With up to 37.5% of children carrying this resistance mutation the findings suggest that current treatment protocols may be losing effectiveness.
A new study conducted in Uganda has found evidence of partial resistance to the key malaria drug artemisinin in children with severe forms of malaria, raising concerns about the long-term effectiveness of current treatment protocols. Published in JAMA, the study identifies specific genetic mutations in the Plasmodium falciparum parasite, particularly the A675V variation in the Pfkelch13 gene, associated with slower parasite clearance in children receiving standard malaria therapies. Despite treatment, the study revealed suboptimal efficacy, suggesting that the drug was not as effective as expected in clearing the infection.1
Of the 100 children aged six months to 12 years enrolled in the study, 11 showed signs of partial resistance to artemisinin. Children with the A675V mutation took significantly longer to clear the infection compared to those without the mutation, with some requiring extended treatment, up to 96 hours.1
The findings revealed that 37.5% of children carrying the A675V mutation had parasite clearance times exceeding five hours, a marker of artemisinin resistance. This contrasted with just 8.9% of children without the mutation. Despite the partial resistance, the study did not find a direct link between the resistance mutations and malaria recurrence (recrudescence) within 28 days, suggesting that other factors may contribute to relapse.1
“The fact that we started seeing evidence of drug resistance before we even started specifically looking for it is a troubling sign,” Study co-author, Chandy John, MD, MS, former ASTMH president said in a press release. “We were further surprised that, after we turned our focus to resistance, we also ended up finding patients who had recurrence after we thought they had been cured.”2
The investigators found that the genetic variation, Pfkelch13 A675V, linked to partial resistance to artemisinin, impacted the effectiveness of the standard treatment regimen, which consists of an intravenous injection of artesunate followed by oral artemether/lumefantrine. The study's other limitations included a small sample size and being conducted at a single location, which may limit the generalizability of the results.
A study in Uganda found partial resistance to artemisinin in children with severe malaria, linked to a genetic mutation in the Plasmodium falciparum parasite.
Children with the A675V mutation had slower parasite clearance, suggesting reduced efficacy of standard artemisinin-based treatments.
80% of malaria deaths occurring in African are children under five.
In an editorial that accompanies the study, Philip Rosenthal, MD, expert in malaria, notes this resistance could impact thousands of children in sub-Saharan Africa who are treated with artesunate. This would likely necessitate changes to current treatment strategies.3
“Sorting out the best means of treating severe malaria in the setting of ART-R [partial artemisinin resistance] will be challenging, but the first step in this process is determining whether currently circulating ART-R parasites are preventing effective treatment,” Rosenthal said. “Thus, trials to determine the effect of ART-R on the efficacy of parenteral artesunate to treat severe malaria are an urgent priority.”3
In conclusion, this research represents a step in recognizing and understanding the emerging threat of drug resistance in malaria treatment across Africa. While many children in the study responded well to treatment, the evidence of partial resistance underscores the need for potential changes to current treatment strategies. According to WHO, Africa accounts for 95% of the 608,000 global malaria deaths each year, with 80% of these fatalities occurring in children under five.4 Addressing this issue will be essential for improving outcomes and saving lives in malaria-endemic regions.
