title: Usefulness of C-reactive protein to define pneumococcal conjugate vaccine efficacy in the prevention of pneumonia.
abstract: OBJECTIVE
  This study explored whether C-reactive protein (CRP) and/or procalcitonin levels were useful to measure vaccine efficacy (VE) and impact against the burden of pneumonia of a 9-valent pneumococcal conjugate vaccine (PCV), compared with chest radiograph-confirmed alveolar consolidation (CXR-AC) as an outcome. Sera obtained from children participating in a phase 3 PCV efficacy trial who were hospitalized for treatment of clinically diagnosed lower respiratory tract infection (C-LRTI) were retrospectively analyzed for CRP and procalcitonin measurements.
  
  
  RESULTS
  For non-human immunodeficiency virus (HIV)-infected children, the VE estimates for C-LRTI with CRP levels of > or =40 mg/dL (VE 26.3%; P = 0.003) or CRP levels of > or =120 mg/dL (VE 41.0%; P = 0.003) were 1.7-fold (P = 0.002) and 2.7-fold (P < 0.0001) greater, respectively, than that for CXR-AC (VE 15.1%; P= 0.15). The sensitivity of CXR-AC as an outcome to detect the burden of pneumonia prevented by PCV was 44% (95% confidence interval, 36-55%) in comparison with C-LRTI with CRP levels of > or =40 mg/dL and 73% (95% confidence interval, 58-92%) in comparison with C-LRTI with CRP levels of > or =120 mg/dL. CRP also helped to measure the PCV efficacy for children with C-LRTI but the absence of CXR-AC, for whom the outcome of C-LRTI with CRP levels of > or =40 mg/dL (VE 31.5%; P = 0.007) increased the VE estimate 19.8-fold (P < 0.0001) in comparison with C-LRTI alone (VE 1.6%; P = 0.78) and 3.2-fold (P = 0.005) in comparison with WHO-defined severe pneumonia (VE 10.0%; P = 0.17). Although there was a significant correlation between CRP and procalcitonin levels (Spearman's rho = 0.45; P < 0.0001), the use of procalcitonin levels did not improve either the specificity or sensitivity of measuring the effect of PCV against pneumonia for non-HIV-infected children. The observations were similar for HIV-infected children.
  
  
  CONCLUSIONS
  CRP levels of > or =40 mg/dL provide a better measure than chest radiographs to assess the effect of PCV in preventing pneumonia.
authors.affiliation: University of the Witwatersrand/Medical Research Council/National Institute of Communicable Diseases-Respiratory and Meningeal Pathogens Research Unit, Johannesburg, South Africa. madhis@hivsa.com
authors.forename: Shabir A
authors.initials: SA
authors.lastname: Madhi
authors.forename: Mariane
authors.initials: M
authors.lastname: Kohler
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: D002097:C-Reactive Protein / Q000032:analysis*; D002116:Calcitonin / Q000097:blood; D015740:Calcitonin Gene-Related Peptide; D015658:HIV Infections / Q000150:complications; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008168:Lung / Q000000981:diagnostic imaging; D022242:Pneumococcal Vaccines / Q000276:immunology*; D011018:Pneumonia, Pneumococcal / Q000150:complications / Q000175:diagnosis / Q000517:prevention & control*; D011498:Protein Precursors / Q000097:blood; D011859:Radiography; D012680:Sensitivity and Specificity; D018074:Vaccines, Conjugate / Q000276:immunology
chemical_list: C000606589:CALCA protein, human; D022242:Pneumococcal Vaccines; D011498:Protein Precursors; D018074:Vaccines, Conjugate; D002116:Calcitonin; D002097:C-Reactive Protein; D015740:Calcitonin Gene-Related Peptide