Invasive meningococcal disease (IMD) is an acute life-threatening infection caused by the gram-negative bacterium, Neisseria meningitidis. Globally, there are approximately half a million cases of IMD each year, with incidence varying across geographical regions. Vaccination has proven to be successful against IMD, as part of controlling outbreaks, and when incorporated into national immunization programs. The South-Eastern Europe Meningococcal Advocacy Group (including representatives from Croatia, the Czech Republic, Greece, Hungary, Poland, Romania, Serbia, Slovenia and Ukraine) was formed in order to discuss the potential challenges of IMD faced in the region. The incidence of IMD across Europe has been relatively low over the past decade; of the countries that came together for the South-Eastern Meningococcal Advocacy Group, the notification rates were lower than the European average for some country. The age distribution of IMD cases was highest in infants and children, and most countries also had a further peak in adolescents and young adults. Across the nine included countries between 2010 and 2020, the largest contributors to IMD were serogroups B and C; however, each individual country had distinct patterns for serogroup distribution. Along with the variations in epidemiology of IMD between the included countries, vaccination policies also differ.
- MeSH
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- meningokokové infekce * epidemiologie prevence a kontrola mikrobiologie MeSH
- meningokokové vakcíny * MeSH
- mladiství MeSH
- mladý dospělý MeSH
- Neisseria meningitidis * MeSH
- séroskupina MeSH
- vakcinace MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- Evropa MeSH
In response to escalating cases of serogroup W (MenW) invasive meningococcal disease (IMD), multiple countries introduced quadrivalent conjugate MenACWY vaccines into their national immunization programs (NIPs). Here, we summarize the real-world impact and vaccine effectiveness (VE) data of MenACWY-TT from Chile, England, the Netherlands, and Australia. Incidence rate reductions (IRRs) and VE from baseline to post-NIP period were extracted from publications or calculated. After the administration of a single dose of MenACWY-TT, substantial IRRs of MenCWY were observed across the countries in vaccine-eligible age groups (83%-85%) and via indirect protection in non-vaccine-eligible age groups (45%-53%). The impact of MenACWY-TT was primarily driven by MenW IRRs, as seen in vaccine-eligible age groups (65%-92%) and non-vaccine-eligible age groups (41%-57%). VE against MenW was reported in vaccine-eligible toddlers (92%) in the Netherlands and in vaccine-eligible adolescents/young adults (94%) in England. These real-world data support the implementation and continued use of MenACWY-TT in NIPs.
- MeSH
- kombinované vakcíny MeSH
- lidé MeSH
- meningokokové infekce * epidemiologie prevence a kontrola MeSH
- mladiství MeSH
- mladý dospělý MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Geografické názvy
- Anglie MeSH
- Austrálie MeSH
- Nizozemsko MeSH
V programu surveillance byl v roce 2022 zjištěn v České republice vzestup počtu invazivních meningokokových onemocnění oproti předchozímu roku: celkem 25 (nemocnost 0,24/100000 obyv.) proti 11 v roce 2021 (nemocnost 0,10/100 000 obyv.). Z 25 onemocnění v roce 2022 tři skončila úmrtím – celková smrtnost 12 %. Jedno úmrtí způsobila séroskupina B, dvě úmrtí séroskupinaY. Tato úmrtí byla preventabilní očkováním. Podobně jako v předchozím roce převažovala i v roce 2022 onemocnění způsobená N. meningitidis B (16 z 25), tři onemocnění byla způsobená séroskupinou Y a po dvou onemocněních způsobily séroskupiny C a W. V roce 2022 došlo ve srovnání s předchozím rokem k výraznému vzestupu nemocnosti v nejmladší věkové skupině 0–11měsíčních (na 5,37/100000 z 1,82/100 000), který byl způsoben zejména séroskupinou B, u níž nemocnost stoupla oproti předchozímu roku na 3,58/100000 z 1,82/100 000. U séroskupin preventabilních konjugovanou tetravakcínou A, C, W, Y stoupla v roce 2022 nemocnost v nejmladší věkové skupině na 1,79/100000 oproti nulové hodnotě v předchozím roce. Ve věkové skupině 1–4letých nemocnost stoupla oproti předchozímu roku (na 0,67/100000 z 0,22/100000) a byla způsobena pouze séroskupinou B.Ve věkové skupině 15–19letých nemocnoststoupla oproti předchozímu roku na 0,79/100000 oproti nulové hodnotě v předchozím roce a byla způsobena pouze séroskupinou B. Z 25 invazivních meningokokových onemocnění bylo 14 prokázáno pouze kultivačně, 6 kultivačně a metodou PCR, 5 pouze metodou PCR. V roce 2022 byla v NRL provedena multilokusová sekvenční typizace (MLST) u 15 kmenů z invazivního meningokokového onemocnění, které byly do NRL pro meningokokové nákazy poslány. MLST prokázala heterogenitu izolátů způsobujících invazivní meningokokové onemocnění: celkem bylo zjištěno 10 klonálních komplexů, z nich nejčastější byl cc213 (4 izoláty), následovaný cc41/44 (2 izoláty).
