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Carriage of Neisseria meningitidisis an accepted endpoint in monitoring meningococcal vaccine effects. We applied molecular methods to assess the impact of menACWY vaccine implementation on meningococcal carriage and genogroup-specific prevalence in young adults in Fall of 2022, four years after the introduction of the tetravalent vaccine in the Netherlands. The overall carriage rate of genogroupable meningococci was not significantly different compared to a pre-menACWY cohort investigated in 2018 (20.8 % or 125 of 601 versus 17.4 % or 52 of 299 individuals, p = 0.25). Of 125 carriers of genogroupable meningococci, 122 (97.6 %) were positive for either vaccine-types menC, menW, menY or genogroups, menB, menE, and menX, which are not targeted by the menACWY vaccine. Compared with a pre-vaccine-implementation cohort, there was 3.8-fold reduction (p < 0.001) in vaccine-type carriage rates and 9.0-fold increase (p < 0.0001) in non-vaccine type menE prevalence. We observe a reduction in menW and menY and an increase in menE, which suggest that implementation of menACWY vaccine affected carriage., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Carriage of Neisseria meningitidis is an accepted endpoint in monitoring meningococcal vaccines effects. We have assessed N. meningitidis and vaccine-type genogroup carriage prevalence in college students at the time of MenACWY vaccine introduction in the Netherlands, and evaluated the feasibility of saliva sampling for the surveillance of carriage. For this, paired saliva and oropharyngeal samples collected from 299 students were cultured for meningococcus. The DNA extracted from all bacterial growth was subjected to qPCRs quantifying meningococcal and genogroup-specific genes presence. Samples negative by culture yet positive for qPCR were cultured again for meningococcus. Altogether 74 (25%) of students were identified as meningococcal carrier by any method. Sixty-one students (20%) were identified as carriers with qPCR. The difference between number of qPCR-positive oropharyngeal (n = 59) and saliva (n = 52) samples was not significant (McNemar's test, p = 0.07). Meningococci were cultured from 72 students (24%), with a significantly higher (p < 0.001) number of oropharyngeal (n = 70) compared with saliva (n = 54) samples. The prevalence of genogroups A, B, C, W, and Y was none, 9%, 1%, 1% and 6%, respectively, and 8% of students carried MenACWY vaccine-type genogroup meningococci. Saliva is easy to collect and when combined with qPCR detection can be considered for meningococcal carriage studies., (© 2021. The Author(s).)

Neisseria meningitidis serogroup B is a major cause of invasive meningococcal disease in Europe. In the absence of a conjugate serogroup B vaccine, a subcapsular 4CMenB vaccine was developed. Data on 4CMenB vaccine efficacy is still limited. Recently, genomic MATS (Meningococcal Antigen Typing System) was developed as a tool to predict strain coverage, using vaccine antigens sequence data. We characterized all invasive meningococcal isolates received by the Netherlands Reference Laboratory for Bacterial Meningitis (NRLBM) in two epidemiological years 2017-2019 using whole-genome sequencing and determined serogroup, clonal complex (cc) and estimated 4CMenB vaccine coverage by gMATS. Of 396 cases of invasive meningococcal disease, corresponding to an incidence of 1.22 cases/10 5 inhabitants, 180 (45%) were serogroup W, 155 (39%) serogroup B, 46 (12%) serogroup Y, 10 (3%) serogroup C, 2 non-groupable (0.5%) and 3 (0.7%) unknown. The incidence was the highest among 0-4 years olds (4 cases/10 5 inhabitants), and 57/72 (79%) of these cases were serogroup B. Serogroup W predominated among persons 45 years of age or older with 110/187 (59%) cases. Serogroup B isolates comprised 11 different clonal complexes, with 103/122 (84%) isolates belonging to 4 clonal complexes: cc32, cc41/44, cc269 and cc213. In contrast, serogroup W isolates were genetically similar with 95% belonging to cc11. Of 122 serogroup B isolates, 89 (73%; 95% CI: 64-80%) were estimated to be covered by 4CMenB and the degree of coverage varied largely by clonal complex and age. Among the 0-4 year olds, 25 of 43 (58%; 95% CI: 43-72%) MenB isolates were estimated to be covered. Since the coverage of the 4CMenB vaccine is dependent on circulating clonal complexes, our findings emphasize the need for surveillance of circulating meningococcal strains. In addition, estimation of age specific coverage is relevant to determine the right target