Leptospira prevalence, cycling, and infection in the peridomestic environment - Project Summary Leptospirosis is an emerging zoonotic threat to US health: cases are increasing, and many infections now arise from domestic rather than travel-associated exposures. Globally, infectious Leptospira cause ~1.03 million reported cases annual, with ~6% mortality, yet prevention remains ineffective because specific sources of human infection have only been inferred, rather than linked with molecular evidence. Ecuador provides a high-incidence, high-signal model system in which human cases, diverse peridomestic animals, contaminated soil and water, and pathogen diversity converge, providing the opportunity to generate molecular evidence of transmission sources and guide prevention that can be applied elsewhere, including the US. Such studies are not practical in lower-incidence U.S. settings but are directly relevant to domestic exposure risk for Americans. The complex ecology of this disease involves various host species, survival in the environment, massive pathogen genetic diversity, and seasonal variation in human cases, all of which are poorly characterized and poorly understood. Difficulties in culturing Leptospira have restricted the use of modern molecular tools, however, we recently developed a culture-free method for high-resolution genotyping of Leptospira, enabling us to characterize cycling patterns across hosts, space, and time, and provide high-quality evidence linking infections to specific sources. For this study, we focus on peridomestic environments (where animals live near human habitations) because they are likely an important, underestimated, and poorly understood source for human infections in rural areas. Our field site is in Calderon Parish in Manabí, where leptospirosis cases are most prevalent in Ecuador. Compared to urban areas where leptospirosis is typically studied, low-income rural areas are fundamentally different: families typically own a variety of animals and livestock that roam in and around homes creating exposure potential that is largely absent from urban environments. We will systematically sample peridomestic environments (humans, other animals, and soil) to characterize variation in prevalence, pathogen load, and genotype across hosts, time, and space. We will also recruit leptospirosis patients to perform microbiological and molecular investigations of their peridomestic environment to determine what, if any, peridomestic reservoirs are likely sources for these human infections. This study will provide novel insights into the prevalence and cycling of this pathogen in hosts and soil in the peridomestic environment and each investigation will generate novel and powerful molecular and microbiological evidence to exclude or confirm the peridomestic environment as the source of each human infection. Comparisons across these investigations will provide insights into how widespread such sources are in this region of Ecuador and will form the basis for future investigations to determine the generalizability of these patterns. Results will fill massive knowledge gaps critical for transmission control and disease prevention.
