Scholarly article on topic 'Water, Sanitation, Hygiene, and Soil-Transmitted Helminth Infection: A Systematic Review and Meta-Analysis'

Water, Sanitation, Hygiene, and Soil-Transmitted Helminth Infection: A Systematic Review and Meta-Analysis Academic research paper on "Health sciences"

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Academic research paper on topic "Water, Sanitation, Hygiene, and Soil-Transmitted Helminth Infection: A Systematic Review and Meta-Analysis"

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Water, Sanitation, Hygiene, and Soil-Transmitted Helminth Infection: A Systematic Review and Meta-Analysis

Eric C. Strunz1*, David G. Addiss1, Meredith E. Stocks2, Stephanie Ogden1,2,3, Jurg Utzinger4,5, Matthew C. Freeman2

1 Children Without Worms, The Task Force for Global Health, Decatur, Georgia, United States of America, 2 Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, United States of America, 3 International Trachoma Initiative, The Task Force for Global Health, Decatur, Georgia, United States of America, 4 Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland, 5 University of Basel, Basel, Switzerland

Abstract

Background: Preventive chemotherapy represents a powerful but short-term control strategy for soil-transmitted helminthiasis. Since humans are often re-infected rapidly, long-term solutions require improvements in water, sanitation, and hygiene (WASH). The purpose of this study was to quantitatively summarize the relationship between WASH access or practices and soil-transmitted helminth (STH) infection.

Methods and Findings: We conducted a systematic review and meta-analysis to examine the associations of improved WASH on infection with STH (Ascaris lumbricoides, Trichuris trichiura, hookworm [Ancylostoma duodenale and Necator americanus], and Strongyloides stercorals). PubMed, Embase, Web of Science, and LILACS were searched from inception to October 28, 2013 with no language restrictions. Studies were eligible for inclusion if they provided an estimate for the effect of WASH access or practices on STH infection. We assessed the quality of published studies with the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. A total of 94 studies met our eligibility criteria;five were randomized controlled trials, whilst most others were cross-sectional studies. We used random-effects meta-analyses and analyzed only adjusted estimates to help account for heterogeneity and potential confounding respectively. Use of treated water was associated with lower odds of STH infection (odds ratio [OR] 0.46, 95% CI 0.36-0.60). Piped water access was associated with lower odds of A. lumbricoides (OR 0.40, 95% CI 0.39-0.41) and T. trichiura infection (OR 0.57, 95% CI 0.45-0.72), but not any STH infection (OR 0.93, 95% CI 0.28-3.11). Access to sanitation was associated with decreased likelihood of infection with any STH (OR 0.66, 95% CI 0.57-0.76), T. trichiura (OR 0.61, 95% CI 0.50-0.74), and A. lumbricoides (OR 0.62, 95% CI 0.44-0.88), but not with hookworm infection (OR 0.80, 95% CI 0.61-1.06). Wearing shoes was associated with reduced odds of hookworm infection (OR 0.29, 95% CI 0.18-0.47) and infection with any STH (OR 0.30, 95% CI 0.11-0.83). Handwashing, both before eating (OR 0.38, 95% CI 0.26-0.55) and after defecating (OR 0.45, 95% CI 0.35-0.58), was associated with lower odds of A. lumbricoides infection. Soap use or availability was significantly associated with lower infection with any STH (OR 0.53, 95% CI 0.29-0.98), as was handwashing after defecation (OR 0.47, 95% CI 0.240.90). Observational evidence constituted the majority of included literature, which limits any attempt to make causal inferences. Due to underlying heterogeneity across observational studies, the meta-analysis results reflect an average of many potentially distinct effects, not an average of one specific exposure-outcome relationship.

Conclusions: WASH access and practices are generally associated with reduced odds of STH infection. Pooled estimates from all meta-analyses, except for two, indicated at least a 33% reduction in odds of infection associated with individual WASH practices or access. Although most WASH interventions for STH have focused on sanitation, access to water and hygiene also appear to significantly reduce odds of infection. Overall quality of evidence was low due to the preponderance of observational studies, though recent randomized controlled trials have further underscored the benefit of handwashing interventions. Limited use of the Joint Monitoring Program's standardized water and sanitation definitions in the literature restricted efforts to generalize across studies. While further research is warranted to determine the magnitude of benefit from WASH interventions for STH control, these results call for multi-sectoral, integrated intervention packages that are tailored to social-ecological contexts.

Please see later in the article for the Editors' Summary.

Citation: Strunz EC, Addiss DG, Stocks ME, Ogden S, Utzinger J, et al. (2014) Water, Sanitation, Hygiene, and Soil-Transmitted Helminth Infection: A Systematic Review and Meta-Analysis. PLoS Med 11(3): e1001620. doi:10.1371/journal.pmed.1001620

Academic Editor: Simon Hales, University of Otago, New Zealand

Received August 21, 2013; Accepted February 13, 2014; Published March 25, 2014

Copyright: © 2014 Strunz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: M.C.F. was funded in part by UK aid from the Department for International Development (DFID) as part of the SHARE Research Programme (www.SHAREResearch.org). However, the views expressed do not necessarily reflect the Department's official policies. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared that no competing interests exist.

Abbreviations: GRADE, Grades of Recommendation, Assessment, Development and Evaluation; MDA, mass drug administration; NTD, neglected tropical disease; OR, odds ratio; PHAST, participatory hygiene and sanitation transformation; RR, risk ratio; STH, soil-transmitted helminth; WASH, water, sanitation, and hygiene; WHO, World Health Organization.

* E-mail: estrunz@taskforce.org

Introduction

More than a billion people are infected with soil-transmitted helminths (STHs) and many more live in high risk areas [1]. The global burden of STH infection is estimated at between 5 and 39 million disability-adjusted life years, largely attributable to anemia, stunting, and reduced cognitive development [2-4]. Humans are infected after ingesting eggs (A. lumbricoides and T. trichiura) or through penetration of the skin by infective larvae in the soil (hookworm [A. duodenale and N. americanus] and S. stercoralis) [1]. Current control strategies have focused on preventive chemotherapy through mass drug administration (MDA), in which at-risk populations are treated once or twice per year with benzimid-azoles, primarily albendazole (usually given as a single oral dose of 400 mg) or mebendazole (500 mg) [5]. While preventive chemotherapy can greatly reduce morbidity from helminth infection, reinfection typically occurs rapidly after treatment [6].

Long-term STH control and eventual elimination require improvements to water, sanitation, and hygiene (WASH) access and practices [7]. The history of STH in the United States of America, South Korea, and Japan—where WASH improvements acted in concert with deworming to eliminate STH as a public health problem—supports the need for an integrated control paradigm [8-10]. WASH interventions are diverse, potentially including improvements in water access (e.g., water quality, water quantity, and distance to water), sanitation access (e.g., access to improved latrines, latrine maintenance, and fecal sludge management), and hygiene practices (e.g., handwashing before eating and/or after defecation, water treatment, soap use, wearing shoes, and water storage practices) [11-20]. Interventions often include multiple components, e.g., building ventilated-improved pit latrines while also providing hygiene education. Work in the WASH sector is often motivated by the view that access to clean water and adequate sanitation is a human right, but health outcomes are also broadly considered, with diarrheal disease burden representing a common measure of impact [21-23].

The successful integration of WASH into a disease control program has already been demonstrated for trachoma, which— like STH—is also considered a neglected tropical disease (NTD). The World Health Organization (WHO) endorses the "SAFE" strategy for trachoma control: surgery to correct advanced stages of trachoma, antibiotics to treat active infection, facial cleanliness to reduce disease transmission, and environmental change (including increased access to water and improved sanitation) [24]. The SAFE strategy explicitly calls for the implementation of improved access to, and use of, water, sanitation, and hygiene through improvements in delivery and/or specific interventions.

Such a fully integrated strategy—including guidelines and targets—does not yet exist for STH control, in part because evidence examining the relationship between WASH and STH is limited. A seminal review by Esrey and colleagues found few investigations that evaluated the association between WASH and STH infection [25]. A recent systematic review and meta-analysis by Ziegelbauer and colleagues found that individuals who have access to and use of sanitation facilities were at lower odds of infection with STH compared to individuals without sanitation [26]. Additional empirical evidence that links WASH improvements to reductions in STH infection is scarce, and an improved

evidence-base may lead to better coordination between the NTD and WASH sectors [27,28].

To fill this gap, we conducted a systematic review and set of meta-analyses to examine evidence of association between STH infection and WASH. We expanded the study's focus to include up-to-date meta-analyses for water and hygiene components, in addition to sanitation. We only used adjusted effect estimates in meta-analyses to help account for potential confounding and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews. Our use of the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach for quality assessment also provides a comprehensive accounting of the limitations of available evidence. We hypothesized that improvements in WASH would be associated with reductions in odds of STH infection. Thus, the purpose of this study was to quantitatively summarize the relationship between WASH access or practices on STH infection, while also synthesizing available data that did not qualify for meta-analysis.

Methods

Search Strategy, Inclusion Criteria, and Data Extraction

Our review adheres to the PRISMA and Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines (see Texts S1 and S2) [29-31]. The methods protocol is available in Text S3. A study investigator (ECS) and two research assistants (Rachel Stelmach [RS] and Claire Still [CS]) systematically searched PubMed, Embase, Web of Science, and LILACS for relevant articles from inception to October 28, 2013. We also indexed relevant studies from the bibliography of reviews by Ziegelbauer and colleagues [26] and Asaolu and Ofoezie [32]. Abstracts without published articles were considered eligible for inclusion. Additionally, we requested available unpublished research from the US Centers for Disease Control and Prevention, The Carter Center, The Task Force for Global Health, the WHO regional offices, and the authors' personal collections.

The native search engines within PubMed, Embase, Web of Knowledge, and LILACS were used to search each respective database using Boolean operators. The search included two clusters of terms: one for STH (i.e., helminth, soil-transmitted helminth, geohelminth, ascaris, lumbricoides, trichuris, trichiura, hookworm, ancylostoma, duodenale, necator, americanus, stron-gyloid*, stercoralis) and one for WASH (i.e., sanitation, sanitary engineering, water supply, waste management, environment*, excre*, faec*, fecal, feces, hand washing, handwashing, hygiene, latrine*, toilet*, water, soap). Results had to contain at least one term from both clusters. ''Extensive search'' was enabled when searching with Embase. Because Embase only allowed for exporting up to 5,000 records, results were stratified by date in order to screen and export all results in smaller segments. All search records were exported to bibliographic files and imported into Endnote X5 (Thomson Reuters), which was used to manage and screen search results. Titles, and when available, abstracts were scanned by an investigator (ECS) and also independently by research assistants (RS and CS) to determine possible relevance. Final selection was based on the full text of all potentially

Table 1. Criteria for study bias assessment.

Criteria Description

Infection diagnostics Is a diagnostic assay clearly mentioned? Is there any form of quality control in the diagnostic process (e.g., a senior technician doing spot-checks)?

Exposure assessment Was exposure assessment (e.g., access to clean water, washing hands) ascertained via a self-reported survey response (unreliable)

or observed directly by investigators (more reliable)? Is there any attempt to gauge proper use of water, hygiene, or some form of ''quality control'' for the exposures?

Confounding assessment Are only crude estimates computed? Has matching and/or multiple logistic regression been undertaken to control for important potential confounders?

Response rate Is the response rate (or loss-to-follow-up) similar for infected versus non-infected individuals?

Selective reporting Is there evidence of selective reporting within an article (e.g., outlining certain variables of interest in the methods but not providing any data on them in the results)?

doi:10.1371/journal.pmed.1001620.t001

applicable articles. Ambiguous articles were examined by a senior reviewer (MCF).

Publications in all languages were considered. Studies in English, Spanish, Portuguese, and French were screened by investigators directly. Chinese-language articles were reviewed by a study collaborator (Shuyuan Huang [SH]) who assessed eligibility and extracted relevant data for the research team. Relevant data from all eligible studies was abstracted by a reviewer (ECS) and independently by assistants (RS and CS). Extracted data included study design, setting, year, population characteristics, WASH components measured, diagnostic approach, STH species, and relevant effect measures. Odds ratios (ORs) served as the primary effect measure in the reviewed literature. We collected both crude and adjusted estimates if available. Excel 2007 (Microsoft) was used to input and manage data using a long format to accommodate multiple effect estimates per study.

