Longitudinal Study of Patients with Chronic Chagas Cardiomyopathy in Brazil.

SaMi-Trop 

Center Program overview

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 neglected infectious diseases in Brazil, with an initial focus on Chagas Disease biomarker discovery and validation. For the past 5 years, the group has worked together on the development of a Chagas Natural History Study as part of the international REDS II program supported by the NHLBI. A total of 1100 Chagas patients and controls were enrolled and submitted to rigorous clinical and laboratory evaluation.

Robust specimen repository was also established, providing the opportunity to perform additional biomarker studies using this large clinically characterized Chagas disease cohort which should enable identification of stand-alone biomarkers, as well as to combine biomarker profiles, to stage disease and predict progression. For the current study we propose to perform a broader exploratory search for new biomarkers, including mRNA expression profiling, followed by a validation process to examine the predictive value of combinations of potentially informative biomarkers, both with respect to prognostic and therapeutic monitoring utility. A key problem for reaching these goals in Brazil has been the lack of scientists trained in large scale biomarker discovery, including genomic and mRNA screening methods and related bioinformatics, especially in the infectious diseases translational research settings. 

To create and sustain research capacity we have included a training component for young Brazilian scientists that will allow them to come to the US to perform sophisticated laboratory and data analysis techniques, for which the Brazilian investigators have limited expertise. The proposed activities will strengthen the 20 years of ongoing collaboration with the Blood Systems Research Institute and University of California San Francisco. Our long term goal is to establish SaMi-Trop as a Center for Excellence in Tropical Medicine and Infectious Disease Research in Latin America.

Chagas disease remains one of the most neglected diseases in the world, with recent estimates indicating 8-10 million infected people in Latin and Central America and only one marginally effective therapeutic. The lack of good biomarkers for active infection or clinical end-points poses a serious problem, both for individual patient prognosis and for assessing the performance of new drugs or other therapeutic interventions. We propose here are focused on discovering and validating new biomarkers for T. cruzi infection and Chagas cardiac disease.

Specific Aims

The main goal of the proposed research is to develop and to test a simple predictive rule for determining the prognosis of patients with Chronic Chagas Cardiopathy (CCC). CCC is a potential lethal condition, but the severity of the disease varies widely and to stratify the risk of death adequately is an unsolved challenge. Although prognostic scores are available, using data from more sophisticated tests, a simple, low-cost and easy-to-use prognostic model, suitable for the primary care setting, is lacking.

We propose to establish a large cohort study, based in a telehealth program designed to support primary care attention, to study and follow for at least two years 2,000 CCC patients, in search of markers of the risk of death and of a simple prognostic rule. We hypothesize that measuring Brain Natriuretic Peptide (BNP), in association with simple electrocardiographic (ECG) measurements and clinical information may be sufficient to predict, in a simple prognostic score, the risk of death in CCC patients and to be useful in the clinical practice.  

A secondary goal of this study is to collect blood for testing for new biomarkers detected in the other branches of this project. CCC has a complex physiopathology and many parasitic, immunological, inflammatory, autonomic and micro-vascular processes may have a role in the development or the progression of the disease. The identification of new biomarkers could help in the stratification of the risk of progression to/of CCC and death, in the detection of occurrence of specific complications and in the guidance of specific and general treatment of CCC patients. Our hypothesis is that hitherto unknown or untested biomarkers could be useful in concert with BNP and ECG in the management of asymptomatic or mildly symptomatic T cruzi infected subjects and cardiac disease patients. 

Preliminary results

The study is being conducted in 21 cities of the northern part of Minas Gerais state in Brazil, and includes a follow up of at least two years.The baseline evaluation includedcollection of socio-demographic information, social determinants of health, health-related behaviours, comorbidities, medicines in use, history of previous treatment for Chagas Disease (ChD), symptoms, functional class (FC), quality of life, blood sample collection and ECG.

Collaborations

Collaborations in this project will be welcome through specific research proposals sent to individual SAMI-TROP investigators.

