This report sets out the case for universal varicella vaccination across Europe as it brings together expert briefings on Latvia's two-dose program, modeling of disease and hospitalization rates in Italy, vaccine effectiveness following regional schedules in Spain, the picture across Central and Eastern Europe, and the case for targeting high-risk groups, alongside a proposed action plan for 2020/2021.
Meeting Report
Policy Focus Group Meeting on Varicella Vaccinations — 11th Excellence in Pediatrics Conference, 5 December 2019
Terence Stephenson1, Anna Odone2, Dace Zavadska3, Paolo Bonanni4, Francisco Gimenez-Sanchez5, Zsofia Meszner6, Simon de Lusignan7, Steffen Amann8, Irena Bralic9, Mihai Craiu10, Vytautas Usonis11, Timo Vesikari12
1Nuffield Professor of Child Health, UCL Great Ormond Street Institute of Child Health, University College London; Honorary Consultant Paediatrician, UCLH and Great Ormond Street Hospital; Chair, Health Research Authority for England, 2Associate Professor of Public Health and Director of the School of Public Health, Vita-Salute San Raffaele University, Milan, Italy, 3Paediatric Infectious Diseases Specialist, Head of the Children Vaccination Centre under the Children's Clinical University Hospital, Riga, Latvia, 4Full Professor of Hygiene in the Faculty of Medicine and Director of the Specialization School for MDs in Hygiene and Preventive Medicine, University of Florence, Italy, 5Hispalense Institute of Pediatrics, Balmis Institute of Vaccines, Spain, 6Director of Methodology, Paediatrician and Specialist in Infectious Diseases, National Institute of Paediatrics Heim Pal, Hungary, 7Professor of Primary Care and Clinical Informatics, University of Oxford, Nuffield Department of Primary Care; Director, Royal College of General Practitioners Research and Surveillance Centre, United Kingdom, 8Director of Professional Development, European Association of Hospital Pharmacist (EAHP), Belgium, 9Associate Professor of Pediatrics, University of Split, School of Medicine, Croatia, 10Professor of Pediatrics, Carol Davila University of Medicine Bucharest, Romania, 11Professor of Paediatrics at the Clinic of Paediatrics, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Lithuania, 12Professor Emeritus of Virology and Paediatrics; Director, Vaccine Research Center, Finland
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. During the Working Groups, speakers were asked to share their opinions on ways to increase vaccination uptake in both the general public and healthcare professionals, on the current state and progress made in increasing vaccination coverage rates in different countries, and to mention the obstacles faced in the process.
The Varicella Working Group was convened to explore the latest available data on varicella vaccination across Europe and to debate the need for a universal vaccination program. The Group was tasked with examining the two-dose strategy, which is often considered superior to the single dose in terms of effectiveness, efficiency and coverage, and with considering how to better engage with HCPs and the public to achieve higher coverage rates by promoting the benefits of varicella vaccination.
The following report summarises the invited experts' briefings, discussions, and proposed action plans debated during the proceedings of the Varicella Vaccinations Working Group meeting, which was tasked with exploring and defining the best path towards universal varicella vaccination across Europe.
Working Group Briefing
Presenter: Dr Dace Zavadska, Paediatric Infectious Diseases Specialist, Riga, LatviaDr Zavadska was invited to share first-hand experience of successfully implementing a two-dose varicella vaccination programme, with a view to helping other country representatives follow the approach taken in Latvia. She opened by declaring that coverage is always the main factor in preventing the disease, showing how the two-dose program in Latvia had resulted in a very high coverage rate. The Latvian program achieved coverage above 90% — well above the 80% threshold below which, according to the WHO, the impact of vaccination cannot be easily perceived. She suggested that a single dose is very efficient in reducing the severity of varicella, whereas two doses protect against any degree of severity; the choice of strategy depends on whether the aim is to eliminate varicella or simply to address severe cases. According to the WHO, the vast majority of the 40 countries reviewed have implemented two-dose strategies.
