MAS-PCR Rapid Screening Test for Multidrug-Resistant Tuberculosis (MDR-TB)

MAS-PCR 耐多药结核病 (MDR-TB) 快速筛查试验

• 批准号: 8502235
• 负责人: Angkana Chaiprasert
• 金额: $ 11.32万
• 依托单位: MAHIDOL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-15 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8502235
• 关键词: Alleles; Chest; China; Country; DNA; Detection; Developing Countries; Disease; Drug Resistant Tuberculosis; Drug usage; Environment; Equipment; Faculty; Gene Mutation; Genotype; Goals; Gold; Hospitals; Infection; Institutes; Laboratories; Medicine; Methods; Microbiology; Molecular; Multidrug-Resistant Tuberculosis; Mycobacterium tuberculosis; Nucleic Acids; Organism; Patients; Pharmaceutical Preparations; Polymerase Chain Reaction; Predisposition; Prospective Studies; Public Health; Reporting; Research; Resistance; Resources; Retrospective Studies; Rifampin; Sampling; Simulate; Specimen; Sputum; Techniques; Test Result; Testing; Thailand; Time; Training; Treatment Protocols; Tuberculosis; Universities; Work; base; clinical practice; clinical research site; cost; design; isoniazid; public health relevance; rapid detection; screening; success; transmission process; tuberculosis treatment

DESCRIPTION (provided by applicant): Resistance of Mycobacterium tuberculosis to drugs used for treatment of TB infection has become a significant problem, and the existence of multidrug-resistant tuberculosis (MDR-TB) is increasing throughout the world. MDR-TB is defined as resistance to both rifampicin (RIF) and isoniazid (INH), two of the first-line drugs used for treatment of TB. The conventional method used today to detect MDR-TB requires growing the TB organism in culture and then testing it against the drugs used for treatment. This is laborious and requires weeks to months before the result is known, which delays starting treatment with more expensive second-line drugs that will be effective. Genetic mutations associated with MDR-TB have been identified, and several rapid polymerase chain reaction (PCR) tests have been developed to screen for MDR-TB. These PCR-based tests provide more rapid results, but they are expensive and require specialized lab equipment that cannot be easily afforded by most labs in high-burden TB countries, which are mostly resource-limited developing countries. The primary objective of the proposed research is to test a simple and inexpensive multiplex allele-specific polymerase chain reaction (MAS-PCR) technique that can be used for rapid screening of MDR-TB in high burden resource-limited countries. The MAS-PCR test has already been developed and tested in a single laboratory environment at the Drug-Resistant Tuberculosis (DRTB) Laboratory, Department of Microbiology, Faculty of Medicine, Siriraj Hospital, Mahidol University, and Bangkok, Thailand. The proposed study consists of two parts designed to confirm that this test is feasible for use in multiple labs and can provide accurate and consistent results across these labs. For the first part of the study, simulated samples of TB with known susceptibility or resistance to RIF and INH will be sent to each of five labs in Thailand and China. The labs will not know whether the samples are susceptible or resistant. Test results from each lab will be compared to the known status of the sample, as well as to the result from another more expensive PCR-based test, the Genotype MTBDR Plus. In the second part of the study, the labs in China and Thailand will receive sputum samples from current patients at their hospitals with confirmed TB and will screen them with the MAS-PCR test to determine whether they might be MDR-TB cases. The results from these tests on local specimens will be confirmed by retesting on the DNA samples from these specimens with Genotype MTBDR Plus at the DRTB Laboratory at Siriraj Hospital. If the MAS-PCR screening test is successfully implemented in the labs in Thailand and China, it will be a candidate for further testing in other high-burden resource limited countries and implementation for routine screening for MDR-TB.

描述（由申请人提供）：结核分枝杆菌对用于治疗结核病感染的药物的耐药性已成为一个重大问题，并且在全球范围内存在多种耐药性结核病（MDR-TB）的存在。 MDR-TB被定义为对利福平（RIF）和异尼二氮二氮（INH）的抗性，这是两种用于治疗结核病的一线药物。如今，用于检测MDR-TB的常规方法需要在培养中种植TB生物，然后对用于治疗的药物进行测试。这很费力，需要在结果才知道的几周到几个月之前，这会延迟使用更昂贵的二线药物开始治疗，这将是有效的。已经鉴定出与MDR-TB相关的遗传突变，并开发了几种快速聚合酶链反应（PCR）测试以筛选MDR-TB。这些基于PCR的测试可提供更快的结果，但是它们很昂贵，并且需要专门的实验室设备，这些设备在高负荷TB国家 /地区的大多数实验室无法轻松提供，这些设备大多是资源有限的发展中国家。拟议研究的主要目的是测试一种简单且廉价的多重等位基因特异性聚合酶链反应（MAS-PCR）技术，该技术可用于在高负担资源有限的国家中快速筛选MDR-TB。 MAS-PCR测试已经在耐药性结核病（DRTB）实验室的单个实验室环境中进行了开发和测试。拟议的研究包括两个部分，旨在确认该测试可用于多个实验室，并且可以在这些实验室中提供准确，一致的结果。在研究的第一部分中，模拟具有已知敏感性或对RIF和INH抗性的结核病样品将发送到泰国和中国的五个实验室中的每个实验室中的每个实验室。实验室将不知道样品是易感还是抗性。将将每个实验室的测试结果与样本的已知状态进行比较，以及另一个基于PCR的另一个基因型MTBDR Plus的结果。在研究的第二部分中，中国和泰国的实验室将通过确认的结核病从其医院的现有患者那里获得痰液样本，并将通过MAS-PCR测试对其进行筛查，以确定它们是否可能是MDR-TB病例。这些对局部标本的测试的结果将通过在Siriraj医院的DRTB实验室中用基因型MTBDR Plus重新测试这些标本的DNA样品来确认。如果在泰国和中国的实验室成功实施了MAS-PCR筛查测试，它将成为其他高负荷资源有限国家进一步测试的候选人，并实施了MDR-TB的常规筛选。