An article was eligible for inclusion if it presented a measure of effect between WASH and STH (e.g., an OR). For studies that pooled multiple intestinal parasites (e.g., Giardia intestinalis and STH) into one outcome measure, we contacted authors to request disaggregated data. We did not exclude studies based on methodology or population characteristics. Studies that evaluated multiple WASH components were included, as long as the components could be assessed separately from deworming medications and other non-WASH interventions.

There are few standard definitions for WASH access and practices, and it is difficult to measure WASH behaviors objectively [33]. We were unable to consistently connect water and sanitation variables reported in retrieved studies to the WHO and UNICEF Joint Monitoring Program's water and sanitation ladder definitions [34,35]. For this review, "treated water'' is defined as the use of any chemical or physical treatment of water to change its potability, whether conducted at the source or at the point of use. Two specific forms of treatment included boiling and filtering water at home. "Piped water'' describes access to, or use of, water collected from a piped infrastructure, regardless of where the water is accessed (public/private) or how well maintained the infrastructure may be. ''Sanitation access'' was our primary sanitation exposure, defined as access to, or use of, any latrine. We did not exclude studies that lacked information about latrine quality, so access to sanitation could refer to anything from simple pit latrines to flush toilets. For hygiene, ''washing after defecation'' refers to the availability of handwashing resources (e.g., a wash basin) near sanitation facilities or reported handwashing behavior after defecation. ''Soap use or availability'' could refer to washing with water alone or no washing as the comparison group. Further,

these definitions do not incorporate any criteria for compliance or consistency, since such details were rare in retrieved literature.

Statistical Methods

We conducted meta-analyses for groups of effect estimates that related similar WASH access or practices (e.g., latrine availability and/or use became ''sanitation access'') to a common outcome. Potential outcomes included infection with a specific STH (i.e., A. lumbricoides, T. trichiura, hookworm, and S. stercoralis) or any STH generally. Note that ''any STH'' reflected infection with an individual species or co-infection with multiple species when authors reported aggregated STH infection results. Meta-analyses were performed for groups of independent effect estimates that numbered three or greater and shared a similar exposure and infection outcome. A study that measured several WASH components could contribute to multiple meta-analyses, but could only supply one effect estimate for any single meta-analysis.

We employed random-effects models to account for the expected heterogeneity between studies [36]. Only adjusted estimates were utilized to limit the impact of confounding on pooled effect measures [37]. When necessary, we inverted estimates to reflect the effect of WASH, rather than the absence ofWASH. This inversion was necessary in order to ensure enough study estimates were available for meta-analysis, but could have resulted in additional heterogeneity. For example, the inverse of ''no sanitation access'' may be similar to, but distinct from, ''sanitation access'' when assessed by questionnaire due to bias associated with socially desirable responses. Further, the presence of WASH access or practices may not necessarily be the same as the inverse effect of their absence, especially if important confounders or effect modifiers remain unexplored. Estimates of effect not included in meta-analyses were summarized in the text. The meta-analysis package MAIS for Stata version 12 (StataCorp) was used to perform the random-effects meta-analyses with the DerSimonian and Laird method [38]. The natural log of reported ORs was the dependent variable. CIs use the 95% level unless otherwise noted.

Bias Assessment and Evidence Quality

We used the GRADE framework to assess potential sources of bias within studies and determine overall strength of evidence for each meta-analysis [39]. The GRADE approach is used to contextualize or justify intervention recommendations with four levels of evidence quality, ranging from very low to high. These levels correspond to how likely it would be for further research to alter conclusions drawn from the current evidence. ''High quality''

Table 2. Criteria for meta-analysis GRADE assessment.

Criteria Description

Imprecision Caused the evidence quality to be downgraded if the pooled effect estimate's 95% CI overlapped with the null (i.e., one for odds ratios). In this context, imprecision is synonymous with a pooled estimate being statistically non-significant at the 0.05 level. Imprecision is used to downgrade evidence quality because some consumers of reviews (e.g., policymakers and practitioners) often do not fully understand statistical uncertainty.

Indirectness Did not cause any evidence quality to be downgraded. Our review had a broad scope that aimed to collect a wide array of

evidence exploring different populations and contexts. Traditionally, indirectness refers to issues that may limit the generalizability of evidence's reported results to the review's specified research question. This could be caused by differences in study population, study design, co-interventions, etc.

Inconsistency Assessed with Moran's I and Cochran's Q-test [46]. If a study exhibited an I value over 50%, there was potential cause for

(i.e., heterogeneity) concern, and the Q-test was also checked for a p-value less than 0.10. Values for 12 over 70% or Q-test p-values lower than

0.05 resulted in the downgrading of a body of evidence.

Publication bias Assessed through a visual inspection of funnel plots, though Egger's test also informed our interpretation [48]. Detecting

publication bias is difficult when dealing with dichotomous outcomes, especially when there is significant between-study heterogeneity. In such circumstances, the popular Egger's test is usually inappropriate, with the potential to result in many false positives. For this reason, qualitative funnel plot analysis served as our primary assessment tool, though we also computed Egger's statistics to inform our judgment. Tests described by Rucker et al. [135] and Peters et al. [136] were also considered, but not performed.

A large magnitude of effect Could upgrade overall evidence quality if pooled odds ratios were less than 0.33 or greater than 3.0 [41]. The standard

(also called ''effect size'') criteria for risk ratios and hazard ratios is that effect estimates be less than 0.5 or greater than 2.0. However, since odds

ratios will show a greater magnitude than risk ratios, especially when an outcome is common, a more conservative cut-off value is needed. No firm rules have been established in the literature, so we increased the relevant effect size magnitude for odds ratios by 50%.

Evidence of a dose-response Can upgrade evidence quality. Dose-response relationships were assessed by examining studies where exposures were

relationship discretized into ranked categories, e.g., analyzing ''always washes hands'' versus both ''sometimes'' and ''never.'' A dose-

response relationship was considered possible if the point estimates improved between the ordinal categories, especially if relevant confidence intervals did not overlap.

Potential confounding Can upgrade a body of evidence if there are plausible factors that may be artificially weakening the observed pooled

measurement. In the case of hygiene, individuals are known to overreport handwashing behaviors, which would systematically lower any apparent benefits. Potential downgrades are also possible, however, especially if established confounding variables are not taken into account by an analysis.

doi:10.1371/journal.pmed.1001620.t002

suggests that it is very unlikely for conclusions about effect estimates to change, whereas ''very low quality'' suggests that any estimate of effect is highly uncertain [40]. We formed our key bias categories from the literature, GRADE recommendations [41], and two instruments highlighted by the Cochrane Collaboration [42]: the Downs and Black tool [43] and the Newcastle-Ottawa scale [44]. We focused on five potential sources of bias in our assessment of individual studies: (i) diagnostic approach for assessing STH infection; (ii) exposure assessment; (iii) confounding assessment; (iv) response rate; and (v) selective reporting. Each study received one of three rankings for each source of bias: low risk, unclear risk, or high risk. Detailed criteria for these categories are available in Table 1. Bias was assessed independently by ECS and one of the two research assistants (RS and CS), compared, and reviewed by a senior assessor (DGA or MCF) if necessary.

We assessed the overall quality of evidence for each meta-analysis after considering seven key characteristics. Each meta-analysis could receive a quality grade of very low, low, moderate, or high [45]. Meta-analyses of observational studies were classified as ''low'' by default, but could be downgraded (because of imprecision, indirectness, inconsistency, publication bias, and potential confounding) or upgraded (because of magnitude of effect, dose-response relationship, and potential confounding) on the basis of the overall strength of the evidence.

Inconsistency (i.e., heterogeneity) was assessed with Moran's I and Cochran's Q-test [46]. I2 provides an estimate of the proportion of variability in a meta-analysis that is explained by differences between the included studies instead of sampling error [47]. If a study exhibited an I2 value over 50%, there was potential cause for concern, and the Q-test was also checked for a p-value

less than 0.10. Values for I2 over 70% or Q-test p-values lower than 0.05 resulted in the automatic downgrading of a body of evidence.

Publication bias was assessed through a visual inspection of funnel plots, though Egger's test also informed our interpretation [48]. Evidence quality was downgraded due to ''imprecision'' if the pooled effect estimate's 95% CI overlapped with the null (i.e., statistical significance at the 0.05 level). Although we provide CIs for pooled point estimates, imprecision remains a valuable criterion since not all consumers of reviews understand the importance of CIs and statistical uncertainty.

Evidence quality was upgraded owing to large magnitude of effect if the meta-analysis yielded a pooled OR less than 0.33 or greater than 3.0 [41]. Traditionally, risk ratios (RRs) are considered to show a large magnitude if they are less than 0.5 or greater than 2.0. However, ORs overstate the effect size compared to RRs, especially when initial risk (i.e., the prevalence of the outcome of interest) is high [49]. Because STH infection is relatively common, a more conservative threshold was needed for ORs in order to qualify as a large magnitude of effect.

Evidence quality could also be upgraded or downgraded on the basis of any unaccounted sources of potential confounding that would likely have a predictable direction on the effect estimate. For example, hygiene behaviors are typically over-reported in surveys, which could reduce the measured strength of effect for hygiene practices since the exposure group includes those who did not practice hygiene [50-52].

Due to the breadth of the review, indirectness was not a common concern, but would be more important for future reviews that focus on specific populations, settings, or interventions. Dose-response relationships were assessed by examining studies where

Figure 1. PRISMA flow diagram.

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exposures were discretized into ranked categories, e.g., analyzing ''always washes hands'' versus both ''sometimes'' and ''never.'' A dose-response relationship was considered possible if the point estimates improved between the ordinal categories, especially if relevant CIs did not overlap. Additional details about the meta-analysis GRADE criteria are available in Table 2.

Results

Retrieved Studies

The search yielded a total of 47,589 articles from PubMed (n =21,718), Embase (n = 18,188), Web of Knowledge (n = 7,502), and LILACS (n = 181), with 42,882 unique records. Our PRISMA flow diagram is available in Figure 1. After reviewing titles and

abstracts, we examined 397 articles more intensively: 264 were excluded for lacking a relevant effect measure, 30 were excluded for aggregating non-STH infections in the outcome, and 11 were excluded for being review or editorial articles (see Tables 3 5 for included studies and S1 for excluded ones). We contacted 11 authors to obtain additional data [53 60], but only three authors responded [61 63]. A total of 94 studies ultimately met our inclusion criteria, yielding over 450 estimates of effect. Retrieved data included findings from one unpublished investigation [64] and one publication with information about two related studies

Most included studies were published in English (n = 86), though articles in Portuguese (n = 4), Chinese (n = 2), and Spanish (n = 2) were also included. Studies researched populations in Asia (n = 42),

CT> NJ O

Table 3. List of included studies with authors A-F.

Author [cite ID], Year - Country Title of Article Setting and Population Sample Size Diagnosis Method Exposure Assessment and Study Method Main WASH Components Adjustment or Controlled Variables

Ahmed [111], 2011 - Malaysia3 The burden of moderate-to-heavy soil-transmitted helminth infections among rural malaysian aborigines: an urgent need for an integrated control programme Satak, Raub district, Pahang-Sekolah Kebangsaan Satak school; Aboriginal schoolchildren, 6-13 years old 254 Kato-Katz and Harada Mori Questionnaire, cross-sectional Toilet, water source, playing in soil Source of drinking water, toilet in house, domestic animals in the house, age, playing barefoot in soil

Aimpun [113], 2004 - Belize3 Survey for intestinal parasites in Belize, Central America 5 villages in the Toledo district; all ages, Ketchi and Mopan ethnic groups 533 Formalin-ethyl-acetate concentration technique Questionnaire, cross-sectional Handwashing, shoes, water, latrine Race, occupation, years of education, population density, presence of trash pit near home, drinking water source, water treatment, and ownership of electrical appliances

Alemu [137], 2011 - Ethiopia Soil transmitted helminths and schistosoma mansoni infections among school children in Zarima town, northwest Ethiopia Elementary school children from Zarima town in NW Ethiopia 319 Kato-Katz Questionnaire, observation, cross-sectional Handwashing, shoe wearing, presence of latrine, latrine usage, water source No adjusted WASH effect estimates identified

Al-Mekhlafi [138], 2007 - Malaysia An unceasing problem: soil-transmitted helminthiases in rural malaysian communities 18 villages around Pos Betau School, Kuala Lipis; Primary schoolchildren (7-12) of Pos Betau School, Kuala Lipis, Pahang, Malaysia. 277 Kato-Katz and Harada Mori Questionnaire, cross-sectional Latrine availability, water access No adjusted WASH effect estimates identified

Al-Mekhlafi [139], 2008 - Malaysia Pattern and predictors of soil-transmitted helminth reinfection among aboriginal schoolchildren in rural Peninsular Malaysia Pos Betau, Kuala Lipis, Pahang; Orang Asli (aborigine) primary schoolchildren, age 7-12 120 Modified cellophane thick smear and Harada Mori Questionnaire, longitudinal Toilet, water source No adjusted WASH effect estimates identified

Alvarado [85], 2006 - Colombia Social determinants, feeding practices and nutritional consequences of intestinal parasitism in children 7-18 months old in Guapi, Cauca Guapi, Cauca; children 7-18 months old 136 Direct examination and concentrate Ritchie-Frick modified Questionnaire, cross-sectional Latrine type, floor type No adjusted WASH effect estimates identified

Table 3. Cont.

Author [cite ID], Year - Country Title of Article Setting and Population Sample Size Diagnosis Method Exposure Assessment and Study Method Main WASH Components Adjustment or Controlled Variables

Amahmid [140], 2005 - Morocco Assessment of the health hazards associated with wastewater reuse: transmission of geohelminthic infections (Marrakech, Morocco) Children (2-14 years) near Marrakech, Morocco 610 Formol-ether concentration Questionnaire, observation, cross-sectional Source of water No adjusted WASH effect estimates identified

Asaolu [123], 2002 - Nigeria3 Effect of water supply and sanitation on the prevalence and intensity of Ascaris lumbricoides among pre-school-age children in Ajebandele and Ifewara, Osun State, Nigeria. Ajebandele and Ifewara, two peri-urban communities near lle-lfe, Osun State, Nigeria; children aged 0 to 108 months from mix of different ethnic groups 516 Kato-Katz (modified) Questionnaire, cross-sectional Latrine type, water source Final, full model not given. Used stepwise selection in multiple regression. Initial model included: village, water source, latrine type, mothers' age and education, fathers' age and education, and gender/age of the child

Awasthi [141], 2008 - India Prevalence and risk factors associated with worm infestation in pre-school children (6-23 months) in selected blocks of Uttar Pradesh and Jharkhand, India Preschool children (6-23 months) from Uttar Pradesh and Jharkhand, India 909 Formol-ether concentration Questionnaire, cross-sectional Drinking water source, toilets in home, washing hands after defecation No adjusted WASH effect estimates identified

Balen [131], 2011 - China3 Risk factors for helminth infections in a rural and a peri-urban setting of the Dongting Lake area, People's Republic of China Wuyi and Laogang, two administrative villages in the Dongting Lake region of Hunan province; all ages from Wuyi, a rural village 1,298 Kato-Katz Questionnaire, cross-sectional Handwashing, water source Village, occupation, socioeconomic status, soil contact, animal ownership, washing hands w/soap before eating/ after defecating

Barreto [142], 2010 - Brazil Impact of a citywide sanitation program in Northeast Brazil on intestinal parasites infection in young children Children (0-36 months) from Salvador, Brazil 1,920 Kato-Katz Questionnaire, observation, cross-sectional Regularity of water supply, hygiene behavior, indoor toilet, household excreta disposal Different variables depending on model, but could include: drainage type, regularity of water supply, absence of rubbish dumps, paved road/ sidewalk, hygiene behavior, indoor toilet, open sewage nearby, household excreta disposal, coverage with program sewerage connections

Basualdo [143], 2007 - Argentina Intestinal parasitoses and environmental factors in a rural population of Argentina, 2002-2003 Children (<15 years) and adults (>15 years) from Buenos Aires, Argentina 504 Telemann Survey, cross-sectional Type of floors, water supply, public/private faucet, excrement disposal Final multivariable model unclear

n* D* fD Author [cite ID], Year - Country Title of Article Setting and Population Sample Size Diagnosis Method Exposure Assessment and Study Method Main WASH Components Adjustment or Controlled Variables

g g g "b o 3 fD Q. n* o' IV O Belo [144], 2005 - Sâo Tomé and Principe Prevalence, behavioural and social factors associated with Schistosoma intercalatum and geohelminth infections in Sao Tome and Principe Three primary schools in S. Marya, Guadalupe and Kilombo; schoolchildren 130 Kato-Katz and Teleman-Lima Questionnaire, cross-sectional Excreta location No adjusted WASH effect estimates identified

i3 Belyhun [70], 2010 - Ethiopia9 Prevalence and risk factors for soil-transmitted helminth infection in mothers and their infants in Butajira, Ethiopia: a population based study Butajira; infants 908 Formol-ether concentration method Questionnaire, cross-sectional Soap use, water source Place of residence, age, domestic animals living together

Bieri [76], 2013 - China Health-Education Package to Prevent Worm Infections in Chinese Schoolchildren Rural Linxiang City District, Hunan province; children 9-10 years old 1,718 Kato-Katz with 10% quality control Experimental, longitudinal Handwashing Clustering, school grade level, sex

00 Carneiro [145], 2002 - Brazil The risk of Ascaris lumbricoides infection in children as an environmental health indicator to guide preventive activities in Caparao' and Alto Caparao', Brazil Rural municipalities of Caparao and Alto Caparao, in Minas Gerais, Brazil; Children under 14 years of age 760 Kato-Katz Questionnaire, cross-sectional Sanitation index, hygiene index, water in washbasin Crowding, water in washbasin, sanitation index, hygiene index, age, socioeconomic index

S OJ n 3" Chongsuvivatwong [65], 1996 - Thailand3 Predictors for the risk of hookworm infection: experience from endemic villages in southern Thailand One village; All age groups (over 6 years old) 245 Kato-Katz Questionnaire, observations, cross-sectional Shoes, latrine availability Education, income level, location in village, number of houses w/in 20 m, latrine, wearing shoes outside

NJ O c Chongsuvivatwong [65], 1996 - Thailand3 Predictors for the risk of hookworm infection: experience from endemic villages in southern Thailand Three villages; All age groups (over 6 years old) 456 Kato-Katz Questionnaire, observations, cross-sectional Shoes, latrine availability Education, income level, location in village, number of houses w/in 20 m, latrine, wearing shoes outside

ne 11 | Issue 3 Corrales [124], 2006 - El Salvador3 Association between intestinal parasitic infections and type of sanitation system in rural El Salvador Eight rural and semi-urban communities in the states of La Libertad and La Paz, El Salvador; Heads of households 127 Evergreen Scientific Fecal Parasite Concentrator kit Questionnaire, cross-sectional Latrine type Household clustering, age, anthelmintic meds in past 3 months, having dirt floor, owning pigs

CT> NJ O

Author [cite ID], Year - Country Title of Article Setting and Population Sample Size Diagnosis Method Exposure Assessment and Study Method Main WASH Components Adjustment or Controlled Variables

Cundill [67], 2011 - Brazil

Rates and intensity of re-infection with human helminths after treatment and the influence of individual, household, and environmental factors in a Brazilian community

Americaninhas, Minas Gérais State; Individuals aged over 5 years

Kato-Katz and formalin ether

Questionnaire, longitudinal

Water source, latrine

Farook [148], 2002 - India

Intestinal Helminthic Infestations among Tribal Populations of Kottoor and Achankovil Areas in Kerala (India)

Kottoor and Acbankovil; All age groups

Formol-ether Questionnaire, cross-

sedimentation technique sectional

Proper handwashing

Fonseca [119], 2010 - Brazil3 Prevalence and factors associated with geohelminth infections in children living in municipalities with low HDI in North and Northeast Brazil

Ten Brazilian municipalities with low human development indices (HDI); Children

Kato-Katz and Sedimentation

Questionnaire, cross-sectional

Improved water

Parental education level, electricity access

Dumba [86], 2013 - Uganda Design and implementation of participatory hygiene and sanitation transformation (PHAST) as a strategy to control soil-transmitted helminth infections in Luweero, Uganda Children in 19 villages around Luweero, Uganda 558 Kato-Katz Assignment, questionnaire, experimental PHAST intervention (participatory hygiene/sanitation transformation) Multivariable modeling used for one part of study, included maintenance condition of household, level of education

Ellis [146], 2007 - China Familial aggregation of human susceptibility to co- and multiple helminth infections in a population from the Poyang Lake region, China Five villages in Poyang Lake region, Jiangxi Province; Individuals aged over 5 years 3,682 Kato-Katz (duplicate) Questionnaire, cross-sectional Water contact No adjusted WASH effect estimates identified

Ensink [147], 2005 - Pakistan High risk of hookworm infection among wastewater farmers in Pakistan Males involved in farming with wastewater or regular water or in textile work and their children (2-12 years) in Faisalabad, Pakistan 1,704 Formolin-ether concentration Questionnaire, observation, cross-sectional Type of water supply, toilet, wearing shoes Toilet, house construction, type of water supply

No adjusted WASH effect estimates identified

Ferreira [149], 2000 - Brazil Secular trends in child Sao Paolo households; 1,044 Sedimentation techniques, Questionnaire, Improved sanitation Age, year of survey, and

intestinal parasitic children (0-5 years old) unstained and Lugol- Longitudinal maternal education (or,

diseases in S. Paulo city, in Sao Paulo stained alternatively, per capita

Brazil (1984-1996) income), housing conditions, access to health services

Maternal education, family income, presence of garbage near home, household crowding, urban/rural, gender (varied depending on worm outcome)

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Africa (n = 29), and the Americas (n = 23). Studies investigated access and practices relating to water (n = 56), sanitation (n = 79), and hygiene (n = 53) (Figure 2); the most commonly explored were access to sanitation (n = 63), access to water (n = 45), handwashing (n = 30), and wearing shoes (n = 27). Studies reported investigating infection with A. lumbricoides (n = 69), T. trichiura (n = 60), hookworm (n = 63), S. stercoralis (n =12), and any STH collectively (n =52). Tables 6 and 7 illustrate the number of articles in which both specific WASH components and helminth infections were investigated.

Of 94 studies, 89 were observational: 75 used a cross-sectional epidemiologic design, 13 were prospective, and the remaining was a case-control study. Most studies investigated multiple potential risk factors for STH infection. Exposure status for WASH access and practices was typically determined through self-report, although 15 studies also used some form of observation to validate self-reported information. All included studies reported the diagnostic method used to assess helminth infection, with the Kato-Katz technique most frequently mentioned (n =63). To assess the independent effect of WASH components on STH infection, authors typically used multiple regression analysis (n = 68), though adjusted effect estimates were often not reported for WASH covariates if they were not statistically significant. Not all multivariable models were reported with a full list of included covariates either. Slightly more than one-third of the studies (n = 33) reported at least one non-significant adjusted effect estimate. Study bias assessment is presented in Table S2. Meta-analysis results are available in Table 8 and grades summarized in Table 9.

Water-related access and practices were generally associated with lower odds of STH infection. We conducted meta-analyses to examine the association of piped water access and use of treated water on STH infection. Using treated water (filtered or boiled) was associated with lower likelihood of having any STH infection (k = 3, OR 0.46, 95% CI 0.36-0.60). The quality of evidence for the analysis was low, as all three studies were observational (Figure 3). Use of piped water was not associated with STH infection in general (k = 5, OR 0.93, 95% CI 0.28-3.11). The quality of evidence for the pooled estimate was very low due to high heterogeneity (I2 = 98.6%, 95% CI 98%-99%, Qp-value< 0.01) among the studies (Figure 4). The heterogeneity could have stemmed from multiple factors, as the five studies shared few methodological characteristics. Use of piped water was associated with reduced likelihood of A. lumbricoides infection (k = 4, OR 0.40, 95% CI 0.39-0.41) and T. trichiura infection (k = 3, OR 0.57, 95% CI 0.45-0.72). Evidence quality for these two meta-analyses was low, based on four studies and three studies respectively (Figures 5 and 6). We did not find a sufficient number of studies to conduct a similar meta-analysis for hookworm infection, although Nasr and colleagues found a significantly lower adjusted odds of infection (OR 0.59, 95% CI 0.34-0.91) for Malaysian children with access to piped water [66]. Other researchers found no statistically significant associations between piped water access and hookworm infection [67,68].

