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: 10661031
• 负责人: Joseph N. S. Eisenberg
• 金额: $ 71.29万
• 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/10661031
• 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; Diarrhea; 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; 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.

项目摘要 肝病大肠杆菌（UPEC）菌株引起大多数尿路感染（UTI） 在全球范围内，导致了巨大的健康和社会成本。在过去的十年中，研究表明 UPEC菌株不仅是传播人的人；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 鉴定出与宿主相关的移动遗传元素（MGE），可用于识别 脊椎动物宿主从中起源。在美国应用这些方法，我们 已经发现，大约8％的人尿路斯可以直接从肉和upec链接 家禽产品。在低收入和中等收入国家（LMIC）中，人类动物的强度 相互作用更大，暗示了UPEC传播的不同生态学。文献综述 我们的团队表明，在LMIC中，UPEC传输对其进行了鲜为人知。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LMIC的贫穷，边缘化社区中UPEC流行病学的驱动因素。我们 将利用在西北厄瓜多尔（Ecuador）工作的20年以上的经验，该地区 历史上在卫生基础设施和社区的地方被历史忽视 与牲畜，家禽和宠物相邻生活。我们已经开发了一个研究平台 研究腹泻和vectorborne疾病，并完全开发了调查工具 捕获人口，社会经济和水，卫生和卫生数据，并完全 开发了处理血液和粪便样品的测定法。 我们的该项目的目标是确定UPEC的主要人畜共患样子，量化 向人类传播并表征行为和环境条件 与殖民和感染的风险相关。我们将在 在30个月内的区域医院，并在420个家庭中前瞻性地关注420个家庭 年期。我们假设家畜将是UPEC的重要来源 在我们的研究地点等LMIC环境中，将成为UPEC殖民化的主要驱动力。这 研究将表征家畜在UPEC传播中的作用 LMIC设置，环境传输途径可能更重要 与高收入设置相比。通过识别UPEC和高风险的特定储层 暴露，我们将定义最佳缓解策略以减轻资源的疾病负担 设置不佳。了解LMIC中宿主特异性遗传标志物的变化对于 开发诊断和治疗干预措施的靶标。