FLUORESCENT DRUG SCREENING FOR THE EVALUATION OF BENZNIDAZOLE SUSCEPTIBILITY OF DIFFERENT Trypanosoma cruzi FIELD ISOLATES

ANDREA RAMOS; PAULA G RAGONE; NICOLÁS TOMASINI; MARÍA MERCEDES MONJE RUMI; PATRICIO DIOSQUE ; MIGUEL A. BASOMBRÍO; CECILIA PÉREZ BRANDÁN

Mar del Plata

Congreso; X Congreso de Protozoología y Enfermedades Parasitarias; 2014

Introduction: Chagas disease is one of the most serious public health problems in Latin America and is the clinical manifestation of the infection by Trypanosoma cruzi. Currently the drugs used to treat Chagas' disease are Benznidazole and Nifurtimox. Therapeutic failure of Benznidazole (BZN) has been widely documented in Chagas disease and has been mainly associated to variations in the drug susceptibility of T. cruzi strains. Objective: To evaluate the in vitro susceptibility to BZN of different T. cruzi genotypes from the Chaco region in Argentina. Materials and methods. 35 T. cruzi stocks from the Chaco region in Argentina, and belonging to the TcI, TcIII, TcV and TcVI Discrete Typing Units (DTUs) were selected to evaluate the in vitro susceptibility to BZN. In this first stage of the study, 5 TcI isolates were transfected with the plasmid pTrex-tdTomato in order to generate fluorescent lines to be analyzed in vitro with a fluorescent plate reader. As a preliminary step, the IC50 to BZN of epimastigotes was determined. Additionally, the in vitro susceptibility was correlated with genetic distances, biological and eco-epidemiologicalparameters. Results. The 5 TcI isolates examined were sensitive to BZN. The IC50 value of only one isolate showed to be slightly higher than the others. Correlations between the IC50 and genetic distances, biological and eco-epidemiological parameters do not predict differences in susceptibility to BZN. Conclusions. Taking into account that in the Chaco region inhabit a large number of eligible individuals to be treated, the evaluation of the susceptibility to benznidazole of the different T. cruzi genotypes circulating in this region is relevant. Further in vitro and in vivo studies involving the rest of the isolates are planned. This work is supported by Fundación Fiorini, CIUNSa and ANPCyT.