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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.