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）的增加威胁着全球结核病控制的成功。需要快速、廉价的方法来检测M。结核病（MTB）的临床标本和药物敏感性测试。最近已经描述了一种依赖于早期细菌生长的显微镜检测的廉价、有效的液体培养方法（“用于检测和敏感性的显微镜观察”，或MODS）。 目的：本K23提案的总体目标是：1）优化用于乙胺丁醇、链霉素和吡嗪酰胺药物敏感性试验的MODS检测方法; 2）确定在结核病流行环境中用于检测肺结核疑似患者中MTB的MODS性能特征; 3）比较MODS与常规Loewenstein-Jensen（LJ）培养检测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中耐多药结核病的临床益处; 5）通过指导经验和课程学习获得临床研究培训。 研究方法：项目1是在约翰霍普金斯大学进行的一项实验室研究，旨在优化乙胺丁醇、链霉素和吡嗪酰胺药敏试验的MODS性能。项目2将是一项关于两种诊断测试的实验室性能的前瞻性研究，研究对象将是巴西里约热内卢一所大学医院的成人肺结核疑似患者。MODS的敏感性和特异性将使用临床TB病例定义作为金标准来确定。将比较两种方法的阳性天数。项目3将是一项前瞻性、随机、对照研究，目的是在里约热内卢社区卫生中心对复治肺结核病例进行药物敏感性试验，以评估MODS的临床益处。主要目的是比较当MODS与LJ用于INH和RIF药敏试验时开始适当抗结核治疗的时间。这些研究将纳入正在里约热内卢进行的结核病合作研究。 相关性：这些研究的结果将提高我们对该测试的实验室性能和临床益处的理解，并导致改进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.