This report examines whether meningococcal vaccination policies across Europe still match current disease trends. It brings together expert briefings on the feasibility of eradicating meningococcal disease, the socio-political factors driving national funding decisions, the remaining barriers to uptake, and the WHO Meningitis 2030 Roadmap, alongside country updates from eight European countries and a proposed action plan for 2020/2021.
Meeting Report
Policy Focus Group Meeting on Meningococcal Vaccinations — 11th Excellence in Pediatrics Conference, 5 December 2019
Simon Kroll1, Philippe de Wals2, Irene Rivero-Calle3, Elena Moya4, Daphne Holt5, Tilen Kozole6, Radovan Bogdanovic7, Mira Kojouharova8, Kare Molbak9, Lieke Sanders10, Hanna Nohynek11, Roman Prymula12, Marc Van Ranst13, Roy Philip14, Gertraud Daye15, Catherine Weil-Olivier16
1Imperial College and St Mary's Hospital, Member of the UK Health Protection Agency Meningococcus Forum, United Kingdom, 2Department of Social and Preventive Medicine at Laval University, Quebec, Canada, 3Clinical Hospital of Santiago de Compostela, Spain, 4Co-ordinator for Europe and Africa — CoMO — Confederation of Meningitis Organisations, Spain, 5Coalition for Life-Course Immunisation (CLCI), 6European Affairs, European Pharmaceutical Students' Association (EPSA), 7Paediatric Association of Serbia, 8National Centre of Infectious and Parasitic Diseases, 9Statens Serum Institut, Faculty of Health and Medical Sciences, University of Copenhagen; Director, State Epidemiologist, Department of Infectious Disease Epidemiology, Statens Serum Institut, 10Utrecht University Medical Centre and Chief Scientific Officer at the Institute of Public Health and the Environment, 11Infectious Disease Control and Vaccinations Unit, Department of Health Security, National Institute for Health and Welfare THL Helsinki, 12School of Medicine, Charles University, Prague, 13Department of Microbiology, Immunology and Transplantation, Head of the Laboratory of Clinical and Epidemiological Virology, Rega Institute for Medical Research, 14University Maternity Hospital Limerick GEMS, University of Limerick, Ireland, 15NGO Committee on Ageing, UN, Vienna, Austria, 16Paris VII University, France
Since 2015 the Excellence in Pediatrics Institute (EIP) has worked with European and global partners to help overcome the many remaining barriers to vaccination uptake. By connecting and working with colleagues across Adolescent Medicine, General Practice, Pharmacy and Nursing, and uniting behind the EU Commission's Coalition on Vaccination, EIP's goal is to promote a LifeCourse approach to vaccines.
Most notably, EIP believes that the following barriers remain: 1) Policy discrepancies — heterogeneous national vaccination policies, with differences in approach, prioritisation and decision-making processes. 2) Overarching barriers — a lack of policies to increase vaccine confidence, counteract misinformation, increase awareness and mobilise medical communities, and 3) Failure to adopt a LifeCourse approach — prevention policies not adapted to demographic changes and an increasingly ageing population. Disease prevention in all stages of life is not yet a priority.
As part of EIP's work within the EU Coalition on Vaccination, 8 Stakeholder Working Groups, as well as a joint EU Commission and WHO plenary briefing, took place at the 11th EIP Annual Conference in Copenhagen in December 2019. One of these Policy Focus Groups was tasked with examining all-cause meningococcal disease — establishing whether eradication is an achievable goal, understanding the factors that drive vaccine decision-making across Europe, identifying the remaining barriers to uptake, and considering how the Group could support the WHO Meningitis 2030 Roadmap.
The following report summarises the invited experts' briefings, discussions, and proposed action plans that were debated during the proceedings of the Policy Focus Group on All-Cause Meningococcal Disease — Time to Expand Meningococcal Vaccination Policies to Match Current Trends.
Working Group Briefing
Presenter: Prof. Simon Kroll, Professor of Paediatrics and Molecular Infectious Diseases, Imperial College and St Mary's Hospital, Member of the UK Health Protection Agency Meningococcus Forum, United KingdomProf. Kroll was invited to deliver the opening statement, with the Group asked to establish whether comprehensive eradication of meningococcal disease is an achievable goal. He stressed that the focus should be on eradicating the disease caused by meningococcus rather than the pathogen itself. The first documented outbreak of meningococcal disease took place at the end of 1885 in Geneva, with larger incidents occurring later in the Sahel of sub-Saharan Africa. His central question was why no outbreaks of such a deadly disease were documented before 1885; he speculated that the pathogen's capacity to be genetically modified over time led to a moment in history when a strain of meningococcus finally became a highly invasive and dangerous pathogen.
Unlike smallpox, many meningococcus strains are genetically variable and unstable, and there are many situations in which one cannot tell whether a person is infected. Prof. Kroll then analysed the main characteristics of serogroups A, C, W and Y. Serogroup A holds limited genetic diversity, and although its outbreaks are mainly geographically contained, it has affected large populations, creating an interest in its elimination given the human cost and the challenge to health systems. The vaccine MenAfriVac was developed in response, achieving over a 99% reduction in cases among fully vaccinated populations and eliminating carriage for a year or more.
Regarding serogroup C, infection rates dropped significantly when the vaccine was introduced in the UK, but its high capacity for mutagenicity made it difficult to control through vaccination. A further problem is its high cost combined with low incidence rates worldwide, which have kept it from becoming an international priority. Serogroup W shares the same problems: low disease rates, very common carriage, the potential to become vaccine-resistant, and high vaccine cost. By contrast, introducing a vaccine against serogroup Y — and strain 22 in particular — may risk an increased threat, as it has low invasive potential, is widely carried, and offers natural protective immunity to those who carry it.
Prof. Kroll pinpointed serogroup B as the principal problem, as vaccines developed against it are frequently rendered ineffective by its different clonal complexes. No vaccine is available that targets its capsular protein, because the polysaccharide may act as a self-antigen and cause major autoimmunity problems. He added that vaccination against serogroup B does not affect carriage, so community immunity is not sufficiently established. In conclusion, he pointed out that the control or elimination of particular strains is a realistic goal both globally and locally, depending on the serogroup and the political will to afford the necessary cost.
Working Group Briefing
Presenter: Prof. Philippe De Wals, MD, PhD, Department of Social and Preventive Medicine at Laval University, Quebec, CanadaProf. De Wals was invited to analyse the main factors influencing the decision-making process on meningococcal vaccines in European countries. He noted that in 1974, when he began his scientific career, there was a MenB outbreak in Belgium — and 45 years later, the problem remains unsolved. As in this and many other countries across Europe, the adoption of a new vaccine into a publicly funded programme is often based on a complex decision-making process involving different social, political and economic factors. In Agendas, Alternatives, and Public Policies (1984), John Kingdon proposed the "multiple streams" theoretical framework for analysing how and why governmental policies are adopted; the framework has been applied to immunization programs and has also been used to describe the adoption of ObamaCare and MediCare.
Prof. De Wals explained that the three streams influencing the decision-making process — Problem (disease burden and epidemiology), Solution (the vaccine) and Political (the agenda, values and interests of stakeholders) — converge, and when the proposal reaches the political agenda a decision is made, although this window of opportunity is highly unpredictable. For conjugate vaccines, the main pattern in Europe consisted of an outbreak or short-term rise in incidence, followed by a mass campaign and then a routine program (UK, Ireland, Netherlands, Belgium, Italy, France), with an easy decision owing to the cost (inexpensive, limited number of doses), safety (not especially reactogenic) and effectiveness (direct and herd community protection) of the meningococcal C and ACWY conjugate vaccines. Although many economic analyses were published, they played little role in decision-making, which was mostly driven by the will to prevent or control outbreaks that were intolerable for public health authorities.
The large variation in schedules across Europe — Belgium recommends a single dose for MenC, France two doses with mandatory catch-up, and Italy two doses for MenACWY with no mandatory catch-up — cannot be explained by epidemiology, but is justified by operational feasibility and the priority considerations of each country. In the case of protein-based vaccines, only three countries in Europe (UK, Ireland, Italy), and latterly South Australia, have jurisdictions recommending the vaccine for high-risk groups or in special circumstances. The justification rested on the low serogroup B disease incidence, uncertainty over the duration of protection, the lack of effect on carriage, considerable reactogenicity, the need for multiple doses, budget impact and various cost-effectiveness considerations. In the UK, Ireland and Italy the outcome was ultimately a political decision reached after considerable effort to tailor the cost-effectiveness evaluations (dropping doses, negotiating cost-effective agreements with companies, and correcting under-notification and under-diagnosis of cases), whereas in South Australia the decision was driven mostly by epidemiology.
In conclusion, Prof. De Wals stressed that decisions on publicly funded immunization programs targeting rare and severe conditions such as meningococcal disease are shaped far more by socio-political and organizational factors than by purely technical considerations such as disease burden or vaccine characteristics. He noted that the results of economic evaluations are very often used to justify decisions that are mainly based on other considerations, and was clear that central funding is required to achieve harmonization of schedules — as is the case in the US or Australia, but not in Canada or across Europe.
Working Group Briefing
Presenter: Dr Irene Rivero-Calle, Consultant in Pediatrics and Pediatric Infectious Diseases, University Clinical Hospital of Santiago de Compostela, SpainDr Rivero-Calle proposed that one of the main barriers is a lack of access, arising from several factors: 1) pathogen diversity among geographical regions, 2) significant use outside of routine immunization, 3) the 29 different marketed products targeting various combinations of the six serogroups (A, B, C, W, X, Y), 4) the discontinued production of polysaccharide vaccines, and 5) increased incidence rates of serogroups C and W. Most importantly, she pointed out that a lack of access is observed not only globally or by country, but also across different regions of the same country, because of the presence of different patient groups — infants, adolescents and immunocompromised individuals — that require special care.
A further significant barrier is financial. MenACWY vaccines cost about $8 per dose, whereas MenB vaccines can rise to as much as $80 per dose. Dr Rivero-Calle also cited herd protection and the impact on carriage: conjugate vaccines are preferred over polysaccharide vaccines for their advantages in direct and indirect protection, but the newer MenB protein vaccines do not cover all strains and may not induce herd protection.
Technical and programmatic barriers include the type of vaccine to be used, the meningococcal serotype to target, the appropriate age to vaccinate, and the different immunocompromised patient groups. For instance, if the desired outcome is carriage coverage, the adolescent group should be targeted, as carriage rates in this group can reach 20–30%. Dr Rivero-Calle noted that a lack of data remains a barrier, although new studies are emerging — including the USA Campaign, the UK Immunization Calendar, the Canada Campaign and the Spanish National Pediatric Association recommendation — which report coverage rate, effectiveness and vaccination impact depending on the chosen vaccine and age group.
Competition with vaccines for other diseases, or even among the different meningococcal vaccines, is another obstacle to elimination, and epidemiology is itself a significant factor, as low incidence rates, differing serotypes or low publicity may alter health-system policies both nationally and internationally. Psychological and social factors are also important: drawing on the Health Belief Model, Dr Rivero-Calle explained that, to be vaccinated, an individual needs to believe they are susceptible to the disease, that the disease is severe, that vaccination provides benefits, and that no significant barriers stand in the way. A recent study among first-year undergraduate students in the UK showed that, although the severity of meningitis was taken into high consideration, susceptibility to it was not — underlining the importance of healthcare specialists in persuading the population toward non-mandatory vaccination.
Dr Rivero-Calle added that miscommunication is another important barrier, and that engaging with social media platforms and providing effective, transparent and objective evidence-based information is required to counter false and misleading claims. In conclusion, she argued that meningitis must be prioritized as a global-health issue; that more accurate, available and easily accessible data on the global burden of meningitis are required; that new, effective and affordable vaccines must be developed and manufactured; that policies and funding are needed to support the introduction and optimization of vaccine schedules; and that vaccine awareness and uptake must be increased and encouraged.
