Sao Paulo-Minas Gerais Tropical Medicine Research Center for Chagas Disease Biomarker Discovery

项目总结/摘要-总体 由寄生虫克氏锥虫感染引起的恰加斯病（ChD）仍然是世界上最严重的疾病之一， 大多数被忽视的疾病，有570万感染者，但只有一种部分有效的治疗方法。的 缺乏活动性感染或临床终点的良好生物标志物， 新药或治疗干预的性能。 圣保罗-米纳斯吉拉斯热带医学研究中心（SaMi-Trop）由以下网络组成： 在米纳斯吉拉斯州和圣保罗州， 开发和开展关于ChD生物标志物发现和验证的研究项目的目的。 在这个建议中，该中心将开展三个相互关联的研究：项目1将研究自然历史， 为了识别与心脏病进展风险相关的预后标志物， 并发症和死亡。为此，我们将描述两个大型队列（REDS）的临床演变特征 和SaMi-Trop）来评估在组群招募时测量的生物标志物的可预测值。项目2将 评估遗传易感性是否调节疾病的发展。我们将使用全基因组关联研究 GWAS将结合来自NIH赞助的两项研究（REDS）招募的约5，500名个体的联合收割机遗传数据 和SaMi-Trop）以及巴西机构（班布伊，心脏研究所）资助的其他研究。项目3将 确定克氏锥虫病媒传播是否在米纳斯吉拉斯州的北部地区（一个地区 自2006年以来被视为无媒介传播）。我们将进行大规模的筛选调查 检测T.儿童唾液中克氏抗体的检测及儿童克氏抗体的问卷调查 向父母通报锥蝽亚科病媒感染的流行情况。两个核心（行政/科学核心 数据库和流行病学核心）将支持这三个项目的活动，并将努力维持 巴西青年科学家的研究培训能力

PROJECT SUMMARY/ABSTRACT -OVERALL Chagas disease (ChD), caused by infection with the parasite Trypanosoma cruzi, remains one of the world's most neglected diseases with 5.7 million infected people, but only a single partially effective treatment. The lack of good biomarkers for active infection or clinical end-points poses a problem for assessing the performance of new drugs or therapeutic interventions. The Sao Paulo-Minas Gerais Tropical Medicine Research Center (SaMi-Trop) consists of a network of collaborating scientists in the States of Minas Gerais and Sao Paulo which has been established for the purpose of developing and conducting research projects on ChD biomarker discovery and validation. In this proposal, the center will develop three interrelated studies: Project 1 will study the natural history of ChD, in order to recognize prognostic markers related to the risk of progression to cardiopathy, cardiac complications and death. To that effect, we will characterize the clinical evolution of two large cohorts (REDS and SaMi-Trop) to assess the predictable values of biomarkers measured at cohort enrollment. Project 2 will assess if genetic susceptibility modulates disease development. We will use genome wide association study (GWAS) that will combine genetic data from ~5,500 individuals recruited by two NIH-sponsored studies (REDS and SaMi-Trop) and other studies funded by Brazilian Agencies (Bambui, Heart Institute). Project 3 will determine if T cruzi vectorial transmission is reemerging in the Northen Region of Minas Gerais State (a region considered free of domiciliary vector transmission since 2006). We will conduct a large-scale screening survey to detect T. cruzi antibody in schoolchildren’s saliva, and a survey with questionnaires applied to the children’s parents about the prevalence of infestation by triatominae vectors. Two cores (Administrative/Scientific Core and Database and Epidemiology Core) will support activities of the three projects, and will seek to sustain research training capacity for young Brazilian scientists