To devise more effective means to reduce spread of tuberculosis (TB) in the U.S., it is critical to understand the transmission dynamics of drug-resistant and drug-susceptible TB in different socioeconomic settings, including small cities, rural areas and locations where foreign-born persons enter the U.S. To address these issues, the investigators propose a population-based molecular epidemiologic study of TB along the U.S.-Mexico border. They hypothesize that: (1) the transmission dynamics of TB in small cities and rural areas differ from those in large cities; (2) Prospective use of molecular epidemiology will delineate the transmission dynamics of drug- susceptible and drug-resistant TB; (3) A rapid method of RFLP analysis of M. tb isolates will enhance timely detection of TB outbreaks. Our specific aims are-1. To determine the nature of epidemiologic links between patients who are infected with the same M. tb strain, and to identify locations and settings where TB is transmitted, including an analysis of transmission across the U.S.-Mexico border. This will be achieved by correlating detailed clinical and epidemiologic data on TB patients with results of RFLP analysis of M. tb isolates. 2. To characterize the development and transmission dynamics of drug- resistant TB, including comparison of the transmission potential of M. tb isolates with or without katG mutations. This will be achieved by evaluation of drug susceptibility patterns, clinical and epidemiologic data, RFLP results and sequencing of the katG gene. 3. To evaluate the utility of spoligotyping, a rapid method of RFLP analysis, to identify unsuspected TB outbreaks and guide public health interventions to reduce TB transmission. Spoligotyping will be adapted for use in clinical samples and early mycobacterial cultures, then prospectively applied to all M. tb isolates. This study will provide insight into the transmission dynamics of TB in mixed urban/rural areas. It will evaluate the relationship between katG mutations and transmission potential, providing clues to the mechanisms underlying mycobacterial virulence. Finally, it will determine if rapid RFLP methods can contribute to TB control efforts. The knowledge gained will permit refinement of TB control strategies along the U.S.-Mexico border and in Latin America.