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F-diagram showing pathways of fecal—oral disease and opportunities to interrupt transmission. Meta-analysis of the association between water source and cholera, including improved and unimproved water sources, bottled drinking water, and contact with surface water. Meta-analysis of the association between water treatment and cholera, including water treatment and no water treatment. Meta-analysis of the association between methods of water transport and storage and cholera, including safe water transport and storage and unsafe transport and storage. Meta-analysis of the association between sanitation and cholera, including improved and unimproved sanitation, shared sanitation, and open defecation. Meta-analysis of the association between hygiene and cholera, including reported good hygiene, reported lack of hygiene, and hygiene materials observed. Cholera: a new homeland in Africa? Am J Trop Med Hyg 77 : — WHO , Global Epidemics and Impact of Cholera. Geneva, Switzerland: World Health Organization. Accessed April 24, The global burden of cholera. Bull World Health Organ 90 : — A. Cholera at the crossroads: the association between endemic cholera and national access to improved water sources and sanitation. Am J Trop Med Hyg 91 : — Lancet : — Water, sanitation, and hygiene interventions in disease outbreak response in low and middle-income countries. Syst Rev In press. Water 1st International , F Diagram—Water1st International. Accessed May 3, Department for International Development , Evidence on the effectiveness of water, sanitation, and hygiene WASH interventions on health outcomes in humanitarian crises: a systematic review. PLoS One 10 : e Water, sanitation, and hygiene in emergencies: summary review and recommendations for further research. Waterlines 31 : 11 — The impact of water, sanitation and hygiene interventions to control cholera: a systematic review. Himmelfarb Health Sciences Library , Study Design —Case Control. Accessed October 10, Transparent Reporting of Systematic Reviews and Meta analyses , Accessed April 6, Higgins J , Green S , eds. Defining the review question and developing inclusion criteria. The Cochrane Collaboration. Modeling the effect of water, sanitation, and hygiene and oral cholera vaccine implementation in Haiti. Am J Trop Med Hyg 89 : — Oslo, Norway: The Campbell Collaboration. Effective Public Health Practice Project. GSDRC , Accessed March 26, Water, sanitation and hygiene for the prevention of diarrhoea. Int J Epidemiol 39 Suppl 1 : i — i Water, sanitation, and hygiene interventions to reduce diarrhoea in less developed countries: a systematic review and meta-analysis. Lancet Infect Dis 5 : 42 — An outbreak of Vibrio cholerae O1 infections on Ebeye island, Republic of the Marshall Islands, associated with use of an adequately chlorinated water source. Clin Infect Dis 38 : 1 — 9. Risk factors associated with cholera in Harare city, Zimbabwe, East Afr J Public Health 7 : — Bhunia R , Ghosh S , Protection from cholera by adding lime juice to food—results from community and laboratory studies in Guinea-Bissau, West Africa. Trop Med Int Health 5 : — Epidemic cholera in West Africa: the role of food handling and high-risk foods. Am J Epidemiol : — Risk factors early in the cholera epidemic, Haiti. Emerg Infect Dis 17 : — Outbreak of cholera in the east Akim municipality of Ghana following unhygienic practices by small-scale gold miners, November Ghana Med J 46 : — Acosta CJ et al. Cholera outbreak in southern Tanzania: risk factors and patterns of transmission. Emerg Infect Dis 7 Suppl : — Waterborne cholera in Riohacha, Colombia, Bull Pan Am Health Organ 27 : — Dunkle SE et al. Epidemic cholera in a crowded urban environment, Port-au-Prince, Haiti. Cholera outbreak linked with lack of safe water supply following a tropical cyclone in Pondicherry, India, J Health Popul Nutr 33 : 31 — Cholera prevention wiith traditional and novel water treatment methods: an outbreak investigation in Fort-Dauphin, Madagascar. Am J Public Health 91 : — Risk factors for cholera infection in the initial phase of an epidemic in Guinea-Bissau: protection by lime juice. Am J Trop Med Hyg 57 : — Transmission of epidemic Vibrio cholerae O1 in rural western Kenya associated with drinking water from lake victoria: an environmental reservoir for cholera? Am J Trop Med Hyg 60 : — Von Seidlein L et al. Is HIV infection associated with an increased risk for Cholera? Findings from a case—control study in Mozambique. Trop Med Int Health 13 : — Availability of safe drinking-water: the answer to cholera outbreak? Nabua, Camarines Sur, Philippines, Western Pac Surveill Response J 6 : 12 — A large cholera outbreak in Kano city, Nigeria: the importance of hand washing with soap and the danger of street-vended water. J Water Health 1 : 45 — Routes of transmission of cholera in the border areas of Zahedan district, Sistan and Baluchestan Province, summer Koo D et al. Epidemic cholera in Guatemala, transmission of a newly introduced epidemic strain by street vendors. Epidemiol Infect : — Mahamud AS et al. Epidemic cholera in Kakuma refugee camp, Kenya, the importance of sanitation and soap. J Infect Dev Ctries 6 : — Assessing the risk factors of cholera epidemic in the Buea health district of Cameroon. BMC Public Health 15 : Nguyen