Natural History of Urban Leptospirosis

城市钩端螺旋体病的自然史

• 批准号: 8433377
• 负责人: Albert Icksang Ko
• 金额: $ 29.97万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-02-15 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8433377
• 关键词: Acute Kidney Failure; Address; Affect; Awareness; Brazil; Cities; Climate; Clinical; Communicable Diseases; Communities; Databases; Disease; Disease Outbreaks; Drainage procedure; Enrollment; Environmental Risk Factor; Epidemic; Epidemiology; Exposure to; Floods; Funding; Geography; Goals; Health; Hemorrhage; Incidence; Infection; Information Systems; Intervention; Intervention Studies; Investigation; Laboratories; Lead; Leptospira; Leptospirosis; Life; Local Government; Longitudinal Studies; Lung; Modeling; Natural History; Order Spirochaetales; Outcome; Outcome Measure; Outpatients; Pattern; Policies; Population; Poverty; Prevention; Prevention Measures; Prospective Studies; Rattus; Recommendation; Recruitment Activity; Reporting; Research; Research Infrastructure; Risk; Risk Factors; Sample Size; Sanitation; Sewage; Site; Slum; Socioeconomic Factors; Spatial Distribution; Statistical Models; Surveys; Syndrome; System; Testing; Time; Universities; Urban Population; Urbanization; Variant; Weil' s Disease; World Bank; base; cohort; effectiveness measure; follow-up; improved; medical schools; prevent; programs; prospective; socioeconomics; transmission process

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.

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典范。快速城市化和不断扩大的城市贫困，加上气候，为螺旋体钩端螺旋体的鼠传传播创造了条件。流行病每年在暴雨季节在贫民窟社区发生，并伴有危及生命的症状，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，但病死率仍高达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。我们对萨尔瓦多市贫民窟社区的9863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明确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，有效预防城市钩端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年以来开展的主动监测发现，严重钩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，而且恰逢世界银行资助的卫生项目的实施，该项目将封闭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。除了腹泻之外，关于大规模卫生项目在预防传染病方面的影响的信息很少。我们的发现说服了当地政府在我们的队列地点和萨尔瓦多周边的其他贫民窟社区建造封闭的污水处理系统。在第一个项目目标中，我们将进行一项干预研究，并前瞻性地确定大型卫生项目是否能有效预防钩端螺旋体病。我们将在我们的站点招募一个队列，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果。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空决定因素，并评估实施市政卫生计划是否有助于观察到的严重疾病发病率下降。我们已经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，并将利用这些信息来模拟改善卫生条件对钩端螺旋体病风险的时空影响。我们期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城市贫困人口的大量环境传播传染病有关。

项目成果

Proteomic features predict seroreactivity against leptospiral antigens in leptospirosis patients.

• DOI: 10.1021/pr500718t
• 发表时间: 2015-01-02
• 期刊: JOURNAL OF PROTEOME RESEARCH
• 影响因子: 4.4
• 作者: Lessa-Aquino, Carolina;Wunder, Elsio A., Jr.;Lindow, Janet C.;Rodrigues, Camila B.;Pablo, Jozelyn;Nakajima, Rie;Jasinskas, Algis;Liang, Li;Reis, Mitermayer G.;Ko, Albert I.;Medeiros, Marco A.;Felgner, Philip L.
• 通讯作者: Felgner, Philip L.

Lvr, a Signaling System That Controls Global Gene Regulation and Virulence in Pathogenic Leptospira.

• DOI: 10.3389/fcimb.2018.00045
• 发表时间: 2018
• 期刊: Frontiers in cellular and infection microbiology
• 影响因子: 5.7
• 作者: Adhikarla H;Wunder EA Jr;Mechaly AE;Mehta S;Wang Z;Santos L;Bisht V;Diggle P;Murray G;Adler B;Lopez F;Townsend JP;Groisman E;Picardeau M;Buschiazzo A;Ko AI
• 通讯作者: Ko AI

Distinct antibody responses of patients with mild and severe leptospirosis determined by whole proteome microarray analysis.

• DOI: 10.1371/journal.pntd.0005349
• 发表时间: 2017-01
• 期刊: PLoS neglected tropical diseases
• 影响因子: 3.8
• 作者: Lessa-Aquino C;Lindow JC;Randall A;Wunder E;Pablo J;Nakajima R;Jasinskas A;Cruz JS;Damião AO;Nery N;Ribeiro GS;Costa F;Hagan JE;Reis MG;Ko AI;Medeiros MA;Felgner PL
• 通讯作者: Felgner PL

Unsuspected leptospirosis is a cause of acute febrile illness in Nicaragua.

尼加拉瓜的诱发诱发是急性发热疾病的原因。

• DOI: 10.1371/journal.pntd.0002941
• 发表时间: 2014-07
• 期刊: PLoS neglected tropical diseases
• 影响因子: 3.8
• 作者: Reller ME;Wunder EA Jr;Miles JJ;Flom JE;Mayorga O;Woods CW;Ko AI;Dumler JS;Matute AJ
• 通讯作者: Matute AJ

An Optimized Method for Quantification of Pathogenic Leptospira in Environmental Water Samples.

• DOI: 10.1371/journal.pone.0160523
• 发表时间: 2016
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Riediger IN;Hoffmaster AR;Casanovas-Massana A;Biondo AW;Ko AI;Stoddard RA
• 通讯作者: Stoddard RA