Recognition of Neisseria meningitidis by the long pentraxin PTX3 and its role as an endogenous adjuvant.

Long pentraxin 3 (PTX3) is a non-redundant component of the humoral arm of innate immunity. The present study was designed to investigate the interaction of PTX3 with Neisseria meningitidis. PTX3 bound acapsular meningococcus, Neisseria-derived outer membrane vesicles (OMV) and 3 selected meningococcal antigens (GNA0667, GNA1030 and GNA2091). PTX3-recognized microbial moieties are conserved structures which fulfil essential microbial functions. Ptx3-deficient mice had a lower antibody response in vaccination protocols with OMV and co-administration of PTX3 increased the antibody response, particularly in Ptx3-deficient mice. Administration of PTX3 reduced the bacterial load in infant rats challenged with Neisseria meningitidis. These results suggest that PTX3 recognizes a set of conserved structures from Neisseria meningitidis and acts as an amplifier/endogenous adjuvant of responses to this bacterium.

Outcomes of invasive meningococcal serogroup B disease in children and adolescents (MOSAIC): a case-control study.

BACKGROUND: Serogroup B meningococcal disease is the commonest cause of meningitis and septicaemia in high-income countries. Assessment of new serogroup B meningococcal vaccines is hampered by a scarcity of data on the burden of disease in survivors. We aimed to estimate the disease burden in children having survived serogroup B meningococcal disease. METHODS: In this case-control study, we recruited children from the UK National Meningococcal Registry between May, 2008, and September, 2010. Eligible children were survivors who had had serogroup B meningococcal disease confirmed by culture or PCR and were aged 1 month to 13 years at disease. Age-matched and sex-matched controls were recruited through the family doctor of the children who had the meningococcal disease. Physical, psychological, neurocognitive, and educational outcomes were assessed through a standardised interview with validated instruments. We did matched analyses using generalised estimating equations (GEE). Researchers were masked to the children's serogroup B meningococcal status. FINDINGS: Of the 537 children who had serogroup B meningococcal disease and were available for recruitment, 245 were assessed. 328 controls were also recruited; 221 controls were matched with a case and 107 were additional unmatched controls. The mean age was 6·5 (SD 2·8) years in children with serogroup B meningococcal disease and 6·9 (2·9) in controls. In the full sample, children who had serogroup B meningococcal disease were more likely than controls to have bilateral sensorineural hearing loss of 40 dB or more (unmatched 11 [5%] of 232 children with meningococcal disease vs three [<1%] of 318 controls; matched odds ratio [OR] 4·8, 95% CI 1·3 to 17·4, p=0·02), lower full-scale IQ (matched mean 99·5 for children with meningococcal disease and 107·2 for controls; matched coefficient -7·6, 95% CI -9·9 to -5·4, p<0·0001), and psychological disorders (61 [26%] of 235 children with meningococcal disease vs 33 (10%) of 322 controls; matched full sample OR 2·6, 1·6 to 4·2, p<0·0001). Disabling amputations were noted in three (1%) of 239 children who had serogroup B meningococcal disease compared with none of the 322 controls. Children with meningococcal disease were also more likely to have deficits in executive function and multiple aspects of memory. Deficits were identified in 87 (36%) of 244 children with serogroup B meningococcal disease and 49 (15%) of 328 controls (matched OR 2·7, 1·8 to 4·1, p<0·0001). Major disabling deficits were identified in 21 (9%) of 244 children with meningococcal disease compared with six (2%) of 328 controls (matched OR 5·0, 2·0 to 12·6, p=0·001). No significant differences were noted in attentional function or post-traumatic stress disorder between children with serogroup B meningococcal disease and controls. INTERPRETATION: Most children survive serogroup B meningococcal disease without major sequelae. However, about a tenth have major disabling deficits and more than a third have one or more deficits in physical, cognitive, and psychological functioning, with the additional burden of memory deficits and executive function problems. These findings should help to guide assessments of new vaccines and suggest that all survivors of serogroup B meningococcal disease should be screened for psychological disorders and cognitive deficits in addition to hearing loss. FUNDING: Meningitis Trust and Big Lottery Fund, UK.

