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  • Biomed Analysis: Tackling drug-resistant malaria

Emerging resistance to artemisinin means efforts to track genetic markers and regulate the drug's use must step up, says Priya Shetty.

When parasites resistant to the anti-malarial drug artemisinin were discovered along the Thailand-Cambodia border in 2006, it sparked concern but not panic because it appeared to be an isolated pocket of resistance.

Now, scientists have found multiple pockets of drug resistance along the Thailand-Myanmar border, triggering fears that resistance could spread to the rest of Asia. Worse, it could spread to Africa, which has 90 per cent of malaria cases, and where public health systems would soon be overwhelmed if artemisinin became powerless to control the disease.

Artemisinin revolutionised malaria control when it was rolled out in 2005. Older drugs such as chloroquine had become largely ineffectual through widespread resistance, and attempts to prevent infection with insecticide-treated bednets and indoor spraying were insufficient.

The new findings published in The Lancet this month sound a warning for health experts in Africa. Ever since artemisinin was first used, scientists have cautioned that its misuse could lead to a new breed of parasites that are unaffected by it.

African health experts and political leaders need to step up efforts to regulate malaria drug treatment, or face losing the only drug that can battle the parasite.

Rising resistance

Resistance to older anti-malarials drugs likely emerged in Cambodia, and then spread to countries in the rest of Asia and Sub-Saharan Africa.  Whether resistance to artemisinin spread from Cambodia to Thailand or emerged separately in both countries, there is much to be concerned about.

The levels of resistance in Cambodia now mean that artemisinin-based drugs take nearly three times as long to clear the infection. Along the Thailand-Myanmar border, resistance is progressing fast enough to reach this level in as little as two years.

And last year in Kenya, researchers found a small decline in the proportion of malaria patients who responded to treatment with artemisinin, suggesting that parasites may be gaining resistance to the drug there. [1]

One of the main reasons for the development of resistance is the misuse of drugs in countries where they are poorly regulated. Artemisinin is often sold on its own, rather than in combination, or it is sold in suboptimal doses. Taking artemisinin in combination with another anti-malarial drug greatly reduces the chance of resistance emerging.

Both practices, as well as patients taking incomplete courses, can raise the risk of resistance developing.

Gene hunting

This time around though, we may have a chance of stopping the spread of resistance. For one thing, we now have a clue to the genetics that underpin it.

A separate group of researchers, publishing in Science [2], has identified an area of the parasite genome associated with artemisinin resistance, paving the way to finding the specific mutations that allow the parasite to survive the drug.

Understanding the genetics is vital. Developing a reliable marker for resistance would help scientists identify which resistant parasite strains are spreading, and which are emerging anew — eventually offering a new type of molecular surveillance.

So far, the battle against malaria has focused on increasing the availability of artemisinin drugs, and on preventing infection through the use of bednets and the development of a malaria vaccine. Clearly these goals are still important, but much more resources need to go towards identifying the molecular basis of resistance, so that this can be accurately tracked.

Stopping the spread

Artemisinins are still the only highly effective anti-malarials available. Now their effectiveness is seriously under threat, research into new drugs seems a higher priority than ever before. But drug discovery is an unpredictable business, and a more long-term solution.

Until then, safeguarding our best weapon against malaria through appropriate use and better regulation in developing countries is going to be our best bet.

And efforts to contain drug resistance need to be targeted to countries, such as Myanmar, where the public-health infrastructure is too weak to cope with large numbers of drug-resistant malaria cases.

Journalist Priya Shetty specialises in developing world issues including health, climate change and human rights. She writes a blog, Science Safari, on these issues. She has worked as an editor at New Scientist, The Lancet and SciDev.Net.

References

[2] Cheeseman I.H., et al. A Major Genome Region Underlying Artemisinin Resistance in Malaria. Science 336, 79-82 (2012)
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