Chagas Heart Disease Pathogenesis: One Mechanism or Many?

Abstract

Chagas heart disease (CHD), caused by the protozoan parasite Trypanosoma cruzi, is the leading cause of infectious myocarditis in the world. The etiology of CHD is unclear and multiple mechanisms have been proposed to explain the pathogenesis of the disease. This review describes the proposed mechanisms of CHD pathogenesis and evaluates the historical significance and evidence supporting each. Although the majority of CHD-related pathologies are currently attributed to parasite persistence in the myocardium and autoimmunity, there is strong evidence that CHD develops as a result of additive and even synergistic effects of several distinct mechanisms rather than one factor.

Humoral Immune Response against P2β from Trypanosoma cruzi in Persons with Chronic Chagas Disease: Its Relationship with Treatment Against Parasites and Myocardial Damage

“…Several lines of evidence implicate that parasite strains and persistence, genetic and nutritional features of patients, and the quality of the immune response are involved in the establishment of CCC. [31][32][33] Results of our longitudinal study do not lend support to the assessment of antibodies to P2β as a surrogate marker of progression from indeterminate disease to heart disease. However, a slight but statistically significant trend to increased antibody reactivity to P2β was seen in patients with evolving CCC.…”

Chagas heart disease: pathophysiologic mechanisms, prognostic factors and risk stratification

“…Numerous contributing mechanisms have been suggested to explain the pathogenesis of CHD (MarinNeto et al 2007). A consensus is now emerging that parasite persistence and the parasite-driven immune response play a pivotal role (Tarleton 2003a, b, Kierszenbaum 2007, Bonney & Engman 2008. In contrast, whether one or more of the autoimmune events described in experimental models and human cases of Chagas disease can contribute to, or aggravate, this pathology, has been more controversial and difficult to validate (Tarleton 2003a, b).…”

“…The release of intracellularly replicated trypanosomes followed by parasite-driven myocyte necrosis and inflammation not only contributes decisively to pathogenesis, but may also trigger additional mechanisms of cardiac damage (Bonney & Engman 2008). Several coronary microvascular abnormalities, including increased platelet activity, microthrombi, microvascular spasm and endothelial dysfunction have been reported in animal models (Rossi 1990) and in some studies in humans (Marin-Neto et al 1992, Simões et al 2000.…”

I Diretriz Latino-Americana para o Diagnóstico e Tratamento da Cardiopatia Chagásica

“…Several mechanisms contribute to the pathogenesis of the cardiac lesions and consequent installation of the pathophysiological disorders, according to recent reviews [24][25][26][27][28] .…”