Predicting Risk of Human Leptospiros by Environmental Surveillance

通过环境监测预测人类钩端螺旋体的风险

• 批准号: 9820811
• 负责人: Joseph M. Vinetz
• 金额: $ 33.14万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-11-01 至 2020-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9820811
• 关键词: Predicting; Risk; Human; Leptospiros; Environmental

DESCRIPTION (provided by applicant): Leptospirosis is among the world's most important zoonotic infectious diseases, annually affecting an estimated 868,000 people globally, with an estimated case fatality rate of 5-10%. Important gaps remain in translating recent fundamental molecular advances in studies of Leptospira and leptospirosis4 to public health approaches to preventing and ameliorating this infectious disease. The long-term goal of this project is to develop and validate new tools and approaches to reduce the impact of leptospirosis on human health. The studies proposed here will test the central hypothesis that human risk for acquiring leptospirosis and clinical outcomes of infection can be predicted by quantifying and identifying infectious Leptospira (pathogenic and intermediately pathogenic species and serovars) in environmental surface waters and soils (most important sources of human infection) using metagenomic and deep sequencing tools. This hypothesis will be tested in three Specific Aims: 1) To determine the incidence of acute leptospirosis, and the prevalence, duration and clinical consequences of Leptospira renal carriage in prospective, observational, population- based cohort studies in urban and rural areas of Iquitos, Peru; 2) To quantify, identify and determine the local distribution of infectious Leptospira in likely environmental sources of transmission in leptospirosis-endemic urban and rural communities of Iquitos, Peru; and 3) To determine whether the urban vs. rural environmental contexts in which Leptospira are found, quantified and typed can predict risk for humans for acquiring severe vs. non-severe leptospirosis. Using recently developed techniques, the natural history and clinical outcomes of highly endemic leptospiral infection will be studied, for the first time, in observational, population-based, prospective cohort studies in contrasting epidemiological settings in the Peruvian Amazon. The patho-biological significance of chronic renal infection will be determined using urinary biomarkers that indicate renal tubular structural damage. The quantity and Leptospira species/serovars in potential environmental sources of transmission will be determined using metagenomic techniques. This multidisciplinary project will provide key data to drive the development of public health policies aimed at reducing the human risk of leptospirosis. The study results will be globally applicable to other regions affected by leptospirosis, and have the potential to be generalizable to other infectious diseases that have key eco/epidemiological contexts, such as those caused by enteric pathogens. For the first time, the natural history and clinical impact of leptospirosis in a highly endemic setting will be precisely determined at a population level, essential data for accurately estimating the burden of this globally-important zoonotic disease. Ultimately, this project will validate whether environmental surveillance can be deployed as a public health tool for identifying and eliminating sources of leptospirosis transmission.

描述(申请人提供)：钩端螺旋体病是世界上最重要的人畜共患传染病之一，每年影响全球约868,000人，估计病死率为5-10%。在将钩端螺旋体和钩端螺旋体研究的最新基本分子进展4转化为预防和改善这一传染病的公共卫生方法方面仍然存在重大差距。该项目的长期目标是开发和验证新的工具和方法，以减少钩端螺旋体病对人类健康的影响。这里提出的研究将检验这一中心假设，即可以通过使用后基因组学和深度测序工具来量化和识别环境表面水和土壤(人类感染的最重要来源)中的传染性钩端螺旋体(致病和中等致病物种和血清型)，从而预测人类感染钩端螺旋体病的风险和临床结果。这一假设将在三个具体目标中得到检验：1)在秘鲁伊基托斯的城市和农村进行前瞻性、观察性、基于人群的队列研究，以确定急性钩端螺旋体病的发病率，以及钩端螺旋体肾携带的患病率、持续时间和临床后果；2)在秘鲁伊基托斯钩端螺旋体病流行的城市和农村社区，量化、确定和确定传染性钩端螺旋体在可能的环境来源中的当地分布；以及3)确定发现、量化和分型钩端螺旋体的城市和农村环境是否可以预测人类感染严重与非严重钩端螺旋体病的风险。利用最近开发的技术，将首次在秘鲁亚马逊地区的对比流行病学环境中进行观察性、基于人群的前瞻性队列研究，研究高度地方性钩端螺旋体感染的自然历史和临床结果。慢性肾脏感染的病理生物学意义将使用指示肾小管结构损害的尿液生物标志物来确定。将使用元基因组技术确定潜在环境传播源中的钩端螺旋体数量和钩端螺旋体物种/血清型。这一多学科项目将提供关键数据，以推动旨在降低人类感染钩端螺旋体病风险的公共卫生政策的制定。研究结果将在全球范围内适用于受钩端螺旋体病影响的其他地区，并有可能推广到具有关键生态/流行病学背景的其他传染病，如由肠道病原体引起的疾病。在高度流行的环境中，钩端螺旋体病的自然历史和临床影响将首次在人口水平上得到准确确定，这是准确估计这种全球重要的人畜共患病负担的基本数据。最终，该项目将验证环境监测是否可以作为一种公共卫生工具来确定和消除钩端螺旋体病的传播源。

项目成果

Vaccination With Leptospira interrogans PF07598 Gene Family-Encoded Virulence Modifying Proteins Protects Mice From Severe Leptospirosis and Reduces Bacterial Load in the Liver and Kidney.

• DOI: 10.3389/fcimb.2022.926994
• 发表时间: 2022
• 期刊: Frontiers in cellular and infection microbiology
• 影响因子: 5.7

Comparison of the PF07598-Encoded Virulence-Modifying Proteins of L. interrogans and L. borgpetersenii.

• DOI: 10.3390/tropicalmed8010014
• 发表时间: 2022-12-26
• 期刊: Tropical medicine and infectious disease
• 影响因子: 2.9
• 作者: Vieira DS;Chaurasia R;Vinetz JM
• 通讯作者: Vinetz JM