Other water-related exposures for STH infection were reported in the literature, but not with sufficient frequency for meta-analyses. In one study examining storage of water, Quintero and colleagues found a significantly higher adjusted odds of T. trichiura infection for Venezuelan children and adults collecting water in "inappropriate'' receptacles (OR 1.12, 95% CI 1.09-1.15) [69]. Limited evidence also was retrieved on the influence of water source location; Belyhun and colleagues [70] found a beneficial

Table 4. List of included studies with authors G-M.

rV =3* Author [cite ID], Setting and Exposure Assessment Main WASH Adjustment or Controlled

fD Year - Country Title of Article Population Sample Size Diagnosis Method and Study Method Components Variables

§ Geissler [150], Geophagy as a risk Children (standards 5-6) 200 Kato-Katz Questionnaire, verified, Geophagy, having toilet No adjusted WASH effect

? 1998 - Kenya factor for geohelminth prospective cohort at home estimates identified

infections: A longitudinal

o study of Kenyan primary

3 schoolchildren

Q. Glickman [151], Nematode intestinal Children (1-18 years) 286 Direct smear and Questionnaire, Source of drinking Age, sex

D* CO 1999 - Guinea parasites of children in from rural Guinea, Africa centrifugal flotation cross-sectional water, sanitary facilities,

0 rural Guinea, Africa: with sugar solution geophagia

to Prevalence and

relationship to geophagia

Gunawardena [130], 2004 - Sri Lanka3

Gunawardena [152], 2005 - Sri Lanka

Guo-Fei [154], 2011 - China

Socio-economic and behavioural factors affecting the prevalence of Ascaris infection in a low-country tea plantation in Sri Lanka

Maliboda estate plantation (low country, <275 m

above sea level); Tea plant workers, 2-50 years (median = 13 years)

Kato-Katz

Questionnaire, cross-sectional

Washing hands, boiling water

Effects of climatic, socioeconomic and behavioural factors on the transmission of hookworm (Necator americanus) on two low-country plantations in Sri Lanka

The "low country" Maliboda and Ayr plantations; 2-74 years old

Kato-Katz

Questionnaire, observations, Longitudinal

Washing behavior, toilet

Full, final model not provided. Used step-wise variable selection in regression. The following variables were entered into the initial model: age, gender, living quarters, educational status and monthly income of each subject, availability of sanitary facilities, water supply source, use of boiled water, handwashing behavior, and cleanliness of each subject's house and immediate environment.

Occupation, level of education, toilet availability, usage, location, water source, use of footwear, playing with mud (if child), cleanliness of home environment

Gunawardena [153], Soil-Transmitted Helminth Nuwara Eliya, Badulla, 1,890 Kato-Katz Questionnaire, Better household Altitude, time since last school

2011 - Sri Lanka Infections among Kegalle, Ratnapura, and cross-sectional sanitation, as reflected sanitary inspection, mother's

Plantation Sector Kandy. These five districts by a latrine score of 74 education, latrine score, gender

Schoolchildren in Sri are centrally located in the or more

Lanka: Prevalence after southern half of Sri Lanka;

Ten Years of Preventive School children (grade 4)

Chemotherapy

Analysis of influencing factors of Trichuris trichiura infection in demonstration plots of comprehensive control of parasitic diseases

Demonstration plots in multiple regions, including Anhui, Jiangxi, Hunan, Guangxi, Hainan, Sichuan, Guizhou, Yunnan; Unclear

Kato-Katz

Questionnaires, cross-sectional

Numerous

Agricultural activity, consumption of raw vegetables, previous anthelmintic treatment; could also have included sex, age, region, education level

rV U* CO Author [cite ID], Year - Country Title of Article Setting and Population Sample Size Diagnosis Method Exposure Assessment and Study Method Main WASH Components Adjustment or Controlled Variables

S Gyorkos [155], Exploring determinants Primary schools in Belen, 927 Kato-Katz Questionnaire, Shoes, improved water Dirty fingernails, presence of

2011 - Peru of hookworm infection in Peru; Grade 5 children cross-sectional potable water at home, wearing

Peruvian schoolchildren shoes

o using a gender analysis

CO Q_ Gyorkos [77], Impact of Health Education Grade 5 schoolchildren in 1,089 Kato-Katz Assignment, questionnaire, Hygiene education Clustering, age, sex, SES status,

nj 2013 - Peru on Soil-Transmitted Peruvian Amazon experimental intervention presence of running water in

D rD Helminth Infections in the home, baseline values of

0 Schoolchildren of the outcome measures (e.g.,

¿2 Peruvian Amazon: A baseline STH values, baseline

Cluster-Randomized knowledge values), time of year

Controlled Trial of baseline visit, length of

follow-up

Habbari [156], Geohelminthic infections Students (7-14) 1,999 Formaldehyde-ether Questionnaire, Source of water, toilet at No adjusted WASH effect

2001 - Morocco associated with raw attending primary cross-sectional home, hand-washing estimates identified

wastewater reuse for school in Beni Ma I la I,

agricultural purposes in Morocco

Beni-Mellal, Morocco

Hall [72], Strongyloides stercoralis Urban slum in Dhaka; 880 Ether sedimentation Questionnaire, longitudinal Sanitation, water source, No adjusted WASH effect

1994 - Bangladesh in an urban slum older than 1 year technique soil estimates identified

community in Bangladesh:

factors independently

associated with infection

Halpenny [157], Regional, Household and The comarca Ngabe- 356 FLOTAC and Kato-Katz Questionnaire, longitudinal Sanitation Clustering, other covariates

2013 - Panama Individual Factors that Bugle, a semi-autonomous depended on worm outcome,

Influence Soil Transmitted political region; children but could include household

Helminth Reinfection from 0-48 months of age density, child HAZ score,

Dynamics in Preschool maternal education

Children from Rural

Indigenous Panama

Henry [158], 1988 - Reinfection with Ascaris Children (0-36 months) 219 Formol-ether concentration Questionnaire, Having piped water, No adjusted WASH effect

OJ St. Lucia lumbricoides after from St. Lucia observation, having a water-sealed estimates identified

n chemotherapy: a prospective cohort toilet

comparative study in

o three villages with varying

sanitation

§ Hidayah [122], Socio-environmental Bachok; children 363 Formol-ether method Questionnaire, Hygiene, indiscriminate Age, location of household

c 1997 - Malaysia3 predictors of cross-sectional defecation

rt) soil-transmitted

helminthiasis in a rural

community in Malaysia

Issue 3 | e1001620 Hohmann [80], 2001 - Lao PDRa Relationship of intestinal parasites to the environment and to behavioral factors in children in the Bolikhamxay province of Lao PDR Bolikhamxay province; children aged below 15 years 709 Kato-Katz Questionnaire, cross-sectional Washing hands Mountainous region, age, material possessions, cleaning after defecation

rV U* CO Author [cite ID], Year - Country Title of Article Setting and Population Sample Size Diagnosis Method Exposure Assessment and Study Method Main WASH Components Adjustment or Controlled Variables

t § Huat [159], Prevalence and Risk Beris Lalang, a rural 79 Saline wet mounting Questionnaire, Eating raw salad BMI, mother's education level

2012 - Malaysia Factors of Intestinal Muslim community; technique cross-sectional

Helminth Infection children 7-9 years old

o Among Rural Malay

3 Q. Children

=3* CO 0 iE Hughes [73], 2004 - Pacific Islands3 Environmental influences on helminthiasis and nutritional status among Pacific schoolchildren 27 primary schools in 13 Pacific Island countries; Primary school children, aged 5-12 years 1,996 Kato-Katz Questionnaire, observations, cross-sectional Water supply, soap available, sanitation facilities (many covariates) All estimates age, sex, nutritional status and school/ cluster.

Humphries [132], Epidemiology of Four communities in 126 Kato-Katz Questionnaire, Latrine use, shoes Age, gender, and community.

2011 - Ghana3 Hookworm Infection in Kintampo North Municipality, Ghana: Patterns of Malaria Coinfection, Anemia, and Albendazole Treatment Failure Kintampo North Municipality: Jato-Akuraa (JA), Cheranda (C), Kawampe (KA), and Gulumpe (GU); study results include only those >15 years old (adults) cross-sectional

Ivan [116], Helminthic infections HIV-positive pregnant 980 Kato-Katz Questionnaire, Water source, shoe ART, employment,

2013 - Rwanda3 rates and malaria in HIV- women cross-sectional wearing, washing hands handwashing, CD4 count

infected pregnant women after defecation

on anti-retroviral therapy in Rwanda

Jiraanankul [133], Incidence and Risk Tungsor Hongsa 585 Kato-Katz, water-ethyl Questionnaire, Latrine use, shoes, Age, raising cats or buffalo

2011 - Thailand3 Factors of Hookworm Infection in a Rural Community of Central Thailand community, Chachoengsao Province, 228 km east of Bangkok, Thailand; all ages acetate sedimentation technique longitudinal washing hands

Khieu [87], 2013 - Cambodia

Diagnosis, Treatment and Risk Factors of Strongyloides stercoralis in Schoolchildren in Cambodia

Semi-rural villages in Kandal province; Primary school children

Kato-Katz, KAP culture, and Questionnaire, Baermann technique cross-sectional

Sanitation, handwashing, shoes

No adjusted WASH effect estimates identified

Knopp [125], From morbidity control to Individuals on the island 2,858 Kato-Katz, koga agar plate Questionnaire, Latrine at home, washing Sex, age, and village

2011 - Zanzibar3 transmission control: time of Unguja method (KAP), and Baermann interview, cross-sectional hands before eating,

to change tactics against technique (BM) washing hands after

helminths on Unguja defecation

Island, Zanzibar

Kounnavong [68], 2011 - Lao PDR

Soil-transmitted helminth infections and risk factors in preschool children in southern rural Lao People's Democratic Republic

Three rural remote districts of Savannakhet Province in southern Lao PDR; Pre-school children aged 12-59 months

Kato-Katz

Questionnaire, cross-sectional

Latrine access, improved water access

No adjusted WASH effect estimates identified

rV U* CO Author [cite ID], Year - Country Title of Article Setting and Population Sample Size Diagnosis Method Exposure Assessment and Study Method Main WASH Components Adjustment or Controlled Variables

S § Koura [160], Prevalence and risk Pregnant women at two 300 Kato-Katz Questionnaire, Wearing shoes No adjusted WASH effect

2011 - Benin factors for soil-transmitted maternity wards cross-sectional estimates identified

helminth infection in

o Beninese women during

Q_ pregnancy

Lee [161], Hookworm infections in Singaporean soldiers 113 Fecal screens via Questionnaire, interview, Water supply source, No adjusted WASH effect

D* rD 2007 - Brunei Singaporean soldiers after returning from jungle microscopy cross-sectional crawling on ground/soil, estimates identified

0 jungle training in Brunei training in Brunei shoe use

to Darussalam Darussalam

Luoba [162], Earth-eating and Pregnant women in 824 Kato-Katz Interview, prospective Geophagy No adjusted WASH effect

2005 - Kenya reinfection with intestinal Nyanza Province cohort (longitudinal estimates identified

helminths among pregnant intervention)

and lactating women in

western Kenya

Mahmud [127], Risk factors for intestinal 12 primary schools; 600 Kato-Katz and direct Questionnaire, Latrine, hygiene, water Age and sex

2013 - Ethiopia3 parasitosis, anaemia, and School children saline wetmount, observations, source

malnutrition among school aged 6-15 formalin ethyl cross-sectional

children in Ethiopia concentration technique

Matthys [71], Risk factors for Six agricultural zones 716 Kato-Katz Questionnaire, Water source, latrine use Clustering, sex, age, education

2007 - Côte d'Ivoire Schistosoma mansoni in the town of Man, cross-sectional level, socioeconomic status,

^ and hookworm in urban western Cote d'lvoire; household crowding

farming communities in Households

western Cote d'lvoire

Mihrshahi [128], The effectiveness of 4 Women of reproductive 366 Kato-Katz Questionnaire, Sanitary latrine system, Age, education status, work

2009 - Vietnam3 monthly albendazole age in Yen Bai province cross-sectional shoe use (inside/outside), number of

treatment in the children, meat consumption,

reduction of shoe use, latrine type, socio-

soil-transmitted helminth economic status, and

infections in women of handwashing

g reproductive age in Viet

OJ Nam

n Moraes [163], Impact of drainage and Nine poor urban areas 1,893 Kato-Katz Questionnaire, Sanitation Child's sex, child's age, number

NJ O 2004 - Brazil sewerage on intestinal of the city of Salvador cross-sectional of children aged 5-14 years in

nematode infections in (pop. 2.44 million), capital the household, crowding

— poor urban areas in of Bahia State, in Northeast (number of people per room),

§ Salvador, Brazil Brazil; children aged years of schooling of the

C between 5 and 14 years household head, monthly per

rt) old capita income, religion, animals

in the house, and the house

floor material

Issue 3 | e1001620 Moraes [164], 2007 - Brazil [Household solid waste bagging and collection and their health implications for children living in outlying urban settlements in Salvador, Bahia State, Brazil]. Nine peri-urban settlements of the city of Salva-pain, Bahia, Brazil; Children 5-14 years old 1,893 Kato-Katz Questionnaire, longitudinal Solid waste collection Age and sex of the child, number of household members, number of persons/ room, monthly family income per capita, religion, presence of lavatory, floor of the home, and excreta disposal of sewage

c V i/l £ « S -D •!•=

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Exposure Assessment and Study Method

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association of using an outside water pipe compared to an indoor tap for infection with any STH among Ethiopian infants (OR 0.21, 95% CI 0.09-0.51). Matthys and colleagues [71] found that having a private well significantly increased the odds of hookworm infection for farming households in western Cote d'Ivoire (OR 2.32, 95% CI 1.24-4.05). No evidence was found of an association between public or private water source and S. stercoralis infection

[72]. Having ''inadequate water supply'' in schools was strongly associated with increased infection with any STH among school children living on Pacific islands (OR 4.93, 95% CI 2.24-10.88)

Sanitation

Sanitation access (availability or use of latrines) was associated with lower likelihood of infection with any STH (k = 8, OR 0.66, 95% CI 0.57-0.76), T. tnchiura (k=7, OR 0.61, 95% CI 0.500.74), and A. lumbricoides (k=6, OR 0.62, 95% CI 0.44-0.88) (Figures 7-9). The quality of evidence for these meta-analyses was low due to the observational nature of included studies. We did not find evidence that sanitation access was associated with hookworm infection (k = 6, OR 0.80, 95% CI 0.61-1.06), which had very low evidence quality due to imprecision (Figure 10).

