AbstractBackgroundCape Verde is an archipelago located off the West African coast and is in a pre-elimination phase of malaria control. Since 2010, fewer than 20Plasmodium falciparummalaria cases have been reported annually, except in 2017, when an outbreak in Praia before the rainy season led to 423 autochthonous cases. It is important to understand the genetic diversity of circulatingP. falciparumto inform on drug resistance, potential transmission networks and sources of infection, including parasite importation.MethodsEnrolled subjects involved malaria patients admitted to Dr Agostinho Neto Hospital at Praia city, Santiago island, Cape Verde, between July and October 2017. Neighbours and family members of enrolled cases were assessed for the presence of anti-P. falciparumantibodies. Sanger sequencing and real-time PCR was used to identify SNPs in genes associated with drug resistance (e.g.,pfdhfr, pfdhps, pfmdr1, pfk13, pfcrt), and whole genome sequencing data were generated to investigate the population structure ofP. falciparumparasites.ResultsThe study analysed 190 parasite samples, 187 indigenous and 3 from imported infections. Malaria cases were distributed throughout Praia city. There were no cases of severe malaria and all patients had an adequate clinical and parasitological response after treatment. Anti-P. falciparumantibodies were not detected in the 137 neighbours and family members tested. No mutations were detected inpfdhps. The triple mutation S108N/N51I/C59R inpfdhfrand the chloroquine-resistant CVIET haplotype in thepfcrtgene were detected in almost all samples. Variations inpfk13were identified in only one sample (R645T, E668K). The haplotype NFD forpfmdr1was detected in the majority of samples (89.7%).ConclusionsPolymorphisms inpfk13associated with artemisinin-based combination therapy (ACT) tolerance in Southeast Asia were not detected, but the majority of the tested samples carried thepfmdr1haplotype NFD and anti-malarial-associated mutations in the thepfcrtandpfdhfrgenes. The first whole genome sequencing (WGS) was performed for Cape Verdean parasites that showed that the samples cluster together, have a very high level of similarity and are close to other parasites populations from West Africa.