title: A randomized controlled trial of folate supplementation when treating malaria in pregnancy with sulfadoxine-pyrimethamine.
abstract: OBJECTIVE
  Sulfadoxine-pyrimethamine (SP) is an antimalarial drug that acts on the folate metabolism of the malaria parasite. We investigated whether folate (FA) supplementation in a high or a low dose affects the efficacy of SP for the treatment of uncomplicated malaria in pregnant women.
  
  
  METHODS
  This was a randomized, placebo-controlled, double-blind trial.
  
  
  METHODS
  The trial was carried out at three hospitals in western Kenya.
  
  
  METHODS
  The participants were 488 pregnant women presenting at their first antenatal visit with uncomplicated malaria parasitaemia (density of >or= 500 parasites/microl), a haemoglobin level higher than 7 g/dl, a gestational age between 17 and 34 weeks, and no history of antimalarial or FA use, or sulfa allergy. A total of 415 women completed the study.
  
  
  METHODS
  All participants received SP and iron supplementation. They were randomized to the following arms: FA 5 mg, FA 0.4 mg, or FA placebo. After 14 days, all participants continued with FA 5 mg daily as per national guidelines. Participants were followed at days 2, 3, 7, 14, 21, and 28 or until treatment failure.
  
  
  METHODS
  The outcomes were SP failure rate and change in haemoglobin at day 14.
  
  
  RESULTS
  The proportion of treatment failure at day 14 was 13.9% (19/137) in the placebo group, 14.5% (20/138) in the FA 0.4 mg arm (adjusted hazard ratio [AHR], 1.07; 98.7% confidence interval [CI], 0.48 to 2.37; p = 0.8), and 27.1% (38/140) in the FA 5 mg arm (AHR, 2.19; 98.7% CI, 1.09 to 4.40; p = 0.005). The haemoglobin levels at day 14 were not different relative to placebo (mean difference for FA 5 mg, 0.17 g/dl; 98.7% CI, -0.19 to 0.52; and for FA 0.4 mg, 0.14 g/dl; 98.7% CI, -0.21 to 0.49).
  
  
  CONCLUSIONS
  Concomitant use of 5 mg FA supplementation compromises the efficacy of SP for the treatment of uncomplicated malaria in pregnant women. Countries that use SP for treatment or prevention of malaria in pregnancy need to evaluate their antenatal policy on timing or dose of FA supplementation.
authors.affiliation: Centre for Vector Biology and Control Research, Kenya Medical Research Institute, Kisumu, Kenya.
authors.forename: Peter
authors.initials: P
authors.lastname: Ouma
authors.forename: Monica E
authors.initials: ME
authors.lastname: Parise
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Hamel
authors.forename: Feiko O
authors.initials: FO
authors.lastname: Ter Kuile
authors.forename: Kephas
authors.initials: K
authors.lastname: Otieno
authors.forename: John G
authors.initials: JG
authors.lastname: Ayisi
authors.forename: Piet A
authors.initials: PA
authors.lastname: Kager
authors.forename: Richard W
authors.initials: RW
authors.lastname: Steketee
authors.forename: Laurence
authors.initials: L
authors.lastname: Slutsker
authors.forename: Anna M
authors.initials: AM
authors.lastname: van Eijk