Most of the deaths from malaria occur among young kids in rural areas. An acute case of malaria can become so severe that the patient cannot swallow and 'keep down' oral treatment.
If patients with severe malaria who cannot be treated orally are several hours of travel away from facilities for injections, rectal artesunate - which acts rapidly on malaria parasites - could be given before setting out on the journey.
Dr Melba Gomes, WHO, Geneva, Switzerland, and colleagues investigated whether pre-referral treatment reduced mortality and permanent disability.
For the study, patients in Bangladesh, Ghana, and Tanzania, with suspected severe malaria who could not be treated orally were allocated randomly to an artesunate (8954 patients) or placebo (8872) suppository (ie, rectal application).
Most had a drop of blood taken beforehand for later examination, and those with no malaria parasites in it were excluded from the main analysis (as they probably had a viral or bacterial infection, which artesunate cannot affect).
The researchers found that for patients who were able to reach the injections clinic within six hours, there was no significant difference in mortality or permanent disability between the two groups.
However, in patients still not in clinic after six hours (and half of these were still not there after 15 hours), pre-referral rectal artesunate halved the risk death or permanent disability (29 of 1566 patients for artesunate vs 57/1519 for placebo).
"Death from malaria reflects delay in administration of effective antimalarial treatment. Our results provide strong evidence that if patients with severe malaria cannot be treated orally and referral is likely to take several hours, an immediate rectal dose of artesunate before referral substantially reduces the risk of death or permanent disability," the authors said.
The study is published in an upcoming edition of The Lancet.