Leptospira prevalence, cycling, and infection in the peridomestic environment

家庭周围环境中钩端螺旋体的流行、循环和感染

• 批准号: 10735030
• 负责人: Talima Ross Pearson
• 金额: $ 71.3万
• 依托单位: NORTHERN ARIZONA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10735030
• 关键词: Address; Animal Sources; Animals; Area; Bacteria; Biological; Biological Assay; Case Study; Cessation of life; Clinical; Communities; Complex; Contracts; Death Rate; Disease; Disease Outbreaks; Domestic Animals; Ecology; Ecuador; Environment; Epidemiology; Exclusion; Exposure to; Family; Fever; Future; Genetic Variation; Genotype; Hawaii; Headache; Home; Human; Icterus; Individual; Infection; Infection Control; Infection prevention; Ingestion; Interview; Investigation; Kidney Failure; Knowledge; Leptospira; Leptospirosis; Link; Liver Failure; Livestock; Location; Low income; Methods; Modernization; Molecular; Mucous Membrane; Outcome; Pathogenicity; Patients; Pattern; Persons; Play; Population Dynamics; Prevalence; Prevention strategy; Resolution; Risk; Risk Factors; Role; Rural; Rural Community; Sampling; Seasonal Variations; Seasons; Site; Slum; Soil; Source; Symptoms; Time; Urine; Variant; Water; Zoonoses; disorder control; disorder prevention; experience; exposed human population; follow-up; genome sequencing; insight; novel; pathogen; recruit; rural area; rural environment; tool; transmission process; urban area; urban setting; whole genome; wound

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.

项目摘要 钩端螺旋病是热带（夏威夷，美国领土和全球）最普遍的常见人畜共患病。 非特异性症状导致报告不足，在全球范围内报告了103万例，死亡约为6％。 传染性钩端螺旋体细菌在哺乳动物宿主中尿液中脱落时会污染环境，而 人类可以直接从感染的尿液或受污染的土壤和水中感染钩端螺旋体病。案件 访谈已经确定了人类感染和潜在储层的危险因素，这是少数分子和 人类病例的微生物学研究几乎总是无法确认假设的来源，这表明 这种暴露和可能的来源尚未得到充分定义，并且跨主机之间的环境循环， 空间和时间对时间很少。这种疾病的复杂生态涉及各种宿主物种，生存 在环境中，人类病例的大量病原体遗传多样性和季节性变异，所有这些都是 特征较差，理解不足。聚类的钩端螺旋体困难限制了现代的使用 对于其他病原体，该工具对于理解骑自行车和确认或驳斥至关重要 来源假设使用传统流行病学方法产生的假设。但是，我们最近开发了 无培养方法用于钩端螺旋体的高分辨率基因分型，使我们能够表征循环模式 跨主机，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。 对于这项研究，我们专注于植物性环境（动物生活在人类居住附近），因为 它们可能是一个重要的，被低估的，并且不了解粗糙地区人类感染的来源。 我们的现场地点位于Manabí的Calderon Parish，那里的钩端螺旋体病病例在厄瓜多尔最为普遍。 与钩端螺旋体病通常是研究的城市地区相比，低收入农村地区是从根本上 不同：家庭通常拥有各种动物和牲畜在房屋中漫游 城市环境中主要没有的暴露潜力。我们将系统地采样植物 环境（人类，其他动物和土壤），以表征患病率，病原体负荷和 跨主机，时间和空间的基因型。我们还将招募钩端螺旋体病患者进行微生物学 以及对其植物环境的分子研究，以确定植物含量（如果有的话） 可能是这些人类感染的来源。 这项研究将提供有关该病原体在宿主和土壤中这种病原体的普遍性和循环的新见解。 Peridementic环境以及每项投资都会产生新颖而强大的分子和微生物学 排除或确认植物性环境作为每种人类感染的来源的证据。 在这些投资中进行比较将提供有关此类来源如何广泛的见解 厄瓜多尔地区，将构成未来研究的基础，以确定这些概括性 模式。结果将填补对传播控制和预防疾病至关重要的大量知识差距。

项目成果

Domestic dogs in indigenous Amazonian communities: key players in Leptospira cycling and transmission?

亚马逊土著社区的家犬：钩端螺旋体循环和传播的关键参与者？

• DOI: 10.1101/2023.09.19.558554
• 发表时间: 2023
• 期刊: bioRxiv : the preprint server for biology
• 作者: Guzmán,DiegoA;Diaz,Eduardo;Sáenz,Carolina;Álvarez,Hernán;Cueva,Rubén;Zapata-Ríos,Galo;Prado-Vivar,Belén;Falconí,Mercy;Pearson,Talima;Barragán,Verónica
• 通讯作者: Barragán,Verónica