Multiple local PfDHFR I164L haplotype expansions drive Plasmodium falciparum antifolate resistance in Uganda.

Multiple local PfDHFR I164L haplotypes have expanded in Uganda, increasing pyrimethamine resistance from 19.4% to 32.4% between 2016 and 2022.

• Why it matters: Understanding the spatial and evolutionary patterns of resistance mutations is crucial for malaria control, especially where SP chemoprevention is the main strategy, but these patterns remain poorly characterized.
• What they did: Genotyping 11 resistance mutations in 4,725 P. falciparum isolates from 16 Ugandan sites over six years, and analyzing haplotype structures and selection signatures to track mutation dynamics.
• The result: Findings reveal that PfDHFR I164L appears on multiple haplotypes and expands locally without widespread recent positive selection, indicating complex, spatially heterogeneous resistance evolution.