title: Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia: randomised, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  Pneumonia is estimated to cause 2 million deaths every year in children. Streptococcus pneumoniae is the most important cause of severe pneumonia. We aimed to assess the efficacy of a nine-valent pneumococcal conjugate vaccine in children.
  
  
  METHODS
  We undertook a randomised, placebo-controlled, double-blind trial in eastern Gambia. Children age 6-51 weeks were randomly allocated three doses of either pneumococcal conjugate vaccine (n=8718) or placebo (8719), with intervals of at least 25 days between doses. Our primary outcome was first episode of radiological pneumonia. Secondary endpoints were clinical or severe clinical pneumonia, invasive pneumococcal disease, and all-cause admissions. Analyses were per protocol and intention to treat.
  
  
  RESULTS
  529 children assigned vaccine and 568 allocated placebo were not included in the per-protocol analysis. Results of per-protocol and intention-to-treat analyses were similar. By per-protocol analysis, 333 of 8189 children given vaccine had an episode of radiological pneumonia compared with 513 of 8151 who received placebo. Pneumococcal vaccine efficacy was 37% (95% CI 27-45) against first episode of radiological pneumonia. First episodes of clinical pneumonia were reduced overall by 7% (95% CI 1-12). Efficacy of the conjugate vaccine was 77% (51-90) against invasive pneumococcal disease caused by vaccine serotypes, 50% (21-69) against disease caused by all serotypes, and 15% (7-21) against all-cause admissions. We also found an efficacy of 16% (3-28) against mortality. 110 serious adverse events arose in children given the pneumococcal vaccine compared with 131 in those who received placebo.
  
  
  CONCLUSIONS
  In this rural African setting, pneumococcal conjugate vaccine has high efficacy against radiological pneumonia and invasive pneumococcal disease, and can substantially reduce admissions and improve child survival. Pneumococcal conjugate vaccines should be made available to African infants.
authors.affiliation: Medical Research Council Laboratories, Banjul, The Gambia.
authors.forename: F T
authors.initials: FT
authors.lastname: Cutts
authors.forename: S M A
authors.initials: SM
authors.lastname: Zaman
authors.forename: G
authors.initials: G
authors.lastname: Enwere
authors.forename: S
authors.initials: S
authors.lastname: Jaffar
authors.forename: O S
authors.initials: OS
authors.lastname: Levine
authors.forename: J B
authors.initials: JB
authors.lastname: Okoko
authors.forename: C
authors.initials: C
authors.lastname: Oluwalana
authors.forename: A
authors.initials: A
authors.lastname: Vaughan
authors.forename: S K
authors.initials: SK
authors.lastname: Obaro
authors.forename: A
authors.initials: A
authors.lastname: Leach
authors.forename: K P
authors.initials: KP
authors.lastname: McAdam
authors.forename: E
authors.initials: E
authors.lastname: Biney
authors.forename: M
authors.initials: M
authors.lastname: Saaka
authors.forename: U
authors.initials: U
authors.lastname: Onwuchekwa
authors.forename: F
authors.initials: F
authors.lastname: Yallop
authors.forename: N F
authors.initials: NF
authors.lastname: Pierce
authors.forename: B M
authors.initials: BM
authors.lastname: Greenwood
authors.forename: R A
authors.initials: RA
authors.lastname: Adegbola
mesh_terms: D002675:Child, Preschool; D005260:Female; D005714:Gambia / Q000453:epidemiology; D006801:Humans; D007115:Immunization Schedule; D015994:Incidence; D007223:Infant; D008297:Male; D011008:Pneumococcal Infections / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D011018:Pneumonia, Pneumococcal / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D018074:Vaccines, Conjugate
chemical_list: D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate