title: Efficacy of RTS,S/AS01E vaccine against malaria in children 5 to 17 months of age.
abstract: BACKGROUND
  Plasmodium falciparum malaria is a pressing global health problem. A previous study of the malaria vaccine RTS,S (which targets the circumsporozoite protein), given with an adjuvant system (AS02A), showed a 30% rate of protection against clinical malaria in children 1 to 4 years of age. We evaluated the efficacy of RTS,S given with a more immunogenic adjuvant system (AS01E) in children 5 to 17 months of age, a target population for vaccine licensure.
  
  
  METHODS
  We conducted a double-blind, randomized trial of RTS,S/AS01E vaccine as compared with rabies vaccine in children in Kilifi, Kenya, and Korogwe, Tanzania. The primary end point was fever with a falciparum parasitemia density of more than 2500 parasites per microliter, and the mean duration of follow-up was 7.9 months (range, 4.5 to 10.5).
  
  
  RESULTS
  A total of 894 children were randomly assigned to receive the RTS,S/AS01E vaccine or the control (rabies) vaccine. Among the 809 children who completed the study procedures according to the protocol, the cumulative number in whom clinical malaria developed was 32 of 402 assigned to receive RTS,S/AS01E and 66 of 407 assigned to receive the rabies vaccine; the adjusted efficacy rate for RTS,S/AS01E was 53% (95% confidence interval [CI], 28 to 69; P<0.001) on the basis of Cox regression. Overall, there were 38 episodes of clinical malaria among recipients of RTS,S/AS01E, as compared with 86 episodes among recipients of the rabies vaccine, with an adjusted rate of efficacy against all malarial episodes of 56% (95% CI, 31 to 72; P<0.001). All 894 children were included in the intention-to-treat analysis, which showed an unadjusted efficacy rate of 49% (95% CI, 26 to 65; P<0.001). There were fewer serious adverse events among recipients of RTS,S/AS01E, and this reduction was not only due to a difference in the number of admissions directly attributable to malaria.
  
  
  CONCLUSIONS
  RTS,S/AS01E shows promise as a candidate malaria vaccine. (ClinicalTrials.gov number, NCT00380393.)
authors.affiliation: Centre for Geographic Medicine Research (Coast), Kenya Medical Research Institute, Kilifi, Kenya. pbejon@kilifi.kemri-wellcome.org
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authors.forename: Marie-Claude
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authors.forename: Marie-Ange
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authors.lastname: Demoitié
authors.forename: Jean-Francois
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authors.lastname: Stallaert
authors.forename: Preeti
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authors.lastname: Vansadia
authors.forename: Terrell
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authors.lastname: Carter
authors.forename: Patricia
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authors.lastname: Njuguna
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authors.lastname: Awuondo
authors.forename: Anangisye
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authors.forename: Samwel
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authors.forename: Neema
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authors.forename: Chris J
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authors.lastname: Drakeley
authors.forename: Barbara
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authors.lastname: Savarese
authors.forename: Tonya
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authors.lastname: Villafana
authors.forename: W Ripley
authors.initials: WR
authors.lastname: Ballou
authors.forename: Joe
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authors.lastname: Cohen
authors.forename: Eleanor M
authors.initials: EM
authors.lastname: Riley
authors.forename: Martha M
authors.initials: MM
authors.lastname: Lemnge
authors.forename: Kevin
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mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D010963:Plasmodium falciparum / Q000276:immunology; D016016:Proportional Hazards Models; D015800:Protozoan Proteins / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C533816:RTS,S-AS01E vaccine; C041595:circumsporozoite protein, Protozoan