Correlation of TcII discrete typing units with severe chronic Chagas cardiomyopathy in patients from various Brazilian geographic regions

Author(s)

de Oliveira, Maykon Tavares ; Fuzo, Carlos Alessandro ; da Silva, Maria Claudia ; Donadi, Eduardo Antonio ; da Silva, Joao Santana ; Moreira, Henrique Turin ; Schmidt, Andre ; Marin-Neto, Jose Antonio

• Document type: Journal article
• Source: PLoS Neglected Tropical Diseases; v. 16, n. 12, p. 13-pg., 2022-12-01.

Abstract

Background Chagas disease (ChD) is caused by Trypanosoma cruzi. The genetic structure of the species is divided into seven distinct genetic groups, TcI to TcVI, and Tcbat, which have shown differences in terms of geographic distribution, biological properties, and susceptibility to drugs. However, the association between genetic variability and clinical forms of ChD has not yet been fully elucidated. The predominance of TcII and TcVI discrete typing units (DTUs) (genetic groups) is known to occur in several Brazilian regions and is associated with both the domestic and the wild cycles of ChD. Thus, this study aimed to verify the genotypes of the parasites present in 330 patients with chronic Chagas cardiomyopathy (CCC) from different Brazilian states attended at the Clinical Hospital of the Ribeirao Preto Medical School and to assess the existence of a correlation between the clinical forms with the main cardiovascular risk factors and the genetics of the parasite. Methodology Principal findings All patients with CCC were clinically evaluated through anamnesis, physical examination, biochemical tests, 12-lead electrocardiogram, echocardiogram and chest X-ray. Peripheral blood (5 mL) was collected in guanidine/ethylenediaminetetraacetic acid from each patient for DNA extraction and real-time polymerase chain reaction (PCR) for Chagas disease and genotyping of the parasite in the 7 DTUs. Parasite genotyping was performed using conventional multilocus PCR. Samples of only 175 patients were positive after amplification of the specific genes contained in the T. cruzi genotyping criteria. TcII (64/175), TcVI (9/175), and TcI (3/175) DTUs were predominant, followed by TcII/TcV/TcVI (74/175), and TcII/TcVI (23/ 175). The TcIII and TcIV DTU ' s was detected in only one sample of CCC patients. Conclusions/Significance Our data corroborate previous findings, indicating the predominance of the TcII genotype in patients with CCC of Brazilian origin. Moreover, this study pioneered disclosing a direct correlation between the TcII DTU and severe CCC. Author summary Trypanosoma cruzi is divided into seven distinct genetic groups (TcI-TcVI) and TcBat. They may be related to several biological parameters, however, the correlation with the clinical forms is not well established. Thus, the work has the important function of identifying the genetic variability of T. cruzi circulating in different regions of Brazil, and trying to correlate the genetics of the parasite with the clinical manifestations presented by the patients. In this work, we showed differences in the prevalence between infectious DTU's (genetic groups), and we were able to identify and describe the correlation between TcII DTU and severe chronic Chagas cardiomyopathy (LVEF < 40%). The information generated in this study should impact the planning of more effective public health interventions to improve the health of chagasic patients, control vertical transmission and the treatment of CD in endemic countries. (AU)

• FAPESP's process: 16/25403-9 - Investigations on the pathogenesis, pathophysiology and therapy in humans and in an experimental model with the chronic cardiomyopathy of Chagas Disease
• Grantee: José Antonio Marin-Neto
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/22093-4 - "Genotyping of Trypanosoma cruzi in samples from patients with Chronic Chagas' Heart Disease''
• Grantee: Maykon Tavares de Oliveira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral