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BACKGROUND: 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. OBJECTIVES: 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. METHODS: Seven-day prevalence of diarrhea was assessed monthly for up to 12 visits from January 2008 to April 2009, and hydrogen sulfide (H2S) 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 H2S using binomial regressions, adjusting for potential confounders, random effects for village, and autoregressive-1 error terms for study week. RESULTS: 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 ≥1 d (vs. 0 d) with rainfall of >16:82 mm (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 H2S prevalence in household water was not associated with heavy rain prior to sample collection. CONCLUSIONS: 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. [ABSTRACT FROM AUTHOR]

Background: 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.Methods and Findings: 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.Conclusions: 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. [ABSTRACT FROM AUTHOR]

Empirical measurement of interventions to address significant global health and development problems is necessary to ensure that resources are applied appropriately. Such intervention programs are often deployed at the group or community level. The gold standard design to measure the effectiveness of community-level interventions is the community-randomized trial, but the conditions of these trials often make it difficult to assess their external validity and sustainability. The sheer number of community interventions, relative to randomized studies, speaks to a need for rigorous observational methods to measure their impact. In this article, we use the potential outcomes model for causal inference to motivate a matched cohort design to study the impact and sustainability of nonrandomized, preexisting interventions. We illustrate the method using a sanitation mobilization, water supply, and hygiene intervention in rural India. In a matched sample of 25 villages, we enrolled 1,284 children <5 y old and measured outcomes over 12 mo. Although we found a 33 percentage point difference in new toilet construction [95% confidence interval (Cl) = 28%, 39%), we found no impacts on height-for-age Z scores (adjusted difference = 0.01. 95% Cl= -0.15,0.19) or diarrhea (adjusted longitudinal prevalence difference = 0.003, 95% Cl = -0.001, 0.008) among children <5 y old. This study demonstrates that matched cohort designs can estimate impacts from nonrandomized, preexistirig interventions that are used widely in development efforts. Interpreting the impacts as causal, however, requires stronger assumptions than prospective, randomized studies. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to determine whether astigmatism or corneal scarring is mediating the reduced visual acuity among patients with fungal keratitis randomized to corneal cross-linking (CXL)., Design: This was a prespecified exploratory outcome from an outcome-masked, 2 × 2 factorial design, randomized controlled clinical trial., Study Participants: Consecutive patients presented with moderate vision loss from a smear-positive fungal ulcer at Aravind Eye Hospital, Madurai, India., Intervention: Study eyes were randomized to one of 4 treatment combinations using an adaptive randomization protocol. The treatment arms included (1) topical natamycin 5% alone, (2) topical natamycin 5% plus CXL, (3) topical amphotericin B 0.15% alone, and (4) topical amphotericin 0.15% plus CXL. Best spectacle-corrected visual acuity (BSCVA), contact lens over-refraction, and scar size and depth as measured by a masked study ophthalmologist using a standardized protocol were recorded at 3 months. Pentacam Scheimpflug imaging was also obtained at 3 months., Main Outcome Measures: BSCVA and contact lens over-refraction, infiltrate and/or scar size and depth, total astigmatism of the front and back of the cornea, total lower-order and higher-order aberrations of the anterior and posterior cornea, and total densitometry of the anterior, central, and posterior stroma were recorded. We performed a mediation analysis looking at the proportion of the effect of CXL on BSCVA that was mediated through scar size, scar depth, astigmatism and density., Results: BSCVA at 3 months was available for 99 of 111 patients (89%) who had a mean of 0.82-LogMAR (SD 0.68). Three-month infiltrate and/or scar size ( P < 0.001), depth ( P < 0.001), and densitometry ( P = 0.001) were statistically significant predictors of 3-month BSCVA. Astigmatism seemed to mediate 23% of the effect of CXL on BSCVA, whereas scar size mediated 23%, scar depth 17%, and densitometry 7%., Conclusions: Corneal scarring and astigmatism are mediators of worse visual acuity after cross-linking in fungal keratitis. Corneal densitometry may be a helpful cornea-specific variable for clinicians and researchers in determining the effect of corneal scarring on visual acuity in specific patients and as an objective study outcome., Trial Registration: NCT02570321., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: 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)., Methods and Findings: 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., Conclusions: 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., Trial Registration: ClinicalTrials.gov NCT01465204. Please see later in the article for the Editors' Summary.

In this large-scale longitudinal study conducted in rural Southern India, we compared a presence/absence hydrogen sulfide (H2S) test with quantitative assays for total coliforms and Escherichia coli as measures of water quality, health risk, and water supply vulnerability to microbial contamination. None of the three indicators showed a significant association with child diarrhea. The presence of H2S in a water sample was associated with higher levels of total coliform species that may have included E. coli but that were not restricted to E. coli. In addition, we observed a strong relationship between the percent positive H2S test results and total coliform levels among water source samples (R(2) = 0.87). The consistent relationships between H2S and total coliform levels indicate that presence/absence of H2S tests provide a cost-effective option for assessing both the vulnerability of water supplies to microbial contamination and the results of water quality management and risk mitigation efforts.