Drug Resistance Acquired during the Treatment of Sleeping-Sickness with Tryparsamide and with Bayer 205

Summary 1. Tests were made in rats on the sensitivity to tryparsamide of 23 strains of trypanosomes (T. rhodesiense) from untreated patients with sleeping sickness and of 5 strains from 4 patients who had received repeated courses of tryparsamide. 2. The minimum effective dose for the strains from untreated patients was 25 to 50 mgm. per 100 gram rat; that for the strains from 3 treated patients was 50, 100, and 200, mgm. respectively. In a fourth patient who relapsed after one course of tryparsamide the M.E.D. of the trypanosomes was ?200 mgm.; he received a second course of tryparsamide but relapsed again, and the M.E.D. of the trypanosomes on the second occasion was 400 mgm, strongly suggesting that the organisms had acquired an increased arsenic-resistance during the treatment. 3. These results show that the trypanosomes of patients who relapse after tryparsamide have a greater resistance than normal; but this resistance is not so great as that which can be obtained in the trypanosomes of laboratory animals. 4. In view of this increased resistance, a second course of tryparsamide is not likely to benefit patients with Rhodesian sleeping sickness who have relapsed after the first course; it is however quite likely to cause blindness. 5. Trypanosomes from patients relapsing after treatment with Bayer 205 showed no increase of resistance to this compound.