Poor sanitation is thought to be a major cause of enteric infections among young children. However, there are no previously published randomized trials to measure the health impacts of large-scale ...sanitation programs. India's Total Sanitation Campaign (TSC) is one such program that seeks to end the practice of open defecation by changing social norms and behaviors, and providing technical support and financial subsidies. The objective of this study was to measure the effect of the TSC implemented with capacity building support from the World Bank's Water and Sanitation Program in Madhya Pradesh on availability of individual household latrines (IHLs), defecation behaviors, and child health (diarrhea, highly credible gastrointestinal illness HCGI, parasitic infections, anemia, growth).
We conducted a cluster-randomized, controlled trial in 80 rural villages. Field staff collected baseline measures of sanitation conditions, behaviors, and child health (May-July 2009), and revisited households 21 months later (February-April 2011) after the program was delivered. The study enrolled a random sample of 5,209 children <5 years old from 3,039 households that had at least one child <24 months at the beginning of the study. A random subsample of 1,150 children <24 months at enrollment were tested for soil transmitted helminth and protozoan infections in stool. The randomization successfully balanced intervention and control groups, and we estimated differences between groups in an intention to treat analysis. The intervention increased percentage of households in a village with improved sanitation facilities as defined by the WHO/UNICEF Joint Monitoring Programme by an average of 19% (95% CI for difference: 12%-26%; group means: 22% control versus 41% intervention), decreased open defecation among adults by an average of 10% (95% CI for difference: 4%-15%; group means: 73% intervention versus 84% control). However, the intervention did not improve child health measured in terms of multiple health outcomes (diarrhea, HCGI, helminth infections, anemia, growth). Limitations of the study included a relatively short follow-up period following implementation, evidence for contamination in ten of the 40 control villages, and bias possible in self-reported outcomes for diarrhea, HCGI, and open defecation behaviors.
The intervention led to modest increases in availability of IHLs and even more modest reductions in open defecation. These improvements were insufficient to improve child health outcomes (diarrhea, HCGI, parasite infection, anemia, growth). The results underscore the difficulty of achieving adequately large improvements in sanitation levels to deliver expected health benefits within large-scale rural sanitation programs.
ClinicalTrials.gov NCT01465204. Please see later in the article for the Editors' Summary.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Accurate estimates of the burden of SARS-CoV-2 infection are critical to informing pandemic response. Confirmed COVID-19 case counts in the U.S. do not capture the total burden of the pandemic ...because testing has been primarily restricted to individuals with moderate to severe symptoms due to limited test availability. Here, we use a semi-Bayesian probabilistic bias analysis to account for incomplete testing and imperfect diagnostic accuracy. We estimate 6,454,951 cumulative infections compared to 721,245 confirmed cases (1.9% vs. 0.2% of the population) in the United States as of April 18, 2020. Accounting for uncertainty, the number of infections during this period was 3 to 20 times higher than the number of confirmed cases. 86% (simulation interval: 64-99%) of this difference is due to incomplete testing, while 14% (0.3-36%) is due to imperfect test accuracy. The approach can readily be applied in future studies in other locations or at finer spatial scale to correct for biased testing and imperfect diagnostic accuracy to provide a more realistic assessment of COVID-19 burden.
Shallow tubewells are the primary drinking water source for most rural Bangladeshis. Fecal contamination has been detected in tubewells, at low concentrations at the source and at higher levels at ...the point of use. We conducted a randomized controlled trial to assess whether improving the microbiological quality of tubewell drinking water by household water treatment and safe storage would reduce diarrhea in children <2 years in rural Bangladesh.
We randomly assigned 1800 households with a child aged 6-18 months (index child) into one of three arms: chlorine plus safe storage, safe storage and control. We followed households with monthly visits for one year to promote the interventions, track their uptake, test participants' source and stored water for fecal contamination, and record caregiver-reported child diarrhea prevalence (primary outcome). To assess reporting bias, we also collected data on health outcomes that are not expected to be impacted by our interventions.
Both interventions had high uptake. Safe storage, alone or combined with chlorination, reduced heavy contamination of stored water. Compared to controls, diarrhea in index children was reduced by 36% in the chlorine plus safe storage arm (prevalence ratio, PR = 0.64, 0.55-0.73) and 31% in the safe storage arm (PR = 0.69, 0.60-0.80), with no difference between the two intervention arms. One limitation of the study was the non-blinded design with self-reported outcomes. However, the prevalence of health outcomes not expected to be impacted by water interventions did not differ between study arms, suggesting minimal reporting bias.
