/ 5 December 2005

Malaria parasite develops a taste for new drug

Malaria parasites found in Africa are showing signs of resistance to the most powerful anti-malarial drug available, say researchers on the Science and Development Network website. Artemisinin was introduced in several African countries, including South Africa, after the parasite developed resistance to the commonly-used anti-malaria drug chloroquine. Yet an international team of researchers from Cambodia, France and Senegal show that resistance to the drug is emerging in Senegal in West Africa.

Ronan Jambou, who led the West African leg of the project at the respected Pasteur Institute in Dakar, Senegal, says that the parasite’s resistance to artemisinin should be carefully monitored to avoid a repetition of the problems with chloroquine, which took 40 years to become widespread. “We think that we have time if we use these compounds carefully,” said Jambou. Jambou said “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 anti-malarial drugs, which makes it harder for the parasite to develop drug resistance.

The team drew blood from 530 malaria patients in Cambodia, French Guiana in South America, 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 Senegal showed signs of resistance. So did those from little-known French Giuana, the only portion of the South American continent still under colonial rule and until now best known for its European Space Agency satellite launch site. 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.

The researchers 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 Organisation 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 anti-malarial. Jambou said 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 artemisinin-based combination therapies,” 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 combinations with other drugs, 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’s research “is a wake-up call,” write US researchers Patrick Duffy and Carol Sibley in a comment published with the report in the British-based medical journal The Lancet.

“We ignore this warning at the risk of a rapid demise of ACTs (artemisinin in combination with other anti-malarial drug therapies) that are currently just being tested and deployed,” they add. Research published in 2004 by University of Cape Town scientists Karen Barnes, Charlotte Muheki and Di McIntyre found that using artemisinin in conjunction with other drugs (and spraying with powerful insecticides at homes in affected regions) reduced the cost of malaria treatment in the province of KwaZulu-Natal, where the disease is epidemic. However, research since then has suggested that these results may not apply to poorer parts of Africa, where many people infected with the parasite do not receive treatment and the state is unable to afford spraying programmes. SciDev.Net