Natural History of Urban Leptospirosis

描述（由申请人提供）：钩端螺旋体病是城市贫民窟健康问题的一个范例。快速城市化和城市贫困的扩大，加上气候，为钩端螺旋体螺旋体的鼠媒传播创造了条件。每年在季节性暴雨期间，贫民窟社区都会发生流行病，并伴有危及生命的表现，如急性肾衰竭和肺出血。干预措施需要侧重于预防，因为尽管进行了积极治疗，但病死率仍>10%。确定干预措施的一个主要障碍是缺乏对钩端螺旋体病的前瞻性研究。我们对来自萨尔瓦多市贫民窟社区的9,863名居民进行了前瞻性队列调查。巴西我们发现，每年有3.6%的社区感染钩端螺旋体。暴露于与露天下水道和洪水有关的确定的基础设施缺陷是感染的主要风险因素。这些发现使我们假设，有效预防城市细螺旋体病需要为贫民窟社区提供足够的污水和排水系统。此外，我们自1996年起进行积极监察，发现严重端螺旋体病的发病率下降了四倍。这一下降与气候的时间变化无关，与世界银行资助的卫生计划的实施相吻合，该计划将封闭式污水系统的人口覆盖率从26%提高到68%。因此，改善卫生条件可能对预防钩端螺旋体病的严重后果产生影响。关于大规模卫生项目在预防传染病方面的影响，除了疟疾之外，几乎没有什么信息。我们的发现说服了当地政府在我们的队列站点和萨尔瓦多周边的其他贫民窟社区建造封闭的污水系统。在第一个项目目标中，我们将进行干预研究，并前瞻性地确定大规模卫生项目是否能有效预防钩端螺旋体病。我们将在我们的研究中心招募一个队列，并在年度血清调查和门诊监测期间测量钩端螺旋体感染和疾病的结局。在第二个项目目标中，我们将确定大城市中心钩端螺旋体病的时间和空间决定因素，并评估市政卫生计划的实施是否有助于观察到的严重疾病发病率的下降。我们为萨尔瓦多建立了一个关于气候、环境属性以及人口和社会经济指标的大型数据库，并将利用这些信息模拟改善卫生条件对钩端螺旋体病风险的影响。我们希望从该项目中获得的信息将导致预防城市钩端螺旋体病的政策建议，这是迫切需要的，因为居住在贫民窟的人口在未来20年内将从10亿增加到20亿。此外，该项目的研究结果可能与控制影响贫困城市人口的大量环境传播传染病有关。钩端螺旋体病是一种严重的危及生命的疾病，是全世界贫困城市贫民窟人口中鼠传流行病的原因，目前尚无有效的预防措施。这里提出的研究旨在确定在巴西的贫民窟社区预防钩端螺旋体病的大规模卫生项目的影响。从该项目中获得的信息将导致提出政策建议，这是在世界上贫民窟住区迅速扩大的区域解决钩端螺旋体病所需要的。

DESCRIPTION (provided by applicant): Leptospirosis is a paradigm for an urban slum health problem. Rapid urbanization and expanding urban poverty, together with climate, have created conditions for rat-borne transmission of the Leptospira spirochete. Epidemics occur each year in slum communities during seasonal periods of heavy rainfall and are associated with life-threatening manifestations such as acute renal failure and pulmonary hemorrhage. Interventions need to focus on prevention since case fatality is >10% despite aggressive treatment. A major barrier to identifying interventions has been the lack of prospective studies on leptospirosis. We conducted a prospective cohort investigation of 9,863 residents from a slum community in the city of Salvador. Brazil. We found that 3.6% of the community was infected each year with Leptospira. Exposures to defined infrastructure deficiencies related to open sewers and flooding were the major risk factors for infection. These findings led us to hypothesize that effective prevention of urban leptospirosis requires providing slum communities with adequate sewage and drainage systems. Furthermore, active surveillance which we conducted since 1996 identified a four-fold decline in the incidence of severe leptospirosis. This decline was unrelated to temporal variations in climate and coincided with implementation of a World Bank-funded sanitation program, which increased the coverage of the population with closed sewage systems from 26 to 68%. Improved sanitation may therefore have an impact in preventing the severe outcomes from leptospirosis. There is little information on the impact of large-scale sanitation programs in preventing infectious diseases, outside of diarrheal disease. Our findings convinced the local government to construct closed sewage systems at our cohort site and other slum communities in the periphery of Salvador. In the 1st project aim, we will perform an intervention study and prospectively determine whether a large-scale sanitation project is effective in preventing leptospirosis. We will enroll a cohort at our site and measure outcomes of Leptospira infection and disease during annual serosurveys and outpatient surveillance. In the 2nd project aim, we will identify the temporal and spatial determinants for leptospirosis in a large urban center and evaluate whether implementation of a municipal sanitation program contributed to an observed decline in severe disease incidence. We have created a large database on climate, environmental attributes and demographic and socioeconomic indicators for Salvador and will use this information to model the effect of improved sanitation on the risk for leptospirosis across time and space. We expect that the information gained from the project will lead to policy recommendations for the prevention of urban leptospirosis, which is urgently needed as the population residing in slum doubles from one to two billion in the next twenty years. Furthermore, the project's findings will likely be relevant to the control of the large number of environmentally-transmitted infectious diseases that affect impoverished urban populations. PUBLIC HEALTH RELEVANCE There is no effective prevention for leptospirosis, a severe life-threatening disease that is the cause of rat-borne epidemics among impoverished urban slum populations worldwide. The research proposed here aims to determine the impact of a large-scale sanitation project in preventing leptospirosis in a slum community in Brazil. The information gained from the project will lead to policy recommendations, which are needed to address leptospirosis in regions of the world where slum settlements are rapidly expanding.