Hindawi Publishing Corporation Mediators of Infammation Volume 2013, Article ID 312476, 12 pages http://dx.doi.org/10.1155/2013/312476 Research Article The Causative Pathogen Determines the Inflammatory Profile in Cerebrospinal Fluid and Outcome in Patients with Bacterial Meningitis Denis Grandgirard, 1 Rahel Gäumann, 1 Boubacar Coulibaly, 2 Jean-Pierre Dangy, 3 Ali Sie, 2 Thomas Junghanss, 4 Hans Schudel, 1 Gerd Pluschke, 3 and Stephen L. Leib 1,5 1 Neuroinfection Laboratory, Institute for Infectious Diseases, University of Bern, Friedbuehlstraße 51, 3010 Bern, Switzerland 2 Centre de Recherche en Sante de Nouna, Nouna, Burkina Faso 3 Swiss Tropical and Public Health Institute and University of Basel, 4051 Basel, Switzerland 4 Section of Clinical Tropical Medicine, Heidelberg University Hospital, 69120 Heidelberg, Germany 5 Biology Division, Spiez Laboratory, Federal Ofce for Civil Protection (FOCP), 3700 Spiez, Switzerland Correspondence should be addressed to Stephen L. Leib; stephen.leib@ifk.unibe.ch Received 22 February 2013; Revised 28 May 2013; Accepted 4 June 2013 Academic Editor: Jonathan P. Godbout Copyright © 2013 Denis Grandgirard et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Te brain’s infammatory response to the infecting pathogen determines the outcome of bacterial meningitis (BM), for example, the associated mortality and the extent of brain injury. Te infammatory cascade is initiated by the presence of bacteria in the cerebrospinal fuid (CSF) activating resident immune cells and leading to the infux of blood derived leukocytes. To elucidate the pathomechanisms behind the observed diference in outcome between diferent pathogens, we compared the infammatory profle in the CSF of patients with BM caused by Streptococcus pneumonia ( = 14), Neisseria meningitidis ( = 22), and Haemophilus infuenza (=9). Methods. CSF infammatory parameters, including cytokines and chemokines, MMP-9, and nitric oxide synthase activity, were assessed in a cohort of patients with BM from Burkina Faso. Results. Pneumococcal meningitis was associated with signifcantly higher CSF concentrations of IFN-, MCP-1, and the matrix-metalloproteinase (MMP-) 9. In patients with a fatal outcome, levels of TNF-, IL-1, IL-1RA, IL-6, and TGF- were signifcantly higher. Conclusion. Te signature of pro- and anti- infammatory mediators and the intensity of infammatory processes in CSF are determined by the bacterial pathogen causing bacterial meningitis with pneumococcal meningitis being associated with a higher case fatality rate than meningitis caused by N. meningitidis or H. infuenzae. 1. Introduction Te three major pathogens causing bacterial meningitis (BM) are Streptococcus pneumoniae (SP), Haemophilus infuenzae type b (Hib) and Neisseria meningitidis (NM). BM is the most severe and frequent infection of the central nervous system (CNS) and is associated with a high mortality rate and adverse neurological outcome in a substantial proportion of survivors [1]. BM caused by SP has the highest case fatality and neurological disability rates compared to those caused by NM or Hib [2, 3]. In a recent systematic review, the median inhospital case fatality ratio among African children with BM was 35% for SP, 25% for Hib, and 4% for NM meningitis [4]. In addition, about a quarter of children surviving pneumococ- cal meningitis and Hib meningitis had neuropsychological sequelae by the time of hospital discharge. A number of factors have been identifed as predictive for a poor outcome in terms of mortality. Coma and seizures were found to be predictive, next to shock, peripheral circula- tory failure, severe respiratory distress, a low peripheral white blood cell (WBC) count, and a high CSF protein level in a recent systematic review of prognostic studies [5]. Te host infammatory reaction in the CNS is initiated by the recognition of the invading pathogens and results in the local production of soluble mediators. Diferences in