An international group of researchers has found evidence indicating partial resistance to artemisinin derivatives, which are the main medications used to treat malaria, particularly in young children suffering from severe malaria.
Researchers from Indiana University School of Medicine, alongside partners at Makerere University in Uganda, have discovered signs of partial resistance to artemisinin derivatives in young children experiencing severe forms of malaria, often referred to as “complicated” malaria.
Previous research has identified partial resistance to artemisinin in children with mild malaria, but the recent study published in the Journal of the American Medical Association (JAMA) is the first to demonstrate this resistance in African children showing clear signs of severe malaria.
“For the last two decades, artemisinin-based treatments have been vital in the battle against malaria,” stated Chandy C. John, MD, a pediatric specialist at the IU School of Medicine and the lead author of the study. “The rise in evidence of partial artemisinin resistance in African children with uncomplicated malaria raises concerns that alternative treatments, such as triple artemisinin combination therapies, might be necessary for uncomplicated cases. Our findings of artemisinin partial resistance in severely ill children, combined with the prevalence of recurring malaria despite standard treatments in these regions, suggest that new therapies might also be essential for severe malaria cases.”
Directed by John and his co-authors Ruth Namazzi, MBChB, MMEd; Robert Opoka, MD, MPH, from Makerere University; Ryan Henrici, MD, PhD, from the University of Pennsylvania; and Colin Sutherland, PhD, MPH, from the London School of Tropical Medicine and Hygiene, the investigation focused on 100 Ugandan children ages 6 months to 12 years being treated for complications of severe malaria caused by the Plasmodium falciparum parasite, which is transmitted by mosquitoes.
In the findings, 10 children were identified with parasites that had genetic mutations linked to partial resistance to artemisinin. The most frequently found mutation, present in eight of these children, was associated with an extended time for parasite clearance — the duration it takes for the parasite’s level in the body to reduce to half its original count. The study also indicated that 10% of the children revisited within 28 days post-treatment with an infection from the same malaria strain as during their initial admittance. Notably, all these children had completed both intravenous and subsequent oral treatments for severe malaria and had cleared the parasite as verified by microscopic analysis. John remarked that these results imply that while standard intravenous and oral treatments effectively diminish the parasite counts to undetectable levels under a microscope, they might not fully eradicate the parasite in some children.
Reports about artemisinin resistance first emerged in Southeast Asia back in 2008 and then appeared in East Africa, a trend that the IU research team unexpectedly spotted during their ongoing research in Uganda. While investigating the reasons behind severe malaria in children, researchers observed that some participants in Uganda exhibited slower responses to artemisinin, triggering the need for this current study.
John emphasized the importance of further data on artemisinin resistance and the recurrence of malaria in severely ill children, stating, “If our study results are verified in other regions, it could indicate that the treatment guidelines for severe malaria might need to be updated.”
John shared the study’s findings at the Annual Meeting of the American Society of Tropical Medicine and Hygiene on November 14 in New Orleans, Louisiana.