VD et al. Cholera epidemic associated with consumption of unsafe drinking water and street-vended water—eastern Freetown, Sierra Leone, Am J Trop Med Hyg 90 : — Rosewell A et al. Cholera risk factors, Papua New Guinea, BMC Infect Dis 12 : Risk factors for cholera in Pohnpei during an outbreak in lessons for Pacific countries and territories. Pac Health Dialog 12 : 17 — Siddiqui FJ et al. Consecutive outbreaks of Vibrio cholerae O and V. Practical field epidemiology to investigate a cholera outbreak in a Mozambican refugee camp in Malawi, Epidemic cholera among refugees in Malawi, Africa: treatment and transmission. An outbreak of cholera in Medipally village, Andhra Pradesh, India, J Health Popul Nutr 33 : 7. Spatial analysis of risk factor of cholera outbreak for — in a Peri-urban area of Lusaka, Zambia. Am J Trop Med Hyg 79 : — Epidemic cholera in Burundi: patterns of transmission in the Great Rift valley lake region. Treating water with chlorine at the point-of-use to improve water quality and reduce child diarrhea in developing countries: a systematic review and meta-analysis. Am J Trop Med Hyg 76 : — Interventions to improve water quality for preventing diarrhoea: systematic review and meta-analysis. BMJ : Household water treatment and safe storage options in developing countries. Navig Epidemiologic study of Vibrio cholerae O1 and O in Thailand: at the advancing edge of the eighth pandemic. The outbreak of cholera among workers of a jute mill in Kolkata, West Bengal, India. J Health Popul Nutr 29 : 9 — Mugoya I et al. Rapid spread of Vibrio cholerae O1 throughout Kenya, Am J Trop Med Hyg 78 : — Quick RE et al. Epidemic cholera in rural El Salvador: risk factors in a region covered by a cholera prevention campaign. Weber JT et al. Epidemic cholera in Ecuador: multidrug-resistance and transmission by water and seafood. Epidemiol Infect : 1 — A cholera outbreak among semi-nomadic pastoralists in northeastern Uganda: epidemiology and interventions. Epidemic cholera in the Amazon: the role of produce in disease risk and prevention. J Infect Dis : — Swerdlow DL et al. Waterborne transmission of epidemic cholera in Trujillo, Peru: lessons for a continent at risk. Lancet : 28 — Epidemic cholera in urban Zambia: hand soap and dried fish as protective factors. Ries AA et al. Cholera in Piura, Peru: a modern urban epidemic. Grandesso F et al. Risk factors for cholera transmission in Haiti during inter-peak periods: insights to improve current control strategies from two case-control studies. Ujjiga TTA et al. Risk factors for sustained cholera transmission, Juba county, South Sudan, Emerg Infect Dis 21 : — Safe water treatment and storage in the home: a practical new strategy to prevent waterborne disease. JAMA : — Cholera outbreak in Kenyan refugee camp: risk factors for illness and importance of sanitation. Am J Trop Med Hyg 80 : — Epidemic cholera during refugee resettlement in Malawi. Int J Epidemiol 23 : — Cholera outbreak in a southwest community of Nigeria: investigation of risk factors and evaluation of a district surveillance system. West Afr J Med 32 : — Zwane AP , Kremer M , What works in fighting diarrheal diseases in developing countries? A critical review. World Bank Res Obs 22 : 1 — Effect of intensive handwashing promotion on childhood diarrhea in high-risk communities in Pakistan: a randomized controlled trial. Cholera outbreak in southeast of Iran: routes of transmission in the situation of good primary health care services and poor individual hygienic practices. Jpn J Infect Dis 59 : — The Joint effects of efficacy and compliance: a study of household water treatment effectiveness against childhood diarrhea. Water Res 47 : — Waddington H , Snilstveit B , Effectiveness and sustainability of water, sanitation, and hygiene interventions in combating diarrhoea. J Dev Effect 1 : — Wolf J et al. Assessing the impact of drinking water and sanitation on diarrhoeal disease in low- and middle-income settings: systematic review and meta-regression. Trop Med Int Health 19 : — Integrating disease control strategies: balancing water sanitation and hygiene interventions to reduce diarrheal disease burden. Am J Public Health 97 : — The sanitation ladder—a need for a revamp? J Water Sanit Hyg Dev 1 : 3 — The sanitation ladder, what constitutes an improved form of sanitation? Environ Sci Technol 49 : — Evidence of the influence of wastewater treatment on improved public health. Water Sci Technol 66 : — Minimizing the risk of disease transmission in emergency settings: novel in situ physico-chemical disinfection of pathogen-laden hospital wastewaters. United Nations , Goal 6. Sustainable Development Knowledge Platform. Accessed October 30, Cholera outbreak secondary to contaminated pipe water in an urban area, West Bengal, India, Indian J Gastroenterol 28 : 62 — The cost of a knowledge silo: a systematic re-review of water, sanitation and hygiene interventions. Health Policy Plan 30 : — Case—control studies are conducted to identify cholera transmission routes. Water, sanitation, and hygiene WASH exposures can facilitate cholera transmission risk factors or interrupt transmission protective factors. To our knowledge, the association between WASH exposures and cholera from case—control studies has not been systematically analyzed. A systematic review was completed to close this