title: Pneumococcal conjugate vaccines for preventing vaccine-type invasive pneumococcal disease and pneumonia with consolidation on x-ray in children under two years of age.
abstract: BACKGROUND
  Pneumonia, most commonly caused by Streptococcus pneumoniae (Pnc), is a major cause of morbidity and mortality among young children especially in developing countries. Recently, the prevalence of antibiotic-resistant Pnc has increased worldwide such that the effectiveness of preventive strategies, like the new pneumococcal conjugate vaccines (PCV) on rates of invasive pneumococcal disease (IPD) and pneumonia, needs to be evaluated.
  
  
  OBJECTIVE
  To determine the efficacy of PCV in reducing the incidence of IPD due to vaccine serotypes (VT) and x-ray confirmed pneumonia with consolidation of unspecified etiology in children who received PCV before 12 months of age.
  
  
  METHODS
  We searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1 2004), MEDLINE (1990 to March 2004) and EMBASE (1990 to December 2003). Reference list of articles, and books of abstracts of relevant symposia, were hand searched. Researchers in the field were also contacted.
  
  
  METHODS
  Randomised controlled trials (RCTs) comparing PCV with placebo, or another vaccine, among children below two years with IPD and clinical/radiographic pneumonia as outcomes.
  
  
  METHODS
  Two reviewers independently identified eligible studies, assessed trial quality, and extracted data. Differences were resolved by discussion. The inverse variance method was used to pool effect sizes.
  
  
  RESULTS
  We identified four trials assessing the efficacy of PCV in reducing the incidence of IPD, two on x-ray confirmed pneumonia as outcome, and one on clinical pneumonia, with or without x-ray confirmation. Results from pooling HIV-1 negative children from the South African study with the other studies were as follows: the pooled vaccine efficacy (VE) for vaccine-type IPD was 88% (95% confidence interval (CI) 73% to 94%; fixed effect and random effects models), the effect measure was statistically significant (p <0.00001) and there was no heterogeneity (p = 0.77I2 0%); the pooled VE for all-serotype IPD was 66% (95% CI 46% to 79%; fixed effect model), the effect measure was statistically significant (p <0.00001) and there was no statistical heterogeneity (p = 0.09, I2 51%); the pooled VE for x-ray confirmed pneumonia was 22% (95% CI 11% to 31%; both fixed effect and random effects models) and there was no statistical heterogeneity (p = 0.80, I2 0%). Analyses that included all the children in the South African study (HIV-1 negative and HIV-1 positive children) and pooled with data from the other studies gave very similar results.
  
  
  CONCLUSIONS
  PCV is effective in reducing the incidence of IPD from all serotypes but exerts a greater effect in reducing VT IPD. Although PCV is also effective in reducing the incidence of x-ray confirmed pneumonia, there are still uncertainties about the definition of this outcome. Additional randomised controlled trials are currently in progress.
authors.affiliation: Department of Medicine, Research Institute for Tropical Medicine, Filinvest Corporate City, Alabang, Muntinlupa City, 1781, Philippines. mglucero@pldtdsl.net
authors.forename: M G
authors.initials: MG
authors.lastname: Lucero
authors.forename: V E
authors.initials: VE
authors.lastname: Dulalia
authors.forename: R N
authors.initials: RN
authors.lastname: Parreno
authors.forename: D M
authors.initials: DM
authors.lastname: Lim-Quianzon
authors.forename: H
authors.initials: H
authors.lastname: Nohynek
authors.forename: H
authors.initials: H
authors.lastname: Makela
authors.forename: G
authors.initials: G
authors.lastname: Williams
mesh_terms: D006801:Humans; D007223:Infant; D011008:Pneumococcal Infections / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000627:therapeutic use*; D011018:Pneumonia, Pneumococcal / Q000000981:diagnostic imaging / Q000517:prevention & control; D011859:Radiography; D018074:Vaccines, Conjugate / Q000627:therapeutic use
chemical_list: D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate