Differential tissue distribution of discrete typing units after drug combination therapy in experimental Trypanosoma cruzi mixed infection

STRAUSS, MARIANA; LO PRESTI, M. SILVINA; RAMÍREZ, JUAN C.; BAZÁN, P. CAROLINA; VELÁZQUEZ LÓPEZ, DANIELA A.; BÁEZ, ALEJANDRA L.; PAGLINI, PATRICIA A.; SCHIJMAN, ALEJANDRO G.; RIVAROLA, HÉCTOR W.

PARASITOLOGY

CAMBRIDGE UNIV PRESS

Año: 2021 vol. 148 p. 1595 - 1601

0031-1820

The aim of the present work was to evaluate the distribution of the different clones of theparasite prevailing after treatment with benznidazole (BZ) and clomipramine (CLO), inmice infected with Trypanosoma cruzi, Casibla isolate which consists of a mixture of two discretetyping units (DTUs). Albino Swiss mice were infected and treated with high and lowconcentrations of BZ (100 or 6.25 mg/kg), CLO (5 or 1.25 mg/kg), or the combination ofboth low doses (BZ6.25 + CLO1.25), during the acute phase of experimental infection.Treatment efficacy was evaluated by comparing parasitaemia, survival and tissular parasitepresence. For DTUs genotyping, blood, skeletal and cardiac muscle samples were analysedby multiplex quantitative polymerase chain reaction. The combined treatment had similaroutcomes to BZ6.25; BZ100 was the most effective treatment, but it failed to reach parasiteclearance and produced greater histological alterations. Non-treated mice and the ones treatedwith monotherapies showed both DTUs while BZ6.25 + CLO1.25 treated mice showed onlyTcVI parasites in all the tissues studied. These findings suggest that the treatment may modifythe distribution of infecting DTUs in host tissues. Coinfection with T. cruzi clones belongingto different DTUs reveals a complex scenario for the treatment of Chagas disease and searchfor new therapies.