We found limited evidence that use of shared or private sanitation facilities influenced odds of STH infection. Worrell and colleagues [74] found in Kenya that participants using toilets located outside of their household premises had significantly increased odds of infection with any STH. In contrast, another study found that sharing latrines with neighboring households, compared with private latrine use, was associated with significantly lower odds of hookworm infection [71]. Few details were provided to contextualize this finding.

Hygiene

Three randomized controlled trials, two carried out in China and one in the Peruvian Amazon, found strong benefits for interventions that focused on promoting hygiene in schools [7577]. Xu and colleagues [75] assessed a randomized intervention that promoted handwashing with soap, both before eating and after defecation among 657 school children in three schools. All infected children were treated at baseline. At the 1-year follow-up, A. lumbricoides prevalence for children in the experimental group had declined by 35.7% (pre-intervention prevalence, 68.3%; postintervention cumulative infection rate, 43.9%) compared with an increase in the control group of 78% (pre-intervention, 41.4%; post-intervention, 73.7%); this was a statistically significant difference (p<0.01). The study's primary limitation was that schools were the unit of randomization, with two primary schools becoming controls and the third receiving the intervention. With so few clusters, it is highly possible that confounding factors were not comparable between the control and experimental groups.

More recently, Bieri and colleagues [76] reported on a singleblind, unmatched, cluster-randomized intervention trial involving 1,718 children (aged 9-10) in 38 schools over the course of one school year. Schools were randomly assigned to a health-education package, which included an entertainment-education cartoon video, or to a control package, which only displayed a health-education poster. All participants were treated with albendazole at baseline. At follow-up at the end of the school year, knowledge about STH was significantly higher in the intervention group, and almost twice as many intervention children (63.3% versus 33.4%, p<0.01) reported washing their hands after defecating. The incidence of STH infection (predominantly T. trichiura and A. lumbricoides) was also significantly improved in the experimental

Table 5. List of included studies with authors N-Z.

Author [cite ID], Year - Country Title of Article Setting and Population Sample Size Diagnosis Method Exposure Assessment and Study Method Main WASH Components Adjustment or Controlled Variables

N ara in [84], 2000 - India3 Prevalence of Trichuris trichiura in relation to socio-economic and behavioral determinants of exposure to infection in rural Assam Dibrugarh district in upper Assam; adults and children aged <15 years 580 Formol-ether concentration technique Questionnaire, cross-sectional Floor material, improved latrine, improved water Age, open defecation, type of flooring, family size, number of children in household

Nasr [66], 2013 - Malaysia3 Towards an effective control programme of soil-transmitted helminth infections among Orang Asli in rural Malaysia. Part 1: Prevalence and associated key factors 13 villages in Lipis district, Pahang; Orang Asli children aged <15 years 484 Formalin-ether sedimentation, Kato Katz, and Harada Mori Questionnaire, cross-sectional Handwashing, water, sanitation Age, family size, other WASH practices

Nguyen [165], 2006 - Vietnam Intestinal helminth infections among reproductive age women in Vietnam: prevalence, co-infection and risk factors 53 provinces; reproductive-age women 5,127 Kato-Katz Questionnaire, cross-sectional Latrine, manure fertilizer use Adjusted for infection with A. lumbricoides, T. trichiura, and interaction term between them.

Nishiura [81], 2002 - Pakistan Ascaris lumbricoides among children in rural communities in the Northern Area, Pakistan: prevalence, intensity, and associated socio-cultural and behavioral risk factors Five rural villages in the northern area of Pakistan; school children 492 Kato-Katz Questionnaire, cross-sectional Washing hands, latrine, eating soil, soap Age, sex, living with child under age of 5, other WASH practices

Norhayati [166], 1999 - Malaysia Some risk factors of Ascaris and Trichuris infection in Malaysian aborigine (Orang Asli) children Children ages 1-13 205 Kato-Katz and Harada Mori Questionnaire, cross-sectional Usage of well-water, usage of toilets No adjusted WASH effect estimates identified

Nwaneri [83], 2012 - Nigeria Intestinal helminthiasis in children with chronic neurological disorders in Benin City, Nigeria: intensity and behavioral risk factors Benin City child neurology clinic; Children with chronic neurological disorders 155 Kato-Katz Questionnaire, case-control with matching on age/sex Hygiene practices Age, sex

Olsen [167], 2001 - Kenya A study of risk factors for intestinal helminth infections using epidemiological and anthropological approaches Villages in Kisumu District, Nyanza Province, Kenya; All inhabitants over the age of 4 years 333 Kato-Katz (duplicate) Questionnaire, cross-sectional Latrine, soap Adjusted for crowding in households, children under five years of age, soap use, latrine presence.

Ortiz Valencia [168], 2005 - Brazil Spatial ascariasis risk estimation using socioeconomic variables. Children ages 1-9 1,550 Unclear Interview, cross-sectional Water filtration No adjusted WASH effect estimates identified

rV 15* Author [cite ID], Exposure Assessment Main WASH Adjustment or

rD Year - Country Title of Article Setting and Population Sample Size Diagnosis Method and Study Method Components Controlled Variables

§ § Parajuli [129], Behavioral and Nutritional Parsauni village in the 95 Direct wetmount Questionnaire, cross- Soap, walking barefoot Adjusts for age,

2009 - Nepal3 Factors and Geohelminth Sakhawaparsauni Village Lugol's iodine sectional ethnicity, gender, height.

"b_ Infection Among Two Ethnic Development Committee thin-smear method

o Groups in the Terai Region, (VDC) of Parsa district, Nepal;

3 rD Nepal Mushar and Tharu (ethnic

Q_ n* groups) inhabitants, aged

5* fD 20-60 years

0 Pham-Duc [115], Ascaris lumbricoides and Nhat Tan and Hoang Tay 1,425 Kato-Katz thick smear Questionnaire, cross- Water, sanitation, Age, sex, and season.

lO 2013 - Vietnam3 Trichuris trichiura infections communes in Kim Bang and forma I in-ether sectional handwashing

associated with wastewater district, Ha nam province; concentration techniques

and human excreta use in Individuals over 1 year old

agriculture in Vietnam

Phiri [134], Urban/rural differences in Two sites in the Blantyre 273 Stoll's egg count Questionnaire, cross- Sewage, walking barefoot Age, sex, mother's

2000 - Malawi3 prevalence and risk factors for area of Malawi: Ndirande a technique sectional education, school

intestinal helminth infection in densely populated, poor, attendance, sewage

southern Malawi urban township in Blantyre around house

city; and Namitambo, a poor

rural community in Chiradzulu

district; children between the

age of 3-14 years

Quintero [69], Household social determinants 55 municipalities of the 3,388; ~4.7 Kato-Katz Questionnaire, cross- Improved water, soil floor, Rural/urban, house

2012 - Venezuela of asearías is and trichuriasis in North Central Venezuela million with sectional sewage disposal vulnerability, waste

North Central Venezuela states Aragua, Carabobo, weights disposal practices

Miranda, Vargas and Capital

District; Children and adults

(3 months-60 years old)

Riess [169], Hookworm Infection and Participants from nine 6,375 Kato-Katz Questionnaire Latrine coverage, latrine Age, previous

2013 - Tanzania Environmental Factors in different sites in Mbeya type anthelmintic treatment,

Mbeya Region, Tanzania: A region, south-western clustering

Cross-Sectional, Tanzania

s OJ Population-Based Study

n Risquez [170], 2010 - Condiciones Students in the Panaquire- 69 Formol-ether Questionnaire Defecation practices No adjusted WASH effect

NJ Venezuela higiénico-sanitarias como Miranda school district concentration estimates identified

O factores de riesgo para las

parasitosis intestinales en una

< comunidad rural venezolana

c Roy [114], 2011 - Patterns and risk factors for 10 villages in Rural Mirzapur; 252 Formalin-ether Questionnaire, Improved water, excreta Adjusted by age, sex,

3 CO Bangladesh3 helminthiasis in rural children Rural children under 2 years sedimentation longitudinal disposal breastfeeding,

aged under 2 in Bangladesh old technique seasonality, and disposal

site of child feces

£ Saathoff [171], 2002 - Geophagy and its association Pupils in third grade 1,161 Kato-Katz Interview, cross-sectional Geophagy Family

c rD South Africa with geohelminth infection in (average age of 10.7 years)

LO rural schoolchildren from

northern KwaZulu-Natal, South

rD O Africa

CT> NJ O

"O 1— O en Table 5. Cont.

S CO Q_

G] 15* Author [cite ID], Exposure Assessment Main WASH Adjustment or

rD Year - Country Title of Article Setting and Population Sample Size Diagnosis Method and Study Method Components Controlled Variables

§ § Schmidlin [126], 2013 - Effects of hygiene and People in villages/hamlets in 1,894 Kato-Katz Questionnaire, interview, Sanitation behavior, Socioeconomic status,

Côte d'Ivoire3 defecation behavior on south-central that were small cross-sectional hygiene behavior age group, and sex

helminths and intestinal populations and similar pop.

0 protozoa infections in Taabo, structure

3 Cote d'lvoire

Q_ n Scolari [172], 2000 - Brazil Prevalence and distribution of School children ages 5-15 236 Kato-Katz Questionnaires (verified by Toilet ownership, location No adjusted WASH effect

=5* rD soil-transmitted helminth (STH) local field assistant), cross- of toilet, safe water access estimates identified

0 infections in urban and sectional

to indigenous schoolchildren in

Ortigueira, State of Parana,

Brasil: implications for control

Sherkhonov [173], 2013 - National intestinal helminth Schools from across country; 1,642 Kato-Katz Questionnaire, cross- Water, sanitation, Clustering, other final

Tajikistan survey among schoolchildren school children, 7-11 years old sectional handwashing covariates unclear

in Tajikistan: Prevalences, risk

factors and perceptions

Soares Magalhaes [174], Geographical analysis of the West African children 18,812 Kato-Katz Questionnaire (health Water source, toilet, floor No adjusted WASH effect

2011 - Ghana, Mali, and role of water supply and survey), cross-sectional material estimates identified

Burkina Faso sanitation in the risk of

helminth infections of children

in West Africa

00 Steenhard [175], 2009 - Concurrent infections and Poor semirural area (Bandim II 706 McMaster technique, formol-Questionnaire, cross- Improved water, improved No adjusted WASH effect

Guinea-Bissau socioeconomic determinants and Belem, near Bissau); school ether technique sectional sanitation estimates identified

of geohelminth infection: a children aged 4-12

community study of

schoolchildren in periurban

Guinea-Bissau

Stein ma nn [79], 2010 - Rapid appraisal of human Osh oblast; school children 1,262 Kato-Katz Questionnaire, cross- Washing vegetables, water Age, sex, ethnic group,

Kyrgyzstan3 intestinal helminth infections (grades 2 or 3, age: 6-15 years) sectional source, toilet use washing vegetables

among schoolchildren in Osh before eating, clustering

s oblast, Kyrgyzstan

QJ n Stothard [120], 2008 - Soitransmitted helminthiasis 10 Ungujan villages; mothers 681 Kato-Katz Questionnaire, cross- Latrine access, wearing Clustering, having

Zanzibar3 among mothers and their and their pre-SAC, 322 mothers, sectional shoes, playing on ground infected household

NJ O preschool children on Unguja 359 children member

Island, Zanzibar with emphasis

- upon ascariasis

Teixeira [176], 2004 - Environmental factors related Children (1-5 years old) in 753 Hoffman n-Pons-Janer Questionnaire Water quality complaints, Family income, age of

Brazil to intestinal helminth infections the subnormal settlement method feces disposal child

rD in subnormal settled areas, Juiz areas in the municipality of

11 | i: de Fora, MG Juiz de Fora, Mina Gerais.

