Clinical trial calls for change in treatment guidelines for severe malaria

The largest ever clinical trial in patients hospitalised with severe malaria has concluded that the drug artesunate should now be the preferred treatment for the disease in both children and adults everywhere in the world. The study, funded by the Wellcome Trust, is published in the latest edition of the journal The Lancet1.

An international consortium of researchers, led by Professor Nick White of the Wellcome Trust-Mahidol University-Oxford Tropical Medicine Research Programme in Bangkok, Thailand, compared treatment with artesunate, which is used in Asia to treat severe malaria, against quinine, which has been in use worldwide for over three hundred years. The trial – known as the African Quinine v. Artesunate Malaria Trial (AQUAMAT) – was carried out over a five year period in hospitals across nine African countries and studied 5,425 children with severe malaria.

Severe malaria kills nearly a million people each year, mainly young children and pregnant women. It is caused by parasites which are injected into the bloodstream by infected mosquitoes. Severe malaria is often the main reason why children are admitted to hospital in Sub-Saharan Africa, and one in ten of these children die.

For over three centuries, doctors have relied upon quinine to cure malaria. Quinine is a reliably effective drug, but it is difficult to give by injection and has unpleasant side effects, some of which are potentially dangerous.

AQUAMAT compared quinine against the more recent drug artesunate both given either intravenously or by intramuscular injection, and showed that treatment with artesunate reduced the number of deaths from severe malaria by 22.5%. With artesunate treatment 8.5% of the patients died, compared to 10.9% with quinine. The results were very similar in all the study sites.

Children treated with artesunate were also less likely to slip into a deeper coma or have seizures after the treatment was started. Severe hypoglycaemia – dangerously low blood sugar – was also less common in children treated with artesunate. In addition, artesunate was easy to administer, well tolerated, and proved very safe.

AQUAMAT was carried out in eleven hospitals across Mozambique, Tanzania, Kenya, Uganda, Rwanda, the Democratic Republic of Congo, Nigeria, Ghana, and The Gambia and involved over 200 collaborators. The Gambian arm of the study took place at the Royal Victoria Teaching Hospital, Banjul. Dr Kalifa Bojang of MRC (UK) The Gambia and study leader of the Gambian arm of AQUAMAT said “Quinine is the only drug recommended for the treatment of severe malaria throughout Africa. But even with prompt administration of quinine in maximum doses the mortality of severe malaria remains high. Our findings in this large multicentre trial show that parenteral artesunate reduces mortality in patients with severe malaria by 23% compared with quinine. We are very excited about this result as we now have a better treatment for severe malaria that has the potential to save the lives of hundreds of thousands of African children.’

1Dondorp, A. et al. AQUAMAT: an open randomised comparison of artesunate versus quinine in the treatment of severe falciparum malaria in African children. Lancet; e-pub 6 Nov 2010
For further information contact
Chris Brierley, Senior Media Officer, Wellcome Trust UK: c.brierley@wellcome.ac.uk
Communications Office, MRC (UK) The Gambia: communications@mrc.gm