Towards a Paradigm Shift in the Treatment of Chronic Chagas Disease

Abstract

Treatment for Chagas disease with currently available medications is recommended universally only for acute cases (all ages) and for children up to 14 years old. The World Health Organization, however, also recommends specific antiparasite treatment for all chronic-phase Trypanosoma cruzi-infected individuals, even though in current medical practice this remains controversial, and most physicians only prescribe palliative treatment for adult Chagas patients with dilated cardiomyopathy. The present opinion, prepared by members of the NHEPACHA network (Nuevas Herramientas para el Diagnóstico y la Evaluación del Paciente con Enfermedad de Chagas/New Tools for the Diagnosis and Evaluation of Chagas Disease Patients), reviews the paradigm shift based on clinical and immunological evidence and argues in favor of antiparasitic treatment for all chronic patients. We review the tools needed to monitor therapeutic efficacy and the potential criteria for evaluation of treatment efficacy beyond parasitological cure. Etiological treatment should now be mandatory for all adult chronic Chagas disease patients.

CD73 Inhibition Shifts Cardiac Macrophage Polarization toward a Microbicidal Phenotype and Ameliorates the Outcome of Experimental Chagas Cardiomyopathy

“…Innate and adaptive immune responses control the parasite levels, but are insufficient to completely clear the infection, and most individuals remain infected for life. The myocardial parasite persistence is central for the etiology of the cardiomyopathy (2,3). Although, it has been recognized that host resistance to T. cruzi infection is exerted mainly by cell-mediated reactions involving specific T lymphocytes and macrophages (Ma) (4), the mechanisms by which the Ma-protective response fails to eliminate the parasite are not well understood.…”

Trypanosoma cruzi I genotype among isolates from patients with chronic Chagas disease followed at the Evandro Chagas National Institute of Infectious Diseases (FIOCRUZ, Brazil)

“…Routine T. cruzi genotyping can be feasible at medical centers with scientific research support, since presently, there are several available molecular techniques for its characterization 8,14,17,72 , and the classical MLEE analysis can reveal the main genetic groups, mixed stocks, and other trypanosome species 14,25,[30][31][32][33] . Despite some controversies and exceptions, nowadays there are recommendations for treating all patients with chronic Chagas disease using new dosing strategies and drug combinations for preventing side effects, thus increasing the chances of treatment completion and monitoring of patients for a longer time [73][74][75] . Identification of the T. cruzi genotype in samples from patients is also important to better understand the possible influence of the parasite type on the clinical manifestations of the human Chagas disease, as it seems to occur in individuals infected with TcI, who rarely present digestive forms.…”

Drugs for the etiologic treatment of Chagas disease: Myths and Truths

“…In contrast to this old paradigm, specific antiparasite treatment for all chronic-phase Trypanosoma cruzi-infected individuals is mandatory. 5 There is an important body of evidence that strongly suggests the involvement of parasitic presence in the disease progression toward cardiomyopathy. 6,7,8 …”