Zoonotic Uropathogenic Escherichia coli in Northwest Ecuador: Incidence and Risk Factors

厄瓜多尔西北部人畜共患泌尿道致病性大肠杆菌：发病率和危险因素

• 批准号: 10417979
• 负责人: Joseph N. S. Eisenberg
• 金额: $ 75.75万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-06 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10417979
• 关键词: Acute; Animal Feed; Animals; Bacteremia; Behavior; Biological Assay; Blood specimen; Cessation of life; Chickens; Clinical; Communities; Comparative Genomic Analysis; Dairy Products; Data; Demographic Factors; Diagnosis; Diagnostic; Domestic Animals; Domestic Fowls; Ecology; Ecuador; Elements; Environment; Epidemiology; Escherichia coli; Etiology; Exposure to; Female; Genetic Markers; Goals; Health; Home environment; Hospitalization; Hospitals; Household; Housing; Human; Hygiene; Incidence; Income; Individual; Infection; Infrastructure; Lead; Link; Livestock; Longitudinal Studies; Measures; Meat Products; Methods; Mobile Genetic Elements; Morbidity - disease rate; Outcome; Pathway interactions; Patients; Persons; Play; Poultry Products; Pregnant Women; Process; Prospective Studies; Research; Resource-limited setting; Review Literature; Risk; Risk Factors; Role; Sampling; Sanitation; Site; Socioeconomic Factors; Source; Surveys; Therapeutic Intervention; United States; Urinary tract infection; Uropathogenic E. coli; Vector-transmitted infectious disease; Water; Zoonoses; burden of illness; comparative genomics; cost; diarrheal disease; experience; high risk; human model; inpatient service; low and middle-income countries; marginalized community; modifiable risk; neglect; pet animal; poor communities; prospective; recurrent infection; social; socioeconomics; spatiotemporal; stool sample; transmission process

PROJECT SUMMARY Uropathogenic Escherichia coli (UPEC) strains cause most urinary tract infections (UTIs) globally, resulting in enormous health and social costs. In the past decade, research has shown that UPEC strains are not just transmitted person-to-person; environmental sources, such as food-animal products, also contribute to transmission. Applying comparative genomics, we have identified host-associated mobile genetic elements (MGEs) that can be used to identify the vertebrate host from which a strain originates. Applying these methods in the United States, we have found that approximately 8% of human UTIs can be linked directly to UPEC from meat and poultry products. In low- and middle-income countries (LMICs), the intensity of human-animal interactions is greater suggesting a different ecology for UPEC transmission. A literature review by our team demonstrates that UPEC transmission is poorly understood in LMICs. In this study, we will integrate comparative genomics, exposure assessment and spatiotemporal analyses to determine the drivers of UPEC epidemiology in poor, marginalized communities of an LMIC. We will leverage over 20 years of experience working in northwestern coastal Ecuador, a region that has been historically neglected in the context of health infrastructure and where communities live in proximity with livestock, poultry, and pets. We have developed a research platform studying diarrheal and vectorborne diseases, and have fully developed survey instruments to capture demographic, socioeconomic, and water, sanitation and hygiene data, and fully developed assays to process blood and stool samples. Our goals for this project are to identify the dominant zoonotic sources of UPEC, quantify the transmission to humans and characterize the behaviors and environmental conditions associated with risk for colonization and infection. We will carry out active surveillance at regional hospitals over a 30-month period and follow 420 households prospectively over a 4- year period. We hypothesize that domestic animal species will be important sources of UPEC within LMIC settings like our study site and will be major drivers for UPEC colonization. The study will characterize the role that domestic animals play in the transmission of UPEC in an LMIC setting, where environmental transmission pathways are likely much more important compared to high-income settings. By identifying specific reservoirs of UPEC and high-risk exposures, we will define optimal mitigation strategies to decrease disease burden in resource poor settings. Understanding how host-specific genetic markers vary in an LMIC is important for developing targets of diagnostics and therapeutic interventions.

项目概要 尿路致病性大肠杆菌 (UPEC) 菌株可引起大多数尿路感染 (UTI) 在全球范围内，造成巨大的健康和社会成本。在过去的十年里，研究表明 UPEC 菌株不仅可以在人与人之间传播；环境来源，例如 食品-动物产品也有助于传播。应用比较基因组学，我们有 鉴定出宿主相关的移动遗传元件（MGE），可用于识别 菌株起源的脊椎动物宿主。在美国应用这些方法，我们 研究发现，大约 8% 的人类尿路感染可与来自肉类和食品的 UPEC 直接相关。 家禽产品。在低收入和中等收入国家 (LMIC)，人类与动物的强度 相互作用更大，表明 UPEC 传播存在不同的生态。文献综述 我们团队的研究表明，中低收入国家对 UPEC 传播知之甚少。在这项研究中， 我们将整合比较基因组学、暴露评估和时空分析 确定中低收入国家贫困、边缘化社区 UPEC 流行病学的驱动因素。我们 将利用在厄瓜多尔西北沿海地区工作 20 多年的经验，该地区 在卫生基础设施和社区的背景下历来被忽视 与牲畜、家禽和宠物生活在一起。我们开发了一个研究平台 研究腹泻和虫媒疾病，并充分开发了调查工具，以 获取人口、社会经济以及水、环境卫生和个人卫生数据，并充分 开发了处理血液和粪便样本的测定方法。 我们这个项目的目标是确定 UPEC 的主要人畜共患病来源，量化 传播给人类并表征行为和环境条件 与定植和感染的风险有关。我们将在 在 30 个月的时间内对地区医院进行跟踪，并在 4-4 个月的时间内对 420 个家庭进行前瞻性跟踪 年期间。我们假设家畜物种将是 UPEC 的重要来源 在像我们的研究地点这样的中低收入国家环境中，这将是 UPEC 殖民化的主要驱动力。这 研究将描述家畜在 UPEC 传播中所扮演的角色 中低收入国家环境，环境传播途径可能更为重要 与高收入环境相比。通过识别 UPEC 的特定储存库和高风险 暴露，我们将制定最佳缓解策略，以减少资源中的疾病负担 糟糕的设置。了解 LMIC 中宿主特异性遗传标记的变化对于 制定诊断和治疗干预的目标。