BACKGROUND: The Meningococcal Antigen Typing System (MATS) was developed to identify meningococcus group B strains with a high likelihood of being covered by the 4CMenB vaccine, but is limited by the requirement for viable isolates from culture-confirmed cases. We examined if antigen genotyping could complement MATS in predicting strain coverage by the 4CMenB vaccine. METHODS: From a panel of 3912 MATS-typed invasive meningococcal disease isolates collected in England and Wales in 2007-2008, 2014-2015 and 2015-2016, and in 16 other countries in 2000-2015, 3481 isolates were also characterized by antigen genotyping. Individual associations between antigen genotypes and MATS coverage for each 4CMenB component were used to define a genetic MATS (gMATS). gMATS estimates were compared with England and Wales human complement serum bactericidal assay (hSBA) data and vaccine effectiveness (VE) data from England. RESULTS: Overall, 81% of the strain panel had genetically predictable MATS coverage, with 92% accuracy and highly concordant results across national panels (Lin's accuracy coefficient, 0.98; root-mean-square deviation, 6%). England and Wales strain coverage estimates were 72-73% by genotyping (66-73% by MATS), underestimating hSBA values after four vaccine doses (88%) and VE after two doses (83%). The gMATS predicted strain coverage in other countries was 58-88%. CONCLUSIONS: gMATS can replace MATS in predicting 4CMenB strain coverage in four out of five cases, without requiring a cultivable isolate, and is open to further improvement. Both methods underestimated VE in England. Strain coverage predictions in other countries matched or exceeded England and Wales estimates.

• Klíčová slova
• 4CMenB vaccine, Genotyping, Neisseria meningitidis serogroup B, Strain coverage, gMATS,
• MeSH
• antigeny bakteriální genetika   MeSH
• celosvětové zdraví MeSH
• genotyp * MeSH
• genotypizační techniky metody   MeSH
• lidé MeSH
• meningokoková meningitida epidemiologie   mikrobiologie   MeSH
• meningokokové vakcíny imunologie   MeSH
• molekulární epidemiologie metody   MeSH
• Neisseria meningitidis séroskupiny B klasifikace   genetika   izolace a purifikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 4CMenB vaccine MeSH Prohlížeč
• antigeny bakteriální MeSH
• meningokokové vakcíny MeSH

Invasive meningococcal disease surveillance in Europe combines isolate characterisation and epidemiological data to support public health intervention. A representative European Meningococcal Strain Collection (EMSC) of IMD isolates was obtained, and whole genome sequenced to characterise 799 EMSC isolates from the epidemiological year July 2011-June 2012. To establish a genome library (GL), the isolate information was deposited in the pubMLST.org/neisseria database. Genomes were curated and annotated at 2,429 meningococcal loci, including those defining clonal complex, capsule, antigens, and antimicrobial resistance. Most genomes contained genes encoding B (n = 525; 65.7%) or C (n = 163; 20.4%) capsules; isolates were genetically highly diverse, with >20 genomic lineages, five of which comprising 60.7% (n = 485) of isolates. There were >350 antigenic fine-types: 307 were present once, the most frequent (P1.7-2,4:F5-1) comprised 8% (n = 64) of isolates. Each genome was characterised for Bexsero Antigen Sequence Typing (BAST): 25.5% (n = 204) of isolates contained alleles encoding the fHbp and/or the PorA VR1 vaccine component, but most genomes (n = 513; 64.2%) did not contain the NadA component. EMSC-GL will support an integrated surveillance of disease-associated genotypes in Europe, enabling the monitoring of hyperinvasive lineages, outbreak identification, and supporting vaccine programme implementation.

• Klíčová slova
• Neisseria meningitidis, genome library, monitor vaccine coverage, surveillance, track antimicrobial susceptibility,
• MeSH
• bakteriální geny genetika   MeSH
• genetická variace MeSH
• genetické lokusy MeSH
• genom bakteriální MeSH
• genomika MeSH
• genomová knihovna * MeSH
• genotyp MeSH
• lidé MeSH
• meningokoková meningitida genetika   mikrobiologie   MeSH
• meningokokové infekce genetika   mikrobiologie   MeSH
• molekulární epidemiologie MeSH
• Neisseria meningitidis séroskupiny B genetika   MeSH
• Neisseria meningitidis klasifikace   genetika   izolace a purifikace   MeSH
• sekvenování celého genomu * MeSH
• séroskupina MeSH
• surveillance populace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH

BACKGROUND: One schedule for the capsular group B meningococcal vaccine 4CMenB is 2 doses that are administered 2 months apart for children aged 12-23 months, with a booster dose 12-24 months later. Our objective was to provide data on persistence of human serum bactericidal antibody (hSBA) titres in children up to 4 years of age after initial doses at 12-24 months, and immunogenicity of a booster dose at 48 months of age compared with vaccine-naive children. METHODS: Children previously immunized, as part of a randomized controlled trial, with 2 doses of 4CMenB vaccine at 12-24 months of age received a booster at 4 years of age. Vaccine-naive age-matched toddlers received 2 doses of 4CMenB. Human serum bactericidal antibody titres against reference strains H44/76, 5/99, NZ98/254 and M10713 were evaluated before and after innoculation with 4CMenB vaccine in 4-year-old children. RESULTS: Of 332 children in the study, 123 had previously received 4CMenB and 209 were vaccine-naive controls. Before the booster, the proportions of participants (previously vaccinated groups compared with controls) with hSBA titres of 1:5 or more were as follows: 9%-11% v. 1% (H44/76), 84%-100% v. 4% (5/99), 0%-18% v. 0% (NZ98/254) and 59%-60% v. 60% (M10713). After 1 dose of 4CMenB in previously immunized children, the proportions of participants achieving hSBA titres of 1:5 or more were 100% (H44/76 and 5/99), 70%-100% (NZ98/254) and 90%-100% (M10713). INTERPRETATION: We found that waning of hSBA titres by 4 years of age occurred after 2 doses of 4CMenB vaccine administered at 12-24 months, and doses at 12-24 months have a priming effect on the immune system. A booster may be necessary to maintain hSBA titres of 1:5 or more among those children with increased disease risk. Trial registration: ClinicalTrials.gov, no. NCT01717638.

• MeSH
• kojenec MeSH
• lidé MeSH
• meningokoková meningitida mikrobiologie   prevence a kontrola   MeSH
• meningokokové vakcíny aplikace a dávkování   MeSH
• následné studie MeSH
• Neisseria meningitidis séroskupiny B imunologie   MeSH
• předškolní dítě MeSH
• protilátky bakteriální krev   MeSH
• retrospektivní studie MeSH
• vakcinace metody   MeSH
• výsledek terapie MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• 4CMenB vaccine MeSH Prohlížeč
• meningokokové vakcíny MeSH
• protilátky bakteriální MeSH

Various meningococcal conjugate vaccines exist against serogroups A, C, W and Y. A new protein-based vaccine targeting serogroup B (MenB) is also now available. The potential of such vaccines to drive serogroup replacement is considered a possible public health concern when implementing nationwide routine immunization programmes. The aim of this work was to investigate if and how serogroup replacement may occur following widespread vaccination with a MenB vaccine that may protect against carriage. To that end, we built a dynamic transmission model with age and serogroup stratification, focusing on European settings where most invasive meningococcal disease (IMD) cases are caused by serogroups B and C. For illustration purposes, the model was employed in 2 such settings: UK (England and Wales) and Czech Republic. Preliminary model-based projections suggest that, under strong serogroup competition for colonization, vaccine-induced serogroup replacement may occur even with a relatively low vaccine efficacy against serogroup B carriage (e.g., 20%), with potential subsequent increase in serogroup C IMD. The magnitude and speed of the model-projected serogroup C IMD increase depend on the MenB vaccination strategy, vaccine efficacy against carriage and the extent of any potential cross-protection against other serogroups. These analyses are neither exhaustive nor definitive, and focused on simulating potential population-level trends in IMD post-vaccination, under certain assumptions. Due to present inherent limitations and uncertainties, this study has limited quantitative value and is best regarded as an explorative qualitative modeling approach, to complement and challenge the current status quo, and suggest areas where collecting additional data may be essential.

• Klíčová slova
• dynamic transmission model, invasive meningococcal disease, mathematical modeling, serogroup B meningococcal vaccine, serogroup replacement,
• MeSH
• dítě MeSH
• hromadná vakcinace MeSH
• kojenec MeSH
• lidé MeSH
• meningokoková meningitida mikrobiologie   prevence a kontrola   MeSH
• meningokokové vakcíny imunologie   MeSH
• mladiství MeSH
• Neisseria meningitidis séroskupiny B imunologie   MeSH
• Neisseria meningitidis séroskupiny C imunologie   MeSH
• předškolní dítě MeSH
• protilátky bakteriální imunologie   MeSH
• teoretické modely MeSH
• vakcinace MeSH
• zkřížená ochrana imunologie   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Spojené království MeSH
• Názvy látek
• meningokokové vakcíny MeSH
• protilátky bakteriální MeSH

