Effectiveness of melarsoprol and eflornithine as first-line regimens for gambiense sleeping sickness in nine Médecins Sans Frontières programmes

Abstract

This paper describes the effectiveness of first-line regimens for stage 2 human African trypanosomiasis (HAT) due to Trypanosoma brucei gambiense infection in nine Médecins Sans Frontières HAT treatment programmes in Angola, Republic of Congo, Sudan and Uganda. Regimens included eflornithine and standard- and short-course melarsoprol. Outcomes for 10461 naïve stage 2 patients fitting a standardised case definition and allocated to one of the above regimens were analysed by intention-to-treat analysis. Effectiveness was quantified by the case fatality rate (CFR) during treatment, the proportion probably and definitely cured and the Kaplan-Meier probability of relapse-free survival at 12 months and 24 months post admission. The CFR was similar for the standard- and short-course melarsoprol regimens (4.9% and 4.2%, respectively). The CFR for eflornithine was 1.2%. Kaplan-Meier survival probabilities varied from 71.4-91.8% at 1 year and 56.5-87.9% at 2 years for standard-course melarsoprol, to 73.0-91.1% at 1 year for short-course melarsoprol, and 79.9-97.4% at 1 year and 68.6-93.7% at 2 years for eflornithine. With the exception of one programme, survival at 12 months was >90% for eflornithine, whilst for melarsoprol it was <90% except in two sites. Eflornithine is recommended where feasible, especially in areas with low melarsoprol effectiveness.

Operational research in low-income countries: what, why, and how?

“…Academics rarely have access to such settings, and national programmes might decide they do not have suffi cient resources to study them. Research in these areas is, nevertheless, needed to better understand how to manage questions such as mental health issues in war zones, 36 treatment and diagnosis of neglected diseases, 37 or off ering of HIV/AIDS care in slum settings. For example, when the Sphere Project guidelines recommended against HIV therapy in confl ict settings, 38 an MSF study by Culbert and colleagues 16 proceeded anyway and showed good outcomes.…”

Trypanocidal Furamidine Analogues: Influence of Pyridine Nitrogens on Trypanocidal Activity, Transport Kinetics, and Resistance Patterns

“…Melarsoprol is highly toxic (27), and the rate of treatment failure with melarsoprol has reached over 30% in some areas (8). Administration of eflornithine, particularly in the form of nifurtimox and eflornithine combination therapy (NECT) (38), has become the treatment of choice since the 1990s in many areas where T. b. gambiense infection is endemic (2). NECT, however, is not proposed for treatment of T. b. rhodesiense infection and may not halt the spread of eflornithine resistance indefinitely.…”

“…Here we present details of transport kinetics, definitively identifying the P2 adenosine transporter as the main entry route for this class of furamidine analogues while still showing the existence of minor routes of uptake in addition to P2. Ϫ/Ϫ (34) and B48 (7) were cultured, using complete HMI-9 media at 37°C in 5% CO 2 . Ex vivo cells were obtained from adult female Wistar rats.…”

In Vitro and In Vivo Activities of 2-Aminopyrazines and 2-Aminopyridines in Experimental Models of Human African Trypanosomiasis

“…Due to adverse side effects and toxicity of current first-line therapies, and the increasing development of resistance toward these agents (20,21), there is a growing need for development of novel treatments of human African trypanosomiasis. Fortunately, there have been a number of interesting compounds developed and novel targets identified within the past few years which hold promise for the development of better and more efficient medicines with which to combat this devastating disease.…”