title: Molecular analysis of Plasmodium falciparum from drug treatment failure patients in Papua New Guinea.
abstract: A study was conducted in Papua New Guinea to analyze Plasmodium falciparum drug resistance polymorphisms in patients presenting with resistant malaria. One hundred ninety-nine P. falciparum-positive patients were recruited at two sites, Madang and Maprik. Exposure to the 4-aminoquinolines chloroquine and amodiaquine was uniformly high, at 84% overall. However, 59% of these were taken in various combinations of sulfadoxine/pyrimethamine and/or primaquine and/or quinine. Two markers for 4-aminoquinoline resistance, P. falciparum chloroquine resistance transporter 76T and P. falciparum multidrug resistance 1, were fixed in the population and two markers for pyrimethamine resistance, dihydrofolate reductase (dhps) 59R and 108N, were found at moderate to high levels, overall 60% and 75%, respectively. No polymorphisms in dhps associated with sulfadoxine resistance were present. Differences between the two sites are analyzed. The study period encompasses a change in standard malaria treatment policy. These findings stress the need for regular monitoring of the effects of standard drug treatment of uncomplicated malaria in Papua New Guinea.
authors.affiliation: Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea.
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Casey
authors.forename: Meza
authors.initials: M
authors.lastname: Ginny
authors.forename: Merolyn
authors.initials: M
authors.lastname: Uranoli
authors.forename: Ivo
authors.initials: I
authors.lastname: Mueller
authors.forename: John C
authors.initials: JC
authors.lastname: Reeder
authors.forename: Blaise
authors.initials: B
authors.lastname: Genton
authors.forename: Alan F
authors.initials: AF
authors.lastname: Cowman
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000634:Aminoquinolines / Q000627:therapeutic use; D000655:Amodiaquine / Q000627:therapeutic use; D000818:Animals; D002738:Chloroquine / Q000627:therapeutic use; D004351:Drug Resistance / Q000235:genetics; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins; D010219:Papua New Guinea; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins; D017211:Treatment Failure
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000634:Aminoquinolines; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D000655:Amodiaquine; D002738:Chloroquine; C001920:4-aminoquinoline