The recommended treatment for malaria worked well, even against strains resistant to the treatment, researchers reported in a new study.
Children with resistant malaria strains and treated with intravenous artesunate experienced about the same outcomes as children with non-resistant strains who also received the treatment, Dr. Kathryn Maitland, director of Imperial College’s Centre of African Research and Engagement, and coauthors said in the study, published in the New England Journal of Medicine on June 3.
The 465 children, aged 3 months to 15 years and many of whom had severe malaria, were hospitalized and treated in Uganda between December 2022 and October 2024.
Children received a minimum of three doses of intravenous artesunate, which has been recommended for years by the World Health Organization (WHO) and others as the primary treatment for severe malaria.
Resistant malaria, which arises from mutations in the parasite that causes malaria, was detected in about half of the children.
The parasites cleared more slowly in children with the resistant strains, but the median hospital stay was about the same, as were hospital readmission rates. The death rates were actually lower among children with the resistant variants, including 1.7 percent versus 5.5 percent by day five.
“The results of our study are reassuring and important for malaria treatment policy,” Maitland said in a statement. “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.”
In 2025, the WHO advised supplementing artesunate with quinine when treating severe malaria in areas with known circulation of resistant malaria strains.
“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,” added Dr. Maurice Okao, who works at the Dr. Ambrosoli Memorial Hospital in Uganda and is another author.
The researchers said it was not clear why infection caused by the resistant parasites did not lead to worse outcomes.
The mutations “have an effect on parasitic clearance only during the early ring stage, whereas mature parasites (sequestered in the microcirculation, resulting in organ dysfunction) remain highly sensitive to artemisinins, which potentially blunts the effect on clinical outcomes,” they wrote. “Alternatively, survivor bias before hospitalization cannot be excluded.”
Funding for the research came from the Wellcome Trust, the National Institutes of Health, and University College London. Outside of grants for the research, authors disclosed no conflicts of interest.