title: In vivo selection of Plasmodium falciparum pfmdr1 86N coding alleles by artemether-lumefantrine (Coartem).
abstract: Artemisinin derivative-based combination therapy is expected to suppress the development of Plasmodium falciparum drug resistance in Africa. We have performed an artemether-lumefantrine (Coartem; Novartis) follow-up clinical trial in Zanzibar, in which pfcrt K76T and pfmdr1 N86Y frequencies were determined before drug administration and in all recurrent parasites during a follow-up period of 42 days. A significant increase in pfmdr1 86N was observed after exposure to the drug. This points to 86N as a potential marker of lumefantrine resistance in vivo, while suggesting that Coartem is not robust enough to avoid selection of resistance-associated mutations in some malarial settings.
authors.affiliation: Malaria Research Laboratory, Unit of Infectious Diseases, Department of Medicine, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden. christin.sisowath@medks.ki.se
authors.forename: Christin
authors.initials: C
authors.lastname: Sisowath
authors.forename: Johan
authors.initials: J
authors.lastname: Strömberg
authors.forename: Andreas
authors.initials: A
authors.lastname: Mårtensson
authors.forename: Mwinyi
authors.initials: M
authors.lastname: Msellem
authors.forename: Christine
authors.initials: C
authors.lastname: Obondo
authors.forename: Anders
authors.initials: A
authors.lastname: Björkman
authors.forename: José P
authors.initials: JP
authors.lastname: Gil
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000483:Alleles; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D000077549:Artemether; D037621:Artemisinins / Q000494:pharmacology* / Q000627:therapeutic use; D002648:Child; D004351:Drug Resistance / Q000235:genetics; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D005449:Fluorenes / Q000494:pharmacology* / Q000627:therapeutic use; D019450:Genes, MDR; D006801:Humans; D007223:Infant; D000078102:Lumefantrine; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D015800:Protozoan Proteins / Q000235:genetics*; D012641:Selection, Genetic; D012717:Sesquiterpenes / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D018528:ATP-Binding Cassette Transporters; D000962:Antimalarials; D037621:Artemisinins; D004983:Ethanolamines; D005449:Fluorenes; D015800:Protozoan Proteins; D012717:Sesquiterpenes; C059987:mdr gene protein, Plasmodium; D000077549:Artemether; D000078102:Lumefantrine