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

Abstract

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.

• Authors: Shabir A Madhi, Mariane Kohler, Locadiah Kuwanda, Clare Cutland, Keith P Klugman
• Journal: The Pediatric infectious disease journal (Pediatr Infect Dis J) Vol. 25 Issue 1 Pg. 30-6 (Jan 2006) ISSN: 0891-3668 [Print] United States
• PMID: 16395099 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, diagnosis, prevention & control)
• Protein Precursors (blood)
• Radiography
• Sensitivity and Specificity
• Vaccines, Conjugate (immunology)