title: Prevalence of Plasmodium falciparum parasites resistant to sulfadoxine/pyrimethamine in pregnant women in Yaoundé, Cameroon: emergence of highly resistant pfdhfr/pfdhps alleles.
abstract: OBJECTIVE
  To determine, 6 years after the adoption of intermittent preventive treatment of pregnant women with sulfadoxine/pyrimethamine (IPTp-SP) in Cameroon, (i) the polymorphism and prevalence of Plasmodium falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) gene mutations associated with sulfadoxine/pyrimethamine resistance and (ii) the consequences of sulfadoxine/pyrimethamine use in the selection of pfdhfr/pfdhps alleles.
  
  
  METHODS
  pfdhfr and pfdhps genes from P. falciparum isolates collected in Yaoundé (Cameroon) from pregnant women with symptomatic malaria before taking IPTp-SP [SP- group (control) (n = 51)] or afterwards [SP+ group (n = 49)] were sequenced.
  
  
  RESULTS
  The pfdhfr N51I, C59R, S108N triple mutant had a prevalence close to 100% (96/100) and no mutations at codons 50 and 164 were detected in either of the groups. The most frequent pfdhps mutation was A437G with a prevalence of 76.5% (39/51) in the SP- group, which was significantly higher in pregnant women who took sulfadoxine/pyrimethamine [95.9% (47/49)] (P = 0.012). Our study confirmed the presence of the pfdhps K540E mutation in Cameroon, but it remained rare. The prevalence of pfdhps A581G and A613S mutations had increased [5.9% (3/51) and 11.8% (6/51) in the control group, respectively] since the last studies in 2005. Surprisingly, the new pfdhps I431V mutation was detected, at a prevalence of 9.8% (5/51), and was found to be associated with other pfdhfr/pfdhps alleles to form an octuple N51I, C59R, S108N/I431V, S436A, A437G, A581G, A613S mutant.
  
  
  CONCLUSIONS
  Significant changes were found in pfdhps polymorphism. In particular, we observed several parasites carrying eight mutations in pfdhfr/pfdhps genes, which are very susceptible to having a high level of resistance to sulfadoxine/pyrimethamine.
authors.affiliation: Service de Parasitologie-Mycologie, CHU Toulouse, Toulouse, France.
authors.forename: Pamela
authors.initials: P
authors.lastname: Chauvin
authors.affiliation: Centre de Physiopathologie de Toulouse Purpan, INSERM U1043, CNRS UMR5282, Université de Toulouse, Toulouse, France.
authors.forename: Sandie
authors.initials: S
authors.lastname: Menard
authors.affiliation: Service de Parasitologie-Mycologie, CHU Toulouse, Toulouse, France Centre de Physiopathologie de Toulouse Purpan, INSERM U1043, CNRS UMR5282, Université de Toulouse, Toulouse, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Iriart
authors.affiliation: Faculté de Médecine et des Sciences Pharmaceutiques, Université de Douala, Douala, Cameroon Laboratoire d'Entomologie Médicale, Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale, Yaoundé, Cameroon.
authors.forename: Sandrine E
authors.initials: SE
authors.lastname: Nsango
authors.affiliation: Laboratoire d'Entomologie Médicale, Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale, Yaoundé, Cameroon UMR MIVEGEC, IRD, 224-CNR, 5290-UM1-UM2, Institut de Recherche pour le Développement, Montpellier, France.
authors.forename: Majoline T
authors.initials: MT
authors.lastname: Tchioffo
authors.affiliation: UMR MIVEGEC, IRD, 224-CNR, 5290-UM1-UM2, Institut de Recherche pour le Développement, Montpellier, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Abate
authors.affiliation: Laboratoire d'Entomologie Médicale, Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale, Yaoundé, Cameroon.
authors.forename: Parfait H
authors.initials: PH
authors.lastname: Awono-Ambéné
authors.affiliation: Laboratoire d'Entomologie Médicale, Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale, Yaoundé, Cameroon UMR MIVEGEC, IRD, 224-CNR, 5290-UM1-UM2, Institut de Recherche pour le Développement, Montpellier, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Morlais
authors.affiliation: Service de Parasitologie-Mycologie, CHU Toulouse, Toulouse, France Centre de Physiopathologie de Toulouse Purpan, INSERM U1043, CNRS UMR5282, Université de Toulouse, Toulouse, France berry.a@chu-toulouse.fr.
authors.forename: Antoine
authors.initials: A
authors.lastname: Berry
mesh_terms: D000328:Adult; D000962:Antimalarials / Q000494:pharmacology*; D002163:Cameroon / Q000453:epidemiology; D004094:Dihydropteroate Synthase / Q000235:genetics; D004338:Drug Combinations; D004351:Drug Resistance; D005260:Female; D005787:Gene Frequency; D006801:Humans; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000469:parasitology*; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000302:isolation & purification; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000453:epidemiology / Q000469:parasitology*; D015995:Prevalence; D011739:Pyrimethamine / Q000494:pharmacology*; D017422:Sequence Analysis, DNA; D013413:Sulfadoxine / Q000494:pharmacology*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D055815:Young Adult
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase; D011739:Pyrimethamine