title: Recent uptake of intermittent preventive treatment during pregnancy with sulfadoxine-pyrimethamine is associated with increased prevalence of Pfdhfr mutations in Bobo-Dioulasso, Burkina Faso.
abstract: The impact of sulfadoxine-pyrimethamine (SP) used as intermittent preventive treatment during pregnancy (IPTp-SP) on mutant parasite selection has been poorly documented in Burkina Faso. This study sought first to explore the relationship between IPTp-SP and the presence of mutant parasites. Second, to assess the relationship between the mutant parasites and adverse pregnancy outcomes.
  
  
  
  From September to December 2010, dried blood spots (DBS) were collected during antenatal care visits and at delivery from 109 pregnant women with microscopically confirmed falciparum malaria infection. DBS were analysed by PCR-restriction fragment length polymorphism (PCR-RFLP) for the polymorphisms at codons 51, 59, 108, and 164 of the Pfdhfr gene and codons 437 and 540 in the Pfdhps gene.
  
  
  
  Both the Pfdhfr and Pfdhps genes were successfully genotyped in 92.7% (101/109) of the samples. The prevalence of Pfdhfr mutations N51I, C59R and S108N was 71.3, 42.6 and 64.4%, respectively. Overall, 80.2% (81/101) of samples carried the Pfdhps A437G mutation. None of the samples had the Pfdhfr I164L and the Pfdhps K540E mutations. The prevalence of the triple mutation N51I + C59R + S108N was 25.7% (26/101). The use of IPTp-SP was associated with a threefold increased odds of Pfdhfr C59R mutation [crude OR 3.29; 95% CI (1.44-7.50)]. Pregnant women with recent uptake of IPTp-SP were at higher odds of both the Pfdhfr C59R mutation [adjusted OR 4.26; 95% CI (1.64-11.07)] and the Pfdhfr intermediate-to-high resistance, i.e., ≥ 2 Pfdhfr mutations [adjusted OR 3.45; 95% CI (1.18-10.07)]. There was no statistically significant association between the presence of the Pfdhfr intermediate-to-high resistance and parasite densities or both maternal haemoglobin level and anaemia.
  
  
  
  The data indicate that despite the possibility that IPTp-SP contributes to the selection of resistant parasites, it did not potentiate pregnancy-associated malaria morbidity, suggesting the continuation of SP use as IPTp in Burkina Faso.
authors.affiliation: Laboratory of Parasitology and Entomology, Centre MURAZ, 01 BP 390, Bobo-Dioulasso, Burkina Faso. cisse_m@yahoo.fr.
authors.forename: Mamoudou
authors.identifier: 0000-0001-8512-8561
authors.initials: M
authors.lastname: Cisse
authors.affiliation: West African Centre for Cell Biology of Infectious Pathogens, College of Basic and Applied Sciences, University of Ghana, Accra, Ghana.
authors.forename: Gordon A
authors.initials: GA
authors.lastname: Awandare
authors.affiliation: Laboratory of Parasitology and Entomology, Centre MURAZ, 01 BP 390, Bobo-Dioulasso, Burkina Faso.
authors.forename: Alamissa
authors.initials: A
authors.lastname: Soulama
authors.affiliation: Department of Clinical Research, Centre MURAZ, Bobo-Dioulasso, Burkina Faso.
authors.forename: Halidou
authors.initials: H
authors.lastname: Tinto
authors.affiliation: Laboratory of Clinical Microbiology, University Hospital of Liège, Liège, Belgium.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Hayette
authors.affiliation: Laboratory of Parasitology and Entomology, Centre MURAZ, 01 BP 390, Bobo-Dioulasso, Burkina Faso.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Guiguemdé
mesh_terms: D000293:Adolescent; D000328:Adult; D000740:Anemia / Q000453:epidemiology / Q000469:parasitology; D000962:Antimalarials / Q000627:therapeutic use*; D002050:Burkina Faso / Q000453:epidemiology; D004338:Drug Combinations; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D016778:Malaria, Falciparum / Q000150:complications / Q000453:epidemiology / Q000469:parasitology*; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011247:Pregnancy; D015800:Protozoan Proteins / Q000235:genetics*; D011739:Pyrimethamine / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; D006454:Hemoglobins; D015800:Protozoan Proteins; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D011739:Pyrimethamine
keywords: Burkina Faso; Drug resistance; Malaria; Pregnancy; Sulfadoxine–pyrimethamine