title: Genetic mutations in pfcrt and pfmdr1 at the time of artemisinin combination therapy introduction in South Pacific islands of Vanuatu and Solomon Islands.
abstract: BACKGROUND
  Chloroquine (CQ), alone or in combination with sulphadoxine-pyrimethamine, was widely used for the treatment of Plasmodium falciparum and Plasmodium vivax for several decades in both Vanuatu and Solomon Islands prior to the introduction of artemether-lumefantrine (AL) in 2008. However, the effect of chloroquine selection on parasite population, which may affect the efficacy of lumefantrine or other partner drugs of artemisinin, has not been well assessed. This study aims to provide baseline data on molecular markers (pfcrt and pfmdr1), along with the origins of pfcrt, prior to the introduction of AL.
  
  
  METHODS
  Blood spots were obtained from epidemiological surveys conducted on Tanna Island, Tafea Province, Vanuatu and Temotu Province, Solomon Islands in 2008. Additional samples from Malaita Province, Solomon Islands were collected as part of an artemether-lumefantrine efficacy study in 2008. Plasmodium falciparum pfcrt and pfmdr1 genes were examined for polymorphisms. Microsatellite markers flanking pfcrt were also examined to ascertain origins of CQ resistance.
  
  
  RESULTS
  Pfcrt analysis revealed 100% of parasites from Tafea Province, Vanuatu and Malaita Province, Solomon Islands and 98% of parasites from Temotu Province, Solomon Islands carried the K76T polymorphism that confers CQ resistance. Comparison of pfcrt allelic patterns and microsatellite markers flanking pfcrt revealed six haplotypes with more than 70% of isolates possessing haplotypes very similar to those observed in Papua New Guinea. The dominant (98.5%) pfmdr1 allele across all island groups was YYCND.
  
  
  CONCLUSIONS
  Prior to the introduction of AL in the Solomon Islands and Vanuatu, P. falciparum isolates possessed point mutations known to confer CQ resistance and possibly associated with a decreased susceptibility to quinine and halofantrine, but an increased susceptibility to artemisinin and lumefantrine. Overall, pfcrt allelic types and the flanking microsatellite markers exhibited similarities to those of Papua New Guinea, suggesting these parasites share a common ancestry. The current use of AL for both P. falciparum and P. vivax infections will enable changes in these markers, in the absence of CQ pressure, to be monitored.
authors.forename: Karryn J
authors.initials: KJ
authors.lastname: Gresty
authors.forename: Karen-Ann
authors.initials: KA
authors.lastname: Gray
authors.forename: Albino
authors.initials: A
authors.lastname: Bobogare
authors.forename: George
authors.initials: G
authors.lastname: Taleo
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Hii
authors.forename: Lyndes
authors.initials: L
authors.lastname: Wini
authors.forename: Qin
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: Australian Army Malaria Institute, Enoggera, Brisbane, Queensland, Australia. norman.c.waters2.mil@mail.mil.
authors.forename: Norman C
authors.initials: NC
authors.lastname: Waters
mesh_terms: D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D059788:Dried Blood Spot Testing; D004359:Drug Therapy, Combination; D006239:Haplotypes; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology*; D008542:Melanesia / Q000453:epidemiology; D026901:Membrane Transport Proteins / Q000235:genetics*; D018895:Microsatellite Repeats; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D010963:Plasmodium falciparum / Q000235:genetics*; D015995:Prevalence; D015800:Protozoan Proteins / Q000235:genetics*; D009514:Vanuatu / Q000453:epidemiology
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015800:Protozoan Proteins; C513498:Mdr1 protein, Plasmodium falciparum; C416369:PfCRT protein, Plasmodium falciparum; C031327:artemisinin