. The goal of this career development plan is to support Dr. Leonardo Martinez, an infectious disease epidemiologist, in developing an independent research program focused on increasing tuberculosis case detection in high-risk groups. In active tuberculosis case finding studies, the majority of individuals are unable to provide sputum. In our previous work in Brazilian prisons, mass screening for tuberculosis among incarcerated individuals found a hyperendemic level of disease burden, 3,900 cases per 100,000 prisoners. We hypothesize that the tuberculosis burden in these prisons is greater than our current estimates, as a majority of prisoners were unable to produce sputum and therefore were not evaluated by diagnostic tools such as GeneXpert, culture, and smear testing. A re-assessment of the tuberculosis burden is urgently needed in this setting as well as an assessment of the feasibility and value of non-sputum-based diagnostic tools to increase case detection and reduce ongoing transmission. Dr. Martinez proposes to: (1) measure the prevalence of undiagnosed TB and characteristics of tuberculosis among Brazilian prisoners who are unable to provide sputum samples at the baseline screening visit; (2) determine the feasibility and sensitivity of Mask Aerosol Sampling system (MASS), a novel tool that directly captures exhaled Mycobacterium tuberculosis from patients, during a mass screening intervention; and (3) identify cost-effective algorithms for tuberculosis screening in prisons. The proposed project will leverage an NIH-funded R01 study (AI130058-01, PI, Andrews/Croda) by the primary mentors, which is ongoing and enrolls adults in several prisons located in Mato Grosso do Sul, Brazil. This research plan forms the basis of a 5-year career development plan for Dr. Martinez under the mentorship of Drs. Jason Andrews (infectious diseases, epidemiology), Julie Parsonnet (adult infectious diseases), Julio Croda (infectious diseases, health policy), Yvonne Maldonado (pediatric infectious diseases), and Upinder Singh (infectious diseases) with consultants Robert Horsburgh (clinical epidemiology), Michael Barer (tuberculosis diagnostics), and Jeremy Goldhaber-Fiebert (cost-effectiveness analyses). This interdisciplinary group has developed a career development program for Dr. Martinez that includes: (1) fostering skills in designing field-based research and data collection; (2) application of statistical methods for the study of novel diagnostics; (3) effective usage of and experience with new advanced statistical methodologies related to decision-tree algorithmic creation, cost- effectiveness analysis, and mathematical modeling; (4) regular meetings with mentors and consultants; (5) presenting results at scientific meetings and seminars; (6) publishing in peer-reviewed journals; and (7) writing and submitting an R01 grant. Completion of this career development plan will allow Dr. Martinez to successfully compete for extramural funding in the future to continue researching non-sputum-based tuberculosis diagnostics in high-risk populations.
. Increasing tuberculosis case detection, especially in high-risk groups, is critical to meet the World Health Organization?s End TB Strategy to reduce tuberculosis incidence by 90% globally by 2035. A significant barrier to achieving this goal is that a large proportion of patients are unable to produce sputum and are therefore are not evaluated with commonly used and recommended diagnostics such as GeneXpert, culture, and smear testing. The overall goal of this proposal is to identify and quantify the burden of undiagnosed tuberculosis in Brazilian prisoners, evaluate the feasibility and value of non-sputum-based diagnostics to improve case detection in this setting, and to identify cost-effective algorithms for tuberculosis screening in prisons.