Modelling the impact of COVID-19 and routine MenACWY vaccination on meningococcal carriage and disease in the UK.

Country-wide social distancing and suspension of non-emergency medical care due to the COVID-19 pandemic will undoubtedly have affected public health in multiple ways. While non-pharmaceutical interventions are expected to reduce the transmission of several infectious diseases, severe disruptions to healthcare systems have hampered diagnosis, treatment, and routine vaccination. We examined the effect of this disruption on meningococcal disease and vaccination in the UK. By adapting an existing mathematical model for meningococcal carriage, we addressed the following questions: What is the predicted impact of the existing MenACWY adolescent vaccination programme? What effect might social distancing and reduced vaccine uptake both have on future epidemiology? Will catch-up vaccination campaigns be necessary? Our model indicated that the MenACWY vaccine programme was generating substantial indirect protection and suppressing transmission by 2020. COVID-19 social distancing is expected to have accelerated this decline, causing significant long-lasting reductions in both carriage prevalence of meningococcal A/C/W/Y strains and incidence of invasive meningococcal disease. In all scenarios modelled, pandemic social mixing effects outweighed potential reductions in vaccine uptake, causing an overall decline in carriage prevalence from 2020 for at least 5 years. Model outputs show strong consistency with recently published case data for England.

Understanding barriers to vaccination against invasive meningococcal disease: a survey of the knowledge gap and potential solutions.

INTRODUCTION: Invasive meningococcal disease (IMD) is a leading cause of life-threatening bacterial meningitis and septicemia. Evidence points to a knowledge gap among parents, teenagers, and healthcare providers (HCPs) regarding IMD and available vaccines, including those against the highly prevalent serogroup B. AREAS COVERED: An online survey was conducted between March 27 and 12 April 2019, to gather insights into the knowledge that parents/guardians have about IMD vaccines. The children were aged 2 months to 10 years in Australia, Brazil, Germany, Greece, Italy, and Spain, 5-20 years in the UK, and 16-23 years in the USA. The findings were discussed in the context of the available literature and solutions were proposed to minimize the knowledge gap and the barriers to vaccination against IMD. EXPERT OPINION: The survey demonstrated that parents have a good understanding of IMD but a limited understanding of the different serogroups and vaccines. The available literature highlighted multiple barriers to IMD vaccine uptake; these may be reduced through education of HCPs, clear recommendations to parents by HCPs, the use of technology, and disease-awareness initiatives that engage parents through physical and digital channels. Further studies are warranted to assess the impact of the COVID-19 pandemic on IMD vaccination.

Outcomes of meningococcal serogroup B disease in children after implementation of routine infant 4CMenB vaccination in England: an active, prospective, national surveillance study.

BACKGROUND: In 2015, the UK included 4CMenB, a multi-component, recombinant protein-based vaccine against meningococcal serogroup B (MenB) disease, in the national infant immunisation programme. We aimed to assess the effect of 4CMenB vaccination on the severity of MenB disease presentation and outcomes. METHODS: In this active, prospective, national surveillance study, we used data from the UK Health Security Agency national surveillance of meningococcal disease. We included data from follow-up of children younger than 5 years with laboratory-confirmed MenB disease who were eligible for 4CMenB vaccination with general practice 3-6 months after disease onset. All invasive MenB isolates were tested using the Meningococcal Antigen Typing System to determine whether the isolate was potentially preventable by 4CMenB. Admission to intensive care, death, and, when possible, reported sequelae in survivors were reviewed alongside vaccine status. For the epidemiological analysis, we compared laboratory-confirmed MenB disease cases before 4CMenB implementation (Sept 1, 2010, to March 31, 2015) with those after implementation (Sept 1, 2015, to March 31, 2020). For clinical follow-up and outcomes, we included all children younger than 5 years with laboratory-confirmed MenB disease between Sept 1, 2015, and March 31, 2021. FINDINGS: Between Sept 1, 2015, and March 31, 2021, there were 371 cases of MenB disease in children younger than 5 years, including 256 (69%) in those younger than 1 year and 128 (35%) in those younger than 3 months. After the introduction of 4CMenB, the peak age of patients with MenB disease shifted from 5-6 months to 1-3 months. Overall, 108 (29%) of 371 children were too young for vaccination, unvaccinated, or developed MenB disease within 14 days of the first dose. Of 110 meningococcal strains characterised, 11 (92%) of 12 were potentially preventable by 4CMenB in unvaccinated children compared with 53 (66%) of 80 in partly vaccinated and 11 (69%) of 16 in fully vaccinated children. 78 (21%) of 371 children required intensive care, and the case fatality ratio was 5% (17 of 371), with 11 of 17 deaths occurring before 1 year of age, including seven in infants who were too young (<8 weeks) for vaccination. Of 354 survivors, 57 (16%) had 74 sequelae reported; 45 (61%) of 74 were neurological, 17 (23%) were physical, two (3%) were behavioural or psychological, and ten (14%) were other complications. Prevalence of sequelae was similar in unvaccinated (15 [15%] of 98) and vaccinated (42 [16%] 256) children, as were composite outcomes of death or sequelae, and intensive care or death or sequelae. INTERPRETATION: Cases of MenB disease in vaccine-eligible children declined after 4CMenB implementation, but morbidity in vaccinated and unvaccinated children remained unchanged, highlighting the importance of vaccination to prevent MenB disease. The lower peak age of infants with MenB disease after 4CMenB implementation, with a higher case fatality ratio in young infants, highlights the importance of timely vaccination. FUNDING: UK Health Security Agency.

Pandemic's influence on parents' attitudes and behaviors toward meningococcal vaccination.

Invasive meningococcal disease is a life-threatening infection preventable through vaccination. Pediatric vaccination rates have declined during the coronavirus disease 2019 (COVID-19) pandemic. This survey aimed to understand how parents' attitudes and behaviors have changed during the pandemic with regard to immunization and, more specifically, meningococcal vaccination. An online survey was emailed to parents of eligible children 0-4 years, following the selection process from UK, France, Germany, Italy, Brazil, Argentina, and Australia; and of adolescents 11-18 years from US. Data collection took place 19 January-16 February 2021. Quotas were set to ensure a representative sample. Eleven questions relating to general perceptions around vaccination and attitudes and behaviors toward meningitis vaccination were displayed. On 4,962 parents (average 35 years) participating in the survey, most (83%) believed important for their child to continue receiving recommended vaccines during the COVID-19 pandemic. Nearly half of routine vaccine appointments were delayed or canceled due to the pandemic, and 61% of respondents were likely to have their children catch up once COVID-19 restrictions were lifted. 30% of meningitidis vaccination appointments were canceled or delayed during the pandemic, and 21% of parents did not intend to reschedule them because of lockdown/stay at home regulations, and fear of catching COVID-19 in public places. It is crucial to communicate clear instructions to health workers and the general population and to provide appropriate safety precautions in vaccination centers. This will help to maintain vaccination rates and limit infections to prevent future outbreaks.

What is the context? Invasive meningococcal disease (IMD) is an uncommon infection that can lead to permanent disabilities and even death.Meningitis vaccination can prevent IMDs caused by Neisseria meningitidis.Vaccination rates have declined during the coronavirus (COVID-19) pandemic.What is new? We collected opinion of parents from the UK, France, Germany, Italy, Brazil, Argentina, Australia, and the US, to understand their attitudes and behaviors toward meningitis vaccination during the COVID-19 pandemic.Results were reviewed by health care professional experts as well as by patient authors (IMD survivors).Most (83%) of the 4,962 parents believed that it is important for their child to continue receiving recommended vaccines during the COVID-19 pandemic.Half of the scheduled appointments for meningitis vaccination were canceled or delayed during the COVID-19 pandemic, mainly due to lockdown regulations and fear of catching COVID-19.Twenty-one percent of the parents who had their child's meningitis vaccination appointment canceled, did not intend to reschedule it.What is the impact? It is crucial that clear information is communicated by health care authorities and practitioners about the availability of vaccination during pandemic and the safety precautions that are taken.Collected opinions emphasize the importance of continuing vaccinations against infectious diseases during a pandemic.

Vaccine Impact and Effectiveness of Meningococcal Serogroup ACWY Conjugate Vaccine Implementation in the Netherlands: A Nationwide Surveillance Study.

