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COHEN AND COLFORD
PATHOGEN-SPECIFIC HEALTH EFFECTS OF BOILING DRINKING WATER
Effects of Boiling Drinking Water on Diarrhea and Pathogen-Specific Infections in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis Alasdair Cohen1,2* and John M. Colford, Jr.1 1 2
Division of Epidemiology, School of Public Health, University of California at Berkeley, Berkeley, California; Department of Environmental Science, Policy and Management, University of California at Berkeley, Berkeley, California
* Address correspondence to Alasdair Cohen, Division of Epidemiology, School of Public Health, University of California at Berkeley, 50 University Hall, Berkeley, CA 94720-7360. E-mail:
[email protected]
Abstract. Globally, approximately 2 billion people lack microbiologically safe drinking water. Boiling is the most prevalent household water treatment method, yet evidence of its health impact is limited. To conduct this systematic review, we searched four online databases with no limitations on language or publication date. Studies were eligible if health outcomes were measured for participants who reported consuming boiled and untreated water. We used reported and calculated odds ratios (ORs) and random-effects meta-analysis to estimate pathogen-specific and pooled effects by organism group and nonspecific diarrhea. Heterogeneity and publication bias were assessed using I2, metaregression, and funnel plots; study quality was also assessed. Of the 1,998 records identified, 27 met inclusion criteria and reported extractable data. We found evidence of a significant protective effect of boiling for Vibrio cholerae infections (OR = 0.31, 95% confidence interval [CI] = 0.13–0.79, N = 4 studies), Blastocystis (OR = 0.35, 95% CI = 0.17–0.69, N = 3), protozoal infections overall (pooled OR = 0.61, 95% CI = 0.43–0.86, N = 11), viral infections overall (pooled OR = 0.83, 95% CI = 0.7–0.98, N = 4), and nonspecific diarrheal outcomes (OR = 0.58, 95% CI = 0.45–0.77, N = 7). We found no evidence of a protective effect for helminthic infections. Although our study was limited by the use of self-reported boiling and non-experimental designs, the evidence suggests that boiling provides measureable health benefits for pathogens whose transmission routes are primarily water based. Consequently, we believe a randomized controlled trial of boiling adherence and health outcomes are needed. INTRODUCTION
Across low- and middle-income countries (LMICs), close to 2 billion people lack reliable access to microbiologically safe drinking water, and approximately 500,000 people, mostly children, die annually due to unsafe or insufficient drinking water.1–6 In the most recent (2015) Global Burden of Disease study,7 unsafe water was ranked 14th among global health risks. Pointof-use household water treatment (HWT) technologies are often recommended when reliable access to safe water is limited. Filtration (ceramic, biosand, and micro), chlorination (with/without flocculation), solar disinfection, and ultraviolet (UV) disinfection are the primary HWT technologies currently promoted in LMICs. When used correctly, these HWT technologies effectively improve drinking water quality and can reduce related morbidity and mortality.8–10 However, after decades of extensive promotion efforts, achieving the widespread and sustained adoption of these HWT technologies remains a challenge.11–15
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Boiling is the most commonly used reported HWT method globally, with an estimated 1.2 billion users (?70% of all HWT users).14,16,17 The reported use of boiling is particularly widespread in many Asian nations, including China, where as many as 85% of rural residents report boiling drinking water,16 as well as an estimated 95% in Mongolia and 91% in Indonesia and Vietnam.14 Compared with HWT products such as chlorine or filters, however, relatively few health or water, sanitation, and hygiene (WASH) studies have focused on boiling specifically. Among the boiling-focused studies, most evaluated boiling and water quality outcomes, but not health outcomes. Water-quality-focused studies in Cambodia, Guatemala, India, Indonesia, Peru, and Vietnam all found significant post-boiling reductions of fecal contamination indicators.18–23 Although boiling is straightforward to use and microbiologically effective, as with other HWT methods, its effectiveness depends on correct and consistent use. Boiled water is also susceptible to recontamination, and the fuels used to boil water in LMIC settings often produce household air pollution (HAP).23–26 In addition, there is a potential for injury via skin exposure to hot or boiling water. The relative paucity of boiling-focused health research has not gone unnoticed. For example, a comprehensive review of point-of-use water treatment technologies and methods for use in emergencies cited a “lack of epidemiological confirmed health impact” for boiling,27 and a recent World Health Organization report noted that there is relatively little research on boiling’s effectiveness for diarrheal reduction.5 Moreover, as noted in the most recent Cochrane Review on interventions to improve drinking water quality, no randomized controlled trials (RCTs) have been conducted to evaluate boiling.28 Similarly, although there are a number of systematic reviews and summary articles on the use of chlorination, filtration, and solar disinfection,3,12,13,29–31 as far as we are aware, there are no such reviews focused on boiling and health outcomes, or on boiling and water quality, specifically (in part because some previous reviews only considered experimental study designs as eligible). Furthermore, these reviews, and most of the WASH studies they are based on, tend to use diarrheal disease as the primary health outcome. Because many pathogens result in diarrheal symptoms, these analyses do little to clarify the relative effectiveness of different HWT methods for exposure to specific pathogens or organism groups. A clearer understanding of boiling’s impact on water-related disease prevention is needed. We conducted this systematic review and meta-analysis to bring together the evidence on boiling and health outcomes in LMICs. This study is also one of the few such reviews to attempt to estimate pooled effects for specific pathogens and organism groups,32,33 as well as for nonspecific diarrheal disease outcomes. MATERIALS AND METHODS
Search strategy and selection criteria. To identify potentially eligible studies, we searched four online databases: PubMed/MEDLINE, EMBASE, Web of Science, and the Cochrane Library. Search terms were selected with the goal of finding all articles that might potentially address health outcomes associated with the boiling of drinking water in LMICs. Four sets of search terms were used to identify all articles focused on drinking water, drinking water treatment (including, but not limited to, boiling), health outcomes known to be associated with the consumption of contaminated drinking water, and the names and alternate names/spellings of all LMICs.
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Because some search engines retrieve fewer results when truncation is used,34 we included all possible word variants in our lists of search terms (e.g., rather than using “boil*,” we searched for “boils,” “boiled,” and “boiling”). The search terms, sets, and an explanation of the Boolean operators used are provided in Supplemental Table 1. The final database literature searches were conducted on January 21, 2016 (the complete searches used for each database are provided in Supplemental Tables 2–5). No restrictions were put in place with regard to publication date, type, or language. In addition, a hand-search was conducted by consulting the reference sections of articles already known to discuss boiling and drinking water treatment as well as a targeted search for papers using Google Scholar (grey literature was not included). Following the convention to define eligibility using the PICO criteria,35 studies were considered eligible if they included human participants in LMICs; measured infectious health outcomes (disease occurrence) due to pathogens with at least one water-related transmission route; and there was a comparison, or data which could be used to make a comparison, for such outcomes between participants reporting to drink boiled water and those reporting to drink non-boiled/untreated water (any study design with data for such a comparison). We did not include unpublished studies. After the databases were searched, the results were exported and compiled using the reference management software Endnote (version X7; Thomson Reuters). Duplicates were removed using Endnote’s automated process, followed by a manual search to identify and remove additional duplicates. For the initial record screening step, to avoid inadvertent bias from viewing author name/s, publication type, journal names, and so on, only the record titles and abstracts were reviewed. Titles/abstracts that did not mention boiling but did describe studies focused on drinking water treatment and health outcomes were retained in the hopes that subgroup or control group data related to boiling and health outcomes were reported in the full text. One reviewer (Alasdair Cohen) screened all the titles and abstracts (when available) to determine which were eligible for full-text review. Titles and abstracts from a randomly selected sample of 5% of the initial records were screened by a second reviewer (John M. Colford) and inter-rater reliability was assessed. Similarly, after full-text review (by Alasdair Cohen), 15% of the full-text articles were randomly selected and reviewed for eligibility (by John M. Colford). Data extraction, calculation, and derivation protocols. For each eligible study with extractable data associated with the health effects of consuming boiled drinking water, the following summary information was extracted from the full text if available: country where the study was conducted, province/state/region within the country, study population (rural, urban, mixed, etc.), study type and design, year/s the study was conducted, study duration in months, total number of individuals (and/or households) sampled, age/s of participants, whether a random sampling/selection process was used, whether the sampling/method was described, the health outcome/s assessed, whether a protocol for outcome assessment was described, and whether the outcome assessment was direct or based on selfreport. To extract or calculate odds ratios (ORs), such that values < 1.0 would signify a reduction in disease associated with the consumption of boiled drinking water, as well as lower and upper 95% confidence intervals (95% CI) from each study for our meta-analysis, our guiding principle was to use the best available data in all cases. When the data were provided, or could be calculated, we constructed 2 2 tables and calculated ORs and 95% CIs. If these values aligned
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with those reported in the text, we used our calculations. For studies that reported the OR but did not provide sufficient data to construct a 2 2 table, we used their reported estimates. When the reported OR reference group was those who did not boil their water, we used the reported upper and lower 95% CI to back-calculate the standard error (SE) of the log(OR) to derive 95% CIs for those who boiled (using the inverse of the reported OR). Similarly, in cases where the authors rounded the 95% CI to one decimal place and the data were available, we back-calculated the SE to derive more precise 95% CIs. When authors provided adjusted estimates, we recorded them in our dataset and also calculated unadjusted estimates when the data were available, but only used the reported adjusted estimates for the primary analyses presented here. For matched case–control studies, we always used the reported matched odds ratio (MOR) when provided, back-calculating to derive the MOR and 95% CI for the boiling group if needed. If the authors only reported a risk ratio (RR), we treated it as an OR. For additional details, see the Supplemental Dataset 1 (“comments” in the data cells provide the table and/or page number/s where we found the data for each study). For our analyses of possible publication bias, for those studies where we had to transform and back-calculate 95% CIs and the resulting SEs of the upper and lower 95% CI were not equal, we used the arithmetic mean of the upper and lower values to estimate the boiling SE of the log(OR) (these instances are marked with yellow font in column “AE” of Supplemental Dataset 1). Following data extraction of all eligible studies (by Alasdair Cohen), 30% were randomly selected for data extraction/derivation by a second reviewer (John M. Colford). All extracted data and related calculations were reviewed and discussed by both reviewers. Data analysis. We used meta-analysis to estimate pooled effects of boiling drinking water on health outcomes. Because of the differences in pathogenesis for the various disease outcomes assessed in the studies, we chose not to estimate an overall pooled effect for boiling across all disease outcomes. Rather, we created outcome groups by combining studies that assessed bacterial, helminthic, protozoal, and viral infections, as well as diarrheal outcomes with no specified etiology. Because some authors adjusted for covariates and others did not, we used the most adjusted estimates when available. Using only unadjusted outcome effects tended to result in more protective pooled estimates, thus our use of the adjusted estimates when available resulted in more conservative point and pooled estimates overall (unadjusted estimates are provided in Supplemental Dataset S1). Given our expectation of inter-study variability (due to differences in study design, data collection methods, testing protocols, etc.) and random error, we used meta-analysis with random-effects-based weighting. Because of the known power issues with regard to detecting heterogeneity in meta-analyses generally, and when using subgroups specifically, in addition to using Mantel–Haenszel estimates of heterogeneity, we used the I2 statistic to assess the degree of variation in subgroups which could be attributed to inter-study heterogeneity.36 For studies where the authors provided adjusted effect estimates, we performed meta-analyses using only the adjusted effect estimates. To further examine heterogeneity and identify potential confounders, we used metaregression analysis with random effects (controlling for the variance within and between studies) to examine the impact of various study characteristics on the log(OR) for boiling. Specifically,
