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Molecular studies of meningococcal and pneumococcal meningitis patients in Ethiopia
Wude Mihret1,2, Berit Sletbakk Brusletto3, Reidun Øvstebø3
11 Department of Microbial and Cellular Molecular Biology, Addis Ababa University, 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.
Insights
Meningococcal meningitis in Ethiopia rarely causes septic shock, unlike in Europe. Bacterial load in Ethiopian patients was significantly lower, with higher concentrations in cerebrospinal fluid than serum.
Area of Science:
- Infectious Diseases
- Microbiology
- Clinical Medicine
Background:
- Neisseria meningitidis infections present differently in sub-Saharan Africa compared to Europe.
- Fulminant septicemia and organ failure are rare in Ethiopian meningococcal disease patients.
Purpose of the Study:
- To investigate the clinical presentation and bacterial load of Neisseria meningitidis infections in Ethiopian patients.
- To compare the inflammatory profiles in cerebrospinal fluid (CSF) between meningococcal and pneumococcal meningitis.
Main Methods:
- Prospective study of 27 Ethiopian patients with meningococcal infection.
- Real-time PCR used to quantify Neisseria meningitidis DNA (NmDNA) in CSF and serum.
- Limulus amebocyte lysate assay measured LPS levels in CSF.
- Inflammatory mediators in CSF compared between meningococcal and Streptococcus pneumoniae meningitis patients.
Main Results:
- All Ethiopian patients presented with meningitis symptoms; none had fulminant septicemia.
- Median NmDNA in serum was low (<3.5 × 10^3/ml), never exceeding 1.8 × 10^5/ml.
- NmDNA levels were 10-1000 times higher in CSF than serum.
- LPS levels in CSF correlated positively with NmDNA, IL-1 receptor antagonist, and MMP-9.
- Nine of 19 inflammatory mediators were significantly higher in pneumococcal meningitis patients.
Conclusions:
- Neisseria meningitidis infections in Ethiopia typically manifest as meningitis with lower bacterial loads than observed in European cases of severe disease.
- Distinct inflammatory profiles exist between meningococcal and pneumococcal meningitis, potentially influencing patient outcomes.
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