title: The impact of a 9-valent pneumococcal conjugate vaccine on the public health burden of pneumonia in HIV-infected and -uninfected children.
abstract: BACKGROUND
  Pneumococcal conjugate vaccine (PnCV) may be used as a probe to define the burden of pneumococcal disease and better characterize the clinical presentation of pneumococcal pneumonia.
  
  
  METHODS
  This study used a 9-valent PnCV to define different end points of vaccine efficacy and the preventable burden of pneumococcal pneumonia in 39,836 children who were randomized in a double-blind, placebo-controlled trial in South Africa.
  
  
  RESULTS
  Whereas the point-estimate of vaccine efficacy was greatest when measured against the outcome of vaccine-serotype specific pneumococcal bacteremic pneumonia (61%; P = .01), the sensitivity of blood culture to measure the burden of pneumococcal pneumonia prevented by vaccination was only 2.6% in human immunodeficiency virus (HIV)-uninfected children and 18.8% in HIV-infected children. Only 37.8% of cases of pneumococcal pneumonia prevented by PnCV were detected by means of chest radiographs showing alveolar consolidation. A clinical diagnosis of pneumonia provided the best estimate of the burden of pneumococcal pneumonia prevented through vaccination in HIV-uninfected children (267 cases prevented per 100,000 child-years) and HIV-infected children (2573 cases prevented per 100,000 child-years).
  
  
  CONCLUSIONS
  Although outcome measures with high specificity, such as bacteremic pneumococcal pneumonia, provide a better estimate as to vaccine efficacy, the burden of disease prevented by vaccination is best evaluated using outcome measures with high sensitivity, such as a clinical diagnosis of pneumonia.
authors.affiliation: National Health Laboratory Service, University of the Witwatersrand, Johannesburg, South Africa. madhis@hivsa.com
authors.forename: Shabir A
authors.initials: SA
authors.lastname: Madhi
authors.forename: Locadiah
authors.initials: L
authors.lastname: Kuwanda
authors.forename: Clare
authors.initials: C
authors.lastname: Cutland
authors.forename: Keith P
authors.initials: KP
authors.lastname: Klugman
mesh_terms: D004311:Double-Blind Method; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D015994:Incidence; D007223:Infant; D022242:Pneumococcal Vaccines / Q000627:therapeutic use*; D011018:Pneumonia, Pneumococcal / Q000150:complications* / Q000453:epidemiology / Q000517:prevention & control*; D013019:South Africa / Q000453:epidemiology; D018074:Vaccines, Conjugate / Q000627:therapeutic use
chemical_list: D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate