Sequential analysis of biomarkers in cerebrospinal fluid and serum during invasive meningococcal disease

The aim of the present study was to determine the profile of different inflammatory molecules in serum and cerebrospinal fluid (CSF) during invasive meningococcal disease (IMD). Their relationship with IMD severity was also assessed. A cohort of 12 patients with IMD was investigated. Paired serum and CSF samples were obtained at the time of diagnostic and follow-up lumbar puncture and were examined using Luminex® analysis. IMD severity correlated with serum interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1ra) on admission. Furthermore, the CSF levels of IL-1β, IL-1ra, IL-6, IL-8, macrophage inflammatory protein-1β (MIP-1β), and monocyte chemoattractant protein-1 (MCP-1) were significantly higher than their respective serum levels. The strongest correlations were found between serum concentrations of IL-1β and IL-1ra, IL-6, IL-8, and MIP-1β, whereas the strongest correlations in CSF were found between endotoxin and IL-8, IL-17, MIP-1β, and MCP-1. As was expected, the concentrations of inflammatory molecules in both serum and CSF significantly decreased after antibiotic treatment. With regard to kinetics, a severe course of IMD correlated positively with rapid declines of CSF IL-6 and cortisol levels. Sequential multiple analyses revealed patterns of inflammatory responses that were associated with the severity of IMD, as well as with the compartmentalization and kinetics of the immune reaction

Dynamics of PCR-based diagnosis in patients with invasive meningococcal disease

ABSTRACTInvasive meningococcal disease continues to be a life-threatening condition and rapid diagnosis is important for the administration of appropriate treatment. This study focused on the use of PCR for the diagnosis of meningococcal aetiology and the dynamics of PCR-based diagnosis over time in various biological samples. Sixty cerebrospinal fluid (CSF) and 144 serum samples collected during the first week of hospitalisation from 37 patients with laboratory-confirmed invasive meningococcal disease were investigated. Overall, 91.9% of CSF samples and 45.9% of serum samples were PCR-positive, while culture of CSF and blood was positive for only 35% and 39% samples, respectively. Positive PCR results were obtained until day 7 with CSF and until day 5 with serum. It is therefore recommended that samples for molecular diagnosis should be collected early in the course of suspected invasive meningococcal disease

Targeted mass spectrometry analysis of neutrophil-derived proteins released during sepsis progression

Early diagnosis of severe infectious diseases is essential for timely implementation of lifesaving therapies. In a search for novel biomarkers in sepsis diagnosis we focused on polymorphonuclear neutrophils (PMNs). Notably, PMNs have their protein cargo readily stored in granules and following systemic stimulation an immediate increase of neutrophil-borne proteins can be observed into the circulation of sepsis patients. We applied a combination of mass spectrometry (MS) based approaches, LC-MS/MS and selected reaction monitoring (SRM), to characterise and quantify the neutrophil proteome in healthy or disease conditions. With this approach we identified a neutrophil-derived protein abundance pattern in blood plasma consisting of 20 proteins that can be used as a protein signature for severe infectious diseases. Our results also show that SRM is highly sensitive, specific, and reproducible and, thus, a promising technology to study a complex, dynamic and multifactorial disease such as sepsis

ESCMID guideline: diagnosis and treatment of acute bacterial meningitis

WOS: 000378628600001PubMed ID: 27062097European Clinical Microbiology and Infectious Disease Society (ESCMID)Funded by a grant of the European Clinical Microbiology and Infectious Disease Society (ESCMID). All authors report no conflicts of interest relevant to this article