Addressing Fecal Contamination in Rural Kenyan Households: The Roles of Environmental Interventions and Animal Ownership.

Combined water, sanitation, and handwashing (WSH) interventions could reduce fecal contamination along more transmission pathways than single interventions alone. We measured Escherichia coli levels in 3909 drinking water samples, 2691 child hand rinses, and 2422 toy ball rinses collected from households enrolled in a 2-year cluster-randomized controlled trial evaluating single and combined WSH interventions. Water treatment with chlorine reduced E. coli in drinking water. A combined WSH intervention improved water quality by the same magnitude but did not affect E. coli levels on hands or toys. One potential explanation for the limited impact of the sanitation intervention (upgraded latrines) is failure to address dog and livestock fecal contamination. Small ruminant (goat or sheep) ownership was associated with increased E. coli levels in stored water and on child hands. Cattle and poultry ownership was protective against child stunting, and domesticated animal ownership was not associated with child diarrhea. Our findings do not support restricting household animal ownership to prevent child diarrheal disease or stunting but do support calls for WSH infrastructure that can more effectively reduce household fecal contamination.

Effects of breastfeeding on children's gut colonization with multidrug-resistant Enterobacterales in peri-urban Lima, Peru.

Children living in low-resource settings are frequently gut-colonized with multidrug-resistant bacteria. We explored whether breastfeeding may protect against children's incident gut colonization with extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-Ec) and Klebsiella, Enterobacter, or Citrobacter spp. (ESBL-KEC). We screened 937 monthly stool samples collected from 112 children aged 1-16 months during a 2016-19 prospective cohort study of enteric infections in peri-urban Lima. We used 52,816 daily surveys to examine how exposures to breastfeeding in the 30 days prior to a stool sample were associated with children's risks of incident gut-colonization, controlling for antibiotic use and other covariates. We sequenced 78 ESBL-Ec from 47 children to explore their diversity. Gut-colonization with ESBL-Ec was increasingly prevalent as children aged, approaching 75% by 16 months, while ESBL-KEC prevalence fluctuated between 18% and 36%. Through 6 months of age, exclusively providing human milk in the 30 days prior to a stool sample did not reduce children's risk of incident gut-colonization with ESBL-Ec or ESBL-KEC. From 6 to 16 months of age, every 3 additional days of breastfeeding in the prior 30 days was associated with 6% lower risk of incident ESBL-Ec gut-colonization (95% CI: 0.90, 0.98, p = .003). No effects were observed on incident ESBL-KEC colonization. We detected highly diverse ESBL-Ec among children and few differences between children who were predominantly breastfed (mean age: 4.1 months) versus older children (10.8 months). Continued breastfeeding after 6 months conferred protection against children's incident gut colonization with ESBL-Ec in this setting. Policies supporting continued breastfeeding should be considered in efforts to combat antibiotic resistance.

Evaluating the relationship between community water and sanitation access and the global burden of antibiotic resistance: an ecological study.

BACKGROUND: Antibiotic resistance is a leading cause of death, with the highest burden occurring in low-resource settings. There is little evidence on the potential for water, sanitation, and hygiene (WASH) access to reduce antibiotic resistance in humans. We aimed to determine the relationship between the burden of antibiotic resistance in humans and community access to drinking water and sanitation. METHODS: In this ecological study, we linked publicly available, geospatially tagged human faecal metagenomes (from the US National Center for Biotechnology Information Sequence Read Archive) with georeferenced household survey datasets that reported access to drinking water sources and sanitation facility types. We used generalised linear models with robust SEs to estimate the relationship between the abundance of antibiotic resistance genes (ARGs) in human faecal metagenomes and community-level coverage of improved drinking water and sanitation within a defined radii of faecal metagenome coordinates. FINDINGS: We identified 1589 metagenomes from 26 countries. The mean abundance of ARGs, in units of log10 ARG fragments per kilobase per million mapped reads classified as bacteria, was highest in Africa compared with Europe (p=0·014), North America (p=0·0032), and the Western Pacific (p=0·011), and second highest in South-East Asia compared with Europe (p=0·047) and North America (p=0·014). Increased access to improved water and sanitation was associated with lower ARG abundance (effect estimate -0·22, [95% CI -0·39 to -0·05]) and the association was stronger in urban (-0·32 [-0·63 to 0·00]) than in rural (-0·16 [-0·38 to 0·07]) areas. INTERPRETATION: Although additional studies to investigate causal effects are needed, increasing access to water and sanitation could be an effective strategy to curb the proliferation of antibiotic resistance in low-income and middle-income countries. FUNDING: Bill & Melinda Gates Foundation.

