Linking community water and sanitation access to the global burden of antibiotic resistance using human gut metagenomes from 26 countries
Authors: Fuhrmeister Erica R. , Harvey Abigail P. , Nadimpalli Maya L. , Gallandat Karin , Ambelu Argaw , Arnold Benjamin F. , Brown Joe , Cumming Oliver , Earl Ashlee M. , Kang Gagandeep , Kariuki Samuel , Levy Karen , Pinto Chris , Swarthout Jenna M. , Trueba Gabriel , Tsukayama Pablo , Worby Colin J. , Pickering Amy J. 
Published: July 2022

AbstractBackgroundAntibiotic resistance is a leading cause of death, with the highest burden in low-resource settings. There is limited evidence on the potential for water, sanitation, and hygiene (WASH) infrastructure to reduce the burden of antibiotic resistance in humans.MethodsWe used geospatially tagged human gut metagenomes and household survey datasets to determine the association between antibiotic resistance gene (ARG) abundance and community-level coverage of improved drinking water points and improved sanitation facilities. Adjusted general linearized models with robust standard errors were used to estimate the relationship between ARG abundance in the human gut and access to water and sanitation.FindingsWe identified 1589 publicly available metagenomes from 26 countries. The average abundance of ARGs, in units of log10 ARG reads per kilobase per million (RPKM) mapped reads classified as bacteria, was highest in Africa compared to other World Health Organization (WHO) regions (one-way ANOVA p<0.001, post hoc Tukey HSD p<0.05). Increased access to both improved water and sanitation was associated with lower ARG abundance (effect estimate: -0.26, 95% CI [-0.44, -0.08]); the association was stronger in urban (−0.37 [-0.68, -0.07]) compared to rural areas (–0.16 [-0.38, 0.07]). Improved sanitation alone was associated with reduced ARG abundance (−0.16 [-0.32, 0.00]) while improved drinking water was not (−0.09 [-0.35, 0.16]).InterpretationWhile additional studies to investigate casual effects are needed, increasing access to water and sanitation could be an effective strategy to curb the proliferation of antibiotic resistance in low- and middle-income countries.FundingBill & Melinda Gates FoundationResearch in ContextEvidence before this studyAntibiotic resistance is a growing global health threat that disproportionately affects low- and middle-income countries (LMICs). In 2019, an estimated 5 million deaths were associated with antibiotic resistance, with the highest death rate in western sub-Saharan Africa. Water, sanitation, and hygiene (WASH) interventions (e.g., household drinking water treatment, flush toilet, hand washing facilities with soap) can reduce diarrheal and respiratory infections, as reported in previous meta-analyses. Estimates, based on probability modeling, suggest improvements in water and sanitation could decrease antibiotic use for diarrheal disease treatment by 47-50% and 69-72%, respectively. Improving WASH infrastructure could theoretically contribute to the control of antibiotic resistance by preventing the release of antibiotics, resistant organisms, or antibiotic resistance genes (ARGs) into the environment, thus decreasing the burden of antibiotic-resistant infections. One global analysis across 73 countries suggested that improved infrastructure, including WASH services, was associated with reduced antibiotic resistance prevalence in isolates, however the independent effect of WASH access was not assessed.We searched PubMed for evidence on the impact of WASH interventions (excluding those related to animals and agriculture) on antibiotic resistance using the following keyword chain: (water OR sanitation OR hygiene OR WASH) AND (antimicrobial OR antibiotic) AND resistance) NOT (“OneHealth” OR “One Health” OR animal OR livestock). We selected reviews and systematic reviews (n=1420) to be screened for relevance to WASH and antibiotic resistance. The reference lists of included reviews were then searched for individual studies. We also consulted international agency guidelines and online resources from the Joint Programming Initiative on Antimicrobial Resistance, the International Scientific Forum on Hygiene, ReAct, Resistomap, and the London School of Hygiene and Tropical Medicine AMR Centre.Studies focusing on centralized water or wastewater treatment technologies in high income countries (HICs) reported variable removal of antibiotics (53 to >90%), antibiotic-resistant bacteria (90-99.9%) and ARGs (90-99.9%) from waste streams. Other studies were conducted on hand hygiene, which has proven effective at reducing human infections and antibiotic use. No studies were identified on the effect of on-site sanitation systems (e.g., pour-flush toilets, pit latrines), which serve an estimated 2.7 billion people globally, or fecal sludge management interventions on antibiotic resistance.Added value of this studyIn this study, we used 1589 publicly available human gut metagenomes from around the world to assess the abundance of ARGs as a function of access to improved drinking water and sanitation infrastructure. This analysis provides new evidence of differences in the abundance of antibiotic resistance in the human gut across the world and finds that decreased gut abundance of ARGs is associated with increased access to improved drinking water and sanitation.Implications of all the available evidenceCurrent approaches to controlling antibiotic resistance in humans predominantly focus on antibiotic stewardship; however, this approach is challenging in LMICs where infectious illnesses are generally more prevalent and unregulated antibiotic usage is common. Along with efforts to provide other known social benefits, such as reducing infectious disease and improving gender equality, improving access to safe drinking water and sanitation could contribute to reducing the burden of antibiotic resistance. This work highlights improving access to adequate water and sanitation as a potentially effective strategy, although additional studies designed to rigorously investigate the casual relationship between WASH and antibiotic resistance are needed.