Researchers at Brown University have identified a genetic mutation that appears to be driving rising resistance to common antimalarial drugs in Uganda, a finding that could complicate efforts to control a disease that remains a major killer across sub-Saharan Africa. The study, published this week in Nature Medicine, points to mutations in a previously overlooked gene encoding a protein called px1, offering the first validated molecular marker for resistance to lumefantrine, a key component of the standard combination treatment artemether-lumefantrine.

The team analysed whole genomes from 157 malaria parasite samples collected in Uganda between 2016 and 2024, identifying a cluster of mutations they named PIN, first detected in a 2008 sample. Its spread has been rapid: by 2016 it was present in half of northern Ugandan samples, and by 2024 prevalence had reached 84% in the north and 55% in the east. Laboratory tests confirmed parasites carrying PIN showed reduced sensitivity to lumefantrine and other antimalarials, while historical global databases showed the mutation was almost absent before 2015, though limited surveillance data make its cross-border spread difficult to track.