Author [cite ID], Year - Country Title of Article Setting and Population Sample Size Diagnosis Method Exposure Assessment and Study Method Main WASH Components Adjustment or Controlled Variables

Trang [121], 2007 - Helminth infections among Yen So commune 807 Direct smear method Questionnaire, cross- Water source, latrine Age, sex, socioeconomic

Vietnam3 people using wastewater and (population 10,500 at the sectional status, other WASH

human excreta in peri-urban time of study), a rural area practices

agriculture and aquaculture in located about 10 km south

Hanoi, Vietnam of central Hanoi; adults of

15-70 years of age engaged in

agricultural activities and

preschool children (less than

72 months of age)

Trang [177], Low risk for helminth infection All females and males from 1,139 Direct smear method Questionnaire, interview, Latrine availability, Clustering, age, gender,

2006 - Vietnam in wastewater-fed rice 15-94 years old from 2 cross-sectional latrine status, handwashing excreta agricultural use

cultivation in Vietnam communes using different (soap), availability

irrigation for rice cultivation of drinking water

(wastewater and river water)

Traub [118], The prevalence, intensities Three tea-growing 328 Kato-Katz Questionnaire, cross- Shoes, water source, Socioeconomic status,

2004 - India3 and risk factors associated communities in Assam, India; sectional latrine use age, household

with geohelminth infection tea-growing communities of crowding, level of

in tea-growing communities rural Assam (no age education, religion, use

of Assam, India restrictions) of footwear when

outdoors, defecation

practices, pig ownership,

water source

Ugbomoiko [178], Socio-environmental factors Small rural village of llobu in 440 Kato-Katz Questionnaire, cross- Water source, latrine, Sex, age, which parent

2009 - Nigeria and ascariasis infection among Irepodu Local Government sectional distance to waste disposal reside with child,

school-aged children in llobu, Area of Osun State, Nigeria; number of playmates <6

Osun State, Nigeria children below 16 years of or >5 years old, period

age of residency, and

previous treatment

status.

Walker [179], 2011 - Individual Predisposition, Dhaka; households 2,929 Ether sedimentation Questionnaire, longitudinal Shared latrines, shared Clustering, age, sex,

Bangladesh Household Clustering and technique water sources, floor household

Risk Factors for Human material socioeconomic status,

Infection with Ascaris ethnicity, and household

lumbricoides: New characteristics

Epidemiological Insights

Wang [112], Soil-Transmitted Helminth 141 impoverished rural areas 1,707 Kato-Katz Questionnaire, cross- Washing hands, boiling STH treatment history,

2012 - China3 Infections and Correlated of Guizhou and Sichuan sectional water, latrine type, use of individual characteristics,

Risk Factors in Preschool Provinces in Southwest China; manure fertilizer health and sanitation

and School-Aged Children SAC and Pre-sac (3-5-year-old behaviors, and

in Rural Southwest China group and an 8-10-year-old household

group) characteristics

Wordemann [97], 2006 - Cuba3 Prevalence and risk factors of intestinal parasites in Cuban children San Juan y Martinez and Fomento; Cuban schoolchildren aged 4-14 1,320 Kato-Katz Questionnaire, cross-sectional Water source, latrine use Age, sex, municipality, urban/rural background, and interaction between municipality and urban/ rural background

Author [cite ID], Year - Country Title of Article Setting and Population Sample Size Diagnosis Method Exposure Assessment and Study Method Main WASH Components Adjustment or Controlled Variables

Worrell [74], 2013 - Kenya Water, Sanitation, and Hygiene-Related Risk Factors for Soil-Transmitted Helminth Infection in Urban School- and Pre-School-Aged Children in Kibera, Nairobi Kibera; pre-school and school-aged children 676 Kato-Katz (three stools) Questionnaire, observations, cross-sectional Numerous Age, presence of an infected sibling(s) in the household, household crowding, deworming in the last year, ability to meet water needs, treating water, and soap use

Xu [75], 2001 - China On cleanliness of hands in diminution of Ascaris lumbricoides infection in children Shaowu, Fujian Province; Children (pupils in preliminary school) 654 Kato-Katz Experimental, longitudinal Handwashing No adjusted WASH effect estimates identified

Yajima [180], 2009 -Vietnam High latrine coverage is not reducing the prevalence of soil-transmitted helminthiasis in Hoa Binh province, Vietnam Residents of Tien Xuan commune, Hoa Binh province, Vietnam 155 Kato-Katz Questionnaire, cross-sectional Latrine at home No adjusted WASH effect estimates identified

Yori [88], 2006 - Peru Seroepidemiology of strongyloidiasis in the Peruvian Amazon Residents of Santo Tom as, Peru 908 Direct smear, Baermann, simple sedimentation agar plate, serologic assays (ELISA) Questionnaire, cross-sectional Source and storage of drinking water, human waste disposal, wearing of shoes Age

Young [82], 2007 -Tanzania3 Association of geophagia with Ascaris, Trichuris and hookworm transmission in Zanzibar, Tanzania Pemba Island, Zanzibar; pregnant women 970 Kato-Katz Questionnaire, cross-sectional Geophagy, improved sanitation Geophagia during current pregnancy, age, urban/rural, number of durable goods, pit toilet in HH, formal education

aStudies contributed to a meta-analysis.

HAZ, height for age Z score; SES, socioeconomic status.

doi:10.1371/journal.pmed.1001620.t005

Figure 2. Retrieved articles by WASH group.

doi:10.1371/journal.pmed.1001620.g002

schools: 50% lower in the intervention group than in the control group (4.1% versus 8.4%, p<0.01).

Gyorkos and colleagues [77] conducted an open-label, cluster-randomized controlled trial using a hygiene education intervention in Peruvian primary schools. Within paired groups, 18 schools (1,089 fifth grade student participants) were randomly allocated to receive albendazole and the hygiene intervention or albendazole alone. The health intervention included a helminth-oriented class for students, a health curriculum workshop for teachers, and educational print materials. Four months after the intervention, the experimental group showed a significant reduction in A. lumbricoides intensity compared to deworming alone (adjusted incidence rate ratio [IRR] 0.42, 95% CI: 0.21-0.85). T. tnchiura and hookworm intensity did not show statistically significant improvements in the experimental group, nor did prevalence of any single STH species. Children in the intervention group showed significant improvements in STH knowledge and water treatment behaviors compared to the control, but not in most other hygiene practices (e.g., handwashing). The authors also noted that the prevalence of hookworm was low (about 5% compared to 30% for A. lumbricoides and 50% for T. trichiura) and that albendazole was less efficacious against T. trichiura than it was against A. lumbricoides.

Our meta-analyses of hygiene-related observational evidence provided estimates that are consistent with findings from these randomized controlled trials. Soap use or availability was significantly associated with lower odds of STH infection at the 5% level (k = 3, OR 0.53, 95% CI 0.29-0.98). The quality of the evidence was low, though the possibility of respondents' over-reporting hygiene behaviors could have underestimated the strength of the association (Figure 11). Handwashing, both before eating (k = 3, OR 0.38, 95% CI 0.26-0.55) and after defecating (k = 3, OR 0.45, 95% CI 0.35-0.58), was associated with lower odds of A. lumbricoides infection (Figures 12 and 13). Both analyses were of low quality due to the observational evidence available. Handwashing after defecation also was associated with reduced odds of any STH infection (k=5, OR 0.47, 95% CI 0.24-0.90). This meta-analysis had very low evidence quality due to high heterogeneity among estimates from the five pooled studies (I2 = 88%, 95% CI 74%-94%, Qp-value<0.01, Figure 14). All studies used Kato-Katz for diagnosis, but varied considerably in

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most other study characteristics, including population age, baseline prevalence, and geographic setting. Balen and colleagues reported limited evidence of a dose-response effect for handwashing; respondents who more frequently washed their hands with soap after defecation had lower odds of infection with any STH, but confidence intervals of the handwashing groups overlapped [78].

Washing vegetables was found to be associated with lower odds of STH infection in two studies. Steinmann and colleagues [79] found washing vegetables to be negatively associated with A. lumbricoides infection in school children (OR 0.69, 95% CI 0.500.95), while Hohmann and colleagues [80] found washing was associated with lower odds of T. trichiura (OR 0.50, 95% CI 0.310.79) and any STH infection (OR 0.71, 95% CI 0.51-0.99).

Our meta-analysis found evidence of a strong association between wearing shoes and lower odds of hookworm infection (k = 5, OR 0.29, 95% CI 0.18-0.47). The quality of the evidence was moderate, upgraded due to the magnitude of effect (Figure 15). Wearing shoes was also associated with lower odds of infection with any STH (k = 3, OR 0.30, 95% CI 0.11-0.83). The evidence quality for that analysis was low, downgraded by heterogeneity (I2 =74%, 95% CI 12-92%, Qp-value = 0.02) (Figure 16) but upgraded by a strong effect magnitude. Heterogeneity could have been introduced by many different factors, as the studies shared few characteristics. Three studies found mostly non-significant associations between geophagy (i.e., consumption of soil) and STH infection [81-83]. In adjusted models, households with dirt floors in India and Venezuela were found to have higher odds of T. trichiura and A. lumbricoides infection than were houses with other more elaborate flooring material [69,84]. Young children living with dirt floors in Colombia also showed higher odds of infection with any STH compared to those with tile or cement floors [85].

Integrated Interventions

In a cluster-randomized controlled trial, Freeman and colleagues examined a comprehensive WASH intervention in Kenyan schools that included hygiene promotion, water treatment and storage, and installation of sanitation infrastructure [27]. The intervention reduced reinfection prevalence (OR 0.56, 95% CI 0.31-1.00) and egg count (IRR 0.34, 95% CI 0.15-0.75) of A. lumbricoides, but not of T. trichiura or hookworm. Effects of the intervention differed by sex, with girls in the intervention group showing a significantly reduced A. lumbricoides infection intensity compared to the control group; boys in the intervention group did not show any significant difference from controls. Shoe-wearing and geophagy also emerged as effect modifiers for hookworm and T. trichiura infection intensity, respectively.

Dumba and colleagues found no statistically significant benefit of a participatory hygiene and sanitation transformation (PHAST) intervention when compared with a control group that only received deworming [86]. PHAST uses training sessions to encourage communities to identify problems in their own environment, decide what aspects need to be improved, and then implement changes. Parents or guardians of participating children in 19 villages received three PHAST education sessions. Participants in both control and experimental villages received albendazole and showed significant reductions in helminth prevalence compared with baseline, but the prevalence in the experimental group did not decline more than that among the control children. This study grouped Hymenolepis nana and Enterobius vermicularis with STH in analysis, but only a handful of participants were infected by H. nana or E. vermicularis, whereas STH prevalence was very high (>80%).

Table 8. Meta-analysis results.

