Cluster of serogroup W invasive meningococcal disease in a university campus.

INTRODUCTION: In France, the expansion of an hypervirulent strain causing serogroup W invasive meningococcal disease (MenW) has been observed since 2015/16. We describe a cluster of three MenW cases, causing two deaths, at the end of 2016 in a university campus, and the vaccination campaign which was consequently organized. METHODS: Epidemiological and microbiological analyses led a multidisciplinary expertise group to recommend the organization of a mass vaccination campaign using ACWY vaccine targeting more than 30,000 students and staff in the university campus. Individual data on vaccination was collected using the lists of students and staff registered at the university to estimate vaccine coverage. RESULTS: Three MenW cases occurred within a 2-month period among students in different academic courses. All three isolates were identical and belonged to the "UK-2013 strain" phylogenetic branch. The attack rate was 10.8/100,000 students. The vaccination campaign was organized only 15 days after the third case occurred. In total, 13,198 persons were vaccinated. Vaccine coverage was estimated at 41% for students of the university and 35% for university staff. CONCLUSION: Timely notification of cases to health authorities was essential for the detection of the cluster and the rapid implementation of the vaccination campaign. No further cases occurred in the campus in the year following the vaccination campaign. This episode is the second cluster of MenW caused by the "UK-2013 strain" in a university since 2016.

Characteristics and changes in invasive meningococcal disease epidemiology in France, 2006-2015.

OBJECTIVES: This work aimed to describe the epidemiology of invasive meningococcal disease (IMD) in France, 2006-2015, including group- and genotype-specific disease burden, incidence trends before and after introduction of meningococcal C conjugate vaccines (MCCV) in 2010, and factors influencing the case fatality rate. METHODS: Mandatory notification data on incidence and IMD case characteristics were used. Genotyping of invasive strains and whole genome sequencing were performed by the French National Reference Center. Vaccination coverage was estimated from the National Health Insurance Information System's reimbursement data. RESULTS: The decrease in annual IMD incidence rates (per 100,000 inhabitants) from 1.23 in 2006 to 0.78 in 2016 was mainly related to the decrease in group B IMD. Group C incidence decreased from 0.29 in 2006 to 0.13 in 2010 but increased thereafter in age groups not targeted by MCCV. From 2010 onwards, MCCV coverage gradually increased but remained below 25% in 15-19 year-olds in 2015. Age, clinical presentation and, to a lesser extent, clonal complex 11 were the most significant factors determining mortality. CONCLUSIONS: The limited impact of vaccination on group C IMD incidence may be explained by the emergence of a new epidemic cycle in 2011 and the low vaccination coverage rates among adolescents and young adults.

[Impact of corticosteroids in the immediate management of invasive meningococcal disease associated with hyperinvasive strains of the ST-11 clonal complex in children]. / Impact des corticoïdes dans la prise en charge immédiate des infections invasives à méningocoque liées aux souches hyper-invasives du complexe clonal ST-11 chez l'enfant.

OBJECTIVES: We used data from the Groupe de pathologie infectieuse pédiatrique and Association clinique et thérapeutique infantile du Val-de-Marne (GPIP/ACTIV) National Survey of Bacterial Meningitis in children and the National Reference Center for Meningococci (CNRM) microbiological data to assess the potential impact of corticosteroids on the immediate management of invasive meningococcal disease (IMD) associated with different genotypes, including highly pro-inflammatory strains of the ST-11 clonal complex (genotype ST-11). METHODS: From 2001 to 2009, 259 pediatric wards and 168 microbiology laboratories distributed throughout France prospectively included all under-18-year-old patients with IMD (meningitis or purpura fulminans). The strains were sent to the CNRM for genotyping. We linked the ACTIV clinical data of IMD cases, where information on corticosteroid therapy was available, to strains isolated by the CRNM. RESULTS: A total of 1981 IMD cases were identified during the 8-year study, 805 cases (712 [88.5%] bacterial meningitis and 93 [11.5%] purpura fulminans) had steroid treatment data (33.8% received corticosteroids). The genotype of the strains was available for 410 patients (24.4% related to genotype ST-11; 100 patients). For all cases and regardless of the corticosteroids, mortality was significantly associated with the genotype ST-11 (OR=2.39, 95% CI [1.29; 4.42], P=0.004). For all cases and regardless of the genotypes of the isolates, mortality was also significantly higher for children with than without corticosteroid therapy (12.7% versus 4.5%, P<0.001). However, this treatment had been prescribed more frequently in severe cases, including shock, PF, coma and/or mechanical ventilation. For children who did not receive corticosteroids, the mortality rate was significantly higher with genotype ST-11 compared to other genotypes (OR=4.68 [1.91, 11.46], P=0.001). This difference disappeared in children who received corticosteroids. CONCLUSION: This study indicates that in the absence of corticosteroids, higher mortality in invasive meningococcal disease is associated with the ST-11 clonal complex strains. This suggests a possible positive effect of corticosteroid therapy depending on the genotype of the strain involved.

Hyperinvasive genotypes of Neisseria meningitidis in France.

Clinical isolates of Neisseria meningitidis from cases of meningococcal disease, collected between January 2000 and December 2004, were identified and typed at the French National Reference Centre. A representative subset of 546 isolates from among 2882 isolates was further genotyped by multilocus sequence typing to determine their genetic lineages (clonal complexes) and the degree of diversification among different clonal complexes. Representative isolates of the main clonal complexes were tested for their virulence in mice and for proapoptotic effects on human epithelial cells. High genetic diversity in some genetic lineages (ST-32 and ST-41/44) was correlated with heterogeneity in virulence in mice and proapoptotic effects on human epithelial cells. In contrast, the homogeneous genetic structure of isolates of the ST-11 clonal complex, regardless of their serogroup, correlated positively with a fatal outcome of the infection, increased virulence in mice and increased proapoptotic effects on human epithelial cells.

Intimate adhesion of Neisseria meningitidis to human epithelial cells is under the control of the crgA gene, a novel LysR-type transcriptional regulator.

PilC1, a pilus-associated protein in Neisseria menin- gitidis, is a key element in initial meningococcal adhesion to target cells. A promoter element (CREN, contact regulatory element of Neisseria) is responsible for the transient induction of this gene upon cell contact. crgA (contact-regulated gene A) encodes a transcriptional regulator whose expression is also induced upon cell contact from a promoter region similar to the CREN of pilC1. CrgA shows significant sequence homologies to LysR-type transcriptional regulators. Its inactivation in meningococci provokes a dramatic reduction in bacterial adhesion to epithelial cells. Moreover, this mutant is unable to undergo intimate adhesion to epithelial cells or to provoke effacing of microvilli on infected cells. Purified CrgA is able to bind to pilC1 and crgA promoters, and CrgA seems to repress the expression of pilC1 and crgA. Our results support a dynamic model of bacteria-cell interaction involving a network of regulators acting in cascade. CrgA could be an intermediate regulator in such a network.