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

项目摘要/摘要--总体 查加斯病(CHD)是由克氏锥虫寄生虫感染引起的，目前仍是世界上最严重的 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。这个 缺乏良好的活动性感染生物标志物或临床终点对评估 新药或治疗干预措施的效果。 圣保罗-米纳斯吉拉斯热带医学研究中心(SAMI-TROP)由 在米纳斯吉拉斯州和圣保罗州合作的科学家已经为 开发和开展冠心病生物标志物发现和验证研究项目的目的。 在这项提案中，该中心将开展三项相互关联的研究：项目1将研究 CHD，为了识别与进展为心脏病风险相关的预后标记物， 并发症和死亡。为此，我们将描述两个大队列(RED)的临床演变 和Sami-trop)，以评估在队列登记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影响疾病的发展。我们将使用全基因组关联研究 这将结合由美国国立卫生研究院赞助的两项研究(REDS)招募的约5,500人的基因数据 和Sami-trop)以及由巴西机构(Bambui，心脏研究所)资助的其他研究。项目3将 确定T-CRUZI媒介传播是否在米纳斯吉拉斯州北部地区(一个地区)重新出现 自2006年以来被认为不存在户籍媒介传播)。我们将进行大规模的筛查调查 目的检测学龄儿童唾液中克氏毛滴虫抗体，并对儿童进行问卷调查。 家长对三毛虫病媒感染的流行情况的了解。两个核心(行政/科学核心 以及数据库和流行病学核心)将支持这三个项目的活动，并将寻求维持 巴西年轻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