title: Increased prevalence of dhfr and dhps mutants at delivery in Malawian pregnant women receiving intermittent preventive treatment for malaria.
abstract: In the context of an Intermittent preventive treatment (IPTp) trial for pregnant women in Malawi, Plasmodium falciparum samples from 85 women at enrollment and 35 women at delivery were genotyped for mutations associated with sulfadoxine-pyrimethamine resistance. The prevalence of the highly resistant haplotype with mutations at codons 51 and 108 of dihydrofolate reductase (dhfr) and codons 437 and 540 of dihydropteroate synthase (dhps) increased from 81% at enrollment to 100% at delivery (P = 0.01). Pregnant women who were smear-positive at enrollment were more likely to have P. falciparum parasitemia at delivery. These results lend support to concerns that IPTp use may lead to increased drug resistance in pregnant women during pregnancy and emphasise the importance of screening pregnant women for malaria parasites in areas with prevalent SP resistance even when they are already on IPTp.
authors.affiliation: Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, NC, USA. jessica_lin@med.unc.edu
authors.forename: Jessica T
authors.initials: JT
authors.lastname: Lin
authors.forename: Bernard
authors.initials: B
authors.lastname: Mbewe
authors.forename: Steve M
authors.initials: SM
authors.lastname: Taylor
authors.forename: Mari
authors.initials: M
authors.lastname: Luntamo
authors.forename: Steven R
authors.initials: SR
authors.lastname: Meshnick
authors.forename: Per
authors.initials: P
authors.lastname: Ashorn
mesh_terms: D000962:Antimalarials / Q000627:therapeutic use*; D016054:DNA, Protozoan / Q000235:genetics; D004094:Dihydropteroate Synthase / Q000235:genetics*; D004338:Drug Combinations; D004351:Drug Resistance; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016778:Malaria, Falciparum / Q000235:genetics / Q000517:prevention & control*; D008295:Malawi; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000188:drug therapy* / Q000235:genetics; D011739:Pyrimethamine / Q000627:therapeutic use; D013413:Sulfadoxine / Q000627:therapeutic use; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*
chemical_list: D000962:Antimalarials; D016054:DNA, Protozoan; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase; D011739:Pyrimethamine