Leptospira prevalence, cycling, and infection in the peridomestic environment

项目摘要 钩端螺旋体病是一种常见的人畜共患病，最流行于热带地区(夏威夷、美国领土和世界各地)。 非特定症状导致报告不足，在全世界每年报告的103万例病例中，约6%死亡。 从哺乳动物宿主的尿液中排出的传染性钩端螺旋体细菌污染环境，以及 人类可通过受感染的尿液或受污染的土壤和水直接感染钩端螺旋体病。While Case 访谈已经确定了人类感染的风险因素和潜在的宿主，少数分子和 对人类病例的微生物学研究几乎总是无法证实假设的来源，这表明 这种暴露和可能的来源还没有得到充分的定义，环境在宿主之间循环， 空间，以及时间，人们对此知之甚少。该病复杂的生态涉及多种寄主物种，生存 在环境中，大量病原体遗传多样性，以及人类病例的季节性变化，所有这些都是 特征不佳，理解也很少。培养钩端螺旋体的困难限制了现代 分子工具，对于其他病原体来说，对于理解循环和证实或驳斥是至关重要的 使用传统流行病学方法产生的来源假说。然而，我们最近开发了一种 钩端螺旋体高分辨率基因分型的无培养方法，使我们能够表征循环模式 跨越宿主、空间和时间，并提供将感染与特定来源联系起来的高质量证据。 在这项研究中，我们关注的是周围环境(动物居住在人类栖息地附近)，因为 它们很可能是农村地区人类感染的一个重要的、被低估的和缺乏了解的来源。 我们的现场地点是马纳贝的卡尔德隆教区，那里的钩端螺旋体病病例在厄瓜多尔最为流行。 与通常研究钩端螺旋体病的城市地区相比，低收入农村地区基本上是 不同：家庭通常拥有各种各样的动物和牲畜，它们在家里和房子周围游荡，创造了 城市环境中基本不存在的暴露潜力。我们将系统地对橄榄岩进行采样 环境(人类、其他动物和土壤)，以表征流行率、病原体负载和 不同宿主、不同时间和不同空间的基因。我们也会招募钩端螺旋体病患者进行微生物检测。 以及对其周围环境的分子研究，以确定是否有周围的储层 很可能是这些人类感染的源头。 这项研究将为该病原体在寄主和土壤中的流行和循环提供新的见解。 围岩环境和每一次研究都将产生新的和强大的分子和微生物 排除或确认牙周病环境是每个人类感染源的证据。 通过对这些调查的比较，将提供关于此类来源在 并将成为未来调查的基础，以确定这些问题的普遍性 模式。结果将填补对传播控制和疾病预防至关重要的大量知识空白。

Project Summary Leptospirosis is a common zoonotic disease most prevalent in the tropics (Hawaii, US territories, and worldwide). Non-specific symptoms cause underreporting and of the 1.03 million reported cases annual worldwide, ~6% die. Infectious Leptospira bacteria contaminate the environment when shed in urine from mammalian hosts, and humans can contract leptospirosis directly from infected urine or from contaminated soil and water. While case interviews have identified risk factors for human infections and potential reservoirs, the few molecular and microbiological investigations of human cases almost always failed to confirm hypothesized sources, suggesting that exposure and possible sources have not been adequately defined and environmental cycling across hosts, space, and time is poorly understood. 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 that, for other pathogens, have been critical for understanding cycling and confirming or refuting source hypotheses generated using traditional epidemiological approaches. 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.