Chronic Chagas’ heart disease: a disease on its way to becoming a worldwide health problem: epidemiology, etiopathology, treatment, pathogenesis and laboratory medicine

Abstract

Chagas' disease, caused by Trypanosoma cruzi infection, is ranked as the most serious parasitic disease in Latin America. Nearly 30% of infected patients develop life-threatening complications, and with a latency of 10-30 years, mostly Chagas' heart disease which is currently the major cause of morbidity and mortality in Latin America, enormously burdening economic resources and dramatically affecting patients' social and labor situations. Because of increasing migration, international tourism and parasite transfer by blood contact, intrauterine transfer and organ transplantation, Chagas' heart disease could potentially become a worldwide problem. To raise awareness of this problem, we reflect on the epidemiology and etiopathology of Chagas' disease, particularly Chagas' heart disease. To counteract Chagas' heart disease, in addition to the general interruption of the infection cycle and chemotherapeutic elimination of the infection agent, early and effective causal or symptomatic therapies would be indispensable. Prerequisites for this are improved knowledge of the pathogenesis and optimized patient management. From economic and logistics viewpoints, this last prerequisite should be performed using laboratory medicine tools. Consequently, we first summarize the mechanisms that have been suggested as driving Chagas' heart disease, mainly those associated with the presence of autoantibodies against G-protein-coupled receptors; secondly, we indicate new treatment strategies involving autoantibody apheresis and in vivo autoantibody neutralization; thirdly, we present laboratory medicine tools such as autoantibody estimation and heart marker measurement, proposed for diagnosis, risk assessment and patient guidance and lastly, we critically reflect upon the increase in inflammation and oxidative stress markers in Chagas' heart disease.

Receptor-activating autoantibodies and disease: preeclampsia and beyond

“…Chagas’ disease is an endemic parasitic disease of Latin American countries and is caused by infection with the flagellate protozoan, Trypanosoma cruzi [28]. Following a long latency period of 10–30 years, nearly 30% of infected individuals develop life-threatening cardiomyopathies associated with arrhythmias, heart failure and frequently sudden death.…”

“…At the cellular and subcellular levels, changes in the action potential duration and contractility of cardiomyocytes have been observed following the addition of autoantibodies [35]. Because of these experiments, Chagas’ heart disease is increasingly considered an autoimmune disease, where agonistic autoantibodies to GPCRs such as the β 1 -ARs, β 2 -ARs and M2-muscarinic receptors contribute to disease pathogenesis [28]. It has been shown for patients with DCM, and suggested for patients with Chagas’ cardiomyopathy, that removal of these pathogenic autoantibodies would yield significant clinical benefit.…”

Molecular imaging, biodistribution and efficacy of mesenchymal bone marrow cell therapy in a mouse model of Chagas disease

“…The disease then enters the chronic phase, generally starting with a long period of clinical latency called the indeterminate form. During the indeterminate form approximately 30% of infected individuals develop a symptomatic chronic phase, of which 10% display gastrointestinal diseases and 90% develop heart disease [8]; there is no consensus regarding the efficacy of anti-parasitic drugs benznidazole and nifurtimox during the chronic phase [9]. …”

Natural sesquiterpene lactones induce programmed cell death in Trypanosoma cruzi: A new therapeutic target?

“…Chagas disease or American Trypanosomiasis is caused by the flagellated protozoan parasite Trypanosoma cruzi (T. cruzi) and is recognized by the World Health Organization as one of the world's 17 neglected tropical diseases (Guhl and Ramirez 2013;Munoz-Saravia et al 2012;Schmunis 2007). It has been identified by the Center for Diseases Control in the U.S.A. as one of the five neglected diseases targeted for public health action (http://www.cdc.gov/parasites/npi.html).…”