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  • 'Resistance is emerging' to antimalarial drug of choice


Malaria parasites found in West Africa are showing signs of resistance to what is thought to be the most powerful antimalarial drug, say researchers.

Artemisinin was introduced in several African countries after the parasite developed resistance to chloroquine, previously one of the most common drugs.

Yet, in The Lancet this week (3 December), a team of researchers from Cambodia, France and Senegal show that some resistance to the drug is emerging in French Guiana and Senegal.

Ronan Jambou, who led the project at the Pasteur Institute in Dakar, Senegal, says that "for the moment we can expect no impact on the treatment of malaria in Africa" because artemisinin is administered not in isolation but only in combination with other antimalarial drugs.

Researchers believe the parasite is less likely to develop resistance to a combination of drugs than to a single drug used in isolation.

He adds, however, that the parasite's resistance to artemisinin should be carefully monitored to avoid a repetition of what happened with chloroquine.

"Forty years separated the first description of chloroquine resistance from its withdrawal. We think that we have time [to avoid widespread resistance] if we use these compounds carefully," Jambou told SciDev.Net.


The team took blood samples from 530 malaria patients in Cambodia, French Guiana and Senegal, and tested the parasites to see if they were resistant to artemisinin.

No resistant parasites were found in the Cambodian samples, but samples from French Guiana and Senegal showed signs of resistance.


The report suggests that the uncontrolled use of artemisinins might have created conditions favourable for the rise of resistant malaria — especially in French Guiana, where the local parasite population has undergone considerable genetic mutation over time.


They also predict that under the carefully controlled regime of artemisinin use prevalent in Cambodia, resistance might be delayed or possibly even prevented.


In response to the widespread emergence of malaria parasite strains that are resistant to several drugs, the World Health Organization (WHO) has recommended the use of artemisinin-based combination drug therapy as first-line treatment.

Artemisinin, which is extracted from a Chinese herb known as sweet wormwood, is the most potent and fastest-acting antimalarial. So far, there has been no evidence of resistance to it in human malaria parasites.


Jambou told SciDev.Net that lowered sensitivity to artemisinin in the parasite was associated with mutations — changes in DNA — in a gene called serca, which is known to be sensitive to this class of compound.


To prevent any widespread incidence of artemisinin-resistant malaria, Jambou says that monitoring and further research are important.


"We need to survey any appearance of new mutations, especially in Africa, where all the control programmes are currently moving their drug policy to ACTs," he says. "We also need to research other genes potentially involved in artemisinin resistance by in vitro studies."


Jambou adds that the drug should only be administered in approved artemisinin-based combination therapies (ACTs), and never alone.


He says it is possible that the Cambodian samples showed no sign of resistance because at the time they were taken, in 2001, artemisinin was only used in combination therapies there. According to the Cambodian health ministry, however, there is now an illegal market for artemisinin in the country.


"Jambou and colleague's paper is a wake-up call," write US researchers Patrick Duffy and Carol Sibley in a comment published with the report.

"We ignore this warning at the risk of a rapid demise of ACTs that are currently just being tested and deployed," they add.

Link to full paper by R. Jambou et al. in The Lancet
[available from 5 December]

Link to full commentary by P. Duffy and C. Sibley in The Lancet
[available from 5 December]

Reference: The Lancet 366, 1908 (2005)

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