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we regressed the log(OR) for boiling on the total number of participants (or households), participant age, whether the study participants lived in rural areas or not, whether the study was an outbreak investigation or not, study duration, whether any type of random selection or sampling method was used to select participants, and lastly, whether the primary health outcome was measured directly, meaning infection was confirmed via analysis of stool and/or serum samples (e.g., with enzyme-linked immunosorbent assay, microscopy, direct smear, cell culture, polymerase chain reaction), or assessed via self-report. Because of the relatively small number of studies available for many organism groups, we also estimated adjusted P values using a Monte Carlo permutation test (with 1,000 random permutations). To attempt to evaluate study quality/bias, we scored each study on a variety of criteria and then aggregated the resulting six components into a composite index which we converted to a 10-point scale to assign grades to each study (we adapted the criteria and grading approach from two recent reviews2,37; see Supplemental Table 6). We then incorporated these quality classifications into an additional meta-regression analysis. Because one might expect baseline exposure and boiling adherence to be higher during outbreak events, pooled estimates that included outbreak investigation studies were estimated with and without outbreak data. Funnel plots were created to visually assess the extent of potential publication bias (aka, “small study” bias) in combination with the use of Egger’s test.38 Though regressing log(OR)s on corresponding SEs may be prone to false positives, we used Egger’s test (at a 95% CI) to attempt to quantitatively assess the degree of potential publication bias (because we did not have complete 2 2 data for all studies, we were limited with regard to the use of other such tests). We analyzed each organism group in isolation (as well as an exploratory analysis stratifying by study design). All analyses were conducted using STATA (v13.1; StataCorp, College Station, TX). A completed PRISMA39 checklist is provided in Supplemental Table 7. RESULTS
After removing duplicates across the four databases and hand-search results, 1,998 records were identified (see Figure 1). Screening by titles and abstracts resulted in the selection of 156 records for full-text review. For the randomly selected subset of 15% (N = 100) records, there was 93% agreement between the two reviewers (kappa = 0.55), which was considered sufficient given the broad inclusion criteria used for the initial screening. One hundred thirty-five full-text articles were found, published during 1955–2015, with 91% (N = 123) in English, 6% (N = 8) in Spanish, and 3% (N = 4) in Chinese (both reviewers read English and Spanish, and Alasdair Cohen’s Chinese reading ability was sufficient for this review). After full-text review (by Alasdair Cohen), 63 articles were deemed ineligible.40–102 For the randomly selected subset of 15% (N = 23) full-text articles reviewed (by John M. Colford), there was 100% agreement with regard to eligibility (none of the randomly selected articles were published in Chinese). Of the 72 articles eligible for inclusion, 27 reported extractable boiling and health outcome data,103–129 whereas 45 did not report sufficient data for interpretation or extraction.130–174 To check the accuracy of data extraction (by Alasdair Cohen), 30% (N = 8) of these articles were randomly selected and the second reviewer (John M. Colford) performed independent data extraction; this resulted in 100% agreement. As discussed earlier, the guiding protocol was to use the best available data, and so when presented with a decision we always used the more conservative and/or broadly relevant data. In
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the interests of consistency and replicability, we only used data provided in the papers, rather than using effect estimates reported elsewhere or non-published data to which we had access (or by contacting authors directly). For example, in Núñez and others,121 we used the verified “Hierve el agua (verificado),” rather than unverified boiling data. Similarly, for our published research on boiling in China,175 since we did not publish the diarrheal RR for all boiling methods, we used the published RR for boiling with metal pots, rather than electric kettle-based boiling (since pot-based boiling is more broadly relevant). In addition, because we could not assume that the water was heated to boiling for all reported boiling cases in all studies, and because pathogen inactivation can occur at temperatures as low as ?55–60°C, depending on the altitude, pathogens, and boiling durations,176 we considered Iijima and others’115 study on water pasteurization eligible. The 27 articles from which data were extracted were published over the years 1992–2015, with 81.5% (N = 22) published in English and 18.5% (N = 5) in Spanish. Studies were conducted in countries around the world, with multiples studies in India (N = 4), Malaysia (N = 4), Cuba (N = 3), Peru (N = 3), and China (N = 2). Slightly more than half of the articles (55.6%, N = 15) described results from cross-sectional designs. Of the studies, 40% (N = 11) were conducted with participants from rural areas, 22% (N = 6) urban, and 37% (N = 10) mixed rural and urban. The median number of participants was 283, with a mean of 1,500 (SD = 2,836, N = 25) and the median duration of the study or data collection was 4 months, with a mean of 11.1 months (SD = 18.8, N = 27). Health outcomes were measured directly in 74% of the articles (N = 20), measured and reported in 11% (N = 3), and only reported in 15% (N = 4) (the specific methods used for direct measurement in each study are provided in Supplemental Dataset S1). See Table 1 for a summary of the study characteristics, specific outcomes, and the data sources and methods used to derive effect estimates. Disease outcomes were organized into bacterial, helminthic, protozoal, and viral groups, as well as nonspecific diarrheal disease outcomes. For bacterial outcomes, as shown in Figure 2, boiling drinking water is associated with a significant and highly protective effect for Vibrio cholerae (OR = 0.31, 95% CI = 0.13–0.79, P = 0.01), though the heterogeneity is somewhat high (I2 = 63.7%). However, effects from the single studies of Helicobacter pylori and Salmonella typhi are neither protective nor significant (P = 0.74 and P = 0.49, respectively). Consequently, although the pooled estimate for these bacterial outcomes is protective, it is not significant (overall OR = 0.54, 95% CI = 0.26–1.11, P = 0.09) and the heterogeneity was high (I2 = 73.7%). In addition, all four V. cholera studies were outbreak investigations; with those studies removed, the pooled estimate for the remaining two bacterial outcomes is neither protective nor significant (overall OR = 1.19, 95% CI = 0.73–1.95, P = 0.48), with essentially zero heterogeneity. As shown in Figure 3, across helminth infection outcomes, the only significant protective effect associated with boiling is for the single study reporting on Strongyloides stercoralis (OR = 0.30, 95% CI = 0.12–0.76, P = 0.01). The two studies of Ascaris reported significant effects on either side of the null, and across helminthic outcomes the pooled effect estimate is essentially null (overall OR = 1.01, 95% CI = 0.53–1.94, P = 0.97) with high heterogeneity (I2 = 68.3%). For studies that measured protozoal infections, the pooled effect across the four studies of Giardia suggests that boiling may have a protective effect, but it is not significant (OR = 0.66, 95% CI = 0.35–1.25, P = 0.20) and the heterogeneity is quite high (I2 = 78.1%). Based on the three available studies, boiling is associated with a significant and strong protective effect for Blastocystis (OR = 0.35, 95% CI = 0.17–0.69, P = 0.003), and the variation in the effects does
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not appear to be attributable to heterogeneity; the heterogeneity statistic also suggests that the underlying effect is relatively constant (P = 0.45). For the two studies that measured the effect of boiling on infection with multiple protozoan parasites, the pooled effect is protective, but not significant (OR = 0.80, 95% CI = 0.49–1.32, P = 0.39) and there is no significant heterogeneity. The one study on Cryptosporidium parvum found a strong and significant protective effect of boiling. The single study on Entamoeba histolytica did not report a protective effect. The overall pooled effect of boiling on protozoan infections was protective and significant (overall OR = 0.61, 95% CI = 0.43–0.86, P = 0.005) with moderate heterogeneity (I2 = 50.7%) (see Figure 4). For viral outcomes, as can be seen in Figure 5, though both of the pooled effect estimates for the two studies of Hepatitis E and the two studies of Rotavirus suggested boiling may be protective, neither were significant (P = 0.42 and P = 0.12, respectively). Although the overall pooled estimate for all viral infection outcomes was both protective and significant (overall OR = 0.83, 95% CI = 0.70–0.98, P = 0.02), with low-to-moderate heterogeneity (I2 = 34.6%), this result was due to the large weighting (52.5%) from the Sarkar 2008–2012 study. With the one outbreak investigation (Aggarwal) excluded, the overall pooled estimate for viral infection outcomes remains protective and significant (overall OR = 0.81, 95% CI = 0.68–0.95, P = 0.01), with low-to-moderate heterogeneity (I2 = 39.1%). Finally, for the studies with nonspecific diarrheal disease outcomes, shown in Figure 6, the pooled effect estimate indicates that reported boiling of drinking water is significant and strongly protective (OR = 0.58, 95% CI = 0.45–0.77, P < 0.001), and with only moderate heterogeneity (I2 = 42.3%). With the outbreak investigation (Cardenas) removed, the pooled effect estimate remains significant and strongly protective (OR = 0.58, 95% CI = 0.43–0.78, P < 0.001), but with slightly higher heterogeneity (I2 = 51.9%). Results of the meta-regression analyses for studies with protozoal and diarrheal outcomes indicated that none of the tested variables significantly impacted the effect estimates for boiling (and except for the covariate for total participants in the protozoal outcomes model, none of the Monte Carlo permutation derived P values fell below the 0.05 threshold). Because of the relatively small number of studies in each organism group, there was too much collinearity (and/or an insufficient number of observations) to estimate covariate coefficients for studies with bacterial, helminthic, and viral outcomes. See Supplemental Tables 8 and 9 for model results. With regard to possible publication bias, Funnel plots for each outcome group were visually inspected and, aside from nonspecific diarrheal outcomes, none indicated likely publication bias (see Supplemental Figures 1–5). Similarly, Egger’s test did not indicate evidence of a “small study” effect for bacterial outcomes (P = 0.17), nonspecific diarrheal outcomes (P = 0.18), helminthic outcomes (P = 0.96), protozoal outcomes (P = 0.78), or viral outcomes (P = 0.31). In an exploratory effort, we also examined a Funnel plot of all study outcomes (Supplemental Figure 6) which likewise did not indicate publication bias (Egger’s test P = 0.26). After stratifying by study design (Supplemental Figures 7 and 8), there did not appear to be publication bias for the cross-sectional outcomes, though there were indications of publication bias for the other study designs (which were mostly case–controls; Egger’s test P = 0.30 and P = 0.03, respectively). Concerning estimated study quality/bias, four studies (11%) received a low score, 10 (29%) a medium score, and 21 (60%) a high score (see Supplemental Table 10). For none of the pathogen-specific outcomes were there more than two studies with significant pooled ORs,
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which also fell into different quality/bias classifications (see Supplemental Table 11). For diarrheal outcomes, the pooled OR for the studies assessed to be of low and medium quality was protective and significant, but approximately equal (though the CI was tighter for the mediumquality studies: low-quality studies OR = 0.60, 95% CI = 0.40–0.89, N = 2; medium-quality studies OR = 0.60, 95% CI = 0.50–0.78, N = 3); the pooled OR for the high-quality diarrheal studies was the lowest, but not significant (high-quality studies OR = 0.31, 95% CI = 0.05–2.03, N = 2). DISCUSSION
The results of our systematic review and meta-analyses suggest that boiling’s protective effect is stronger for some pathogens and organism groups than for others. These findings appear to align with current understandings of transmission pathways for different pathogens and the role of drinking water treatment,177 such that for those pathogens with primarily water-related transmission routes, reported boiling appears to be protective. One potential complication with regard to understanding boiling’s differential effect on specific pathogens is related to whether water is actually boiled, or merely heated.176 Although boiling water at 100°C (at sea level) should inactivate all known pathogenic organisms in the water, at temperatures less than 100°C rates of pathogen inactivation vary by temperature, duration, and the organism in question (as altitude increases the boiling point decreases).176,178 For example, at sea level, a one log reduction in the concentration of S. typhi can be achieved in ?77 seconds at 55°C, or approximately 4 seconds at 60°C, whereas for pathogenic Escherichia coli (O157:H7) a one log reduction is achieved in ?223 seconds at 55°C, or ?67 seconds at 60°C.179 Inactivation levels for a protozoa, such as C. parvum, also vary considerably based on the temperature and exposure duration.180 When boiling is promoted, generally or in the context of boiling advisories, the usual recommendation is to bring water to a rolling boil since this treatment endpoint can be easily observed.178 If we assume that most study participants who reported boiling did bring their water to a rolling boil, then—putting aside for the moment issues of safe storage, secondary contamination, and consistent adherence—full pathogen inactivation is to be expected.176 In this respect, boiling is superior to other HWT methods wherein the susceptibility of pathogens in drinking water varies based on the method of treatment, water turbidity, and the pathogen in question.177 There is also considerable variation in inactivation effects for different pathogens depending on which specific variant of given HWT is used (e.g., the variable effectiveness of different forms of chlorine on E. coli).181 Looking to our results for bacterial outcomes, V. cholerae bacteria are transmitted via the fecal–oral route with contaminated drinking water serving as the most common transmission pathway182; it is, therefore, not surprising that boiling appears to provide such a strong preventative effect. For H. pylori, on the other hand, the global prevalence is relatively high and quite varied geographically, infection is often asymptomatic, and though transmission remains poorly understood, the oral–oral route is suspected to be the primary method of transmission183,184; as such, the lack of evidence for boiling’s preventative effect is perhaps not surprising. Salmonella typhi, on the other hand, is also spread via the fecal–oral route, and foodborne transmission appears to be more common than water-related transmission,185 hence boiling alone would not be expected to reliably prevent infection.