gap, including describing the theory of risk and protection, developing inclusion criteria, searching and selecting studies, assessing quality of evidence, and summarizing associations between cholera and seven predicted WASH protective factors and eight predicted WASH risk factors using meta-analysis and sensitivity analysis. Overall, 47 articles describing 51 individual studies from 30 countries met the inclusion criteria. Meta-analysis results highlight that predicted risk factors are associated with cholera; however, predicted protective factors are not as consistently protective. This variable protection is attributed to 1 cholera transmission via multiple routes and 2 WASH intervention implementation quality variation. Water, sanitation, and hygiene interventions should address multiple transmission routes and be well implemented, according to international guidance, to ensure that field effectiveness matches theoretical efficacy. In addition, future case—control studies should detail WASH characteristics to contextualize results. Cholera is an acute, diarrheal disease caused by toxigenic Vibrio cholerae. Water, sanitation, and hygiene WASH interventions are commonly implemented to prevent and control cholera by blocking exposures assumed to be risk factors for disease transmission Figure 1. In , to fill an identified evidence gap, 8 — 11 a systematic review of the efficacy and effectiveness of WASH interventions in outbreaks was completed by Yates et al. More commonly, evaluations documented reductions of transmission risk, such as chlorine residual presence in household drinking water. Simple WASH interventions that were appropriately timed, community-driven, and had linkages between relief and development were found to be most effective. Overall, WASH interventions reduced both the risk of disease and the risk of disease transmission in outbreaks; however, program design and beneficiary preferences were important considerations to ensure WASH intervention field effectiveness matched efficacy. A limitation of the Yates review is that case—control studies were not included, as the methodology to assess case—control studies is different from that of other study types that were included, which were population-based. Case—control studies are observational studies in which individuals with a disease cases are recruited along with individuals who have not had the disease controls. Exposures are retrospectively compared to determine how frequently various exposures are present in each group. Although they cannot determine causality, case—control studies provide some of the best evidence on health in emergencies and outbreaks because they are relatively easy to conduct even in a crisis and can yield information about the sources of the outbreak that can then be used to develop response activities. To our knowledge, the evidence on the association between WASH exposures and cholera transmission has not been summarized from case—control studies. To fill this evidence gap, we performed a systematic review of cholera case—control studies to summarize the association between WASH exposures and cholera transmission. We conducted a systematic review of published literature to evaluate the association between WASH exposures and cholera transmission. The review was developed based on the guidelines for the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 13 and included the development of 1 a definition of risk and protection, 2 a search strategy, 3 the inclusion criteria, 4 a selection and data extraction strategy, 5 the framework for appraising risk of bias, and 6 an analysis plan. Each of these steps is described in the following paragraphs. A priori, and based on the F-diagram Figure 1 , five WASH groups that theoretically impact cholera transmission were defined, including water source, water treatment, water management, sanitation, and hygiene. During analysis, the exposures included within each WASH group were subdivided into predicted protective factors and predicted risk factors, based on the F-diagram. Note that data are presented herein for predicted protective and risk factors with at least five exposures from case—control studies in at least three included articles. Because exposures were chosen for inclusion based on the presence of data among the selected studies, the theory of risk and protection for each predicted protective and risk factor is specifically described in the Results section. Because WASH exposures are often evaluated but not highlighted in the abstracts of these articles, the search was kept intentionally broad without reference to WASH exposures in the search string. The search was limited to peer-reviewed English-language articles published from References were stored in Zotero 4. Inclusion criteria were defined according to the populations, interventions, comparisons, outcomes, and study type PICOS framework, a model recommended by the Cochrane Library to structure rigorous reviews on health-related questions. Populations included in the review must have been affected by cholera. All age, gender, and socioeconomic populations in cholera were included. Because this review is based on case—control studies, we define studies evaluating eligible exposures, rather than interventions. Although we were not able to evaluate interventions, protective