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.

项目概要 在本次拨款申请中，我们建议开发一种针对结核病（TB）的快速表型药物敏感性测试 基于我们的结核病快速痰诊断测试。结核病（TB）已出现耐药性 是全世界人类感染性死亡最常见的原因，引起了全球的重大关注 健康。世界卫生组织 (WHO) 在其《终结结核病战略》中设定了一个重要的里程碑，即 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 具有耐药性的菌株威胁着全球实现这一里程碑的进展，并阻碍了所有结核病的发展 根除计划。导致耐药性的因素包括患者接受的药物治疗 不影响耐药菌、药品供应和质量管理不善以及较高的风险 结核病在公共场所的传播。此外，患者在接受治疗时面临灾难性的费用 耐药性并常常因此得不到治疗，从而进一步加剧了这一问题。 减少和遏制这些抗生素耐药菌株的关键是及早发现所有形式的菌株 结核病耐药性。为了解决这个问题，我们正在开发一种快速表型药物敏感性测试 基于我们新颖的基于 REFtb 痰液的结核病诊断系统，该系统可以极大地改变药物的使用方式 目前，易感性诊断是在资源匮乏的公共场所进行的。拟议的总体目标 本次一期申请的研究目的是开发用于一线的快速表型药物敏感性测试 结核病药物。 在本次一期申请中，我们计划开发一种优化的快速表型药物敏感性 测试并测试抗生素抗性卡介苗加标痰样本。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 旨在开发一种在环境温度下稳定储存并可用于结核病诊断的药敏试验 无需依赖冷链即可运送到世界各地。这项研究的中心假设是我们的痰- 基于 REFtb 的诊断可适用于包括药物敏感性测试。没有正确的药物敏感性 如果在患者寻求治疗的地方附近进行检测，大多数耐多药结核病患者将不会被发现，其次 一线治疗将无法启动，世界卫生组织消除结核病的目标也将无法实现。顺利完成 上述一期任务将开始开发快速药敏试验，可用于达到 更多的这些患者生活在资源匮乏的环境中，这样他们就可以被转介接受额外的检测和治疗，从而 为消除结核病的目标做出了重大贡献。