Rapid Serodiagnostic Test for Leptospirosis

描述(申请人提供)：钩端螺旋体病被认为是世界上传播最广泛的人畜共患病。人类疾病主要通过接触被受感染的野生或家养动物的尿液污染的水而感染。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广泛疫情。在欠发达国家，钩端螺旋体病是一个主要的公共卫生问题，是自给自足的农民和城市贫民窟居民大量患病和死亡的原因。由于几乎没有实验室有设备来进行过时的微量凝集试验，这是现在诊断所依赖的，人们很好地认识到，人类钩端螺旋体病是一种未被认识到的疾病。到目前为止，还没有有效预防钩端螺旋体病的方法。钩端螺旋体感染可以用廉价的抗菌剂治疗。然而，及时的治疗被认为是防止疾病进展为肾或肝功能衰竭和/或大量肺出血的关键。成功治疗的主要障碍是难以作出早期和准确的诊断。这里提出的研究目标是开发一种基于研究机构化学诊断系统公司的创新专利横向流动技术(DPP，Dual Path Platform)的人类钩端螺旋体病快速护理点诊断测试。这项测试的开发将通过与康奈尔大学威尔医学院和巴西的奥斯瓦尔多·克鲁兹基金会合作实现，奥斯瓦尔多·克鲁兹基金会是拉丁美洲最大的研究机构。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，并确立进入第二阶段评估的可行性：1.使用化学生物公司开发的一种新的抗原筛选方法(称为MAPIA)；将确定在钩端螺旋体病急性阶段识别的最具血清反应的抗原。2.最具血清反应活性的抗原组合将被用于开发一种原型侧向血流诊断试验，以检测最多数量的急性期患者，同时避免被对照对象识别的抗原。将在这里开发的护理点诊断可能会通过允许第一个与潜在患者接触的医疗提供者立即诊断出钩端螺旋体病并开始治疗，从而彻底改变临床实践。侧向流动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，因为它们不需要设备即可使用，室温稳定，保质期长。此外，这些特点也使这类检测成为流行病学调查的理想方法。

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.