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|Obihiro University of Agriculture and Veterinary Medicine, Japan|
|ScientificTracks Abstracts: J Bacteriol Parasitol|
|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 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 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 mono chemotherapy.|
Ikuo Igarashi is currently a Professor at National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Japan and an OIE expert for equine piroplasmosis and bovine babsiosis. He has done researches on the in vitro cultivation of Babesia and Theileria and its application for drug screening. In addition, he is investigating the molecular mechanisms of invasion and multiplication of Babesia parasites in red blood cells and the development of highly specific and sensitive serological and molecular diagnostic assays. He has published more than 250 parasitology papers in peer-reviewed scientific journals, book chapters, and patents. He has been also serving as a member of the Editorial Advisory Board for Veterinary Parasitology since 2005 and an Academic Editor of PLoS ONE from 2012 to 2015. He is currently a Co-Editor-in-Chief for Veterinary Parasitology.
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