Rapid DPP test for tuberculosis

描述（由申请人提供）：结核病是一种由结核分枝杆菌引起的慢性传染病，目前全球估计有20亿人感染，全球每年新发现病例超过900万例。这是艾滋病患者的最大杀手。目前的诊断方法复杂、耗时、不可靠或对该病构成重大公共卫生威胁的大多数国家负担不起。迫切需要新的诊断方法来解决全球结核病负担并改善控制规划。我们的第一阶段研究已经清楚地证明了开发一种快速准确的结核病检测方法的可行性。与传染病研究所合作，Chembio诊断系统公司的科学家们已经确定了一组新的血清反应性抗原，设计了几种高性能的多肽类融合蛋白，并将选定的抗原应用于Chembio创新的免疫分析格式，双路径平台（DPP(R)），具有高准确性的快速血清诊断。我们发现，对巴西和印度尼西亚流行地区培养确诊的活动性肺结核患者的血清样本进行评估时，DPP测试原型的灵敏度为81%，特异性为95%。在这个II期申请中，我们建议完成结核病快速诊断测试的开发和评估，该测试将具有所需的性能和操作特性。具体目标是：1)优化分析设计，2)确定诊断测试性能，3)验证测试生产方案，为监管批准做准备。我们期望拟议的DPP检测将比现有的快速检测显示出更高的灵敏度和特异性，并将适用于全球范围内的结核病快速诊断。

DESCRIPTION (provided by applicant): Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis with an estimated two billion people currently infected worldwide and over nine million new cases detected annually worldwide. This is the largest killer of patients with HIV/AIDS. Current methods of diagnosis are complex, time-consuming, unreliable or unaffordable for most countries where the disease presents a significant public health threat. New diagnostics are critically needed to address the global tuberculosis burden and improve control programs. Our Phase I studies have clearly demonstrated the feasibility of developing a rapid and accurate test for tuberculosis. In collaboration with the Infectious Disease Research Institute, scientists at Chembio Diagnostic Systems, Inc. have identified a set of novel seroreactive antigens, designed several highly performing polyepitope fusion proteins, and applied the selected antigens in the Chembio's innovative immunoassay format, the Dual Path Platform (DPP(R)), with proven high accuracy of rapid serodiagnosis. We found that a DPP test prototype had a sensitivity of 81% and specificity of 95% in evaluations with serum samples obtained from culture-confirmed patients with active pulmonary tuberculosis from endemic regions in Brazil and Indonesia. In this Phase II application we propose to complete development and evaluation of the rapid diagnostic test for tuberculosis which will have required performance and operational characteristics. The specific aims are to: 1) optimize assay design, 2) determine diagnostic test performance, and 3) validate test production protocols in preparation for regulatory approval. We expect that the proposed DPP assay will demonstrate improved sensitivity and specificity over the existing rapid tests and will be applicable for expedited diagnosis of tuberculosis worldwide. PUBLIC HEALTH RELEVANCE: Tuberculosis remains one of the leading causes of mortality due to infectious disease worldwide. The current methods for diagnosis of tuberculosis are time-consuming, complex and laborious, and/or too expensive for routine use in resource-limited settings where most of patients live. The delayed or missed diagnosis leads to spreading of infection, progression of disease, and increased mortality. The research proposed here aims at developing a simple and rapid (20 minutes) point-of-care diagnostic test that would improve control programs by helping accurately detect new cases of tuberculosis, enabling timely antibiotic therapy, and preventing disease transmission. In addition to the visual reading, there will be an option for automated readout of the test result. The proposed assay will be fully validated and evaluated with serum samples from six countries representing various geographical areas and epidemiological setting associated with tuberculosis. These studies will demonstrate superior sensitivity and specificity as well as improved operational characteristics over the existing technologies.