The surveillance programme data showed an increase in the number of invasive meningococcal disease cases in the Czech Republic in 2022 compared to the previous year: a total of 25 (0.24/100000) compared to 11 in 2021 (0.10/100000). Three of the 25 cases in 2022 were fatal, and the overall case fatality rate was 12%. One death was caused by serogroup B, two by serogroup Y. These deaths were vaccine preventable. As in the previous year, N. meningitidis B accounted for the majority of the cases in 2022 (16 out of 25), three cases were caused by serogroup Y, and two cases each were caused by serogroups C and W. In 2022, there was a significant increase in morbidity in the youngest age group of 0–11 months (to 5.37/100,000 from 1.82/100,000), mainly due to serogroup B, which increased to 3.58/100,000 from 1.82/100,000 compared to the previous year. In serogroups preventable withA, C, W,Y conjugated tetravaccine, the morbidity in the youngest age group increased to 1.79/100,000 in 2022 compared to zero in the previous year. In the 1–4-year age group, morbidity increased from the previous year (to 0.67/100,000 from 0.22/100,000) and was due to serogroup B only. In the 15–19 age group, the morbidity increased from the previous year to 0.79/100 000 compared to zero in the previous year and was due to serogroup B only. Of the 25 cases of invasive meningococcal disease, 14 were proven by culture only, 6 by culture and PCR, and 5 by PCR only. In 2022, multilocus sequence typing (MLST) was performed on 15 strains from invasive meningococcal disease that were sent to the National Reference Laboratory for Meningococcal Infections. MLST demonstrated heterogeneity of the isolates causing invasive meningococcal disease: a total of 10 clonal complexes were identified, with cc213 (4 isolates) being the most common, followed by cc41/44 (2 isolates).
- MeSH
- lidé MeSH
- meningokokové infekce * epidemiologie mortalita MeSH
- séroskupina MeSH
- vakcinace MeSH
- věkové rozložení MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- zprávy MeSH
- Geografické názvy
- Česká republika MeSH
- MeSH
- dítě MeSH
- lidé MeSH
- meningokokové infekce * diagnóza komplikace prevence a kontrola MeSH
- meningokokové vakcíny farmakologie terapeutické užití MeSH
- Neisseria meningitidis imunologie patogenita ultrastruktura MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- přehledy MeSH
BACKGROUND: Meningococcal serogroups A, B, C, W, and Y cause nearly all meningococcal disease, and comprehensive protection requires vaccination against all five serogroups. We aimed to assess the immunogenicity and safety of a pentavalent MenABCWY vaccine comprising two licensed vaccines-meningococcal serogroup B-factor H binding protein vaccine (MenB-FHbp) and a quadrivalent meningococcal serogroup ACWY tetanus toxoid conjugate vaccine (MenACWY-TT)-compared with two doses of MenB-FHbp and a single dose of quadrivalent meningococcal serogroup ACWY CRM197-conjugate vaccine (MenACWY-CRM) as the active control. We previously reported the primary safety and immunogenicity data relating to the two-dose MenB-FHbp schedule. Here we report secondary outcomes and ad-hoc analyses relating to MenABCWY immunogenicity and safety. METHODS: We did an observer-blind, active-controlled trial at 68 sites in the USA, Czech Republic, Finland, and Poland. Healthy individuals (aged 10-25 years) who had or had not previously received a MenACWY vaccine were randomly assigned (1:2) using an interactive voice or web-based response system, stratified by previous receipt of a MenACWY vaccine, to receive 0·5 mL of MenABCWY (months 0 and 6) and placebo (month 0) or MenB-FHbp (months 0 and 6) and MenACWY-CRM (month 0) via intramuscular injection into the upper deltoid. All individuals were masked to group allocation, except staff involved in vaccine dispensation, preparation, and administration; and protocol adherence. Endpoints for serogroups A, C, W, and Y included the proportion of participants who achieved at least a four-fold increase in serum bactericidal