O1 Inaba (83% vs. 84%) serotypes showed that Cholvax was non-inferior to Shanchol, with the non-inferiority margin of -10%. For O1 Inaba, GMT was 462.60 (Test group), 450.84 (Comparator group) with GMR 1.02(95% CI: 0.92, 1.13). For O1 Ogawa, GMT was 419.64 (Test group), 387.22 (Comparator group) with GMR 1.12 (95% CI: 1.02, 1.23). Cholvax was safe and non-inferior to Shanchol in terms of immunogenicity in the different age groups. These results support public use of Cholvax to contribute for reduction of the cholera burden in Bangladesh. ClinicalTrials.gov number: NCT027425581., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In Bangladesh and West Bengal cholera is seasonal, transmission occurs consistently annually. By contrast, in most African countries, cholera has inconsistent seasonal patterns and long periods without obvious transmission. Transmission patterns in Africa occur during intermittent outbreaks followed by elimination of that genetic lineage. Later another outbreak may occur because of reintroduction of new or evolved lineages from adjacent areas, often by human travelers. These then subsequently undergo subsequent elimination. The frequent elimination and reintroduction has several implications when planning for cholera's elimination including: a) reconsidering concepts of definition of elimination, b) stress on rapid detection and response to outbreaks, c) more effective use of oral cholera vaccine and WASH, d) need to readjust estimates of disease burden for Africa, e) re-examination of water as a reservoir for maintaining endemicity in Africa. This paper reviews major features of cholera's epidemiology in African countries which appear different from the Ganges Delta., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

This study is to examine the cost-effectiveness of deployment strategies of oral cholera vaccines (OCVs) in controlling cholera in Bangladesh. We developed a dynamic compartment model to simulate costs and health outcomes for 12 years for four OCVs deployment scenarios: (1) vaccination of children aged one and above with two doses of OCVs, (2) vaccination of population aged 5 and above with a single dose of OCVs, (3) vaccination of children aged 1-4 with two doses of OCVs; and (4) combined strategy of (2) and (3). We obtained all parameters from the literature and performed a cost-effectiveness analysis from both health systems and societal perspectives, in comparison with the base scenario of no vaccination.The incremental cost-effectiveness ratios (ICERs) for the four strategies from the societal perspective were $2,236, $2,250, $1,109, and $2,112 per DALY averted, respectively, with herd immunity being considered. Without herd immunity, the ICERs increased substantially for all four scenarios except for the scenario that vaccinates children aged 1-4 only. The major determinants of ICERs were the case fatality rate and the incidence of cholera, as well as the efficacy of OCVs. The projection period and frequency of administering OCVs would also affect the cost-effectiveness of OCVs. With the cut-off of 1.5 times gross domestic product per capita, the four OCVs deployment strategies are cost-effective. The combined strategy is more efficient than the strategy of vaccinating the population aged one and above with two doses of OCVs and could be considered in the resource-limited settings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Vaccine herd protection assessed in a cluster-randomized trial (CRT) may be masked by disease transmission into the cluster from outside. However, herd effects can be unmasked using a 'fried-egg' approach whereby the analysis, restricted to the innermost households of clusters, 'yolk', creates an insulating 'egg-white' periphery. This approach has been demonstrated to unmask vaccine herd protection in reanalyses of cholera and typhoid vaccine CRTs. We applied this approach to an earlier CRT in Bangladesh of rotavirus vaccine (RV) whose overall analysis had failed to detect herd protection. Herein we present the results of this analysis., Methods: In the study area, infants in 142 villages were randomized to receive two doses of RV with routine EPI vaccines (RV villages) or only EPI vaccines (non-RV villages). We analyzed RV protection against acute rotavirus diarrhoea for the entire cluster (P100) and P75, P50, P25 clusters, representing 75%, 50% and 25% of the innermost households for each cluster, respectively., Results: During 2 years of follow-up, there was evidence of 27% overall (95 %CI: 7, 43) and 42% total protection (95 %CI: 23, 56) in the P100 cluster, but it did not increase when moved in smaller yolks. There was no evidence of indirect vaccine protection in the yolks at any cluster size., Conclusion: Our reanalysis of the CRT using the fried- egg approach did not detect RV herd protection. Whether these findings reflect a true inability of the RV to confer herd protection in this setting, or are due to limitations of the approach, requires further study., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The World Health Organization (WHO) recommends the use of oral cholera vaccines (OCVs) as part of an integrated control program, both in highly endemic settings and during cholera epidemics. The available and internationally recommended WHO-prequalified OCVs (Dukoral, Shanchol, Euvichol) contain multiple heat and formalin-killed V. cholerae strains of Inaba and Ogawa serotypes. MSD Wellcome Trust Hilleman Laboratories Pvt. Ltd. in technical collaboration with University of Gothenburg, Sweden has developed a new single strain OCV, Hillchol. This vaccine consists of formaldehyde-inactivated whole cell El Tor V. cholerae O1 bacteria engineered into the Hikojima serotype for stable expression of both the Ogawa (AB) and Inaba (AC) LPS antigens on the bacterial surface. We evaluated the safety and immunogenicity of this novel and potentially much less expensive OCV in comparison with Shanchol., Methods: We conducted a randomized, non-inferiority, age-descending clinical trial of OCV (Hillchol vs. Shanchol) in the Mirpur area of Dhaka city from July 2016 to May 2017. This study was carried out in three different age cohorts (1-<5, 5-17 and ≥18 years old). Two doses of vaccine were given at 14 days intervals to 560 healthy participants., Findings: No serious adverse events were reported. There were no significant differences in the rates of adverse events between the test vaccine (Hillchol) and the comparator (Shanchol) group. Serum vibriocidal antibody responses in all age groups combined were comparable for all the O1 Ogawa (59% vs. 67%; 90% CI of difference: -14.55, -0.84) and Inaba (70% vs. 71%; 90% CI of difference: -7.24, 5.77) serotypes, showing that the Hillchol vaccine was non-inferior to Shanchol. This new vaccine was also non-inferior to Shanchol in the different age strata., Conclusion: The safety and immunogenicity profile of the new OCV Hillchol is comparable to Shanchol in persons residing in a cholera-endemic setting. ClinicalTrials.gov number: NCT02823899., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier Ltd.)

Cholera, a devastating diarrheal disease that caused several global pandemics in the last centuries, may share some similarities with the new COVID-19. Cholera has affected many populations in history and still remains a significant burden in developing countries. The main transmission route was thought to be predominantly through contaminated drinking water. However, revisiting the historical data collected during the Copenhagen 1853 cholera outbreak allowed us to re-evaluate the role of drinking-water transmission in a city-wide outbreak and reconsider some critical transmission routes, which have been neglected since the time of John Snow. Recent empirical and cohort data from Bangladesh also strengthened the dynamic potentiality of other transmission routes (food, fomite, fish, flies) for transmitting cholera. Analyzing this particular nature of the cholera disease transmission, this paper will describe how the pattern of transmission routes are similar to COVID-19 and how the method of revisiting old data can be used for further exploration of new and known diseases., (© 2021 APMIS. Published by John Wiley & Sons Ltd.)