The Dataset will be open access for two years at the end of the data collection process (August, 2018). In the meantime, applications to use the data should be made by contacting the researchers of the SAMI-TROP cohort and filling up the application form available at  http.collaboration.form. The questionnaires and interviewer guides of the baseline and follow-up visits will also be available in electronic formats at http.questionnaire .

Personnel

Dr Antonio Ribeiro MD, PhD.  He will serve as PI of this project. Dr Ribeiro is Full Professor of Internal Medicine at the Federal University of Minas Gerais. He is a clinical cardiologist and has a long experience in research with Chagas disease, ECG reading centers and BNP studies. He has published more than 130 papers, including in important journals, as The Lancet, BMJ and Stroke. During the last five years, he conducted as PI or Co-PI several major studies, with a total budget over 10 million dollars.

Ester Sabino, MD, PhD. She will serve as PI of this project. She is Full Professor of the Department of Infectious Disease at USP. She was a Fogarty Foundation Fellow during 1991-93 at Irwin Memorial Blood Centers (now BSRI) in San Francisco. This work on HIV led to her PhD and she subsequently established a major research program on TT-ID based in Sao Paulo. She is a Sao Paulo, and a consultant to the Brazilian Ministry of Health AIDS Program and Blood Control Program as well as to PAHO and WHO.  She served as the Brazilian PI of the REDS II, and have conducted 4 major protocols during the 5 years period of the program.  She has published over 90 manuscripts.

Edécio Cunha Neto MD, PhD. He is an immunologist with a scientific career on Chagas disease pathogenesis in humans.   He is a tenured Professor of the Department of Medicine at the School of Medicine, University of Sao Paulo, head of the Laboratory of Clinical Immunology and Allergy of the School of Medicine, University of Sao Paulo and Head of the Proteomics and Gene Expression unit of the Laboratory of immunology at the Heart Institute. He will devote 10% of the time in the first year and 5% in the subsequent years.

Clareci Silva Cardoso, PhD.She is epidemiologist, associated professor at
Federal University of São João del-Rei. Visiting Scholar in epidemiology at University of California, Berkeley. In this project, she has been participating both telehealth and in field/epidemiology teams. She has a large experience in coordinating data collecting in large sample and epidemiologic studies.

Ana Bierrembach, MD, PhD. She isan epidemiologist trained at the London School of Hygiene and Tropical Medicine/UK. With expertise in impact evaluation of health interventions, Dr. Bierrenbach has worked for four years at the Brazilian Ministry of Health and coordinating the Monitoring & Evaluation Project of the National Tuberculosis (TB) Control Programme and for three years at the World Health Organization HQ in Switzerland coordinating the WHO Global Task Force on TB Impact Measurement. 

Lea Campos de Oliveira, PhD,has experience in molecular biology and gene expression and will be responsible to direct with all technicians involved in the laboratory part of the study and will help in the analysis.

João Eduardo Ferreira, PI, PhD. He is associate professor of the Institute of Mathematic and Statistics (IME) of the University of São Paulo and head of the DATA group (http://www.data.ime.usp.br) laboratory. He has a long history of experience in developing RD systems and was responsible for all of the in Brazil database activities of the REDS II program. In addition, he has a strong publication record in database development and architecture.

Maria Beatriz Alkmim, MD, MSc,is the coordinator of the Center for Telehealth of University Hospital of Federal University of Minas Gerais. She has been working in the telemedicine/telehealth field for 10 years and has experience in management of large scale projects and telemedicine research.

Cláudia Di Lorenzo Oliveira, MD, PhD.She is epidemiologist, associated professor at
Federal University of São João del-Rei, will work as a research assistant. In this project, she will participate in the field coordination and epidemiology team. She has a good experience in coordinating data collecting in large sample and epidemiologic studies. She also has a large experience in working with epidemiology and control and preventive approach of vector-borne disease.

Última atualização: 04/12/2015