Rapid Drug Susceptibility Test for Tuberculosis

项目摘要 在这项拨款申请中，我们建议开发一种结核病（TB）的快速表型药物敏感性测试 根据我们的结核病快速痰液诊断测试结核病耐药性的出现， 这是全世界人类感染性死亡的最常见原因，构成了全球的一个重大问题。 健康世界卫生组织（世卫组织）在其终止结核病战略中设定了一个重要的里程碑， 从2015年到2025年的十年内，结核病死亡人数减少75%。然而，结核病的出现 耐药性菌株威胁着全球朝着这一里程碑的进展，并阻碍了所有结核病 根除计划。导致耐药性的因素包括用一种药物治疗患者， 不影响耐药微生物，药物供应和质量管理不善， 在公共场所传播结核病。此外，患者在接受治疗时面临灾难性的费用， 耐药性，结果往往得不到治疗，进一步加剧了问题。 减少和遏制这些耐药菌株的关键是早期发现所有形式 结核病的耐药性。为了解决这个问题，我们正在开发一种快速表型药敏试验 基于我们的新型REFtb结核病诊断系统， 目前在资源匮乏的公共环境中进行易感性诊断。建议的广泛目标 在这一阶段的研究1应用是发展快速表型药物敏感性测试的第一线 肺结核药物。 在第1阶段申请中，我们计划开发优化的快速表型药物敏感性 测试和测试抗结核BCG加标痰液样本。对于第二阶段，我们计划继续开发 在初步临床试验中将这些发现扩展到耐药结核病。因此，我们研究的长期目标 是开发一种药物敏感性测试结核病诊断，在环境温度下储存稳定， 不依赖冷链就能运往世界各地这项研究的中心假设是我们的痰- 基于REFtb的诊断可适于包括药物敏感性测试。如果没有正确的药物敏感性 如果在患者寻求治疗的地方附近提供检测，大多数耐多药结核病患者将不会被发现，其次- 线治疗将无法启动，世卫组织消除结核病的目标将无法实现。成功完成 第一阶段的上述任务将开始开发一种快速药物敏感性试验， 更多的患者处于资源匮乏的环境中，因此他们可以被转诊接受额外的检测和治疗， 为实现消除结核病的目标做出了重大贡献。

Project Summary In this grant application, we propose to develop a rapid phenotypic drug susceptibility test for tuberculosis (TB) based on our rapid sputum diagnostic test for TB. The emergence of drug resistance in tuberculosis (TB), already the most frequent cause of infectious death in humans worldwide, constitutes a significant concern in global health. The World Health Organization (WHO) set as a critical milestone in their End TB Strategy, a goal of a 75% reduction in tuberculosis deaths over the ten years from 2015 to 2025. However, the emergence of TB strains with drug resistance threatens global progress toward this milestone and hinders all tuberculosis eradication programs. Factors contributing to drug resistance include the treatment of patients with a drug that does not affect resistant organisms, poor management of the supply and quality of drugs, and higher transmission of TB in public places. Moreover, patients face catastrophic costs while undergoing treatment for drug resistance and often go untreated as a result, further exacerbating the problem. The key to the reduction and containment of these antibiotic-resistant strains is the early detection of all forms of drug resistance in TB. To solve this problem, we are developing a rapid phenotypic drug susceptibility test based on our novel REFtb sputum-based TB diagnostic system that can dramatically transform how the drug susceptibility diagnosis is currently made in low-resource public settings. The broad objective of the proposed research in this Phase 1 application is to develop the rapid phenotypic drug susceptibility test to the front-line tuberculosis drugs. In this Phase 1 application, we plan to carry out development of an optimized rapid phenotypic drug susceptibility test and test antibiotic-resistant BCG spiked sputum samples. For the Phase 2, we plan to continue development to extend these findings to drug resistant TB in preliminary clinical trials. Thus, the long-term goal of our research is to develop a drug susceptibility test TB diagnostic that is stable in storage at ambient temperature and can be shipped worldwide without reliance on a cold-chain. The central hypothesis of this research is that our sputum- based REFtb diagnostic can be adapted to include drug susceptibility testing. Without the right drug susceptibility tests available near where patients seek care, the majority of patients with MDR-TB will go undetected, second- line treatments will not be started, and the WHO goal of TB elimination will not be met. Successful completion of the above tasks in Phase I will begin the development of a rapid drug susceptibility test that can be used to reach more of these patients in low-resource settings so they can be referred for additional testing and treatment, thus significantly contributing to the goal of TB elimination.