TcI, TcII and TcVI Trypanosoma cruzi samples from Chagas diseasepatients with distinct clinical forms and critical analysis of in vitro andin vivo behavior, response to treatment and infection evolution inmurine model.

Abstract

tThe clonal evolution of Trypanosoma cruzi sustains scientifically the hypothesis of association betweenparasite’s genetic, biological behavior and possibly the clinical aspects of Chagas disease in patientsfrom whom they were isolated. This study intended to characterize a range of biological properties ofTcI, TcII and TcVI T. cruzi samples in order to verify the existence of these associations. Several biologicalfeatures were evaluated, including in vitro epimastigote-growth, “Vero”cells infectivity and growth, alongwith in vivo studies of parasitemia, polymorphism of trypomastigotes, cardiac inflammation, fibrosis andresponse to treatment by nifurtimox during the acute and chronic murine infection. The global resultsshowed that the in vitro essays (acellular and cellular cultures) TcII parasites showed higher values for allparameters (growth and infectivity) than TcVI, followed by TcI. In vivo TcII parasites were more virulentand originated from patients with severe disease. Two TcII isolates from patients with severe pathologywere virulent in mice, while the isolate from a patient with the indeterminate form of the disease causedmild infection. The only TcVI sample, which displayed low values in all parameters evaluated, was alsooriginated of an indeterminate case of Chagas disease. Response to nifurtimox was not associated toparasite 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 behaviorin vitro and in vivo (murine model) and the clinical form of human disease from whom the samples wereisolated was verified.