title: Efficacy of atovaquone against Babesia gibsoni in vivo and in vitro.
abstract: The therapeutic efficacy of atovaquone against Babesia gibsoni was examined in three dogs experimentally infected with B. gibsoni isolated from naturally infected dogs in Aomori Prefecture, Japan. Once parasitemia reached 10%, atovaquone was administered orally (30 mg/kg twice daily for 7 days). Within 2 days of atovaquone treatment, the parasite disappeared from blood smears without any clinical side effects. Anemia and thrombocytopenia were significantly improved in all the dogs. However, a polymerase chain reaction assay revealed that a B. gibsoni marker gene was intermittently present in peripheral blood after atovaquone therapy, indicating that the organism had not been eliminated, and parasites reappeared in blood smears 33 days after the last treatment. To investigate the change in sensitivity against atovaquone, an in vitro sensitivity test was performed using peripheral blood obtained from an untreated dog that was infected with the original parasite isolate, and from two of the experimentally infected and atovaquone-treated animals (blood was collected at the time of the post-treatment recurrence of the B. gibsoni infection). Atovaquone was added to the culture medium to final concentrations of 0.1, 1, 10, 100, and 1000 nM. For the untreated parasites, complete growth inhibition occurred at 1000 nM of atovaquone, whereas the recurrent parasites were inhibited by only 39.52 +/- 8.34% and 31.31 +/- 8.14% at this concentration after 48 h of incubation. Thus, the recurring parasites were less sensitive to atovaquone than the untreated originally isolated parasites.
authors.affiliation: Department of Small Animal Medicine, School of Veterinary Medicine and Animal Sciences, Kitasato University, Towada, Aomori 034-8628, Japan. matsuu@vmas.kitasato-u.ac.jp
authors.forename: Aya
authors.initials: A
authors.lastname: Matsuu
authors.forename: Yushi
authors.initials: Y
authors.lastname: Koshida
authors.forename: Megumi
authors.initials: M
authors.lastname: Kawahara
authors.forename: Kenichi
authors.initials: K
authors.lastname: Inoue
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ikadai
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Hikasa
authors.forename: Shozo
authors.initials: S
authors.lastname: Okano
authors.forename: Seiichi
authors.initials: S
authors.lastname: Higuchi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D053626:Atovaquone; D001403:Babesia / Q000187:drug effects*; D001404:Babesiosis / Q000188:drug therapy / Q000662:veterinary*; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D009285:Naphthoquinones / Q000494:pharmacology / Q000627:therapeutic use*; D021261:Parasitic Sensitivity Tests / Q000662:veterinary; D013921:Thrombocytopenia / Q000469:parasitology / Q000662:veterinary; D016896:Treatment Outcome
chemical_list: D000981:Antiprotozoal Agents; D009285:Naphthoquinones; D053626:Atovaquone