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This same logic may be applied to pathogens in the helminthic, protozoal, and viral outcome groups. Broadly speaking, helminth infections are usually the result of consuming foods contaminated with feces or soils that contain helminth eggs, or via contact with exposed skin.58,177 That water is not the primary transmission route for helminthic infections is consistent with our overall null findings for the impact of boiling on various helminthic pathogens (aside from the significant protective effect associated with S. stercoralis, based on one study). Though water is not the only transmission route for protozoal infections, reported boiling appears to be broadly protective across specific protozoa. Boiling’s highly protective effect for C. parvum (though based only on one study) is noteworthy, given C. parvum’s extreme resistance to chlorine inactivation.186 The apparent effectiveness of boiling on viral outcomes may also be of interest, given that enteric viruses are primarily transmitted through the fecal–oral route via contaminated food or water, though airborne transmission has also been reported.187,188 The possible protective effect of boiling for rotavirus is noteworthy, given the relative challenge of inactivating rotavirus with non-boiling HWT (as compared with other viral pathogens).177 Our results also show that reported boiling has a strong, and highly significant, protective effect for nonspecific diarrheal disease outcomes. To better contextualize these findings, in Table 2 we provide a side-by-side comparison of the pooled OR for diarrheal outcomes associated with reported boiling and the pooled effect estimates from previous systematic reviews on diarrheal outcomes and other HWT methods (as mentioned earlier, most HWT health studies use nonspecific diarrhea as the primary outcome, so we cannot create similar tables to compare pathogen-specific outcomes). An important caveat, however, is that in contrast to most of these other systematic reviews, we did not restrict our inclusion criteria to include only experimental designs (i.e., those using randomized or quasi-randomized assignment and control groups), because there are no published reports of such studies for boiling. Therefore, it is likely that the effect estimates in Table 2 have lower likelihoods of bias as compared with our pooled estimate for reported boiling and diarrheal outcomes. In addition, the pooled estimate from our study does not control for safe post-boiling water storage (with consistent boiling adherence and safe storage, the protective effect might be stronger). With these caveats in mind, we see that the pooled effects associated with filtration are the strongest, followed closely by the pooled estimate for reported boiling from our study (based on data from seven studies). With regard to HWT methods and their impact on diarrheal outcomes, this side-by-side comparison suggests that boiling is at least as effective as the other primary methods of HWT, and perhaps more effective than some. Our study had a number of limitations. The primary limitations were 2-fold: none of the included studies were based on experimental designs, and boiling was assessed via self-report in almost all studies, meaning there was likely substantial heterogeneity in boiling consistency and adherence. Indeed, there is likely substantial heterogeneity between (and within) studies due to differences in boiling methods, frequencies, durations, consistency of use, and methods for storing boiled water and associated risks of secondary contamination.23,25,26 Though the results we present here do not control for post-boiling safe storage (due to a lack of data), if we assume that many or most of the households from which data were collected did not practice safe postboiling storage, boiling combined with safe storage would likely result in an even more preventative net effect for water-related infectious disease outcomes. For example, in Wolf and others’ systematic review,3 when the authors controlled for the use of safe storage, the pooled effect estimates for filtration and chlorine/solar disinfection were more protective (with and without adjustment for non-blinding). Page 9 of 48
There were other limitations as well. Among the 156 studies identified for full-text review, we were unable to retrieve the full-text for nine records, meaning potentially eligible data may not be included in our meta-analyses. Another limitation of our study (common to many such systematic reviews) is the treatment of reported RRs as ORs, because in cases where outcomes are not rare, ORs tend to be larger than RRs. In addition, as may be apparent from our assessment of study bias/quality, for a number of studies there were nontrivial differences in the apparent methodological rigor underlying data collection and analysis. In addition, six of the studies included in this meta-analysis were outbreak-motivated studies, meaning the effect associated with boiling might have been less pronounced during non-outbreak periods when the disease incidence and associated risks were lower. However, the potential bias associated with these outbreak investigations only had the potential to change our conclusions for the interpretation of reported boiling’s impact on bacterial outcomes (since four of the six outbreak studies focused on V. cholera, which we controlled for [see Figure 2]). Finally, the comparatively limited number of studies identified for some of the pathogen-specific outcomes makes it challenging to interpret many of the results, or to speak to the generalizability of our findings with regard to other populations and regions. With regard to broader limitations, the current global estimates of boiling prevalence are mostly based on self-report, may be overreported in some instances, and do not provide sufficient data on differences in the consistency of boiling or on the use of safe or unsafe postboiling storage. In addition, although many of the HWT RCT studies we identified and reviewed did mention the use of boiling in study control groups, none provided health outcome data for participants who practiced boiling (in the main text or online supplementary information). Similarly, in many of these and similar HWT-focused papers, baseline water treatment practices in the control group, such as boiling or filtration, are often aggregated into a catch-all category “water treatment.” Consequently, we were unable to extract data from many of the studies we identified as otherwise eligible (a point we sought to highlight in Figure 1). In the interests of improved reporting, replication, and facilitating systematic reviews, we therefore recommend that, when feasible, more comprehensive results and/or data from WASH RCTs should be provided in supplementary information and/or data repositories. As mentioned earlier, the use of boiling in LMIC settings itself has a number of limitations: boiled water is susceptible to recontamination, boiling does not remove chemical or metal contaminants, the fuels needed for boiling can be relatively costly, and many of the fuels currently used to boil drinking water produce HAP. The first two limitations are, however, not unique to boiling: solar and UV disinfection, as well as filtration, provide no residual disinfectant (and therefore require safe storage)25; and aside from flocculants and relatively expensive filters, none of the primary HWT methods adequately remove chemical or metal contaminants. In many LMIC settings, fuel costs may be a significant barrier to the adoption of boiling, and HAP is especially problematic in rural areas where households use wood, agricultural refuse, coal, or other biomass to boil their water, as well as for cooking and heating. Resulting HAP exposure causes a number of cardiovascular and respiratory diseases. HAP exposure is ranked eighth among global health risks,7 and HAP is one of the primary environmental causes of premature death, with 3.9 million attributable deaths in 2010.24 As discussed earlier, unlike the variable effectiveness of other HWT methods, if drinking water is heated to boil, full pathogen inactivation should be achieved regardless of the organism groups, pathogens, or water turbidity. In light of the evidence of reported boiling’s impact on
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health outcomes presented here, and taking into consideration its widespread use globally and the well-documented challenges promoting retail HWT products,11,12,15 it may be worthwhile to evaluate the potential health gains that could be realized by building upon existing preferences for boiled water to promote safer and more reliable methods or technologies for water boiling. Such an effort would also require a clearer understanding of the sociocultural factors underlying preferences for boiling, as well as would-be barriers to adoption. In conclusion, we believe the evidence presented here highlights the need for a more proportionate focus on boiling in the WASH policy, practitioner, and research communities, and that a definitive boiling-focused RCT is justified. Received March 10, 2017. Accepted for publication June 5, 2017. Note: Supplemental figures, tables and dataset appear at www.ajtmh.org. Authors’ addresses: Alasdair Cohen and John M. Colford, School of Public Health, University of California at Berkeley, Berkeley, CA, E-mails:
[email protected] and
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146. Ercumen A, Naser AM, Unicomb L, Arnold BF, Colford JM, Luby SP, 2015. Effects of source-versus household contamination of tubewell water on child diarrhea in Rural Bangladesh: a randomized controlled trial. PLoS One 10: e0121907 147. Graf J, Meierhofer R, Wegelin M, Mosler H-J, 2008. Water disinfection and hygiene behaviour in an urban slum in Kenya: impact on childhood diarrhoea and influence of beliefs. Int J Environ Health Res 18: 335–355. 148. Graf J, Togouet SZ, Kemka N, Niyitegeka D, Meierhofer R, Pieboji JG, 2010. Health gains from solar water disinfection (SODIS): evaluation of a water quality intervention in Yaounde, Cameroon. J Water Health 8: 779–796. 149. Gruber JS, Reygadas F, Arnold BF, Ray I, Nelson K, Colford JM, 2013. A stepped wedge, cluster-randomized trial of a household UV-disinfection and safe storage drinking water intervention in rural Baja California Sur, Mexico. Am J Trop Med Hyg 89: 238– 245. 150. Gungoren B, Latipov R, Regallet G, Musabaev E, 2007. Effect of hygiene promotion on the risk of reinfection rate of intestinal parasites in children in rural Uzbekistan. Trans R Soc Trop Med Hyg 101: 564–569. 151. Guo Z, Li Y, Xu Z, Ji F, Wang L, Chen K, 2002. A case-control study on risk factors of helicobacter pylori infection in out-patients with stomach diseases. Zhonghua yu fang yi xue za zhi. Chin J Prev Med 36: 187–190. 152. Ilechukwu GC, Ilechukwu CG, Ozumba AN, Ojinnaka NC, Ibe BC, Onwasigwe CN, 2010. Some behavioural risk factors for intestinal helminthiasis in nursery and primary school children in Enugu, south eastern Nigeria. Niger J Clin Pract 13: 288–293. 153. Imanishi M, Kweza PF, Slayton RB, Urayai T, Ziro O, Mushayi W, FrancisChizororo M, Kuonza LR, Ayers T, Freeman MM, 2014. Household water treatment uptake during a public health response to a large typhoid fever outbreak in Harare, Zimbabwe. Am J Trop Med Hyg 90: 945–954. 154. Kinuthia GK, Gicheru MM, Ngure PK, Kabiru EW, 2012. Lifestyles and practices that enhance malaria and typhoid fever in Njoro District, Kenya. J Community Health 37: 224–233. 155. Lindquist ED, George CM, Perin J, Neiswender De Calani KJ, Norman WR, Davis Jr TP, Perry H, 2014. A cluster randomized controlled trial to reduce childhood diarrhea using hollow fiber water filter and/or hygiene-sanitation educational interventions. Am J Trop Med Hyg 91: 190–197. 156. Nguyen VD, Sreenivasan N, Lam E, Ayers T, Kargbo D, Dafae F, Jambai A, Alemu W, Kamara A, Islam MS, 2014. Cholera epidemic associated with consumption of unsafe drinking water and street-vended water—eastern Freetown, Sierra Leone, 2012. Am J Trop Med Hyg 90: 518–523. 157. Novoa Reyes I, et al., 2014. Recurrence rate of Helicobacter pylori infection two years after successful eradication in Peruvian patients presenting with postprandial distress syndrome [in Spanish]. Rev Gastroenterol Peru 34: 15–21.
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188. Ijaz MK, Zargar B, Wright KE, Rubino JR, Sattar SA, 2016. Generic aspects of the airborne spread of human pathogens indoors and emerging air decontamination technologies. Am J Infect Control 44: S109–S120. FIGURE 1. Flowchart of the systematic review process used to identify eligible studies. This figure appears in color at www.ajtmh.org. FIGURE 2. Forest plot for studies measuring bacterial outcomes. This figure appears in color at www.ajtmh.org. FIGURE 3. Forest plot of studies measuring helminthic outcomes. This figure appears in color at www.ajtmh.org. FIGURE 4. Forest plot of studies measuring protozoal outcomes. This figure appears in color at www.ajtmh.org. FIGURE 5. Forest plot of studies measuring viral outcomes. This figure appears in color at www.ajtmh.org. FIGURE 6. Forest plot of studies measuring non-specific diarrheal outcomes. This figure appears in color at www.ajtmh.org.
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TABLE 1 Characteristics of studies included in meta-analysis, organized by organism group
Bacteria
Helminths
Country Specific where Year/s Study pathogen or Published study study duration outcome First author year conducted conducted (months) Helicobacter 2002– Lee 2012 Malaysia 72 pylori 2008 2005– Salmonella typhi Sharma 2009 India 17 2006 1991– Vibrio cholerae Cardenas 1993 Colombia 10 1992
R&U
161
A
CC
U
M
OR, C
R&U
246
M
MCC
Y
M
MOR, R
R&U
(209)
M
CS
Y
R
OR, R
V. cholerae
Fredrick
2015
India
2012
1
R&U
154
M
MCC
U
M&R
MOR, RT
V. cholerae
Ries
1992
Peru
1991
1
U
150
M
MCC
U
M
MOR, R
V. cholerae
Weber
1994
Ecuador
1991
1
U
189
C
CC
U
M
OR, C
Gunawardena
2004
Sri Lanka
2000
6
R
176
M
CS
Y
M
OR, RAT
2006
Peru
2003
2
R
100
M
CC
U
M
OR, C
2006
Cuba
2003 & 2004
2
R&U
1320
C
CS
Y
M
OR, RT
2014
Malaysia
2012
4
R
498
C
CS
N
M
OR, C
Ascaris
Strongyloides Herrera sterocoralis Ascaris, Trichuris, Wordemann hookworm, and multiple Multiple Al-Delaimy Protozoa
Random Number of selection Outcome measured Rural participants or or or (number of Participant Study sampling age design used reported OR data source urban households)
Blastocystis
Carrero
2013
Columbia
–
1
R&U
50
C
CS
N
M
OR, C
Blastocystis Blastocystis
Li Rondon
2007 2003
China Peru
– 1999
1 3
R R&U
283 144
M M
CS CC
Y U
M M
OR, RT, & RAT OR, C
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Cryptosporidium parvum Giardia
Viruses
Diarrhea
U
580
C
NCC
U
M
OR, C, & RA
6
R&U
351
C
CC
N
M
OR, C, & RAT
22
R
1330
M
CS
Y
M
OR, C, & RAT
18
U
119
C
L
U
M
OR, C
2003 and 2004
2
R and U
1320
C
CS
Y
M
OR, RT
Venezuela
2012
2
U
324
M
CS
U
M
OR, C
2002
India
1998
5
R and U
1088
M
CS
Y
M
RR, R
1995
Indonesia
1993 1993– 2014b Bangladesh 1997 2008– 2014b Bangladesh 2012
1
R
445
M
CS
U
M
OR, C
48
U
9879
C
CCh
U
M
OR, C, and RA
48
U
6204
C
CCh
U
M
OR, C, and RA
1991– 1992
10
R and U
(209)
M
CS
Y
R
OR, R
Mexico
1992
5
R
9435
M
CS
U
M
OR, C
2015
China
2013
1
R
(450)
M
CS
Y
R
RR, R
Iijima
2001
Kenya
1995
4
R
3420
M
CS
U
R
OR, C
Kelly
1997
Zambia
1995– 1996
5
R and U
6702
A
CS
U
M and R
OR, R
Knight
1992
Malaysia
1989
2
R
196
C
MCC
Y
M and R
OR, RAT
Psutka
2013
Kiribati
2011
1
R
153
C
CS
Y
R
RR, RT
2014a
India
Bello
2011
Cuba
Giardia
Choy
2014
Malaysia
Giardia Entamoeba histolytica, Giardia, and multiple Multiple
Nunez
2003
Cuba
Wordemann
2006
Cuba
Marcano
2013
Hepatitis E
Aggarwal
Hepatitis E
Corwin
Rotavirus
Sarkar
Rotavirus
Sarkar
Nonspecific diarrhea
Cardenas
1993
Colombia
Cifuentes
1998
Cohen
Nonspecific diarrhea Nonspecific diarrhea Nonspecific diarrhea Nonspecific diarrhea Nonspecific diarrhea Nonspecific diarrhea
2008– 2013 2003 2011– 2013 –
60
Sarkar
Rural or urban: R = rural, U = urban; participant age: C = children (age < 18), A = adults (age > 18), M = mixed (all ages), study design: CS = cross-sectional, CC = case–control, MCC = matched case–control, NCC = nested case–control, L = longitudinal, CCh = case-cohort; random selection: Y = yes, N = no, U =
Page 27 of 48
unclear; outcome measurement: M = measured directly (details in Supplemental Dataset 1, column CG), R = based on self-report. Outbreak investigations marked in italics (N = 6); OR data source: RR = risk ratio, OR = odds ratio, MOR = matched odds ratio, R = reported, T = transformed, A = adjusted, C = calculated (2 2 data).
