Safety and Efficacy of the 10-Day Melarsoprol Schedule for the Treatment of Second Stage Rhodesiense Sleeping Sickness

Abstract

Assessment of the safety and efficacy of a 10-day melarsoprol schedule in second stage T.b. rhodesiense patients and the effect of suramin-pretreatment on the incidence of encephalopathic syndrome (ES) during melarsoprol therapy. Sequential conduct of a proof-of-concept trial (n = 60) and a utilization study (n = 78) using historic controls as comparator. Two trial centres in the T.b. rhodesiense endemic regions of Tanzania and Uganda. Participants: Consenting patients with confirmed second stage disease and a minimum age of 6 years were eligible for participation. Unconscious and pregnant patients were excluded. The primary outcome measures were safety and efficacy at end of treatment. The secondary outcome measure was efficacy during follow-up after 3, 6 and 12 months. The incidence of ES in the trial population was 11.2% (CI 5–17%) and 13% (CI 9–17%) in the historic data. The respective case fatality rates were 8.4% (CI 3–13.8%) and 9.3% (CI 6–12.6%). All patients discharged alive were free of parasites at end of treatment. Twelve months after discharge, 96% of patients were clinically cured. The mean hospitalization time was reduced from 29 to 13 days (pT.b. gambiense in West and Central Africa and in an acute form caused by T.b. rhodesiense in East and South Africa. In the first stage of the disease parasites are detectable in blood and lymph. Once they enter the central nervous system, patients are in the so-called second stage, which is fatal if left untreated. Melarsoprol, an old and highly toxic drug, remains the only available treatment for second stage T.b. rhodesiense HAT. The empirically developed treatment regimens are a high burden to affected patients and health care providers due to very long hospitalization times and complicated dosing schemes. An improved 10-day melarsoprol treatment schedule was developed and tested in second stage T.b. gambiense patients from 1997–2004 and was approved for large-scale use by the International Scientific Committee for Trypanosomiasis Research and Control (ISCTRC) in 2003. To test its adequacy also in T.b. rhodesiense patients, a series of clinical trials were conducted from 2005–2009. Based on these results the ISCTRC has officially recommended the use of the 10-day melarsoprol schedule also for treatment of second stage Rhodesiense HAT in 2009.