BACKGROUND: In response to the recent serogroup W invasive meningococcal disease (IMD-W) epidemic in the Netherlands, meningococcal serogroup C (MenC) conjugate vaccination for children aged 14 months was replaced with a MenACWY conjugate vaccination, and a mass campaign targeting individuals aged 14-18 years was executed. We investigated the impact of MenACWY vaccination implementation in 2018-2020 on incidence rates and estimated vaccine effectiveness (VE). METHODS: We extracted IMD cases diagnosed between July 2014 and December 2020 from the national surveillance system. We calculated age group-specific incidence rate ratios by comparing incidence rates before (July 2017-March 2018) and after (July 2019-March 2020) MenACWY vaccination implementation. We estimated VE in vaccine-eligible cases using the screening method. RESULTS: Overall, the IMD-W incidence rate declined by 61% (95% confidence interval [CI], 40 to 74). It declined by 82% (95% CI, 18 to 96) in the vaccine-eligible age group (individuals aged 15-36 months and 14-18 years) and by 57% (95% CI, 34 to 72) in vaccine-noneligible age groups. VE was 92% (95% CI, -20 to 99.5) in vaccine-eligible toddlers (aged 15-36 months). No IMD-W cases were reported in vaccine-eligible teenagers after the campaign. CONCLUSIONS: The MenACWY vaccination program was effective in preventing IMD-W in the target population. The IMD-W incidence reduction in vaccine-noneligible age groups may be caused by indirect effects of the vaccination program. However, disentangling natural fluctuation from vaccine effect was not possible. Our findings encourage the use of toddler and teenager MenACWY vaccination in national immunization programs.

Impact of COVID-19 Containment Strategies and Meningococcal Conjugate ACWY Vaccination on Meningococcal Carriage in Adolescents.

OBJECTIVES: To examine if COVID-19 containment strategies were associated with reduced pharyngeal carriage of meningococci in adolescents. Also, to observe if carriage prevalence of meningococcal A, C, W and Y differed in meningococcal conjugate ACWY vaccinated and unvaccinated adolescents. DESIGN: Repeat cross-sectional study of pharyngeal carriage. SETTING: In 2020, recruitment commenced from February to March (pre-COVID-19) and recommenced from August to September (during COVID-19 measures) in South Australia. PARTICIPANTS: Eligible participants were between 17 and 25 years of age and completed secondary school in South Australia in 2019. RESULTS: A total of 1338 school leavers were enrolled in 2020, with a mean age of 18.6 years (standard deviation 0.6). Pharyngeal carriage of disease-associated meningococci was higher during the COVID-19 period compared with the pre-COVID-19 period (41/600 [6.83%] vs. 27/738 [3.66%]; adjusted odds ratio [aOR], 2.03; 95% CI: 1.22-3.39; P = 0.01). Nongroupable carriage decreased during COVID period (1.67% vs. 3.79%; aOR, 0.45; 95% CI: 0.22-0.95). Pharyngeal carriage of groups A, C, W and Y was similar among school leavers vaccinated with meningococcal conjugate ACWY (7/257 [2.72%]) compared with those unvaccinated (29/1081 [2.68%]; aOR, 0.86; 95% CI: 0.37-2.02; P = 0.73). Clonal complex 41/44 predominated in both periods. CONCLUSIONS: Meningococcal carriage prevalence was not impacted by public health strategies to reduce severe acute respiratory syndrome coronavirus 2 transmission and is unlikely to be the mechanism for lower meningococcal disease incidence. As international travel resumes and influenza recirculates, clinicians must remain vigilant for signs and symptoms of meningococcal disease. Vaccinating people at the highest risk of invasive meningococcal disease remains crucial despite containment strategies.

Meningococcal disease in North America: Updates from the Global Meningococcal Initiative.

