Sleeping sickness drugs should be used in combination, say researchers

WHO/TDR/Crump/ 9704663

[CAPE TOWN] Hopes for an effective new combination treatment for sleeping sickness have been challenged by the discovery of resistance to two of the drugs.

Sleeping sickness, or human African trypanosomiasis, is one of Africa's most deadly and neglected diseases, transmitted by the bite of the tsetse fly. The WHO estimates that there are around 70,000 cases, with an estimated 18,000 new cases in 2004. There is still no simple treatment for the disease: most drugs, such as melarsoprol or eflornithine, are highly toxic or difficult to administer.

The combination therapy — launched a year ago by the Drugs for Neglected Diseases initiative (DNDi), a non-profit organisation based in Switzerland — is shorter, cheaper and easier to administer in rural areas of Sub-Saharan Africa, where the disease is most prevalent, than the other drugs.

But despite the initial success of nifurtimox and eflornithine combination treatment, the sleeping sickness parasites, trypanosomes, can quickly develop resistance to nifurtimox, according to a study published this month (July) in Antimicrobial Agents and Chemotherapy.

Alan Fairlamb, a parasite specialist at UK-based University of Dundee, said tests showed there is a danger that the parasites' resistance to nifurtimox could increase to the point where the disease is no longer curable with the drug.

He added this may mean reverting to a more costly single treatment with eflornithine, a longer infusion therapy which may also be losing its efficacy or arsenic-based melarsoprol, which kills one in 20 people who receive it.

The solution is to find new, safe and effective drug combinations to slow the emergence of resistant parasites, Fairlamb told SciDev.Net.

Rob Don, discovery and preclinical director at DNDi, said that development of drug resistance by parasites is the norm rather than the exception.

He agreed there was a risk of resistance, but said that two other drugs are in the pipeline: fexinidazole, an oral treatment similar to nifurtimox, is now in clinical trials, and oxaborole, a new class of drugs, is in development.

The Dundee unit is also working on a new drug, which has so far been shown to be effective only against the first stage of the infection.

But Dundee researchers have warned that parasites resistant to nifurtimox also quickly develop resistance to fexinidazole, through a cross-resistance mechanism and have suggested that it should only be used in a combination therapy, which would reduce the likelihood of resistance developing.

Link to full paper in Antimicrobial Agents and Chemotherapy