Rapid DPP test for tuberculosis

描述(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，全球每年发现超过900万新病例。这是艾滋病毒/艾滋病患者的最大杀手。目前的诊断方法复杂、耗时、不可靠或对大多数疾病构成重大公共卫生威胁的国家来说是负担不起的。迫切需要新的诊断方法来解决全球结核病负担和改善控制方案。我们的第一阶段研究清楚地证明了开发一种快速和准确的结核病检测方法的可行性。化学诊断系统公司的科学家与传染病研究所合作，确定了一套新的血清反应抗原，设计了几种高效的多表位融合蛋白，并将选定的抗原应用于化学生物的创新免疫分析格式--双路径平台(DPP(R))，证明了快速血清诊断的高准确性。我们发现，在对来自巴西和印度尼西亚流行地区经培养确认的活动性肺结核患者的血清样本进行评估时，DPP测试原型具有81%的敏感性和95%的特异性。在这一第二阶段的应用中，我们提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点。具体目标是：1)优化测试设计，2)确定诊断测试性能，3)验证测试生产方案，为监管部门批准做准备。我们预计，与现有的快速检测方法相比，建议的DPP检测方法将显示出更高的敏感性和特异性，并将适用于全球结核病的快速诊断。

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.