This review summarizes the recent Global Meningococcal Initiative (GMI) regional meeting, which explored meningococcal disease in North America. Invasive meningococcal disease (IMD) cases are documented through both passive and active surveillance networks. IMD appears to be decreasing in many areas, such as the Dominican Republic (2016: 18 cases; 2021: 2 cases) and Panama (2008: 1 case/100,000; 2021: <0.1 cases/100,000); however, there is notable regional and temporal variation. Outbreaks persist in at-risk subpopulations, such as people experiencing homelessness in the US and migrants in Mexico. The recent emergence of ß-lactamase-positive and ciprofloxacin-resistant meningococci in the US is a major concern. While vaccination practices vary across North America, vaccine uptake remains relatively high. Monovalent and multivalent conjugate vaccines (which many countries in North America primarily use) can provide herd protection. However, there is no evidence that group B vaccines reduce meningococcal carriage. The coronavirus pandemic illustrates that following public health crises, enhanced surveillance of disease epidemiology and catch-up vaccine schedules is key. Whole genome sequencing is a key epidemiological tool for identifying IMD strain emergence and the evaluation of vaccine strain coverage. The Global Roadmap on Defeating Meningitis by 2030 remains a focus of the GMI.

A policy review of the introduction of the MenACWY vaccine in toddlers across multiple countries.

INTRODUCTION: Immunization is the best strategy to protect individuals from invasive meningococcal disease (IMD). To support decision-making around immunization, this paper considers what has led four countries and regions of two more to introduce the quadrivalent MenACWY vaccine in toddlers (ages 12-24 months). AREAS COVERED: A narrative literature review was conducted to identify countries that have introduced a MenACWY vaccination program for toddlers. Information from peer-reviewed publications, reports, and policy documents for each identified country was extracted. Australia, Chile, the Netherlands, Switzerland, and regions of Italy and Spain have introduced the MenACWY vaccine in their toddler programs, driven by the rising incidence of MenW and MenY and the vaccine's ability to provide protection against other serogroups. Australia and the Netherlands considered the economic impacts of implementing a MenACWY toddler vaccination program. Vaccination uptake and effects are reported for three countries; however, in two, isolating the vaccine's effect from the collateral effect of COVID-related measures is difficult. EXPERT OPINION: Increased convergence of vaccination policies and programs is needed internationally, as IMD recognizes no borders.PL AIN LANGUAGE SUMMARYVaccination is the best defense against meningitis, a deadly disease. While someone of any age can contract it, children 0-24 months of age are disproportionately affected. The increasing number of cases of meningitis has led four countries plus regions of two more to introduce into their vaccination schedules for toddlers (ages 12-24 months) a vaccine that protects against four different serogroups rather than one serogroup alone. This paper considers what has driven that shift.

Invasive Meningococcal X Disease during the COVID-19 Pandemic, Brazil.

Invasive meningococcal disease persists as a fulminant disorder worldwide. Although cases caused by Neisseria meningitidis serogroup X (MenX) occur infrequently, outbreaks have been reported in countries in Africa in recent decades. We report 2 cases of MenX invasive meningococcal disease in São Paulo, Brazil, in 2021 and 2022, during the COVID-19 pandemic.

Effectiveness and impact of the 4CMenB vaccine against invasive serogroup B meningococcal disease and gonorrhoea in an infant, child, and adolescent programme: an observational cohort and case-control study.

