Background We report efficacy and safety outcomes from a prospective case series of 31 late-stage T.b. gambiense sleeping sickness (Human African Trypanosomiasis, HAT) patients treated with a combination of nifurtimox and eflornithine (N+E) in Yumbe, northwest Uganda in 2002–2003, following on a previously reported terminated trial in nearby Omugo, in which 17 patients received the combination under the same conditions. Methodology/Principal findings Eligible sequential late-stage patients received 400 mg/Kg/day eflornithine (Ornidyl, Sanofi-Aventis) for seven days plus 15 mg/Kg/day (20 mg for children <15 years old) nifurtimox (Lampit, Bayer AG) for ten days. Efficacy (primary outcome) was monitored for 24 months post discharge. Clinical and laboratory adverse events (secondary outcome) were monitored during treatment. All 31 patients were discharged alive, but two died post-discharge of non-HAT and non-treatment causes, and one was lost to follow-up. Efficacy ranged from 90.3% to 100.0% according to analysis approach. Five patients experienced major adverse events during treatment, and neutropenia was common (9/31 patients). Conclusions/Significance Combined with the previous group of 17 trial patients, this case series yields a group of 48 patients treated with N+E, among whom no deaths judged to be treatment- or HAT-related, no treatment terminations and no relapses have been noted, a very favourable outcome in the context of late-stage disease. N+E could be the most promising combination regimen available for sleeping sickness, and deserves further evaluation.
References
[1]
Stich A, Barrett MP, Krishna S (2003) Waking up to sleeping sickness. Trends Parasitol 19: 195–197. doi: 10.1016/S1471-4922(03)00055-2
[2]
Barrett MP, Burchmore RJ, Stich A, Lazzari JO, Frasch AC, et al. (2003) The trypanosomiases. Lancet 362: 1469–1480. doi: 10.1016/S0140-6736(03)14694-6
[3]
Stewart ML, Krishna S, Burchmore RJ, Brun R, de Koning HP, et al. (2005) Detection of arsenical drug resistance in Trypanosoma brucei with a simple fluorescence test. Lancet 366: 486–487. doi: 10.1016/S0140-6736(05)66793-1
[4]
Balasegaram M, Harris S, Checchi F, Ghorashian S, Hamel C, et al. (2006) Melarsoprol versus eflornithine for treating late-stage Gambian trypanosomiasis in the Republic of the Congo. Bull World Health Organ 84: 783–791. doi: 10.2471/BLT.06.031955
[5]
Chappuis F, Udayraj N, Stietenroth K, Meussen A, Bovier PA (2005) Eflornithine is safer than melarsoprol for the treatment of second-stage Trypanosoma brucei gambiense human African trypanosomiasis. Clin Infect Dis 41: 748–751. doi: 10.1086/432576
[6]
Burri C, Brun R (2003) Eflornithine for the treatment of human African trypanosomiasis. Parasitol Res 90: Supp 1S49–52. doi: 10.1007/s00436-002-0766-5
[7]
Pepin J, Khonde N, Maiso F, Doua F, Jaffar S, et al. (2000) Short-course eflornithine in Gambian trypanosomiasis: a multicentre randomized controlled trial. Bull World Health Organ 78: 1284–1295.
[8]
Bisser S, N'Siesi FX, Lejon V, Preux PM, Van Nieuwenhove S, et al. (2007) Equivalence Trial of Melarsoprol and Nifurtimox Monotherapy and Combination Therapy for the Treatment of Second-Stage Trypanosoma brucei gambiense Sleeping Sickness. J Infect Dis 195: 322–329. doi: 10.1086/510534
[9]
Medecins Sans Frontieres Campaign for Access to Essential Medicines (2006) Human African trypanosomiasis: facing the challenges causes by neglect: The need for new treatment and diagnostics. Geneva: Medecins Sans Frontieres.
[10]
Priotto G, Fogg C, Balasegaram M, Erphas O, Louga A, et al. (2006) Three Drug Combinations for Late-Stage Trypanosoma brucei gambiense Sleeping Sickness: A Randomized Clinical Trial in Uganda. PLoS Clin Trials 1: e39. doi: 10.1371/journal.pctr.0010039
[11]
Legros D, Fournier C, Gastellu Etchegorry M, Maiso F, Szumilin E (1999) [Therapeutic failure of melarsoprol among patients treated for late stage T.b. gambiense human African trypanosomiasis in Uganda]. Bull Soc Pathol Exot 92: 171–172.
[12]
National Cancer Institute CTEP, National Institutes of Health (1999) Common Toxicity Criteria, version 2.0.
[13]
Schmid C, Nkunku S, Merolle A, Vounatsou P, Burri C (2004) Efficacy of 10-day melarsoprol schedule 2 years after treatment for late-stage gambiense sleeping sickness. Lancet 364: 789–790. doi: 10.1016/S0140-6736(04)16940-7
[14]
Schmid C, Richer M, Bilenge CM, Josenando T, Chappuis F, et al. (2005) Effectiveness of a 10-Day Melarsoprol Schedule for the Treatment of Late-Stage Human African Trypanosomiasis: Confirmation from a Multinational Study (Impamel II). J Infect Dis 191: 1922–1931. doi: 10.1086/429929
[15]
Mpia B, Pepin J (2002) Combination of eflornithine and melarsoprol for melarsoprol-resistant Gambian trypanosomiasis. Trop Med Int Health 7: 775–779. doi: 10.1046/j.1365-3156.2002.00933.x
[16]
Croft SL, Barrett MP, Urbina JA (2005) Chemotherapy of trypanosomiases and leishmaniasis. Trends Parasitol 21: 508–512. doi: 10.1016/j.pt.2005.08.026