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)的快速表型药敏试验。 基于我们对结核病的快速痰诊断测试。结核病(TB)中出现的耐药性，已经 这是全球人类传染性死亡的最常见原因，在全球范围内构成了一个重大关切 健康。世界卫生组织(世卫组织)在其结束结核病战略中设定了一个关键里程碑，目标是 从2015年到2025年的十年间，结核病死亡人数减少了75%。然而，结核病的出现 具有抗药性的菌株威胁着全球迈向这一里程碑的进展，并阻碍所有结核病 根除计划。导致耐药性的因素包括患者使用的药物治疗 不影响耐药微生物，对药品供应和质量管理不善，以及更高 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成本 抗药性和经常不治疗的结果，进一步加剧了问题。 减少和遏制这些抗药性菌株的关键是及早发现所有形式 结核病中的抗药性。为了解决这个问题，我们正在开发一种快速的表型药敏试验。 基于我们的新型REFtb痰结核病诊断系统，可以极大地改变药物 目前，敏感性诊断是在低资源的公共环境中进行的。建议的总体目标是 这一阶段的研究应用是将快速表型药敏试验发展到一线 结核病药物。 在这一阶段的应用中，我们计划进行一种优化的快速表型药物敏感性的开发 检测抗药性卡介苗添加的痰样本。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 是开发一种药敏试验结核病诊断方法，这种方法在常温下储存稳定，可以 在不依赖冷链的情况下运往全球。这项研究的中心假设是我们的痰- 基于REFtb的诊断可以修改为包括药敏试验。如果没有正确的药物敏感性 在患者就诊地点附近提供检测，大多数耐多药结核病患者将不会被发现，其次- 一线治疗将不会开始，世卫组织消除结核病的目标也将无法实现。成功完成 上述第一阶段的任务将开始开发一种快速药敏试验，可用于 这些患者中有更多处于低资源环境中，因此他们可以被转介进行额外的检测和治疗，因此 为实现消除结核病的目标作出了重大贡献。

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.