title: High prevalence of mutation in the Plasmodium falciparum dhfr and dhps genes in field isolates from Sabah, Northern Borneo.
abstract: BACKGROUND
  Sulphadoxine-pyrimethamine (SP) has been in use for the treatment of uncomplicated falciparum malaria in Malaysia since the 1970s and is still widely employed in spite of widespread clinical resistance. Resistance to SP is known to be mediated by mutations in the pfdhfr and pfdhps genes. The aim of the present study was to investigate the distribution of pfdhfr and pfdhps gene polymorphism in Plasmodium falciparum field isolates from Kalabakan, Sabah, in northern Borneo.
  
  
  METHODS
  A total number of 619 individuals were screened from 23 study sites of which 31 were positive for P. falciparum. Analysis of restriction fragment length polymorphisms (RFLP) was used to identify polymorphism in the pfdhfr and pfdhps genes at positions 16, 51, 59, 108, 164 and 437, 540, 581, respectively.
  
  
  RESULTS
  All samples had at least one mutation in each of the genes associated with drug resistance. The prevalence of pfdhfr 59arg, 164leu and 108asn were 100%, 80.65% and 58.06%, respectively. Pfdhps mutants 437gly and 581gly accounted for 100% and 74.19% respectively. In pfdhfr, the most common mutant genotypes were combination 59arg + 164leu (22.58%) and 59arg + 108asn + 164leu (51.61%). In pfdhps the most common genotype was 437gly + 581gly (74.19%). One individual (3.22%) harboured parasites with four pfdhfr (16 val + 59arg + 108asn + 164leu) and two pfdhps (437gly + 581gly) mutations. The highest quintuple pfdhfr/pfdhps (41.94%) was three pfdhfr (59arg + 108asn + 164gly) and two pfdhps (437gly + 581gly).
  
  
  CONCLUSIONS
  The data suggest a high prevalence of genetic variations conferring resistance to SP which can predict treatment failure before becoming clinically evident. In areas like this, the use of SP may no longer be indicated.
authors.forename: Noor Rain
authors.initials: NR
authors.lastname: Abdullah
authors.forename: Nor Azrina
authors.initials: NA
authors.lastname: Norahmad
authors.forename: Jenarun
authors.initials: J
authors.lastname: Jelip
authors.forename: Lokman Hakim
authors.initials: LH
authors.lastname: Sulaiman
authors.forename: Hasidah
authors.initials: H
authors.lastname: Mohd Sidek
authors.forename: Zakiah
authors.initials: Z
authors.lastname: Ismail
authors.forename: Harald
authors.initials: H
authors.lastname: Noedl
mesh_terms: D000962:Antimalarials / Q000494:pharmacology; D001893:Borneo / Q000453:epidemiology; D004094:Dihydropteroate Synthase / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics; D006801:Humans; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000469:parasitology*; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology / Q000235:genetics* / Q000302:isolation & purification; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D015800:Protozoan Proteins / Q000235:genetics*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*
chemical_list: D000962:Antimalarials; D015800:Protozoan Proteins; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase