Development of a Health Related Quality of Life Measure for Adolescents and Young Adults Following Invasive Meningococcal Disease

This study describes the key areas that matter to adolescent survivors of Invasive Meningococcal Disease (IMD). Satisfaction with Life After Meningitis is a brief multidimensional measure of health related quality of life that is reliable and correlates with criterion variables in a theoretically meaningful way. To develop a Health Related Quality of Life (HRQoL) measure for adolescent and young adult survivors of (IMD) we used a cross-sectional study and focus groups. The study was conducted in two phases. In Phase 1 a pool of potential items were generated based on the following: a review of existing measures, focus groups with IMD survivors, and an expert group consultation. Phase 2 involved administration of the questionnaire to a sample of adolescent and young adult IMD survivors. Factor analysis suggested a correlated four factor solution: Wellbeing, Positive about Future, Social Support, and Confidence. These factors were significantly correlated in a theoretically predictable way with scores from the Beck Depression Inventory (correlations ranged from −0.77 to −0.81) and the eight domains of the SF-36 Health Survey (correlations ranged from 0.32 to 0.79). The reliability of all subscales was high ranging from 0.85 to 0.92. The Satisfaction with Life After Meningitis (SLAM) questionnaire is a HRQoL self-report measure that produces reliable scores and is appropriate for use with young survivors of IMD. There is also evidence of concurrent validity with existing measures of physical and psychological well-being

Cognitive outcome in adults with moderate disability after pneumococcal meningitis

Objectives To assess cognitive outcome and quality of life in patients with moderate disability after bacterial meningitis as compared to patients with good recovery. Methods Neuropsychological evaluation was performed in 40 adults after pneumococcal meningitis; 20 patients with moderate disability at discharge on the glasgow outcome scale (GOS score 4) and 20 with good recovery (GOS score 5). Results Patients with GOS score 4 had similar test results as compared to patients with GOS score 5 for the neuropsychological domains ‘intelligence’, ‘memory’ and ‘attention and executive functioning’. Patients with GOS score 4 showed less cognitive slowness than patients with GOS score 5. In a linear regression analysis cognitive speed was related to current intelligence, years of education and time since meningitis. Overall performance on the speed composite score correlated significantly with time since meningitis (−0.62; P<0.001). Therefore, difference between both groups may have been related to a longer time between meningitis and testing for GOS four patients (29 vs. 12 months; P<0.001). Conclusions Patients with moderate disability after bacterial meningitis are not at higher risk for neuropsychological abnormalities than patients with good recovery. In addition, cognitive slowness after bacterial meningitis may be reversible in time

Novel Complement Blocking Antibodies Against Serogroup B \u3cem\u3eN. meningitidis\u3c/em\u3e: A Dissertation

N. meningitidis is a common commensal of the human upper respiratory tract and a leading cause of bacterial meningitis and septicemia worldwide. The classical pathway of complement (C) is essential for both naturally acquired and vaccine induced immunity against N. meningitidis. Qualitative and/or quantitative differences in anti-meningococcal antibodies (Abs) in serum is one reason for variations in C-dependent bactericidal Ab activity among individuals. I showed that IgG isolated from select individuals could block killing of group B meningococci by Abs that were otherwise bactericidal. Ligand overlay immunoblots revealed that these blocking IgG Abs were directed against a meningococcal antigen called H.8, Killing of meningococci in reactions containing bactericidal mAbs and human blocking Abs was restored when blocking Ab binding to meningococci was inhibited (or competed for) using either synthetic peptides corresponding to H.8 or a non-blocking mAb against H.8. Further, genetic deletion of H.8 from target organisms abrogated blocking. The Fc region of the blocking IgG was required for blocking because F(ab)2 fragments alone generated by pepsin treatment were ineffective. Blocking required IgG glycosylation; deglycosylation of blocking IgG with peptide:N-glycanase (PNGase) eliminated blocking. C4 deposition mediated by a bactericidal mAb directed against a meningococcal vaccine candidate, called factor H-binding protein (fHbp), was reduced by blocking Ab. Anti-fHbp-mediated C4 deposition was unaffected, however, by deglycosylated blocking IgG. Although preliminary, our data suggests blocking of serum bactericidal activity by human anti-H.8 blocking antibody may require mannan-binding lectin (MBL), which itself is a complement activator. Also, whether MBL recruits a complement inhibitor(s) that facilitates blocking remains to be determined. In conclusion, we have identified H.8 as a meningococcal target for novel blocking antibodies that are commonly found in human serum. Blocking Ab may reduce the efficacy of meningococcal vaccines. We propose that outer membrane vesicle-containing meningococcal vaccines may be more efficacious if purged of subversive immunogens such as H.8