exposures represent interventions that should limit cholera transmission. Studies were eligible for inclusion if they included exposures from one of the five WASH groups identified in the theory of risk and protection development: water source, water treatment, water management, sanitation, and hygiene. Studies were excluded if they were designed to evaluate a cholera vaccine program, as the interaction between WASH exposures and vaccination is currently unknown. Studies were eligible for inclusion if they reported an association between cholera and at least one WASH exposure using an odds ratio OR. Studies were screened by two independent authors in each of the two screening stages: Screening 1 articles were excluded if the outcome was not cholera cases or the study design was not case—control in title and abstract screening and Screening 2 the full text of the articles selected in Screening one was examined and studies that did not meet the aforementioned PICOS criteria were excluded. Discrepancies between reviewers were resolved through discussion and consensus. Relevant data were extracted from each article according to the framework in Waddington et al. Individual WASH exposures were grouped into WASH-predicted protective factors and predicted risk factors as described earlier in the theory of risk and protection section. The risk of bias was assessed across five categories: 1 selection and confounding, 2 spillover and contamination, 3 incomplete outcomes, 4 selective reporting, and 5 other bias. Meta-analyses were performed in Stata 14 using the ORs associated with exposures for each of the 15 factors seven predicted protective factors and eight predicted risk factors to determine an overall association. A summary OR was generated for each of these 15 factors using a Mantel—Haenszel random effects analysis. Random effects analysis was used because of the high heterogeneity that was observed between estimates from case—control studies. Despite heterogeneity between studies, meta-analysis was deemed appropriate to use because of the universality of fecal exposure risk in transmitting cholera. To assess the robustness of the overall associations, five sensitivity analyses were completed, by performing the same analysis by factors including only exposures from 1 studies assessed as low and medium risk of bias, 2 studies assessed as low risk of bias, 3 studies of any risk level that used the WHO case definition for cholera, 4 low- and medium-risk studies that used the WHO case definition, and 5 low-risk studies using the WHO case definition. Sensitivity analysis is reported in the main text when the association changed direction or became either newly significant or insignificant. Overall, articles were identified in the initial search, articles were included after reviewing title and abstract in the first screening, and 47 articles, including 51 individual case—control studies, were included after full-text review in the second screening Supplemental Table 1 , Figure 2. The articles represent studies from 30 countries; five were from Kenya, followed by four each from India, Haiti, Papua New Guinea, and Malawi. In total, 15 factors were found to fall under the five WASH groups defined as impacting cholera transmission, including seven predicted protective factors and eight predicted risk factors Table 1. Predicted protective factors improved water source and bottled water source and predicted risk factors unimproved water source and surface water contact were developed based on exposures identified in the review. Improved water source was defined according to JMP standards and includes sources that adequately protect water from outside contamination such as piped water, boreholes, protected springs, and rainwater. Contact with surface water was reported in included studies as an exposure and a predicted risk factor, as surface water is considered unimproved by the JMP. Water treatment was defined as measures taken to make water safer to drink, including boiling, filtering, or treating with chlorine. Water treatment was a predicted protective factor, as these interventions are intended to remove or inactivate bacteria introduced through fecal—oral contamination. There were no changes in direction of association or significance in sensitivity analysis Supplemental Table 2. Water management includes practices related to water transport and storage. Safe water transport and storage prevents contamination of water through the use of protected containers such as covered buckets and jerricans, and constitutes a barrier to fecal-oral contamination. Unsafe water management practices include transporting or storing water in a container with no lid, and were predicted risk factors as they allow for contamination of water. Sanitation facilities and proper waste disposal separate feces from the environment. Sanitation facilities were classified based on their description in the articles into the four subcategories of the JMP sanitation ladder: open defecation, unimproved sanitation, shared sanitation, and improved sanitation. Open defecation and unimproved sanitation do not create a barrier between feces and humans, and were predicted risk factors. Shared sanitation may consist of facilities that adequately separate feces from the environment but are used by two or more households. These