Rapid Serodiagnostic Test for Leptospirosis

描述（由申请方提供）：钩端螺旋体病被认为是世界上最广泛的人畜共患病。人类疾病主要是通过接触被受感染的野生或家养动物的尿液污染的水而获得的。钩端螺旋体病在美国被认为是一种新出现的传染病，在那里它已经引起了与洪水和淡水娱乐相关的大规模爆发。在欠发达国家，钩端螺旋体病是一个主要的公共卫生问题，是自给农民和城市贫民窟居民发病率和死亡率很高的原因。由于很少有实验室配备进行过时的微量凝集试验，诊断现在依赖，它是公认的，人类钩端螺旋体病是一个认识不足的疾病。到目前为止，还没有有效的预防钩端螺旋体病。钩端螺旋体感染可以用便宜的抗菌剂治疗。然而，认为及时治疗对于防止疾病进展为肾或肝衰竭和/或大量肺出血至关重要。成功治疗的主要障碍是难以作出早期和准确的诊断。本文提出的研究目标是基于研究者组织Chembio诊断系统公司的创新专有侧向流技术（DPP，双路径平台）开发人类钩端螺旋体病的快速即时诊断测试。该测试的开发将通过与康奈尔大学威尔医学院和巴西奥斯瓦尔多克鲁兹基金会（拉丁美洲最大的研究机构）的合作而成为可能。合作的研究人员已经开发出独特的钩端螺旋体抗原，将用于拟议的工作。第一阶段研究的两个具体目标将导致原型测试，并确定进行第二阶段评估的可行性：1。使用Chembio开发的一种新的抗原筛选方法（称为MAPIA）;将鉴定钩端螺旋体病急性期识别的最具血清反应性的抗原。2.最血清反应性抗原的组合将用于开发原型侧流诊断测试，以检测最大数量的急性期患者，同时避免对照受试者识别的抗原。这里将要开发的即时诊断可以彻底改变临床实践，允许第一个与潜在患者接触的医疗提供者立即诊断钩端螺旋体病并开始治疗。侧流测试非常适合在发展中国家以及各种现场或社区环境中使用，因为它们不需要使用设备，室温稳定，并且具有长的保质期。此外，这些特点也使这种类型的测试理想的流行病学调查。

DESCRIPTION (provided by applicant): Leptospirosis is considered to be the most widespread zoonotic disease in the world. Human disease is acquired primarily through contact with water contaminated with the urine of infected wild or domestic animals. Leptospirosis is recognized as an emerging infectious disease in the US, where it has caused extensive outbreaks associated with flooding and fresh water recreation. In less developed countries, leptospirosis is a major public health problem as the cause of substantial morbidity and mortality among subsistence farmers and urban slum dwellers. Because few laboratories are equipped to perform the antiquated microagglutination test upon which diagnosis now depends, it is well recognized that human leptospirosis is an under-recognized disorder. To date there is no effective prevention for leptospirosis. Leptospiral infections can be treated with inexpensive antimicrobial agents. However, timely treatment is considered to be essential to prevent disease progression to renal or hepatic failure, and/or massive pulmonary hemorrhage. The major obstacle to successful treatment is the difficulty in making an early and accurate diagnosis. The goal of the research proposed here is the development of a rapid, point-of-care diagnostic test for human leptospirosis, based upon the innovative proprietary lateral flow technology (DPP, Dual Path Platform) of the investigator organization, Chembio Diagnostic Systems Incorporated. Development of the test will be made possible by collaboration with Weill Medical College of Cornell University and the Oswaldo Cruz Foundation in Brazil - the largest research institution in Latin America. The collaborating investigators have developed unique leptospiral antigens that will be used in the proposed work. The two specific aims of the Phase I studies will result in a prototypic test and establish the feasibility of proceeding into Phase II evaluations: 1. Using a novel antigen screening method developed by Chembio (termed MAPIA); the most seroreactive antigens recognized during the acute phase of leptospirosis will be identified. 2. A combination of the most seroreactive antigens will be used to develop a prototype lateral flow diagnostic test to detect the greatest number of acute-phase patients, while avoiding antigens recognized by control subjects. The point-of-care diagnostic to be developed here could revolutionize clinical practice by allowing the first medical provider in contact with a potential patient to make an immediate diagnosis of leptospirosis and initiate treatment. Lateral flow tests are highly suitable for use in developing countries, as well as in a variety of field or community settings, because they require no equipment to use, are room temperature stable, and have long shelf lives. Furthermore, these features also make this type of test ideal for epidemiological investigations.