title: Plasmodium falciparum dihydrofolate reductase alleles and pyrimethamine use in pregnant Ghanaian women.
abstract: Drug resistance in Plasmodium falciparum affects prevention of malaria in pregnancy. In a cross-sectional study of 530 pregnant Ghanaian women, P. falciparum dihydrofolate reductase (DHFR) gene mutations linked with pyrimethamine resistance were assessed and associations with pyrimethamine intake were analyzed. P. falciparum infected 69% of women without pyrimethamine use, 59% of those who had a history of pyrimethamine consumption but a negative urine test, and 53% of individuals with a positive urine test. Eighty-one percent, 43%, and 74% of the isolates contained the mutations Asn-108, Ile-51, and Arg-59, respectively. Thr-108 occurred in 8%. Pyrimethamine use was associated with increased frequencies of Asn-108 and Arg-59 but not of Ile-51 or Thr-108. In women with prophylaxis, wild-type parasites were absent and anemia tended to be more common with an increasing number of DHFR gene mutations. Pyrimethamine appears to be not adequately effective in this part of Ghana, most likely due to the predominance of resistant parasites. Selection for resistance following insufficient prophylaxis could possibly affect the efficacy of future intermittent sulfadoxine-pyrimethamine treatment.
authors.affiliation: Institut für Tropenmedizin, Medizinische Fakultät Charité, Humboldt Universität zu Berlin, Germany.
authors.forename: F P
authors.initials: FP
authors.lastname: Mockenhaupt
authors.forename: T A
authors.initials: TA
authors.lastname: Eggelte
authors.forename: T
authors.initials: T
authors.lastname: Böhme
authors.forename: W N
authors.initials: WN
authors.lastname: Thompson
authors.forename: U
authors.initials: U
authors.lastname: Bienzle
mesh_terms: D000483:Alleles; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005869:Ghana; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology / Q000517:prevention & control*; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000469:parasitology / Q000517:prevention & control*; D011739:Pyrimethamine / Q000627:therapeutic use*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*
chemical_list: D000962:Antimalarials; D016054:DNA, Protozoan; D013762:Tetrahydrofolate Dehydrogenase; D011739:Pyrimethamine