Chronic Chagas’ heart disease – From pathogenesis to treatment regimes

Chagas’ disease, caused by Trypanosoma cruzi infection, was discovered nearly 100 years ago (1909) by the Brazilian physician Carlos Chagas. Chronic Chagas’ disease is still ranked as the most serious parasitic disease in Latin America. Infected patients remain lifelong parasite carriers. With a latency of 10 to 30 years, nearly one third of parasite carriers develop life-threatening complications: the majority develop Chagas’ heart disease (90%). Gastrointestinal disorders (megaesophagus, megacolon) and neuronal afflictions mainly affecting the parasympathetic nerve system were found in the others. Chagas’ heart disease presenting with sudden death, heart failure, malign cardiac arrhythmia, and thromboembolism is currently the major cause of morbidity and mortality in Latin America, enormously burdening economic resources and dramatically affecting patients’ social and employment situations. Chagas’ disease is starting to become a worldwide problem due to migration, international tourism and parasite transfer by blood contact, intrauterine transfer and organ transplantation. In this review, we reflect on the epidemiology and etiopathology of Chagas’ heart disease. We summarize the mechanisms that have been suggested to drive Chagas’ heart disease, mainly those based on autoimmunity phenomena. In this context, we focus on autoantibodies directed to G-protein coupled receptors. Following the autoimmunity story in chronic Chagas’ heart disease – and in addition to antiparasitic therapy, the treatment of heart failure, arrhythmia and thromboembolism and under study strategies such as heart transplantation and cell therapy – we describe regimes that use peptides and aptamers for autoantibody removal or neutralization. At present, such regimes are mostly proposed for beta-1-receptor autoantibodies in patients with dilated cardiomyopathy but, in principle, they can be adapted for patients with chronic Chagas’ heart disease who are positive for comparable autoantibodies.