title: Seven-Year Efficacy of RTS,S/AS01 Malaria Vaccine among Young African Children.
abstract: BACKGROUND
  The candidate malaria vaccine RTS,S/AS01 is being evaluated in order to inform a decision regarding its inclusion in routine vaccination schedules.
  
  
  METHODS
  We conducted 7 years of follow-up in children who had been randomly assigned, at 5 to 17 months of age, to receive three doses of either the RTS,S/AS01 vaccine or a rabies (control) vaccine. The end point was clinical malaria (temperature of ≥37.5°C and infection with Plasmodium falciparum of >2500 parasites per cubic millimeter). In an analysis that was not prespecified, the malaria exposure of each child was estimated with the use of information on the prevalence of malaria among residents within a 1-km radius of the child's home. Vaccine efficacy was defined as 1 minus the hazard ratio or the incidence-rate ratio, multiplied by 100, in the RTS,S/AS01 group versus the control group.
  
  
  RESULTS
  Over 7 years of follow-up, we identified 1002 episodes of clinical malaria among 223 children randomly assigned to the RTS,S/AS01 group and 992 episodes among 224 children randomly assigned to the control group. The vaccine efficacy, as assessed by negative binomial regression, was 4.4% (95% confidence interval [CI], -17.0 to 21.9; P=0.66) in the intention-to-treat analysis and 7.0% (95% CI, -14.5 to 24.6; P=0.52) in the per-protocol analysis. Vaccine efficacy waned over time (P=0.006 for the interaction between vaccination and time), including negative efficacy during the fifth year among children with higher-than-average exposure to malaria parasites (intention-to-treat analysis: -43.5%; 95% CI, -100.3 to -2.8 [P=0.03]; per-protocol analysis: -56.8%; 95% CI, -118.7 to -12.3 [P=0.008]).
  
  
  CONCLUSIONS
  A three-dose vaccination with RTS,S/AS01 was initially protective against clinical malaria, but this result was offset by rebound in later years in areas with higher-than-average exposure to malaria parasites. (Funded by the PATH Malaria Vaccine Initiative and others; ClinicalTrials.gov number, NCT00872963.).
authors.affiliation: From the Kenya Medical Research Institute (KEMRI)-Wellcome Trust Programme, Kilifi, Kenya (A.O., G.F., J.W., G.N., P.N., K.M., P.B.); Ifakara Health Institute, Bagamoyo, Tanzania (A.O.); the Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom (G.F., K.M., P.B.); GlaxoSmithKline Vaccines, Wavre, Belgium (A.L., M.L.); and PATH, Seattle (D.C.K.).
authors.forename: Ally
authors.initials: A
authors.lastname: Olotu
authors.affiliation: From the Kenya Medical Research Institute (KEMRI)-Wellcome Trust Programme, Kilifi, Kenya (A.O., G.F., J.W., G.N., P.N., K.M., P.B.); Ifakara Health Institute, Bagamoyo, Tanzania (A.O.); the Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom (G.F., K.M., P.B.); GlaxoSmithKline Vaccines, Wavre, Belgium (A.L., M.L.); and PATH, Seattle (D.C.K.).
authors.forename: Gregory
authors.initials: G
authors.lastname: Fegan
authors.affiliation: From the Kenya Medical Research Institute (KEMRI)-Wellcome Trust Programme, Kilifi, Kenya (A.O., G.F., J.W., G.N., P.N., K.M., P.B.); Ifakara Health Institute, Bagamoyo, Tanzania (A.O.); the Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom (G.F., K.M., P.B.); GlaxoSmithKline Vaccines, Wavre, Belgium (A.L., M.L.); and PATH, Seattle (D.C.K.).
authors.forename: Juliana
authors.initials: J
authors.lastname: Wambua
authors.affiliation: From the Kenya Medical Research Institute (KEMRI)-Wellcome Trust Programme, Kilifi, Kenya (A.O., G.F., J.W., G.N., P.N., K.M., P.B.); Ifakara Health Institute, Bagamoyo, Tanzania (A.O.); the Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom (G.F., K.M., P.B.); GlaxoSmithKline Vaccines, Wavre, Belgium (A.L., M.L.); and PATH, Seattle (D.C.K.).
authors.forename: George
authors.initials: G
authors.lastname: Nyangweso
authors.affiliation: From the Kenya Medical Research Institute (KEMRI)-Wellcome Trust Programme, Kilifi, Kenya (A.O., G.F., J.W., G.N., P.N., K.M., P.B.); Ifakara Health Institute, Bagamoyo, Tanzania (A.O.); the Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom (G.F., K.M., P.B.); GlaxoSmithKline Vaccines, Wavre, Belgium (A.L., M.L.); and PATH, Seattle (D.C.K.).
authors.forename: Amanda
authors.initials: A
authors.lastname: Leach
authors.affiliation: From the Kenya Medical Research Institute (KEMRI)-Wellcome Trust Programme, Kilifi, Kenya (A.O., G.F., J.W., G.N., P.N., K.M., P.B.); Ifakara Health Institute, Bagamoyo, Tanzania (A.O.); the Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom (G.F., K.M., P.B.); GlaxoSmithKline Vaccines, Wavre, Belgium (A.L., M.L.); and PATH, Seattle (D.C.K.).
authors.forename: Marc
authors.initials: M
authors.lastname: Lievens
authors.affiliation: From the Kenya Medical Research Institute (KEMRI)-Wellcome Trust Programme, Kilifi, Kenya (A.O., G.F., J.W., G.N., P.N., K.M., P.B.); Ifakara Health Institute, Bagamoyo, Tanzania (A.O.); the Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom (G.F., K.M., P.B.); GlaxoSmithKline Vaccines, Wavre, Belgium (A.L., M.L.); and PATH, Seattle (D.C.K.).
authors.forename: David C
authors.initials: DC
authors.lastname: Kaslow
authors.affiliation: From the Kenya Medical Research Institute (KEMRI)-Wellcome Trust Programme, Kilifi, Kenya (A.O., G.F., J.W., G.N., P.N., K.M., P.B.); Ifakara Health Institute, Bagamoyo, Tanzania (A.O.); the Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom (G.F., K.M., P.B.); GlaxoSmithKline Vaccines, Wavre, Belgium (A.L., M.L.); and PATH, Seattle (D.C.K.).
authors.forename: Patricia
authors.initials: P
authors.lastname: Njuguna
authors.affiliation: From the Kenya Medical Research Institute (KEMRI)-Wellcome Trust Programme, Kilifi, Kenya (A.O., G.F., J.W., G.N., P.N., K.M., P.B.); Ifakara Health Institute, Bagamoyo, Tanzania (A.O.); the Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom (G.F., K.M., P.B.); GlaxoSmithKline Vaccines, Wavre, Belgium (A.L., M.L.); and PATH, Seattle (D.C.K.).
authors.forename: Kevin
authors.initials: K
authors.lastname: Marsh
authors.affiliation: From the Kenya Medical Research Institute (KEMRI)-Wellcome Trust Programme, Kilifi, Kenya (A.O., G.F., J.W., G.N., P.N., K.M., P.B.); Ifakara Health Institute, Bagamoyo, Tanzania (A.O.); the Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom (G.F., K.M., P.B.); GlaxoSmithKline Vaccines, Wavre, Belgium (A.L., M.L.); and PATH, Seattle (D.C.K.).
authors.forename: Philip
authors.initials: P
authors.lastname: Bejon
mesh_terms: D066264:Datasets as Topic; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D057194:Intention to Treat Analysis; D017780:Malaria Vaccines / Q000009:adverse effects / Q000276:immunology*; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D018512:Parasitemia; D010963:Plasmodium falciparum / Q000276:immunology / Q000302:isolation & purification; D016016:Proportional Hazards Models; D016896:Treatment Outcome; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000276:immunology*
chemical_list: D017780:Malaria Vaccines; C577001:RTS,S-AS01 vaccine; D014614:Vaccines, Synthetic