Dr Zavadska then shared efficacy and effectiveness data from Latvia. Over a 10-year period, the Merck vaccine was measured at 94% efficacy for one dose and 98% for two doses, while the GSK vaccine measured 64–65% for one dose and 94% for two doses. For effectiveness, one dose ranged from 55–87% against any type of varicella and 84–98% against moderate or severe varicella, rising to 70–98% and 95–98% respectively for two doses. Breakthrough rates also fell with the second dose, from 8–32% after a single dose to about 4% after two doses, and studies showed that shifting to two-dose vaccination reduced the number, size and duration of varicella outbreaks.
She noted that, for several years, Latvia implemented a single-dose strategy, but outbreaks continued and a disbelief in the necessity of vaccination began to prevail, making it difficult for experts to explain to parents — and even to some GPs — why vaccination remained important in protecting against severe cases. With the success of the two-dose strategy, confidence has since grown again among both parents and healthcare professionals. On the interval between doses, Dr Zavadska suggested that the second dose should be given at least three months after the first, or 3–4 years later. In Latvia the first dose is given at 15 months of age together with the MMR, and the second at or just before seven years of age, again with the MMR.
Concerns were raised at the end of this part of the discussion over whether the mild cases of varicella that are expected — especially under a single-dose strategy — have any adverse effect on the risk of suffering from herpes zoster later in life. It was concluded that further data and research are needed to establish a firm understanding of any possible link.
Working Group Briefing
Presenter: Prof. Paolo Bonanni, Full Professor of Hygiene, Faculty of Medicine, and Director of the Specialization School for MDs in Hygiene and Preventive Medicine, University of Florence, ItalyProf. Bonanni explained that the first region in Italy to introduce a specific varicella vaccination program was Sicily, but one of the best performers was Puglia, where a single-dose strategy was implemented in 2006 and a second dose added in 2009. In Puglia, incidence rates fell from 6–7 patients per 1,000 to below 1 — and almost zero in some areas — while hospitalisation rates decreased by a factor of 3.5 from the point at which the universal program was first introduced. Data from eight Italian regions showed an average of 3–4 cases per 1,000 inhabitants per year, with almost no reported cases now, all within a very small amount of time. The fall in hospitalisation numbers, and their associated cost, was both statistically significant and rapid.
A study in Tuscany from 2009 to 2012 revealed that the impact of vaccination extended not only to the age groups that were vaccinated, but also to children below one year of age, with a clear impact noted in the 25–49 age group as well. Prof. Bonanni outlined the model study used in Italy, which helps to determine which of three parameters — coverage, efficacy or dose interval — matters most for impact. According to the model, coverage rate is the most important factor: when high coverage is reached, the influence of the dosing interval and of first-dose vaccine efficacy on disease prevalence in the population is relatively lower. Effectiveness, efficacy and dose interval are also important, but not as much as coverage, which he described as the key factor for successful implementation.
Continuing his analysis, Prof. Bonanni discussed endogenous and exogenous boosting, citing an increase in zoster cases noted several years after the implementation of universal varicella vaccination in Tuscany. Endogenous boosting occurs through the reactivation of internal varicella zoster virus, while exogenous boosting results from exposure to VZV from other people with varicella; in principle, reducing the circulation of VZV could therefore reduce exogenous boosting. He argued, however, that using this as a reason to avoid vaccination makes no sense, because exogenous boosting is not the only way to boost immunity. In his view there is no point in trying to protect the elderly by letting children suffer from varicella; it is far better to implement a universal vaccination program.
During the discussion that followed, it was stated that cellular immunity boosting is the most important factor when trying to prevent herpes zoster in the elderly — so the weaker a patient's immune system, the more likely they are to suffer from herpes zoster.
Working Group Briefing
Presenter: Prof. Francisco Gimenez-Sanchez, Hispalense Institute of Pediatrics, SpainProf. Gimenez-Sanchez opened by reminding the Working Group of the severe complications that can accompany varicella, including bacterial infection — precisely the reason Spain has insisted on the need for a universal varicella vaccination program. He set out the four options for tackling varicella in Spain: i) vaccinating susceptible adolescents only; ii) one dose of the vaccine at 12–15 months of age; iii) two doses, at 12–15 months and 3–4 years of age; and iv) doing nothing, which is equivalent to condemning everyone to suffer from the disease.
At first, the National Council recommended varicella vaccination for adolescents aged 10–14, but most were already ill by the time they reached the vaccination age. Madrid was the first region to move ahead, introducing a single dose at 12 months of age with very good results in terms of disease burden — 92% effectiveness, followed by a decline after 2–3 years. In the Navarra community, where all four strategies were implemented consecutively, results were even stronger, with a rapid reduction from 8 cases per 1,000 inhabitants to just 0.21 per 1,000 — a 97% reduction — in only six years. Effectiveness over these years was calculated at 96% for any dose schedule (one or two); one-dose effectiveness was 93% but declined to 61% after three years, and this decrease was even more significant when only susceptible adolescents were vaccinated.
Finally, in 2016, the National Council in Spain decided to introduce two doses of the vaccine at 15 months and 3–4 years of age across the whole country. Up to October 2019 there were 37,000 cases in Spain (compared with more than 50,000 in 2018), with an epidemic index of 0.47. Prof. Gimenez-Sanchez concluded that one dose of varicella vaccine may be highly effective, but that this effectiveness is expected to decline over the years, so the second dose is necessary to control the disease.
During the subsequent discussion, the optimum dose interval was debated, including whether it could be shortened. It was agreed to be a significant factor, but not as significant as high coverage. The group agreed that at least 60% coverage is needed before any impact on infection rates is seen, and that the goal should always be to reduce the circulation of the virus — something that can only be achieved with the additional catch-up dose.
Working Group Briefing
Presenter: Dr Zsofia Meszner, Director of Methodology, Paediatrician and Specialist in Infectious Diseases, National Institute of Paediatrics Heim Pal, HungaryDr Meszner set out the two main goals of vaccination — immunization against chickenpox and against the risk of severe chickenpox — and presented data for several countries in the region, including Poland, the Czech Republic, Estonia, Slovenia and Greece. She noted that it is very difficult to find supportive data because of the different policies, strategies, cultures and reporting methods across countries and regions. Nevertheless, one common finding was that the majority of children fall ill from chickenpox between one and nine years of age, and that complications are always more severe in older age groups.
She described a group of countries known as C-vac, comprising the Baltic countries, the Czech Republic, Slovakia, Poland, Croatia, Slovenia, Romania, Bulgaria and the European part of Turkey. At the time of the systematic literature reviews, none of these countries apart from Latvia had implemented a universal varicella vaccination program, although several countries that had adopted universal vaccination achieved quite low incidence rates per 100,000 inhabitants. Dr Meszner observed that severe cases of chickenpox usually go unnoticed by GPs, in Hungary and elsewhere, and that the cost of fighting varicella exceeds €1 million — very likely an underestimate, before the wider societal impact is even considered.
A further finding of her review was that younger age groups have higher hospitalisation rates, while older age groups suffer more severe chickenpox. The socio-economic impact of leaving chickenpox unvaccinated was discussed as one of the main reasons to move towards immunization. Because many decision-makers follow WHO guidance, Dr Meszner's strong recommendation was that the WHO should be very clear on the best route, as many countries depend heavily on its published position papers.
Working Group Briefing
Presenter: Prof. Simon de Lusignan, Professor of Primary Care and Clinical Informatics, University of Oxford; Director, Royal College of General Practitioners Research and Surveillance Centre, United KingdomProf. de Lusignan was invited to weigh the benefits of targeting varicella vaccination at high-risk groups, as opposed to universal vaccination. As a member of the Royal College of GPs research units, which run one of Europe's oldest surveillance systems, he explained that in the UK a two-dose vaccination is recommended for immunocompromised persons, for healthcare workers, and for non-immune women planning pregnancy. He then presented new data on varicella vaccination by age group, North–South location, ethnicity and household size.
Vaccination rates were significantly higher in London and Southern England than in the North of England, where uptake is quite low. He also found, perhaps unsurprisingly, that households of six or more people saw much more vaccination than smaller households, with uptake stacking up neatly in order of household size.
The discussion that followed made clear that the varicella vaccine, being a live vaccine, should not be given to pregnant women, but rather to non-immune women who plan to become pregnant. The group also discussed a recurring tactic by which some paediatricians tend to over-ICD-code varicella vaccination as being for immunocompromised patients.
