Dogma among researchers exaggerates threat of resistance to best anti-malarial drugs, says malaria expert

In an opinion article published on World Malaria Day today (25 April 2013) -- online in the journal Trends in Parasitology, Professor Sanjeev Krishna of St George's, University of London argues that much of the evidence of the malaria parasite's resistance to artemisinin has been misinterpreted. He says this has led to the extent of artemisinin resistance being overstated, and that fears of its demise as an effective treatment are premature.

The artemisinin class of drugs are the best anti-malarial treatments available, and are used most effectively with other drugs as artemisinin-based combination therapies (ACTs). Recent research has suggested that the malaria parasite is developing resistance to ACTs, particularly in Southeast Asia. Experts fear that if artemisinins became obsolete -- as previous anti-malarials have -- the effect could be devastating, as there are currently no other effective alternatives.

However, Professor Krishna argues that -- despite being accepted as dogma by the malaria research community -- most of the descriptions of artemisinin resistance do not meet the criteria by which resistance to other anti-malarials and drugs for other diseases have been measured.

For true resistance to exist, according to criteria used for other drugs, there needs to be: a significant failure in treatment (by not meeting the World Health Organization's target of a 95 per cent cure rate 28 days after treatment); a reduced sensitivity to the drug when the parasite is examined in the lab; and a visible delay in ridding the patient of parasites.

Currently, Professor Krishna says, it seems to be accepted that artemisinin treatment failure has occurred when a three-day course of ACT does not meet the target cure rate. This has been observed in a number of studies and has been used to try and understand 'artemisinin resistance.'

But other studies of seven-day courses of artemisinin monotherapies -- in which artemisinins are used alone, without partner drugs -- have shown up to 100 per cent cure rates after 28 days.

This, Professor Krishna, says, indicates proof of resistance to ACTs, but that there is no compelling evidence that artemisinins themselves are becoming less effective. He says this resistance will usually "be to a combination of an artemisinin with another drug against which there is usually a high background of resistance already."

"Contending that there is artemisinin resistance when cure of patients relies on the partner drug of an artemisinin is difficult to substantiate without additional studies," writes Professor Krishna. "It is more appropriate to describe the lack of observed efficacy as resistance to an artemisinin combination therapy rather than as being artemisinin resistance."

He adds that "crying wolf" and raising fears of artemisinin resistance when it is not yet proven "will itself have significant costs, so that when the wolf finally turns up, exhausted villagers no longer respond."

To ensure better understanding of when true artemisinin resistance occurs, and to learn how to fight it, Professor Krishna says there needs to be further research into the how the drugs work against the parasite. He also urges the development of molecular markers to predict the failure of the partner drugs used in ACTs, as well as further studies on artemisinin monotherapies.