title: Molecular characterisation of drug-resistant Plasmodium falciparum from Thailand.
abstract: BACKGROUND
  The increasing levels of Plasmodium falciparum resistance to chloroquine (CQ) in Thailand have led to the use of alternative antimalarials, which are at present also becoming ineffective. In this context, any strategies that help improve the surveillance of drug resistance, become crucial in overcoming the problem.
  
  
  METHODS
  In the present study, we have established the in vitro sensitivity to CQ, mefloquine (MF), quinine (QUIN) and amodiaquine (AMQ) of 52 P. falciparum isolates collected in Thailand, and assessed the prevalence of four putative genetic polymorphisms of drug resistance, pfcrt K76T, pfmdr1 N86Y, pfmdr1 D1042N and pfmdr1 Y1246D, by PCR-RFLP.
  
  
  RESULTS
  The percentage of isolates resistant to CQ, MF, and AMQ was 96% (50/52), 62% (32/52), and 58% (18/31), respectively, while all parasites were found to be sensitive to QUIN. In addition, 41 (79%) of the isolates assayed were resistant simultaneously to more than one drug; 25 to CQ and MF, 9 to CQ and AMQ, and 7 to all three drugs, CQ, MF and AMQ. There were two significant associations between drug sensitivity and presence of particular molecular markers, i) CQ resistance / pfcrt 76T (P = 0.001), and ii) MF resistance / pfmdr1 86N (P < 0.001)
  
  
  CONCLUSIONS
  i) In Thailand, the high levels of CQ pressure have led to strong selection of the pfcrt 76T polymorphism and ii) pfmdr1 86N appears to be a good predictor of in vitro MF resistance.
authors.affiliation: Centro de Malária e Outras Doenças Tropicais/IHMT/UNL, Rua da Junqueira, 96, 1349-008, Lisbon, Portugal. dmlopes@ihmt.unl.pt
authors.forename: Dinora
authors.initials: D
authors.lastname: Lopes
authors.forename: Kanchana
authors.initials: K
authors.lastname: Rungsihirunrat
authors.forename: Fátima
authors.initials: F
authors.lastname: Nogueira
authors.forename: Aree
authors.initials: A
authors.lastname: Seugorn
authors.forename: José Pedro
authors.initials: JP
authors.lastname: Gil
authors.forename: Virgilio E
authors.initials: VE
authors.lastname: do Rosário
authors.forename: Pedro
authors.initials: P
authors.lastname: Cravo
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000655:Amodiaquine / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics*; D018432:Drug Resistance, Multiple / Q000235:genetics; D005787:Gene Frequency; D015767:Mefloquine / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000235:genetics*; D011803:Quinine / Q000494:pharmacology; D013785:Thailand
chemical_list: D018528:ATP-Binding Cassette Transporters; D000962:Antimalarials; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; C059987:mdr gene protein, Plasmodium; D000655:Amodiaquine; D002738:Chloroquine; D011803:Quinine; D015767:Mefloquine