FREQUENCY OF DIMINAZENE-RESISTANT TRYPANOSOMES IN POPULATIONS OF TRYPANOSOMA-CONGOLENSE ARISING IN INFECTED ANIMALS FOLLOWING TREATMENT WITH DIMINAZENE ACETURATE

The frequency of trypanosomes resistant to diminazene aceturate at a d ose of 25 mg/kg of body weight was investigated for populations of Try panosoma congolense IL 3274 which reappeared in infected mice after in traperitoneal treatment with diminazene aceturate at the same dosage. At inoculum sizes of 10(2), 10(3), 10(4), 10(5), and 10(6) trypanosome s per mouse, the relapse populations were used to initiate infections in five groups of 100 mice each by the intravenous route. Immediately after infection, 50 mice in each group were treated intraperitoneally with diminazene aceturate at the aforementioned dosage; the other 50 m ice functioned as untreated controls. Thereafter, all animals were mon itored for 100 days for the presence of trypanosomes. In each group, t rypanosomes were detected in 50 of 50 control mice, indicating 100% in fectivity for all five inoculum sizes. In contrast, in the groups of 5 0 mice infected with 10(2), 10(3), 10(4), 10(5), and 10(6) trypanosome s and treated with diminazene aceturate, trypanosomes were detected in 4, 11, 13, 28, and 39 of 50 mice, respectively. By logistic regressio n, a good fit was found between the number of mice identified as paras itemic and the inoculum sizes. Maximum likelihood estimates for the pr oportions of trypanosomes resistant to diminazene aceturate at 25 mg/k g of body weight for the inoculum of 10(2), 10(3), 10(4), 10(5), and 1 0(6) organisms were 8.335 x 10(-4), 2.485 x 10(-4), 3.02 x 10(-5), 8.3 x 10(-6), and 1.6 x 10(-6), respectively. These findings indicate tha t the majority of the relapse trypanosomes were susceptible to the dru g dosage used for selecting the population and that, surprisingly, the calculated proportion of organisms which survived drug exposure varie d inversely with the inoculum size, Further experiments with mice indi cated that the inverse relationship did not result from alterations in the pharmacokinetics of the drug with different inoculum sizes. The d ata therefore suggest that parasite inoculum size and drug dosage are important factors in estimating the apparent frequency of diminazene-r esistant trypanosomes in populations of T. congolense occurring in viv o.