Working Group Briefing — CoMO
Presenter: Dr Elena Moya, Co-ordinator for Europe and Africa, CoMO — Confederation of Meningitis Organisations, SpainDr Moya briefed the Group on the wider context of the WHO Meningitis 2030 Roadmap and where the Working Group could link in and support the current plans. She explained that the WHO roadmap to defeat meningitis has three main goals: 1) to eliminate bacterial meningitis epidemics, 2) to reduce cases and deaths from vaccine-preventable bacterial meningitis, and 3) to reduce disability and improve quality of life after meningitis due to any cause.
She noted that, during the consultations, the main outcomes were a need for prevention to become a higher-priority topic, followed by improved surveillance. In conclusion, Dr Moya highlighted that, in order to reach a world free of meningitis, the importance of the patient voice should not be understated, as it will support both the healthcare experts and the political will needed to protect against meningitis.
Dr Holt underlined that vaccines against meningitis should be available to all who need them, in every age and stage of life. At the same time, she asked the scientific community whether there is an actual benefit or prospect in vaccinating age groups beyond adolescents or patient groups with chronic medical conditions who are more susceptible to infection.
CLCI advocates a LifeCourse approach and believes that immunisation across the LifeCourse can reduce cases of meningitis as well as other infectious diseases. Further LifeCourse-based campaigns aimed at healthcare professionals and policymakers are needed to change the current targeted vaccine strategies and approach across Europe.
Dr Kozole presented the work of EPSA, which advocates for vaccination in public health by organizing campaigns in Europe and globally. He pointed out that the educational element is lacking not only in pharmaceutical studies but also across other healthcare disciplines, and that the lack of scientific data is an important point to address in the effort to eliminate meningitis.
He argued that everyone should advocate for the accessibility and affordability of vaccines, and that pharmacists play an important role in recommending vaccination — a role that is arguably underutilised as a channel to increase uptake through family contact, consultations and education, highlighting a need for further campaigns and activities in this area. He concluded that disease elimination is a genuine possibility and a goal we should all drive toward.
Dr Sanders commented that in the Netherlands there was an outbreak of MenW in 2006 that mostly affected infants under two years old, adolescents and elderly people, and resulted in high mortality. She noted that there are no scientific data on the effectiveness of vaccination in the elderly, a subject that needs further examination, and that healthcare professionals should focus on the herd effect in order to protect immunocompromised individuals and elderly people.
She stressed that, even though there is an increase in meningitis cases among elderly people, attention remains focused on infants and adolescents — and that this needs to change.
Prof. Bogdanovic described the current rules on meningococcal vaccination in Serbia and provided recent statistical data. The rules now apply to MenA, C, Y and W, whereas formerly they covered only MenA and MenC. Two categories exist: Mandatory and Recommended. The mandatory group comprises patients at special risk (asplenia, C5–C9 deficiency, bone marrow transplantation, and similar conditions), laboratory staff routinely exposed to Neisseria meningitidis isolates, and travellers (transit or sojourn) to endemic regions, while the recommended group generally consists of individuals in specific age ranges (infants, children, adolescents and young adults).
The proportion of reported meningococcal disease cases in Serbia over 2013–2017 was similar to that of other countries such as France and the Netherlands (ranging from 0.05 to 0.17 per 100,000 population, compared with 0.07 and 0.29 per 100,000 respectively in 2016). Even so, the number of people vaccinated over the last two years remained considerably lower than anticipated under the new rules, with 196 recorded in 2017 and 255 in 2018, of whom 109 were vaccinated for travel to endemic regions. In conclusion, Prof. Bogdanovic speculated that this reflects the very recent changes to the law and rules, with a lead time before they take full effect, and expected the numbers vaccinated in Serbia to rise substantially in the near future.
Dr Kojouharova updated the Group on meningococcal epidemiology and vaccination rules in Bulgaria. Meningitis is not a major concern there: over the last 18 years (2001–2019), only 428 cases were reported, an average of 0.3 per 100,000 population (ranging annually from 0.7 to 0.07 per 100,000), and only five cases were reported in the most recent year. She recognised, however, a problem with the death-to-case ratio, which is higher in Bulgaria than the European Union average (19.4% over the last 18 years). Although there were no deaths in the most recent year, in 2015 there were 20 deaths from meningococcal disease, a death-to-case ratio of 33.33%.