As the world's longest running pandemic, cholera poses a substantial public health burden in Bangladesh, where human vulnerability intersects with climatic variability. Barriers to safe water and sanitation place the health of millions of Bangladeshis in jeopardy - especially those who have highly constrained choices in preventing and responding to cholera. In this paper we investigate demand for cholera prevention among residents in the Mirpur and Karail slum areas of urban Dhaka. Using survey data from 2023 households in two slum areas, we analyze responses from a contingent valuation questionnaire that elicited willingness to pay (WTP) for cholera vaccines across household members and under varying disease risk scenarios, finding higher valuation for cholera prevention for children and under scenarios of greater epidemic risk. We estimate the average WTP for a cholera vaccine for a child ranges from TK 134-167 (US$ 1.58-1.96). Consistently, respondents with prior knowledge of the cholera vaccine reported lower WTP valuations, providing suggestive evidence of concerns about vaccine effectiveness and preferences for cholera treatment over prevention. We supplement the contingent valuation analysis with cost of illness estimates from both our household sample as well as from administrative hospital records of over 34,000 cholera patients. We estimate that a household incurs costs of TK 801-922 (US$ 9.43-10.50) per episode of cholera that requires medical treatment. Taken together, these findings indicate higher WTP for cholera treatment compared to prevention, but increased interest in prevention under early warning system scenarios of high disease risk., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Cholera has been endemic in India and Bangladesh for the greater part of recorded history, giving this region the reputation of being the 'homeland of cholera'. The causative organism Vibrio cholerae O1 has been responsible for large epidemics and pandemics. Bangladesh and India have conducted several sequential studies of Oral Cholera Vaccine (OCV) to ascertain its safety, efficacy, effectiveness, field feasibility and acceptance in high-risk urban populations. The objective of this article is to illustrate the experience of OCV use in these endemic settings, its major challenges, and how policymakers can grant vaccine licenses as well as implement its use in the national immunization programme. The relevant aspects of the OCV studies, such as boosting the effect of vaccine, single-dose versus double-dose trials and thermal stability of the vaccine during delivery have generated strong evidence for recommendation of vaccine use in these settings. Studies have shown that a single dose is effective for children of five years of age and older age groups. The locally manufactured vaccine in India is thermostable and can be delivered in field settings without use of cold chain. The vaccine delivery is feasible and the protective efficacy (PE) of this vaccine above five years of age against cholera was 53-65%. Administration of an OCV boosting regimen elicits an immune response similar to those who received a two-dose vaccine five years back. OCV can be used as a preemptive measure in endemic settings, in natural calamities and during political instability when there is total disruption as well as collapse of safe water supply, sanitation and hygiene (WASH) facilities and other control measures. Clear identification of areas and target population (who will gain benefit from the OCVs) is required to be developed in endemic settings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019. Published by Elsevier Ltd.)

In the summer of 2017, an estimated 745,000 Rohingya fled to Bangladesh in what has been described as one of the largest and fastest growing refugee crises in the world. Among numerous health concerns, an outbreak of acute jaundice syndrome (AJS) was detected by the disease surveillance system in early 2018 among the refugee population. This paper describes the investigation into the increase in AJS cases, the process and results of the investigation, which were strongly suggestive of a large outbreak due to hepatitis A virus (HAV). An enhanced serological investigation was conducted between 28 February to 26 March 2018 to determine the etiologies and risk factors associated with the outbreak. A total of 275 samples were collected from 18 health facilities reporting AJS cases. Blood samples were collected from all patients fulfilling the study specific case definition and inclusion criteria, and tested for antibody responses using enzyme-linked immunosorbent assay (ELISA). Out of the 275 samples, 206 were positive for one of the agents tested. The laboratory results confirmed multiple etiologies including 154 (56%) samples tested positive for hepatitis A, 1 (0.4%) positive for hepatitis E, 36 (13%) positive for hepatitis B, 25 (9%) positive for hepatitis C, and 14 (5%) positive for leptospirosis. Among all specimens tested 24 (9%) showed evidence of co-infections with multiple etiologies. Hepatitis A and E are commonly found in refugee camps and have similar clinical presentations. In the absence of robust testing capacity when the epidemic was identified through syndromic reporting, a particular concern was that of a hepatitis E outbreak, for which immunity tends to be limited, and which may be particularly severe among pregnant women. This report highlights the challenges of identifying causative agents in such settings and the resources required to do so. Results from the month-long enhanced investigation did not point out widespread hepatitis E virus (HEV) transmission, but instead strongly suggested a large-scale hepatitis A outbreak of milder consequences, and highlighted a number of other concomitant causes of AJS (acute hepatitis B, hepatitis C, Leptospirosis), albeit most likely at sporadic level. Results strengthen the need for further water and sanitation interventions and are a stark reminder of the risk of other epidemics transmitted through similar routes in such settings, particularly dysentery and cholera. It also highlights the need to ensure clinical management capacity for potentially chronic conditions in this vulnerable population. [ABSTRACT FROM AUTHOR]

Background: Cholera remains an important public health problem in major cities in Bangladesh, especially in slum areas. In response to growing interest among local policymakers to control this disease, this study estimated the impact and cost-effectiveness of preventive cholera vaccination over a ten-year period in a high-risk slum population in Dhaka to inform decisions about the use of oral cholera vaccines as a key tool in reducing cholera risk in such populations., Methodology/principal Findings: Assuming use of a two-dose killed whole-cell oral cholera vaccine to be produced locally, the number of cholera cases and deaths averted was estimated for three target group options (1-4 year olds, 1-14 year olds, and all persons 1+), using cholera incidence data from Dhaka, estimates of vaccination coverage rates from the literature, and a dynamic model of cholera transmission based on data from Matlab, which incorporates herd effects. Local estimates of vaccination costs minus savings in treatment costs, were used to obtain incremental cost-effectiveness ratios for one- and ten-dose vial sizes. Vaccinating 1-14 year olds every three years, combined with annual routine vaccination of children, would be the most cost-effective strategy, reducing incidence in this population by 45% (assuming 10% annual migration), and costing was $823 (2015 USD) for single dose vials and $591 (2015 USD) for ten-dose vials per disability-adjusted life year (DALY) averted. Vaccinating all ages one year and above would reduce incidence by >90%, but would be 50% less cost-effective ($894-1,234/DALY averted). Limiting vaccination to 1-4 year olds would be the least cost-effective strategy (preventing only 7% of cases and costing $1,276-$1,731/DALY averted), due to the limited herd effects of vaccinating this small population and the lower vaccine efficacy in this age group., Conclusions/significance: Providing cholera vaccine to slum populations in Dhaka through periodic vaccination campaigns would significantly reduce cholera incidence and inequities, and be especially cost-effective if all 1-14 year olds are targeted., Competing Interests: The cost analysis under “The impact and cost-effectiveness of controlling cholera through the use of oral cholera vaccines in urban Bangladesh: A disease modeling and economic analysis” was undertaken with Levin and Morgan, a commercial entity. Levin and Morgan contributed to the analysis and writing in the economic analysis component of this paper. AL is also employed by Levin and Morgan.