Effects of High Temperature and Heavy Precipitation on Drinking Water Quality and Child Hand Contamination Levels in Rural Kenya.

Climate change may impact human health through the influence of weather on environmental transmission of diarrhea. Previous studies have found that high temperatures and heavy precipitation are associated with increased diarrhea prevalence, but the underlying causal mechanisms have not been tested and validated. We linked measurements of Escherichia coli in source water (n = 1673), stored drinking water (n = 9692), and hand rinses from children <2 years old (n = 2634) with publicly available gridded temperature and precipitation data (at ≤0.2 degree spatial resolution and daily temporal resolution) by the GPS coordinates and date of sample collection. Measurements were collected over a 3-year period across a 2500 km2 area in rural Kenya. In drinking water sources, high 7-day temperature was associated with a 0.16 increase in log10 E. coli levels (p < 0.001, 95% CI: 0.07, 0.24), while heavy 7-day total precipitation was associated with a 0.29 increase in log10 E. coli levels (p < 0.001, 95% CI: 0.13, 0.44). In household stored drinking water, heavy 7-day precipitation was associated with a 0.079 increase in log10 E. coli levels (p = 0.042, 95% CI: 0.07, 0.24). Heavy precipitation did not increase E. coli levels among respondents who treated their water, suggesting that water treatment can mitigate effects on water quality. On child hands, high 7-day temperature was associated with a 0.39 decrease in log10 E. coli levels (p < 0.001, 95% CI: -0.52, -0.27). Our findings provide insight on how climate change could impact environmental transmission of bacterial pathogens in Kenya. We suggest water treatment is especially important after heavy precipitation (particularly when preceded by dry periods) and high temperatures.

Human Colonization with Antibiotic-Resistant Bacteria from Nonoccupational Exposure to Domesticated Animals in Low- and Middle-Income Countries: A Critical Review.

Data on community-acquired antibiotic-resistant bacterial infections are particularly sparse in low- and middle-income countries (LMICs). Limited surveillance and oversight of antibiotic use in food-producing animals, inadequate access to safe drinking water, and insufficient sanitation and hygiene infrastructure in LMICs could exacerbate the risk of zoonotic antibiotic resistance transmission. This critical review compiles evidence of zoonotic exchange of antibiotic-resistant bacteria (ARB) or antibiotic resistance genes (ARGs) within households and backyard farms in LMICs, as well as assesses transmission mechanisms, risk factors, and environmental transmission pathways. Overall, substantial evidence exists for exchange of antibiotic resistance between domesticated animals and in-contact humans. Whole bacteria transmission and horizontal gene transfer between humans and animals were demonstrated within and between households and backyard farms. Further, we identified water, soil, and animal food products as environmental transmission pathways for exchange of ARB and ARGs between animals and humans, although directionality of transmission is poorly understood. Herein we propose study designs, methods, and topical considerations for priority incorporation into future One Health research to inform effective interventions and policies to disrupt zoonotic antibiotic resistance exchange in low-income communities.

Differential Overlap in Human and Animal Fecal Microbiomes and Resistomes in Rural versus Urban Bangladesh.

Low- and middle-income countries (LMICs) bear the largest mortality burden of antibiotic-resistant infections. Small-scale animal production and free-roaming domestic animals are common in many LMICs, yet data on zoonotic exchange of gut bacteria and antibiotic resistance genes (ARGs) in low-income communities are sparse. Differences between rural and urban communities with regard to population density, antibiotic use, and cohabitation with animals likely influence the frequency of transmission of gut bacterial communities and ARGs between humans and animals. Here, we determined the similarity in gut microbiomes, using 16S rRNA gene amplicon sequencing, and resistomes, using long-read metagenomics, between humans, chickens, and goats in a rural community compared to an urban community in Bangladesh. Gut microbiomes were more similar between humans and chickens in the rural (where cohabitation is more common) than the urban community, but there was no difference for humans and goats in the rural versus the urban community. Human and goat resistomes were more similar in the urban community, and ARG abundance was higher in urban animals than rural animals. We identified substantial overlap of ARG alleles in humans and animals in both settings. Humans and chickens had more overlapping ARG alleles than humans and goats. All fecal hosts from the urban community and rural humans carried ARGs on chromosomal contigs classified as potentially pathogenic bacteria, including Escherichia coli, Campylobacter jejuni, Clostridioides difficile, and Klebsiella pneumoniae. These findings provide insight into the breadth of ARGs circulating within human and animal populations in a rural compared to urban community in Bangladesh. IMPORTANCE While the development of antibiotic resistance in animal gut microbiomes and subsequent transmission to humans has been demonstrated in intensive farming environments and high-income countries, evidence of zoonotic exchange of antibiotic resistance in LMIC communities is lacking. This research provides genomic evidence of overlap of antibiotic resistance genes between humans and animals, especially in urban communities, and highlights chickens as important reservoirs of antibiotic resistance. Chicken and human gut microbiomes were more similar in rural Bangladesh, where cohabitation is more common. Incorporation of long-read metagenomics enabled characterization of bacterial hosts of resistance genes, which has not been possible in previous culture-independent studies using only short-read sequencing. These findings highlight the importance of developing strategies for combatting antibiotic resistance that account for chickens being reservoirs of ARGs in community environments, especially in urban areas.

