title: Amplification of Plasmodium falciparum multidrug resistance gene 1 in isolates from Gabon.
abstract: The study of molecular markers of drug resistance is particularly important in surveillance studies of drugs, such as mefloquine, that still retain efficacy in sub-Saharan Africa yet have encountered resistance elsewhere. In a recent study in Thailand, we identified amplification of the Plasmodium falciparum multidrug resistance gene 1 (pfmdr1) as being the most important predictor of in vitro drug resistance and in vivo failure of mefloquine monotherapy. Here we report amplification of pfmdr1 in >5% of patient samples from Lambarene, Gabon, collected in 1995. None of the samples collected 7 years later showed pfmdr1 amplification, suggesting that parasites with increased numbers of pfmdr1 copies have not substantially spread through the population. Nevertheless, the detection of multicopy pfmdr1 in African parasites suggests a high potential for rapid selection for resistance, implying that mefloquine use in Africa should be considered only as part of combination therapy.
authors.affiliation: Department of Cellular and Molecular Medicine, Infectious Diseases Group, St. George's Hospital Medical School, London, UK. au2110@columbia.edu
authors.forename: Anne-Catrin
authors.initials: AC
authors.lastname: Uhlemann
authors.forename: Michael
authors.initials: M
authors.lastname: Ramharter
authors.forename: Bertrand
authors.initials: B
authors.lastname: Lell
authors.forename: Peter G
authors.initials: PG
authors.lastname: Kremsner
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Krishna
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D004338:Drug Combinations; D004351:Drug Resistance; D005681:Gabon; D019450:Genes, MDR; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology*; D015767:Mefloquine / Q000494:pharmacology / Q000627:therapeutic use; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D015800:Protozoan Proteins / Q000235:genetics*; D011739:Pyrimethamine / Q000494:pharmacology / Q000627:therapeutic use; D013413:Sulfadoxine / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D018528:ATP-Binding Cassette Transporters; D000962:Antimalarials; D004338:Drug Combinations; D015800:Protozoan Proteins; C059987:mdr gene protein, Plasmodium; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D015767:Mefloquine; D011739:Pyrimethamine