In Bangladesh, cholera poses a significant environmental health risk. Yet, information about the severity of cholera risk is limited as risk varies over time and changing weather patterns make historical cholera risk predictions less reliable. In this paper, we examine how households use geographically and temporally personalized cholera risk predictions to inform their beliefs and behaviors related to cholera and its aversion. We estimate how access to a smartphone application containing monthly cholera risk predictions unique to a user's home location affects households' beliefs about their cholera risk and their water use and hygiene behaviors. We find that households with access to this application feel more equipped to respond to environmental and health risks and reduce their reliance on surface water for bathing and washing – a common cholera transmission pathway. We do not find that households invest additional resources into drinking water treatment, nor do we find reductions in self-reported cholera incidence. Further, households with a static, non-personalized app containing public health information about cholera exhibit similar patterns of beliefs updating. Taken together, our results suggest that access to risk information can help households make safer water choices, yet improving design and credibility remain important dimensions for increasing application usability. • Satellite observations provide improved information for cholera risk. • Households in rural Bangladesh find improved information for cholera risk valuable. • Dynamic, personalized cholera risk information can change household water behaviors. • Households with a cholera early warning system reduce reliance on surface water. • Early warning system design affects sustained application use. [ABSTRACT FROM AUTHOR]

Background: In Bangladesh, pharmacy-purchased oral rehydration solution (ORS) is often used to treat diarrhea, including cholera. Over-the-counter sales have been used for epidemiologic surveillance in the past, but rarely, if ever, in low-income countries. With few early indicators for cholera outbreaks in endemic areas, diarrhea-related product sales may serve as a useful surveillance tool., Methodology/principal Findings: We tracked daily ORS sales at 50 pharmacies and drug-sellers in an urban Bangladesh community of 129,000 for 6-months while simultaneously conducting surveillance for diarrhea hospitalizations among residents. We developed a mobile phone based system to track the sales of ORS and deployed it in parallel with a paper-based system. Our objectives were to determine if the mobile phone system was practical and acceptable to pharmacists and drug sellers, whether data were reported accurately compared to a paper-based system, and whether ORS sales were associated with future incidence of cholera hospitalizations within the community. We recorded 47,215 customers purchasing ORS, and 315 hospitalized diarrhea cases, 22% of which had culture-confirmed cholera. ORS sales and diarrhea incidence were independently associated with the mean daily temperature; therefore both unadjusted and adjusted models were explored. Through unadjusted cross-correlation statistics and generalized linear models, we found increases in ORS sales were significantly associated with increases in hospitalized diarrhea cases up to 9-days later and hospitalized cholera cases up to one day later. After adjusting for mean daily temperature, ORS was significantly associated with hospitalized diarrhea two days later and hospitalized cholera one day later., Conclusions/significance: Pharmacy sales data may serve as a feasible and useful surveillance tool. Given the relatively short lagged correlation between ORS sales and diarrhea, rapid and accurate sales data are key. More work is needed in creating actionable algorithms that make use of this data and in understanding the generalizability of our findings to other settings.

We build a new dataset covering 90 years of Cholera spreading in Hindustan from 1814 to 1904. We gather data from a collection of primary sources issued from medical reports. We propose a harmonization procedure to make these data comparable and corresponding to the current borders of India, Pakistan, Nepal, and Bangladesh. Our methodology is corroborated when comparing our newly produced data with other accounts, in particular Roger (1926)'s estimations. It opens the door to research aiming at estimating the effect of the successive waves of Cholera on the economic, social and epidemiological dynamics of the region. [ABSTRACT FROM AUTHOR]

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.

This paper identifies groups vulnerable to the effect of flooding on hospital visits due to diarrhoea during and after a flood event in 1998 in Dhaka, Bangladesh. The number of observed cases of cholera and non-cholera diarrhoea per week was compared to expected normal numbers during the flood and post-flood periods, obtained as the season-specific average over the two preceding and subsequent years using Poisson generalised linear models. The expected number of diarrhoea cases was estimated in separate models for each category of potential modifying factors: sex, age, socio-economic status and hygiene and sanitation practices. During the flood, the number of cholera and non-cholera diarrhoea cases was almost six and two times higher than expected, respectively. In the post-flood period, the risk of non-cholera diarrhoea was significantly higher for those with lower educational level, living in a household with a nonconcrete roof, drinking tube-well water (vs. tap water), using a distant water source and unsanitary toilets. The risk for cholera was significantly higher for those drinking tube-well water and those using unsanitary toilets. This study confirms that low socio-economic groups and poor hygiene and sanitation groups were most vulnerable to flood-related diarrhoea.

Background: Disease maps can serve to display incidence rates geographically, to inform on public health provision about the success or failure of interventions, and to make hypothesis or to provide evidences concerning disease etiology. Poisson kriging was recently introduced to filter the noise attached to rates recorded over sparsely populated administrative units. Its benefit over simple population-weighted averages and empirical Bayesian smoothers was demonstrated by simulation studies using county-level cancer mortality rates. This paper presents the first application of Poisson kriging to the spatial interpolation of local disease rates, resulting in continuous maps of disease rate estimates and the associated prediction variance. The methodology is illustrated using cholera and dysentery data collected in a cholera endemic area (Matlab) of Bangladesh., Results: The spatial analysis was confined to patrilineally-related clusters of households, known as baris, located within 9 kilometers from the Matlab hospital to avoid underestimating the risk of disease incidence, since patients far away from the medical facilities are less likely to travel. Semivariogram models reveal a range of autocorrelation of 1.1 km for dysentery and 0.37 km for cholera. This result translates into a cholera risk map that is patchier than the dysentery map that shows a large zone of high incidence in the south-central part of the study area, which is quasi-urban. On both maps, lower risk values are found in the Northern part of the study area, which is also the most distant from the Matlab hospital. The weaker spatial continuity of cholera versus dysentery incidence rates resulted in larger kriging variance across the study area., Conclusion: The approach presented in this paper enables researchers to incorporate the pattern of spatial dependence of incidence rates into the mapping of risk values and the quantification of the associated uncertainty. Differences in spatial patterns, in particular the range of spatial autocorrelation, reflect differences in the mode of transmission of cholera and dysentery. Our risk maps for cholera and dysentery incidences should help identifying putative factors of increased disease incidence, leading to more effective prevention and remedial actions in endemic areas.

Background: Developing countries in South Asia, such as Bangladesh, bear a disproportionate burden of diarrhoeal diseases such as Cholera, Typhoid and Paratyphoid. These seem to be aggravated by a number of social and environmental factors such as lack of access to safe drinking water, overcrowdedness and poor hygiene brought about by poverty. Some socioeconomic data can be obtained from census data whilst others are more difficult to elucidate. This study considers a range of both census data and spatial data from other sources, including remote sensing, as potential predictors of typhoid risk. Typhoid data are aggregated from hospital admission records for the period from 2005 to 2009. The spatial and statistical structures of the data are analysed and Principal Axis Factoring is used to reduce the degree of co-linearity in the data. The resulting factors are combined into a Quality of Life index, which in turn is used in a regression model of typhoid occurrence and risk. Results: The three Principal Factors used together explain 87% of the variance in the initial candidate predictors, which eminently qualifies them for use as a set of uncorrelated explanatory variables in a linear regression model. Initial regression result using Ordinary Least Squares (OLS) were disappointing, this was explainable by analysis of the spatial autocorrelation inherent in the Principal factors. The use of Geographically Weighted Regression caused a considerable increase in the predictive power of regressions based on these factors. The best prediction, determined by analysis of the Akaike Information Criterion (AIC) was found when the three factors were combined into a quality of life index, using a method previously published by others, and had a coefficient of determination of 73%. Conclusions: The typhoid occurrence/risk prediction equation was used to develop the first risk map showing areas of Dhaka Metropolitan Area whose inhabitants are at greater or lesser risk of typhoid infection. This, coupled with seasonal information on typhoid incidence also reported in this paper, has the potential to advise public health professionals on developing prevention strategies such as targeted vaccination. [ABSTRACT FROM AUTHOR]

