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. [unreadable] [unreadable] 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. [unreadable] [unreadable] 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. [unreadable] [unreadable] 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. [unreadable] [unreadable]