title: Stage-specific activity in vitro on the Theileria infection process of serum from calves treated prophylactically with buparvaquone.
abstract: An in vitro method for testing activity of buparvaquone in serum on the infection and development of Theileria in its bovine host mononuclear cells is described and results compared with the effect exhibited in vivo. Serum samples were collected over a time course from calves in a clinical trial of 5 mg kg(-1) buparvaquone prophylaxis on Theileria annulata or T. parva experimental infection. To evaluate drug levels and persistence in each animal for a period of 14 days and its effect on the early infection stages, the sera were tested on established macroschizont infected cell lines and against the in vitro infection and development process of the sporozoite and trophozoite stages of the two Theileria species. Results from the in vitro assays show that buparvaquone in serum can completely prevent the establishment of Theileria infection during the first 48 h after administration at 5 mg kg(-1). After seven days, levels are sufficient to delay the establishment of infection. The drug is more effective in the prevention of the de novo development of the parasite in cells than against established macroschizont infected cell culture. At low concentrations, it is more effective against T. parva than against T. annulata. Drug effect peaks during the first 24 h but residual effect persists for 14 days, particularly against T. parva infection. These novel findings demonstrate how high doses of buparvaquone could over-protect calves if used in the 'infection-and-treatment' method of immunisation when drug is administered prophylactically at the same time as infection with live sporozoites. It is suggested that in certain high Theileria risk situations there may be potential for the immunoprophylactic use of buparvaquone without simultaneous infection. The in vitro assay itself has been shown to be of value as a model for Theileria establishment in cattle.
authors.affiliation: Centre for Tropical Veterinary Medicine, R(D)SVS, The University of Edinburgh, Scotland, UK. gwilkie@lab0.ed.ac.uk
authors.forename: G M
authors.initials: GM
authors.lastname: Wilkie
authors.forename: E
authors.initials: E
authors.lastname: Kirvar
authors.forename: E M
authors.initials: EM
authors.lastname: Thomas
authors.forename: O
authors.initials: O
authors.lastname: Sparagano
authors.forename: C G
authors.initials: CG
authors.lastname: Brown
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001681:Biological Assay / Q000662:veterinary; D002417:Cattle; D002460:Cell Line; D009285:Naphthoquinones / Q000494:pharmacology* / Q000627:therapeutic use; D016796:Theileria annulata / Q000187:drug effects / Q000254:growth & development*; D016797:Theileria parva / Q000187:drug effects / Q000254:growth & development*; D013801:Theileriasis / Q000188:drug therapy / Q000517:prevention & control*; D013997:Time Factors
chemical_list: D000981:Antiprotozoal Agents; D009285:Naphthoquinones; C046326:buparvaquone