Anticoccidial activity of an azauracil derivative

Abstract

A substituted azauracil derivative has been shown to have marked anticoccidial activity. Chickens given large challenge doses of Eimeria tenella were protected from mortality by a dietary level of 0·25 ppm drug, while oocyst output was controlled by 10 ppm. Under conditions of continuous medication using 15 ppm of the azauracil derivative the development of E. tenella was arrested at the multinucleate first generation schizont stage; in the majority of parasites merozoite differentiation was inhibited. Experiments using restricted medication indicated that, with E. tenella in the chick, the drug was coccidiocidal rather than coccidiostatic, and that treatment for as little as one day could control the infection. Medication started during the second asexual cycle again resulted in inhibition at the multinucleate schizont stage just before merozoite differentiation. Mortality in birds inoculated with E. brunetti was controlled by 1 ppm azauracil in the diet and oocyst output by 2.5 ppm; unlike the situation with E. tenella, the drug had no influence on the first two asexual cycles of reproduction. There was some inhibition of the third schizogony cycle, but the main effect of the drug in the case of E. brunetti was found to be against sexual reproduction. Effects similar to those noted in vivo were seen with E. tenella and E. brunetti growing in tissue culture. Occasional schizonts of E. tenella under the influence of drug were able to produce a peripheral array of merozoites surrounding a multinucleate residual mass. In contrast to the situation in vivo, with drawal of drug from tissue cultures infected with E. tenella allowed the further development of some inhibited parasites. E. necatrix responded to the azauracil derivative in a manner similar to E. tenella.