There has been little evidence of a decline in the global burden of cholera in recent years as the number of cholera cases reported to WHO continues to rise. Cholera remains a global threat to public health and a key indicator of lack of socioeconomic development. Overall socioeconomic development is the ultimate solution for control of cholera as evidenced in developed countries. However, most research has focused on cross-county comparisons so that the role of individual- or small area-level socioeconomic status (SES) in cholera dynamics has not been carefully studied. Reported cases of cholera in Matlab, Bangladesh have fluctuated greatly over time and epidemic outbreaks of cholera continue, most recently with the introduction of a new serotype into the region. The wealth of longitudinal data on the population of Matlab provides a unique opportunity to explore the impact of socioeconomic status and other demographic characteristics on the long-term temporal dynamics of cholera in the region. In this population-based study we examine which factors impact the initial number of cholera cases in a bari at the beginning of the 0139 epidemic and the factors impacting the number of cases over time. Cholera data were derived from the ICDDR,B health records and linked to socioeconomic and geographic data collected as part of the Matlab Health and Demographic Surveillance System. Longitudinal zero-inflated Poisson (ZIP) multilevel regression models are used to examine the impact of environmental and socio-demographic factors on cholera counts across baris. Results indicate that baris with a high socioeconomic status had lower initial rates of cholera at the beginning of the 0139 epidemic (γ01 = −0.147, p = 0.041) and a higher probability of reporting no cholera cases (α01 = 0.156, p = 0.061). Populations in baris characterized by low SES are more likely to experience higher cholera morbidity at the beginning of an epidemic than populations in high SES baris. Author Summary: Cholera is a bacterial disease usually spread through contaminated water that causes severe diarrhea and dehydration. Modern sewage and water treatment have virtually eliminated cholera in industrialized countries but cholera is still present throughout much of SE Asia, Latin America and sub-Saharan Africa. One of the reasons cholera is still problematic is that genetically distinct forms of the bacteria (often called biotypes) have developed and spread rapidly because the population has no natural immunity to the new biotype. In Bangladesh, the 0139 biotype developed in 1993 and caused a large epidemic. Although it is widely accepted that poor conditions place people at risk for cholera, very few studies have examine what role low socioeconomic status plays in cholera risk, especially during a new epidemic of the disease. In this paper, we explore how local-level socioeconomic status, measured using assets, education and sanitation, affect the severity of the cholera outbreak experienced during the O139 epidemic in Matlab, Bangladesh. We believe our study highlights the importance of improving overall socioeconomic status, not just sanitation and water treatment, in controlling the spread of cholera. [ABSTRACT FROM AUTHOR]

This paper defines high-risk areas of cholera based on environmental risk factors of the disease in an endemic area of Bangladesh. The risk factors include proximity to surface water, high population density, and low educational status, which were identified in an earlier study by the authors. Cholera data were analyzed by spatially referenced extended household units for two time periods, 1983-1987 and 1992-1996. These periods were chosen because they had different dominant cholera agents. From 1983-1987 classical cholera was dominant and from 1992-1996 El Tor was dominant. By defining high-risk areas based on risk factors, this study builds a spatial risk model for cholera. The model is then evaluated based on the locations of observed cholera cases. The study also identifies the determinants of death due to cholera for the two different time periods dominated by the different cholera agents. The modeled risk areas that were based on the risk factors were found to correspond with actual distributions of cholera morbidity and mortality. The high-risk areas of the dominant cholera agents are relatively stable over time. However, from 1983-1987 El Tor cholera, which was not the dominant agent during that period, was not associated with high-risk areas, suggesting that the El Tor habitat may have changed over time. The case fatality rate for cholera was related to proximity to a diarrhea treatment hospital in the study area.

Ecologists have begun to describe an environmental distress syndrome, whereby widespread loss of top predators and harsh environmental conditions are encouraging the selection of opportunistic pests and pathogens across a wide taxonomic range of plants and animals. Environmental change and pollutants stress individuals and populations, and this may be reflected in the global resurgence of infectious disease as these stresses cascade through the community assemblages of species. In 1993, the sudden appearance of a virulent, rodent-borne hantavirus in the arid US Southwest accompanied anomalous weather patterns, and a novel Vibrio cholerae variant (O139 Bengal) emerged in Asia where marine ecosystems are experiencing a pandemic of coastal algal blooms, apparently harboring and amplifying the agent. This paper suggests a framework for integrating the surveillance of health outcomes and key reservoir and vector species, with ecological and climatic monitoring.

Four lines of evidence suggest that the recent outbreak strains of Vibrio cholerae O139 could have emerged from serogroup O1 strains typified by isolates M01 and M0477 described in this paper, which are neither truly classical nor truly E1 Tor in their biotype attributes. Firstly, like all O139 isolates, these O1 strains, isolated in Madras during and before the O139 outbreak, were resistant not only to polymyxin B but also to all biotype-specific choleraphages, i.e. classical phage phi 149 and E1 Tor phages e4 and e5. Secondly, the restriction fragment pattern (RFP) polymorphism displayed by these strains for the cholera toxin (ctx) gene, were identical with those produced by O139 isolates but were different from those of O1 type strains, namely V. cholerae 569B (classical) and V. cholerae MAK757 (E1 Tor). Thirdly, all the O139 isolates and the two O1 isolates carried an identical large number of copies of cholera toxin gene in their chromosomes. Finally, the outer-membrane protein profiles of strains M01 and M0477 were identical to those of O139 isolates but were different from those displayed by strains 569B and MAK757.

The potentially deadly and sporadic diarrhea-causing agent, Vibrio cholerae, is present in a great number in the freshwater aquatic environment and can be transmitted to humans by different aquatic organisms. In the perspective of Bangladesh, an anadromous fish species Hilsha (Tenualosa ilisha) can act as a transmission vehicle of V. cholerae from the aquatic to the household kitchen environment. The present study was carried out to investigate the presence of V. cholerae in the aquatic habitat of Bangladesh with a major emphasis on freshly caught Hilsha fish, along with river water and plankton samples from the fish capture site. The study also detected the biofilm formation capability of V. cholerae within Hilsha fish that might help the transmission and persistence of the pathogen in aquatic habitat. Twenty out of 65 freshly caught fish (30.8%) and 1 out of 15 water samples (6.67%) showed the presence of V. cholerae and none of the plankton samples were positive for V. cholerae. The isolated strains were identified as non-O1 and non-O139 serogroups of V. cholerae and contain some major toxin and virulence genes. A few strains showed cellular cytotoxicity on the HeLa cell line. All strains were able to form biofilm on the microtiter plate and the detection of three genes related to biofilm formation (vpsA, vpsL, and vpsR) were also assayed using qPCR. In this study, the in vitro biofilm formation ability of the isolated strains may indicate the long-term persistence of V. cholerae in different parts of Hilsha fish. The abundance of V. cholerae only in freshly caught Hilsha fish and the absence of the pathogen in the surrounding aquatic environment could stipulate the role of Hilsha fish as one of the major transmission routes of V. cholerae from the freshwater aquatic environment of Bangladesh to the household kitchen environment. [ABSTRACT FROM AUTHOR]

This paper analyses a few selected features from the history and clinical examination of 1258 patients with acute diarrhoea and a single laboratory diagnosis of either cholera, rotavirus, or enterotoxigenic (ETEC) Escherichia coli infection. Age distribution and seasonality in Bangladesh were also studied. The duration of illness before admission was not significantly different in the 3 groups. Cholera occurred especially in the spring and early winter. Most cholera patients were between 3 and 10 years of age. Over 37% of the patients developed severe dehydration. In about 90% of cholera cases, the stools were alkaline (pH greater than 7). ETEC infections were seen mostly in April-May and September-October. Infants were frequently affected but from age 25 onwards the age distribution closely followed that of cholera. Severe dehydration occurred in 8.3% of patients and was more frequent than in rotavirus cases. Stool pH was as frequently acidic as basic. Rotavirus cases were concentrated during the winter in patients under 2 years of age. They had marked vomiting, yet severe dehydration was almost absent. Cough was present in half of them. The stools were usually acidic. In spite of considerable overlap of signs and symptoms between the 3 aetiological groups, a presumptive diagnosis of cholera could be made in patients past infancy and early childhood who showed very severe dehydration. However, age-specific prevalence was strikingly different and seasonal variations considerable.

