Abstract
<title>Abstract</title> <p> <bold>Background</bold> : Between 2022-2023, as part of a therapeutic efficacy study in Liberia, children were recruited from two rural health facilities in Saclepea and Sinje. Participants were treated with artemisinin-based combination therapy and monitored for 28 days. Following treatment, samples were analyzed to identify molecular markers of antimalarial drug resistance. <bold>Methods</bold> : Blood from participants was collected and dried on filter paper. All baseline (D0) and Day of Failure (DoF) samples with recurrent parasitemia were sent to the Centers for Disease Control and Prevention in Atlanta. A total of 91 samples (all treatment failure pairs and 34% of unpaired D0) were first screened for <italic>P. falciparum monoinfection</italic> using a multiplex real-time PCR assay, and polymorphisms associated with antimalarial drug resistance in the <italic>Pfk13</italic> , <italic>Pfmdr1</italic> , <italic>Pfcrt, Pfdhfr</italic> , <italic>Pfdhps</italic> and <italic>Pfcytb</italic> genes were determined using the NGS-based Malaria Resistance Surveillance protocol. <bold>Results</bold> : A total of 90 samples were confirmed to be <italic>P. falciparum mono infections.</italic> There was no evidence of any known <italic>Pfk13</italic> mutations associated with artemisinin partial resistance. There were low rates of both <italic>Pfmdr1</italic> N86Y (0.83-5.5%) and <italic>Pfcrt</italic> K76T (12-22%) mutations. Moderate rates of the <italic>Pfmdr1</italic> Y184F (41-51%) were observed. The triplet canonical mutations conferring chloroquine resistance in <italic>Pfcrt</italic> were detected in 12 and 17% of samples from Saclepea and Sinje, respectively. Considering the World Health Organization thresholds for sulfadoxine-pyrimethamine (SP) resistance, the rates of the <italic>Pfdhfr</italic> mutations were above, but rates of the <italic>Pfdhps</italic> mutation were below the thresholds. <bold>Conclusions</bold> : This study shows high efficacy of artemisinin derivatives in Liberia. There is no indication of SP resistance in either site; however, circulating parasite population may be predisposed to reduced lumefantrine susceptibility. <bold>Trial Registration: ClinicalTrials.gov ID NCT06300970</bold> </p>