Mosquitoes bite back

Observations on malaria

Just over a month ago, I reported in these pages on a surge in optimism in the fight against malaria, thanks to unprecedented investment in drug development and new ways to combat one of the world’s most pervasive infectious diseases. There had just been a pledge of £150m to subsidise the purchase and distribution of the best class of antimalarial drug, artemisinin combination therapies, or ACTs. These compounds have steadily replaced cheaper drugs such as chloroquine and antifolates as the parasites that cause malaria have developed resistance to them.

Sadly, reports now indicate that in Cambodia parasites are taking longer to clear when treated with ACTs, too. It would seem that resistance has also emerged to artemisinin. The parasites are still cleared by the combinations, but after five days of treatment, rather than the usual two.

International anti-malaria policy has, for several years, recommended that artemisinin be administered in combination with at least one other antimalarial for precisely this reason. A genetic mutation of the disease that offers resistance to one of the drugs should be countered by the second. This does indeed appear to be happening in Cambodia – so what is the problem? It had been naively hoped that artemisinin itself was such a potent compound that malaria parasites would find it difficult to develop resistance. But evolution ensures that resistance to any antimalarial compound will occur eventually.

In principle, it should be possible to block the spread of artemisinin resistance. The aggressive introduction of other drugs, mosquito control and the use of insecticide-treated bed nets in those areas where resistance has emerged could obliterate the resistant strain. The World Health Organisation, with financial support from the Bill and Melinda Gates Foundation, is already attempting to cleanse those parts of western Cambodia where artemisinin resistance has emerged. But it remains worrying that the resistance has emerged at all. Much of the optimism that we might actually be able to eliminate malaria has been built
on the concept of combinations using artemisinin.

The resistance that ultimately rendered earlier drugs obsolete also emerged from the Cambodian-Thai borderlands before spreading to other parts of the world. In the case of artemisinin, it is distressingly clear why this region has become an incubator for such a selection of drug-resistant malaria parasites. Health services are poorly regulated, and in spite of WHO recommendations, people can buy antimalarial drugs in their local markets. Artemisinin on its own is cheaper than an ACT: simple economics dictates that it will be used by itself, rather than in combination. Even cheaper are fake drugs, packaged in replica boxes indistinguishable from the real thing. Small amounts of the real drug are often added to the fakes, so that any tests show the drug to be present. Sublethal doses of drugs create the perfect conditions for the parasites to mutate.

The notion that fake versions of drugs desperately needed to save lives are flooding the marketplace seems repugnant. However, with 300 million victims each year and half the world’s population living in malarious regions, the antimalarial market is sufficient to stimulate such activity. While medical science offers solutions to malaria, socio-economic factors continue to thwart efforts to eliminate this scourge.