antibody using human complement (hSBA) titres between baseline and 1 month after each vaccination. For serogroup B, secondary endpoints included the proportion of participants who achieved at least a four-fold increase in hSBA titres from baseline for each of four primary test strains and the proportion of participants who achieved titres of at least the lower limit of quantitation against all four test strains combined at 1 month after the second dose. Endpoints for serogroups A, C, W, and Y were assessed in the modified intent-to-treat (mITT) population, which included all randomly assigned participants who received at least one vaccine dose and had at least one valid and determinate MenB or serogroup A, C, W, or Y assay result before vaccination up to 1 month after the second dose, assessed in ACWY-experienced and ACWY-naive participants separately. Secondary endpoints for serogroup B were analysed in the evaluable immunogenicity population, which included all participants in the mITT population who were randomly assigned to the group of interest, received all investigational products as randomly assigned, had blood drawn for assay testing within the required time frames, had at least one valid and determinate MenB assay result after the second vaccination, and had no important protocol deviations; outcomes were assessed in both ACWY-experienced and ACWY-naive populations combined. Non-inferiority of MenABCWY to MenACWY-CRM and MenB-FHbp was determined using a -10% non-inferiority margin for these endpoints. Reactogenicity and adverse events were assessed among all participants who received at least one vaccine dose and who had available safety data. This trial is registered with Clinicaltrials.gov, NCT03135834, and is complete. FINDINGS: Between April 24 and November 10, 2017, 1610 participants (809 MenACWY-naive; 801 MenACWY-experienced) were randomly assigned: 544 to receive MenABCWY and placebo (n=272 MenACWY-naive; n=272 MenACWY-experienced) and 1066 to receive MenB-FHbp and MenACWY-CRM (n=537 MenACWY-naive; n=529 MenACWY-experienced). Among MenACWY-naive or MenACWY-experienced MenABCWY recipients, 75·5% (95% CI 69·8-80·6; 194 of 257; serogroup C) to 96·9% (94·1-98·7; 254 of 262; serogroup A) and 93·0% (88·4-96·2; 174 of 187; serogroup Y) to 97·4% (94·4-99·0; 224 of 230; serogroup W) achieved at least four-fold increases in hSBA titres against serogroups ACWY after dose 1 or 2, respectively, in ad-hoc analyses. Additionally, 75·8% (71·5-79·8; 320 of 422) to 94·7% (92·1-96·7; 396 of 418) of MenABCWY and 67·4% (64·1-70·6; 563 of 835) to 95·0% (93·3-96·4; 782 of 823) of MenB-FHbp recipients achieved at least four-fold increases in hSBA titres against MenB strains after dose 2 in secondary analyses; 79·9% (334 of 418; 75·7-83·6) and 74·3% (71·2-77·3; 605 of 814), respectively, achieved composite responses. MenABCWY was non-inferior to MenACWY-CRM (single dose) and to MenB-FHbp in ad-hoc analyses based on the proportion of participants with at least a four-fold increase in hSBA titres from baseline and (for MenB-FHbp only) composite responses. Reactogenicity events after vaccination were similarly frequent across groups, were mostly mild or moderate, and were unaffected by MenACWY experience. No adverse events causing withdrawals were related to the investigational product. Serious adverse events were reported in four (1·5%; 0·4-3·7) MenACWY-naive individuals in the MenABCWY group versus six (2·2%; 0·8-4·8) among MenACWY-experienced individuals in the MenABCWY group and 14 (1·3%; 0·7-2·2) in the active control group (MenACWY-experienced and MenACWY-naive individuals combined); none of these were considered related to the investigational product. INTERPRETATION: MenABCWY immune responses were robust and non-inferior to MenACWY-CRM and MenB-FHbp administered separately, and MenABCWY was well tolerated. The favourable benefit-risk profile supports further MenABCWY evaluation as a simplified schedule compared with current adolescent meningococcal vaccination programmes. FUNDING: Pfizer.
