Molecular studies of meningococcal and pneumococcal meningitis patients in Ethiopia

Abstract

Neisseria meningitidis infections in sub-Saharan Africa usually present with distinct symptoms of meningitis but very rarely as fulminant septicemia when reaching hospitals. In Europe, development of persistent meningococcal shock and multiple organ failure occurs in up to 30% of patients and is associated with a bacterial load of >10⁶/ml plasma or serum. We have prospectively studied 27 Ethiopian patients with meningococcal infection as diagnosed and quantified with real-time PCR in the cerebrospinal fluid (CSF) and serum. All presented with symptoms of meningitis and none with fulminant septicemia. The median N. meningitidis copy number (NmDNA) in serum was < 3.5 × 10³/ml, never exceeded 1.8 × 10⁵/ml, and was always 10-1000 times higher in CSF than in serum. The levels of LPS in CSF as determined by the limulus amebocyte lysate assay were positively correlated to NmDNA copy number ( r = 0.45, P = 0.030), levels of IL-1 receptor antagonist, ( r = 0.46, P = 0.017), and matrix metallopeptidase-9 (MMP-9; r = 0.009). We also compared the inflammatory profiles of 19 mediators in CSF of the 26 meningococcal patients (2 died and 2 had immediate severe sequelae) with 16 patients with Streptococcus pneumoniae meningitis (3 died and 3 with immediate severe sequelae). Of 19 inflammatory mediators tested, 9 were significantly higher in patients with pneumococcal meningitis and possibly linked to worse outcome.

Keywords: Bacterial meningitis; cerebrospinal fluid; chemokine; cytokine; lipopolysaccharides; matrix metallopeptidase-9; septic shock; septicemia.

Figure 1.

Scatterplot with median value of the concentrations (pg/mL) of inflammatory mediators in cerebrospinal fluids from Ethiopian meningococcal and pneumococcal patients with significant differences between the patient groups. IL-4: P = 0.0268, IL-12p70: P = 0.0260, IFN-ϒ: P = 0.0104, IP10: P = 0.0395, MCP-1: P = 0.0063, MIP-1α: P = 0.0198, MIP-1α: P = 0.0116, RANTES: P = 0.0395, MMP-9: P = 0.0486.