The Sleep without Rest.
Tsetse fly. Photo: Geoffrey Attardo
by Jan McColm
The blood-sucking tsetse fly lives in sub-Saharan Africa and can carry a rather nasty parasite called a trypanosome. If a tsetse fly bites you, millions of these tiny parasites can flow from the fly to you. The parasites multiply and eventually enter your nerves and brain, keeping you up all night and drowsy all day. The diagnosis: African sleeping sickness. The prognosis without treatment: coma and death.
Around sixty million people in sub-Saharan Africa live in areas where African sleeping sickness is endemic. According to the Centers for Disease Control, around half a million people are infected. Yet the disease remains one of the most under-funded and under-researched. Richard Tidwell, professor of pathology and laboratory medicine, is changing that.
Tidwell has been researching parasitic diseases for twenty years. In 2001, his group received a grant from the Bill and Melinda Gates Foundation to discover new drugs for sleeping sickness and to take those drugs through early clinical trials. The success of this research led to one drug, pafuramidine maleate, which has many advantages over previous treatments. Current drugs necessitate multiple injections or intravenous infusion, Tidwell says, and because of side effects must be carefully monitored during administration. “Pafuramidine is the first oral drug ever for African sleeping sickness,” he says, and the drug appears to be much less toxic than current drugs.
But pafuramidine does have one drawback—it’s only effective against the first stage of the disease.
The first stage, when parasites are still in the blood, is usually without symptoms, and can last years as the parasites multiply. Symptoms, when they do appear, can include headaches, fever, and joint pain, but are easily confused with other diseases common to the area. The second stage, when parasites cross into the nervous system and brain, causes confusion, sensory hallucinations, and poor coordination. The coma, which gives the disease its name, is fatal without treatment.
For pafuramidine to be effective, “patients must have an invasive test to be sure they haven’t progressed to the late-stage disease,” Tidwell says—which is just one of the very tricky issues of conducting clinical trials in Africa. “African sleeping sickness is only in rural settings; it’s not widespread,” he explains. It can be confined to one village and the village two miles down the road may be unaffected. “We have to do a lot of testing and bring in a lot of patients,” Tidwell says. And this approach does have one advantage: it is ramping up the surveillance of the disease.
Back in the 1960s, African sleeping sickness had practically disappeared. Mobile teams throughout the region were monitoring it and treating the early stages with drugs. Insecticides helped keep the fly population down. But as increasing numbers of African countries gained independence, money wasn’t available for monitoring and treatment. Tsetse flies became resistant to insecticide, and their parasites became resistant to drugs. Consequently, Africa is now in the midst of another epidemic.
Tidwell has just received another grant from the Bill and Melinda Gates Foundation to take pafuramidine through more clinical trials in Africa and to complete the regulatory requirements to get the drug registered.
“This is the first real effort being made in this disease,” Tidwell says, and he is optimistic for more than one reason. “Pafuramidine can have a huge impact because it’s an oral drug, easily administered, and it’s a lot less toxic. And if you use pafuramidine correctly you have the potential to control or perhaps even eliminate the disease.” Tidwell and his team are also working on new approaches to treating the late stage, with encouraging preliminary results. “And that would be the real coup,” he says, “to treat both stages with a single medication.”
Jan McColm is Managing Editor for Genetics in Medicine.