- MeSH
- imunogenicita vakcíny MeSH
- kombinované vakcíny MeSH
- lidé MeSH
- meningokokové infekce * prevence a kontrola farmakoterapie MeSH
- meningokokové vakcíny * MeSH
- mladiství MeSH
- mladý dospělý MeSH
- Neisseria meningitidis séroskupiny B * MeSH
- Neisseria meningitidis * MeSH
- protilátky bakteriální MeSH
- vakcinace metody MeSH
- vakcíny konjugované MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
Cíl: Analýza potenciálních genů virulence metodou sekvenace celého genomu (WGS) u invazivních a neinvazivních izolátů Neisseria meningitidis příbuzných epidemiologicky a/nebo klinicky z období 2005–2021. Materiál a metody: Pro analýzu bylo vybráno 79 izolátů ze tří různých kategorií: z případů invazivního meningokokového onemocnění (IMO) a od jejich zdravých kontaktů; z různého klinického materiálu téhož případu IMO; z různého klinického materiálu téhož případu IMO a od jejich zdravých kontaktů. Metodou WGS byly analyzovány sekvenční změny v genech potenciálních faktorů virulence N. meningitidis, jednalo se o více než 250 lokusů. Výsledky: Četnost sekvenčních změn v potenciálních genech virulence N. meningitidis byla u studovaných invazivních a neinvazivních izolátů značně variabilní. Nejvyšší míra genetické variability byla pozorována u genů pilu, především pilE a pglA. V naší studii byly detekovány změny v genu opacitního proteinu opaA u více než poloviny studovaných izolátů, u MenC izolátů dosahovala četnost změn genu opaA téměř 70 %. Zvýšená četnost změn byla pozorována i v genech, které jsou zodpovědné za produkci kapsule, především genech kapsulárního regionu D+D’. Závěry: Získané výsledky podporují hypotézu, že v patogenitě N. meningitidis se uplatňují i genetické mechanismy, které jsou séroskupinově specifické. Tyto výsledky přispívají k rozšíření vědeckého poznání, které je nezbytné pro vývoj nových účinných vakcín proti IMO.
Aim: Whole genome sequencing (WGS) analysis of candidate virulence genes of epidemiologically and/or clinically related invasive and non-invasive isolates of Neisseria meningitidis from 2005–2021. Material and Methods: Seventy-nine isolates were selected for analysis from three different categories: cases of invasive meningococcal disease (IMD) and their healthy contacts, different clinical specimens from the same IMD case, and different clinical specimens from the same IMD case and their healthy contacts. WGS was used to analyse sequence variability in candidate N. meningitidis virulence factor genes, with more than 250 loci studied. Results: The frequency of sequence changes in the candidate N. meningitidis virulence factor genes of invasive and non-invasive isolates varied widely. The highest level of variability was observed in the pilus genes, especially pilE and pglA. Our study detected variability in the opacity protein A (opaA) gene in more than half of the isolates analysed, with the frequency of opaA gene changes reaching almost 70% in MenC isolates. Higher frequency of changes were also observed in the genes for capsule production, especially in those of the D+D’ capsular region. Conclusions: The results obtained support the hypothesis that serogroup-specific genetic mechanisms are also involved in the pathogenicity of N. meningitidis. These data add to the body of knowledge necessary for the development of new effective IMD vaccines.