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TABLE 2 Pooled effect estimates of HWT methods on diarrheal outcomes from other SRMA HWT method Pooled estimate 95% CI Boiling OR = 0.58 0.45–0.77 Chlorine RR = 0.71 0.58–0.87 Chlorine OR = 0.77 0.58–1.02 Chlorine RR = 0.77 0.65–0.91 Filtration OR = 0.37 0.27–0.49 Filtration RR = 0.48 0.38–0.59 Filtration RR = 0.53* 0.41–0.67 Filtration: adjusted for non-blinding RR = 0.66* 0.47–0.92 Flocculant and disinfection RR = 0.69 0.58–0.82 Flocculant and disinfection OR = 0.77 0.65–0.90 Solar disinfection RR = 0.62 0.42–0.94 Solar disinfection OR = 0.69 0.63–0.74 Chlorine or solar disinfection‡ RR = 0.82* 0.69–0.96 Chlorine or solar disinfection: adjusted‡ RR = 0.99* 0.76–1.27 Various HWT RR = 0.65 0.48–0.88 Various HWT OR = 0.65 0.56–0.76 Various HWT ES = 0.56§ 0.48–0.65
Studies 7 10 3 14 2 18 (?14)† (?14)† 4 2 4 2 (?22)† (?22)† 12 10 28
Source This study 13 30 28 30 28 3 3 28 30 28 30 3 3 29 30 12
CI = confidence interval; HWT = household water treatment; ES = effect size; OR = odds ratio; RR = risk ratio. * The presented pooled effects from Wolf and others (2014) do not include studies/estimates with safe-storage. † It was unclear from the text (or SI) how many studies were used to derive these pooled estimates. ‡ The authors explained their decision to calculate the RR for chlorination and solar disinfection as follows: “The results for chlorine and solar interventions were very similar and so, for convenience, they were combined in all analyses” [p935].3 § Waddington and others (2009) transformed study effect estimates into a “common metric” ES. SUPPLEMENTAL DATASET 1. Data for eligible studies. SUPPLEMENTAL FIGURE 1. Funnel plot for all bacterial outcome studies (using all study outcomes). SUPPLEMENTAL FIGURE 2. Funnel plot for all diarrheal outcome studies (using all study outcomes). SUPPLEMENTAL FIGURE 3. Funnel plot for all helminthic outcome studies (using all study outcomes). SUPPLEMENTAL FIGURE 4. Funnel plot for all protozoal outcome studies (using all study outcomes). SUPPLEMENTAL FIGURE 5. Funnel plot for all viral outcome studies (using all study outcomes). SUPPLEMENTAL FIGURE 6. Funnel plots for all study outcomes. SUPPLEMENTAL FIGURE 7. Funnel plots for cross-sectional study outcomes. SUPPLEMENTAL FIGURE 8. Funnel plots for non-cross-sectional study outcomes.
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SUPPLEMENTAL TABLE 1 Full list of search terms by search sets 1 2 3 Boiling and GI-related drinking water Drinking diseases water treatment “Domestic water” “Drinking water” “Potable water” “Tap water” Water “Water consumption” “Well water”
Boil
4 Low-/middle-income countries* (with “OR” inserted between names)
Boiled
“Acute gastrointestinal” “AGI”
Boiling
“AGII”
Decontamination Disinfect
“HCGI” “Highly credible gastrointestinal” Campylobacter
Disinfectant Disinfection Domestic Household Inactivation Pasteurise Pasteurised Pasteurize Pasteurized “Point of use” Point-of-use “POU” Purification Purified Purify Residential “Safe water” Treat Treated Treating Treatment “Water disinfection” “Water purification” “Water quality” “Water treatment”
Cholera Cholerae Cryptosporidium Diarrhea Diarrheal “Diarrheal disease” Diarrheoa Diarrheoal “Diarrheoal disease” Dysentery “E. coli” Enteric “Enteric virus” “Enteric viruses” Enterovirus Enteroviruses “E. coli” “Escherichia coli” Gastrointestinal “Gastro intestinal” Gastro-enteric Giardia Helicobacter Helminth Hepatitis Intestinal Norovirus “Norwold-like
Afghanistan OR Algeria OR Angola OR Anguilla OR Antigua OR Barbuda OR Argentina OR Armenia OR Armenian OR Aruba OR Azerbaijan OR Bahamas OR Bahrain OR Bangladesh OR Barbados OR Benin OR Byelarus OR Byelorussian OR Belarus OR Belorussian OR Belorussia OR Belize OR Bhutan OR Bolivia OR Botswana OR Brazil OR Brunei OR Burkina Faso OR “Burkina Fasso” OR “Upper Volta” OR Burundi OR Urundi OR Cambodia OR “Khmer Republic” OR Kampuchea OR Cameroon OR Cameroons OR Cameron OR Camerons OR “Cape Verde” OR “Cayman Islands” OR “Central African Republic” OR Chad OR Chile OR China OR Colombia OR Comoros OR “Comoro Islands” OR Comores OR Mayotte OR Congo OR Zaire OR “Cook Islands” OR “Costa Rica” OR “Cote dIvoire” OR “Ivory Coast” OR Croatia OR Cuba OR Cyprus OR Djibouti OR “French Somaliland” OR Dominica OR “Dominican Republic” OR “East Timor” OR “East Timur” OR “Timor Leste” OR Ecuador OR Egypt OR “United Arab Republic” OR “El Salvador” OR Eritrea OR Ethiopia OR “Falkland Islands” OR “Las Malvinas” OR Fiji OR Gabon OR “Gabonese Republic” OR Gambia OR Gaza OR “Georgia Republic” OR “Georgian Republic” OR Ghana OR “Gold Coast” OR Greece OR Grenada OR Guatemala OR Guinea OR Guam OR Guadeloupe OR Guiana OR Guyana OR Haiti OR Honduras OR “Hong Kong” OR India OR Maldives OR Indonesia OR Iran OR Iraq OR Jamaica OR Jordan OR Kazakhstan OR Kazakh OR Kenya OR Kiribati OR Korea OR Kosovo OR Kuwait OR Kyrgyzstan OR Kirghizia OR “Kyrgyz Republic” OR Kirghiz OR Kirgizstan OR “Lao PDR” OR Laos OR Lebanon OR Lesotho OR Basutoland OR Liberia OR Libya OR Macau OR Madagascar OR “Malagasy Republic” OR Maldives OR Malaysia OR Malaya OR Malay OR Sabah OR Sarawak OR Malawi OR Nyasaland OR Mali OR Malta OR “Marshall Islands” OR Martinique OR Mauritania OR Mauritius OR “Agalega Islands” OR Mexico OR Micronesia OR “Middle East” OR Mongolia OR Montserrat OR Morocco OR Ifni OR Mozambique OR Myanmar OR Myanma OR Burma OR Namibia OR Nauru OR Nepal OR Niui OR “Netherlands Antilles” OR “New Caledonia” OR Nicaragua OR Niger OR Nigeria OR “Northern Mariana Islands” OR Oman OR Mayotte OR Muscat
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virus” Rotavirus Salmonella Shigella “Vibrio cholera” “Vibrio cholerae” Waterborne Water-borne “Waterborne pathogen” “Waterborne pathogens”
OR Pakistan OR Palau OR Palestine OR Panama OR Paraguay OR Peru OR Philippines OR Philipines OR Phillipines OR Phillippines OR Polynesia OR “Puerto Rico” OR Qatar OR Reunion OR Rwanda OR Ruanda OR “Saint Kitts” OR “St Kitts” OR Nevis OR “Saint Lucia” OR “St Lucia” OR “Saint Vincent” OR “St Vincent” OR Grenadines OR Samoa OR “Samoan Islands” OR “Navigator Island” OR “Navigator Islands” OR “Sao Tome” OR “Saudi Arabia” OR Senegal OR Serbia OR Montenegro OR Seychelles OR “Sierra Leone” OR Singapore OR “Sri Lanka” OR Ceylon OR “Solomon Islands” OR Somalia OR “South Africa” OR Sudan OR Suriname OR Surinam OR Swaziland OR Syria OR Tajikistan OR Tadzhikistan OR Tadjikistan OR Tadzhik OR Tanzania OR Thailand OR Togo OR “Togolese Republic” OR Tokelau OR Tonga OR Trinidad OR Tobago OR Tunisia OR Turkey OR Turkmenistan OR Turkmen OR “Turks Caicos” OR “Tuvalu Uganda” OR “United Arab Emirates” OR Uruguay OR Uzbekistan OR Uzbek OR Vanuatu OR “New Hebrides” OR Venezuela OR Vietnam OR “Viet Nam” OR “Virgin Islands” OR “West Bank” OR Yemen OR Yugoslavia OR Zambia OR Zimbabwe
Boolean operators: “OR” between row terms in each column, “AND” between full columns. * This list was adapted from Bain and others.2 SUPPLEMENTAL TABLE 2 Search terms, notes, and results for PubMed (MEDLINE and other sources) Boolean operators used between Database searched (date of search) search term sets 1 AND 2 AND 3 AND 4
PubMed (Jan 21, 2016) https://www.ncbi.nlm.nih.gov/pubmed/
Fields searched (limitations) Title/Abstract, MeSH Major Topics (none) [only “Title/Abstract” for set #4]
Results
Search text
1,306
((((((“Domestic water”[Title/Abstract] OR “Drinking water”[Title/Abstract] OR “Potable water”[Title/Abstract] OR “Tap water”[Title/Abstract] OR “Water consumption”[Title/Abstract] OR “Well water”[Title/Abstract])) OR (“Domestic water” OR “Drinking water” OR “Potable water” OR “Tap water” OR “Water consumption” OR “Well water”[MeSH Major Topic]))) AND (((Boil[Title/Abstract] OR Boiled[Title/Abstract] OR Boiling[Title/Abstract] OR Decontamination[Title/Abstract] OR Disinfect[Title/Abstract] OR Disinfectant[Title/Abstract] OR Disinfection[Title/Abstract] OR Domestic[Title/Abstract] OR Household[Title/Abstract] OR Inactivation[Title/Abstract] OR Pasteurise[Title/Abstract] OR Pasteurised[Title/Abstract] OR Pasteurize[Title/Abstract] OR Pasteurized[Title/Abstract] OR “Point of use”[Title/Abstract] OR Point-of-use[Title/Abstract] OR “POU”[Title/Abstract] OR Purification[Title/Abstract] OR Purified[Title/Abstract] OR Purify[Title/Abstract] OR Residential[Title/Abstract] OR “Safe water”[Title/Abstract] OR Treat[Title/Abstract] OR Treated[Title/Abstract] OR Treating[Title/Abstract] OR Treatment[Title/Abstract] OR “Water disinfection”[Title/Abstract] OR “Water purification”[Title/Abstract] OR “Water quality”[Title/Abstract] OR “Water treatment”[Title/Abstract])) OR (Boil OR Boiled OR Boiling OR Decontamination OR Disinfect OR Disinfectant OR Disinfection OR Domestic OR Household OR Inactivation OR Pasteurise OR Pasteurised OR Pasteurize OR Pasteurized OR “Point of use” OR Point-of-use OR “POU” OR
