Nifurtimox in combination with eflornithine is safe, effective, and more affordable than current treatments for sleeping sickness and should be implemented as a matter of priority by control programmes across sub-Saharan Africa, according to an Article in this week's issue of the Lancet.
Human African trypanosomiasis (HAT) or sleeping sickness affects tens of thousands of people every year in sub-Saharan Africa and is a fatal disease with few treatment options. For 60 years melarsoprol has been the most commonly used treatment, but it is a highly toxic drug which causes severe adverse reactions. A newer alternative, eflornithine, has been shown to be more effective and better tolerated, but is difficult to administer requiring one slow infusion every 6 hours for 14 days—which has limited its use in resource-poor settings. A third orally administered drug, nifurtimox, currently used in the treatment of Chagas disease and not yet registered for the treatment of sleeping sickness, has shown some promising results in combination with eflornithine.
To investigate further, Gerardo Priotto and colleagues conducted a randomised trial of patients with second-stage sleeping sickness (where infection has reached the brain and prognosis is normally very poor) to compare the efficacy and safety of nifurtimox-eflornithine combination therapy (NECT) with standard eflornithine, the best currently available treatment.
In total, 287 patients aged 15 years or older were recruited from four treatment centres in Congo and the Democratic Republic of Congo between 2003 and 2006. Patients were randomly assigned to either intravenous eflornithine (400mg/kg per day, every 6 h) for 14 days or intravenous eflornithine (400mg/kg per day, every 12 h) for 7 days with oral nifurtimox (15mg/kg per day, every 8 h) for 10 days (NECT). Patients were followed up for 18 months and examined at regular intervals for relapses.
Overall, results showed that NECT is non-inferior to the best current treatment, eflornithine. Cure rates were substantially higher in the NECT group (96.5% to 97.9%) compared with rates of 91.6% to 92.3% in patients given eflornithine alone.
In addition, NECT was fairly well tolerated with half as many major adverse events reported and a lower frequency of infections such as diarrhoea and fever in the NECT group compared to the eflornithine group.
The authors conclude that because NECT has safety advantages, is easier to administer (infusion every 12 h for 7 days vs every 6 h for 14 days), is more affordable, and as a combination of drugs might potentially be protected against the development of drug resistance, call for its first-line use in sleeping sickness control programmes.
In an accompanying Comment, Charles Woodrow from St George's, University of London, UK, and Jimmy Opigo from Moyo District Hospital, Uganda, say that these findings provide a strong evidence base to support the promotion of NECT within national treatment strategies. They go on to discuss the challenges that remain including the urgent need to develop improved treatments for patients with first-stage sleeping sickness.
Dr Gerardo Priotto, Epicentre, Paris, France. T) +33 1 4021 2848 E) gpriotto@epicentre.msf.org
Dr Charles Woodrow, St George's, University of London, UK. T) +44 (0)208 7255 827 E) charlie@tropmedres.ac
For full Article and Comment, see: http://press.thelancet.com/sleeping.pdf
Journal
The Lancet