New vaccines targeting meningococci expressing serogroup B polysaccharide have been developed, with some being licensed in Europe. Coverage depends on the distribution of disease-associated genotypes, which may vary by age. It is well established that a small number of hyperinvasive lineages account for most disease, and these lineages are associated with particular antigens, including vaccine candidates. A collection of 4,048 representative meningococcal disease isolates from 18 European countries, collected over a 3-year period, were characterized by multilocus sequence typing (MLST). Age data were available for 3,147 isolates. The proportions of hyperinvasive lineages, identified as particular clonal complexes (ccs) by MLST, differed among age groups. Subjects <1 year of age experienced lower risk of sequence type 11 (ST-11) cc, ST-32 cc, and ST-269 cc disease and higher risk of disease due to unassigned STs, 1- to 4-year-olds experienced lower risk of ST-11 cc and ST-32 cc disease, 5- to 14-year-olds were less likely to experience ST-11 cc and ST-269 cc disease, and ≥25-year-olds were more likely to experience disease due to less common ccs and unassigned STs. Younger and older subjects were vulnerable to a more diverse set of genotypes, indicating the more clonal nature of genotypes affecting adolescents and young adults. Knowledge of temporal and spatial diversity and the dynamics of meningococcal populations is essential for disease control by vaccines, as coverage is lineage specific. The nonrandom age distribution of hyperinvasive lineages has consequences for the design and implementation of vaccines, as different variants, or perhaps targets, may be required for different age groups.

• MeSH
• antigeny bakteriální imunologie   MeSH
• bakteriální pouzdra imunologie   MeSH
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• meningokoková meningitida imunologie   mikrobiologie   prevence a kontrola   MeSH
• meningokokové vakcíny imunologie   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• multilokusová sekvenční typizace MeSH
• Neisseria meningitidis séroskupiny B imunologie   MeSH
• Neisseria meningitidis imunologie   izolace a purifikace   MeSH
• předškolní dítě MeSH
• sekvence nukleotidů MeSH
• sekvenční analýza DNA MeSH
• věkové rozložení MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny bakteriální MeSH
• capsular polysaccharide, meningococcal group B MeSH Prohlížeč
• meningokokové vakcíny MeSH

Most studies of bacterial pathogen populations have been based on isolates collected from individuals with disease, or their contacts, over short time periods. For commensal organisms that occasionally cause disease, such as Neisseria meningitidis, however, the analysis of isolates from long-term asymptomatic carriage is necessary to elucidate their evolution and population structure. Here, we use mathematical models to analyse the structuring and dynamics of three vaccine-candidate antigens among carried meningococcal isolates collected over nearly 30 years in the Czech Republic. The data indicate that stable combinations of antigenic alleles were maintained over this time period despite evidence for high rates of recombination, consistent with theoretical models in which strong immune selection can maintain non-overlapping combinations of antigenic determinants in the presence of recombination. We contrast this antigenic structure with the overlapping but relatively stable combinations of the housekeeping genes observed among the same isolates, and use a novel network approach to visualize these relationships.

• MeSH
• alely MeSH
• antigeny bakteriální genetika   imunologie   MeSH
• bakteriální proteiny genetika   MeSH
• biologické modely MeSH
• genetická variace MeSH
• lidé MeSH
• meningokoková meningitida mikrobiologie   MeSH
• molekulární evoluce * MeSH
• Neisseria meningitidis genetika   imunologie   MeSH
• poriny genetika   imunologie   MeSH
• přenašečství mikrobiologie   MeSH
• proteiny vnější bakteriální membrány genetika   imunologie   MeSH
• rekombinace genetická MeSH
• selekce (genetika) MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• antigeny bakteriální MeSH
• bakteriální proteiny MeSH
• FrpB protein, bacteria MeSH Prohlížeč
• porin protein, Neisseria MeSH Prohlížeč
• poriny MeSH
• proteiny vnější bakteriální membrány MeSH

Cytokine production was determined in vitro after stimulation with three different Neisseria meningitidis (NM) strains. Virulent NM B strain isolated from a patient with mild course of invasive meningococcal disease (IMD) elicited higher cytokine production than NM B and NM C hypervirulent strains isolated from patients with moderate and fatal course of IMD, respectively. Endotoxin concentration after in vitro stimulation correlated with cytokine production: the highest endotoxin levels were observed with virulent NM B strain. Serum cytokines and endotoxin levels showed an opposite trend. These results suggest that inflammatory response during IMD is predominantly influenced by host factors.