Safe storage significantly improved drinking water quality at the point of use and reduced child diarrhea in rural Bangladesh. There was no added benefit from combining safe storage with chlorination. Efforts should be undertaken to implement and evaluate long-term efforts for safe water storage in Bangladesh.
ClinicalTrials.gov NCT01350063.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Efforts to monitor malaria transmission increasingly use cross-sectional surveys to estimate transmission intensity from seroprevalence data using malarial antibodies. To date, seroconversion rates ...estimated from cross-sectional surveys have not been compared to rates estimated in prospective cohorts. Our objective was to compare seroconversion rates estimated in a prospective cohort with those from a cross-sectional survey in a low-transmission population.
The analysis included two studies from Haiti: a prospective cohort of 142 children ages ≤ 11 years followed for up to 9 years, and a concurrent cross-sectional survey of 383 individuals ages 0-90 years old. From all individuals, we analyzed 1,154 blood spot specimens for the malaria antibody MSP-1(19) using a multiplex bead antigen assay. We classified individuals as positive for malaria using a cutoff derived from the mean plus 3 standard deviations in antibody responses from a negative control set of unexposed individuals. We estimated prospective seroconversion rates from the longitudinal cohort based on 13 incident seroconversions among 646 person-years at risk. We also estimated seroconversion rates from the cross-sectional survey using a reversible catalytic model fit with maximum likelihood. We found the two approaches provided consistent results: the seroconversion rate for ages ≤ 11 years was 0.020 (0.010, 0.032) estimated prospectively versus 0.023 (0.001, 0.052) in the cross-sectional survey.
The estimation of seroconversion rates using cross-sectional data is a widespread and generalizable problem for many infectious diseases that can be measured using antibody titers. The consistency between these two estimates lends credibility to model-based estimates of malaria seroconversion rates using cross-sectional surveys. This study also demonstrates the utility of including malaria antibody measures in multiplex assays alongside targets for vaccine coverage and other neglected tropical diseases, which together could comprise an integrated, large-scale serological surveillance platform.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Intermittent delivery of piped water can lead to waterborne illness through contamination in the pipelines or during household storage, use of unsafe water sources during intermittencies, and limited ...water availability for hygiene. We assessed the association between continuous versus intermittent water supply and waterborne diseases, child mortality, and weight for age in Hubli-Dharwad, India.
We conducted a matched cohort study with multivariate matching to identify intermittent and continuous supply areas with comparable characteristics in Hubli-Dharwad. We followed 3,922 households in 16 neighborhoods with children <5 y old, with four longitudinal visits over 15 mo (Nov 2010-Feb 2012) to record caregiver-reported health outcomes (diarrhea, highly credible gastrointestinal illness, bloody diarrhea, typhoid fever, cholera, hepatitis, and deaths of children <2 y old) and, at the final visit, to measure weight for age for children <5 y old. We also collected caregiver-reported data on negative control outcomes (cough/cold and scrapes/bruises) to assess potential bias from residual confounding or differential measurement error. Continuous supply had no significant overall association with diarrhea (prevalence ratio PR = 0.93, 95% confidence interval CI: 0.83-1.04, p = 0.19), bloody diarrhea (PR = 0.78, 95% CI: 0.60-1.01, p = 0.06), or weight-for-age z-scores (Δz = 0.01, 95% CI: -0.07-0.09, p = 0.79) in children <5 y old. In prespecified subgroup analyses by socioeconomic status, children <5 y old in lower-income continuous supply households had 37% lower prevalence of bloody diarrhea (PR = 0.63, 95% CI: 0.46-0.87, p-value for interaction = 0.03) than lower-income intermittent supply households; in higher-income households, there was no significant association between continuous versus intermittent supply and child diarrheal illnesses. Continuous supply areas also had 42% fewer households with ≥1 reported case of typhoid fever (cumulative incidence ratio CIR = 0.58, 95% CI: 0.41-0.78, p = 0.001) than intermittent supply areas. There was no significant association with hepatitis, cholera, or mortality of children <2 y old; however, our results were indicative of lower mortality of children <2 y old (CIR = 0.51, 95% CI: 0.22-1.07, p = 0.10) in continuous supply areas. The major limitations of our study were the potential for unmeasured confounding given the observational design and measurement bias from differential reporting of health symptoms given the nonblinded treatment. However, there was no significant difference in the prevalence of the negative control outcomes between study groups that would suggest undetected confounding or measurement bias.
Continuous water supply had no significant overall association with diarrheal disease or ponderal growth in children <5 y old in Hubli-Dharwad; this might be due to point-of-use water contamination from continuing household storage and exposure to diarrheagenic pathogens through nonwaterborne routes. Continuous supply was associated with lower prevalence of dysentery in children in low-income households and lower typhoid fever incidence, suggesting that intermittently operated piped water systems are a significant transmission mechanism for Salmonella typhi and dysentery-causing pathogens in this urban population, despite centralized water treatment. Continuous supply was associated with reduced transmission, especially in the poorer higher-risk segments of the population.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
CONTEXT Chorioamnionitis has been implicated in the pathogenesis of cerebral
palsy, but most studies have not reported a significant association. Cystic
periventricular leukomalacia (cPVL) is ...believed to be a precursor of cerebral
palsy in preterm infants. OBJECTIVES To determine whether chorioamnionitis is associated with cerebral palsy
or cPVL and to examine factors that may explain differences in study results. DATA SOURCES Searches of MEDLINE (1966-1999), Index Medicus (1960-1965), Doctoral
Dissertation Abstracts On-Line (1861-1999), bibliographies, and online conference
proceedings (1999) were performed for English-language studies with titles
or abstracts that discussed prenatal risk factors for cerebral palsy or cPVL. STUDY SELECTION Of 229 initially identified publications, meta-analyses were performed
on studies that addressed the association between clinical (n = 19) or histologic
(n = 7) chorioamnionitis and cerebral palsy or cPVL in both preterm and full-term
infants. Inclusion criteria were: presence of appropriate exposure and outcome
measures, case-control or cohort study design, and provision of sufficient
data to calculate relative risks (RRs) or odds ratios with 95% confidence
intervals (CIs). Studies evaluating risk of cerebral palsy following maternal
fever, urinary tract infection, or other maternal infection were collected,
but not included in the meta-analysis. DATA EXTRACTION Information from individual studies was abstracted using standardized
forms by 2 independent observers blinded to authors' names, journal titles,
and funding sources. DATA SYNTHESIS Using a random effects model, clinical chorioamnionitis was significantly
associated with both cerebral palsy (RR, 1.9; 95% CI, 1.4-2.5) and cPVL (RR,
3.0; 95% CI, 2.2-4.0) in preterm infants. The RR of histologic chorioamnionitis
and cerebral palsy was 1.6 (95% CI, 0.9-2.7) in preterm infants, and histologic
chorioamnionitis was significantly associated with cPVL (RR, 2.1; 95% CI,
1.5-2.9). Among full-term infants, a positive association was found between
clinical chorioamnionitis and cerebral palsy (RR, 4.7; 95% CI, 1.3-16.2).
Factors explaining differences in study results included varying definitions
of clinical chorioamnionitis, extent of blinding in determining exposure status,
and whether individual studies adjusted for potential confounders. CONCLUSION Our meta-analysis indicates that chorioamnionitis is a risk factor for
both cerebral palsy and cPVL.
Current guidelines recommend the use of Escherichia coli (EC) or thermotolerant ("fecal") coliforms (FC) as indicators of fecal contamination in drinking water. Despite their broad use as measures of ...water quality, there remains limited evidence for an association between EC or FC and diarrheal illness: a previous review found no evidence for a link between diarrhea and these indicators in household drinking water.
We conducted a systematic review and meta-analysis to update the results of the previous review with newly available evidence, to explore differences between EC and FC indicators, and to assess the quality of available evidence.
We searched major databases using broad terms for household water quality and diarrhea. We extracted study characteristics and relative risks (RR) from relevant studies. We pooled RRs using random effects models with inverse variance weighting, and used standard methods to evaluate heterogeneity and publication bias.
We identified 20 relevant studies; 14 studies provided extractable results for meta-analysis. When combining all studies, we found no association between EC or FC and diarrhea (RR 1.26 95% CI: 0.98, 1.63). When analyzing EC and FC separately, we found evidence for an association between diarrhea and EC (RR: 1.54 95% CI: 1.37, 1.74) but not FC (RR: 1.07 95% CI: 0.79, 1.45). Across all studies, we identified several elements of study design and reporting (e.g., timing of outcome and exposure measurement, accounting for correlated outcomes) that could be improved upon in future studies that evaluate the association between drinking water contamination and health.
Our findings, based on a review of the published literature, suggest that these two coliform groups have different associations with diarrhea in household drinking water. Our results support the use of EC as a fecal indicator in household drinking water.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The effects of weather on diarrhea could influence the health impacts of climate change. Children have the highest diarrhea incidence, especially in India, where many lack safe water and sanitation.
...In a prospective cohort of 1,284 children under 5 y of age from 900 households across 25 villages in rural Tamil Nadu, India, we examined whether high temperature and heavy rainfall was associated with increased all-cause diarrhea and water contamination.
Seven-day prevalence of diarrhea was assessed monthly for up to 12 visits from January 2008 to April 2009, and hydrogen sulfide (Formula: see text) presence in drinking water, a fecal contamination indicator, was tested in a subset of households. We estimated associations between temperature and rainfall exposures and diarrhea and Formula: see text using binomial regressions, adjusting for potential confounders, random effects for village, and autoregressive-1 error terms for study week.
There were 259 cases of diarrhea. The prevalence of diarrhea during the 7 d before visits was 2.95 times higher (95% CI: 1.99, 4.39) when mean temperature in the week before the 7-d recall was in the hottest versus the coolest quartile of weekly mean temperature during 1 December 2007 to 15 April 2009. Diarrhea prevalence was 1.50 times higher when the 3 weeks before the diarrhea recall period included Formula: see text (vs. 0 d) with rainfall of Formula: see text (95% CI: 1.12, 2.02), and 2.60 times higher (95% CI: 1.55, 4.36) for heavy rain weeks following a 60-d dry period. The Formula: see text prevalence in household water was not associated with heavy rain prior to sample collection.
The results suggest that, in rural Tamil Nadu, heavy rainfall may wash pathogens that accumulate during dry weather into child contact. Higher temperatures were positively associated with diarrhea 1-3 weeks later. Our findings suggest that diarrhea morbidity could worsen under climate change without interventions to reduce enteric pathogen transmission through multiple pathways. https://doi.org/10.1289/EHP3711.
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CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Inadequate access to safe drinking water remains a global health problem, particularly in rural areas. Boiling is the most commonly used form of point-of-use household water treatment (HWT) globally, ...although the use of bottled water in low- and middle-income countries (LMICs) is increasing rapidly.
We assessed the regional and seasonal prevalence of HWT practices (including bottled water use) in low-income rural areas in two Chinese provinces, evaluated the microbiological safety of drinking water and associated health outcomes, and estimated the air pollution burden associated with the use of solid fuels for boiling.
We conducted cross-sectional surveys and collected drinking water samples from 1,033 rural households in Guangxi and Henan provinces. Temperature sensors affixed to pots and electric kettles were used to corroborate self-reported boiling frequencies and durations, which were used to model household air pollution (HAP) in terms of estimated particulate matter
in aerodynamic diameter (
) concentrations.
Based on summer data collection in both provinces, after controlling for covariates, boiling with electric kettles was associated with the largest log reduction in thermotolerant coliforms (TTCs) (
TTC most probable number
), followed by boiling with pots (
), and bottled water use (
); all were statistically significant (
). Boiling with electric kettles was associated with a reduced risk of TTC contamination risk ratio
,
and reported diarrhea (
,
). TTCs were detected in 51% (
) of bottled water samples. For households boiling with biomass, modeled
concentrations averaged
(
).
Our findings suggest that where boiling is already common and electricity access is widespread, the promotion of electricity-based boiling may represent a pragmatic stop-gap means of expanding safe water access until centralized, or decentralized, treated drinking water is available; displacing biomass use for water boiling could also reduce HAP concentrations and exposures. Our results also highlight the risks of increasing bottled water use in rural areas, and its potential to displace other sources of safe drinking water, which could in turn hamper efforts in China and other LMICs toward universal and affordable safe water access. https://doi.org/10.1289/EHP7124.
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CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Despite numerous studies, uncertainty remains about how water quality indicators can best be used in the regulation of recreational water. We conducted a systematic review of this topic with the goal ...of quantifying the association between microbial indicators of recreational water quality and gastrointestinal (GI) illness. A secondary goal was to evaluate the potential for GI illness below current guidelines. We screened 976 potentially relevant studies and from these identified 27 studies. From the latter, we determined summary relative risks for GI illness in relation to water quality indicator density. Our results support the use of enterococci in marine water at U.S. Environmental Protection Agency guideline levels. In fresh water, Escherichia coli was a more consistent predictor of GI illness than are enterococci and other bacterial indicators. A log (base 10) unit increase in enterococci was associated with a 1.34 95% confidence intervals (CI), 1.00-1.75 increase in relative risk in marine waters, and a log (base 10) unit increase in E. coli was associated with a 2.12 (95% CI, 0.925-4.85) increase in relative risk in fresh water. Indicators of viral contamination were strong predictors of GI illness in both fresh and marine environments. Significant heterogeneity was noted among the studies. In our analysis of heterogeneity, studies that used a nonswimming control group, studies that focused on children, and studies of athletic or other recreational events found elevated relative risks. Future studies should focus on the ability of new, more rapid and specific microbial methods to predict health effects, and estimating the risks of recreational water exposure among susceptible persons.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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