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Purification OR Purified OR Purify OR Residential OR “Safe water” OR Treat OR Treated OR Treating OR Treatment OR “Water disinfection” OR “Water purification” OR “Water quality” OR “Water treatment”[MeSH Major Topic]))) AND (((“Acute gastrointestinal”[Title/Abstract] OR “AGI” [Title/Abstract] OR “AGII” [Title/Abstract] OR “HCGI” [Title/Abstract] OR “Highly credible gastrointestinal” [Title/Abstract] OR Campylobacter[Title/Abstract] OR Cholera[Title/Abstract] OR Cholerae[Title/Abstract] OR Cryptosporidium[Title/Abstract] OR Diarrhea[Title/Abstract] OR Diarrheal[Title/Abstract] OR “Diarrheal disease” [Title/Abstract] OR Diarrheoa[Title/Abstract] OR Diarrheoal[Title/Abstract] OR “Diarrheoal disease” [Title/Abstract] OR Dysentery[Title/Abstract] OR “E. coli” [Title/Abstract] OR Enteric[Title/Abstract] OR “Enteric virus” [Title/Abstract] OR “Enteric viruses” [Title/Abstract] OR Enterovirus[Title/Abstract] OR Enteroviruses[Title/Abstract] OR “E. coli” [Title/Abstract] OR “Escherichia coli” [Title/Abstract] OR Gastrointestinal[Title/Abstract] OR “Gastro intestinal” [Title/Abstract] OR Gastro-enteric[Title/Abstract] OR Giardia[Title/Abstract] OR Helicobacter[Title/Abstract] OR Helminth[Title/Abstract] OR Hepatitis[Title/Abstract] OR Intestinal[Title/Abstract] OR Norovirus[Title/Abstract] OR “Norwold-like virus” [Title/Abstract] OR Rotavirus[Title/Abstract] OR Salmonella[Title/Abstract] OR Shigella[Title/Abstract] OR “Vibrio cholera” [Title/Abstract] OR “Vibrio cholerae” [Title/Abstract] OR Waterborne[Title/Abstract] OR Water-borne[Title/Abstract] OR “Waterborne pathogen” [Title/Abstract] OR “Waterborne pathogens”[Title/Abstract])) OR (“Acute gastrointestinal” OR “AGI” OR “AGII” OR “HCGI” OR “Highly credible gastrointestinal” OR Campylobacter OR Cholera OR Cholerae OR Cryptosporidium OR Diarrhea OR Diarrheal OR “Diarrheal disease” OR Diarrheoa OR Diarrheoal OR “Diarrheoal disease” OR Dysentery OR “E. coli” OR Enteric OR “Enteric virus” OR “Enteric viruses” OR Enterovirus OR Enteroviruses OR “E. coli” OR “Escherichia coli” OR Gastrointestinal OR “Gastro intestinal” OR Gastro-enteric OR Giardia OR Helicobacter OR Helminth OR Hepatitis OR Intestinal OR Norovirus OR “Norwold-like virus” OR Rotavirus OR Salmonella OR Shigella OR “Vibrio cholera” OR “Vibrio cholerae” OR Waterborne OR Water-borne OR “Waterborne pathogen” OR “Waterborne pathogens”[MeSH Major Topic]))) AND ((Afghanistan[Title/Abstract] OR Algeria[Title/Abstract] OR Angola[Title/Abstract] OR Anguilla[Title/Abstract] OR Antigua[Title/Abstract] OR Barbuda[Title/Abstract] OR Argentina[Title/Abstract] OR Armenia[Title/Abstract] OR Armenian[Title/Abstract] OR Aruba[Title/Abstract] OR Azerbaijan[Title/Abstract] OR Bahamas[Title/Abstract] OR Bahrain[Title/Abstract] OR Bangladesh[Title/Abstract] OR Barbados[Title/Abstract] OR Benin[Title/Abstract] OR Byelarus[Title/Abstract] OR Byelorussian[Title/Abstract] OR Belarus[Title/Abstract] OR Belorussian[Title/Abstract] OR Belorussia[Title/Abstract] OR Belize[Title/Abstract] OR Bhutan[Title/Abstract] OR Bolivia[Title/Abstract] OR Botswana[Title/Abstract] OR Brazil[Title/Abstract] OR Brunei[Title/Abstract] OR Burkina Faso[Title/Abstract] OR “Burkina Fasso”[Title/Abstract] OR “Upper Volta”[Title/Abstract] OR Burundi[Title/Abstract] OR Urundi[Title/Abstract] OR Cambodia[Title/Abstract] OR “Khmer Republic”[Title/Abstract] OR Kampuchea[Title/Abstract] OR Cameroon[Title/Abstract] OR Cameroons[Title/Abstract] OR Cameron[Title/Abstract] OR Camerons[Title/Abstract] OR “Cape Verde”[Title/Abstract] OR “Cayman Islands”[Title/Abstract] OR “Central African Republic”[Title/Abstract] OR Chad[Title/Abstract] OR Chile[Title/Abstract] OR China[Title/Abstract] OR Colombia[Title/Abstract] OR Comoros[Title/Abstract] OR “Comoro Islands”[Title/Abstract] OR Comores[Title/Abstract] OR Mayotte[Title/Abstract] OR Congo[Title/Abstract] OR Zaire[Title/Abstract] OR “Cook Islands”[Title/Abstract] OR “Costa Rica”[Title/Abstract] OR “Cote dIvoire”[Title/Abstract] OR “Ivory Coast”[Title/Abstract] OR Croatia[Title/Abstract] OR Cuba[Title/Abstract] OR Cyprus[Title/Abstract] OR Djibouti[Title/Abstract] OR “French Somaliland”[Title/Abstract] OR Dominica[Title/Abstract] OR “Dominican Republic”[Title/Abstract] OR “East Timor”[Title/Abstract] OR “East Timur”[Title/Abstract] OR “Timor Leste”[Title/Abstract] OR Ecuador[Title/Abstract] OR Egypt[Title/Abstract] OR “United Arab Republic”[Title/Abstract] OR “El Salvador”[Title/Abstract] OR Eritrea[Title/Abstract] OR Ethiopia[Title/Abstract] OR “Falkland Islands”[Title/Abstract] OR “Las Malvinas”[Title/Abstract] OR Fiji[Title/Abstract] OR Gabon[Title/Abstract] OR “Gabonese Republic”[Title/Abstract] OR Gambia[Title/Abstract] OR Gaza[Title/Abstract] OR “Georgia Republic”[Title/Abstract] OR “Georgian Republic”[Title/Abstract] OR Ghana[Title/Abstract] OR “Gold Coast”[Title/Abstract] OR Greece[Title/Abstract] OR Grenada[Title/Abstract] OR Guatemala[Title/Abstract] OR Guinea[Title/Abstract] OR Guam[Title/Abstract] OR Guadeloupe[Title/Abstract] OR Guiana[Title/Abstract] OR
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Guyana[Title/Abstract] OR Haiti[Title/Abstract] OR Honduras[Title/Abstract] OR “Hong Kong”[Title/Abstract] OR India[Title/Abstract] OR Maldives[Title/Abstract] OR Indonesia[Title/Abstract] OR Iran[Title/Abstract] OR Iraq[Title/Abstract] OR Jamaica[Title/Abstract] OR Jordan[Title/Abstract] OR Kazakhstan[Title/Abstract] OR Kazakh[Title/Abstract] OR Kenya[Title/Abstract] OR Kiribati[Title/Abstract] OR Korea[Title/Abstract] OR Kosovo[Title/Abstract] OR Kuwait[Title/Abstract] OR Kyrgyzstan[Title/Abstract] OR Kirghizia[Title/Abstract] OR “Kyrgyz Republic”[Title/Abstract] OR Kirghiz[Title/Abstract] OR Kirgizstan[Title/Abstract] OR “Lao PDR”[Title/Abstract] OR Laos[Title/Abstract] OR Lebanon[Title/Abstract] OR Lesotho[Title/Abstract] OR Basutoland[Title/Abstract] OR Liberia[Title/Abstract] OR Libya[Title/Abstract] OR Macau[Title/Abstract] OR Madagascar[Title/Abstract] OR “Malagasy Republic”[Title/Abstract] OR Maldives[Title/Abstract] OR Malaysia[Title/Abstract] OR Malaya[Title/Abstract] OR Malay[Title/Abstract] OR Sabah[Title/Abstract] OR Sarawak[Title/Abstract] OR Malawi[Title/Abstract] OR Nyasaland[Title/Abstract] OR Mali[Title/Abstract] OR Malta[Title/Abstract] OR “Marshall Islands”[Title/Abstract] OR Martinique[Title/Abstract] OR Mauritania[Title/Abstract] OR Mauritius[Title/Abstract] OR “Agalega Islands”[Title/Abstract] OR Mexico[Title/Abstract] OR Micronesia[Title/Abstract] OR “Middle East”[Title/Abstract] OR Mongolia[Title/Abstract] OR Montserrat[Title/Abstract] OR Morocco[Title/Abstract] OR Ifni[Title/Abstract] OR Mozambique[Title/Abstract] OR Myanmar[Title/Abstract] OR Myanma[Title/Abstract] OR Burma[Title/Abstract] OR Namibia[Title/Abstract] OR Nauru[Title/Abstract] OR Nepal[Title/Abstract] OR Niui[Title/Abstract] OR “Netherlands Antilles”[Title/Abstract] OR “New Caledonia”[Title/Abstract] OR Nicaragua[Title/Abstract] OR Niger[Title/Abstract] OR Nigeria[Title/Abstract] OR “Northern Mariana Islands”[Title/Abstract] OR Oman[Title/Abstract] OR Mayotte[Title/Abstract] OR Muscat[Title/Abstract] OR Pakistan[Title/Abstract] OR Palau[Title/Abstract] OR Palestine[Title/Abstract] OR Panama[Title/Abstract] OR Paraguay[Title/Abstract] OR Peru[Title/Abstract] OR Philippines[Title/Abstract] OR Philipines[Title/Abstract] OR Phillipines[Title/Abstract] OR Phillippines[Title/Abstract] OR Polynesia[Title/Abstract] OR “Puerto Rico”[Title/Abstract] OR Qatar[Title/Abstract] OR Reunion[Title/Abstract] OR Rwanda[Title/Abstract] OR Ruanda[Title/Abstract] OR “Saint Kitts”[Title/Abstract] OR “St Kitts”[Title/Abstract] OR Nevis[Title/Abstract] OR “Saint Lucia”[Title/Abstract] OR “St Lucia”[Title/Abstract] OR “Saint Vincent”[Title/Abstract] OR “St Vincent”[Title/Abstract] OR Grenadines[Title/Abstract] OR Samoa[Title/Abstract] OR “Samoan Islands”[Title/Abstract] OR “Navigator Island”[Title/Abstract] OR “Navigator Islands”[Title/Abstract] OR “Sao Tome”[Title/Abstract] OR “Saudi Arabia”[Title/Abstract] OR Senegal[Title/Abstract] OR Serbia[Title/Abstract] OR Montenegro[Title/Abstract] OR Seychelles[Title/Abstract] OR “Sierra Leone”[Title/Abstract] OR Singapore[Title/Abstract] OR “Sri Lanka”[Title/Abstract] OR Ceylon[Title/Abstract] OR “Solomon Islands”[Title/Abstract] OR Somalia[Title/Abstract] OR “South Africa”[Title/Abstract] OR Sudan[Title/Abstract] OR Suriname[Title/Abstract] OR Surinam[Title/Abstract] OR Swaziland[Title/Abstract] OR Syria[Title/Abstract] OR Tajikistan[Title/Abstract] OR Tadzhikistan[Title/Abstract] OR Tadjikistan[Title/Abstract] OR Tadzhik[Title/Abstract] OR Tanzania[Title/Abstract] OR Thailand[Title/Abstract] OR Togo[Title/Abstract] OR “Togolese Republic”[Title/Abstract] OR Tokelau[Title/Abstract] OR Tonga[Title/Abstract] OR Trinidad[Title/Abstract] OR Tobago[Title/Abstract] OR Tunisia[Title/Abstract] OR Turkey[Title/Abstract] OR Turkmenistan[Title/Abstract] OR Turkmen[Title/Abstract] OR “Turks Caicos”[Title/Abstract] OR “Tuvalu Uganda”[Title/Abstract] OR “United Arab Emirates”[Title/Abstract] OR Uruguay[Title/Abstract] OR Uzbekistan[Title/Abstract] OR Uzbek[Title/Abstract] OR Vanuatu[Title/Abstract] OR “New Hebrides”[Title/Abstract] OR Venezuela[Title/Abstract] OR Vietnam[Title/Abstract] OR “Viet Nam”[Title/Abstract] OR “Virgin Islands”[Title/Abstract] OR “West Bank”[Title/Abstract] OR Yemen[Title/Abstract] OR Yugoslavia[Title/Abstract] OR Zambia[Title/Abstract] OR Zimbabwe[Title/Abstract]))
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SUPPLEMENTAL TABLE 3 Search terms, notes, and results for EMBASE (and EMBASE Classic) Boolean operators used between Database searched (date of search) search term sets EMBASE (Jan 21, 2016) 1 AND 2 AND 3 AND 4 https://www.elsevier.com/solutions/embasebiomedical-research Results Search text 1,329
Fields searched (limitations) Abstracts, Titles, Index terms (none)
