The Epidemiology, Clinical Manifestations, and Management of Chagas Heart Disease

Abstract

Chagas disease results from infection by the protozoan parasite Trypanosoma cruzi and is endemic in Latin America. T cruzi is most commonly transmitted through the feces of an infected triatomine, but can also be congenital, via contaminated blood transfusion or through direct oral contact. In the acute phase, the disease can cause cardiac derangements such as myocarditis, conduction system abnormalities, and/or pericarditis. If left untreated, the disease advances to the chronic phase. Up to one‐half of these patients will develop a cardiomyopathy, which can lead to cardiac failure and/or ventricular arrhythmias, both of which are major causes of mortality. Diagnosis is confirmed by serologic testing for specific immunoglobulin G antibodies. Initial treatment consists of the antiparasitic agents benznidazole and nifurtimox. The treatment of Chagas cardiac disease comprises standard medical therapy for heart failure and amiodarone for ventricular arrhythmias, with consideration for implantable cardioverter‐defibrillator. Chagas disease causes the highest infectious burden of any parasitic disease in the Western Hemisphere, and increased awareness of this disease is essential to improve diagnosis, enhance management, and reduce spread.

Chagas Disease by Oral Transmission: Cardiovascular Manifestations

“…Once within host cells they reproduce, which leads to cell lysis and hematogenous dissemination. When triatomine vector ingesting T. cruzi from the blood of human host, the cycle is complete [2]. Chagas disease can also be transmitted by alternative mechanisms such as blood transfusion, organ transplants, and vertical transmission or by accidental contamination in a laboratory in persons handling tissue or the blood from infected animals.…”

“…In the acute phase of Chagas disease, cardiac involvement can occur in up to 90% of cases and after 6 to 9 weeks most patients show recovery of the clinical picture [2]. Following the acute phase, about 30% of patients directly enter the symptomatic chronic phase, but the majority of patients proceed to the indeterminate phase, when the infestation is only diagnosed by serological or parasitological tests; subclinical cardiac involvement may be demonstrated by imaging studies in some patients [6].…”

“…The exodus of Latin Americans to more developed countries, accounts for the estimates 100.000 or more chronically infected persons now living in the United States and Europe [2]. Despite sanitary measures that have reduced transmission rates through vector control and serological screening of blood donors, Chagas disease persist as a public health problem, observing a progressive increase in cases in the Amazon basin [4].…”

Hypoxia-activated cytotoxicity of benznidazole against clonogenic tumor cells

“…28,29 Although it had been studied for radiosensitization and chemosensitization, 26,27 it remains to be fully evaluated whether Benznidazole can directly kill tumor cells, especially those with clonogenic potentials. Because the cytotoxicity of Benznidazole against the parasitic protozoan Trypanosoma cruzi results from its emzymatic reduction, 24,25 we hypothesized that hypoxia may also lead to bioreduction of Benznidazole and formation of chemically reactive intermediates toxic to hypoxic tumor cells. Toward this end, we examined whether Benznidazole could specifically kill hypoxic cells using the clonogenicity assay for stringent assessment of clonogenic potentials.…”

“…Benznidazole is best known as a widely used drug to treat Chagas disease caused by the parasitic protozoan Trypanosoma cruzi. 24,25 It has also been investigated as a radiosensitizer or a chemosensitizer, 26,27 but its anti-cancer activities remain poorly understood. Our results have revealed a previously unrecognized anti-cancer function of Benznidazole with hypoxia-activated cytotoxic effects against clonogenic tumor cells.…”