When two drugs are less deadly than one

It begins with the bite of a tsetse fly.

For months, the parasite that causes human African trypanosomiasis (HAT), or sleeping sickness, multiplies quietly in the body. The few symptoms that do occur — headache, fever, joint pain — are commonly confused with other diseases.

It is in the second stage that the microscopic parasites begin to do their worst. After crossing into the central nervous system, the parasite produces the neurological symptom of sleepiness that gives the disease its nickname. Those with the disease also suffer confusion, wild hallucinations, behavior changes and a lack of coordination.

Without treatment, the disease is fatal.

For years, the only treatment for sleeping sickness was a toxic arsenic-based drug that killed one in 20 people who took it. But now, researchers from Medecins Sans Frontieres, Epicentre and the Drugs for Neglected Diseases Initiative (DNDi) have shown that a combination of existing drugs is easier to administer, less toxic and more effective than other treatments for the West African form of sleeping sickness, which makes up 90 percent of cases.

“For the patients, this is going to change their situation dramatically,” said Epicentre's Dr. Gerardo Priotto, the principal investigator for the study. There are an estimated 50,000 to 70,000 patients with sleeping sickness in sub-Saharan Africa, usually in the poorest, rural and most conflict-ridden parts of the continent.

Millions more people are at risk if a large-scale epidemic were to break out, as has happened three times in the past century.

The Democratic Republic of Congo, riven by years of civil war, has the majority of all cases, although other war-torn countries such as Angola, Central African Republic, southern Sudan and Uganda have been hit hard as well.

For years, 70 percent of HAT patients received melarsoprol, an arsenic-based medicine that was developed in the 1940s. Patients describe the sensation of taking it as having fire in their veins. One in 20 patients dies from the treatment itself and high failure rates have begun emerging in many areas.

Doctors also treat patients with eflornithine, which is far less toxic and more effective, but has not been widely adopted in Africa. The drug is administered in 56 infusions over 14 days, a nearly impossible dosing schedule in the understaffed clinics and hospitals in the rural areas where this disease is found.

“The majority of patients are in the poorest parts of Africa, where health staff is limited, competency is really low, hospitals are sometimes run without doctors, and no supplies,” Priotto said. “We cannot go around realities like that. You have to adapt the treatment to the realities so that it can be accessible to the patients.”

The five-year study found that a treatment that combines a lower dosage of eflornithine with another drug, nifurtimox, is more effective and easier to administer than eflornithine alone. The combination, which uses just 14 infusions and 30 pills, has a 98 percent efficacy rate, and fewer side effects than either of the other drugs, according to the researchers.

These results have instilled hope in patients and doctors in sub-Saharan Africa, said Dr. Constantin Miaka Bilenge, the special advisor to the HAT National Control Program of the Democratic Republic of Congo.

“We are looking for an easy-to-use treatment that can improve case management in the field, and NECT provides us this practical improvement,” Bilenge said.

“Any time you can develop a treatment that’s easier to administer, that’s an important advance,” said Dr. Peter Hotez, president of the Sabin Vaccine Institute and a professor studying neglected diseases at George Washington University. He was not involved in this study.

“The fact that there (are) two drugs instead of one also means that the potential for emerging drug resistance is reduced,” he added.

Despite the promise of this new combination, researchers are continuing to look for new drugs to treat sleeping sickness — ideally ones that can be taken orally.

“Even though we are very excited about this improved therapy, it’s clear that this is not the best solution for sleeping sickness. To treat more people, we need to even do better,” said Els Torreele, senior project manager of the research and development team at DNDi.

She and her team have found a compound, originally developed by Sanofi-Aventis, that has shown promise in animal studies against sleeping sickness. Clinical trials begin this year.

In the meantime, the researchers are starting a new trial to test the combination therapy in more rural clinics throughout the DRC and Congo. If all goes well, they hope to begin distributing kits of the combination therapy through Medecins Sans Frontieres within a few years.

“Within three years, 50 percent of people in the DRC will be treated with NECT,” predicted Torreele.

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