Persistence of legacy antimalarial resistance markers in The Gambia from a malaria genomic surveillance study

We conducted genomic surveillance of P. falciparum in The Gambia (2013–2022) using targeted amplicon sequencing to monitor drug resistance markers and genetic diversity in this low transmission setting. The analysis of 3,624 dried blood spot samples revealed predominantly single-strain infections (70–100%) across most sites, indicating low complexity of infection. Antimalarial resistance markers were highly prevalent; specifically, triple Pfdhfr mutations exceeded 90% in frequency. When combined with Pfdhps mutations, these formed stable quadruple haplotypes associated with partial Sulfadoxine-pyrimethamine (SP) resistance. Despite chloroquine's withdrawal in 2006, the CVIET resistance haplotype remained at approximately 60% prevalence, effectively splitting the parasite population into two major genetic clusters. Additionally, the Pfmdr1 Y184 F mutation—associated with increased lumefantrine tolerance—rose rapidly to over 60% by 2022. While low frequency Pfkelch13 mutations were detected between 2019 and 2022, none were validated markers for artemisinin resistance. Continued surveillance is crucial for guiding targeted malaria elimination strategies.