MALARIA is on the march across Africa, but help may be at hand for millions of infected people. It takes the form of an old, cheap anti-malarial drug, poised to make a comeback after parasite resistance had rendered it almost useless.
Last week UNICEF, the United Nations Children鈥檚 Fund, warned that 6 million people in Ethiopia, many of them children under 5, were at risk of contracting malaria. The World Health Organization also dispatched new anti-malarial therapies to Niger, where the beginning of the peak malaria season has coincided with widespread malnutrition triggered by failing harvests. The WHO fears that 100,000 extra children could die as a result.
But the drugs sent by the WHO, known as artemisinin-based combination therapies (ACTs), cost at least $2.40 per course 鈥� way beyond the means of many sufferers across Africa. The need for new, cheap anti-malarials has prompted researchers to turn their attention back to chloroquine, a drug first used in the 1950s with spectacular success until the malaria parasite Plasmodium falciparum developed widespread resistance to it.
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Chloroquine gets to work in the digestive vacuole, effectively the stomach, of P. falciparum. The drug stops the parasite crystallising molecules of haem as it breaks down human haemoglobin from a red blood cell. The uncrystallised haem is toxic and kills the parasite.
To be effective, chloroquine has to reach a high concentration in the digestive vacuole, but in resistant parasites a mutated protein-transport molecule lets chloroquine escape through pores in the vacuole cell-membrane, reducing its concentration. That means that while chloroquine may ease malaria symptoms, it won鈥檛 cure the infection.
However, lab tests show that chloroquine鈥檚 potency appears to be restored when combined with another drug, called primaquine.
Primaquine is normally used to treat a less severe form of malaria, caused by infection with the parasite P. vivax, though no one quite understands how it works, says Leann Tilley of La Trobe University in Melbourne, Australia, who led the new work.
On its own, primaquine has no effect on P. falciparum, but it is structurally similar to chloroquine. The team thinks that when the two drugs are used together on P. falciparum, primaquine blocks the pores in the membrane, preventing chloroquine from leaking out and allowing it to kill off the parasite.
鈥淭ests show that chloroquine鈥檚 potency appears to be restored when combined with another drug, called primaquine鈥�
鈥淚f you put chloroquine and primaquine together at the right concentration in the lab, it鈥檚 as effective on chloroquine-resistant parasites as chloroquine is on sensitive parasites,鈥� says Tilley, who presented her work this week at a meeting of the Australian Society for Microbiology in Canberra. Even better, the new combination therapy should cost about 25 cents per course. Tilley hopes field trials that test the efficacy of the drug combination in people could start soon, perhaps in Indonesia.