Mr Amann pointed to a recurring dynamic in the way public threats are perceived: when a threat is large, it is relatively easy to convince people that something can solve the problem — but once the problem is being solved, many of those same people begin to feel threatened by the solution itself. He argued that pharmacists, alongside GPs and other healthcare workers, need to be better at convincing parents that vaccination and medication are there to do good and cause no harm.
He also underlined the significance of drug shortages in pharmacies and hospitals, which extend to the vaccines available.
Prof. de Lusignan opened the discussion by suggesting that the people who need vaccination most — even where it is free — often have the greatest difficulty accessing a doctor or general practitioner, citing statistical examples from South Wales. He warned that, as services move increasingly online, we are likely to identify still greater disparity between socio-economic groups. He also noted low vaccine hesitancy within high-risk groups, suggesting that only a tiny fraction of those who refuse to vaccinate themselves and their children do so on philosophical or specific religious grounds.
Prof. Timo Vesikari intervened on the need to overcome vaccine hesitancy in the wider population, proposing that addressing hesitancy in general is the primary issue when trying to eliminate the circulation of the virus in high-risk groups. In his argument, if we reduce virus circulation, there will be no need to discuss the improved targeting of high-risk populations at all.
The Working Group turned to HCPs as agents of change, and their pivotal role in effectively communicating the benefits of the varicella vaccine to parents. It was agreed that frightening people by showing severe cases and pictures of complicated cases is only a short-term solution and will not work in the long run; explaining the issue and genuinely connecting with parents is both the desired outcome and the best way to achieve it. The group also discussed how famous athletes and actors can play a hugely positive role, given their impact on decision-making — especially among younger people — while a celebrity who publicly discourages vaccination after a bad experience can be catastrophic for a campaign in favour of universal vaccination.
Mr Amann suggested aiming at both the mind and the soul — providing parents with the necessary information on the one hand, and sharing real stories on the other. Dr Mihai Craiu addressed the phenomenon through the lens of social media, noting that three out of four patients google their symptoms before visiting a physician. He proposed two solutions to the communication gap between doctors and the public: infotainment, using graphics, videos and other interactive tools, and gamification, giving children information about vaccines in a more fun and enthusiastic way so that it penetrates and has as large an impact as possible.
The Working Group explored how policymakers are hard to persuade because of the political and socio-economic costs involved, and how devising a single plan for all countries is made harder still by the vast differences between them and their populations. Healthcare associations do not make matters easier, as there is often considerable conflict of interest, compounded by the inherent difficulty of getting scientists to agree on a specific agenda. It was agreed that a strong surveillance system must be implemented to improve the efficiency of money spent on public health, and that the advantages of vaccination need to be communicated through social platforms so that penetration and positive impact grow alongside coverage rates.
There were several important take-home messages from the Working Group. In particular, it raised the following areas that need to be explored in more detail, with the necessary actions taken to achieve increased varicella vaccination rates across Europe:
Vaccine hesitancy is growing, and pharmacists, GPs and physicians must play a critical role in convincing undecided or wavering parents to vaccinate their children. HCPs need to be better at reassuring parents that vaccination and medication are there to do good and cause no harm.
A dedicated educational campaign designed to help HCPs understand that they are the trusted and preferred agents of change, equipping them with the tools, information and communication skills — and the real stories — needed to increase vaccination uptake.
Anti-vaccination activity and material on social media is rife, yet public health authorities and HCPs have been slow to respond. HCPs must make better use of social media to overcome the communication gap between doctors and the public, especially as three out of four patients google their symptoms before visiting a physician.
The development of infotainment (graphics, videos and other interactive tools) for use by HCPs and the public directly, alongside gamification — vaccine information delivered to children in a more fun and enthusiastic way.
Increased coverage universally across Europe is needed to guarantee varicella vaccination effectiveness. All countries must commit to implementing two doses of the vaccine, as well as agreeing the optimum dose interval.
A dedicated Policy Working Group formed to agree the adoption of the two-dose schedule and to settle the optimum dose interval, including whether it should be shortened from current recommendations.
