The effect of isometamidium chloride on insect forms of drug-sensitive and drug-resistant stocks of Trypanosoma vivax: studies in vitro and in tsetse flies.

Isometamidium chloride-resistant and -sensitive Trypanosoma vivax insect forms were continuously propagated in vitro without feeder-layer cells in a semi-defined liquid medium at 27 degrees C. The effect of isometamidium chloride (Samorin) on T. vivax was assessed by monitoring the viability of epimastigotes and the production of metacyclic forms. Populations of insect forms of T. vivax stock IL 1392 and clone IL 3185 showed reduced growth and died after 10 days when cultivated in the presence of 1 ng/ml isometamidium chloride and after 6 days in the presence of 10 ng/ml. In contrast, populations of the isometamidium-resistant T. vivax stocks CP 2171 and CP 2331 continued to grow for 17 days in the presence of 1 ng/ml isometamidium chloride. The production of metacyclics was inhibited in cultures of T. vivax IL 1392 after incubation in medium containing 1 or 10 ng/ml isometamidium chloride. Epimastigotes of T. vivax CP 2171 and CP 2331 produced metacyclic forms in the presence of 1 ng/ml isometamidium chloride but not 10 ng/ml. When tsetse infected with drug-sensitive T. vivax IL 1392 were fed on a Boran steer that had previously been treated with 1 mg/kg isometamidium chloride, trypanosome infection rates were greatly reduced. In contrast, infection rates in Glossina morsitans centralis infected with drug-resistant T. vivax CP 2171 were not affected when these flies were fed on the same drug-treated animal.