title: Molecular Epidemiology of Plasmodium falciparum kelch13 Mutations in Senegal Determined by Using Targeted Amplicon Deep Sequencing.
abstract: The emergence ofPlasmodium falciparumresistance to artemisinin in Southeast Asia threatens malaria control and elimination activities worldwide. Multiple polymorphisms in theP. falciparum kelchgene found in chromosome 13 (Pfk13) have been associated with artemisinin resistance. Surveillance of potential drug resistance loci within a population that may emerge under increasing drug pressure is an important public health activity. In this context,P. falciparuminfections from an observational surveillance study in Senegal were genotyped using targeted amplicon deep sequencing (TADS) forPfk13polymorphisms. The results were compared to previously reportedPfk13polymorphisms from around the world. A total of 22Pfk13propeller domain polymorphisms were identified in this study, of which 12 have previously not been reported. Interestingly, of the 10 polymorphisms identified in the present study that were also previously reported, all had a different amino acid substitution at these codon positions. Most of the polymorphisms were present at low frequencies and were confined to single isolates, suggesting they are likely transient polymorphisms that are part of naturally evolving parasite populations. The results of this study underscore the need to identify potential drug resistance loci existing within a population, which may emerge under increasing drug pressure.
authors.affiliation: Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA etalundzic@cdc.gov.|Atlanta Research and Education Foundation, VAMC, Atlanta, Georgia, USA.
authors.forename: Eldin
authors.initials: E
authors.lastname: Talundzic
authors.affiliation: Laboratory of Parasitology Mycology, Aristide le Dantec Hospital, Université Cheikh Anta Diop, Dakar, Senegal.
authors.forename: Yaye D
authors.initials: YD
authors.lastname: Ndiaye
authors.affiliation: Laboratory of Parasitology Mycology, Aristide le Dantec Hospital, Université Cheikh Anta Diop, Dakar, Senegal.
authors.forename: Awa B
authors.identifier: 0000-0002-3119-6419
authors.initials: AB
authors.lastname: Deme
authors.affiliation: Torq Informatics, Mebane, North Carolina, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Olsen
authors.affiliation: Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Dhruviben S
authors.initials: DS
authors.lastname: Patel
authors.affiliation: School of Biology, Georgia Institute of Technology, Atlanta, Georgia, USA.
authors.forename: Shweta
authors.initials: S
authors.lastname: Biliya
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.|Infectious Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Daniels
authors.affiliation: School of Biology, Georgia Institute of Technology, Atlanta, Georgia, USA.
authors.forename: Fredrik O
authors.initials: FO
authors.lastname: Vannberg
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.|Infectious Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|School of Nursing and Health Sciences, Simmons College, Boston, Massachusetts, USA.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Volkman
authors.affiliation: Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Venkatachalam
authors.initials: V
authors.lastname: Udhayakumar
authors.affiliation: Laboratory of Parasitology Mycology, Aristide le Dantec Hospital, Université Cheikh Anta Diop, Dakar, Senegal.
authors.forename: Daouda
authors.initials: D
authors.lastname: Ndiaye
mesh_terms: D000595:Amino Acid Sequence; D000962:Antimalarials / Q000494:pharmacology; D037621:Artemisinins / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics*; D062665:Epidemiological Monitoring; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology; D017720:Molecular Epidemiology; D009687:Nuclear Proteins / Q000235:genetics*; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D020641:Polymorphism, Single Nucleotide; D015800:Protozoan Proteins / Q000235:genetics*; D012675:Senegal; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D015800:Protozoan Proteins; C031327:artemisinin
keywords: Plasmodium falciparum; artemisinin resistance; kelch13; molecular epidemiology