title: Amplification of pfmdr 1 associated with mefloquine and halofantrine resistance in Plasmodium falciparum from Thailand.
abstract: Drug resistance in Plasmodium falciparum is an expanding problem in most endemic areas. Recent studies have suggested the potential involvement of genes in the MDR gene family in resistance to quinoline-containing compounds in P. falciparum. In this study a molecular analysis of pfmdr 1 in recent isolates from Thailand was done (1) to further examine the role of pfmdr 1 in drug-resistant isolates and (2) to examine the reported association of pfmdr 1 intragenic alleles and chloroquine resistance. Most of the isolates (10 of 11) were resistant to all compounds tested. Analysis of pfmdr 1 revealed an apparent association between increased gene copy number and increased level of expression of pfmdr 1 and decreased susceptibility to mefloquine and halofantrine. Sequence analysis of pfmdr 1 in these isolates revealed no association of intragenic alleles with chloroquine resistance.
authors.affiliation: Department of Tropical Public Health, Harvard School of Public Health, Boston, MA 02115.
authors.forename: C M
authors.initials: CM
authors.lastname: Wilson
authors.forename: S K
authors.initials: SK
authors.lastname: Volkman
authors.forename: S
authors.initials: S
authors.lastname: Thaithong
authors.forename: R K
authors.initials: RK
authors.lastname: Martin
authors.forename: D E
authors.initials: DE
authors.lastname: Kyle
authors.forename: W K
authors.initials: WK
authors.lastname: Milhous
authors.forename: D F
authors.initials: DF
authors.lastname: Wirth
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D001483:Base Sequence; D016054:DNA, Protozoan / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics*; D005784:Gene Amplification; D017125:Genes, Protozoan; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy; D015767:Mefloquine / Q000494:pharmacology; D008969:Molecular Sequence Data; D010616:Phenanthrenes / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics; D016053:RNA, Protozoan / Q000235:genetics; D013785:Thailand
chemical_list: D000962:Antimalarials; D016054:DNA, Protozoan; D010616:Phenanthrenes; D012333:RNA, Messenger; D016053:RNA, Protozoan; C023768:halofantrine; D015767:Mefloquine