Usefulness of C-reactive protein to define pneumococcal conjugate vaccine efficacy in the prevention of pneumonia

Pediatr Infect Dis J. 2006 Jan;25(1):30-6. doi: 10.1097/01.inf.0000195787.99199.4a.


Objectives and methods: 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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • C-Reactive Protein / analysis*
  • Calcitonin / blood
  • Calcitonin Gene-Related Peptide
  • HIV Infections / complications
  • Humans
  • Infant
  • Infant, Newborn
  • Lung / diagnostic imaging
  • Pneumococcal Vaccines / immunology*
  • Pneumonia, Pneumococcal / complications
  • Pneumonia, Pneumococcal / diagnosis
  • Pneumonia, Pneumococcal / prevention & control*
  • Protein Precursors / blood
  • Radiography
  • Sensitivity and Specificity
  • Vaccines, Conjugate / immunology


  • CALCA protein, human
  • Pneumococcal Vaccines
  • Protein Precursors
  • Vaccines, Conjugate
  • Calcitonin
  • C-Reactive Protein
  • Calcitonin Gene-Related Peptide