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High Pneumococcal DNA Loads Are Associated With Mortality in Malawian Children With Invasive Pneumococcal Disease

Carrol, Enitan D. MRCPCH, MD*†‡§; Guiver, Malcolm PhD∥; Nkhoma, Standwell PhD*; Mankhambo, Limangeni A. MBBS*†; Marsh, John BSc∥; Balmer, Paul PhD∥; Banda, Daniel L. DBS*; Jeffers, Graham BSc‡; The IPD Study Group; White, Sarah A. PhD*; Molyneux, Elizabeth M. FRCPCH†; Molyneux, Malcolm E. FRCP*; Smyth, Rosalind L. FRCPCH, MD‡; Hart, C Anthony FRCPath, PhD§

Pediatric Infectious Disease Journal:
doi: 10.1097/01.inf.0000260253.22994.61
Original Studies
Abstract

Background: In bacteremia owing to Streptococcus pneumoniae, high bacterial counts at presentation have been shown to be predictive of the development of serious invasive disease. Using real-time PCR, we aimed to determine pneumococcal DNA loads in blood and CSF, and their relationship to cytokine concentrations, clinical presentation and outcome.

Methods: Children with confirmed meningitis (n = 82) or pneumonia (n = 13) were prospectively recruited, and blood and CSF samples taken for pneumococcal bacterial DNA loads and cytokine determination.

Results: At the time of admission, the median bacterial load in blood was 1.6 × 103 DNA copies/mL (range 0.00–1.54 × 106) and in CSF it was 5.77 × 107 DNA copies/mL (range 4.42 × 102 to 6.15 × 108). Median blood and CSF bacterial loads (log DNA copies/mL) were significantly higher in nonsurvivors than in survivors; blood (3.80 vs. 2.97, P = 0.003), CSF (8.17 vs. 7.50, P = 0.03). In HIV-infected children (n = 59), blood and CSF loads and plasma tumor necrosis factor-α, interleukin-1β (IL-1β), IL-6 and IL-10 were all significantly higher in nonsurvivors than in survivors, but in HIV-uninfected children (n = 36) this difference was not significant. Blood bacterial loads and plasma cytokine concentrations were significantly associated, and were all significantly higher in children with meningitis than in those with pneumonia. In children with meningitis, median CSF cytokine concentrations were significantly higher than median plasma cytokine concentrations (P < 0.001) and CSF bacterial loads were significantly associated with CSF IL-1β (P = 0.002) and IL-10 (P = 0.001) concentrations.

Conclusions: Pneumococcal DNA loads are associated with plasma cytokine concentrations, and are higher in meningitis than in pneumonia. High blood and CSF pneumococcal DNA loads are associated with a fatal outcome.

Author Information

From the *Malawi-Liverpool-Wellcome Trust Clinical Research Programme, †Department of Paediatrics, College of Medicine, University of Malawi, Blantyre, Malawi; ‡Division of Child Health, The University of Liverpool, Institute of Child Health, Royal Liverpool Children's Hospital, Liverpool, United Kingdom; §Division of Medical Microbiology, The University of Liverpool, Duncan Building, Liverpool, United Kingdom; and ∥Health Protection Agency, Manchester Medical Microbiology Partnership, Clinical Sciences Building, Manchester Royal Infirmary, Manchester, United Kingdom.

Accepted for publication January 30, 2007.

Address for correspondence: E. D. Carrol, Malawi Liverpool Wellcome Research Programme, PO Box 30096, Chichiri, Blantyre 3, Malawi. E-mail: edcarrol@liv.ac.uk. Reprints not available.

© 2007 Lippincott Williams & Wilkins, Inc.