Rapid Drug Susceptibility Test for Tuberculosis

结核病快速药敏试验

• 批准号: 10379831
• 负责人: Jeffrey D. Cirillo
• 金额: $ 30.65万
• 依托单位: PULMONESCENCE DIAGNOSTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10379831
• 关键词: Address; Aliquot; Antibiotic Resistance; Antibiotics; Applications Grants; Biological Assay; Blinded; Buffers; Cause of Death; Cessation of life; Clinical Trials; Cold Chains; Complex; Containment; Country; Data; Development; Diagnosis; Diagnostic; Diagnostic tests; Drug resistance; Drug resistance in tuberculosis; Drug usage; Early Diagnosis; Enzymes; Equipment; Face; Fluorescence; Foundations; Fund Raising; Funding; Goals; Growth; Health Personnel; Hour; Human; Human Resources; Infectious Agent; Life; Methods; Multidrug-Resistant Tuberculosis; Nucleic Acids; Organism; Organizational Objectives; Outcome; Patients; Peripheral; Pharmaceutical Preparations; Phase; Phenotype; Predisposition; Problem Solving; Public Health; Reporter; Reporting; Reproducibility; Research; Research Personnel; Resistance; Resource-limited setting; Resources; Running; Sampling; Ships; Signal Transduction; Sputum; Technology; Temperature; Test Result; Testing; Texas; Training; Triage; Tuberculosis; Universities; Work; World Health Organization; bactericide; base; care seeking; combat; compliance behavior; cost; design; detection sensitivity; diagnostic platform; drug quality; economic impact; expectation; experience; experimental study; global health; laboratory equipment; low and middle-income countries; mortality; novel; novel therapeutics; pandemic disease; performance tests; prevent; product development; programs; reagent testing; resistant strain; transmission process; tuberculosis diagnostics; tuberculosis drugs; virtual

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.

项目摘要 在此拨款应用中，我们建议开发结核病快速的表型药物敏感性测试（TB） 基于我们对结核病的快速痰诊断测试。结核病（TB）中耐药性的出现已经存在 全球人类传染性死亡的最常见原因是全球的重大关注点 健康。世界卫生组织（WHO）将结核病战略的关键里程碑设定为一个关键里程碑，这是一个目标 从2015年到2025年的十年来，结核病死亡减少了75％。但是，结核病的出现 耐药性的菌株威胁着全球进步这一里程碑，并阻碍了所有结核病 根除计划。导致耐药性的因素包括用药物治疗患者 不会影响耐药的生物，药物的供应和质量管理不佳，并且更高 在公共场所传播结核病。此外，患者在接受治疗的同时面临灾难性的成本 耐药性，因此经常不受治疗，进一步加剧了问题。 减少和遏制这些抗生素抗性菌株的关键是所有形式的早期检测 结核病中的耐药性。为了解决这个问题，我们正在开发快速的表型药物敏感性测试 基于我们新颖的基于REFTB痰的TB诊断系统，该系统可以显着改变药物的方式 目前在低资源的公共环境中进行了敏感性诊断。提议的广泛目标 该阶段1的研究是为了将快速的表型药物敏感性测试开发到前线 结核病药物。 在此第1阶段应用中，我们计划开发优化的快速表型药物敏感性 测试和测试抗抗生素的BCG尖峰样品。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 是开发药物敏感性测试结核病诊断，该诊断稳定在环境温度下的储存量，可以是 在全球范围内发货，而无需依赖冷链。这项研究的核心假设是我们的痰液 - 基于REFTB的诊断可以适应包括药物敏感性测试。没有正确的药物易感性 可在患者寻求护理的地方可用的测试，大多数MDR-TB患者将未被发现，第二 不会开始线路治疗，并且将无法实现结核病淘汰的WHO目标。成功完成 一阶段中的上述任务将开始开发快速的药物敏感性测试，可用于达到 这些患者在低资源环境中的更多患者，因此可以将其引用以进行其他测试和治疗，从而可以 显着促进了消除结核病的目标。