Increased incidence of meningococcal disease in HIV-infected individuals associated with higher case-fatality ratios in South Africa.

OBJECTIVES: We aimed to compare the incidence of meningococcal disease amongst HIV-infected and uninfected individuals and to evaluate whether HIV is a risk factor for mortality and bacteremia amongst patients with meningococcal disease. DESIGN: Cohort surveillance study. METHODS: We conducted laboratory-based surveillance for meningococcal disease in Gauteng Province, South Africa. HIV status and outcome data were obtained at sentinel sites. Incidence in HIV-infected and uninfected persons was calculated assuming a similar age-specific HIV prevalence in tested and untested individuals. Risk factors for death and bacteremia (as compared with meningitis) were evaluated using multivariable logistic regression. RESULTS: From 2003 to 2007, 1336 meningococcal cases were reported. Of 504 patients at sentinel sites with known outcome, 308 (61%) had HIV serostatus data. HIV prevalence amongst cases of meningococcal disease was higher than the population HIV prevalence in all age groups. The incidence of meningococcal disease in HIV-infected individuals was elevated in all age groups with an age-adjusted relative risk of 11.3 [95% confidence interval (CI) 8.9-14.3, P < 0.001]. The case-fatality ratio (CFR) was 20% (27/138) amongst HIV-infected and 11% (18/170) amongst HIV-uninfected individuals [odds ratio (OR) 2.1, 95% CI 1.1-3.9]. On multivariable analysis, CFR was greater amongst patients with bacteremia (35%, 29/82) compared with meningitis (7%, 16/226) (OR 7.8, 95% CI 3.4-17.7). HIV infection was associated with increased odds of bacteremia (OR 2.7, 95% CI 1.5-5.0). CONCLUSION: HIV-infected individuals may be at increased risk of meningococcal disease. The increased CFR in HIV-infected patients may be explained by their increased odds of bacteremia compared to meningitis.

[Epidemiological characteristics of meningococcal meningitis in Guangxi Zhuang Autonomous Region during 1996 and 2007].

OBJECTIVE: To analyze the epidemiological characteristics of meningococcal meningitis and provide evidences for disease control. METHOD: The method of descriptive epidemiology has been used to analyze the data collected. RESULTS: A total of 419 cases were reported with meningococcal meningitis between 1996-2007, annual incidence rate was 0.07/100,000. 68 cases were dead and mortatity was 16.23% . Highly sporadic distribution by areas was observed in the cases reported. And the incidence peak was between January and April. The aged was mainly at 0-9 years There was trace that the incidence move to aged at 10 19 years old in recent years. The in-cidence rate was higher in male than that in female. And it was mainly attacked in peasants, students and children left-behined at home. Outbreaks had occasionally occurred in Guangxi. The first outbreak caused by Neisseria meningitidis group C in China was reported. The strains isola-ted mainly were with Neisseria meningitidis group A, which accounting for 61.53% of the strains,followed by group C(15. 38%)and Group B (7.69%). Group A was found to be 100% re-sistant to SMZ-TMP,and both group C and B were 100% resistant to sulfanilamide. 1.28% the prevalence of carrier was confirmed by the throat swabs. The positive rate of titer to group A and C were 29. 95o and 21. 720 respectively, and the mean titers were 4.57 microg/ml and 1.70 microg/ml re-spectively. CONCLUSIONS: The characteristics of Meningococcal meningitis are summarized as low incidence,high mortabity,highly sporadic distribution, grouping diversity and increasing incidence in older population. Comprehensive measures with the priority of vaccination is the key measure for meningococcal meningitis control.

Meningococcal immunology.

There is a major need for an effective vaccine against serogroup B disease. The long-term efficacy of the serogroups A, C, Y and W135 conjugate vaccines and the need for booster vaccines has to be determined, as does the effect of changing epidemiology in the United States and worldwide. Control of serogroup A disease in sub-Saharan Africa is a major challenge.