Sao Paulo- Minas Gerais Neglected Tropical Disease Research Center for Biomarker

圣保罗-米纳斯吉拉斯州被忽视的热带疾病生物标记研究中心

• 批准号: 9110882
• 负责人: Ester Cerdeira Sabino
• 金额: $ 31.29万
• 依托单位: FUNDACAO FACULDADE DE MEDICINA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9110882
• 关键词: Address; Admission activity; Aftercare; Age; Algorithms; Amyloid; Antibodies; Area; Benznidazole; Bioinformatics; Biological Assay; Biological Markers; Blood; Blood donor; Blood donor screening; Blood specimen; Brazil; CCL2 gene; Candidate Disease Gene; Cardiac; Cardiology; Cessation of life; Chagas Cardiomyopathy; Chagas Disease; Clinical; Clinical Trials; Coagulation Process; Code; Cohort Studies; Collaborations; Consensus; Creatine Kinase MB Isoenzyme; Data; Databases; Development; Disease; Disease Progression; Echocardiography; Electrocardiogram; Enrollment; Epidemiologist; Epidemiology; Evaluation; Foundations; Funding; Future; Gelatinase B; Gender; Gene Expression; Gene Expression Profiling; Genetic Transcription; Genomic DNA; Goals; Health; Health system; Heart Diseases; Hospitals; Human Resources; IL8 gene; Immune; Individual; Infection; Infectious Diseases Research; Institutes; Interleukin-1; Interleukin-10; Interleukin-6; Laboratories; Leishmania; Leprosy; Mathematics; Measures; Messenger RNA; Modeling; Myocarditis; Myoglobin; National Heart, Lung, and Blood Institute; Natural History; Natural Immunity; One-Step dentin bonding system; Parasitemia; Parasites; Patients; Performance; Peripheral Blood Mononuclear Cell; Peroxidases; Pharmaceutical Preparations; Plasma; Plasminogen Activator Inhibitor 1; Population; Procedures; Process; Proteomics; Public Health; Questionnaires; RNA; Reading; Recording of previous events; Registries; Research; Research Infrastructure; Research Personnel; Research Training; Resources; Retroviridae; Risk; Sampling; Sampling Studies; San Francisco; Scientist; Selectins; Series; Serological; Serum; Serum amyloid A protein; Staging; Strategic Planning; Subgroup; Surrogate Markers; System; Technology; Testing; Therapeutic; Therapeutic Intervention; Time; Training Programs; Troponin I; Trypanosoma cruzi; Universities; Validation; Variant; Visit; Whole Blood; Work; adiponectin; adjudicate; base; biomarker discovery; care systems; chemokine; clinical biomarkers; clinical care; clinical efficacy; cohort; cytokine; data management; efficacy trial; experience; forest; genomic RNA; high risk; indexing; inflammatory marker; meetings; neglect; neglected tropical diseases; novel therapeutics; pro-brain natriuretic peptide (1-76); programs; sample collection; seropositive; standard care; standard of care; statistics; symposium; tool; transcriptome; treatment response

Our long term goal is to establish SaMi-Trop as a Center of Excellence for Neglected Infectious Disease Research in Brazil. The Specific Aims of the current application are to begin that process by focusing on T. cruzi infection with the goal of finding an array of biomarkers that correlate with parasite persistence and Chagas cardiac disease that can be used to infer risk of disease progression and death as well used as surrogate markers of cure or efficacy of novel drugs. We will develop three interrelated studies: Project 1 will focus on applying gene expression tools to existing whole blood RNA samples from the NHLBI REDS-II cohort to discover and validate new biomarkers of active infection and disease progression, these will be combined with parasite specific (PCR load and antibody profiling and titers) and plasma proteomic biomarkers (chemokines, cytokines, and inflamatory, coagulation and cardiac parameters) that are being generated through already funded collaborations, to generate composite biomarker profiles and scores that coorelate with pre-defined disease stages. In Project 2 we plan to treat a subgroup of 100 T cruzi PCR-positive patients from the REDS-II cohort using standard treatment with benznidazole (BZN) and follow subjects for 2 years after treatment. We will use these samples to validate the utility of biomarkers and composite biomarker profiles found in project 1 for assessment of therapeutic responses including clearance or suppression of parasitemia or normalization of immune perturbations and markers of cardiac damage. In Project 3 we plan to take advantage of the Public Health System in the State of Minas by enrolling and collecting blood samples from 2000 Chagas disease patients. These patients will be followed for two years for the endpoints of death or admission to a hospital for cardiac disease. The main goal is to obtain a simple risk score based on biomarker levels and ECG fndings that could identify high risk patients in order to guide therapeutic approaches and serve as a foundation for future clinical trials. Two cores will be established: the Administrative Core and Database and Epidemiology Core that will support activities of the 3 projects, as well as create and sustain research training capacity for young Brazilian scientists.

我们的长期目标是将萨米-特罗普建立为巴西被忽视的传染病研究卓越中心。当前申请的具体目标是通过关注克氏锥虫感染来开始这一过程，目标是找到一系列与寄生虫持久性和恰加斯心脏病相关的生物标志物，这些标志物可用于推断疾病进展和死亡的风险，例如：很好地用作新药治愈或功效的替代标志。我们将开展三项相互关联的研究：项目 1 将侧重于将基因表达工具应用于 NHLBI REDS-II 队列的现有全血 RNA 样本，以发现和验证活动性感染和疾病进展的新生物标志物，这些将与寄生虫特异性（ PCR 负载和抗体分析和滴度）和血浆蛋白质组生物标志物（趋化因子、细胞因子以及炎症、凝血和心脏参数）正在通过已资助的合作生成，以生成复合生物标志物与预先定义的疾病阶段相关的概况和评分。在项目 2 中，我们计划使用苯并硝唑 (BZN) 标准治疗方法治疗来自 REDS-II 队列的 100 名 T cruzi PCR 阳性患者亚组，并在治疗后对受试者进行 2 年随访。我们将使用这些样本来验证项目 1 中发现的生物标志物和复合生物标志物概况的效用，以评估治疗反应，包括清除或抑制寄生虫血症或免疫扰动和心脏损伤标志物的正常化。在项目 3 中，我们计划利用米纳斯州的公共卫生系统，登记并采集 2000 名恰加斯病患者的血液样本。这些患者将被跟踪两年，了解死亡终点或因心脏病入院的情况。主要目标是根据生物标志物水平和心电图结果获得简单的风险评分，可以识别高风险患者，以指导治疗方法并作为未来临床试验的基础。将建立两个核心：行政核心以及数据库和流行病学核心，这将支持这三个项目的活动，并为巴西年轻科学家创建和维持研究培训能力。

项目成果

Prevalence of Treponema pallidum DNA among blood donors with two different serologic tests profiles for syphilis in São Paulo, Brazil.

在巴西圣保罗进行两种不同梅毒血清学检测的献血者中梅毒螺旋体 DNA 的患病率。

• DOI: 10.1111/vox.12111
• 发表时间: 2014
• 期刊: Vox sanguinis
• 影响因子: 2.7
• 作者: Ferreira,SC;deAlmeida-Neto,C;Nishiya,AS;Di-Lorenzo-Oliveira,C;Ferreira,JE;Alencar,CS;Levi,JE;Salles,NA;Mendrone-Junior,A;Sabino,EC
• 通讯作者: Sabino,EC

MicroRNA Transcriptome Profiling in Heart of Trypanosoma cruzi-Infected Mice: Parasitological and Cardiological Outcomes.

• DOI: 10.1371/journal.pntd.0003828
• 发表时间: 2015
• 期刊: PLoS neglected tropical diseases
• 影响因子: 3.8
• 作者: Navarro IC;Ferreira FM;Nakaya HI;Baron MA;Vilar-Pereira G;Pereira IR;Silva AM;Real JM;De Brito T;Chevillard C;Lannes-Vieira J;Kalil J;Cunha-Neto E;Ferreira LR
• 通讯作者: Ferreira LR