Background Neisseria meningitidis is an encapsulated Gram-negative diplococcus that asymptomatically colonises the upper respiratory tract in up to 25% of the population (mainly adolescents and young adults). Invasive meningococcal disease (IMD) caused by Neisseria meningitidis imposes a substantial public health burden,. The case fatality rate (CFR) of IMD remains high. IMD epidemiology varies markedly by region and over time, and there appears to be a shift in the epidemiology towards older adults. The objective of our review was to assess the published data on the epidemiology of IMD in older adults (those aged ≥ 55 years)in North America and Europe. Such information would assist decision-makers at national and international levels in developing future public health programmes for managing IMD. Methods A comprehensive literature review was undertaken on 11 August 2020 across three databases: EMBASE, Medline and BIOSIS. Papers were included if they met the following criteria: full paper written in the English language; included patients aged ≥ 56 years; were published between 1/1/2009 11/9/2020 and included patients with either suspected or confirmed IMD or infection with N. meningitidis in North America or Europe. Case studies/reports/series were eligible for inclusion if they included persons in the age range of interest. Animal studies and letters to editors were excluded. In addition, the websites of international and national organisations and societies were also checked for relevant information. Results There were 5,364 citations identified in total, of which 76 publications were included in this review. We identified that older adults with IMD were mainly affected by serogroups W and Y, which are generally not the predominant strains in circulation in most countries. Older adults had the highest CFRs, probably linked to underlying comorbidities and more atypical presentations hindering appropriate timely management. In addition, there was some evidence of a shift in the incidence of IMD from younger to older adults. Conclusions The use of meningococcal vaccines that include coverage against serogroups W and Y in immunization programs for older adults needs to be evaluated to inform health authorities’ decisions of the relative benefits of vaccination and the utility of expanding national immunization programmes to this age group.

Background Invasive meningococcal disease (IMD) causes high fatality in untreated patients alongside long-term sequelae in 20% survivors. For a comprehensive assessment of epidemiology, an analysis of these sequelae is required. This study aims to investigate the epidemiology of disease between 2008 and 2017 including a description of the sequelae, through the analysis of data collected from the UK Clinical Practice Research Datalink (CPRD) linked with data from the Hospital Episode Statistics (HES), and Office for National Statistics (ONS) mortality registry data. Methods This was a 10-year retrospective observational cohort study designed to describe the incidence, case-fatality rate (CFR) and occurrence of sequelae due to meningococcal disease, in the UK between 2007 and 2017 using data from the UK CPRD-HES-ONS. Cases were identified and matched on age, gender, date of diagnosis of IMD and followed-up-time with a control group without IMD. Demographics, clinical characteristics, mortality, and IMD-related sequelae were examined for IMD cases and compared with matched controls for a more comprehensive assessment. Results The study analysed 640 IMD patients with majority of the cases diagnosed (76.9%) in a hospital setting. Age-group analysis showed a decrease in the incidence rate of IMD in patients aged <1 year (30.4 – 7.5%) and an increase in those >50 years (10.4 – 27.8%). CFR was slightly higher among females, toddlers, and adults >50 years. No significant change in CFR was observed over study period. Case-control study showed a higher number of IMD sequelae among cases compared to age- and gender-matched controls, especially in those ≥ 50 years. Conclusion The study showed that, despite a relatively low incidence rate, IMD is responsible for a high CFR, namely in older age groups and by a high number of IMD sequelae. The study showed that leveraging data from existing databases can be used to complement surveillance data in truly assessing the epidemiology of IMD. Despite the availability of routine vaccination programs, IMD still poses a significant burden in the healthcare system of the UK. Optimization of vaccination programs may be required to reduce the disease burden.

