Melarsoprol versus eflornithine for treating late-stage Gambian trypanosomiasis in the Republic of Congo

Abstract

Objective To compare the effectiveness of melarsoprol and eflornithine in treating late-stage Gambian trypanosomiasis in the Republic of the Congo. Methods We analysed the outcomes of death during treatment and relapse within 1 year of discharge for 288 patients treated with eflornithine, 311 patients treated with the standard melarsoprol regimen and 62 patients treated with a short-course (10-day) melarsoprol regimen between April 2001 and April 2005. Findings A total of 1.7% (5/288) of patients treated with eflornithine died compared with 4.8% (15/311) of those treated with standard melarsoprol and 6.5% (4/62) of those treated with short-course melarsoprol. Patients treated with eflornithine tended to be younger and were more likely to have trypanosomes or higher white blood cell counts in their cerebrospinal fluid. The cumulated incidence of relapse among patients who attended at least one follow-up visit 1 year after discharge was 8.1% (11/136) for those treated with eflornithine, 14% (36/258) for those treated with standard melarsoprol and 15.5% (9/58) for those treated with shortcourse melarsoprol. In a multivariate analysis, when compared with eflornithine, standard melarsoprol was found to be a risk factor for both death (odds ratio (OR) = 2.87; 95% confidence interval (CI) = 1.03-8.00) and relapse (hazard ratio (HR) = 2.47; 95% CI = 1.22-5.03); when compared with eflornithine, short-course melarsoprol was also found to be a risk factor for death (OR = 3.90; 95% CI = 1.02-14.98) and relapse (HR = 6.65; 95% CI = 2.61-16.94). Conclusion The effectiveness of melarsoprol treatment appears to have diminished. Eflornithine seems to be a better first-line therapy for treating late-stage Gambian trypanosomiasis in the Republic of the Congo. IntroductionAfrican trypanosomiasis is a public health hazard in many countries in sub-Saharan Africa, with an incidence of around 20 000 new cases a year.1,2 The disease is fatal if untreated. Control programmes have been severely weakened by war and civil instability in many of the countries with the highest prevalence. 3,4 In central and west Africa the disease is predominantly caused by the protozoan Trypanosoma brucei gambiense and is transmitted by the tsetse fly (Glossina spp.) in a human-fly-human cycle. Pentamidine, first-line treatment for early-stage disease, cannot be used if the parasites have invaded the central nervous system because the drug does not cross the blood-brain barrier. The principal treatment options for late-stage (or stage-2) disease are either melarsoprol (an organoarsenic compound that in--hibits parasite glycolysis) or eflornithine (an irreversible inhibitor of ornithine decarboxylase which is necessary for the parasite's synthesis of DNA and RNA). Both drugs must be adminis--tered intravenously over a period of 1-4 weeks, which is logistically challenging in health-care systems in the developing world. Melarsoprol is a highly toxic drug that causes encephalopathy in 5-10% of patients and approximately 40% of these patients will die. 1,5 Eflo...

6-Arylpyrazine-2-carboxamides: A New Core for Trypanosoma brucei Inhibitors

“…The mode of action requires a sufficiently active immune system to achieve cure (47,156). The case fatality rate during eflornithine treatment is consistently < 2% and is lower than that with melarsoprol (157,158). Administration of four daily infusions for 14 days necessitates good nursing care, including strict aseptic precautions during catheter insertion and fixation, to prevent local (phlebitis) and disseminated (abscess, sepsis) infections.…”

“…Environmental modifications and human or livestock population movements can, however, result in shifts in geographical location and extent. Thus, disease mapping has always been a key element of HAT control (157,158).…”

Chemotherapy against human African trypanosomiasis: Is there a road to success?

“…Several studies comparing melarsoprol and eflornithine showed a clearly reduced mortality and cumulative incidence of relapses under eflornithine and the drug is therefore recommended as first line treatment for second stage T. b. gambiense HAT Balasegaram et al 2006a;Checchi et al 2007), but the use of eflornithine against T. b. rhodesiense is not advised because of the innately reduced susceptibility of this parasite due to a higher ornithine decarboxylase turnover (Iten et al 1997). The most commonly used dosage regimen for the treatment of T. b. gambiense HAT consists of 100 mg kg -1 body weight at intervals of 6 h for 14 days of eflornithine given as short infusions (Burri and Brun, 2008).…”

Update on field use of the available drugs for the chemotherapy of human African trypanosomiasis

“…The major issue being melarsorpol's unacceptable toxicity whilst the less toxic, albeit cumbersome to administer, eflornithine has been available for over 20 years (Chappuis et al 2005;Balasegaram et al 2006;Robays et al 2008;Priotto et al 2008).…”