facilities are considered unimproved and were predicted risk factors. Improved sanitation facilities ensure separation of feces from the environment, and because this should provide a barrier against fecal—oral transmission, they are predictive protective factors. Hygiene includes behaviors that promote cleanliness such as handwashing with soap and water. There were no changes in direction of association or significance in the sensitivity analysis Supplemental Table 2. A systematic review and meta-analysis was conducted to determine the relationship between WASH exposures and cholera. Overall, 47 articles describing 51 case—control studies were included in the review. Water, sanitation, and hygiene exposures were grouped into eight predicted risk factors and seven predicted protective factors. Among the predicted protective factors, neither improved water source nor improved sanitation was associated with cholera. These results highlight 1 the consistency in association of risk factors with cholera, adding support to current knowledge on the mechanisms of cholera transmission, 2 the inconsistency in the association of cholera with protective factors compared with risk factors, 3 the unexpected finding that no sanitation factor or improved water source with the exception of bottled water was significantly protective, and 4 the need for more specific reporting of intervention details in case—control studies. Summary ORs for each factor suggest that overall, predicted risk factors are a risk for cholera transmission. These data underscore the importance of WASH factors for the transmission of cholera, with all suspected pathways showing an association with cholera across a diversity of contexts. Although the most important transmission pathways may differ by context and an assessment of these pathways may be undertaken during an outbreak to target interventions, these results show that even pathways that are less commonly focused on during outbreaks e. Results were less consistent for predicted protective factors. Only five of seven protective factors showed a significant negative association with cholera, and all protective factors had wide CIs and statistically significant heterogeneity. Our findings suggest that risk factors are consistently risky, and factors expected to interrupt cholera transmission have the potential to do so, but are not always effective. This is likely partly because cholera is transmitted via multiple pathways Figure 1 such that removing one source of contamination may not effectively prevent disease, whereas the introduction of contamination through a single pathway can effectively cause disease. Our results are consistent with literature which shows that individual interventions can have differing levels of effectiveness in different contexts and that the efficacy of an intervention under ideal conditions and its effectiveness for preventing disease transmission in given context are different. We suspect that cultural differences around WASH practices, eating, and drinking also contribute this variation, in addition to differences in the exposures themselves. Effectiveness depends on, among other factors, a good program design that targets pathways contributing to disease transmission and accounts for beneficiary preferences to ensure correct and consistent use. The one WASH group in which no factor was protective was sanitation; all four factors were associated with increased cholera. These factors were adopted from the JMP sanitation ladder, which provides a detailed framework for assessing sanitation; rather than considering sanitation as simply improved or unimproved, sanitation facilities are classified into open defection, unimproved facilities, shared facilities, and improved facilities. The current sanitation ladder does not include treatment of waste, which has been shown to reduce disease transmission. The other predicted protective factor that did not show an association with cholera was improved water source. Although improved sources should protect water from outside contamination, they do not always provide safe water. For example, piped water supply may be intermittent, allowing for backflow and intrusion of contaminated water, or rainwater collection containers may be contaminated. This variability in quality of water from improved sources is seen in the lack of association between improved source and cholera. In some case—control studies, it even appeared that improved water sources were the source of an outbreak, especially from failing piped water systems. As described previously, good implementation and consistent uptake are critical for WASH interventions to interrupt disease transmission. One of the challenges in completing this review was that WASH interventions are often incompletely described in case—control studies, making it difficult to assess what the WASH intervention was or why it may or may not have been successful. It has been documented that the success or failure of interventions often occurs at least partly through pathways that are not considered for primary assessments e. We suspect that the high degree of heterogeneity seen among protective factors is due to undescribed differences, rather than the innate ability of an intervention to provide efficacious protection. Considering this, we recommend that reports