age group for vaccination., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: An increase in invasive meningococcal disease (IMD) serogroup W (IMD-W) cases caused by sequence type-11 clonal complex (cc11) was observed from October 2015 in the Netherlands. We compared the clinical picture and disease outcome of IMD-W cases with other serogroups, adjusting for host characteristics., Methods: We included IMD cases reported from January 2015 to June 2018 in the Netherlands and assessed clinical manifestation and symptoms at disease onset and calculated case fatality rates (CFRs). We used logistic regression to compare clinical manifestations and mortality of IMD-W with IMD caused by meningococci serogroup B, Y, or C, adjusting for age, gender, and comorbidities., Results: A total of 565 IMD cases were reported, of which 204 were IMD-W, 270 IMD-B, 63 IMD-Y, and 26 IMD-C. Most IMD-W isolates belonged to cc11 (93%; 175/188). Compared with other serogroups, IMD-W patients were diagnosed more often with septicemia (46%) or pneumonia (12%) and less often with meningitis (17%, P < .001). IMD-W cases presented more often with respiratory symptoms (45%, P < .001); 16% of IMD-W patients presented with diarrhea without IMD-specific symptoms (P = .061). The CFR for IMD-W was 16% (32/199, P < .001). The differences between IMD-W and other serogroups remained after adjusting for age, gender, and comorbidities., Conclusions: The atypical presentation and severe outcome among IMD-W cases could not be explained by age, gender, and comorbidities. Almost all our IMD-W cases were caused by cc11. More research is needed to identify the bacterial factors involved in clinical presentation and severity of IMD-W cc11., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Since 2009, the incidence of meningococcal serogroup W disease has increased rapidly in the UK because of a single strain (the so-called original UK strain) belonging to the hypervirulent sequence type-11 clonal complex (cc11), with a variant outbreak strain (the so-called 2013 strain) emerging in 2013. Subsequently, the Netherlands has had an increase in the incidence of meningococcal serogroup W disease. We assessed the temporal and phylogenetic associations between the serogroup W outbreaks in the Netherlands and England, and the historical serogroup C outbreaks in both countries., Methods: For this observational cohort study, we used national surveillance data for meningococcal serogroup W and serogroup C disease in the Netherlands and England for the epidemiological years (July to June) 1992-93 to 2015-16. We also did whole genome sequencing and core genome multilocus sequence typing (1546 loci) on serogroup W disease isolates from both countries for surveillance years 2008-09 to 2015-16. We used Poisson regression to compare the annual relative increase in the incidence of serogroup W and serogroup C between both countries., Findings: In the Netherlands, the incidence of meningococcal serogroup W disease increased substantially in 2015-16 compared with 2014-15, with an incidence rate ratio of 5·2 (95% CI 2·0-13·5) and 11% case fatality. In England, the incidence increased substantially in 2012-13 compared with 2011-12, with an incidence rate ratio of 1·8 (1·2-2·8). The relative increase in the Netherlands from 2014-15 to 2015-16 was 418% (95% CI 99-1248), which was significantly higher than the annual relative increase of 79% (61-99) per year in England from 2011-12 to 2014-15 (p=0·03). Cases due to meningococcal serogroup W cc11 (MenW:cc11) emerged in 2012-13 in the Netherlands. Of 29 MenW:cc11 cases found up to 2015-16, 26 (90%) were caused by the 2013 strain. For both the current serogroup W outbreak and the historical serogroup C outbreak, the increase in incidence started several years later in the Netherlands than in England, the rate of increase was higher in the Netherlands, and age distributions were similar in both countries., Interpretation: Given the historical similarities of meningococcal serogroup W with meningococcal serogroup C emergence, the rapid expansion of the MenW:cc11 2013 strain in the Netherlands, its high case fatality, and the availability of a safe and effective vaccine, urgent consideration is needed for public health interventions in the Netherlands and other affected countries to prevent further serogroup W cases and deaths., Funding: National Institute for Public Health and the Environment (Netherlands), Academic Medical Center (Netherlands), and Public Health England., (Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)