Nutritional factors and infectious agents may contribute to paediatric growth deficits in low- and middle-income countries; however, the contribution of enteric pathogens is only beginning to be understood. We analysed the stool from children <5 years old from an open cohort, cluster-randomised controlled trial of a point-of-collection water chlorinator in urban Bangladesh. We compared the presence/absence of 15 enteric pathogens detected via multiplex, molecular methods in the stool with concurrent Z-scores/Z-score cut-offs (-2 standard deviations (s.d.)) for height-for-age (HAZ/stunting), weight-for-age (WAZ/underweight) and weight-for-height (WHZ/wasting), adjusted for sociodemographic and trial-related factors, and measured caregiver-reported diarrhoea. Enteric pathogen prevalence in the stool was high (88% had ≥1 enteric pathogen, most commonly Giardia spp. (40%), Salmonella enterica (33%), enterotoxigenic E. coli (28%) and Shigella spp. (27%)) while reported 7-day diarrhoea prevalence was 6%, suggesting high subclinical infection rates. Many children were stunted (26%) or underweight (24%). Adjusted models suggested Giardia spp. detection was associated with lower HAZ (-0.22 s.d., 95% CI -0.44 to 0.00; prevalence ratio for stunting: 1.39, 95% CI 0.94-2.06) and potentially lower WAZ. No pathogens were associated with reported diarrhoea in adjusted models. Giardia spp. carriage may be associated with growth faltering, but not diarrhoea, in this and similar low-income settings. Stool-based enteric pathogen detection provides a direct indication of previous exposure that may be useful as a broader endpoint of trials of environmental interventions.

Almost half of all deaths from drinking microbiologically unsafe water occur in Sub-Saharan Africa. Household water treatment and safe storage (HWTS) systems, when consistently used, can provide safer drinking water and improve health. Social marketing to increase adoption and use of HWTS depends both on the prices of and preferences for these systems. This study included 556 households from rural Tanzania across two low-income districts with low-quality water sources. Over 9 months in 2012 and 2013, we experimentally evaluated consumer preferences for six "low-cost" HWTS options, including boiling, through an ordinal ranking protocol. We estimated consumers' willingness to pay (WTP) for these options, using a modified auction. We allowed respondents to pay for the durable HWTS systems with cash, chickens or mobile money; a significant minority chose chickens as payment. Overall, our participants favored boiling, the ceramic pot filter and, where water was turbid, PuR™ (a combined flocculant-disinfectant). The revealed WTP for all products was far below retail prices, indicating that significant scale-up may need significant subsidies. Our work will inform programs and policies aimed at scaling up HWTS to improve the health of resource-constrained communities that must rely on poor-quality, and sometimes turbid, drinking water sources.

The transmission of antimicrobial resistant bacteria in the urban environment is poorly understood. We utilized genomic sequencing and phylogenetics to characterize the transmission dynamics of antimicrobial resistant Escherichia coli (AMR-Ec) cultured from putative canine (canine_p) and human feces present on urban sidewalks in San Francisco, California. We isolated a total of fifty-six AMR-Ec isolates from human (n = 20) and canine_p (n = 36) fecal samples from the Tenderloin and South of Market (SoMa) neighborhoods of San Francisco. We then analyzed phenotypic and genotypic antimicrobial resistance (AMR) of the isolates, as well as clonal relationships based on cgMLST and single nucleotide polymorphisms (SNPs) of the core genomes. Using Bayesian inference, we reconstructed the transmission dynamics between humans and canines_p from multiple local outbreak clusters using the marginal structured coalescent approximation (MASCOT). Our results provide evidence for multiple sharing events of AMR-Ec between humans and canines_p. In particular, we found one instance of likely transmission from canines_p to humans as well as an additional local outbreak cluster consisting of one canine_p and one human sample. Based on this analysis, it appears that non-human feces act as an important reservoir of clinically relevant AMR-Ec within the urban environment for this study population. This work showcases the utility of genomic epidemiology to reconstruct potential pathways by which antimicrobial resistance spreads.

