African trypanosomiasis, also called sleeping sickness, is a serious parasitic disease that left untreated is always fatal. The disease is spread by the bite of tsetse flies, found only in Africa. It occurs in two forms: East African trypanosomiasis and West African trypanosomiasis. Worldwide, 20,000 new cases of both types of the disease are reported each year. Unfortunately, treatment is hindered by a lack of effective drugs. Now, new treatments may be on the way. Results from a recent clinical trial point to promising drug combinations.

The international humanitarian medical aid agency Medecins Sans Frontieres (MSF) and its research arm, Epicentre, carried out the clinical trial evaluating new drug combinations for African trypanosomiasis. The study appears in the Public Library of Science's journal PloS Clinical Trials.

To date, there have been few treatment options for this devastating disease, which begins with fever, headache, and extreme tiredness, progresses to attack the central nervous system, and, ultimately, results in death several months or years after infection. Presently, treatments include pentamidine, thought it is ineffective against the late stages of the disease and some parasite strains are resistant to it. Suramin is also used but must be administered intravenously and can have adverse side effects. Finally, melarsoprol—the most commonly used drug—is highly toxic. An arsenical drug developed more than 50 years ago, it is used against late-stage disease, but often induces serious—sometimes fatal—side effects.

Clearly, new treatments are needed. MSF and Epicentre jointly carried out a trial that started in 2001 in Uganda to evaluate the efficacy and safety of three specific drug combinations. The aim was to find out if any of the combinations would provide a viable treatment option for patients with second-stage sleeping sickness, where infection has spread to the brain and prognosis is typically very poor.

In the trial, the drug combinations compared were melarsoprol-nifurtimox, melarsoprol-eflornithine, and nifurtimox-eflornithine. However, after 54 patients had been recruited (435 were planned), it was obvious that the death rate was much higher amongst individuals receiving one of the combinations, so the trial was stopped.

Here is what the researchers discovered. The cure rate for nifurtimox-eflornithine was over twice that for melarsoprol-nifurtimox and substantially higher than that for melarsoprol-eflornithine. The rates of adverse events were also lower for patients treated with nifurtimox-eflornithine. While further clinical trials will be needed, these findings are encouraging and suggest that the nifurtimox-eflornithine combination has potential as a future therapy for second-stage African trypanosomiasis.