Project Summary Tuberculosis remains one of the leading causes of death worldwide, despite the widespread availability of effective treatment and prevention measures. Prisons harbor among the highest rates of tuberculosis worldwide, and, in many regions, tuberculosis burden in correctional settings is growing. The WHO now recommends active case finding for tuberculosis in prisons and other high burden settings, but there is a dearth of evidence for how to accurate and efficiently identify cases early to reduce transmission. To address these gaps, we propose to a prospect cohort study among incarcerated individuals in high tuberculosis burden prisons in Central Western Brazil to: 1) evaluate the use of portable, digital x-rays with automated interpretation for intensive case finding; 2) determine whether genomic data can be used to track transmission rates at the population level; and 3) use mathematical models to identify effective, scalable strategies for tuberculosis case finding and prevention in prisons. We will test the hypotheses that: 1) x-ray with automated interpretation can achieve WHO target product profile thresholds for accuracy as a screening test among incarcerated individuals, even among those with asymptomatic or early disease; 2) emerging phylodynamic methods can be used to monitor trends in transmission; and 3) serial screening combined with preventive therapy would be a cost-effective and impactful approach for tuberculosis control in high-burden prisons globally. Overall, this project will address critical gaps in tuberculosis diagnosis and prevention among a large, underserved, high-risk population, to protect their health and the health of their communities.