Evidence suggests drug resistance in Ugandan children with severe malaria
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Key takeaways:
- Eleven percent of children with complicated or severe malaria showed evidence of drug resistance.
- Ten percent had evidence of their infections returning because it was not completely eliminated.
Researchers found evidence of artemisinin partial resistance in Ugandan children with complicated malaria, according to data presented at the Annual Meeting of the American Society of Tropical Medicine and Hygiene.
“In an earlier study of children with severe malaria, we saw that a number of them were taking 4 or even 5 days to clear parasites on blood smear, despite treatment with artesunate [a semisynthetic derivative of artemisinin], the recommended drug for severe malaria,” Chandy C. John, MD, MS, Ryan White professor of pediatrics and director of the Ryan White Center for Pediatric Infectious Disease and Global Health at Indiana University, told Healio.
“This is much longer than expected (parasites should clear by day 3), so it made us wonder if artemisinin partial resistance was present in the parasites that infected these children,” he said.
Because the researchers had not studied drug resistance in the earlier study, John said they dedicated a separate study specifically to drug resistance in children with severe malaria.
“Previous studies had largely looked at children with uncomplicated malaria, and we wanted to know if children with well-defined severe malaria — who are at the highest risk of death and long-term complications — had evidence of artemisinin partial resistance,” John said.
To assess this resistance, the researchers performed a prospective study of children in Jinja, Uganda aged 6 months to 12 years with complicated malaria who were treated with parenteral artesunate, followed by oral artemether/lumefantrine between 2021 and 2022. According to the study, outcomes included parasite clearance half-life, artemisinin partial resistance and early treatment failure.
Data from the study, which were also published in the Journal of the American Medical Association, showed that 11% of children with complicated or severe malaria showed evidence of artemisinin partial resistance. John explained that the researchers determined the artemisinin partial resistance was related to the presence of a specific mutation — A675V — in the PfKelch13 gene. He added that the presence of this mutation being associated with artemisinin partial resistance was observed in other studies as well.
During the study, two children also had early treatment failure with “persistence of parasites” for 72 hours or more. According to John, this required the children to receive prolonged IV artesunate treatment.
The study also demonstrated that 10% of children had evidence of their original infections returning because it was not eliminated despite these children receiving initial treatments until blood smears were negative. John said that this suggests that the partner drug in the oral treatment — lumefantrine — may not be as effective as initially hoped because the recurrence was not related to the PfKelch13 mutation or to artemisinin partial resistance.
“We need more studies of artemisinin resistance and post-treatment recrudescence in children with severe malaria,” John said. “Because if other studies confirm our findings, we will need to consider whether current treatment guidelines for severe malaria need to be modified or added to.”
References:
- John CC, et al. JAMA. 2024;doi:10.1001/jama.2024.22343.
- New study provides first evidence of African children with severe malaria experiencing partial resistance to world’s most powerful malaria drug. Published Nov. 14, 2024. Accessed Nov. 14, 2024. [Provided prior to publication online.]
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