title: Selection of N86F184D1246 haplotype of Pfmrd1 gene by artemether-lumefantrine drug pressure on Plasmodium falciparum populations in Senegal.
abstract: The use of artemisinin as a monotherapy resulted in the emergence of artemisinin resistance in 2005 in Southeast Asia. Monitoring of artemisinin combination therapy (ACT) is critical in order to detect and prevent the spread of resistance in endemic areas. Ex vivo studies and genotyping of molecular markers of resistance can be used as part of this routine monitoring strategy. One gene that has been associated in some ACT partner drug resistance is the Plasmodium falciparum multidrug resistance protein 1 (pfmdr1) gene. The purpose of this study was to assess the drug susceptibility of P. falciparum populations from Thiès, Senegal by ex vivo assay and typing molecular markers of resistance to drug components of ACT currently used for treatment.
  
  
  
  The ex vivo susceptibility of 170 P. falciparum isolates to chloroquine, amodiaquine, lumefantrine, artesunate, and artemether was determined using the DAPI ex vivo assay. The high resolution melting technique was used to genotype the pfmdr1 gene at codons 86, 184 and 1246.
  
  
  
  A significant decrease in IC50 values was observed between 2012 and 2013: from 13.84 to 6.484 for amodiaquine, 173.4 to 113.2 for lumefantrine, and 39.72 to 18.29 for chloroquine, respectively. Increase of the wild haplotype NYD and the decrease of the mutant haplotype NFD (79 and 62.26 %) was also observed. A correlation was observed between the wild type allele Y184 in pfmdr1 and higher IC50 for all drugs, except amodiaquine.
  
  
  
  This study has shown an increase in sensitivity over the span of two transmission seasons, marked by an increase in the WT alleles at pfmdr1. Continuous the monitoring of the ACT used for treatment of uncomplicated malaria will be helpful.
authors: Laboratory of Parasitology/Mycology HALD, Cheikh Anta Diop University of Dakar, PO Box 5005, Dakar, Senegal. aminatambaye155@gmail.com.
authors: Aminata
authors: 0000-0001-5481-8623
authors: A
authors: Mbaye
authors: Laboratory of Parasitology/Mycology HALD, Cheikh Anta Diop University of Dakar, PO Box 5005, Dakar, Senegal.
authors: Baba
authors: B
authors: Dieye
authors: Laboratory of Parasitology/Mycology HALD, Cheikh Anta Diop University of Dakar, PO Box 5005, Dakar, Senegal.
authors: Yaye D
authors: YD
authors: Ndiaye
authors: Laboratory of Parasitology/Mycology HALD, Cheikh Anta Diop University of Dakar, PO Box 5005, Dakar, Senegal.|Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA.
authors: Amy K
authors: AK
authors: Bei
authors: Malaria Research Centre, Serrekunda, Gambia.
authors: Affara
authors: A
authors: Muna
authors: Laboratory of Parasitology/Mycology HALD, Cheikh Anta Diop University of Dakar, PO Box 5005, Dakar, Senegal.
authors: Awa B
authors: AB
authors: Deme
authors: Laboratory of Parasitology/Mycology HALD, Cheikh Anta Diop University of Dakar, PO Box 5005, Dakar, Senegal.
authors: Mamadou S
authors: MS
authors: Yade
authors: Laboratory of Parasitology/Mycology HALD, Cheikh Anta Diop University of Dakar, PO Box 5005, Dakar, Senegal.
authors: Khadim
authors: K
authors: Diongue
authors: Laboratory of Parasitology/Mycology HALD, Cheikh Anta Diop University of Dakar, PO Box 5005, Dakar, Senegal.
authors: Amy
authors: A
authors: Gaye
authors: Laboratory of Parasitology/Mycology HALD, Cheikh Anta Diop University of Dakar, PO Box 5005, Dakar, Senegal.
authors: Ibrahima M
authors: IM
authors: Ndiaye
authors: Laboratory of Parasitology/Mycology HALD, Cheikh Anta Diop University of Dakar, PO Box 5005, Dakar, Senegal.
authors: Tolla
authors: T
authors: Ndiaye
authors: Laboratory of Parasitology/Mycology HALD, Cheikh Anta Diop University of Dakar, PO Box 5005, Dakar, Senegal.
authors: Mouhamad
authors: M
authors: Sy
authors: Laboratory of Parasitology/Mycology HALD, Cheikh Anta Diop University of Dakar, PO Box 5005, Dakar, Senegal.
authors: Mamadou A
authors: MA
authors: Diallo
authors: Laboratory of Parasitology/Mycology HALD, Cheikh Anta Diop University of Dakar, PO Box 5005, Dakar, Senegal.
authors: Aida S
authors: AS
authors: Badiane
authors: Laboratory of Parasitology/Mycology HALD, Cheikh Anta Diop University of Dakar, PO Box 5005, Dakar, Senegal.
authors: Mouhamadou
authors: M
authors: Ndiaye
authors: Laboratory of Parasitology/Mycology HALD, Cheikh Anta Diop University of Dakar, PO Box 5005, Dakar, Senegal.
authors: Mame C
authors: MC
authors: Seck
authors: Laboratory of Parasitology/Mycology HALD, Cheikh Anta Diop University of Dakar, PO Box 5005, Dakar, Senegal.
authors: Ngayo
authors: N
authors: Sy
authors: University of Bamako, Bamako, Mali.
authors: Ousmane
authors: O
authors: Koita
authors: Tulane University, New Orleans, LA, USA.
authors: Donald J
authors: DJ
authors: Krogstad
authors: Malaria Research Centre, Serrekunda, Gambia.
authors: Davis
authors: D
authors: Nwakanma
authors: Laboratory of Parasitology/Mycology HALD, Cheikh Anta Diop University of Dakar, PO Box 5005, Dakar, Senegal.|Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA.
authors: Daouda
authors: D
authors: Ndiaye
mesh_terms: D000293:Adolescent; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000494:pharmacology* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D004983:Ethanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005449:Fluorenes / Q000494:pharmacology* / Q000627:therapeutic use; D005787:Gene Frequency; D005828:Genetics, Population; D060005:Genotyping Techniques; D006239:Haplotypes; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D010963:Plasmodium falciparum / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D012641:Selection, Genetic; D012675:Senegal; D055815:Young Adult
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C513498:Mdr1 protein, Plasmodium falciparum
keywords: Artemether–lumefantrine; Haplotype; Plasmodium falciparum; Senegal; pfmdr1