The parasite responsible for the deadliest form of malaria is rapidly spreading mutations that blunt the drugs used to treat it, according to genomic research in Uganda — a worrying signal for one of global health’s most important therapies.
Researchers sequenced the whole genomes of Plasmodium falciparum from hundreds of infected people in Uganda and identified three mutations and two deletions associated with reduced susceptibility to artemether-lumefantrine (AL), a widely used artemisinin-based combination therapy (ACT). The work was published in Nature Medicine in 2026.
A new gene in the picture
The team linked changes in a gene they call PX1 (encoding a phosphoinositide-binding protein) to decreased drug response — described as the first time a single gene mutation has been correlated with reduced response to multiple drugs used together in combination malaria therapy. The study was led by Jeffrey Bailey of Brown University with colleague Karamoko Niaré.
Why it matters
Artemisinin-based combination therapies are the frontline treatment for P. falciparum malaria worldwide. Emerging resistance in Africa — which bears the greatest malaria burden — threatens hard-won gains against the disease. “It’s very concerning that these new mutations are spreading so rapidly — it tells us they are important to the parasite’s survival,” Bailey said. The findings strengthen the case for close genomic surveillance to track resistance as it emerges.