Growing evidence for the existence of an aquatic reservoir of Vibrio cholerae has led some observers to postulate the existence of two distinct modes of disease transmission: primary and secondary. In primary transmission vibrios pass from the aquatic reservoir to humans via edible aquatic flora or fauna, or drinking water. Secondary transmission consists of faecal-oral transmission from person-to-person and may spawn epidemics. Cholera outbreaks are particularly well documented for the Matlab area of Bangladesh, where a field station has been run since 1963, at which patients from a study population of nearly 200,000 are treated for diarrhoeal diseases and monitored in a longitudinal demographic surveillance system. This paper seeks to illuminate the process of secondary transmission by presenting preliminary results of an analysis of the time-space distribution of cholera cases in Matlab for the period 1970-1982. It is argued that the detection of time-space clusters of cases resulting from secondary transmission requires locational data below the level of the village, that is at the level of the bari, or patrilineally-related household group because this is where inter-personal contact is greatest. The mapping of the study area at the bari level is described briefly and it is argued that the proportion of all asymptomatic infections and cases which can be mapped is great enough to enable inferences about transmission processes to be drawn. Results of the analysis of time-space interaction using the Knox method are presented and provide some support for within-bari clustering of cases resulting from secondary transmission.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract: 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. [Copyright &y& Elsevier]

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

Background: Bangladesh experienced a sudden, large influx of forcibly displaced persons from Myanmar in August 2017. A cholera outbreak occurred in the displaced population during September-December 2019. This study aims to describe the epidemiologic characteristics of cholera patients who were hospitalized in diarrhea treatment centers (DTCs) and sought care from settlements of Forcibly Displaced Myanmar Nationals (FDMN) as well as host country nationals during the cholera outbreak. Methods: Diarrhea Treatment Center (DTC) based surveillance was carried out among the FDMN and host population in Teknaf and Leda DTCs hospitalized for cholera during September-December 2019. Results: During the study period, 147 individuals with cholera were hospitalized. The majority, 72% of patients reported to Leda DTC. Nearly 65% sought care from FDMN settlements. About 47% of the cholera individuals were children less than 5 years old and 42% were aged 15 years and more. Half of the cholera patients were females. FDMN often reported from Camp # 26 (45%), followed by Camp # 24 (36%), and Camp # 27 (12%). Eighty-two percent of the cholera patients reported watery diarrhea. Some or severe dehydration was observed in 65% of cholera individuals. Eighty-one percent of people with cholera received pre-packaged ORS at home. About 88% of FDMN cholera patients reported consumption of public tap water. Pit latrine without water seal was often used by FDMN cholera individuals (78%). Conclusion: Vigilance for cholera patients by routine surveillance, preparedness, and response readiness for surges and oral cholera vaccination campaigns can alleviate the threats of cholera. Author summary: Bangladesh observed a large-scale arrival of forcibly displaced individuals from Myanmar in August 2017. The Bangladesh Government, UN agencies, and international and national non-governmental organizations responded immediately with extensive humanitarian response. However, threats of cholera outbreaks were prevailing. The Government of Bangladesh as lead, with technical support from icddr,b collaborating with international agencies undertook a massive oral cholera vaccination (OCV) campaign immediately as a pre-emptive measure to alleviate threats of the cholera outbreak. Despite that mass OCV campaign, threats of cholera outbreak were existing due to new arrivals of the displaced population with compromised host susceptibility, frequent visits to settlements by Bangladesh nationals without exposure to OCV, and the declining vaccine immunity among OCV recipients as well as an increasing number of cohort children without any exposure to OCV. The population faced a cholera outbreak during September-December 2019. This study aims to describe the characteristics of cholera patients, their care-seeking pattern, camp-wise distribution, source of drinking water, sanitation facility, OCV status, and share the experiences from effective interventions to prevent a cholera outbreak. Vigilance for cholera patients by routine surveillance, preparedness for both preventive and control measures, and response readiness for surges and OCV campaigns can alleviate the threats of cholera. [ABSTRACT FROM AUTHOR]

Background: Following an influx of an estimated 742,000 Rohingya refugees in Bangladesh, Médecins sans Frontières (MSF) established an active indicator-based Community Based Surveillance (CBS) in 13 sub-camps in Cox's Bazar in August 2017. Its objective was to detect epidemic prone diseases early for rapid response. We describe the surveillance, alert and response in place from epidemiological week 20 (12 May 2019) until 44 (2 November 2019). Methods: Suspected cases were identified through passive health facility surveillance and active indicator-based CBS. CBS-teams conducted active case finding for suspected cases of acute watery diarrhea (AWD), acute jaundice syndrome (AJS), acute flaccid paralysis (AFP), dengue, diphtheria, measles and meningitis. We evaluate the following surveillance system attributes: usefulness, Positive Predictive Value (PPV), timeliness, simplicity, flexibility, acceptability, representativeness and stability. Results: Between epidemiological weeks 20 and 44, an average of 97,340 households were included in the CBS per surveillance cycle. Household coverage reached over 85%. Twenty-one RDT positive cholera cases and two clusters of AWD were identified by the CBS and health facility surveillance that triggered the response mechanism within 12 hours. The PPV of the CBS varied per disease between 41.7%-100%. The CBS required 354 full-time staff in 10 different roles. The CBS was sufficiently flexible to integrate dengue surveillance. The CBS was representative of the population in the catchment area due to its exhaustive character and high household coverage. All households consented to CBS participation, showing acceptability. Discussion: The CBS allowed for timely response but was resource intensive. Disease trends identified by the health facility surveillance and suspected diseases trends identified by CBS were similar, which might indicate limited additional value of the CBS in a dense and stable setting such as Cox's Bazar. Instead, a passive community-event-based surveillance mechanism combined with health facility-based surveillance could be more appropriate. [ABSTRACT FROM AUTHOR]

Introduction: Cholera is a highly infectious disease and remains a serious public health burden in Bangladesh. The objective of the study was to measure the private demand for oral cholera vaccines (OCV) in Bangladesh and to investigate the key determinants of this demand, reflected in the household's willingness to pay (WTP) for oral cholera vaccine. Methods: A contingent valuation method was employed in an urban setting of Bangladesh during December 2015 to January 2016. All respondents (N = 1051) received a description of World Health Organization (WHO) prequalified OCV, Shanchol™. Interviews were conducted with either the head of households or their spouse or a major economic contributor of the households. Respondents were asked about how much at maximum they were willing to pay for OCV for their own and their household members' protection. Results are presented as the average and median of the reported maximum WTP of the respondents with standard deviations and 95% confidence interval. Natural log-linear regression model was employed to examine the factors influencing participants' WTP for OCV. Results: About 99% of the respondents expressed WTP for OCV with a maximum mean and median WTP per vaccination (2 doses) of US$ 2.23 and US$ 1.92 respectively. On the household level with an average number of 4.62 members, the estimated mean WTP was US$ 10 (median: US$ 7.69) which represents the perceived demand for OCV of a household to vaccinate against cholera. Conclusions: The demand of vaccination further indicates that there is a potential scope for recovering a certain portion of the expenditure of immunization program by introducing direct user fees for future cholera vaccination in Bangladesh. Findings from this study will be useful for the policy-makers to make decision on cost-recovery in future oral cholera vaccination programs in Bangladesh and in similar countries. [ABSTRACT FROM AUTHOR]