BACKGROUND: A programme of vaccination with the four-component serogroup B meningococcal (4CMenB) vaccine was introduced in South Australia for infants and children aged 0-3 years on Oct 1, 2018, and for senior school students in school years 10 and 11 (aged 15-16 years) and young adults aged 17-20 years on Feb 1, 2019. We aimed to evaluate vaccine effectiveness and impact on serogroup B meningococcal disease and gonorrhoea 2 years after implementation of the programme. METHODS: We did a cohort and case-control study among those targeted by the South Australia 4CMenB vaccination programme. We obtained disease notification data from SA Health, Government of South Australia, and vaccine coverage data from the South Australian records of the Australian Immunisation Register. Vaccine effectiveness was estimated as the reduction in the odds of infection using the screening and case-control methods. Vaccine impact was estimated as incidence rate ratios (IRRs), obtained by comparing case numbers in each year following the start of the vaccination programme with cases in the equivalent age cohort during the pre-vaccination programme years. We used Poisson or negative binomial models, as appropriate, with adjustment for changes in the incidence of serogroup B meningococcal disease in age cohorts not eligible for vaccination through the state programme. FINDINGS: 4CMenB vaccine coverage 2 years after introduction of the childhood vaccination programme was 94·9% (33 357 of 35 144 eligible individuals) for one dose, 91·4% (26 443 of 28 922) for two doses, and 79·4% (15 440 of 19 436) for three doses in infants. The one-dose (77·1%, 16 422 of 21 305) and two-dose (69·0%, 14 704 of 21 305) coverage was highest in adolescents born in 2003 (approximately year 10 students). 2 years after implementation of the childhood vaccination programme, incidence of serogroup B meningococcal disease was significantly reduced compared with before programme implementation in infants aged 12 weeks to 11 months (adjusted IRR [aIRR] 0·40 [95% CI 0·23-0·69], p=0·0011), but not in those aged 1 year (0·79 [0·16-3·87], p=0·77), 2 years (0·75 [0·18-3·14], p=0·70), or 4 years (3·00 [0·47-18·79], p=0·24). aIRRs were not calculable in those aged 3 or 5 years because of no cases occurring after programme implementation. aIRR for serogroup B meningococcal disease was 0·27 (0·06-1·16, p=0·078) in adolescents aged 15-18 years 2 years after implementation of the adolescent and young adult programme, and 1·20 (0·70-2·06, p=0·51) in those aged 19-21 years in the first year. Two-dose vaccine effectiveness against serogroup B meningococcal disease was estimated to be 94·2% (95% CI 36·6-99·5) using the screening method and 94·7% (40·3-99·5) using the case-control method in children, and 100% in adolescents and young adults (no cases reported after implementation). Estimated two-dose vaccine effectiveness against gonorrhoea in adolescents and young adults was 32·7% (8·3-50·6) based on the case-control method using age-matched individuals with chlamydia infection as controls. INTERPRETATION: 4CMenB vaccine shows sustained effectiveness against serogroup B meningococcal disease 2 years after introduction in infants and adolescents, and moderate effectiveness against gonorrhoea in adolescents. The high vaccine effectiveness against serogroup B meningococcal disease is likely due to high coverage in the target age groups and close antigenic match between the 4CMenB vaccine and the disease-associated serogroup B meningococcal strains circulating in South Australia. COVID-19-related physical distancing policies might have contributed to further declines in serogroup B meningococcal disease cases during the programme's second year. FUNDING: SA Health, Government of South Australia.

Population-based study of influenza and invasive meningococcal disease among Greek children during the COVID-19 pandemic.

BACKGROUND: Aiming to the containment of the coronavirus disease 2019 (COVID-19) pandemic, governments worldwide have implemented a series of non-pharmaceutical interventions. Many of them and especially school closures have impacted the circulation of multiple airborne pathogens among children and adolescents. This study investigates the incidence of influenza and invasive meningococcal disease among children aged 0-14 years in Greece during the COVID-19 pandemic. METHODS: Data regarding the number of influenza-like illness cases, influenza-related paediatric intensive care unit (PICU) admissions and invasive meningococcal disease cases among children 0-14 years old were obtained from the National Public Health Organization. The incidence of the two diseases during the COVID-19 pandemic period (2020/2021) was compared with that of the six preceding seasons (2014-2019). RESULTS: A notable decrease was observed in both influenza and invasive meningococcal disease cases during the period 2020/2021 compared with the years 2014-2019. The mean annual rate of influenza-like illness cases and influenza-related PICU admissions in children 0-14 years old has reduced by 66.9% and 100%, respectively, while the mean annual invasive meningococcal disease rate has declined by 70%. Both weekly influenza-like illness and monthly invasive meningococcal disease rates were significantly decreased. CONCLUSIONS: The activity of influenza and invasive meningococcal disease in the children and adolescents of Greece has decreased during the COVID-19 pandemic period. Reduced transmission is likely related to the public health measures that were implemented to control the pandemic. The value of these measures may have relevance to the future management of influenza or invasive meningococcal disease epidemics.

Excess Invasive Meningococcal Disease Associated With Seasonal Influenza, South Africa, 2003-2018.

