Artesunate, the standard treatment for severe malaria in children, remains effective even in areas where drug-resistant malaria parasites are emerging, offering reassurance for malaria treatment across Africa, according to a new study led by researchers at the KEMRI-Wellcome Trust Research Programme.
The findings, published in the New England Journal of Medicine, show that although resistant parasites take longer to clear from the body, they do not worsen outcomes for children treated with the drug.
Malaria remains one of Africa's biggest killers, claiming an estimated 610,000 lives globally every year, with about 95 per cent of the deaths occurring among African children.
Researchers warned that the spread of Kelch (PfK13) mutations in Plasmodium falciparum, the parasite responsible for the deadliest form of malaria, had raised concerns because the mutations are linked to slower response to artesunate.
However, the new evidence suggests the standard treatment continues to save lives despite the emerging resistance.
The findings are based on the SMAART-CHARISMA clinical study conducted in northern and eastern Uganda between December 2022 and October 2024.
Researchers followed 465 hospitalised children aged between three months and 15 years. Of these, 360 had severe malaria while 105 had less severe illnesses for comparison. All received the standard treatment of intravenous artesunate followed by a three-day course of oral artemether-lumefantrine.
The study found that nearly half of the children carried the resistant PfK13 mutations.
Although the parasites cleared more slowly in children with the mutations, researchers found no significant differences in death rates, length of hospital stay, need for blood transfusions, recovery from lactic acid build-up, malaria recurrence or hospital readmission compared to children infected with non-resistant parasites.
Speaking on the findings, KEMRI Director General Prof. Elijah Songok said the study provides confidence that existing treatment guidelines remain effective.
"These findings provide timely reassurance that current treatment protocols for severe malaria remain effective for African children, even in the face of emerging drug resistance. They underscore the importance of evidence-based policy decisions and sustained investment in locally led research to safeguard the gains made in malaria control across the continent."
The findings come after the World Health Organization recommended in 2025 that quinine be added to artesunate in areas with established artemisinin resistance.
However, lead researcher Prof. Kath Maitland said the study suggests the additional drug may not be necessary.
"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."
She added that continued surveillance remains important as resistant malaria parasites spread across Africa.
"Further research is still needed to monitor how the PfK13 mutation responds to artesunate in larger cohorts and in other countries in Africa where these mutations are emerging."
Artesunate replaced quinine as the first-line treatment for severe malaria in 2012 after clinical trials showed it reduced deaths by 23 per cent, a breakthrough estimated to save more than 100,000 African children every year. The new findings reinforce confidence in the treatment while highlighting the need for continued monitoring of emerging drug resistance.
