Pathogenesis of Chronic Chagas Heart Disease

Abstract

Background-Chagas disease remains a significant public health issue and a major cause of morbidity and mortality in Latin America. Despite nearly 1 century of research, the pathogenesis of chronic Chagas cardiomyopathy is incompletely understood, the most intriguing challenge of which is the complex host-parasite interaction. Methods and Results-A systematic review of the literature found in MEDLINE, EMBASE, BIREME, LILACS, and SCIELO was performed to search for relevant references on pathogenesis and pathophysiology of Chagas disease. Evidence from studies in animal models and in anima nobile points to 4 main pathogenetic mechanisms to explain the development of chronic Chagas heart disease: autonomic nervous system derangements, microvascular disturbances, parasite-dependent myocardial aggression, and immune-mediated myocardial injury. Despite its prominent peculiarities, the role of autonomic derangements and microcirculatory disturbances is probably ancillary among causes of chronic myocardial damage. The pathogenesis of chronic Chagas heart disease is dependent on a low-grade but incessant systemic infection with documented immune-adverse reaction. Parasite persistence and immunological mechanisms are inextricably related in the myocardial aggression in the chronic phase of Chagas heart disease. Conclusions-Most clinical studies have been performed in very small number of patients. Future research should explore the clinical potential implications and therapeutic opportunities of these 2 fundamental underlying pathogenetic mechanisms.

Ergosterol biosynthesis and drug development for Chagas disease

“…However, more recent studies using more sensitive methodologies have shown clear correlations between the presence of the parasite and the inflammatory processes that underlie the pathological processes associated with chronic Chagas disease (Tarleton et al 1997, Tarleton & Zhang 1999, Tarleton 2001, Marin-Neto et al 2007). This fact, coupled with the finding that T. cruzi-specific CD8+ and CD4+ T cells, are consistently associated with inflammatory infiltrates rich in Th1 cytokines, has led to the notion that parasite persistence is a necessary and sufficient condition to generate and sustain a Th1-biased inflammatory response in infected tissues, which may include autoimmune phenomena (Tarleton et al 1997, Tarleton & Zhang 1999, Tarleton 2001, Marin-Neto et al 2007.…”

“…This fact, coupled with the finding that T. cruzi-specific CD8+ and CD4+ T cells, are consistently associated with inflammatory infiltrates rich in Th1 cytokines, has led to the notion that parasite persistence is a necessary and sufficient condition to generate and sustain a Th1-biased inflammatory response in infected tissues, which may include autoimmune phenomena (Tarleton et al 1997, Tarleton & Zhang 1999, Tarleton 2001, Marin-Neto et al 2007.…”

ELISA seroprevalence of Trypanosoma cruzi in a cohort of heart disease patients

“…It has been estimated that approximately 30% of infected persons evolve toward the chronic phase, which may include pathological involvement/damage to the heart, esophagus and/or colon [11]. Cardiac damage is the most severe and frequent outcome [10].…”

Seroprevalencia de la infección por Trypanosoma cruzi en Canis familiaris del estado Sucre, Venezuela

“…Las principales formas de transmisión de la enfermedad de Chagas son vectorial, transfusional y congénita, así como otras (oral, trasplantes, accidentes en laboratorios) (6,7). La vía más importante de transmisión y mantenimiento de la endemia chagásica se asocia con la pobreza y ocurre en viviendas con condiciones precarias, tanto en áreas rurales como en periurbanas, en las cuales abundan las colonias de triatominos asociadas con reservorios domésticos y peridomésticos que sirven como fuente de alimentación (8).…”