An end goal of fecal source tracking (FST) is to provide information on risk of transmission of waterborne illnesses associated with fecal contamination. Ideally, concentrations of FST markers in ambient waters would reflect exposure risk. Human mtDNA is an FST marker that is exclusively human in origin and may be elevated in feces of individuals experiencing gastrointestinal inflammation. In this study, we examined whether human mtDNA is elevated in fecal samples from individuals with symptomatic norovirus infections using samples from the United States (US), Mozambique, and Bangladesh. We quantified hCYTB484 (human mtDNA) and HF183/BacR287 (human-associated Bacteroides) FST markers using droplet digital polymerase chain reaction. We observed the greatest difference in concentrations of hCYTB484 when comparing samples from individuals with symptomatic norovirus infections versus individuals without norovirus infections or diarrhea symptoms: log₁₀ increase of 1.42 in US samples (3,820% increase, p-value = 0.062), 0.49 in Mozambique (308% increase, p-value = 0.061), and 0.86 in Bangladesh (648% increase, p-value = 0.035). We did not observe any trends in concentrations of HF183/BacR287 in the same samples. These results suggest concentrations of fecal mtDNA may increase during symptomatic norovirus infection and that mtDNA in environmental samples may represent an unambiguously human source-tracking marker that correlates with enteric pathogen exposure risk.

Access to continuous water supply is key for improving health and economic outcomes in rural areas of low- and middle-income countries, but the factors associated with continuous water access in these areas have not been well-characterized. We surveyed 4786 households for evidence of technical, financial, institutional, social, and environmental predictors of rural water service continuity (WSC), defined as the percentage of the year that water is available from a source. Multiple imputed fractional logistic regression models that account for the survey design were used to assess operational risks to WSC for piped supply, tube wells, boreholes, springs, dug wells, and surface water for the rural populations of Bangladesh, Pakistan, Ethiopia, and Mozambique. Multivariable regressions indicate that households using multiple water sources were associated with lower WSC in Bangladesh, Pakistan, and Mozambique. However, the possibility must be considered that households may use more than one water source because services are intermittent. Water scarcity and drought were largely unassociated with WSC, suggesting that service interruptions may not be primarily due to physical water resource constraints. Consistent findings across countries may have broader relevance for meeting established targets for service availability as well as human health.

Uncontained fecal wastes in cities may present exposure risks to the public. We collected discarded feces from public spaces in San Francisco, CA for analysis by RT-qPCR for a range of enteric pathogens. Out of 59 samples, we found 12 (20%) were of human origin and 47 (80%) were non-human; 30 of 59 stools were positive for ≥1 of the 35 pathogens assessed, including pathogenic E. coli, Shigella, norovirus, Cryptosporidium, and Trichuris. Using quantitative enteric pathogen estimates and data on observed fecal waste from a public reporting system, we modeled pathogens removed from the environment attributable to a recently implemented program of public toilet construction. We estimated that each new public toilet reduced the annual number of enteric pathogens released into the immediate environment (within 500 m walking distance), including 6.3 x 1012 enteropathogenic E. coli (95% CI: 4.0 x 1012–7.9 x 1012), 3.2 x 1011 enteroaggregative E. coli (95% CI: 1.3 x 1011–6.3 x 1011), and 3.2 x 108 Shigella (6.3 x 107–2.5 x 109). Improving access to public sanitation can reduce enteric pathogen hazards in cities. Interventions must also consider the hygienic disposal of animal waste to reduce microbial hazards with zoonotic infection potential.

Despite some progress, universal access to safe water, sanitation and hygiene (WASH) by 2030-a remit of Sustainable Development Goal 6-remains a distant prospect in many countries. Policy-makers and implementers of the WASH sector are challenged to track a new path. This research aimed to identify core orienting themes of the sector, as legacies of past processes, which can provide insights for its future. We reviewed global policy, science and programmatic documents and carried out 19 expert interviews to track the evolution of the global WASH sector over seven decades. We situated this evolution in relation to wider trends in global health and development over the same time period.With transnational flows of concern, expertise and resources from high-income to lower-income countries, the WASH sector evolved over decades of international institutionalisation of health and development with (1) a focus on technologies (technicalisation), (2) a search for generalised solutions (universalisation), (3) attempts to make recipients responsible for environmental health (responsibilisation) and (4) the shaping of programmes around quantifiable outcomes (metricisation). The emergent commitment of the WASH sector to these core themes reflects a pragmatic response in health and development to depoliticise poverty and social inequalities in order to enable action. This leads to questions about what potential solutions have been obscured, a recognition which might be understood as 'uncomfortable knowledge'-the knowns that have had to be unknown, which resonate with concerns about deep inequalities, shrinking budgets and the gap between what could and has been achieved.

Background

Estimates of the effectiveness of water, sanitation, and hygiene (WASH) interventions that provide high levels of service on childhood diarrhoea are scarce. We aimed to provide up-to-date estimates on the burden of disease attributable to WASH and on the effects of different types of WASH interventions on childhood diarrhoea in low-income and middle-income countries (LMICs).