After the large influx of Rohingya nationals (termed Forcibly Displaced Myanmar National; FDMN) from Rakhine State of Myanmar to Cox's Bazar in Bangladesh, it was apparent that outbreaks of cholera was very likely in this setting where people were living under adverse water and sanitation conditions. Large campaigns of oral cholera vaccine (OCV) were carried out as a preemptive measure to control cholera epidemics. The aim of the study was to evaluate the immune responses of healthy adults and children after administration of two doses of OCV at 14 days interval in FDMN population and compare with the response observed in Bangladeshi's vaccinated earlier. A cross-sectional immunogenicity study was conducted among FDMNs of three age cohort; in adults (18+years; n = 83), in older children (6–17 years; n = 63) and in younger children (1–5 years; n = 80). Capillary blood was collected at three time points to measure vibriocidal antibodies using either plasma or dried blood spot (DBS) specimens. There was a significant increase of responder frequency of vibriocidal antibody titer at day 14 in all groups for Vibrio cholerae O1 (Ogawa/Inaba: adults-64%/64%, older children-70%/89% and younger children-51%/75%). There was no overall difference of vibriocidal antibody titer between FDMN and Bangladeshi population at baseline (p = 0.07–0.08) and at day 14, day 28 in all age groups for both serotypes. The seroconversion rate and geometric mean titer (GMT) of either serotype were comparable using both plasma and DBS specimens. These results showed that OCV is capable of inducing robust immune responses in adults and children among the FDMN population which is comparable to that seen in Bangladeshi participants in different age groups or that reported from other cholera endemic countries. Our results also suggest that the displaced population were exposed to V. cholerae prior to seeking shelter in Bangladesh. Author summary: Oral cholera vaccines (OCV) are now on the WHO stockpile and targeted for use for countries with outbreaks and epidemics but also for control of endemic cholera. In Bangladesh many studies have been carried out to assess the safety, immunogenicity as well as feasibility of vaccination in the endemic settings of the country. However, with the large recent influx of displaced Rohingya nationals from Myanmar (termed Forcibly Displace Myanmar National; FDMN), mass campaigns with OCV were conducted between October 2017-December 2018. However, no data is available of the previous exposure to cholera of this population, prior to their arrival in Bangladesh. An assessment of immunogenicity status of FDMN is needed to find out if OCV is able to elicit comparable immune response and whether the same dose regimen of OCV was immunogenic among the FDMNs. In this study, we have measured the immune responses to the OCV, Shanchol, in adults (18 years and above), older children (6–17 years), and younger children (1–5 years). The results of this study shows that the oral cholera vaccine capable of inducing an immune response in adults and children among this FDMN population and the responses were comparable to that seen in Bangladeshi participants in earlier studies. [ABSTRACT FROM AUTHOR]

Background Past research has suggested that the most cost-effective approach to using oral cholera vaccines (OCVs) to control endemic cholera may be to target only children <15 y of age. However, the assumption that vaccination of children with OCVs protects unvaccinated adults has never been tested. Methods We reanalyzed the data of an OCV trial in Bangladesh in which children 2–15 y of age and women >15 y of age were allocated to OCV or placebo and assessed herd protection by relating the risk of cholera in each nonvaccinated adult (>15 y) to OCV coverage (OCVC) of residents residing in virtual clusters within 500 m of the residence of that unvaccinated adult. Results The risk of cholera in unvaccinated adults decreased by 14% with each 10% increase of OCVC of all targeted age groups (95% 7 to 21%, p=0.0004). Also, the risk of cholera in unvaccinated adults decreased by 13% with each 10% increase in OCVC of children 2–15 y of age (95% CI 6 to 20%, p=0.0007). A high correlation between levels of OCVC of children and adult females precluded an assessment of the herd protection of unvaccinated adults by vaccinating children <16 y of age, independent of concomitant vaccination of adult women. Conclusions Unvaccinated adults benefitted from herd protection conferred by OCVs in this trial. Vaccination of children may be sufficient to confer this protection, but this possibility needs to be evaluated in further studies. [ABSTRACT FROM AUTHOR]

Analyses of stool from patients with acute watery diarrhea (AWD) using sensitive molecular diagnostics have challenged whether fecal microbiological cultures have acceptably high sensitivity for cholera diagnosis. If true, these findings imply that current estimates of the global burden of cholera, which rely largely on culture-confirmation, may be underestimates. We conducted a vaccine probe study to evaluate this possibility, assessing whether an effective killed oral cholera vaccine (OCV) tested in a field trial in a cholera-endemic population conferred protection against cholera culture-negative AWD, with the assumption that if cultures are indeed insensitive, OCV protection in such cases should be detectable. We re-analysed the data of a Phase III individually-randomized placebo-controlled efficacy trial of killed OCVs conducted in Matlab, Bangladesh in 1985. We calculated the protective efficacy (PE) of a killed whole cell-only (WC-only) OCV against first-episodes of cholera culture-negative AWD during two years of post-dosing follow-up. In secondary analyses, we evaluated PE against cholera culture-negative AWD by age at vaccination, season of onset, and disease severity. In this trial 50,770 people received at least 2 complete doses of either WC-only OCV or placebo, and 791 first episodes of AWD were reported during the follow-up period, of which 365 were culture-positive for Vibrio cholerae O1. Of the 426 culture-negative AWD episodes, 215 occurred in the WC group and 211 occurred in the placebo group (adjusted PE = -1.7%; 95%CI -23.0 to 13.9%, p = 0.859). No measurable PE of OCV was observed against all or severe cholera culture-negative AWD when measured overall or by age and season subgroups. In this OCV probe study we detected no vaccine protection against AWD episodes for which fecal cultures were negative for Vibrio cholera O1. Results from this setting suggest that fecal cultures from patients with AWD were highly sensitive for cholera episodes that were etiologically attributable to this pathogen. Similar analyses of other OCV randomized controlled trials are recommended to corroborate these findings. [ABSTRACT FROM AUTHOR]

Bangladesh has historically been cholera endemic, with seasonal cholera outbreaks occurring each year. In collaboration with the government of Bangladesh, the Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) initiated operational research to test strategies to reach the high-risk urban population with an affordable oral cholera vaccine (OCV) "ShancholTM" and examine its effectiveness in reducing diarrhea due to cholera. Here we report a sub-analysis focusing on the organization, implementation and effectiveness of different oral cholera vaccine delivery strategies in the endemic urban setting in Bangladesh. We described how the vaccination program was planned, prepared and implemented using different strategies to deliver oral cholera vaccine to a high-risk urban population in Dhaka, Bangladesh based on administrative data and observations made during the program. The objective of this study is to evaluate the organization, implementation and effectiveness of different oral cholera vaccine delivery strategies in the endemic urban setting in Bangladesh. OCV administration by trained local volunteers through outreach sites and mop-up activities yielded high coverage of 82% and 72% of 172,754 targeted individuals for the first and second dose respectively, using national Expanded Program on Immunization (EPI) campaign mechanisms without disrupting routine immunization activities. The cost of delivery was low. Safety and cold chain requirements were adequately managed. The adopted strategies were technically and programmatically feasible. Current evidence on implementation strategies in different settings together with available OCV stockpiles should encourage at-risk countries to use OCV along with other preventive and control measures. [ABSTRACT FROM AUTHOR]

