Regional Prospective Observational Research in Tuberculosis (RePORT) – Brazil Network - PROJECT SUMMARY Brazil has the highest tuberculosis (TB) burden in the Western Hemisphere, and among the highest in the world. Advances in TB diagnosis, treatment, and prevention are necessary to improve the incidence, morbidity, and mortality of TB in Brazil, and globally. Regional Prospective Observational Research in TB (RePORT)- Brazil was initiated by our group in 2013, and enrolled 1,188 pulmonary TB patients and 1,930 of their close contacts in Phase 1. Clinical data and stored biorepository specimens have facilitated studies of predictors of TB and TB/HIV treatment outcomes, predictors of M. tuberculosis (Mtb) infection and progression to TB disease and incipient TB, TB-diabetes, drug-resistant TB, TB diagnostics, and Mtb transmission. Strong collaborations have been established with investigators in Brazil and the United States, as well as other RePORT networks (e.g., South Africa and India), the Caribbean Central America South America network for HIV epidemiology (CCASAnet) and its TB Sentinel Research Network (TB-SRN), which is part of the International epidemiologic Databases to Evaluate AIDS (IeDEA) network. In Phase 2 of RePORT-Brazil we will utilize the rich, high-quality clinical, genomic, and transcriptomic data generated in Phase 1, together with new participant enrollment, to extend our understanding of TB epidemiology and pathogenesis, and improve the diagnosis, treatment, and prevention of TB. This will be accomplished through three Specific Aims: 1) Gain insights that improve TB diagnosis, treatment, and outcomes. This will include external validation utilizing the TB case registry in Brazil (SINAN; the Brazilian National System of Diseases Notification), and other Brazilian registries as appropriate; 2) Improve our understanding of Mtb transmission and infection, including latent, incipient, and sub-clinical disease; predictors of progression to TB, and protection against TB; and 3) Support and develop the next generation of TB scientists, and enhance the scope and collaboration of RePORT-Brazil. For Aim 3, we will fund Fellowships in TB Science, focusing on Brazilian investigators. This will include two Early Career Development Fellowships per year, for pilot projects that support Brazil-US partnerships, and generate preliminary data for subsequent grant funding; and two Post-Doctoral Fellowships per year. Both categories of support will be for studies that utilize RePORT-Brazil data and/or specimens; proposals that also include data and specimens from other TB cohorts will be encouraged. The three Aims will facilitate further growth and strengthening of RePORT-Brazil, and generate insights that improve the diagnosis, treatment, and prevention of TB in Brazil.
