Resistance to ACT therapy in Africa mirrors patterns found in Asia.Credit: Matthew Oldfield Editorial Photography / Alamy Stock Photo
Researchers have identified partial resistance to artemisinin-based combination therapy (ACT) in malaria treatment across Africa.
Emergence of such resistance poses a potential threat to the effectiveness of ACT, the primary treatment for uncomplicated malaria in the continent.
The resistance, attributed to mutations in the kelch13 (or K13) gene of the Plasmodium falciparum parasite, mirrors patterns observed in Southeast Asia. While the full clinical impact remains unclear, monitoring by scientists underscores the importance of understanding and addressing this evolving challenge in malaria management.
In Africa, artemisinin-based combination therapy, or ACT is the first-line treatment for ‘uncomplicated’ malaria caused by Plasmodium falciparum —the deadliest malaria parasite and the one most prevalent in Africa. Compounds related to the fast-acting drug artemisinin, first developed in China in the 1970s, do the initial cleaning up of parasites from the human system. Longer-acting partner drugs (of which there are a number) follow in its wake, killing and removing any remaining parasites.
ACTs are also used in other regions, notably Asia, for forms of malaria caused by other parasites. But over the past two decades, partial resistance — in the form of delayed clearance and increased survival rates of the parasites — has been reported in Southeast Asia, both clinically and in lab studies. Resistance has been seen to both artemisinins and partner drugs.
This has raised the spectre of similar resistance developing independently in Africa. (Unlike as with chloroquine, where resistance was passed on from Asia to Africa.)
Researchers have linked this emerging resistance to an array of mutations in a gene in P. falciparum known as kelch13 (or K13),highly “conserved” in the Plasmodium parasites, its DNA having gone unchanged for some 50 million years.
There is evidence that such mutations are increasingly being observed around Africa, notably in Rwanda, Uganda and the Horn of Africa (specifically Ethiopia and Eritrea).
“Since about 2015/2016, we started to see fairly high prevalence of the same mutations that were first identified in Southeast Asia — that’s how we knew what to look for — in different parts of Africa,” says Philip Rosenthal of the University of California, San Francisco, who has been working with colleagues in the US and Africa tracking the mutations.
The clinical consequences of the emergence of mutant parasites is as yet unclear, but public health organisations are understandably concerned. Africa accounts for the overwhelming share of malaria cases in the world (over 230 million cases estimated in 2022). Children under five make up 80% of the over 500,000 estimated fatalities every year, reports the World Health Organization (WHO).
Rosenthal and colleagues from the US and Uganda recently published a review in Nature Reviews Microbiology on the emergence of artemisinin partial resistance in malaria parasites in Africa, based in part on ongoing primary research that they’re conducting.
It appears that Africa is following the Southeast Asia playbook. Partial resistance to artemisinin has been observed, possibly the result of artemisinin monotherapies, where, against recommended policies, the drug is used as a stand-alone treatment without the benefit of a partner drug.
“Suboptimal efficacy” — by WHO standards — has been observed for the most commonly used ACT, artemether-lumefantrine. But these low efficacies have so far been noted only in places where partial resistance to artemisinins has not been recorded, so the mechanism of decreased efficacy is uncertain, notes Rosenthal.
“The important point is that as of right now, we don’t have convincing evidence that there are important clinical consequences,” says Rosenthal. “A few studies have shown delayed clearance but not treatment failure associated with these mutations. Of course, we are very concerned that true treatment failures will be seen as resistance takes hold.”
While not wishing to ring premature alarm bells, scientists are monitoring the spread and distribution of the mutations, and their implications for malaria management in the long run.
