Expanding Safe Water Access to Improve Health Outcomes in Appalachia: The Rural Water Filtration and Health (RWELL) Trial - PROJECT SUMMARY Consumption of unsafe drinking water is associated with a substantial burden of disease. For children <5 years old, unsafe drinking water is one of the leading risk factors for enteric pathogen infection and diarrhea incidence. Violations of health-based regulations in public drinking water systems are highest in lower-income rural areas of the United States (US) overall, and particularly in the Central Appalachia region. Appalachia is also impacted by substantial disparities in health outcomes, including higher mortality rates for 7 of the 10 leading causes of death. Estimates indicate ~40 million people in the US live in homes with unregulated private wells. However, our understanding of drinking water contaminants and associated health impacts for individuals living in house- holds with private water supply in rural areas of the US is severely limited by a lack of data – particularly for individuals living in low-income households in rural areas of Appalachia, and Central Appalachia especially. Our preliminary studies in Central Appalachia indicate that many lower-income households with private wells or spring water have relatively higher exposures to waterborne pathogens (and some chemical contaminants). Our overarching goal is to assess the potential of a low-cost, household-level, water treatment intervention for ex- panding safe water access and improving health outcomes and wellbeing for rural households without utility- supplied water. We propose to enroll 480 lower-income households (~1,584 individuals) with well or spring water and conduct a cluster-randomized controlled trial in 10 Central Appalachia counties (in VA and TN) to evaluate the hypothesized benefits of point-of-use water treatment using countertop water filters. We will build on estab- lished relationships with a range of state and local agencies for recruitment, and will address the following aims: 1) Measure the effect of drinking water filtration on the incidence of acute gastrointestinal illness among infants, children, and adults; 2) Measure the effect of drinking water filtration on the presence and quantity of bacterial, protozoal, and viral waterborne pathogens detected in saliva and stool biospecimens; and 3) Quantify fecal indicator organisms, waterborne pathogens, and regulated chemical contaminants in drinking water samples from treatment and control households. This will be the first randomized controlled trial in the US to evaluate point-of-use water filtration for households with well water. This effort is designed to rigorously assess and quan- tify the benefits of a relatively low-cost and easy to use water treatment approach that can also improve the taste of water, and is a less-costly alternative to bottled water reliance. Findings from this study will also substantially improve our understanding of which waterborne and enteric pathogens infants, children, and adults living in households with private water supplies in rural areas are exposed to and infected with, enabling more informed estimates of the associated burden of disease for rural populations without utility-supplied water. Such results will help to increase awareness of the need for improved policies and programs to expand access to safe drinking water for vulnerable and underserved populations in rural Appalachia and other rural areas of the US and beyond.