('domestic water':de,ab,ti OR 'drinking water':de,ab,ti OR 'potable water':de,ab,ti OR 'tap water':de,ab,ti OR 'water consumption':de,ab,ti OR 'well water':de,ab,ti) AND (boil:de,ab,ti OR boiled:de,ab,ti OR boiling:de,ab,ti OR decontamination:de,ab,ti OR disinfect:de,ab,ti OR disinfectant:de,ab,ti OR disinfection:de,ab,ti OR domestic:de,ab,ti OR household:de,ab,ti OR inactivation:de,ab,ti OR pasteurise:de,ab,ti OR pasteurised:de,ab,ti OR pasteurize:de,ab,ti OR pasteurized:de,ab,ti OR 'point of use':de,ab,ti OR 'pou':de,ab,ti OR purification:de,ab,ti OR purified:de,ab,ti OR purify:de,ab,ti OR residential:de,ab,ti OR 'safe water':de,ab,ti OR treat:de,ab,ti OR treated:de,ab,ti OR treating:de,ab,ti OR treatment:de,ab,ti OR 'water disinfection':de,ab,ti OR 'water purification':de,ab,ti OR 'water quality':de,ab,ti OR 'water treatment':de,ab,ti) AND ('acute gastrointestinal':de,ab,ti OR 'agi':de,ab,ti OR 'agii':de,ab,ti OR 'hcgi':de,ab,ti OR 'highly credible gastrointestinal':de,ab,ti OR Campylobacter:de,ab,ti OR cholera:de,ab,ti OR cholerae:de,ab,ti OR cryptosporidium:de,ab,ti OR diarrhea:de,ab,ti OR diarrheal:de,ab,ti OR 'diarrheal disease':de,ab,ti OR diarrheoa:de,ab,ti OR diarrheoal:de,ab,ti OR 'diarrheoal disease':de,ab,ti OR dysentery:de,ab,ti OR enteric:de,ab,ti OR 'enteric virus':de,ab,ti OR 'enteric viruses':de,ab,ti OR enterovirus:de,ab,ti OR enteroviruses:de,ab,ti OR 'E. coli':de,ab,ti OR 'Escherichia coli':de,ab,ti OR gastrointestinal:de,ab,ti OR 'gastro intestinal':de,ab,ti OR 'gastro enteric':de,ab,ti OR Giardia:de,ab,ti OR helicobacter:de,ab,ti OR helminth:de,ab,ti OR hepatitis:de,ab,ti OR intestinal:de,ab,ti OR norovirus:de,ab,ti OR 'norwoldlike virus':de,ab,ti OR rotavirus:de,ab,ti OR Salmonella:de,ab,ti OR shigella:de,ab,ti OR 'vibrio cholera':de,ab,ti OR 'vibrio cholerae':de,ab,ti OR waterborne:de,ab,ti OR 'water borne':de,ab,ti OR 'waterborne pathogen':de,ab,ti OR 'waterborne pathogens':de,ab,ti) AND (afghanistan:de,ab,ti OR algeria:de,ab,ti OR angola:de,ab,ti OR anguilla:de,ab,ti OR antigua:de,ab,ti OR barbuda:de,ab,ti OR argentina:de,ab,ti OR armenia:de,ab,ti OR armenian:de,ab,ti OR aruba:de,ab,ti OR azerbaijan:de,ab,ti OR bahamas:de,ab,ti OR bahrain:de,ab,ti OR bangladesh:de,ab,ti OR barbados:de,ab,ti OR benin:de,ab,ti OR byelarus:de,ab,ti OR byelorussian:de,ab,ti OR belarus:de,ab,ti OR belorussian:de,ab,ti OR belorussia:de,ab,ti OR belize:de,ab,ti OR bhutan:de,ab,ti OR bolivia:de,ab,ti OR botswana:de,ab,ti OR brazil:de,ab,ti OR brunei:de,ab,ti OR burkina:de,ab,ti AND faso:de,ab,ti OR 'burkina fasso':de,ab,ti OR 'upper volta':de,ab,ti OR burundi:de,ab,ti OR urundi:de,ab,ti OR cambodia:de,ab,ti OR 'khmer republic':de,ab,ti OR kampuchea:de,ab,ti OR cameroon:de,ab,ti OR cameroons:de,ab,ti OR cameron:de,ab,ti OR camerons:de,ab,ti OR 'cape verde':de,ab,ti OR 'cayman islands':de,ab,ti OR 'central african republic':de,ab,ti OR chad:de,ab,ti OR chile:de,ab,ti OR china:de,ab,ti OR colombia:de,ab,ti OR comoros:de,ab,ti OR 'comoro islands':de,ab,ti OR comores:de,ab,ti OR congo:de,ab,ti OR zaire:de,ab,ti OR 'cook islands':de,ab,ti OR 'costa rica':de,ab,ti OR 'cote divoire':de,ab,ti OR 'ivory coast':de,ab,ti OR croatia:de,ab,ti OR cuba:de,ab,ti OR cyprus:de,ab,ti OR djibouti:de,ab,ti OR 'french somaliland':de,ab,ti OR dominica:de,ab,ti OR 'dominican republic':de,ab,ti OR 'east timor':de,ab,ti OR 'east timur':de,ab,ti OR 'timor leste':de,ab,ti OR ecuador:de,ab,ti OR egypt:de,ab,ti OR 'united arab republic':de,ab,ti OR 'el salvador':de,ab,ti OR eritrea:de,ab,ti OR ethiopia:de,ab,ti OR 'falkland islands':de,ab,ti OR 'las malvinas':de,ab,ti OR fiji:de,ab,ti OR gabon:de,ab,ti OR 'gabonese republic':de,ab,ti OR gambia:de,ab,ti OR gaza:de,ab,ti OR 'georgia republic':de,ab,ti OR 'georgian republic':de,ab,ti OR ghana:de,ab,ti OR 'gold coast':de,ab,ti OR greece:de,ab,ti OR grenada:de,ab,ti OR guatemala:de,ab,ti OR guinea:de,ab,ti OR guam:de,ab,ti OR guadeloupe:de,ab,ti OR guiana:de,ab,ti OR guyana:de,ab,ti OR haiti:de,ab,ti OR honduras:de,ab,ti OR 'hong kong':de,ab,ti OR india:de,ab,ti OR indonesia:de,ab,ti OR iran:de,ab,ti OR iraq:de,ab,ti OR jamaica:de,ab,ti OR jordan:de,ab,ti OR kazakhstan:de,ab,ti OR kazakh:de,ab,ti OR kenya:de,ab,ti OR kiribati:de,ab,ti OR korea:de,ab,ti OR kosovo:de,ab,ti OR kuwait:de,ab,ti OR kyrgyzstan:de,ab,ti OR kirghizia:de,ab,ti OR 'kyrgyz republic':de,ab,ti OR kirghiz:de,ab,ti OR kirgizstan:de,ab,ti OR 'lao pdr':de,ab,ti OR laos:de,ab,ti OR lebanon:de,ab,ti OR lesotho:de,ab,ti OR
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basutoland:de,ab,ti OR liberia:de,ab,ti OR libya:de,ab,ti OR macau:de,ab,ti OR madagascar:de,ab,ti OR 'malagasy republic':de,ab,ti OR maldives:de,ab,ti OR malaysia:de,ab,ti OR malaya:de,ab,ti OR malay:de,ab,ti OR sabah:de,ab,ti OR sarawak:de,ab,ti OR malawi:de,ab,ti OR nyasaland:de,ab,ti OR mali:de,ab,ti OR malta:de,ab,ti OR 'marshall islands':de,ab,ti OR martinique:de,ab,ti OR mauritania:de,ab,ti OR mauritius:de,ab,ti OR 'agalega islands':de,ab,ti OR mexico:de,ab,ti OR micronesia:de,ab,ti OR 'middle east':de,ab,ti OR mongolia:de,ab,ti OR montserrat:de,ab,ti OR morocco:de,ab,ti OR ifni:de,ab,ti OR mozambique:de,ab,ti OR myanmar:de,ab,ti OR myanma:de,ab,ti OR burma:de,ab,ti OR namibia:de,ab,ti OR nauru:de,ab,ti OR nepal:de,ab,ti OR niui:de,ab,ti OR 'netherlands antilles':de,ab,ti OR 'new caledonia':de,ab,ti OR nicaragua:de,ab,ti OR niger:de,ab,ti OR nigeria:de,ab,ti OR 'northern mariana islands':de,ab,ti OR oman:de,ab,ti OR mayotte:de,ab,ti OR muscat:de,ab,ti OR pakistan:de,ab,ti OR palau:de,ab,ti OR palestine:de,ab,ti OR panama:de,ab,ti OR paraguay:de,ab,ti OR peru:de,ab,ti OR philippines:de,ab,ti OR philipines:de,ab,ti OR phillipines:de,ab,ti OR phillippines:de,ab,ti OR polynesia:de,ab,ti OR 'puerto rico':de,ab,ti OR qatar:de,ab,ti OR reunion:de,ab,ti OR rwanda:de,ab,ti OR ruanda:de,ab,ti OR 'saint kitts':de,ab,ti OR 'st kitts':de,ab,ti OR nevis:de,ab,ti OR 'saint lucia':de,ab,ti OR 'st lucia':de,ab,ti OR 'saint vincent':de,ab,ti OR 'st vincent':de,ab,ti OR grenadines:de,ab,ti OR samoa:de,ab,ti OR 'samoan islands':de,ab,ti OR 'navigator island':de,ab,ti OR 'navigator islands':de,ab,ti OR 'sao tome':de,ab,ti OR 'saudi arabia':de,ab,ti OR senegal:de,ab,ti OR serbia:de,ab,ti OR montenegro:de,ab,ti OR seychelles:de,ab,ti OR 'sierra leone':de,ab,ti OR singapore:de,ab,ti OR 'sri lanka':de,ab,ti OR ceylon:de,ab,ti OR 'solomon islands':de,ab,ti OR somalia:de,ab,ti OR 'south africa':de,ab,ti OR sudan:de,ab,ti OR suriname:de,ab,ti OR surinam:de,ab,ti OR swaziland:de,ab,ti OR syria:de,ab,ti OR tajikistan:de,ab,ti OR tadzhikistan:de,ab,ti OR tadjikistan:de,ab,ti OR tadzhik:de,ab,ti OR tanzania:de,ab,ti OR thailand:de,ab,ti OR togo:de,ab,ti OR 'togolese republic':de,ab,ti OR tokelau:de,ab,ti OR tonga:de,ab,ti OR trinidad:de,ab,ti OR tobago:de,ab,ti OR tunisia:de,ab,ti OR turkey:de,ab,ti OR turkmenistan:de,ab,ti OR turkmen:de,ab,ti OR 'turks caicos':de,ab,ti OR 'tuvalu uganda':de,ab,ti OR 'united arab emirates':de,ab,ti OR uruguay:de,ab,ti OR uzbekistan:de,ab,ti OR uzbek:de,ab,ti OR vanuatu:de,ab,ti OR 'new hebrides':de,ab,ti OR venezuela:de,ab,ti OR vietnam:de,ab,ti OR 'viet nam':de,ab,ti OR 'virgin islands':de,ab,ti OR 'west bank':de,ab,ti OR yemen:de,ab,ti OR yugoslavia:de,ab,ti OR zambia:de,ab,ti OR zimbabwe:de,ab,ti) SUPPLEMENTAL TABLE 4 Search terms, notes, and results for Web of Science Boolean operators used between Database searched (date of search) Fields searched (limitations) search-term sets Web of Science (Jan 21, 2016) Topic (none) For search set #4: 1 AND 2 AND 3 AND 4 http://apps.webofknowledge.com/ [Web Title of Science database only] Results Search text 1,270 (TS=(“Domestic water” OR “Drinking water” OR “Potable water” OR “Tap water” OR “Water consumption” OR “Well water”)) AND (TS=(Boil OR Boiled OR Boiling OR Decontamination OR Disinfect OR Disinfectant OR Disinfection OR Domestic OR Household OR Inactivation OR Pasteurise OR Pasteurised OR Pasteurize OR Pasteurized OR “Point of use” OR Point-of-use OR “POU” OR Purification OR Purified OR Purify OR Residential OR “Safe water” OR Treat OR Treated OR Treating OR Treatment OR “Water disinfection” OR “Water purification” OR “Water quality” OR “Water treatment”)) AND (TS=(Acute gastrointestinal OR AGI OR AGII OR HCGI OR Highly credible gastrointestinal OR Campylobacter OR Cholera OR Cholerae OR Cryptosporidium OR Diarrhea OR Diarrheal OR Diarrheal disease OR Diarrheoa OR Diarrheoal OR Diarrheoal disease OR Dysentery OR E. coli OR Enteric OR Enteric virus OR Enteric viruses OR Enterovirus OR Enteroviruses OR E. coli OR Escherichia coli OR Gastrointestinal OR Gastro intestinal OR Gastroenteric OR Giardia OR Helicobacter OR Helminth OR Hepatitis OR Intestinal OR Norovirus OR Norwold-like virus OR Rotavirus OR Salmonella OR Shigella OR Vibrio cholera OR Vibrio cholerae OR Waterborne OR Water-borne OR Waterborne pathogen OR Waterborne pathogens)) AND (TI=(Afghanistan OR Algeria OR Angola OR Anguilla OR Antigua OR Barbuda OR Argentina OR Armenia OR Armenian OR Aruba OR Azerbaijan OR Bahamas OR Bahrain OR Bangladesh OR
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Barbados OR Benin OR Byelarus OR Byelorussian OR Belarus OR Belorussian OR Belorussia OR Belize OR Bhutan OR Bolivia OR Botswana OR Brazil OR Brunei OR Burkina Faso OR “Burkina Fasso” OR “Upper Volta” OR Burundi OR Urundi OR Cambodia OR “Khmer Republic” OR Kampuchea OR Cameroon OR Cameroons OR Cameron OR Camerons OR “Cape Verde” OR “Cayman Islands” OR “Central African Republic” OR Chad OR Chile OR China OR Colombia OR Comoros OR “Comoro Islands” OR Comores OR Mayotte OR Congo OR Zaire OR “Cook Islands” OR “Costa Rica” OR “Cote dIvoire” OR “Ivory Coast” OR Croatia OR Cuba OR Cyprus OR Djibouti OR “French Somaliland” OR Dominica OR “Dominican Republic” OR “East Timor” OR “East Timur” OR “Timor Leste” OR Ecuador OR Egypt OR “United Arab Republic” OR “El Salvador” OR Eritrea OR Ethiopia OR “Falkland Islands” OR “Las Malvinas” OR Fiji OR Gabon OR “Gabonese Republic” OR Gambia OR Gaza OR “Georgia Republic” OR “Georgian Republic” OR Ghana OR “Gold Coast” OR Greece OR Grenada OR Guatemala OR Guinea OR Guam OR Guadeloupe OR Guiana OR Guyana OR Haiti OR Honduras OR “Hong Kong” OR India OR Maldives OR Indonesia OR Iran OR Iraq OR Jamaica OR Jordan OR Kazakhstan OR Kazakh OR Kenya OR Kiribati OR Korea OR Kosovo OR Kuwait OR Kyrgyzstan OR Kirghizia OR “Kyrgyz Republic” OR Kirghiz OR Kirgizstan OR “Lao PDR” OR Laos OR Lebanon OR Lesotho OR Basutoland OR Liberia OR Libya OR Macau OR Madagascar OR “Malagasy Republic” OR Maldives OR Malaysia OR Malaya OR Malay OR Sabah OR Sarawak OR Malawi OR Nyasaland OR Mali OR Malta OR “Marshall Islands” OR Martinique OR Mauritania OR Mauritius OR “Agalega Islands” OR Mexico OR Micronesia OR “Middle East” OR Mongolia OR Montserrat OR Morocco OR Ifni OR Mozambique OR Myanmar OR Myanma OR Burma OR Namibia OR Nauru OR Nepal OR Niui OR “Netherlands Antilles” OR “New Caledonia” OR Nicaragua OR Niger OR Nigeria OR “Northern Mariana Islands” OR Oman OR Mayotte OR Muscat OR Pakistan OR Palau OR Palestine OR Panama OR Paraguay OR Peru OR Philippines OR Philipines OR Phillipines OR Phillippines OR Polynesia OR “Puerto Rico” OR Qatar OR Reunion OR Rwanda OR Ruanda OR “Saint Kitts” OR “St Kitts” OR Nevis OR “Saint Lucia” OR “St Lucia” OR “Saint Vincent” OR “St Vincent” OR Grenadines OR Samoa OR “Samoan Islands” OR “Navigator Island” OR “Navigator Islands” OR “Sao Tome” OR “Saudi Arabia” OR Senegal OR Serbia OR Montenegro OR Seychelles OR “Sierra Leone” OR Singapore OR “Sri Lanka” OR Ceylon OR “Solomon Islands” OR Somalia OR “South Africa” OR Sudan OR Suriname OR Surinam OR Swaziland OR Syria OR Tajikistan OR Tadzhikistan OR Tadjikistan OR Tadzhik OR Tanzania OR Thailand OR Togo OR “Togolese Republic” OR Tokelau OR Tonga OR Trinidad OR Tobago OR Tunisia OR Turkey OR Turkmenistan OR Turkmen OR “Turks Caicos” OR “Tuvalu Uganda” OR “United Arab Emirates” OR Uruguay OR Uzbekistan OR Uzbek OR Vanuatu OR “New Hebrides” OR Venezuela OR Vietnam OR “Viet Nam” OR “Virgin Islands” OR “West Bank” OR Yemen OR Yugoslavia OR Zambia OR Zimbabwe)) Refined by: Databases: (WOS) Timespan: All years. Search language=Auto SUPPLEMENTAL TABLE 5 Search terms, notes, and results for Cochrane Library Boolean operators used between Database searched (date of search) search-term sets Cochrane Library (Jan 21, 2016) 1 AND 2 AND 3 AND 4 http://www.cochranelibrary.com/ Results Search text 71
