National genomic profiling ofPlasmodium falciparumantimalarial resistance in Zambian children participating in the 2018 Malaria Indicator Survey

Abstract

AbstractThe emergence of antimalarial drug resistance is a major threat to malaria control and elimination. Using whole genome sequencing of 282P. falciparumsamples collected during the 2018 Zambia National Malaria Indicator Survey, we determined the prevalence and spatial distribution of known and candidate antimalarial drug resistance mutations. High levels of genotypic resistance were found across Zambia to pyrimethamine, with over 94% (n=266) of samples having thePfdhfrtriple mutant (N51I, C59R, and S108N), and sulfadoxine, with over 84% (n=238) having thePfdhpsdouble mutant (A437Gand K540E). In northern Zambia, 5.3% (n=15) of samples also harbored thePfdhpsA581Gmutation. Although 29 mutations were identified inPfkelch13, these mutations were present at low frequency (<2.5%), and only three were WHO-validated artemisinin partial resistance mutations: P441L(n=1, 0.35%), V568M(n=2, 0.7%) and R622T(n=1, 0.35%). Notably, 91 (32%) of samples carried the E431Kmutation in thePfatpase6gene, which is associated with artemisinin resistance. No specimens carried any known mutations associated with chloroquine resistance in thePfcrtgene (codons 72-76).P. falciparumstrains circulating in Zambia were highly resistant to sulfadoxine and pyrimethamine but remained susceptible to chloroquine and artemisinin. Despite this encouraging finding, early genetic signs of developing artemisinin resistance highlight the urgent need for continued vigilance and expanded routine genomic surveillance to monitor these changes.