of outbreaks should include detailed information on the design and implementation of interventions, so that factors leading to success or failure can be directly assessed and implemented in the future, to prevent disease transmission. Our study had several limitations. Our analysis was limited to peer-reviewed articles published in English; more data are likely available in other languages and gray literature. Because we used data from studies in peer-reviewed articles, it is possible that publication bias led to underreporting of null findings; this would affect results by making summary ORs more extreme. This suggests that although in general the results are relatively robust, low-quality studies could falsely influence associations and caution should be used in interpreting all results. Although every effort was made to place factors in the correct category, lack of intervention detail may have led to misclassification bias. Data were self-reported, which may have also resulted in misclassification. Included studies also lacked data that would have enabled us to better describe the context of the observed associations. Ideally, we would be able to perform a multivariate meta-analysis that would account for effect modification when factors coexist. However, although multiple exposures were often reported in a single study, studies were of low enough quality with missing data on exposures and interstudy correlations that we did not feel it was possible to construct a robust multivariate analysis. We suspect that effect modification within an outbreak is another piece of context that might explain the variability observed in interventions. Although we have data on outbreak setting i. Future research might also be designed to include a theory of behavior change and incorporate factors such as exposure to cholera risk messaging. Last, although we suspect that methods and quality of implementation of interventions would have an impact on their effectiveness, the included studies did not provide sufficient detail to assess this and include in analysis. Despite these limitations, we feel that these results add value and highlight ways future case—control studies could collect detailed intervention data to address these limitations. Overall, our results support the conclusion that risk factors allowing for disease transmission are associated with greater odds of cholera during an outbreak and should be addressed to limit disease transmission, and protective factors expected to provide a barrier to transmission are associated with lower odds of cholera. However, the effect of predicted protective factors was inconsistent, as interventions may not have the intended effect if they are not implemented properly. We recommend that interventions delivered during cholera outbreaks should be implemented in a way that promote correct and consistent use, and future case—control studies should detail the design and implementation characteristics of WASH interventions so that factors leading to success or failure can be more directly assessed and implemented in the future to prevent disease transmission. The authors would like to thank the Humanitarian Evidence Programmer and 3ie for encouraging this work, and Karen Vagts, Tufts Librarian, for assistance in developing the search strategy. Financial support: M. Sign in Sign up. Members Institutions Cost. Advanced Search Help. Search strategy. Inclusion criteria. Selection and data extraction. Risk of bias appraisal. Water treatment. Water management. Export Figures. Figure 1. Figure 2. Study selection and quality assessment flow chart. Figure 3. Figure 4. Figure 5. Figure 6. Figure 7. Close View raw image Figure 1. View raw image Figure 2. View raw image Figure 3. View raw image Figure 4. View raw image Figure 5. View raw image Figure 6. View raw image Figure 7. Export References. PubMed WHO , PubMed Water 1st International , PubMed Department for International Development , PubMed Acosta CJ PubMed Dunkle SE PubMed Von Seidlein L PubMed Koo D PubMed Mahamud AS PubMed Nguyen VD PubMed Rosewell A PubMed Siddiqui FJ PubMed Mugoya I PubMed Quick RE PubMed Weber JT PubMed Swerdlow DL PubMed Ries AA PubMed Grandesso F PubMed Wolf J PubMed United Nations , Authors: W. Authors: Ahmad Hajian. Gordon H. Two Nosological Forms of Cutaneous Leishmaniasis. Author: P. Author: Humberto Menezes. Authors: Guillermo Pacheco. Previous Article Next Article. Page s : — Open access. Download PDF. Theory of risk and protection. Specific comparisons were not required for inclusion. Study types. Only case—control studies were eligible for review. RESULTS Overall, articles were identified in the initial search, articles were included after reviewing title and abstract in the first screening, and 47 articles, including 51 individual case—control studies, were included after full-text review in the second screening Supplemental Table 1 , Figure 2. Water source. Supplementary Material. Author Notes. E-mail: marlene. Improved water source. Unimproved water source. Bottled water source. Surface water contact. Safe water storage and transport. Unsafe water storage and transport. Unimproved sanitation. Self-report good hygiene. Self-reported lack of hygiene. Observation of hygiene materials. Self-reported good hygiene.

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