How Many More Children Must Die from a Mutant Strain of Malaria?

I am slightly ashamed of how much I liked Burma when I visited it nearly a third of a century ago. What a delight it was to go to a country in which there had been no progress for 40 years! Of course it was a xenophobic, klepto-socialist, Buddho-Marxist military dictatorship run by the shadowy, sinister and corrupt General Ne Win, and so, in theory, I should have hated it. Instead, I loved it and wished I could have stayed.

Since then there has probably been some progress, no doubt to the detriment of the country’s charm. Burma (now Myanmar) is slowly rejoining the rest of the world, and one consequence of this will be the more rapid advance of treatment-resistant malaria.

A recent paper in the Lancet examined the proportion of patients in Burma with malaria in whom the parasite, Plasmodium falciparum, was resistant to what is now the mainstay of treatment, artemisinin, a derivative of a herbal remedy known for hundreds of years to Chinese medicine. The results are not reassuring.

There was a time, not so very long ago, when the global eradication of malaria was envisaged by the WHO, and it looked for a time as if it might even be achieved. The means employed to eradicate it was insecticide that killed the mosquitoes that transmitted the malarial parasites, but a combination of pressure from environmentalists who were worried about the effects of DDT on the ecosystem and mosquito resistance to insecticides led to a recrudescence of the disease.

At the same time, unfortunately, resistance to antimalarial drugs emerged. Control of malaria, not its eradication, became the goal; an insect and a protozoan had defeated the best efforts of mankind. And this is no small matter: the last time resistance to a mainstay of treatment for malaria, chloroquine, emerged in South-East Asia, millions of people died as a result in Africa for lack of an alternative treatment.

What most surprised me about this paper was the method the authors used to determine the prevalence of resistance to artemisinin in the malarial parasites of Burma: for I remember the days when such prevalence was measured by the crude clinical method of giving patients chloroquine and estimating how many of them failed to get better.

The genetic mutations that make the parasite resistant to artemisinin have been recognized. The authors were able to estimate the percentage of patients with malarial parasites that had mutations associated with drug resistance. Nearly 40 percent of their sample had such mutations, and in a province nearest to India the figure was nearly half. The prospects for the geographical spread of resistance are therefore high.

Nor is this all. Artemisinin resistance was first recognized in Cambodia 10 years ago but the mutations in Burma were different, suggesting that resistance can arise spontaneously in different places at the same time. From the evolutionary point of view, this is not altogether surprising: selection pressure to develop resistance to artemisinin exists wherever the drug is widely used.

One way of reducing the spread of resistance is the use in treatment of malaria of more than one antimalarial drug at a time, but this will only retard the spread, not prevent it altogether. As with tuberculosis, it is likely that parasites resistant to all known drugs will emerge. The authors of the paper end on a pessimistic note:

The pace at which the geographical extent of artemisinin resistance is spreading is faster than the rate at which control and elimination measures are being developed and instituted, or new drugs being introduced.

In other words, deaths from malaria will increase rather than continue to decrease, which is what we have come to think of as the normal evolution of a disease.