Another Nature Communications paper reports a common DNA deletion immediately downstream of the mdr1 gene in P. vivax parasites from Cambodian patients. Unlike classic resistance mutations that alter protein sequences, this 837-base-pair deletion lies in a non-coding region and does not change the mdr1 protein itself, but it does alter the 3’ untranslated region (UTR) of the gene’s mRNA. Parasites carrying this deletion exhibited higher levels of mdr1 transcripts and were less susceptible to mefloquine in ex-vivo assays. Genomic surveillance also showed that this deletion has increased in frequency since mefloquine was adopted as a partner drug in ACTs for vivax malaria, suggesting that regulatory changes affecting gene expression can contribute to emerging drug tolerance. This highlights the need to broaden molecular surveillance beyond coding mutations to include regulatory variation that may influence treatment outcomes.

Read the article: https://www.nature.com/articles/s41467-026-68456-7