title: Intermittent preventive treatment in infants for the prevention of malaria in rural Western kenya: a randomized, double-blind placebo-controlled trial.
abstract: BACKGROUND
  Intermittent preventive treatment in infants (IPTi) with sulphadoxine-pyrimethamine (SP) for the prevention of malaria has shown promising results in six trials. However, resistance to SP is rising and alternative drug combinations need to be evaluated to better understand the role of treatment versus prophylactic effects.
  
  
  METHODS
  Between March 2004 and March 2008, in an area of western Kenya with year round malaria transmission with high seasonal intensity and high usage of insecticide-treated nets, we conducted a randomized, double-blind placebo-controlled trial with SP plus 3 days of artesunate (SP-AS3), 3 days of amodiaquine-artesunate (AQ3-AS3), or 3 days of short-acting chlorproguanil-dapsone (CD3) administered at routine expanded programme of immunization visits (10 weeks, 14 weeks and 9 months).
  
  
  RESULTS
  1,365 subjects were included in the analysis. The incidence of first or only episode of clinical malaria during the first year of life (primary endpoint) was 0.98 episodes/person-year in the placebo group, 0.74 in the SP-AS3 group, 0.76 in the AQ3-AS3 group, and 0.82 in the CD3 group. The protective efficacy (PE) and 95% confidence intervals against the primary endpoint were: 25.7% (6.3, 41.1); 25.9% (6.8, 41.0); and 16.3% (-5.2, 33.5) in the SP-AS3, AQ3-AS3, and CD3 groups, respectively. The PEs for moderate-to-severe anaemia were: 27.5% (-6.9, 50.8); 23.1% (-11.9, 47.2); and 11.4% (-28.6, 39.0). The duration of the protective effect remained significant for up to 5 to 8 weeks for SP-AS3 and AQ3-AS3. There was no evidence for a sustained beneficial or rebound effect in the second year of life. All regimens were well tolerated.
  
  
  CONCLUSIONS
  These results support the view that IPTi with long-acting regimens provide protection against clinical malaria for up to 8 weeks even in the presence of high ITN coverage, and that the prophylactic rather than the treatment effect of IPTi appears central to its protective efficacy.
authors.affiliation: Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, Kenya. fodhiambo@ke.cdc.gov
authors.forename: Frank O
authors.initials: FO
authors.lastname: Odhiambo
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Hamel
authors.forename: John
authors.initials: J
authors.lastname: Williamson
authors.forename: Kim
authors.initials: K
authors.lastname: Lindblade
authors.forename: Feiko O
authors.initials: FO
authors.lastname: ter Kuile
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Peterson
authors.forename: Peter
authors.initials: P
authors.lastname: Otieno
authors.forename: Simon
authors.initials: S
authors.lastname: Kariuki
authors.forename: John
authors.initials: J
authors.lastname: Vulule
authors.forename: Laurence
authors.initials: L
authors.lastname: Slutsker
authors.forename: Robert D
authors.initials: RD
authors.lastname: Newman
mesh_terms: D000740:Anemia; D000962:Antimalarials / Q000008:administration & dosage*; D037621:Artemisinins / Q000008:administration & dosage; D000077332:Artesunate; D003622:Dapsone / Q000008:administration & dosage; D004311:Double-Blind Method; D004338:Drug Combinations; D006801:Humans; D015994:Incidence; D007223:Infant; D007630:Kenya; D008288:Malaria / Q000188:drug therapy / Q000517:prevention & control*; D011292:Premedication / Q000379:methods; D002727:Proguanil / Q000008:administration & dosage / Q000031:analogs & derivatives; D011739:Pyrimethamine / Q000008:administration & dosage; D013413:Sulfadoxine / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; C519882:chloroguanil, dapsone drug combination; C001205:fanasil, pyrimethamine drug combination; D000077332:Artesunate; D013413:Sulfadoxine; D003622:Dapsone; D002727:Proguanil; D011739:Pyrimethamine