Project Summary Tuberculosis remains the leading cause of death by an infectious disease worldwide, despite the widespread availability of effective therapy. Two major scientific knowledge gaps constrain our ability to effectively respond this epidemic: 1) understanding characteristics of individuals who are transmitting infection within the population; and 2) identifying efficient means of diagnosing these individuals early in their course of disease to prevent ongoing transmission. Our preliminary research and that of others has demonstrated that, for any given time in a population, a substantial proportion of individuals with microbiologically confirmed tuberculosis have few or no classical symptoms. This state has been described as “subclinical tuberculosis”. What fraction of cases are subclinical, how infectious these individuals are, and the total contribution of subclinical tuberculosis towards transmission in the population is poorly understood. This proposal leverages our unique research infrastructure in prisons in Central-Western Brazil to evaluate novel tools, including a disposable mask to capture exhaled bioaerosols, for early detection of tuberculosis in asymptomatic individuals. We will test the following hypotheses: 1) individuals with tuberculosis who lack symptoms are on average at least 50% as infectious as those with symptoms, and contribute equally to overall transmission; 2) mask aerosol sampling will be more effective than sputum testing for tuberculosis diagnosis in individuals with few or no symptoms; 3) biannual mass screening with diagnostics targeted at subclinical tuberculosis would be cost- effective in prisons. Overall, this project will address fundamental questions about tuberculosis transmission, while testing practical approaches to control tuberculosis in high burden settings.