Variation in sensitivity of Trypanosoma congolense to diminazene during the early phase of tsetse-transmitted infection in goats

Twenty-five goats were randomly allocated to five groups of five animals each and infected with Trypanosoma congolense IL 3274 via the bites of infected Glossina morsitans centralis. At intervals of 1, 4, 8, 12 or 19 days following infection, each group of five animals was treated intramuscularly with diminazene aceturate at a dose of 7.0 mg kg-1 body weight (b.w.). While treatment on Day 1 eliminated infections in all five goats, treatment on Day 19 did not cure any of the animals; in groups treated 4, 8 or 12 days following infection, two of five goats in each group were cured. Since the alteration in apparent resistance of T. congolense IL 3274 between Day 1 and Day 19 could have been due to alteration in expression of drug resistance by trypanosomes as the population expanded, the experiment was repeated using trypanosomes that reappeared in the animals that had been treated with diminazene aceturate on Day 19. On Day 36, when all five animals were parasitaemic, five groups of teneral G. m. centralis, each containing 160 flies, were fed on one occasion on each of the five goats (one group of testse flies per goat). Thereafter, each group of tsetse flies was maintained on clean rabbits. When infective, five flies from each group were allowed to feed on two naive goats each (i.e. two goats per group of tsetse flies). One animal in each pair was treated 24 h after infection with diminazene aceturate at a dose of 7.0 mg kg-1 b.w., the other was treated on Day 19, when parasitaemic, with the same drug dosage. As before, treatment 24 h following infection eliminated infections in all animals, but when treatment was delayed until Day 19, trypanosomes in all animals were refractory to treatment. Thus, although tsetse flies were infected with trypanosomes that had arisen in infected goats following treatment with diminazene aceturate at a dose of 7.0 mg kg-1 b.w., when the same flies were allowed to feed on clean goats, the resultant infections were sensitive to treatment with the same drug dosage when administered 24 h following infection. These data therefore indicate that there is a significant alteration in diminazene sensitivity of IL 3274 between Day 1 and Day 19 and that this is associated with an alteration in the resistance phenotype of the trypanosomes.