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Artesunate – the standard treatment for severe malaria in children – is still effective, even in regions of Africa where drug-resistant malaria parasites are becoming more common.

This according to new research led by , director of the Centre of African Research and Engagement, and published today in the . 

African children account for most malaria deaths

Of the estimated 610,000 annual global deaths from malaria, some 95 per cent (c.580,000 deaths) occur in African children.  The replacement of quinine by artesunate as the first-line treatment for severe malaria in 2012, following a clinical trial which demonstrated that artesunate reduced mortality by 23 per cent, has saved the lives of over 100,000 African children annually. 

New variants pose new health threat

However, a new health threat is now posed by Kelch (PfK13) mutations of Plasmodium falciparum (the parasite that causes malaria) becoming resistant to artesunate and taking longer to clear infection from the body after treatment.  This represents a major public health threat because most severe malaria deaths in children occur soon after they are admitted to hospital, so treating it quickly is vital. 

Artesunate effective at treating variants

In 2025, the World Health Organization recommended adding quinine to artesunate to treat severe malaria in areas with established artemisinin resistance, but this research suggests that is unnecessary. 

The findings are based on the SMAART-CHARISMA clinical study conducted in northern and eastern Uganda between December 2022 and October 2024. The researchers looked at 465 hospitalised children aged between three months and 15 years – 360 of whom had severe malaria, the other 105 had less severe illnesses for comparison.

All the children were given the standard treatment for malaria – at least three doses of intravenous artesunate, followed by a three-day course of oral artemether-lumefantrine. 

The team used advanced genetic testing to identify PfK13 mutations and compared the outcomes for the children with mutated parasites to those with normal parasites. 

Key findings

They found that:  

• about half of all the children carried the PfK13 mutations  
• all the children were similarly ill when hospitalised
• the parasites cleared more slowly in the children with mutations but did not negatively affect their outcomes
• death rates were low and did not differ significantly between the two groups 

Furthermore, there were no meaningful differences between the two groups in:  

• how long the children stayed in hospital
• whether they needed a blood transfusion  
• how long it took their body to clear lactic acid
• whether the malaria reoccurred
• whether they were readmitted to hospital 

Changes would be unnecessary, complex and costly

The results of our study are reassuring and important for malaria treatment policy. Artesunate remains highly effective at treating severe malaria in children in real-world clinical settings, so WHO recommendations to add quinine to the treatment protocol would be unnecessary, complex and costly. Professor Kath Maitland Director, Centre of African Research and Engagement

Professor Maitland added: 

"Further research is still needed to monitor how the PfK13 mutation responds to the artesunate in larger cohorts and in other countries in Africa where these mutations are emerging.” 

Dr Maurice Okao, local study principal investigator, said of the findings:  

“These findings provide empirical validation for the sustained clinical efficacy of intravenous artesunate in severe malaria, substantially alleviating – though not entirely dispelling – concerns surrounding potential therapeutic failure of the current first-line agent.” 

is published today in the New England Journal of Medicine. 

The research was funded by Wellcome and the National Institutes of Health, National Institute of Allergy and Infectious Diseases. Additional funding for individual researchers was provided by the Medical Research Council and Wellcome.