• MeSH
• cytokiny krev   MeSH
• dospělí MeSH
• endotoxiny krev   MeSH
• lidé MeSH
• lipopolysacharidy krev   MeSH
• meningokoková meningitida imunologie   mikrobiologie   MeSH
• Neisseria meningitidis klasifikace   imunologie   izolace a purifikace   patogenita   MeSH
• virulence MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cytokiny MeSH
• endotoxiny MeSH
• lipid-linked oligosaccharides MeSH Prohlížeč
• lipopolysacharidy MeSH

A PCR amplification was performed to detect Neisseria meningitidis insertion sequence 1106 (IS-1106) in the human CerebroSpinal Fluid (CSF) in cases of meningitis. The study included 27 CSF samples from suspected meningitis patients. Although the inflammatory response in most of the samples was slightly increased, the results showed that 7 (26%) and 8 (30%) CSF samples were diagnosed as meningococcal meningitis by Gram staining and by culture, respectively. The primers of the IS-1106 were used for direct diagnosis of N. meningitidis in the human spinal fluid after a minor treatment of the CSF samples. The sample was diagnosed as meningococcal meningitis, if a DNA band of about 600 bp was detected in the ethidium bromide-stained agarose gel. The 27 CSF samples were analyzed in a random manner. Of these, 18 samples including the Gram staining- and culture-positive samples were also positive in PCR amplification. However, a CSF sample, which was diagnosed to be meningococcal meningitis in culture was negative in both Gram staining and PCR analysis. The specificity of the IS-1106 primers was determined to be 95%, with 100% sensitivity in comparison to Gram staining and culture. The primers were sensitive to 10 pg or more of meningococcal DNA. In addition, the PCR amplification showed high predictive values (89 and 100%) in diagnosing meningitis in patients that were negative and positive responders when tested by culture and by Gram staining. In conclusion, the PCR amplification of IS-1106 of N. meningitidis is specific and sensitive to both culture-positive and -negative meningococcal meningitis. Hence, PCR assay is highly recommended for use in a rapid diagnosis of suspected meningitis patients.

• MeSH
• DNA primery genetika   MeSH
• lidé MeSH
• meningokoková meningitida mozkomíšní mok   diagnóza   mikrobiologie   MeSH
• mozkomíšní mok mikrobiologie   MeSH
• Neisseria meningitidis genetika   izolace a purifikace   MeSH
• polymerázová řetězová reakce metody   MeSH
• sekvence nukleotidů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DNA primery MeSH

Neisseria meningitidis is a highly variable bacterium. Indeed, N. meningitidis is naturally competent for transformation, and horizontal DNA exchange between strains may lead to mosaic genetic loci in N. meningitidis. We studied such an exchange in nature during an epidemic provoked by N. meningitidis. This epidemic started in the Czech Republic in 1993 and the original epidemic clone was shown to have the antigenic formula (serogroup:serotype:serosubtype) C:2a:P1.2,5. We analysed 145 meningococcal strains isolated in the Czech Republic between 1993 and 1997 using serological and genetic typing methods (multilocus enzyme electrophoresis and polymorphism of pilA and pilD genes). This analysis showed that genetic exchange between epidemic and endemic strains had occurred. Exchanges involved mostly surface-exposed structures such as the capsule, giving rise to new meningococcal variants. The expansion of these variants should be kept under close surveillance.

• MeSH
• alely MeSH
• DNA bakterií chemie   MeSH
• epidemický výskyt choroby MeSH
• genetická variace MeSH
• lidé MeSH
• meningokoková meningitida genetika   mikrobiologie   MeSH
• molekulární evoluce MeSH
• Neisseria meningitidis genetika   MeSH
• polymerázová řetězová reakce MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• DNA bakterií MeSH

Serogroup C strains of Neisseria meningitidis were isolated from a Germany patient with severe meningococcal disease after a trip to the Czech Republic. These strains (case isolates) were characterized by classical and molecular techniques, as were other strains (carrier isolates) isolated from healthy contacts. Five of 10 carrier isolates had switched off the expression of capsular polysaccharide, as demonstrated by a serogroup-specific PCR. The two case isolates were indistinguishable by multilocus sequence typing and belonged to the ET-37 complex. The carrier isolates belonged to four different sequence types, all unrelated to that of the case strains. Pulsed-field gel electrophoresis showed that the case isolates differed from reference ET-37 complex strains from the Czech Republic and Canada as well as from all the carrier isolates. The isolate from the patient's nasopharynx was indistinguishable from the blood isolate except for a 40,000-bp chromosomal deletion that had occurred during systemic spread.

• MeSH
• bakteriální geny MeSH
• lidé MeSH
• meningokoková meningitida mikrobiologie   MeSH
• mladiství MeSH
• Neisseria meningitidis klasifikace   genetika   izolace a purifikace   MeSH
• polymerázová řetězová reakce metody   MeSH
• přenašečství mikrobiologie   MeSH
• rodiče MeSH
• sérotypizace MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Geografické názvy
• Česká republika MeSH
• Německo MeSH