Fields searched (limitations) Title, abstract, keywords (none)
(“Domestic water” OR “Drinking water” OR “Potable water” OR “Tap water” OR “Water consumption” OR “Well water”) AND (Boil OR Boiled OR Boiling OR Decontamination OR Disinfect OR Disinfectant OR Disinfection OR Domestic OR Household OR Inactivation OR Pasteurise OR Pasteurised OR Pasteurize OR Pasteurized OR “Point of use” OR Point-of-use OR “POU” OR Purification OR Purified OR Purify OR Residential OR “Safe water” OR Treat OR Treated OR Treating OR Treatment OR “Water disinfection” OR “Water purification” OR “Water quality” OR “Water treatment”) AND (“Acute gastrointestinal” OR “AGI” OR “AGII” OR “HCGI”
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OR “Highly credible gastrointestinal” OR Campylobacter OR Cholera OR Cholerae OR Cryptosporidium OR Diarrhea OR Diarrheal OR “Diarrheal disease” OR Diarrheoa OR Diarrheoal OR “Diarrheoal disease” OR Dysentery OR “E. coli” OR Enteric OR “Enteric virus” OR “Enteric viruses” OR Enterovirus OR Enteroviruses OR “E. coli” OR “Escherichia coli” OR Gastrointestinal OR “Gastro intestinal” OR Gastro-enteric OR Giardia OR Helicobacter OR Helminth OR Hepatitis OR Intestinal OR Norovirus OR “Norwold-like virus” OR Rotavirus OR Salmonella OR Shigella OR “Vibrio cholera” OR “Vibrio cholerae” OR Waterborne OR Water-borne OR “Waterborne pathogen” OR “Waterborne pathogens”) AND (Afghanistan OR Algeria OR Angola OR Anguilla OR Antigua OR Barbuda OR Argentina OR Armenia OR Armenian OR Aruba OR Azerbaijan OR Bahamas OR Bahrain OR Bangladesh OR Barbados OR Benin OR Byelarus OR Byelorussian OR Belarus OR Belorussian OR Belorussia OR Belize OR Bhutan OR Bolivia OR Botswana OR Brazil OR Brunei OR Burkina Faso OR “Burkina Fasso” OR “Upper Volta” OR Burundi OR Urundi OR Cambodia OR “Khmer Republic” OR Kampuchea OR Cameroon OR Cameroons OR Cameron OR Camerons OR “Cape Verde” OR “Cayman Islands” OR “Central African Republic” OR Chad OR Chile OR China OR Colombia OR Comoros OR “Comoro Islands” OR Comores OR Mayotte OR Congo OR Zaire OR “Cook Islands” OR “Costa Rica” OR “Cote dIvoire” OR “Ivory Coast” OR Croatia OR Cuba OR Cyprus OR Djibouti OR “French Somaliland” OR Dominica OR “Dominican Republic” OR “East Timor” OR “East Timur” OR “Timor Leste” OR Ecuador OR Egypt OR “United Arab Republic” OR “El Salvador” OR Eritrea OR Ethiopia OR “Falkland Islands” OR “Las Malvinas” OR Fiji OR Gabon OR “Gabonese Republic” OR Gambia OR Gaza OR “Georgia Republic” OR “Georgian Republic” OR Ghana OR “Gold Coast” OR Greece OR Grenada OR Guatemala OR Guinea OR Guam OR Guadeloupe OR Guiana OR Guyana OR Haiti OR Honduras OR “Hong Kong” OR India OR Maldives OR Indonesia OR Iran OR Iraq OR Jamaica OR Jordan OR Kazakhstan OR Kazakh OR Kenya OR Kiribati OR Korea OR Kosovo OR Kuwait OR Kyrgyzstan OR Kirghizia OR “Kyrgyz Republic” OR Kirghiz OR Kirgizstan OR “Lao PDR” OR Laos OR Lebanon OR Lesotho OR Basutoland OR Liberia OR Libya OR Macau OR Madagascar OR “Malagasy Republic” OR Maldives OR Malaysia OR Malaya OR Malay OR Sabah OR Sarawak OR Malawi OR Nyasaland OR Mali OR Malta OR “Marshall Islands” OR Martinique OR Mauritania OR Mauritius OR “Agalega Islands” OR Mexico OR Micronesia OR “Middle East” OR Mongolia OR Montserrat OR Morocco OR Ifni OR Mozambique OR Myanmar OR Myanma OR Burma OR Namibia OR Nauru OR Nepal OR Niui OR “Netherlands Antilles” OR “New Caledonia” OR Nicaragua OR Niger OR Nigeria OR “Northern Mariana Islands” OR Oman OR Mayotte OR Muscat OR Pakistan OR Palau OR Palestine OR Panama OR Paraguay OR Peru OR Philippines OR Philipines OR Phillipines OR Phillippines OR Polynesia OR “Puerto Rico” OR Qatar OR Reunion OR Rwanda OR Ruanda OR “Saint Kitts” OR “St Kitts” OR Nevis OR “Saint Lucia” OR “St Lucia” OR “Saint Vincent” OR “St Vincent” OR Grenadines OR Samoa OR “Samoan Islands” OR “Navigator Island” OR “Navigator Islands” OR “Sao Tome” OR “Saudi Arabia” OR Senegal OR Serbia OR Montenegro OR Seychelles OR “Sierra Leone” OR Singapore OR “Sri Lanka” OR Ceylon OR “Solomon Islands” OR Somalia OR “South Africa” OR Sudan OR Suriname OR Surinam OR Swaziland OR Syria OR Tajikistan OR Tadzhikistan OR Tadjikistan OR Tadzhik OR Tanzania OR Thailand OR Togo OR “Togolese Republic” OR Tokelau OR Tonga OR Trinidad OR Tobago OR Tunisia OR Turkey OR Turkmenistan OR Turkmen OR “Turks Caicos” OR “Tuvalu Uganda” OR “United Arab Emirates” OR Uruguay OR Uzbekistan OR Uzbek OR Vanuatu OR “New Hebrides” OR Venezuela OR Vietnam OR “Viet Nam” OR “Virgin Islands” OR “West Bank” OR Yemen OR Yugoslavia OR Zambia OR Zimbabwe)
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SUPPLEMENTAL TABLE 6 Criteria and associated scoring used to assess likely impact of bias and/or poor study quality Score = 0 (bias or poor Score = 1 (uncertain about Score = 2 (bias or poor Criteria quality likely) bias/quality) quality less likely 1. Country and region where Country but not region Both country and region Neither specified study conducted specified specified 2. Study year and data Neither year nor duration Both year and duration Year or duration specified collection period reported specified specified 3. Random No or not specified Possibly, but unclear Yes, clearly stated sampling/selection used 4. Sampling/selection method No Yes, but unclear Yes clearly described 5.1. Health outcome No Yes assessment protocol described Direct measurement 5.2. Health outcome assessed Reported (by or for (blood, stool, other directly or reported participant) samples, or tests) 6.1. 2 2 table (or data needed to construct one) provided 6.2. Adjusted effect estimates provided
No
Yes
No
Yes
SUPPLEMENTAL TABLE 7 Completed PRISMA 2009 checklist Section/topic
#
Checklist item
Reported on page #
TITLE Title ABSTRACT Structured summary
1
Identify the report as a systematic review, meta-analysis, or both.
2
Provide a structured summary including, as applicable: background; objectives; data sources; study eligibility criteria, participants, and interventions; study appraisal and synthesis methods; results; limitations; conclusions and implications of key findings; systematic review registration number.
1
INTRODUCTION Rationale
3
2–3
Objectives
4
Describe the rationale for the review in the context of what is already known. Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design (PICOS).
METHODS Protocol and registration
5
–
Eligibility criteria
6
Information sources
7
Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide registration information including registration number. Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale. Describe all information sources (e.g., databases with dates of
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Title page
4
4
4
Search
8
Study selection
9
Data collection process
10
Data items
11
Risk of bias in individual studies
12
Summary measures
13
Synthesis of results
14
Risk of bias across studies Additional analyses
15 16
coverage, contact with study authors to identify additional studies) in the search and date last searched. Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated. State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis). Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators. List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made. Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis. State the principal summary measures (e.g., risk ratio, difference in means). Describe the methods of handling data and combining results of studies, if done, including measures of consistency (e.g., I2) for each meta-analysis. Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective reporting within studies). Describe methods of additional analyses (e.g., sensitivity or subgroup analyses, meta-regression), if done, indicating which were prespecified.
RESULTS Study selection
17
Study characteristics
18
Risk of bias within studies Results of individual studies
19
Synthesis of results
21
Risk of bias across studies
22
Additional analysis
23
Give results of additional analyses, if done (e.g., sensitivity or subgroup analyses, meta-regression [see Item 16]).
DISCUSSION Summary of evidence
24
Limitations
25
Conclusions
26
Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy makers). Discuss limitations at study and outcome level (e.g., risk of bias), and at review-level (e.g., incomplete retrieval of identified research, reporting bias). Provide a general interpretation of the results in the context of other evidence, and implications for future research.
FUNDING Funding
27
20
Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram. For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and provide the citations. Present data on risk of bias of each study and, if available, any outcome level assessment (see item 12). For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each intervention group (b) effect estimates and confidence intervals, ideally with a forest plot. Present results of each meta-analysis done, including confidence intervals and measures of consistency. Present results of any assessment of risk of bias across studies (see Item 15).
