Stage-specific activity in vitro on the Theileria infection process of serum from calves treated prophylactically with buparvaquone

An in vitro method for testing activity of buparvaquone in serum on the inf ection and development of Theileria in its bovine host mononuclear cells is described and results compared with the effect exhibited in vivo. Serum sa mples 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 expe rimental 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 s era were tested on established macroschizont infected cell lines and agains t the in vitro infection and development process of the sporozoite and trop hozoite stages of the two Theileria species. Results from the in vitro assays show that buparvaquone in serum can comple tely prevent the establishment of Theileria infection during the first 48 h after administration at 5 mg kg(-1). After seven days, levels are sufficie nt to delay the establishment of infection. The drug is more effective in t he prevention of the de novo development of the parasite in cells than agai nst established macroschizont infected cell culture. At low concentrations, it is more effective against T. parva than against T. annulata. Drug effec t peaks during the first 24 h but residual effect persists for 14 days, par ticularly 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 immunisat ion when drug is administered prophylactically at the same time as infectio n with live sporozoites. It is suggested that in certain high Theileria ris k situations there may be potential for the immunoprophylactic use of bupar vaquone without simultaneous infection. The in vitro assay itself has been shown to be of value as a model for Theileria establishment in cattle. (C) 1998 Elsevier Science B.V. All rights reserved.