Benznidazole, itraconazole and their combination in the treatment of acute experimental chagas disease in dogs.

Abstract

Chagas disease (CD) is a serious public health problem in Latin America and its treatment remains neglected. Benznidazole (BZ), the only drug available in Brazil, presents serious side effects and low therapeutic efficacy, especially at the chronic phase. The last clinical trials demonstrated that the first generation of azole compounds were less successful than BZ in CD chemotherapy, which stimulated studies of these compounds associated to BZ and nifurtimox (NF). This study evaluated the therapeutic efficacy of BZ, itraconazole (ITZ) and their combination (BZ + ITZ) in dogs infected with the VL-10 T. cruzi strain in the acute phase of the disease. Twenty young mongrel dogs were inoculated with 2.0 × 103 blood trypomastigotes/kg and divided into four groups: treated with BZ, ITZ and BZ + ITZ for 60 days, and control group (INT). The parasitemia of the BZ + ITZ and BZ groups were similar and showed significant reduction compared to the INT group. The group treated with ITZ also showed significant parasitemia reduction compared to the INT group. The global analysis of hemoculture (HC), blood PCR, conventional serology (CS-ELISA), heart qPCR and histopathology techniques, used in the post-treatment evaluation, revealed that BZ + ITZ combination lead to a more reduction of parasitemia during the acute phase and heart qPCR positivity, less cardiac damage (inflammation and fibrosis in the left ventricle) and total survival. According to the classical cure criteria one animal treated with BZ + ITZ can be considered cured in its final evaluation and two other dogs, one of this group and one treated with ITZ were in process of cure. At least for BZ-resistant T. cruzi strains such as VL-10, BZ + ITZ was not effective to induce parasitological cure or a profound and sustained reduction of the parasite burden in blood and infected organs.