Background: Information on the impact of hygiene interventions on severe outcomes is limited. As a pre-specified secondary outcome of a cluster-randomized controlled trial among >400 000 low-income residents in Dhaka, Bangladesh, we examined the impact of cholera vaccination plus a behaviour change intervention on diarrhoea-associated hospitalization.Methods: Ninety neighbourhood clusters were randomly allocated into three areas: cholera-vaccine-only; vaccine-plus-behaviour-change (promotion of hand-washing with soap plus drinking water chlorination); and control. Study follow-up continued for 2 years after intervention began. We calculated cluster-adjusted diarrhoea-associated hospitalization rates using data we collected from nearby hospitals, and 6-monthly census data of all trial households.Results: A total of 429 995 people contributed 500 700 person-years of data (average follow-up 1.13 years). Vaccine coverage was 58% at the start of analysis but continued to drop due to population migration. In the vaccine-plus-behaviour-change area, water plus soap was present at 45% of hand-washing stations; 4% of households had detectable chlorine in stored drinking water. Hospitalization rates were similar across the study areas [events/1000 person-years, 95% confidence interval (CI), cholera-vaccine-only: 9.4 (95% CI: 8.3-10.6); vaccine-plus-behaviour-change: 9.6 (95% CI: 8.3-11.1); control: 9.7 (95% CI: 8.3-11.6)]. Cholera cases accounted for 7% of total number of diarrhoea-associated hospitalizations.Conclusions: Neither cholera vaccination alone nor cholera vaccination combined with behaviour-change intervention efforts measurably reduced diarrhoea-associated hospitalization in this highly mobile population, during a time when cholera accounted for a small fraction of diarrhoea episodes. Affordable community-level interventions that prevent infection from multiple pathogens by reliably separating faeces from the environment, food and water, with minimal behavioural demands on impoverished communities, remain an important area for research. [ABSTRACT FROM AUTHOR]

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The emergence of mobile technology offers new opportunities to improve clinical guideline adherence in resource-limited settings. We conducted a clinical pilot study in rural Bangladesh to evaluate the impact of a smartphone adaptation of the World Health Organization (WHO) diarrheal disease management guidelines, including a modality for age-based weight estimation. Software development was guided by end-user input and evaluated in a resource-limited district and sub-district hospital during the fall 2015 cholera season; both hospitals lacked scales which necessitated weight estimation. The study consisted of a 6 week pre-intervention and 6 week intervention period with a 10-day post-discharge follow-up. Standard of care was maintained throughout the study with the exception that admitting clinicians used the tool during the intervention. Inclusion criteria were patients two months of age and older with uncomplicated diarrheal disease. The primary outcome was adherence to guidelines for prescriptions of intravenous (IV) fluids, antibiotics and zinc. A total of 841 patients were enrolled (325 pre-intervention; 516 intervention). During the intervention, the proportion of prescriptions for IV fluids decreased at the district and sub-district hospitals (both p < 0.001) with risk ratios (RRs) of 0.5 and 0.2, respectively. However, when IV fluids were prescribed, the volume better adhered to recommendations. The proportion of prescriptions for the recommended antibiotic azithromycin increased (p < 0.001 district; p = 0.035 sub-district) with RRs of 6.9 (district) and 1.6 (sub-district) while prescriptions for other antibiotics decreased; zinc adherence increased. Limitations included an absence of a concurrent control group and no independent dehydration assessment during the pre-intervention. Despite limitations, opportunities were identified to improve clinical care, including better assessment, weight estimation, and fluid/ antibiotic selection. These findings demonstrate that a smartphone-based tool can improve guideline adherence. This study should serve as a catalyst for a randomized controlled trial to expand on the findings and address limitations. [ABSTRACT FROM AUTHOR]

Background: : 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.Methods: : 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.Results: : 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.Conclusion: : 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Close interpersonal contact likely drives spatial clustering of cases of cholera and diarrhea, but spatial clustering of risk factors may also drive this pattern. Few studies have focused specifically on how exposures for disease cluster at small spatial scales. Improving our understanding of the micro-scale clustering of risk factors for cholera may help to target interventions and power studies with cluster designs. We selected sets of spatially matched households (matched-sets) near cholera case households between April and October 2013 in a cholera endemic urban neighborhood of Tongi Township in Bangladesh. We collected data on exposures to suspected cholera risk factors at the household and individual level. We used intra-class correlation coefficients (ICCs) to characterize clustering of exposures within matched-sets and households, and assessed if clustering depended on the geographical extent of the matched-sets. Clustering over larger spatial scales was explored by assessing the relationship between matched-sets. We also explored whether different exposures tended to appear together in individuals, households, and matched-sets. Household level exposures, including: drinking municipal supplied water (ICC = 0.97, 95%CI = 0.96, 0.98), type of latrine (ICC = 0.88, 95%CI = 0.71, 1.00), and intermittent access to drinking water (ICC = 0.96, 95%CI = 0.87, 1.00) exhibited strong clustering within matched-sets. As the geographic extent of matched-sets increased, the concordance of exposures within matched-sets decreased. Concordance between matched-sets of exposures related to water supply was elevated at distances of up to approximately 400 meters. Household level hygiene practices were correlated with infrastructure shown to increase cholera risk. Co-occurrence of different individual level exposures appeared to mostly reflect the differing domestic roles of study participants. Strong spatial clustering of exposures at a small spatial scale in a cholera endemic population suggests a possible role for highly targeted interventions. Studies with cluster designs in areas with strong spatial clustering of exposures should increase sample size to account for the correlation of these exposures. [ABSTRACT FROM AUTHOR]

Background: Cholera is endemic in Bangladesh, with outbreaks reported annually. Currently, the majority of epidemic cholera reported globally is El Tor biotype Vibrio cholerae isolates of the serogroup O1. However, in Bangladesh, outbreaks attributed to V. cholerae serogroup O139 isolates, which fall within the same phylogenetic lineage as the O1 serogroup isolates, were seen between 1992 and 1993 and in 2002 to 2005. Since then, V. cholerae serogroup O139 has only been sporadically isolated in Bangladesh and is now rarely isolated elsewhere. Methods: Here, we present case histories of four cholera patients infected with V. cholerae serogroup O139 in 2013 and 2014 in Bangladesh. We comprehensively typed these isolates using conventional approaches, as well as by whole genome sequencing. Phenotypic typing and PCR confirmed all four isolates belonging to the O139 serogroup. Findings: Whole genome sequencing revealed that three of the isolates were phylogenetically closely related to previously sequenced El Tor biotype, pandemic 7, toxigenic V. cholerae O139 isolates originating from Bangladesh and elsewhere. The fourth isolate was a non-toxigenic V. cholerae that, by conventional approaches, typed as O139 serogroup but was genetically divergent from previously sequenced pandemic 7 V. cholerae lineages belonging to the O139 or O1 serogroups. Conclusion: These results suggest that previously observed lineages of V. cholerae O139 persist in Bangladesh and can cause clinical disease and that a novel disease-causing non-toxigenic O139 isolate also occurs. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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. Conclusions: This study demonstrated the role of phytoplankton in maintaining endemicity and seasonality of cholera in Bangladesh. [ABSTRACT FROM AUTHOR]