Odds Ratio

Meta-Analysis (95% CI) Tau Squared Q p-Value /2 (95% Uncertainty) Egger's Test P n Studies GRADE

Piped water use (any STH) 0.93 (0.28-3.11) 1.86 <0.01 98.6 (98-99) <0.01 5 Very low

Piped water use 0.40 (0.39-0.41) 0 0.62 0 (0-85) 0.08 4 Low (A. lumbricoides)

Piped water use (T. trichiura) 0.57 (0.45-0.72) 0 0.93 0 (0-90) 0.67 3 Low

Treated water use (any STH) 0.46 (0.36-0.60) 0 0.82 0 (0-90) 0.36 3 Low

Wearing shoes (hookworm) 0.29 (0.18-0.47) 0.09 0.09 30 (0-73) 0.03 5 Moderate

Wearing Shoes (any STH) 0.30 (0.11-0.83) 0.60 0.02 74 (12-92) 0.29 3 Low

Soap use/availability 0.53 (0.29-0.98) 0.07 0.28 21 (0-92) 0.98 3 Low (any STH)

Handwashing before eating 0.38 (0.26-0.55) 0 0.90 0 (0-90) 0.59 3 Low (A. lumbricoides)

Handwashing after defecation 0.45 (0.35-0.58) 0 0.55 0 (0-90) 0.29 3 Low (A. lumbricoides)

Handwashing after defecation 0.47 (0.24-0.90) 0.44 <0.01 88 (74-94) 0.58 5 Very low (any STH)

Sanitation access (any STH) 0.66 (0.57-0.76) 0 0.70 0 (0-68) 0.57 8 Low

Sanitation access (T. trichiura) 0.61 (0.50-0.74) 0.01 0.29 19 (0-62) 0.49 7 Low

Sanitation access (A. lumbricoides) 0.62 (0.44-0.88) 0.05 0.22 28 (0-70) 0.83 6 Low

Sanitation access (hookworm) 0.80 (0.61-1.06) 0.01 0.34 11 (0-77) 0.13 6 Very low

doi:10.1371/journal.pmed.1001620.t008

Strongyloides stercorals

We found 12 studies that investigated the relationship between WASH and S. stercoralis infection, but only located relevant effect estimates in five. Among school children in Cambodia, Khieu and colleagues found crude associations between infection and handwashing, shoe-wearing, and sanitation access [87]. Hall and colleagues found mixed results for a range of sanitation-related exposures, with some evidence that open defecation and use of community latrines were associated with higher odds of S. stercoralis infection in children [72]. In a multivariable model using data from a rural Peruvian community, Yori and colleagues found that wearing shoes never or occasionally (versus more frequently) was associated with higher odds of infection (OR 1.89, 95% CI 1.10— 3.27) [88]. Knopp and colleagues did not find a significant association between S. stercoralis infection and home latrine ownership or handwashing after defecation [89].

Discussion

We conducted a systematic review and meta-analysis of the relationship between WASH access and practices and STH infection. Our analysis revealed that WASH access and practices are generally, but not universally, associated with lower odds of STH infection. Particularly strong associations emerged between wearing shoes and hookworm infection (OR 0.29, 95% CI 0.180.47), piped water use and A. lumbricoides infection (OR 0.40, 95% CI 0.39-0.41), and treated water use and infection by any STH (OR 0.46, 95% CI 0.36-0.60). Pooled estimates for all meta-analyses, except for two (i.e., piped water use for any STH and sanitation access for hookworm), indicated at least a 33% lower odds of STH infection associated with specific WASH behaviors or access (Table 8). All but two of the meta-analyses were statistically significant at the 5% level.

On the basis of the evidence available, this review primarily draws upon observational studies. Observational research typically

has greater risks to internal validity than randomized controlled trials, but such research is also key to providing a broad evidence base. When conducted well, randomized controlled trials provide the strongest evidence of a causal relationship between an exposure (e.g., an intervention) and an outcome. In the WASH context, however, conducting RCTs can be ethically and financially challenging. Traditional randomized designs can be costly and require that a subset of the target population be allocated to the control group, receiving only a limited intervention. Observational studies can be conducted more quickly and affordably in a wide array of contexts, allowing for WASH access and practices to be investigated in different social-ecological systems. This diversity is critical, since the effectiveness of specific WASH interventions can vary widely across settings, and interventions will most likely provide the greatest impact after being tailored to local conditions. Looking forward, a stepped wedge design represents a powerful compromise between ethics, operational feasibility, and internal validity. With a stepped wedge approach, the rollout of an intervention is randomized so that all participants eventually receive the study benefits, but at different times. Because many WASH interventions require staggered implementation owing to limited financial and human resources, randomizing the order in which communities are visited is often feasible. Combined with longitudinal data analysis, this design allows for robust assessments that can integrate with many interventions without radically altering implementing organizations' plans.

This review highlights important gaps in the WASH and STH body of literature. For example, only a few of the studies that met our inclusion criteria investigated the impact of sharing latrines (n = 6) or latrine maintenance (n = 3) on STH infection. The effect of treating water (n =7) and geophagy (n =10) were also infrequently explored. S. stercoralis was by far the least commonly

investigated STH infection, reflecting another important knowledge gap.

Table 9. Meta-analysis grades.

s co Q_

n] U* CO Meta-Analysis Group Internal Bias Inconsistency Indirect Imprecise Publication Bias Large Effect Dose Response Confounding Towards Null Overall

S § "b o 3 Q. Piped water access (any STH) Moderate, used help of observations to assess exposure and used adjusted estimates Yes, l2 = 98.6% Nothing serious Yes, 95% CI includes null Likely, but unclear due to strong heterogeneity Nothing strong Not found Nothing strong Very low, due to heterogeneity and wide confidence interval

=3* rD 0 to Piped water access (A lumbricoides) Moderate, observational studies but all use adjusted estimates l2 = (0°/ 0%, 95% CI -85%) Nothing serious Nothing serious Likely, but direction suggests slightly more protective effect Nothing strong Not found Nothing strong Low

Piped water access (7. trichiura) Moderate, observational studies but all use adjusted estimates l2 = (0°/ 0%, 95% CI -90%) Nothing serious Nothing serious Undetected Nothing strong Not found Nothing strong Low

Treated water use (any STH) Moderate, observational studies but all use adjusted estimates l2 = (0°/ 0%, 95% CI -90%) Nothing serious Nothing serious Undetected Nothing strong Not found Nothing strong Low

NJ Wearing shoes (hookworm) Moderate, observational studies but all use adjusted estimates /2 = (0°/ 29.7%, 95% CI -73%) Nothing serious Nothing serious Likely Strong effect evident (OR 0.29) Not found Yes, hygiene behaviors overreported Moderate, due to strong effect size

Wearing shoes (any STH) Moderate, observational studies but all use adjusted estimates Yes, I2 = 74% Nothing serious Nothing serious Likely, but unclear due to strong heterogeneity Strong effect evident (OR 0.30) Not found Yes, hygiene behaviors overreported Low, upgraded from effect size, downgraded from heterogeneity

Soap use/availability (any STH) Moderate, observational studies but all use adjusted estimates l2 = (0°/ 20.8%, 95% CI -92%) Nothing serious Nothing serious Undetected Nothing strong Not found Yes, hygiene behaviors overreported Low

S OJ n NJ O Handwashing before eating (A. lumbricoides) Moderate, observational studies but all use adjusted estimates l2 = (0°/ 0%, 95% CI -90%) Nothing serious Nothing serious Undetected Nothing strong Not found Yes, hygiene behaviors overreported Low

§ c 3 CO Handwashing after defecation (A. lumbricoides) Moderate, observational studies but all use adjusted estimates l2 = (0°/ 0%, 95% CI -90%) Nothing serious Nothing serious Undetected Nothing strong Not found Yes, hygiene behaviors overreported Low

11 I Issue Handwashing after defecation (any STH) Moderate, observational studies but all use adjusted estimates Yes - I2 =88% Nothing serious Yes, 95% CI includes null Undetected Nothing strong Not found Yes, hygiene behaviors overreported Very low, due to high heterogeneity

LO rD O O Sanitation access (any STH) Moderate, observational studies but all use adjusted estimates l2 = (0°/ 0%, 95% CI -68%) Nothing serious Nothing serious Undetected Nothing strong N/A Nothing strong Low

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A total of 35 studies contributed data to the 14 meta-analyses. A lack of standardized WASH definitions across studies limited our ability to pool results via additional meta-analyses. More consistent use of the Joint Monitoring Program's water and sanitation ladder definitions would aid future review efforts. Additional meta-analyses could have been conducted if all reviewed studies had provided relevant adjusted estimates of association. For example, many studies investigated the relationship between "toilet sharing'' on any STH infection and ''water access'' on hookworm infection, but a dearth of reported adjusted estimates stymied meta-analyses of these relationships (Table 7).

Few studies analyzed the relationship between fecal egg count, a proxy for intensity of infection, and WASH [27,81,90], even though intensity of infection represents a more relevant predictor for morbidity than prevalence alone [91]. A lack of measures on this relationship represents a considerable gap in the literature, though many studies did report broadly on intensity of infection. Zero-inflated modeling strategies have recently shown promise in analyzing fecal egg count datasets, which often contain excess zero counts due to some individuals not harboring infections [92-94]. Contemporary analysis of existing data represents a potentially cost-effective mechanism for yielding additional insights into this topic.

Our findings build upon past reviews by Asaolu and Ofoezie [32] and Ziegelbauer and colleagues [26], which both concluded that WASH represents a valuable strategy for STH control. Although Asaolu and Ofoezie did not conduct a meta-analysis, their comprehensive review found broad evidence of reductions in STH prevalence and intensity resulting from multiple types of WASH interventions. Asaolu and Ofoezie concluded that improvements in sanitation systems and hygiene practices were important tools to not only sustain preventive chemotherapy benefits, but also help protect the uninfected. Results from our meta-analyses support their conclusion using systematically aggregated quantitative data. Ziegelbauer and colleagues focused more specifically on latrine access and use, conducting a rigorous meta-analysis using primarily crude odds ratios. The results from our meta-analyses, which drew upon adjusted odds ratios, are consistent with their findings and lend additional support to the value of sanitation improvements for STH control. Our meta-analyses also broadened focus to include water and hygiene components, allowing for a quantitative summary of currently available evidence across the three core WASH domains.

Our analysis of the relationship between access to a piped water source and STH infection yielded significantly protective associations for A. lumbricoides and T. trichiura, but not for any STH infection generally. The meta-analysis of any STH yielded strong heterogeneity statistics, reflecting a spread in observed effects. While the inclusion of hookworm infections in the ''any STH'' analysis may seem like a possible source of the variability, we found no clear evidence to support this explanation. The only study that analyzed hookworm infection and piped water use with an adjusted model found a significantly protective association, so other sources of heterogeneity should be considered.

The presence of heterogeneity can be systematically investigated by statistics like Moran's I2 and Cochran's Q, but these global tests do not themselves uncover specific causes of heterogeneity. Diversity among studies can originate from a plethora of sources: population, setting, diagnostic approach, study design, analytic method, definitions, and so on. Without additional subgroup analysis or meta-regression, which both require a large body of studies, it is difficult to investigate the myriad potential causes of heterogeneity. Without clarification, the presence of heterogeneity indicates that pooled results are averaging multiple related, but

[Citation] First Author (Year)

Odds Ratio (95% Confidence Interval)

1 1 1 [111] Ahmed (2011) -•-1- 1 1 0.37 (0.18, 0.78)

1 [112] Wang (2012) -«- 1 0.48 (0.35, 0.65)

1 [113] Aimpun (2004) -■- 1 0.46 (0.25, 0.85)

Overall ! 12:0% (95% CI: 0 - 90) T^ 1 1 1 1 1 1 1 II 0.46 (0.36, 0.60) I I I

.25 .5124

Odds Ratio - Log Scale Less than One Favors WASH

Figure 3. Meta-analysis of the association between use of treated water and infection with any STH [111-113].

doi:10.1371/journal.pmed.1001620.g003

Figure 4. Meta-analysis of the association between use of piped water use and any STH infection [70,97,114-116].

doi:10.1371/journal.pmed.1001620.g004

Figure 5. Meta-analysis of the association between use of piped water and A. lumbricoides infection [66,69,79,117].

doi:10.1371/journal.pmed.1001620.g005

distinct effects. For example, access to piped water could have different levels of benefit depending on distance to the source [95,96], water quality [70,97], or other unknown factors— especially when studies use different diagnostic assays and are conducted in a variety of community settings.

Concerning sanitation, our meta-analyses of access to sanitation yielded considerably lower odds of infection with A. lumbricoides, T. trichiura, or any STH for those with latrine access. We did not find evidence of a statistically significant association between sanitation and hookworm, though the pooled estimate suggested reduced

Figure 6. Meta-analysis of the association between use of piped water and T. trichiura infection [115,118,119].

doi:10.1371/journal.pmed.1001620.g006

Figure 7. Meta-analysis of the association between sanitation access and infection with any STH [97,111,112,114,115,120-122].

doi:10.1371/journal.pmed.1001620.g007

odds of infection. Our sanitation findings were comparable to those found by Ziegelbauer and colleagues, who asserted that improved sanitation access should be prioritized alongside preventive chemotherapy to achieve a sustainable reduction in helminthiasis burden. They found an overall pooled odds ratio of 0.51 (95% CI 0.44-0.61) for the effect of sanitation availability and use, while we found an odds ratio of 0.66 (95% CI 0.57-0.76). Species-specific results were similar as well, with the exception of hookworm. Differences in the magnitude of our findings may be attributed to the use of adjusted measures in our analysis, since Ziegelbauer and colleagues used unadjusted estimates. In addition, we did not include separate estimates for sanitation use and access. Taken together, these two reviews support the hypothesis that improved access to, and use of, sanitation prevents STH infection. Additional research could help explore the complementarity of sanitation promotion with MDA.

