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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) available in Brazil, presents serious side effects and low therapeutic efficacy at chronic phase. This study evaluated the therapeutic efficacy of BZ, itraconazole (ITZ) and BZ?+?ITZ in dogs infected with VL-10?T. cruzi strain in the acute phase (Ethic protocol number 2013/28). 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-infected not treated). The parasitemia of the BZ?+?ITZ and BZ groups were similar and showed significant reduction compared to the INT group. The ITZ group also showed significant parasitemia reduction compared to the INT group. For cure control the global analysis of hemoculture (HC), blood PCR, conventional serology (CS-ELISA), heart qPCR and histopathology revealed that BZ?+?ITZ lead to more reduction of parasitemia during the acute phase and heart qPCR positivity, less cardiac damage and total survival than BZ or ITZ. Moreover, two other dogs, one treated with ITZ and other treated with BZ?+?ITZ, were always negative in all parasitological tests what indicates parasitological cure or that these dogs are in process of cure. •BZ?+?ITZ lead to more reduction of parasitemia, total survival, less heart qPCR positivity and cardiac damage.•According to the classic cure criterion cure was observed only in one dog submitted to BZ?+?ITZ treatment.•Two dogs, one treated with ITZ and other treated with BZ?+?ITZ were always parasitologically negative.

SUBMITTER: Cunha ELA

PROVIDER: S-EPMC6939041 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Cunha Eleonora Lima Alves ELA Torchelsen Fernanda Karoline Vieira da Silva FKVDS Cunha Lucas Maciel LM Oliveira Maykon Tavares MT Reis Levi Eduardo Soares LES Fonseca Kátia da Silva KDS Vieira Paula Melo Abreu PMA Carneiro Cláudia Martins CM Lana Marta M

MethodsX 20191021

Chagas disease (CD) is a serious public health problem in Latin America and its treatment remains neglected. Benznidazole (BZ) available in Brazil, presents serious side effects and low therapeutic efficacy at chronic phase. This study evaluated the therapeutic efficacy of BZ, itraconazole (ITZ) and BZ + ITZ in dogs infected with VL-10 T. cruzi strain in the acute phase (Ethic protocol number 2013/28). Twenty young mongrel dogs were inoculated with 2.0 × 10<sup>3</sup> blood trypomastigotes/kg a ...[more]

PMID: 31908981

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Project description:BackgroundCurrent chemotherapy for Chagas disease is unsatisfactory due to its limited efficacy, particularly in the chronic phase, with frequent side effects that can lead to treatment discontinuation. Combined therapy is envisioned as an ideal approach since it may improve treatment efficacy whilst decreasing toxicity and the likelihood of resistance development. We evaluated the efficacy of posaconazole in combination with benznidazole on Trypanosoma cruzi infection in vivo.Methods and findingsBenznidazole and posaconazole were administered individually or in combination in an experimental acute murine infection model. Using a rapid treatment protocol for 7 days, the combined treatments were more efficacious in reducing parasitemia levels than the drugs given alone, with the effects most evident in combinations of sub-optimal doses of the drugs. Subsequently, the curative action of these drug combinations was investigated, using the same infection model and 25, 50, 75 or 100 mg/kg/day (mpk) of benznidazole in combination with 5, 10 or 20 mpk of posaconazole, given alone or concomitantly for 20 days. The effects of the combination treatments on parasitological cures were higher than the sum of such effects when the drugs were administered separately at the same doses, indicating synergistic activity. Finally, sequential therapy experiments were carried out with benznidazole or posaconazole over a short interval (10 days), followed by the second drug administered for the same period of time. It was found that the sequence of benznidazole (100 mpk) followed by posaconazole (20 mpk) provided cure rates comparable to those obtained with the full (20 days) treatments with either drug alone, and no cure was observed for the short treatments with drugs given alone.ConclusionsOur data demonstrate the importance of investigating the potential beneficial effects of combination treatments with marketed compounds, and showed that combinations of benznidazole with posaconazole have a positive interaction in murine models of Chagas disease.

Dataset Information

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

Publications

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

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