Ikuo Igarashi Obihiro
University of Agriculture and Veterinary Medicine, Japan
Title: Efficacy of combination chemotherapy with clofazimine and diminazene aceturate against Babesia and Theileria infections
Biography
Biography: Ikuo Igarashi Obihiro
Abstract
In the present study, we evaluated the growth-inhibitory effects of clofazimine, currently used for treating leprosy, against Babesia bovis, B. bigemina, B. caballi, and Theileria equi in vitro culture, and B. microti in mice. The IC50 values of clofazimine against the in vitro growth of B. bovis, B. bigemina, B. caballi, and T. equi were 4.5, 3, 4.3, and 0.29 μM, respectively. In mice infected with B. microti, treatment with oral administration of 20 mg/kg clofazimine resulted in a significant lower peak parasitemia (5.3%) as compared to a control group (45.9%), which was comparable to subcutaneous administration of 25 mg/kg diminazene aceturate. However, the growth of parasites was observed in mice after blood transfusions from clofazimine-treated mice on day 40 post-infection when parasites were not found in the blood smears. These results suggest that clofazimine has excellent inhibitory effects against Babesia and Theileria in vitro and in vivo, but it could not completely eliminate parasites in the host. Therefore, we evaluated the combination treatment with clofazimine and diminazene aceturate against piroplasms both in vitro and in vivo for the development of a novel chemotherapy with high efficacy and safety against animal piroplasmosis. The clofazimine-diminazene aceturate combination showed to have additive or synergistic effects on in vitro growths of Babesia bovis, B. bigemina, B. caballi, and Theileria equi. The lower dosages of clofazimine-diminazene aceturate combination showed to have a higher chemotherapeutic efficacy against B. microti in mice as compared to clofazimine or diminazene aceturate monotherapy. B. microti was not detected in blood, brain, spleen, and heart DNA samples by PCR from combination therapy on day 51 post infection. Furthermore, the parasite did not grow in blood-transfused mice from combination therapy groups. All results suggest that the clofazimine-diminazene aceturate combination chemotherapy will be a better choice to treat animal piroplasmosis instead of diminazene aceturate monochemotherapy.