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.

项目摘要 尿路致病性大肠杆菌（UPEC）菌株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菌株不仅仅是人与人之间的传播;环境来源，如 食用动物产品也有助于传播。应用比较基因组学，我们有 鉴定的宿主相关的移动的遗传元件（MGE），其可用于鉴定 一种菌株起源的脊椎动物宿主。在美国使用这些方法，我们 发现大约8%的人类UTI可以直接与来自肉类的UPEC相关， 家禽产品。在低收入和中等收入国家， 相互作用更大，表明UPEC传播的生态不同。文献综述 我们的团队证明，UPEC传播在LMIC中知之甚少。在本研究中， 我们将整合比较基因组学、暴露评估和时空分析， 确定UPEC流行病学在LMIC贫困，边缘化社区的驱动因素。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 在卫生基础设施方面一直被忽视， 与牲畜、家禽和宠物住在一起。我们开发了一个研究平台 研究疟疾和病媒传播疾病，并充分开发了调查工具， 获取人口、社会经济以及水、环境卫生和个人卫生数据， 开发了处理血液和粪便样本的分析方法。 本项目的目标是确定UPEC的主要人畜共患病来源， 传播给人类并描述行为和环境条件 与定植和感染的风险相关。我们会积极进行监视， 地区医院超过30个月的时间，并前瞻性地跟踪420个家庭超过4- 年期间。我们推测家畜物种将是UPEC的重要来源 在LMIC环境中，如我们的研究地点，将是UPEC殖民化的主要驱动力。的 研究将描述家畜在UPEC传播中的作用， LMIC环境，环境传播途径可能更重要 与高收入的环境相比。通过识别UPEC的特定储层和高风险 暴露，我们将确定最佳的缓解战略，以减少疾病负担的资源， 可怜的设置。了解宿主特异性遗传标记在LMIC中的变化对于以下方面很重要： 制定诊断和治疗干预的目标。