TcI, TcII and TcVI Trypanosoma cruzi samples from Chagas disease patients with distinct clinical forms and critical analysis of in vitro and in vivo behavior, response to treatment and infection evolution in murine model

Abstract

The clonal evolution of Trypanosoma cruzi sustains scientifically the hypothesis of association between parasite’s genetic, biological behavior and possibly the clinical aspects of Chagas disease in patients from whom they were isolated. This study intended to characterize a range of biological properties of TcI, TcII and TcVI T. cruzi samples in order to verify the existence of these associations. Several biological features were evaluated, including in vitro epimastigote-growth, “Vero”cells infectivity and growth, along with in vivo studies of parasitemia, polymorphism of trypomastigotes, cardiac inflammation, fibrosis and response to treatment by nifurtimox during the acute and chronic murine infection. The global results showed that the in vitro essays (acellular and cellular cultures) TcII parasites showed higher values for all parameters (growth and infectivity) than TcVI, followed by TcI. In vivo TcII parasites were more virulent and originated from patients with severe disease. Two TcII isolates from patients with severe pathology were virulent in mice, while the isolate from a patient with the indeterminate form of the disease caused mild infection. The only TcVI sample, which displayed low values in all parameters evaluated, was also originated of an indeterminate case of Chagas disease. Response to nifurtimox was not associated to parasite genetic and biology, as well as to clinical aspects of human disease. Although few number of T. cruzi samples have been analyzed, a discreet correlation between parasite genetics, biological behavior in vitro and in vivo (murine model) and the clinical form of human disease from whom the samples were isolated was verified.