title: Clofazimine Inhibits the Growth of Babesia and Theileria Parasites In Vitro and In Vivo.
abstract: The present study evaluated the growth-inhibitory effects of clofazimine, currently used for treating leprosy, against Babesia bovis, B. bigemina, B. caballi, and Theileria equi in in vitro culture and against Babesia microti in mice. The 50% inhibitory concentrations (IC50s) 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 20 mg/kg of body weight of clofazimine administered orally resulted in a significantly lower peak parasitemia (5.3%) than that in the control group (45.9%), which was comparable to the subcutaneous administration of 25 mg/kg diminazene aceturate, the most widely used treatment for animal piroplasmosis. Although slight anemia was observed in both clofazimine- and diminazene aceturate-treated infected mice, the level and duration of anemia were lower and shorter, respectively, than those in untreated infected mice. Using blood transfusions and PCR, we also examined whether clofazimine completely killed B. microti On day 40 postinfection, when blood analysis was performed, parasites were not found in blood smears; however, the DNA of B. microti was detected in the blood of clofazimine-treated animals and in several tissues of clofazimine- and diminazene aceturate-treated mice by PCR. The growth of parasites was observed in mice after blood transfusions from clofazimine-treated mice. In conclusion, clofazimine showed excellent inhibitory effects against Babesia and Theileria in vitro and in vivo, and further study on clofazimine is required for the future development of a novel chemotherapy with high efficacy and safety against animal piroplasmosis and, possibly, human babesiosis.
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan Laboratory of Molecular Genetics, Institute of Veterinary Medicine, Ulaanbaatar, Mongolia.
authors.forename: Bumduuren
authors.initials: B
authors.lastname: Tuvshintulga
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan Department of Parasitology, Faculty of Veterinary Medicine, University of Sadat City, Sadat City, Menoufiya, Egypt.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: AbouLaila
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan Laboratory of Molecular Genetics, Institute of Veterinary Medicine, Ulaanbaatar, Mongolia.
authors.forename: Batdorj
authors.initials: B
authors.lastname: Davaasuren
authors.affiliation: Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Ishiyama
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan.
authors.forename: Thillaiampalam
authors.initials: T
authors.lastname: Sivakumar
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan.
authors.forename: Naoaki
authors.initials: N
authors.lastname: Yokoyama
authors.affiliation: Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Iwatsuki
authors.affiliation: Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Otoguro
authors.affiliation: Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ōmura
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan igarcpmi@obihiro.ac.jp.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Igarashi
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D001403:Babesia / Q000187:drug effects* / Q000472:pathogenicity*; D002991:Clofazimine / Q000627:therapeutic use*; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D010963:Plasmodium falciparum / Q000187:drug effects / Q000472:pathogenicity; D016133:Polymerase Chain Reaction; D016794:Theileria / Q000187:drug effects* / Q000472:pathogenicity*
chemical_list: D000962:Antimalarials; D002991:Clofazimine