Rapid DPP test for tuberculosis

描述（由申请人提供）：结核病是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900多万新发病例。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、不可靠或对大多数国家来说负担不起，在这些国家，这种疾病构成了重大的公共卫生威胁。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方案。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Chembio已经鉴定了一组新型血清反应性抗原，设计了几种高性能的多表位融合蛋白，并将选定的抗原应用于Chembio的创新免疫测定形式，即双路径平台（DPP（R）），具有经证明的快速血清诊断的高准确性。我们发现，DPP测试原型的敏感性为81%，特异性为95%，从巴西和印度尼西亚流行地区的活动性肺结核患者的培养获得的血清样本进行评估。在本II期申请中，我们建议完成结核病快速诊断检测试剂的开发和评估，该试剂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，和3）验证测试生产方案以准备监管批准。我们预计，拟议的DPP检测将显示出比现有快速检测更高的灵敏度和特异性，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.