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.

Figure 1

Proposed mechanisms of CHD pathogenesis. (i) Parasite-specific immunity may contribute to cardiac pathology due to destruction and displacement of myocytes leading to disruption of contractility and microvasculature. (ii) Parasite-induced myocytolysis occurs following differentiation of intracellular amastigotes into bloodform trypomastigotes and this may result in significant cardiac damage. (iii) Dysautonomia consisting of parasympathetic impairment and overactivation of sympathetic and neurohormonal pathways as reported in many cases of CHD may contribute to disease pathology. (iv) Microcirculatory malformations leading to ischemia, including occlusive platelet aggregations is speculated to contribute to cardiac pathology. (v) Non-specific damage caused by eosinophil granule components and (vi) antibody-mediated cytotoxicity may cause significant bystander injury to cardiomyocytes. (vii) A toxic hemolysin secreted by T. cruzi may cause a minor degree of myocytolysis. (viii) Parasite-induced autoimmunity generated by a number of different mechanisms including molecular mimicry and epitope spreading is thought to be a major contributor to CHD pathology.