-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

Public Health Relevance

- OVERALL Chagas disease remains one of the most neglected diseases in the world, with 5,7 million infected people and only one marginally effective therapeutic. 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. This proposal will focus on the discovery and validation of Chagas biomarkers.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI098461-08
Application #
9673655
Study Section
Special Emphasis Panel (ZAI1)
Program Officer
Rao, Malla R
Project Start
2012-08-01
Project End
2022-03-31
Budget Start
2019-04-01
Budget End
2020-03-31
Support Year
8
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Fundacao Faculdade de Medicina
Department
Type
DUNS #
902096528
City
Sao Paulo
State
Country
Brazil
Zip Code
05401-000
Chevillard, Christophe; Nunes, João Paulo Silva; Frade, Amanda Farage et al. (2018) Disease Tolerance and Pathogen Resistance Genes May Underlie Trypanosoma cruzi Persistence and Differential Progression to Chagas Disease Cardiomyopathy. Front Immunol 9:2791
Zrein, Maan; Granjon, Elodie; Gueyffier, Lucie et al. (2018) A novel antibody surrogate biomarker to monitor parasite persistence in Trypanosoma cruzi-infected patients. PLoS Negl Trop Dis 12:e0006226
Ferreira, Ludmila Rodrigues Pinto; Ferreira, Frederico Moraes; Nakaya, Helder Imoto et al. (2017) Blood Gene Signatures of Chagas Cardiomyopathy With or Without Ventricular Dysfunction. J Infect Dis 215:387-395
Capuani, Ligia; Bierrenbach, Ana Luiza; Pereira Alencar, Airlane et al. (2017) Mortality among blood donors seropositive and seronegative for Chagas disease (1996-2000) in São Paulo, Brazil: A death certificate linkage study. PLoS Negl Trop Dis 11:e0005542
Ferreira, Ariela Mota; Sabino, Ester Cerdeira; de Oliveira, Lea Campos et al. (2016) Benznidazole Use among Patients with Chronic Chagas' Cardiomyopathy in an Endemic Region of Brazil. PLoS One 11:e0165950
Cardoso, Clareci Silva; Sabino, Ester Cerdeira; Oliveira, Claudia Di Lorenzo et al. (2016) Longitudinal study of patients with chronic Chagas cardiomyopathy in Brazil (SaMi-Trop project): a cohort profile. BMJ Open 6:e011181
Keating, S M; Deng, X; Fernandes, F et al. (2015) Inflammatory and cardiac biomarkers are differentially expressed in clinical stages of Chagas disease. Int J Cardiol 199:451-9
Carmo, Andre A L; Rocha, Manoel O C; Silva, Jose L P et al. (2015) Amiodarone and Trypanosoma cruzi parasitemia in patients with Chagas disease. Int J Cardiol 189:182-4
Capuani, Ligia; Bierrenbach, Ana Luiza; Abreu, Fatima et al. (2014) Accuracy of a probabilistic record-linkage methodology used to track blood donors in the Mortality Information System database. Cad Saude Publica 30:1623-32