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（由申请人提供）：钩端螺旋体病是世界上最重要的人畜共患疾病之一，每年影响全球估计有868,000人，估计病例死亡率为5-10％。在翻译钩端螺旋体和钩端螺旋体病研究的最新分子进步中，重要的差距仍然是预防和改善这种传染病的公共卫生方法。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。此处提出的研究将检验以下一个中心假设，即可以通过量化和识别感染性的钩端螺旋体（致病性和中间的致病性物种和血清循环）在环境表面和土壤中（最重要的人类人类人类人类最重要的人类来源）来预测人类获得钩端螺旋病和感染临床结果的风险。感染）使用宏基因组和深度测序工具。该假设将以三个特定的目的进行检验：1）确定急性钩端螺旋体病的发生率，以及在预期的，观察性的，基于人口的同类群体研究中，钩端螺旋体肾脏运输的患病率，持续时间和临床后果在Iquitos的城市和农村地区，基于人群的同类群体研究秘鲁; 2）量化，识别和确定秘鲁Iquitos的钩端螺旋体病态的城市和农村社区的可能环境传播来源中传染性钩端螺旋体的局部分布； 3）确定发现，量化和键入的城市与农村环境环境是否可以预测人类获得严重与非严重钩端螺旋体病的风险。利用最近开发的技术，将首次研究高度流行诱导性感染的自然史和临床结果，这是在观察性的，基于人群的，基于人群的前瞻性研究中，以与秘鲁亚马逊的流行病学环境进行对比。慢性肾脏感染的病原生物学意义将使用指示肾小管结构损伤的尿生物标志物确定。潜在的环境传播中的数量和钩端螺旋体/血清物种将使用元基因组技术确定。这个多学科项目将提供关键数据，以推动旨在降低钩端螺旋体病风险的公共卫生政策的制定。该研究结果将在全球范围内适用于其他受钩端螺旋体病影响的地区，并有可能推广到具有关键生态/流行病学环境的其他传染病，例如由肠道病原体引起的。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首次将在人口水平上精确确定，这是准确估计这种全球最重要的人畜共患病负担的基本数据。最终，该项目将验证是否可以将环境监测作为识别和消除钩端螺旋体病来源的公共卫生工具部署。

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