Methods

In this systematic review and meta-analysis, we updated previous reviews following their search strategy by searching MEDLINE, Embase, Scopus, Cochrane Library, and BIOSIS Citation Index for studies of basic WASH interventions and of WASH interventions providing a high level of service, published between Jan 1, 2016, and May 25, 2021. We included randomised and non-randomised controlled trials conducted at household or community level that matched exposure categories of the so-called service ladder approach of the Sustainable Development Goal (SDG) for WASH. Two reviewers independently extracted study-level data and assessed risk of bias using a modified Newcastle-Ottawa Scale and certainty of evidence using a modified Grading of Recommendations, Assessment, Development, and Evaluation approach. We analysed extracted relative risks (RRs) and 95% CIs using random-effects meta-analyses and meta-regression models. This study is registered with PROSPERO, CRD42016043164.

Findings

19 837 records were identified from the search, of which 124 studies were included, providing 83 water (62 616 children), 20 sanitation (40 799 children), and 41 hygiene (98 416 children) comparisons. Compared with untreated water from an unimproved source, risk of diarrhoea was reduced by up to 50% with water treated at point of use (POU): filtration (n=23 studies; RR 0·50 [95% CI 0·41-0·60]), solar treatment (n=13; 0·63 [0·50-0·80]), and chlorination (n=25; 0·66 [0·56-0·77]). Compared with an unimproved source, provision of an improved drinking water supply on premises with higher water quality reduced diarrhoea risk by 52% (n=2; 0·48 [0·26-0·87]). Overall, sanitation interventions reduced diarrhoea risk by 24% (0·76 [0·61-0·94]). Compared with unimproved sanitation, providing sewer connection reduced diarrhoea risk by 47% (n=5; 0·53 [0·30-0·93]). Promotion of handwashing with soap reduced diarrhoea risk by 30% (0·70 [0·64-0·76]).

Interpretation

WASH interventions reduced risk of diarrhoea in children in LMICs. Interventions supplying either water filtered at POU, higher water quality from an improved source on premises, or basic sanitation services with sewer connection were associated with increased reductions. Our results support higher service levels called for under SDG 6. Notably, no studies evaluated interventions that delivered access to safely managed WASH services, the level of service to which universal coverage by 2030 is committed under the SDG.

Funding

WHO, Foreign, Commonwealth & Development Office, and National Institute of Environmental Health Sciences.

Healthy development of the gut microbiome provides long-term health benefits. Children raised in countries with high infectious disease burdens are frequently exposed to diarrhoeal pathogens and antibiotics, which perturb gut microbiome assembly. A recent cluster-randomized trial leveraging >4,000 child observations in Dhaka, Bangladesh, found that automated water chlorination of shared taps effectively reduced child diarrhoea and antibiotic use. In this substudy, we leveraged stool samples collected from 130 children 1 year after chlorine doser installation to examine differences between treatment and control children's gut microbiota. Water chlorination was associated with increased abundance of several bacterial genera previously linked to improved gut health; however, we observed no effects on the overall richness or diversity of taxa. Several clinically relevant antibiotic resistance genes were relatively more abundant in the gut microbiome of treatment children, possibly due to increases in Enterobacteriaceae. While further studies on the long-term health impacts of drinking chlorinated water would be valuable, we conclude that access to chlorinated water did not substantially impact child gut microbiome development in this setting, supporting the use of chlorination to increase global access to safe drinking water.

Infections with enteric pathogens impose a heavy disease burden, especially among young children in low-income countries. Recent findings from randomized controlled trials of water, sanitation, and hygiene interventions have raised questions about current methods for assessing environmental exposure to enteric pathogens. Approaches for estimating sources and doses of exposure suffer from a number of shortcomings, including reliance on imperfect indicators of fecal contamination instead of actual pathogens and estimating exposure indirectly from imprecise measurements of pathogens in the environment and human interaction therewith. These shortcomings limit the potential for effective surveillance of exposures, identification of important sources and modes of transmission, and evaluation of the effectiveness of interventions. In this review, we summarize current and emerging approaches used to characterize enteric pathogen hazards in different environmental media as well as human interaction with those media (external measures of exposure), and review methods that measure human infection with enteric pathogens as a proxy for past exposure (internal measures of exposure). We draw from lessons learned in other areas of environmental health to highlight how external and internal measures of exposure can be used to more comprehensively assess exposure. We conclude by recommending strategies for advancing enteric pathogen exposure assessments.