A new study from Uganda (Makerere University in Kampala) provides the first evidence that resistance to a lifesaving malaria drug may be emerging in the group of patients that accounts for most of the world’s malaria deaths: young African children.
The study has been presented to the Annual Meeting of the American Society of Tropical Medicine and Hygiene. Here researchers presented evidence pf partial resistance to the malaria drug artemisinin in 11 of 100 children, ages 6 months to 12 years, who were being treated for “complicated” malaria, that is, malaria with signs of severe disease caused by the malaria parasite Plasmodium falciparum.
Furthermore, 10 patients who were thought to have been cured suffered a repeat malaria attack within 28 days from the same strain of malaria that caused the original infection, suggesting that the initial treatment did not fully kill the infecting parasites.
The use of artemisinin therapies, which began some 20 years ago, was a major advance in the global fight against malaria due to their power to rapidly cure infections.
Yet, in 2008, there were reports from Cambodia noting partial resistance to artemisinin. By 2013 there was evidence that in some patients, the drug was completely failing. In the last few years, there has been increasing evidence that artemisinin resistance has now spread from that region into East Africa.
The prospect of artemisinin losing its efficacy is particularly alarming for Africa and especially for African children. The region accounts for 95 percent of the 608,000 people who die from malaria each year and a large majority of malaria deaths in Africa are children under 5.
While all of the children in the study eventually recovered, 10 of them were infected with malaria parasites that harbour genetic mutations that have been linked to artemisinin-resistance in Southeast Asia.
The study noted that while these mutations have been documented in Africa in less severe cases, this was the first time they have been seen in parasites that were causing complicated malaria in hospitalized African children.
The term “complicated” malaria is used to define cases where the disease is at risk of causing potentially life-threatening complications, like severe anaemia or brain-related problems known as cerebral malaria.
The researchers classified patients as suffering from partial resistance based on the World Health Organization’s defined half-life cutoff for parasite clearance of more than five hours, meaning requiring more than five hours to reduce a patient’s parasite burden by 50 percent. Two children required longer than the standard maximum of three days of artesunate therapy because they failed to clear their parasites with three days of therapy.
The Ugandan children in the study received what is considered to be the gold standard for treating complicated malaria infections: an intravenous infusion of artesunate followed by oral treatment with an ACT that combines another derivative of artemisinin, a drug called artemether, with the malaria drug lumefantrine.
The study emerged from ongoing work in Uganda that is investigating outcomes of children who experience episodes of severe malaria. Researchers pivoted to a focus on drug resistance because they noticed some children appeared to be slower to respond to the infusion of artesunate followed by an oral ACT.
The findings have been published in the Journal of the American Medical Association (JAMA). The research is titled “Artemisinin Partial Resistance in Ugandan Children With Complicated Malaria”.
