Rapid Detection of Mycobacterium tuberculosis

描述(申请人提供)：背景：结核病(TB)是全球传染病死亡的主要原因。耐多药结核病(MDR)的增加威胁到全球结核病控制的成功。需要一种快速、廉价的方法来检测临床标本中的结核分枝杆菌(MTB)并进行药敏试验。最近描述了一种廉价、高效的液体培养方法(检测和药敏显微镜观察，或MODS)，这种方法依赖于对早期细菌生长的显微检测。 目的：本K23提案的总体目标是：1)优化乙胺丁醇、链霉素和吡津胺的MODS药敏试验；2)确定MODS在结核病流行环境中检测结核杆菌的性能特征；3)比较MODS和传统的洛文斯坦-詹森(LJ)培养法检测MTB生长的时间；4)确定MODS在结核病流行环境中检测高危人群耐多药结核病的临床益处；以及5)通过指导经验和课程工作获得临床研究方面的培训。 方法：项目1将是在约翰霍普金斯大学进行的一项实验室研究，旨在优化多器官功能障碍综合征对乙胺丁醇、链霉素和吡津酰胺的药敏试验。项目2将对巴西里约热内卢一所大学医院的两项诊断测试的实验室性能进行前瞻性研究，研究对象将是成年肺结核嫌疑人。将以临床结核病病例定义作为金标准来确定MODS的敏感性和特异性。将对两种方法的阳性天数进行比较。项目3将是一项前瞻性、随机性、对照研究，目的是在里约热内卢的社区卫生中心对再治疗肺结核患者进行多器官功能障碍综合征药物敏感性测试的临床益处。主要目的是比较MODS和LJ用于异烟肼和RIF敏感性检测时开始适当的抗结核治疗的时间。这些研究将嵌套在里约热内卢正在进行的合作结核病研究中。 相关性：这些研究的结果将提高我们对这项检测的实验室表现和临床益处的理解，并导致改善结核病的检测和治疗。

DESCRIPTION (provided by applicant): Background: Tuberculosis (TB) is a leading cause of infectious disease mortality worldwide. The increase in multi-drug resistant (MDR) TB threatens the success of global TB control. There is a need for rapid, inexpensive methods for detection of M. tuberculosis (MTB) in clinical specimens and for drug susceptibility testing. An inexpensive, efficient, liquid culture method ("Microscopic Observation for Detection and Susceptibility", or MODS) that relies on microscopic detection of early bacterial growth has been described recently. Objectives: The overall objectives of this K23 proposal are 1) to optimize the MODS assay for drug susceptibility testing for ethambutol, streptomycin, and pyrazinamide; 2) to determine the performance characteristics of MODS for detection of MTB among pulmonary TB suspects in a TB-endemic setting; 3) to compare the time to detection of MTB growth for MODS versus conventional Loewenstein-Jensen (LJ) culture; 4) to determine the clinical benefit of MODS for detection of MDR TB among high risk persons in a TB-endemic setting; and 5) to gain training in clinical research through mentored experience and coursework. Methods: Project 1 will be a laboratory study performed at Johns Hopkins University to optimize MODS performance for drug susceptibility testing for ethambutol, streptomycin, and pyrazinamide. Project 2 will be a prospective study of laboratory performance of two diagnostic tests in which study subjects will be adult pulmonary TB suspects at a university-based hospital in Rio de Janeiro, Brazil. Sensitivity and specificity of MODS will be determined using a clinical TB case definition as the gold standard. Days to positivity will be compared for the two methods. Project 3 will be a prospective, randomized, controlled study of the clinical benefit of MODS for drug susceptibility testing among retreatment pulmonary TB cases at community Health Centers in Rio de Janeiro. The primary objective is to compare the time to initiation of appropriate anti-tuberculosis therapy when MODS versus LJ is used for INH and RIF susceptibility testing. These studies will be nested into ongoing collaborative TB studies in Rio de Janeiro. Relevance: Results of these studies will improve our understanding of the laboratory performance and clinical benefit of this test, and lead to improved detection and treatment of TB.