- MeSH
- faktory virulence MeSH
- lidé MeSH
- meningokokové infekce epidemiologie MeSH
- Neisseria meningitidis * genetika izolace a purifikace MeSH
- sekvenování celého genomu * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
Invasive meningococcal disease belongs among the most dangerous infectious diseases in the world. Several polysaccharide conjugate vaccines against serogroups A, C, W and Y are available and two recombinant peptide vaccines against serogroup B (MenB vaccines) have been developed: MenB-4C (Bexsero) and MenB-fHbp (Trumenba). The aim of this study was to define the clonal composition of the Neisseria meningitidis population in the Czech Republic, to determine changes in this population over time and to estimate the theoretical coverage of isolates by MenB vaccines. This study presents the analysis of whole genome sequencing data of 369 Czech N. meningitidis isolates from invasive meningococcal disease covering 28 years. Serogroup B isolates (MenB) showed high heterogeneity and the most common clonal complexes were cc18, cc32, cc35, cc41/44, and cc269. Isolates of clonal complex cc11 were predominately serogroup C (MenC). The highest number of serogroup W isolates (MenW) belonged to clonal complex cc865, which we described as exclusive to the Czech Republic. Our study supports the theory that this cc865 subpopulation originated in the Czech Republic from MenB isolates by a capsule switching mechanism. A dominant clonal complex of serogroup Y isolates (MenY) was cc23, which formed two genetically quite distant subpopulations and which showed constant representation throughout the observed period. The theoretical coverage of isolates by two MenB vaccines was determined using the Meningococcal Deduced Vaccine Antigen Reactivity Index (MenDeVAR). Estimated Bexsero vaccine coverage was 70.6% (for MenB) and 62.2% (for MenC, W, Y). For Trumenba vaccine, estimated coverage was 74.6% (for MenB) and 65.7% (for MenC, W, Y). Our results demonstrated sufficient coverage of Czech heterogeneous population of N. meningitidis with MenB vaccines and, together with surveillance data on invasive meningococcal disease in the Czech Republic, were the basis for updating recommendations for vaccination against invasive meningococcal disease.
- MeSH
- antigeny bakteriální MeSH
- lidé MeSH
- meningokokové infekce * epidemiologie MeSH
- meningokokové vakcíny * MeSH
- Neisseria meningitidis séroskupiny B * genetika MeSH
- Neisseria meningitidis * MeSH
- sekvenování celého genomu MeSH
- séroskupina MeSH
- syntetické vakcíny genetika MeSH
- vakcinace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
- MeSH
- dítě MeSH
- lidé MeSH
- meningokoková meningitida * epidemiologie mortalita prevence a kontrola MeSH
- meningokokové vakcíny * aplikace a dávkování terapeutické užití MeSH
- Neisseria meningitidis patogenita MeSH
- vakcinace statistika a číselné údaje MeSH
- vakcíny konjugované aplikace a dávkování terapeutické užití MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- přehledy MeSH
- Geografické názvy
- Česká republika MeSH
V období 2006-2022 bylo v České republice hlášeno v programu surveillance 958 případů invazivního meningokokového onemocnění (IMO), z nichž bylo u 21 (2,19 %) hlášeno v anamnéze očkování některou z vakcín proti meningokokovým onemocněním. Analýza dat ukazuje, že tyto vakcíny velmi dobře chrání proti IMO. Nejčastější bylo zjištění, že u pacientů s IMO, kteří měli v anamnéze očkování proti tomuto onemocnění, se jednalo o absenci očkování proti dané séroskupině a/nebo nedošlo k přeočkování. Výsledky této analýzy upozorňují na vhodnost aplikace obou vakcín, které jsou v České republice dostupné: rekombinantní vakcína obsahující antigeny meningokoka séroskupiny B (vakcína MenB) a konjugovaná tetravalentní vakcína obsahující antigeny čtyř séroskupin meningokoka A, C, W, Y (konjugovaná vakcína A, C, W, Y). Výsledky rovněž upozorňují na vhodnost přeočkování vakcínami proti meningokokovým onemocněním a na nezbytnost co nejvčasnějšího očkování vakcínou MenB u malých dětí.
In 2006–2022, 958 cases of invasive meningococcal disease (IMD) were reported to the surveillance programme in the Czech Republic, of which 21 (2.19%) had a history of vaccination with one of the meningococcal vaccines. Data analysis shows that these vaccines provide a very good protection against IMD. It was found that vaccinated patients with IMD either were not vaccinated against the causative serogroup and/or did not receive a booster dose. The results of this analysis show the benefit of both vaccines available in the Czech Republic: recombinant vaccine containing meningococcal serogroup B antigens (MenB vaccine) and tetravalent conjugate vaccine containing antigens of four meningococcal serogroups A, C, W, Y (A, C, W, Y conjugate vaccine). The results also show the benefit of meningococcal vaccine booster doses and the need for giving MenB vaccine to young children as early as possible.
- MeSH
- lidé MeSH
- meningokokové infekce * epidemiologie prevence a kontrola MeSH
- meningokokové vakcíny terapeutické užití MeSH
- Neisseria meningitidis MeSH
- surveillance populace MeSH
- vakcinace metody MeSH
- vakcíny konjugované terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Geografické názvy
- Česká republika MeSH
