title: Genetic mutations in Plasmodium falciparum and Plasmodium vivax dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) in Vanuatu and Solomon Islands prior to the introduction of artemisinin combination therapy.
abstract: BACKGROUND
  Plasmodium falciparum and Plasmodium vivax are endemic in Vanuatu and the Solomon Islands. While both countries have introduced artemether-lumefantrine (AL) as first-line therapy for both P. falciparum and P. vivax since 2008, chloroquine and sulphadoxine-pyrimethamine (SP) were used as first-line therapy for many years prior to the introduction of AL. Limited data are available on the extent of SP resistance at the time of policy change.
  
  
  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 AL therapeutic efficacy study conducted in 2008. Plasmodium vivax and P. falciparum dhfr and dhps genes were sequenced to detect nucleotide polymorphisms.
  
  
  RESULTS
  All P. falciparum samples analysed (n=114) possessed a double mutant pfdhfr allele (C59R/S108N). Additionally, mutation A437G in pfhdps was detected in a small number of samples 2/13, 1/17 and 3/26 from Tanna Island, Vanuatu and Temotu and Malaita Provinces Solomon Islands respectively. Mutations were also common in pvdhfr from Tanna Island, Vanuatu, where 33/51 parasites carried the double amino acid substitution S58R/S117N, while in Temotu and Malaita Provinces, Solomon Islands 32/40 and 39/46 isolates carried the quadruple amino acid substitution F57L/S58R/T61M/S117T in DHFR respectively. No mutations in pvdhps (n=108) were detected in these three island groups.
  
  
  CONCLUSIONS
  Prior to the introduction of AL, there was a moderate level of SP resistance in the P. falciparum population that may cause SP treatment failure in young children. Of the P. vivax isolates, a majority of Solomon Islands isolates carried quadruple mutant pvdhfr alleles while a majority of Vanuatu isolates carried double mutant pvdhfr alleles. This suggests a higher level of SP resistance in the P. vivax population in Solomon Islands compared to the sympatric P. falciparum population and there is a higher level of SP resistance in P. vivax parasites from Solomon Islands than Vanuatu. This study demonstrates that the change of treatment policy in these countries from SP to ACT was timely. The information also provides a baseline for future monitoring.
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: Lyndes
authors.initials: L
authors.lastname: Wini
authors.forename: George
authors.initials: G
authors.lastname: Taleo
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Hii
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; D037621:Artemisinins; D003430:Cross-Sectional Studies; D004094:Dihydropteroate Synthase / Q000235:genetics*; D059788:Dried Blood Spot Testing; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005819:Genetic Markers; D006801:Humans; D008288:Malaria / Q000453:epidemiology / Q000469:parasitology; D008542:Melanesia / Q000453:epidemiology; D009154:Mutation / Q000235:genetics; D010963:Plasmodium falciparum / Q000201:enzymology / Q000235:genetics*; D010966:Plasmodium vivax / Q000201:enzymology / Q000235:genetics*; D011739:Pyrimethamine; D013413:Sulfadoxine; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*; D009514:Vanuatu / Q000453:epidemiology
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D005819:Genetic Markers; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; C031327:artemisinin; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase; D011739:Pyrimethamine