Malaria Drug Resistance

Bulletin of the World Health Organization, March 2000 | Go to article overview

Malaria Drug Resistance


The principal malaria parasite, Plasmodium falciparum, develops resistance to three first-line antimalarial drugs when mutations occur in just one gene, say researchers in Australia. Moreover, resistance to a fourth and relatively new antimalarial agent, artemisinin, can be influenced by mutations in the same gene, despite artemisinin being structurally different from the other three drugs.(a)

Alan Cowman at the Walter and Eliza Hall Institute of Medical Research in Melbourne and colleagues end a ten-year controversy that has included "fierce debate" with the publication of their findings. The team first isolated the P. falciparum pfmdr1 gene more than a decade ago and suggested it was involved in resistance. "This manuscript proves the role of the mutations in the pfmdr1 gene," says Cowman.(b) Mutations that affect the protein encoded by the gene, known as P-glycoprotein homologue 1 (Pgh1), prevent the drugs mefloquine, halofantrine and quinine from being concentrated in the parasite, allowing the parasite to grow even in their presence. The researchers also show that the same mutations influence the resistance of the parasite towards chloroquine in some strains and that they affect the sensitivity of the parasite to artemisinin. …

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