Describe sources of funding for the systematic review and other
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Supplemental Tables 2–5 4–5
5–6
4–5 6–7
5 5–7
6–7 6–7
8–10
8–13 11–13 14–21
14–21 21 and Supplemental Tables 8–10 Supplemental Tables 6–7 22–28
26–27
27–28
29
support (e.g., supply of data); role of funders for the systematic review. Source: http://www.prisma-statement.org/documents/PRISMA%202009%20checklist.doc From: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 6(7): e1000097. doi:10.1371/journal.pmed1000097 Page numbers reference the submitted manuscript and may not align with the published version. SUPPLEMENTAL TABLE 8 Meta-regression results for studies reporting protozoal and diarrheal outcomes Protozoal outcome studies (N = 11) Diarrheal outcome studies (N = 7) P Monte Monte OR 95% CI 95% CI P value Carlo P Variables value Carlo P OR value value Total participants (or households) 0.99 to 1.00 0.99–1.01 0.054 0.02 1.00 0.69 0.65 1.00 Participant age < 15 (vs. adults) 0.00 to > 1.16 0.36–3.74 0.74 0.73 0.19 0.28 0.19 3k U participants (vs. only R) 1.40 0.22–9.02 0.65 0.60 – – – – U and R participants (vs. only R) 1.46 0.18–12.05 0.64 0.61 – – – – Outbreak investigation (vs. other) – – – – – – – – Study duration (months) 0.98 0.94–1.01 0.17 0.10 0.98 0.44to 2.20 0.79 0.44 Random sampling (vs. no) 0.12 0.01–2.49 0.12 0.08 1.47 0.01 to 332 0.53 0.56 Outcome measured (vs. reported) – – – – 0.89 0.00 to 713 0.86 0.89 CI = confidence interval; OR = odds ratio; R = rural; U = urban; k = 1,000. Cells with “–” indicate instances where there was too much collinearity with the associated covariate. Cells with “–” indicate instances where there were an insufficient number of observations available. SUPPLEMENTAL TABLE 9 Meta-regression results for studies reporting protozoal and diarrheal outcomes: controlling for study quality Protozoal outcome studies (N = 11) Diarrheal outcome studies (N = 7) P Monte Monte OR 95% CI 95% CI P value Carlo P Variables value Carlo P OR value value Total participants (or households) 0.99 to 1.00 0.99–1.00 0.42 0.43 1.00 0.53 0.48 1.00 Participant age < 15 (vs. adults) 0.00 to 1.24 0.16–9.68 0.79 0.72 0.21 0.25 0.09 665.7 U participants (vs. only R) 4.56 0.35–59.5 0.18 0.14 – – – – U and R participants (vs. only R) 1.33 0.01–127.7 0.87 0.93 – – – – Outbreak investigation (vs. other) 0.00 to > – – – – 6.82 0.59 0.67 999k Study duration (months) 0.00 to 0.97 0.86–1.08 0.47 0.42 0.76 0.60 0.59 88.9 Quality index grade high (vs. 0.00 to > 3.53 0.03–480.3 0.52 0.47 0.72 0.79 0.72 medium/low) 200k CI = confidence interval; OR = odds ratio; R = rural; U = urban; k = 1,000. Cells with “–” indicate instances where there was too much collinearity with the associated covariate. Cells with “–” indicate instances where there were an insufficient number of observations available
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SUPPLEMENTAL TABLE 10 Assessment of likely impact of bias and/or poor study quality: Results for each study Bias/quality criteria 5 6 Author Year Quality index* 1 2 3 4 5.1 5.2 6.1 62 Aggarwal Al-Delaimy Bello Cardenas Carrero Choy Cifuentes Cohen Corwin Fredrick Gunawardena Herrera Iijima Kelly Knight Lee Li Marcano Nunez Psutka Ries Rondon Sarkar Sarkar Sharma Weber Wordemann
2002 2014 2011 1993 2013 2014 1998 2015 1995 2015 2004 2006 2001 1997 1992 2012 2007 2013 2003 2013 1992 2003 2014a 2014b 2009 1994 2006
2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2
2 2 2 2 1 2 2 2 2 2 2 2 2 2 2 2 1 1 1 1 2 2 2 2 2 2 2
2 0 0 2 0 2 1 2 1 1 2 1 1 1 2 1 2 1 1 2 1 1 1 1 2 1 2
2 2 2 0 2 2 0 2 0 2 0 1 1 0 2 1 0 0 0 2 2 1 1 0 1 0 1
1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 0 1 1 1 1 1 1 1
1 1 1 0 1 1 1 0 1 1 1 1 0 1 1 1 1 1 1 0 1 1 1 1 1 1 1
0 1 0 1 1 0 1 0 1 1 0 1 1 0 0 1 0 1 1 0 1 1 0 0 1 1 0
0 0 1 0 0 1 0 0 0 1 1 0 0 0 1 0 1 0 0 0 1 0 1 1 1 0 0
8.3 7.5 7.5 6.7 6.7 9.2 6.7 7.5 6.7 9.2 7.5 7.5 6.7 5.8 9.2 7.5 6.7 5.8 5.8 5.8 9.2 7.5 7.5 6.7 9.2 6.7 7.5
Grade† High High High Medium Medium High Medium High Medium High High High Medium Low High High Medium Low Low Low High High High Medium High Medium High
* Quality index calculating as a composite index of criteria 1–6, using equal weights and then converted to a 0–10 scale. † Low score: < 6; medium score: 6–7; high score: 7.
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SUPPLEMENTAL TABLE 11 Pooled OR by outcome and stratified by estimated study quality grade Low Medium High Study quality grade Pooled OR (n) 95% CI Pooled OR (n) Bacterial Vibrio cholerae Helicobacter pylori Salmonella typhi Helminthic Multiple helminthic infections Ascaris Strongyloides stercoralis Trichuris Hookworm Protozoal Giardia Blastocystis Multiple protozoan parasites Cryptosporidium parvum Entamoeba histolytica/dispar Viral Hepatitis E Rotavirus Diarrheal Diarrheal disease outcomes
0.53 (2)
0.27 (1) 0.80 (1)
0.60 (2)
95% CI
Pooled OR (n)
95% CI
0.29–0.96
0.11 (2) 1.12 (1) 1.30 (1)
0.01–1.12 0.58–2.16 0.62–2.71
1.21 (2)
0.80–1.81
1.18 (2) 0.30 (1) 1.62 (1) 1.16 (1)
0.09–14.9 0.12–0.76 0.46–5.70 0.26–5.10
0.84 (3) 0.40 (1) 0.83 (1) 0.49 (1) 1.49 (1)
0.43–1.62 0.19–0.86 0.32–2.16 0.25–0.97 0.19–11.6
0.12–0.59 0.17 (2)
0.03–0.94
0.77 (1) 0.83 (2)
0.51–1.17 0.65–1.05
1.11 (1)
0.61–1.97
0.60 (3)
0.50–0.78
0.31 (2)
0.05–2.03
0.45–1.43
0.40–0.89
CI = confidence interval; OR = odds ratio.
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Figure 1
Identification
Records identified via PubMed/MEDLINE (n = 1,306)
Records identified via EMBASE (n = 1,329)
Records identified via database searching (n = 3,976)
Records identified via Web of Science (n = 1,270)
Records identified via Cochrane Library (n = 71)
Additional records identified via hand-search (n = 84)
Screening
Records after duplicates removed (n = 1,998)
Records screened by title & abstract (n = 1,998)
Records eligible for full-text review (n = 156)
Records excluded (n = 1,842)
Conference abstract only (n = 12) Could not find or access full-text (n = 9)
Eligibility
Full-text articles excluded (n = 63)
Full-text articles assessed for eligibility (n = 135)
Boiling data collected in study but not sufficiently reported to enable results interpretation or data extraction (n = 45)
Articles eligible for inclusion (n = 72)
Included
Only data on water source, general treatment, or non-boiling treatment (n = 43) Only data on water storage (n = 7) No water treatment or boiling data (n = 7) Data reported in another article (n = 5) Health outcome not measured (n = 1)
Articles which reported extractable data for meta-analysis (n = 27) Page 43 of 48
Figure 2 First Author
Drinking Water Boiling & Bacterial Infection Outcomes Year of Publication
OR (95% CI)
% Weight
0.03 (0.00, 0.20) 0.30 (0.10, 0.60) 0.48 (0.25, 0.93) 0.80 (0.20, 3.29) 0.31 (0.13, 0.79)
8.33 17.96 20.53 12.87 59.69
1.12 (0.58, 2.16)
20.58
. SALMONELLA TYPHI Sharma 2009
1.30 (0.60, 2.61)
19.72
. Overall (I-squared = 73.7%, p = 0.002)
0.54 (0.26, 1.11)
100.00
VIBRIO CHOLERAE Fredrick 2015 1992 Ries Weber 1994 Cardenas 1993 Subtotal (I-squared = 63.7%, p = 0.041) . HELICOBACTER PYLORI 2012 Lee
.01
.1
1 5 Odds Ratio (95% Confidence Interval)
Black diamond = study OR; Yellow diamond = pooled OR and CI; Box sizes are proportional to study weights (based on random effects analysis) Page 44 of 48
Figure 3 First Author
Drinking Water Boiling & Helminthic Infection Outcomes Year of Publication
MULTIPLE HELMINTH INFECTIONS 2014 Al-Delaimy 2006 Wordemann Subtotal (I-squared = 0.0%, p = 0.667) . ASCARIS Gunawardena 2004* 2006 Wordemann Subtotal (I-squared = 90.8%, p = 0.001) . STRONGYLOIDES STERCORALIS 2006 Herrera
OR (95% CI)
% Weight
1.16 (0.75, 1.80) 1.49 (0.52, 4.26) 1.21 (0.80, 1.81)
20.38 14.13 34.52
0.33 (0.11, 0.93) 4.35 (1.40, 13.46) 1.18 (0.09, 14.94)
14.13 13.35 27.48
0.30 (0.12, 0.76)
15.52
. TRICHURIS Wordemann
2006
1.62 (0.46, 5.70)
12.14
. HOOKWORM Wordemann
2006
1.16 (0.26, 5.10)
10.34
. Overall (I-squared = 68.3%, p = 0.004)
1.01 (0.53, 1.94)
100.00
.01
.1
1 10 Odds Ratio (95% Confidence Interval)
Black diamond = study OR (*adjusted effect); Yellow diamond = pooled OR and CI; Box sizes are proportional to study weights (based on random effects analysis) Page 45 of 48
Figure 4
First Author
Drinking Water Boiling & Protozoal Outcomes Year of Publication
OR (95% CI)
% Weight
0.27 (0.12, 0.59) 0.48 (0.32, 0.75) 0.90 (0.58, 1.32) 2.03 (0.71, 5.87) 0.66 (0.35, 1.25)
10.10 16.17 16.45 7.19 49.92
0.11 (0.01, 0.79) 0.40 (0.18, 0.85) 0.58 (0.03, 13.07) 0.35 (0.17, 0.69)
2.63 10.51 1.17 14.31
0.79 (0.44, 1.43) 0.83 (0.32, 2.16) 0.80 (0.49, 1.32)
13.35 8.12 21.47
0.49 (0.25, 0.97)
11.78
. ENTAMOEBA HISTOLYTICA/DISPAR Wordemann 2006
1.49 (0.19, 11.59)
2.52
. Overall (I-squared = 50.7%, p = 0.027)
0.61 (0.43, 0.86)
100.00
GIARDIA Nunez 2003 Choy 2014* Bello 2011* Wordemann 2006 Subtotal (I-squared = 78.1%, p = 0.003) . BLASTOCYSTIS Li 2007* Rondon 2003 Carrero 2013 Subtotal (I-squared = 0.0%, p = 0.452) . MULTIPLE PROTOZOAN PARASITES Marcano 2013 Wordemann 2006 Subtotal (I-squared = 0.0%, p = 0.944) . CRYPTOSPORIDIUM PARVUM Sarkar 2014a*
.01
.1
1 10 Odds Ratio (95% Confidence Interval)
Black diamond = study OR (*adjusted effect); Yellow diamond = pooled OR and CI; Box sizes are proportional to study weights (based on random effects analysis) Page 46 of 48
Figure 5
Drinking Water Boiling & Viral Infection Outcomes
First Author
% Year of Publication
OR (95% CI)
Weight
HEPATITIS E Corwin
1995
0.77 (0.51, 1.17)
12.87
Aggarwal
2002
1.11 (0.61, 1.97)
7.12
0.87 (0.62, 1.22)
20.00
Subtotal (I-squared = 0.0%, p = 0.325) . ROTAVIRUS Sarkar
2014b [2008-2012 study]*
0.75 (0.67, 0.84)
52.47
Sarkar
2014b [1993-1997 study]*
0.96 (0.75, 1.22)
27.54
0.83 (0.65, 1.05)
80.00
0.83 (0.70, 0.98)
100.00
Subtotal (I-squared = 69.5%, p = 0.070) . Overall (I-squared = 34.6%, p = 0.205)
.5
1 2 Odds Ratio (95% Confidence Interval)
Black diamond = study OR (*adjusted effect); Yellow diamond = pooled OR and CI; Box sizes are proportional to study weights (based on random effects analysis) Page 47 of 48
Figure 6
Drinking Water Boiling & Diarrheal Disease Outcomes
First
Year of
Author
Publication
% OR (95% CI)
Weight
DIARRHEA (NOT FURTHER SPECIFIED) Knight
1992*
0.11 (0.03, 0.35)
4.67
Psutka
2013
0.42 (0.08, 72.97)
0.62
Iijima
2001
0.55 (0.38, 0.80)
22.06
Cardenas
1993
0.60 (0.20, 1.70)
5.49
Kelly
1997
0.60 (0.40, 0.89)
21.07
Cifuentes
1998
0.66 (0.44, 1.00)
20.83
Cohen
2015
0.74 (0.54, 1.02)
25.26
0.58 (0.45, 0.76)
100.00
. Overall (I-squared = 42.3%, p = 0.109)
.01
.1
1 10 Odds Ratio (95% Confidence Interval)
Black diamond = study OR (*adjusted effect); Yellow diamond = pooled OR and CI; Box sizes are proportional to study weights (based on random effects analysis)
Page 48 of 48
