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。 与公共卫生的相关性：结核病仍然是全世界传染病导致死亡的主要原因之一。目前诊断结核病的方法耗时、复杂、费力，和/或过于昂贵，无法在大多数患者生活的资源有限的环境中进行常规使用。延误或漏诊会导致感染的扩散、疾病的发展和死亡率的增加。这里提出的研究旨在开发一种简单快速(20分钟)的护理点诊断测试，通过帮助准确发现新的结核病病例、实现及时的抗生素治疗和防止疾病传播来改进控制程序。除了视觉读数之外，还将有一个自动读出测试结果的选项。建议的化验方法将用来自6个国家和地区的血清样本进行全面验证和评估，这些国家代表与结核病相关的不同地理区域和流行病学环境。这些研究将显示出比现有技术更高的灵敏度和特异度以及更好的操作特性。

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.