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

项目总结 尿路感染(UTIs)主要由致尿性大肠埃希菌(UPEC)菌株引起 在全球范围内，造成了巨大的健康和社会成本。在过去的十年里，研究表明 UPEC菌株不仅在人与人之间传播；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 识别的寄主相关移动遗传元件(MGE)，可用于识别 一种菌株起源的脊椎动物宿主。在美国应用这些方法，我们 发现大约8%的人类尿路感染可以直接与肉类和尿路感染的UPEC有关 家禽产品。在低收入和中等收入国家(LMIC)，人与动物的接触强度 相互作用更大，这表明UPEC传播的生态环境不同。文献综述 我们团队的研究表明，在LMIC中，对UPEC传输的了解很少。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，以 确定LMIC贫困、边缘化社区中UPEC流行病学的驱动因素。我们 将利用在厄瓜多尔西北沿海工作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 与家畜、家禽和宠物生活在一起。我们已经开发了一个研究平台 研究腹泻和媒介传播疾病，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，并充分 开发了处理血液和粪便样本的分析方法。 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，并描述其行为和环境条件 与殖民和感染的风险有关。我们将在以下地点开展主动监视 在30个月的时间里，对420个家庭进行了4个月的前瞻性跟踪- 一年期间。我们假设家养动物物种将是UPEC的重要来源 在像我们的研究地点这样的LMIC环境中，并将成为UPEC殖民的主要驱动因素。这个 研究将确定家畜在UPEC传播中所起的作用 LMIC环境，其中环境传输路径可能更重要 与高收入环境相比。通过识别UPEC和高风险的特定水库 暴露，我们将定义最佳缓解策略，以减少资源中的疾病负担 糟糕的设置。了解寄主特异性遗传标记在LMIC中的变化对 制定诊断和治疗干预的目标。

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.