For hygiene, three randomized controlled trials provided strong evidence linking hygiene practices—especially handwashing with soap—to reductions in STH infection [75-77]. However, not all hygiene interventions may be effective in reducing STH infection [86]. Our meta-analyses of the effect of handwashing before eating and after defecation for A. lumbricoides infection, along with handwashing after defecation and soap use for any STH infection, also yielded significant results that suggest protective effects. Accurately assessing handwashing is challenging; self-reported and observed measures are often highly biased [33]. Many studies rely on self-report, but individuals have consistently been shown to

over-report handwashing behaviors [98]. Heterogeneity was exhibited in the analysis of handwashing after defecation, suggesting that the benefits of handwashing may vary considerably depending on circumstances and definitions. Beyond handwash-ing, our analysis also showed that wearing shoes was associated with significantly lower odds of infection with hookworm and any STH.

These results may be of interest to several audiences. Researchers can take note of the gaps in the literature identified by this review and focus investigation on key outstanding questions (e.g., the impact of WASH on S. stercoralis infections). Policymakers should understand that, despite gaps in data, these findings provide a broad evidence base in support of WASH for STH control—especially from randomized trials for hygiene interventions. WASH practitioners will recognize that these findings provide further support for their efforts and, we hope, will consider partnering with STH researchers to evaluate future interventions.

Strengths and Limitations

Our review included only adjusted effect estimates in metaanalyses, which lends greater strength to our pooled results [37]. Many different variables were controlled across studies, which may contribute to heterogeneity. However, this variation in adjusted models may also serve as a small buffer against the inherent heterogeneity across observational studies. Different covariates will vary in importance for different populations and circumstances, so a broad review like ours may benefit from pooling estimates from

Figure 8. Meta-analysis of the association between sanitation access and A. lumbricoides infection [66,82,115,121,123,124].

doi:10.1371/journal.pmed.1001620.g008

Figure 9. Meta-analysis of the association between sanitation access and T. trichiura infection [82,84,97,115,124-126].

doi:10.1371/journal.pmed.1001620.g009

Figure 10. Meta-analysis of the association between sanitation access and hookworm infection [65,124,126-128]. Note: Chongsuvivatwong et al [65]. reported on two separate studies in their 1996 article.

doi:10.1371/journal.pmed.1001620.g010

Figure 11. Meta-analysis of the association between soap use and infection with any STH [70,73,129].

doi:10.1371/journal.pmed.1001620.g011

Figure 12. Meta-analysis of the association between handwashing before eating and infection with A. lumbricoides [80,125,130].

doi:10.1371/journal.pmed.1001620.g012

models that were adapted by researchers to best fit their data and contexts. There are many factors that could confound the relationship between WASH access or practices and STH prevalence, including socioeconomic status, age, and gender. Consideration of only crude associations would likely overstate the magnitude of effect for WASH exposures or even misinterpret the true direction of effect [99]. Limiting our focus to adjusted

measures of effect reduces the number of eligible studies, which may impact the generalizability of our results. This strategy also amplifies the impact of selective reporting, since many authors reported only statistically significant adjusted estimates.

Evidence quality was typically "low"—the default GRADE for observational research—meaning that our confidence in pooled effect estimates is limited, and that the true effect may be markedly

Figure 13. Meta-analysis of the association between handwashing after defecation and infection with A. lumbricoides [66,80,116].

doi:10.1371/journal.pmed.1001620.g013

Figure 14. Meta-analysis of the association between handwashing after defecation and infection with any STH [73,80,112,116,131].

doi:10.1371/journal.pmed.1001620.g014

Figure 15. Meta-analysis of the association between wearing shoes and hookworm infection [65,118,132,133]. Note: Chongsuvivatwong et al. [65] reported on two separate studies in their 1996 article.

doi:10.1371/journal.pmed.1001620.g015

Figure 16. Meta-analysis of the association between wearing shoes and infection with any STH [111,129,134].

doi:10.1371/journal.pmed.1001620.g016

different from the results reported here [40]. A much stronger case can be made for the benefit of hygiene because of the evidence provided by recent randomized controlled trials, but results from our meta-analyses suggest that the protective effect of hygiene practices on STH infection may be variable depending on context.

Publication bias also represents a concern. Five meta-analyses (piped water for any STH and A. lumbricoides, wearing shoes for hookworm and any STH, sanitation access for hookworm) showed evidence of publication bias in funnel plot assessments. However, two of those plots (piped water for A. lumbricoides and sanitation access for hookworm) showed that larger studies yielded more protective associations, suggesting that the results from those analyses may be underestimating the true relationship strength. This was unexpected—and possibly caused by the natural heterogeneity across observational studies—since larger studies are traditionally expected to show smaller magnitudes of effect. Heterogeneity creates great difficulty in assessing publication bias accurately with statistical tests, so it is impossible to know how pronounced publication bias may be throughout our meta-analyses [100].

Conclusion

A vibrant discussion continues in the literature about the role of MDA in measurably mitigating morbidity from STH infection at the population level [101-106]. MDA alone is unlikely to permanently interrupt STH transmission. Our review provides evidence that WASH is a valuable component for STH control strategies, but guidelines and targets for the integration of these approaches are needed. Increased attention towards WASH for STH also has great potential to catalyze synergies with integrated NTD control programs, while jointly elevating awareness of WASH and NTDs [5,28,107]. Additional high-quality research into the potential of integrated WASH interventions is merited,

specifically on the complementarity of WASH and MDA. Recent and ongoing research continues to build an evidence-base that can guide policymaking and programmatic decisions [27,28,108]. Increased collaboration between the health and WASH sectors represents a key enterprise for the future of NTD control and elimination [109,110].

Supporting Information

Figure S1 Funnel plot for treated water use and any STH infection.

Figure S2 Funnel plot for piped water use and any STH infection.

Figure S3 Funnel plot for piped water use and A. lumbricoies infection.

Figure S4 Funnel plot for piped water use and T. trichiura infection.

Figure S5 Funnel plot for sanitation access and any STH infection.

Figure S6 Funnel plot for sanitation access and A. lumbricoides infection.

Figure S7 Funnel plot for sanitation access and T. trichiura infection.

Figure S8 Funnel plot for sanitation access and hookworm infection.

Figure S9 Funnel plot for soap use and any STH infection.

Figure S10 Funnel plot for handwashing before eating and A. lumbricoides infection.

Figure S11 Funnel plot for handwashing after defecating and A. lumbricoides infection.

Figure S12 Funnel plot for handwashing after defecating and any STH infection.

Figure S13 Funnel plot for wearing shoes and hookworm infection.

Figure S14 Funnel plot for wearing shoes and any STH infection.

Table S1 Excluded studies.

Table S2 Study bias assesment.

Text S1 PRISMA checklist.

Text S2 MOOSE checklist.

Text S3 Original methods protocol.

Acknowledgments

We thank Rachel Stelmach and Claire Still for their stellar work on data collection and extraction. We also thank Shuyuan Huang, Peiling Yap, and Yingsi Lai for their assistance translating Chinese-language articles.

Author Contributions

Conceived and designed the experiments: ECS DGA MES SO MCF. Performed the experiments: ECS DGA MCF. Analyzed the data: ECS. Contributed reagents/materials/analysis tools: ECS MES. Wrote the first draft of the manuscript: ECS DGA MCF. Contributed to the writing of the manuscript: ECS DGA MES SO JU MCF. ICMJE criteria for authorship read and met: ECS DGA MES SO JU MCF. Agree with manuscript results and conclusions: ECS DGA MES SO JU MCF.

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Editors' Summary

Background. Worldwide, more than a billion people are infected with soil-transmitted helminths (STHs), parasitic worms that live in the human intestine (gut). These intestinal worms, including roundworm, hookworm, and whipworm, mainly occur in tropical and subtropical regions and are most common in developing countries, where personal hygiene is poor, there is insufficient access to clean water, and sanitation (disposal of human feces and urine) is inadequate or absent. STHs colonize the human intestine and their eggs are shed in feces and enter the soil. Humans ingest the eggs, either by touching contaminated ground or eating unwashed fruit and vegetables grown in such soil. Hookworm may enter the body by burrowing through the skin, most commonly when barefooted individuals walk on infected soil. Repeated infection with STHs leads to a heavy parasite infestation of the gut, causing chronic diarrhea, intestinal bleeding, and abdominal pain. In addition the parasites compete with their human host for nutrients, leading to malnutrition, anemia, and, in heavily infected children, stunting of physical growth and slowing of mental development.

Why Was This Study Done? While STH infections can be treated in the short-term with deworming medication, rapid re-infection is common, therefore a more comprehensive program of improved water, sanitation, and hygiene (WASH) is needed. WASH strategies include improvements in water access (e.g., water quality, water quantity, and distance to water), sanitation access (e.g., access to improved latrines, latrine maintenance, and fecal sludge management), and hygiene practices (e.g., handwashing before eating and/or after defecation, water treatment, soap use, wearing shoes, and water storage practices). WASH strategies have been shown to be effective for reducing rates of diarrhea and other neglected tropical diseases, such as trachoma;how-ever, there is limited evidence linking specific WASH access or practices to STH infection rates. In this systematic review and meta-analysis, the researchers investigate whether WASH access or practices lower the risk of STH infections. A systematic review uses predefined criteria to identify all the research on a given topic; a meta-analysis is a statistical method that combines the results of several studies.

What Did the Researchers Do and Find? The researchers identified 94 studies that included measurements of the relationship between WASH access and practices with one or more types of STHs. Meta-analyses of the data from 35 of these studies indicated that overall people with access to WASH strategies or practices were about half as likely to be infected with any STH. Specifically, a lower odds of infection with any STH was observed for those people who use treated water (odd ratio [OR] of 0.46), have access to sanitation (OR of 0.66), wear shoes (OR of 0.30), and use soap or have soap availability (OR of 0.53) compared to those without access to these practices or strategies. In addition, infection with roundworm was less than half as likely in those who practiced handwashing both before eating and after defecating than those who did not practice handwashing (OR of 0.38 and 0.45, respectively).

What Do These Findings Mean? The studies included in this systematic review and meta-analysis have several shortcomings. For example, most were cross-sectional surveys—studies that examined the effect of WASH strategies on STH infections in a population at a single time point. Given this study design, people with access to WASH strategies may have shared other characteristics that were actually responsible for the observed reductions in the risk of STH infections. Consequently, the overall quality of the included studies was low and there was some evidence for publication bias (studies showing a positive association are more likely to be published than those that do not). Nevertheless, these findings confirm that WASH access and practices provide an effective control measure for STH. Controlling STHs in developing countries would have a huge positive impact on the physical and mental health of the population, especially children, therefore there should be more emphasis on expanding access to WASH as part of development guidelines and targets, in addition to short-term preventative chemotherapy currently used.

Additional Information. Please access these websites via the online version of this summary at http://dx.doi.org/10. 1371/journal.pmed.1001620.

• The US Centers for Disease Control and Prevention also provides detailed information on roundworm, whipworm, and hookworm infections

• The World Health Organization provides information on soil-transmitted helminths, including a description of the current control strategy

• Children Without Worms (CWW) partners with Johnson & Johnson, GlaxoSmithKline, the World Health Organization, national ministries of health and education, non-governmental organizations, and others to promote treatment and prevention of soil-transmitted helminthiasis. CWW advocates a four-pronged, comprehensive control strategy—Water, Sanitation, Hygiene Education, and Deworming (WASHED) to break the cycle of reinfection

• The Global Network for Neglected Tropical Diseases, an advocacy initiative dedicated to raising the awareness, political will, and funding necessary to control and eliminate the most common neglected tropical diseases, provides information on infections with roundworm (ascariasis), whipworm (trichuriasis), and hookworm

• WASH for the Neglected Tropical Diseases is a repository of information on WASH and the neglected tropical diseases (NTDs) such as soil-transmitted helminthiasis, and features a resource titled ''WASH and the NTDs: A Manual for WASH Implementers.''

• Two international programs promoting water sanitation are the World Health Organization Water Sanitation and Health program and the World Health Organization/United Nations Childrens Fund Joint Monitoring Programme for Water Supply and Sanitation

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