Scientists sound alarm over emerging drug-resistant malaria in Uganda

Scientists have identified previously unknown genetic mutations in malaria parasites in Uganda that are associated with reduced susceptibility to several widely used antimalarial drugs, raising concerns about the future effectiveness of malaria treatment.

The study, led by researchers at Brown University and published in Nature Medicine, analyzed the whole genomes of malaria parasites collected from hundreds of infected patients in Uganda.

Researchers identified a cluster of genetic variants linked to decreased susceptibility to artemisinin and lumefantrine, the two components of artemether-lumefantrine (AL), the primary treatment for uncomplicated malaria in Uganda for the past two decades. The variants were also associated with reduced susceptibility to mefloquine.

The mutations were concentrated in a region containing 69 genes. Further analysis identified three mutations and two deletions associated with the reduced drug susceptibility, with the mutations most likely driving the process located in the PX1 gene, which encodes a phosphoinositide-binding protein.

"It's very concerning that these new mutations are spreading so rapidly—it tells us they are important to the parasite's survival," said study author Dr. Jeffrey Bailey, an associate professor of translational research and of pathology and laboratory medicine at Brown University.

"Malaria still is a major killer, particularly in sub-Saharan Africa. As drug resistance continues to emerge, we worry it will undermine control of its spread and result in even more deaths for a large number of people there and beyond," he added.

Karamoko Niaré, the study’s first author, said researchers had previously lacked a validated molecular marker for lumefantrine resistance.

"We didn't have any validated molecular marker of lumefantrine resistance—we knew that there was a gene involved in partial resistance to artemisinin but couldn't explain changes observed for lumefantrine," Niaré said. 

"Our work identifies a molecular marker that could be used by surveillance studies to track the emergence and spread of reduced susceptibility to frontline malaria treatments across Africa. That's a very important tool for public health,” Niaré noted.

The researchers said the mutation should be incorporated into malaria surveillance systems and further investigated. They also stressed that future studies must determine whether the mutations affect clinical treatment outcomes and how far the variants have spread beyond Uganda.

By Vafa Guliyeva