Study shows effective malaria drug combinations

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Researchers have identified two combinations of drugs to treat malaria in Africa that could replace the widely used combination of chloroquine and sulfadoxine-pyrimethamine (SP), which has been rendered ineffective as the malaria parasite has grown resistant to it.

The researchers, led by Philip J Rosenthal at the University of California at San Francisco, published their findings in last week’s issue of The Lancet.

They gave 1,017 Ugandan children with malaria one of three drug combinations, then monitored them for 28 days to see whether the initial infection recurred or if the children got a new infection (by being bitten again by mosquitoes carrying the malaria parasite).

When amodiaquine was used in combination with SP the risk of treatment failing was higher than when it was combined with artesunate. However, when the former combination was used, the risk of children getting a new infection was much lower.

The researchers argue that although treatment failure is usually used as an indicator of how effective a treatment is, these two opposing factors ‘balance’ each other out. As a result, they estimate that the need to re-treat patients was about the same for both combinations. 

They say, therefore, that either of combinations including amodiaquine would be preferable to the third combination tested — chloroquine and SP — which they say has an “unacceptably high” risk of failing to treat the patient.

But Amir Attaran of the Institute of Population Health and Faculty of Law at the University of Ottawa, Canada, disagrees. In an accompanying article in The Lancet, he calls the researchers’ argument to equate the two treatments “unpersuasive” and “qualitatively illogical”.

“A treatment failure means that a sick patient gets sicker — possibly until he or she is dead,” writes Attaran. “A new infection means that the patient returns to clinic for treatment — certainly a bother. Death and bother are highly different. They never balance.”

Attaran’s comments may be too harsh, says Sanjeev Krishna at St George’s Hospital Medical School in London. He points out that Attaran does not mention cost — a crucial factor in drug choice for developing countries. The treatment that reduces the risk of a new infection is five times more expensive than the other.

Krishna told SciDev.Net that the question of whether it is worse to have a recurrence of the same infection or a new infection is “academic”. Krishna believes that the researchers’ conclusions are “cautious, balanced and reasonably fair”.

Attaran also points out that Uganda has now changed its malaria policy to favour a different drug regime any of those under study, one combining artemether with lumefantrine. Attaran says this makes Rosenthal and colleagues’ work out of date already.

This treatment has proved to be so effective, and is in such high demand, that the World Health Organisation recently declared that there could be a shortage of it until next year.

The short supply has pushed the drug’s market value up three- to five-fold, says Krishna.

A drug that works brilliantly but is expensive and in short supply is no good to the thousands of children currently dying of malaria, Krishna points out. Until we have cheap and freely available drug combinations that work, research such as Rosenthal’s will always be needed, he adds.

Link to full paper by Staedke et al in The Lancet*

Link to accompanying article by Amir Attaran in The Lancet*

References: The Lancet 364, 1922 (2004) / The Lancet 364, 1950 (2004)

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