Tracking Drug Resistance in : Genetic Diversity of Key Resistance Markers in Brazilian Malaria Hotspots.

Malaria remains a health problem, with accounting for 96% of cases in Africa and 15% in Brazil. The growing threat of drug resistance to artemisinin-based combination therapies (ACTs) jeopardizes progress toward elimination. This study examined samples collected from 141 patients in Brazil (2013-2023) by PCR and DNA sequencing to identify single-nucleotide polymorphisms in the , , and genes. Half of the samples carried the VMNMCGI haplotype in , and none of the samples showed C350 mutations. In , the NY haplotype was dominant (70%), with low occurrences of N86 (4%) and no Y184 polymorphisms. No mutations linked to artemisinin partial resistance were detected in . Only one Amazonas sample exhibited wild-type haplotypes across all genes. Genetic diversity was more pronounced in than , reflecting selective drug pressure. Significant linkage disequilibrium (LD) was observed within (C72S and K76T) and (S1034C and N1042D), but not between the two genes. The absence of -resistant mutations and the low prevalence of key markers support the efficacy of ACTs. The persistence of diverse haplotypes and intragenic LD reflects ongoing drug pressure, underscoring the need for continuous genetic surveillance to anticipate emerging resistance.