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 钩端螺旋体病是一种常见的人畜共患病，在热带地区（夏威夷、美国领土和全世界）最为流行。 非特异性症状导致报告不足，在全球每年报告的103万例病例中，约6%死亡。 感染性钩端螺旋体细菌在哺乳动物宿主的尿液中脱落时污染环境， 人类可直接从受感染的尿液或受污染的土壤和水感染端螺旋体病。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 人类病例的微生物调查几乎总是未能证实假设的来源，这表明 暴露和可能的来源尚未充分界定，宿主之间的环境循环， 时间和空间都不太清楚。这种疾病的复杂生态涉及各种宿主物种， 在环境中，大量的病原体遗传多样性，以及人类病例的季节性变化，所有这些都是 特征不明显，也不容易理解。培养钩端螺旋体的困难限制了现代 对于其他病原体来说，这些分子工具对于理解循环以及确认或反驳 使用传统流行病学方法生成的源假设。然而，我们最近开发了一种 一种用于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，我们关注的是生活环境（动物生活在人类居住地附近）， 它们很可能是农村地区人类感染的一个重要、被低估和知之甚少的来源。 我们的实地考察地点位于马纳比的卡尔德龙教区，那里的钩端螺旋体病病例在厄瓜多尔最为普遍。 与典型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 不同：家庭通常拥有各种各样的动物和牲畜，在家中和周围漫游， 城市环境中基本上不存在的暴露潜力。我们将系统地采集 环境（人类，其他动物和土壤），以表征流行率，病原体负荷和 跨越宿主、时间和空间的基因型。我们亦会招募端螺旋体病患者， 并对其生活环境进行分子研究，以确定是否存在生活环境储库， 很可能是人类感染的源头 这项研究将提供新的见解，这种病原体在宿主和土壤中的流行和循环， 生活环境和每次调查将产生新的和强大的分子和微生物 排除或确认居住环境是每种人类感染源的证据。 通过对这些调查的比较，我们将深入了解这些来源在这一领域的广泛程度。 厄瓜多尔地区，并将构成未来调查的基础，以确定这些 模式.研究结果将填补对于传播控制和疾病预防至关重要的巨大知识空白。

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