MenACYW-TT (MenQuadfi®) is a quadrivalent meningococcal tetanus toxoid conjugate vaccine licensed in Europe for use in individuals ≥12 months. This study assessed whether serogroup C immune responses with MenACYW-TT were at least non-inferior, or superior, to those of quadrivalent meningococcal ACWY (MCV4-TT; Nimenrix®) and monovalent meningococcal C (MenC-TT; NeisVac-C®) vaccines in toddlers (12–23 months). In this modified, double-blind Phase III study (NCT03890367), 701 toddlers received one dose of MenACYW-TT (n = 230), MCV4-TT (n = 232) or MenC-TT (n = 239). Serum bactericidal assays with human (hSBA) and baby rabbit (rSBA) complement were used to measure anti-meningococcal serogroup C antibodies at baseline and 30 days post-vaccination. A sequential statistical approach was used for primary and secondary objectives. For the primary objectives, superiority of serogroup C was assessed in terms of hSBA seroprotection rates (defined as titers ≥1:8) and GMTs for MenACYW-TT compared to MCV4-TT, and rSBA GMTs compared to MenC-TT. The safety of all vaccines within 30 days post-vaccination was described. When administered as a single dose to meningococcal vaccine-naïve healthy toddlers the superiority of the MenACYW-TT serogroup C immune response versus MCV4-TT was demonstrated for hSBA GMTs (ratio 16.3 [12.7–21.0]) and seroprotection (difference 10.43% [5.68–16.20]); and versus MenC-TT in terms of rSBA GMTs (ratio 1.32 [1.06–1.64]). The safety profiles of a single dose of MenACYW-TT, MCV4-TT and MenC-TT were similar. In meningococcal vaccine-naïve toddlers, MenACYW-TT induced superior immune responses to serogroup C versus MCV4-TT in terms of hSBA seroprotection and GMTs and versus MenC-TT in terms of rSBA GMTs.

Introduction: Although quadrivalent meningococcal conjugate vaccines have been effective in preventing invasive meningococcal disease (IMD) caused by serogroups A, C, W, and Y across age groups from infants to adults, data on their efficacy and safety in adults ≥56 years of age are lacking. Moreover, multiple available quadrivalent conjugate vaccines require reconstitution prior to administration, introducing the potential for error. A novel quadrivalent meningococcal conjugate vaccine, MenACYW-TT (MenQuadfi ® ) was approved in 2020 for use in individuals ≥12 months of age as a single dose in the European Union and some other countries and in individuals ≥2 years of age in the United States. Areas covered: The findings of Phase II/III studies that included >6600 individuals and evaluated the immunogenicity and safety of MenACYW-TT beyond the first year of life are comprehensively summarized and discussed. Expert opinion: Extensive data on immunogenicity and safety, co-administration with routine vaccines, elicitation of robust booster responses, and significantly higher Men C responses versus monovalent MenC or MenACWY standard-of-care vaccines in toddlers suggest that MenACYW-TT may be suitable for inclusion in National Immunization Programs (NIPs) globally. The authors provide their perspectives on the clinical use of MenACYW-TT across age groups from toddlers through adults.

BackgroundInvasive meningococcal disease (IMD) causes high fatality in untreated patients alongside long-term sequelae in 20% survivors. For a comprehensive assessment of disease burden, an analysis of these sequelae is required. This study aims to investigate the burden of disease between 2008 and 2017 including a description of the sequelae, through the analysis of data collected from the UK Clinical Practice Research Datalink (CPRD) linked with data from the Hospital Episode Statistics (HES), and Office for National Statistics (ONS) mortality registry data.MethodsThis was a 10-year retrospective observational cohort study designed to describe the incidence, case-fatality rate (CFR) and occurrence of sequelae due to meningococcal disease, in the UK between 2007 and 2017 using data from the UK CPRD-HES-ONS. Cases were identified and matched on age, gender, date of diagnosis of IMD and followed-up-time with a control group without IMD. Demographics, clinical characteristics, mortality, and IMD-related sequelae were examined for IMD cases and compared with matched controls for a more comprehensive burden of disease assessment.ResultsThe study analysed 640 IMD patients with majority of the cases diagnosed (76.9%) in a hospital setting. Age-group analysis showed a decrease in the incidence rate of IMD in patients aged <1 year (30.4 – 7.5%) and an increase in those >50 years (10.4 – 27.8%). CFR was slightly higher among females, toddlers, and adults >50 years. No significant change in CFR was observed over study period. Case-control study showed a higher number of IMD sequelae among cases compared to age- and gender-matched controls, especially in those ≥ 50 years.ConclusionThe study showed that, despite a relatively low incidence rate, IMD is responsible for a high CFR, namely in older age groups and by a high number of IMD sequelae. The study showed that leveraging data from existing databases can be used to complement surveillance data in truly assessing the burden of IMD. Despite the availability of routine vaccination programs, IMD still poses a significant burden in the healthcare system of the UK. Optimization of vaccination programs may be required to reduce the disease burden.