Partial resistance to a life-saving antimalarial drug has been detected in Uganda among children experiencing severe forms of the disease.
The findings of a new study published in the Journal of the American Medical Association (JAMA) paint a worrying picture. The authors reported evidence of partial resistance to the antimalarial drug artemisinin among 11 out of 100 children treated for severe malaria at a hospital in Uganda. They found that, for these 11 children, it took longer than expected for the drug to kill the parasites within three days of treatment. In addition, once authors began to focus on drug resistance, they discovered patients who had experienced recurrent malaria, even after they were thought to have been cured.
This is a worrying development. As the first-line treatment for malaria, artemisinin and artemisinin-based combination therapies — in which artemisinin is combined with partner drugs such as lumefantrine, mefloquine and amodiaquine — are a crucial weapon against this disease.
There have been growing concerns about the rise of antimalarial drug resistance spreading across Africa. Resistance develops when the malaria-carrying parasite Plasmodium falciparum mutates, allowing the parasite to continue to survive until the drug concentration has reduced. The longer the parasite can stay alive in the body, the higher the chance the treatment can fail. In the case of malaria, this places children with severe malaria at a high risk of death.
In July of 2024, a group of scientists published a call to action in the journal Science to tackle artemisinin-resistant malaria. The same month, another editorial in The Lancet Microbe posed the question: “How do we stop the global health catastrophe of artemisinin resistance in Africa?” The authors warn that although the catastrophe in question has not yet arrived, “therein lies an opportunity to be proactive rather than reactive,” they wrote.
This is not the first time that antimalarial drug resistance has emerged. In southeast Asia, partial resistance has been reported for years. But the development of partial resistance in Africa threatens to be devastating, given that the overwhelming majority of malaria cases and deaths occur in the continent. In 2022, 94 percent of malaria cases and 95 percent of malaria deaths were in Africa. A 2015 study modelled the potential impact of widespread resistance to both artemisinin and a partner drug in Africa. It estimated that there could be 16 million more malaria cases each year, and around 360,000 more severe cases that would require hospitalisation.
Experts have made several recommendations on how to contain the issue. For one, adding another drug to the mix when administering artemisinin can make it trickier for parasites to develop resistance.
Concerns about resistance also inform Malaria Consortium’s work in deploying seasonal malaria chemoprevention (SMC) to children as a way of preventing malaria in areas of highly seasonal transmission. Evidence that resistance was developing towards the drug sulfadoxine-pyrimethamine, which is administered alongside amodiaquine for SMC delivery, led to work by Malaria Consortium to explore alternative drug regimens, and the results of recent research found that the drug dihydroartemisinin- piperaquine (DP) is a potential alternative for use in SMC.
“The battle against malaria means always staying one step ahead. This is why Malaria Consortium is driving work to research alternative drugs for our arsenal in case the existing therapies develop resistance to malaria parasites,” says Anthony Nuwa, Senior Country Technical Coordinator at Malaria Consortium Uganda.
Another recommendation is increasing data surveillance and sharing, a critical aspect for improving interventions generally but of particular importance in the case of resistance. In Mozambique, Malaria Consortium, alongside IS Global, Centro de Investigação de Saúde de Manhiça, the Ministry of Health, Mozambique and National Malaria Control Programme, are monitoring for genetic markers of the Plasmodium falciparum parasite that indicate resistance to antimalarial drugs and diagnostics, helping to spot when resistance is on the rise and make the best decisions accordingly.
“Monitoring for evidence of resistance is crucial to catching the problem before it grows bigger and to prevent severe cases or mortality. And this kind of work is needed in Africa now more than ever,” says Sonia Maria Enosse, Country Technical Coordinator for Malaria Consortium Mozambique.
The time to act is now. Containing the issue will be crucial to preventing avoidable deaths.
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26 April 2024A cluster randomised controlled trial to compare sulfadoxine-pyrimethamine and amodiaquine with dihydroartemisinin-piperaquine for seasonal malaria chemoprevention in Karamoja region, UgandaType: Presentation