Background: Killed, oral cholera vaccines have proven safe and effective, and several large-scale mass cholera vaccination efforts have demonstrated the feasibility of widespread deployment. This study uses a mathematical model of cholera transmission in Bangladesh to examine the effectiveness of potential vaccination strategies. Methods & Findings: We developed an age-structured mathematical model of cholera transmission and calibrated it to reproduce the dynamics of cholera in Matlab, Bangladesh. We used the model to predict the effectiveness of different cholera vaccination strategies over a period of 20 years. We explored vaccination programs that targeted one of three increasingly focused age groups (the entire vaccine-eligible population of age one year and older, children of ages 1 to 14 years, or preschoolers of ages 1 to 4 years) and that could occur either as campaigns recurring every five years or as continuous ongoing vaccination efforts. Our modeling results suggest that vaccinating 70% of the population would avert 90% of cholera cases in the first year but that campaign and continuous vaccination strategies differ in effectiveness over 20 years. Maintaining 70% coverage of the population would be sufficient to prevent sustained transmission of endemic cholera in Matlab, while vaccinating periodically every five years is less effective. Selectively vaccinating children 1–14 years old would prevent the most cholera cases per vaccine administered in both campaign and continuous strategies. Conclusions: We conclude that continuous mass vaccination would be more effective against endemic cholera than periodic campaigns. Vaccinating children averts more cases per dose than vaccinating all age groups, although vaccinating only children is unlikely to control endemic cholera in Bangladesh. Careful consideration must be made before generalizing these results to other regions. Author Summary: Bangladesh has a high burden of cholera and may become the first country to use cholera vaccine on a large scale. Mass cholera vaccination may be hard to justify to international funding agencies because of the modest efficacy of existing vaccines and their limited duration of protection. However, mass cholera vaccination can induce high levels of indirect protection in a population, i.e., protecting even unvaccinated individuals by lowering cholera incidence, and a case for cost-effective cholera vaccination could be made. Mathematical modeling is one way to predict the magnitude of indirect protection conferred by a proposed vaccination program. Here, we predict the effectiveness of various mass cholera vaccination strategies in Bangladesh using a mathematical model. We found that maintaining high levels of vaccination coverage in children could be very effective in reducing the burden of cholera, and secondary transmission of cholera would virtually stop when 70% of the population is vaccinated. Mathematical modeling may play a key role in planning widespread cholera vaccination efforts in Bangladesh and other countries. [ABSTRACT FROM AUTHOR]

Background: 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. Methodology/Principal Findings: 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. Conclusions: Direct exposure contributes substantially to endemic transmission of symptomatic cholera in an urban setting. We provide the first estimate of the transmissibility of endemic cholera within prospectively-followed members of households. The role of direct transmission must be considered when planning cholera control activities. Author Summary: Since John Snow's ground-breaking investigations of the devastating outbreaks in 19th-century London, cholera has been considered the quintessential waterborne human infection, transmitting via fecal contamination of environmental water sources. Recently, renewed interest has been paid to the potential importance of transmission through direct exposure within close-contact groups, such as, via fecal contamination of surfaces, food, or drinking water within households. Significant direct transmission of cholera within close contact groups would represent a new target for innovative prevention and control strategies. We estimated the probability of transmission 1) via direct contact within 364 urban households located in an endemic cholera setting (Dhaka, Bangladesh) and 2) via exposure to sources located outside of these households. In this setting we estimated a 4 to 8 percent probability of becoming infected with cholera via direct exposure within households in this setting versus a 2 to 3 percent likelihood of infection due to exposure to external sources over a comparable time period. Our results demonstrate that direct (within-household) transmission is a significant component of endemic cholera transmission, suggesting that biomedical and behavioral-modification interventions specifically targeting this mode of transmission could substantially reduce the cholera burden in this type of setting. [ABSTRACT FROM AUTHOR]

Background: Enterotoxigenic Escherichia coli (ETEC) is one of the most common causes of bacterial diarrhea. Over the last decade, from 1996 to 2012, changes in the virulence antigen properties of ETEC such as heat labile (LT) and heat stable (ST) toxins, colonization factors (CFs), and 'O'-serogroups have been observed. The aim of this prospective study was to compare changes in antigenic profiles of ETEC strains isolated from a 2% surveillance system at the icddr,b hospital in Dhaka, Bangladesh between 2007–2012 and an earlier time period of 1996–1998 conducted at the same surveillance site. Methodology: In the surveillance system every 50th patient attending the hospital was screened for major enteric pathogens including ETEC, Vibrio cholerae, Shigella spp. and Salmonella spp. from January 2007 to December 2012. Principal Findings: Of the 15,152 diarrheal specimens tested between 2007–2012, the overall rate of ETEC isolation was 11%; of these, 43% were LT/ST, 27% LT and 30% ST positive. Isolation rate of ST-ETEC (p<0.009) and LT/ST ETEC (p<0.011) during 2007–2012 period differed significantly compared to those seen between 1996–1998. In comparison to the 1996–1998 period, difference in CF profile of ETEC isolates during 2007–2012 was observed particularly for strains expressing CS7 (12.4%), CS14 (9.5%) and CS17 (10.0%). The predominant CF types were CS5+CS6, CFA/I, CS7, CS17, CS1+CS3, CS6 and CS14. The most common serogroups among the CF positive ETEC isolates were O115, O114, O6, O25 and O8. A strong association was found between CFs and 'O' serogroups i.e. between CS5+CS6 and (O115 and O126); CS7 and (O114), CFA/I and (O78 and O126), CS17 and (O8 and O167) and CS1/CS2+CS3 and (O6). Conclusion: The analyses show a shift in prevalence of antigenic types of ETEC over the study period; the information is important in designing effective ETEC vaccines with broad protective coverage. Author Summary: Diarrheal diseases constitute a major health problem in Bangladesh, where Vibrio cholerae and enterotoxigenic Escherichia coli (ETEC) are two most important causes of bacterial diarrhea. Prevention through vaccination is helpful to reduce the incidence and severity of diarrheal disease due to ETEC, particularly among children in low-resource settings. In this context, we collected stool and/or rectal swab (RS) specimens from patients with diarrhea between 2007 to 2012 under the 2% systematic routine surveillance system at the icddr,b hospital in Dhaka, Bangladesh and screened for ETEC infection. We tested the specimens for two major virulence factors of ETEC: toxins and colonization factors. In this research article, we have focused on changes in toxin as well as colonization factor profiles of ETEC strains isolated from diarrheal patients seeking care at the icddr,b hospital between 2007–2012 and an earlier time period of 1996–1998. We concluded that, such shift in antigenic profile of ETEC over the study period is important in designing effective ETEC vaccines with broad protective coverage. [ABSTRACT FROM AUTHOR]

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 cholerarelated 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 < 0.05) association between the respondents' knowledge and sex, education, occupation, monthly overall household expenditure, attitudes and practice. In the adjusted model, male sex, having a lower monthly overall household expenditure, and having a less positive attitude toward 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. [ABSTRACT FROM AUTHOR]

Background: A stationary (i.e., constant through time) association between El Niño Southern Oscillation (ENSO), the Indian Ocean Dipole (IOD) and epidemics of cholera in Bangladesh has been widely assumed. However, whether or not elements of the local climate that are relevant for cholera transmission have stationary signatures of the IOD on their dynamics over different time scales is still not clear. Here we report results on the time-varying relationships between the various remote and local environmental drivers and cholera incidence in Bangladesh. Methodology/Principal Findings: We performed a cross wavelet coherency analysis to examine patterns of association between monthly cholera cases in the hospitals in Dhaka and Matlab (1983–2008) and indices for both IOD and ENSO. Our results showed that the strength of both the IOD and ENSO associations with cholera hospitalizations changed across time scales during the study period. In Dhaka, 4-year long coherent cycles were observed between cholera and the index of IOD in 1988–1997. In Matlab, the effect of ENSO was more dominant while there was no evidence for an IOD effect on cholera hospitalizations. Conclusions/Significance: Our results call for the consideration of non-stationary, possibly non-linear, patterns of association between cholera hospitalizations and climatic factors in cholera epidemic early warning systems. [ABSTRACT FROM AUTHOR]

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