Researchers from Brown University conducted a whole-genome analysis of 157 malaria parasite samples collected in Uganda from 2016 to 2024, revealing that mutations in a gene encoding a protein called px1 may contribute to the rise in drug-resistant malaria. The findings, published in Nature Medicine, highlight the urgent need to understand the genetic factors behind this resistance.
Jeffrey Bailey, an associate professor at Brown University, stated, "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."
The research team discovered a cluster of mutations, named PIN, consisting of three amino acid mutations and two deletions, which has been passed down through generations. The study indicates that the PIN mutation has spread rapidly, first appearing in a sample from 2008, with prevalence reaching 84% in northern Uganda and 55% in eastern Uganda by 2024.
The team compared the response of malaria parasites with and without the PIN mutation to common antimalarial drugs, finding that those with the mutation showed reduced sensitivity to lumefantrine, a component of the artemether-lumefantrine combination drug. In experiments with parasites lacking the px1 gene, a stronger response to treatments was observed, while no significant differences were noted regarding resistance to artemisinin.
Karamoko Niare, the lead author of the paper, emphasized the importance of incorporating the new mutation into surveillance systems for malaria treatment. Historical genetic databases showed that the PIN mutation was rare between 2001 and 2015, with only five samples identified in neighboring countries, and it was not detected in Ugandan samples from 2010.
The study indicates changes in drug susceptibility at the laboratory level, but the impact on clinical outcomes for malaria patients remains uncertain. The researchers stress the need for systems to predict drug effectiveness and the development of new treatments to combat malaria effectively.