title: High rates of parasite recrudescence following intermittent preventive treatment with sulphadoxine-pyrimethamine during pregnancy in Benin.
abstract: BACKGROUND
  Despite widespread parasite resistance to sulphadoxine-pyrimethamine (SP) its use for intermittent preventative treatment during pregnancy remains the policy in Benin and throughout most of sub-Saharan Africa.
  
  
  METHODS
  In a prospective study, 982 pregnant women were recruited in Benin and followed until delivery. The prevalence of point mutations in the pfdhfr and pfdhps genes associated with Plasmodium falciparum resistance to SP during consecutive antenatal visits was determined. Parasites clearance among women infected at SP intake was assessed by microscopy and PCR. Association between the persistence of parasites and malaria consequences, were investigated. Recurrent parasites were genotyped to identify recrudescences from re-infections.
  
  
  RESULTS
  The prevalence of pfdhfr/pfdhps quadruple mutants (triple pfdhfr + single pfdhps) was consistently above 80% while quintuple and sextuple mutants remained low. Importantly the higly mutated parasites apparently never included the two key mutations, pfdhfr 164 L or pfdhps 540E. Based on PCR results, SP failed to clear existing parasitaemia in half (48%) of the women who were infected at IPTp schedule. The frequency of recrudescence reached 76% after the second dose. Women with persistent parasitaemia had an increased prevalence of anaemia (P = 0.03).
  
  
  CONCLUSIONS
  The data presented here, highlight the inability of SP to ensure optimal antiplasmodial protection in late pregnancy, and invite urgent consideration of an alternative drug or strategy.
authors.forename: Azizath
authors.initials: A
authors.lastname: Moussiliou
authors.forename: Yolande Sissinto-Savi
authors.initials: YS
authors.lastname: De Tove
authors.forename: Justin
authors.initials: J
authors.lastname: Doritchamou
authors.forename: Adrian J F
authors.initials: AJ
authors.lastname: Luty
authors.forename: Achille
authors.initials: A
authors.lastname: Massougbodji
authors.forename: Michael
authors.initials: M
authors.lastname: Alifrangis
authors.forename: Philippe
authors.initials: P
authors.lastname: Deloron
authors.forename: Nicaise Tuikue
authors.initials: NT
authors.lastname: Ndam
mesh_terms: D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001541:Benin / Q000453:epidemiology; D004094:Dihydropteroate Synthase / Q000235:genetics; D004338:Drug Combinations; D005260:Female; D006239:Haplotypes; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology / Q000517:prevention & control; D018512:Parasitemia; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D017354:Point Mutation / Q000187:drug effects; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology / Q000517:prevention & control; D015995:Prevalence; D011446:Prospective Studies; D015800:Protozoan Proteins / Q000235:genetics; D011739:Pyrimethamine / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D012008:Recurrence; D013413:Sulfadoxine / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D055815:Young Adult
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; D015800:Protozoan Proteins; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase; D011739:Pyrimethamine