Regional Prospective Observational Research in Tuberculosis (RePORT) – Brazil Network

项目总结 巴西是西半球结核病负担最高的国家，也是世界上结核病负担最高的国家之一。 世界。在结核病的诊断、治疗和预防方面取得进展是必要的，以提高发病率、发病率、 以及巴西和全球的结核病死亡率。结核病区域前瞻性观察研究(报告)- 巴西是由我们小组在2013年发起的，招募了1188名肺结核患者和1930名他们的近亲 临床数据和储存的生物信息库样本促进了对预测因素的研究 结核病和结核病/艾滋病毒治疗结果、结核分枝杆菌(Mtb)感染和进展为结核病的预测因素 疾病和初发结核病、结核病糖尿病、耐药结核病、结核病诊断和结核分枝杆菌传播。强壮 已经与巴西和美国以及其他国家的调查人员建立了合作关系 报告网络(例如南非和印度)、加勒比中美洲和南美洲网络 艾滋病毒流行病学(CCASAnet)及其结核病哨兵研究网络(TB-SRN)，这是 评估艾滋病国际流行病学数据库(IeDEA)网络。在报告的第二阶段-巴西我们 将利用在阶段1中生成的丰富、高质量的临床、基因组和转录数据，以及 招募新的参与者，以扩大我们对结核病流行病学和发病机制的了解，并提高 结核病的诊断、治疗和预防。这将通过三个具体目标来实现：1)获得 改进结核病诊断、治疗和结果的见解。这将包括使用 巴西(SINAN；巴西国家疾病通报系统)和其他巴西国家的结核病病例登记 酌情登记；2)提高我们对结核分枝杆菌传播和感染的了解，包括潜伏期， 早期和亚临床疾病；发展为结核病的预测因素，以及预防结核病；以及3)支持 并培养下一代结核病科学家，并加强报告的范围和合作--巴西。 对于目标3，我们将资助结核病科学研究奖学金，重点是巴西的研究人员。这将包括两个 每年的早期职业发展奖学金，用于支持巴西-美国伙伴关系的试点项目，以及 为随后的赠款资金生成初步数据；以及每年两个博士后奖学金。两者都有 支持的类别将是利用报告--巴西的数据和/或标本的研究；还 将鼓励纳入来自其他结核病队列的数据和样本。这三个目标将进一步促进 报告的增长和加强-巴西，并产生改进诊断、治疗和 巴西的结核病预防工作。

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.