BACKGROUND: Invasive meningococcal disease (IMD) is a devastating illness with high mortality rates. Like influenza, endemic IMD is seasonal, peaking in winter. Studies suggest that circulation of influenza virus may influence the timing and magnitude of IMD winter peaks. METHODS: This ecological study used weekly data from 2 nationwide surveillance programs: Viral Watch (proportion of outpatient influenza-positive cases from throat or nasal swab samples) and GERMS-SA (laboratory-confirmed cases of IMD), occurring across South Africa from 2003 through 2018 in all age bands. A bivariate time series analysis using wavelet transform was conducted to determine cocirculation of the diseases and the time lag between the peak seasons. We modeled excess meningococcal disease cases attributable to influenza cocirculation, using univariate regression spline models. Stata and R statistical software packages were used for the analysis. RESULTS: A total of 5256 laboratory-confirmed IMD cases were reported, with an average annual incidence of 0.23 episodes per 100 000 population and a mean seasonal peak during week 32 (±3 weeks). Forty-two percent of swab samples (10 421 of 24 741) were positive for influenza during the study period. The mean peak for all influenza occurred at week 26 (±4 weeks). There was an average lag time of 5 weeks between annual influenza and IMD seasons. Overall, 5% (1%-9%) of IMD cases can be attributable to influenza cocirculation, with, on average, 17 excess IMD cases per year attributable to influenza. CONCLUSIONS: A quantifiable proportion of IMD in South Africa is associated with influenza cocirculation; therefore, seasonal influenza vaccination may have an effect on preventing a small portion of IMD in addition to preventing influenza.

Seroprevalence of meningococcal ACWY antibodies across the population in the Netherlands: Two consecutive surveys in 2016/17 and 2020.

BACKGROUND: Meningococcal serogroup C (MenC) vaccination was introduced for 14-month-olds in the Netherlands in 2002, alongside a mass campaign for 1-18 year-olds. Due to an outbreak of serogroup W disease, MenC vaccination was replaced for MenACWY vaccination in 2018, next to introduction of a booster at 14 years of age and a catch-up campaign for 14-18 year-olds. We assessed meningococcal ACWY antibodies across the Dutch population in 2016/17 and 2020. METHODS: In a nationwide cross-sectional serosurvey in 2016/17, sera from participants aged 0-89 years (n = 6886) were tested for MenACWY-polysaccharide-specific (PS) serum IgG concentrations, and functional MenACWY antibody titers were determined in subsets. Moreover, longitudinal samples collected in 2020 (n = 1782) were measured for MenACWY-PS serum IgG concentrations. RESULTS: MenC antibody levels were low, except in recently vaccinated 14-23 month-olds and individuals who were vaccinated as teenagers in 2002, with seroprevalence of 59% and 20-46%, respectively. Meningococcal AWY antibody levels were overall low both in 2016/17 and in 2020. Naturally-acquired MenW immunity was limited in 2020 despite the recent serogroup W outbreak. CONCLUSIONS: This study demonstrates waning of MenC immunity 15 years after a mass campaign in the Netherlands. Furthermore, it highlights the lack of meningococcal AWY immunity across the population and underlines the importance of the recently introduced MenACWY (booster) vaccination.

Did social distancing measures deployed for SARS-CoV-2/COVID-19 control have an impact on invasive meningococcal disease?

We investigated the impact of social distancing measures, used to contain or mitigate SARS-CoV-2 spread, on the transmission of invasive meningococcal disease (IMD) in Italy. To this end, the temporal correlation between the implementation of lockdown measures in 2020 and IMD incidence was evaluated. A dramatic decline of IMD incidence was observed, suggesting that the measures applied to contain SARS-CoV-2 in Italy affected other infectious diseases transmitted through direct contact and droplets, at least in the early phase of the COVID-19 pandemic.

Surveillance and control of meningococcal disease in the COVID-19 era: A Global Meningococcal Initiative review.

This review article incorporates information from the 4th Global Meningococcal Initiative summit meeting. Since the introduction of stringent COVID-19 infection control and lockdown measures globally in 2020, there has been an impact on IMD prevalence, surveillance, and vaccination compliance. Incidence rates and associated mortality fell across various regions during 2020. A reduction in vaccine uptake during 2020 remains a concern globally. In addition, several Neisseria meningitidis clonal complexes, particularly CC4821 and CC11, continue to exhibit resistance to antibiotics, with resistance to ciprofloxacin or beta-lactams mainly linked to modifications of gyrA or penA alleles, respectively. Beta-lactamase acquisition was also reported through horizontal gene transfer (blaROB-1) involving other bacterial species. Despite the challenges over the past year, progress has also been made on meningococcal vaccine development, with several pentavalent (serogroups ABCWY and ACWYX) vaccines currently being studied in late-stage clinical trial programmes.