Drinking water chlorination has minor effects on the intestinal flora and resistomes of Bangladeshi children.

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.

Effective Demand for In-Line Chlorination Bundled with Rental Housing in Dhaka, Bangladesh.

Delivering safe water in cities of lower- and middle-income countries remains elusive even where there is a piped supply. Passive, in-line chlorination upstream of the point of water collection reduces child diarrhea without the behavior change required for point-of-use water treatment products or manual chlorine dispensers. We conducted a price experiment to measure effective demand (willingness and ability to pay) for an in-line chlorination service using tablet chlorinators among 196 landlords of rental housing properties in Dhaka, Bangladesh. We offered a 12-month subscription using Becker-DeGroot-Marschak auctions with real money payments. The service consistently delivered chlorinated water and satisfied tenants. Landlords' effective demand for in-line chlorination was similar to or greater than that for point-of-use treatment products and manual chlorine dispensers previously documented among Dhaka households. Over the service period, landlords renting to low-income households had lower effective demand than those renting to middle-income households despite similar initial rates of payment across both groups. Making in-line chlorination financially viable for the lowest-income consumers would likely require service cost reductions, subsidies, or both. Our findings suggest that even revealed preference experiments may overestimate the effective demand needed to sustain water supply improvements, especially in low-income populations, if they only measure demand once.

Longitudinal Monitoring of SARS-CoV-2 RNA on High-Touch Surfaces in a Community Setting.

Environmental surveillance of surface contamination is an unexplored tool for understanding transmission of SARS-CoV-2 in community settings. We conducted longitudinal swab sampling of high-touch non-porous surfaces in a Massachusetts town during a COVID-19 outbreak from April to June 2020. Twenty-nine of 348 (8.3%) surface samples were positive for SARS-CoV-2 RNA, including crosswalk buttons, trash can handles, and door handles of essential business entrances (grocery store, liquor store, bank, and gas station). The estimated risk of infection from touching a contaminated surface was low (less than 5 in 10,000) by quantitative microbial risk assessment, suggesting fomites play a minimal role in SARS-CoV-2 community transmission. The weekly percentage of positive samples (out of n = 33 unique surfaces per week) best predicted variation in city-level COVID-19 cases with a 7-day lead time. Environmental surveillance of SARS-CoV-2 RNA on high-touch surfaces may be a useful tool to provide early warning of COVID-19 case trends.

Longitudinal monitoring of SARS-CoV-2 RNA on high-touch surfaces in a community setting.

Environmental surveillance of surface contamination is an unexplored tool for understanding transmission of SARS-CoV-2 in community settings. We conducted longitudinal swab sampling of high-touch non-porous surfaces in a Massachusetts town during a COVID-19 outbreak from April to June 2020. Twenty-nine of 348 (8.3 %) surface samples were positive for SARS-CoV-2, including crosswalk buttons, trash can handles, and door handles of essential business entrances (grocery store, liquor store, bank, and gas station). The estimated risk of infection from touching a contaminated surface was low (less than 5 in 10,000), suggesting fomites play a minimal role in SARS-CoV-2 community transmission. The weekly percentage of positive samples (out of n=33 unique surfaces per week) best predicted variation in city-level COVID-19 cases using a 7-day lead time. Environmental surveillance of SARS-CoV-2 RNA on high-touch surfaces could be a useful tool to provide early warning of COVID-19 case trends.