Nature Medicine | Spoonful of Medicine

Once-maligned malaria drug could get a second chance

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The medication sulfadoxine-pyrimethamine, or “SP”, is currently used to treat malaria in pregnant women in the developing world. It works by disrupting the malaria parasite’s ability to make folic acid, which is a key component of nucleotide synthesis. It’s inexpensive, too, costing 15 cents for a course of treatment as opposed to $1 for a similar course of artemisin-based therapy. This alone should make it an attractive option for widespread use, but for a not-so-slight problem: up until now, research seemed to show that the most common malaria parasite, Plasmodium falciparum, was rapidly becoming resistant to SP.

Now come two papers that challenge that notion. Reporting in the International Journal for Parasitology, researchers from the University of Bamako in Mali working with American and European collaborators suggest that the severity of SP resistance has been overplayed. Although administration of SP does increase the prevalence of SP-resistant genes, it’s possible that SP affects the infectiousness of the malaria parasite to such a degree that the effect of that resistance is negligible.

In the first study, 14 volunteers in Mali who had been previously treated with SP were exposed to the bites of mosquitoes (Anopheles gambiae) uninfected with the malaria parasite. A week after feeding on the participants, the mosquitoes were dissected to look for malaria spores. Out of 928 mosquitoes, only seven had them.

The second article looks closer at the mechanism by which SP affects gametocytes, the sexually reproductive stage of P. falciparum that is transmitted via the gut of mosquitos. They found that SP causes those gametocytes to become deformed, and they don’t mature to the next stage of the parasite’s life cycle.

If the results can be replicated, it could be a strong argument for using SP to treat malaria in infants and children in areas where the drug is effective.

Image: SP-treated Plasmodium falciparum gametocytes from Kone et al.

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