Analysing the age groups most affected, 70% of cases occur in young children aged 0–14 years; for other age groups meningococcus does not pose a serious threat, in contrast with Streptococcus pneumoniae, which is the main concern in Bulgaria. By serogroup, 60% of cases are MenB and 36% MenC, with almost no cases of MenA, Y or W. There is currently no vaccination schedule in effect; MenACWY and MenB vaccines are available on the market, but the costs are not covered, as meningococcal vaccination is not mandatory for any group and is mostly recommended to medical risk groups. Dr Kojouharova proposed that vaccination should at least be made mandatory for high-medical-risk groups, arguing that covering the expenses for this group would be a feasible plan even where it is not feasible for the whole population.
Prof. Molbak analysed the current status of meningococcal vaccination in Denmark and explained the reasons for not following a general vaccination schedule. Reported cases, counted at around 300 per year (5 per 100,000 population) at the end of the 1980s, fell dramatically to about 40 per year (0.7 per 100,000). In 2011 an increase in MenC cases raised concern among the authorities about introducing serogroup C vaccination into the national immunization program. The economic-technical assessment found that a two-dose schedule (at 15 months and 12 years of age) would prevent an estimated 2.1 cases of invasive meningococcal disease and 0.1 deaths per year at an annual cost of €6.4 million; adding a catch-up program for 13-to-18-year-olds would prevent 9 cases and 0.4–0.5 deaths annually, but raise the cost to €30 million.
The political decision was therefore against introducing the meningococcal vaccine into the national vaccination program. Meningococcal vaccination is currently used mainly to prevent outbreaks, for high-risk populations and in the military. In general, high-medical-risk groups still have to pay for vaccination, though not always — some hospitals, for example, provide it free of charge. Prof. Molbak concluded that MenC does not appear to be a serious threat in Denmark at present (6 cases in the previous year and 2 this year), but the same cannot be said for MenW and MenY, which have shown a recent increase.
Prof. Sanders presented two major issues the Netherlands has faced with meningococcal disease, both related to the recent MenW outbreak. The first was the need to change approach — moving from a catch-up program for adolescents to a vaccine schedule for children, while organizing to implement a routine MenACWY program at 14 months and 14 years of age the following year — during which they had to wait almost a year for the vaccines to be ready. The second concerned the elderly (the 80+ group), for whom no policy decision was made during this period.
Notably, no economic analysis was carried out for this vaccine schedule; the decisions were driven mostly by the outbreak itself and by public opinion, as many patients complained publicly about the lack of vaccines and, in conjunction with the situation in the UK, there was enormous pressure on policymakers to reach a swift decision. Prof. Sanders underlined that meningococcal serogroup B cases are currently at an all-time low, with the other serogroups also low at baseline. She concluded that reaching the optimal decision on a vaccination program is of high importance, because it is nearly impossible to change once it is already in effect.
Dr Nohynek briefly described meningococcal epidemiology and vaccination rules in Finland. In the 1970s a major outbreak of meningococcal disease drew the attention of the authorities and initiated meningococcal vaccine research, mainly through randomized controlled trials. Since then there has been a steady reduction in reported cases — from 4 per 100,000 population among children under five down to 0.3 per 100,000 — without any vaccination program in effect, except in the army, where an ACWY conjugate vaccine is scheduled, as joining the army is compulsory in Finland.
The dominant strain of meningococcus was B until 2013, after which cases divided roughly equally among serogroups C, B, W and Y. Health-technology assessments concerning meningococcal vaccination were not conducted over the years, mostly because of the high cost. In conclusion, Dr Nohynek underlined that meningococcal vaccination is still not compulsory in Finland, although it is recommended to some high-risk groups, for example travellers.
Prof. Prymula analysed epidemiological data for meningococcal disease in the Czech Republic alongside the current vaccination rules. Reported cases are low in general and have seen a steady drop over recent years (a ratio of 0.6 per 100,000 population over the last decade); there were 6 cases in 2017, halving to 3 this year (one each of serogroups B, C and Y). The most affected cohort was young children under one year of age, while adults and elderly people were the least affected group (only 5 cases among those aged 65 and over).
