Treatment of late stage sleeping sickness caused by T.b. gambiense: a new approach to the use of an old drug.

Melarsoprol is the standard treatment of late stage trypanosomiasis. The development of treatment schedules was previously purely empirical. Generally melarsoprol is given in 3 series of three to four consecutive injections, given every 24 hours, with an interval of about one week between the series. Based on pharmacokinetic analysis, computer simulations and extensive literature research covering all schedules previously used and tested, a new schedule, consisting of ten daily consecutive doses of 2.16 mg/kg of the drug was suggested. The pharmacokinetic model was validated in uninfected vervet monkeys. No unexpected drug accumulation and no systemic toxic effects were observed. In a pilot clinical trial in Congo RDC a small group of T. b. gambiense patients (n = 11) was treated successfully with the new schedule. In an open randomised clinical trial conducted in 500 patients in Angola the clinical efficacy and safety of this new concise treatment were compared to those of standard protocol treatment. Parasitological cure 24 hours after treatment was 100% in both groups. Statistical analysis yielded no significant differences for adverse events between the two treatment protocols. The new schedule reduces the amount and cost for the drug by about one third, and those for hospitalisation by about half.