Treatment for Dormant Malaria Shows Promise

14 November 2013 5:15 pm
Vivax malaria, shown here in the blood stream, can hide out—undetectable—in liver cells.


Stealthy foe. Vivax malaria, shown here in the blood stream, can hide out—undetectable—in liver cells.

The first new drug in half a century to target malaria parasites in one of their best hideouts is showing encouraging results. The researchers developing the drug, called tafenoquine, said today that data from a recently completed phase II trial were promising enough that they will soon start a phase III trial—the last step before asking drug regulators for approval.

Tafenoquine kills the malaria parasite when it is lurking in liver cells, in a form called the hypnozoite, or “sleeping parasite.” Hypnozoites don’t cause any symptoms and are impossible to detect with blood tests. But when triggered by signals that aren’t fully understood, they can reactivate to cause a new bout of malaria—which can then be picked up by mosquitoes and passed on to new victims. Five species of Plasmodium can cause malaria in humans. Two of them—Plasmodium vivax, which is widespread, and the relatively rare P. ovale—can form hypnozoites. This ability to hide is one of the things that makes P. vivax so difficult to eliminate from a region.

Now, the only treatment that can cure vivax malaria—hiding parasites and all—is a 14-day course of a drug called primaquine, which was developed in the 1940s. It works fairly well, but it is difficult for people who don’t feel ill to complete the whole 2 weeks. “The compliance with the current regimen is really a problem,” says JP Kleim, director of clinical development for the pharmaceutical company GlaxoSmithKline (GSK). “The acute malaria is gone after a few days [of treatment],” so patients’ motivation to continue taking drugs is low. That’s why GSK decided to develop tafenoquine, together with the Medicines for Malaria Venture, a Geneva-based nonprofit. The partners launched a trial in 2011 to test whether a single dose of tafenoquine could work as well as the 2-week course of primaquine.

The data, presented today at the American Society of Tropical Medicine and Hygiene Annual Meeting in Washington, D.C., suggest that a single dose works very well. The trial involved 329 patients in Brazil, India, Thailand, and Peru. In patients who received either a 300 mg or 600 mg dose of the drug, 90% had no relapses after 4 months. The partners will now go forward with a phase III trial, testing the safety and efficacy of the 300 mg dose in 600 patients, says Marcus Lacerda of the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado in Manaus, Brazil, who helped coordinate the study and presented the results at the meeting today.

A single-dose drug would be a huge advantage in the fight against vivax malaria, says Ric Price of the Menzies School of Health Research in Darwin, Australia, and the University of Oxford in the United Kingdom. “One of the biggest challenges we face is how can we adequately and reliably treat the hypnozoite stage.”

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