Prof. Prymula explained that the Czech Republic recently decided to change its national immunization strategy and include all doses of meningococcal vaccination in the insurance policy; previously only the first dose was covered by insurance, with the remainder paid directly by citizens, though medical risk groups are already fully covered. He underlined that, as of 1 July 2020, a new meningococcal vaccination program will take effect in the Czech Republic, offering MenB vaccination to young children (one dose at one year and one dose at two years of age), as well as a MenC vaccination in the early months of life.
Prof. Van Ranst offered epidemiological data and the current meningococcal vaccination rules for Belgium. There has been a steady drop in cases, with MenC in particular falling to 3–4 cases per year, as Belgium has run a vaccination program against MenC since 2002 with a 95% coverage rate. The opposite trend is seen for serogroups Y and W, which rose steadily from 1% of cases in 1993 to 15% in 2011 and nearly 42% today — prompting the High Health Council to decide, in August 2019, to change the program from MenC to MenACWY for young children at 15 months of age, with an added catch-up program for people aged 15–19.
A brief economic analysis was completed before the change took place. As for MenB, it is only recommended to individuals and is not on the schedule in Belgium. Prof. Van Ranst noted a concern that, if MenB were also placed on the schedule, it would probably adversely affect other vaccination programs currently running in Belgium, given the high number of doses required and the high reactogenicity of the MenB vaccine.
Dr Philip highlighted two public-health messages: that one should not wait for late symptoms, such as a rash, to appear before seeking medical assistance, and that if an infant is unwell one should act immediately. He noted two main developments in the Irish healthcare system — the introduction of MenACWY for college students and for 13-year-old children — and described the introduction of pharmacies into the vaccination strategy as a successful move that improved vaccination rates.
Dr Daye spoke about improving European surveillance of meningococcus. The main barrier to achieving this is the lack of common goals and objectives that would define the criteria, characteristics and timing of an incident that needs to be reported. A further problem is that not every country offers the same resources for surveillance of meningitis cases, which makes common standards, such as a shared diagnostic technique, difficult to meet.
Dr Weil-Olivier pointed out that reaching the adolescent group may seem difficult given the nature of their age, but that the positive factor is that adolescents are socially active and constantly informed through modern technology. She added that attention should also be given to parents, because a well-informed parent makes the adolescent more reachable.
Meningitis continues to be a serious threat to public health and is a disease that can often result in life-changing consequences. It is clear that the different serogroups require very different vaccination strategies, yet there remains great debate over which type of vaccine each country should choose to use and which age group to focus on.
Beyond infants, the Working Group concluded that great care should also be given to adolescents, elderly people and immunocompromised individuals. Pursuing a LifeCourse approach would be preferable, and highlights an ongoing need for the current political will to change and to take more decisive measures toward eliminating meningitis globally.
In addition to the concluding points above, the Focus Group raised the following areas that need to be explored in more detail, with the necessary actions taken to expand meningococcal vaccination policies to match current trends:
Improved European surveillance and modelling, alongside stronger local surveillance networks, is needed. A central question is how we can help countries that are falling behind.
A dedicated Focus Group on improving European surveillance and modelling.
Adolescents are a difficult group to reach. How can we increase adolescent coverage rates, including the adolescent booster dose, and improve herd protection for teenagers as well as the wider population? And how effective is directly targeting the elderly with meningitis vaccination?
1) A campaign to improve adolescent coverage, booster uptake and herd protection. 2) A pilot project to collect scientific data on the effectiveness of vaccination in the elderly.
Meningococcal vaccinations are often viewed with less scepticism by the public because of the severe nature of the disease they protect against. How can we better harness this positive public opinion, improve healthcare professionals' knowledge of the latest surveillance data, and work more effectively with pharmacists and allied HCPs?
An educational campaign designed to use positive public opinion, improve HCPs' knowledge and strengthen patient communication — working with pharmacists to promote meningitis vaccination at every opportunity.
