Pediatricians and infectious disease experts examined the evidence for rotavirus vaccination, from vaccine effectiveness and cost-effectiveness to the perceived low public health priority of the disease. The Working Group made the case for universal, state-funded vaccination and set out targets to raise public awareness and strengthen surveillance across Europe.
Meeting Report
Policy Focus Group Meeting on Rotavirus Vaccination — 11th Excellence in Pediatrics Conference, 5 December 2019
Timo Vesikari1, Vytautas Usonis2, Roman Prymula3, Irena Bralic4, Francisco Gimenez-Sanchez5, Zsofia Meszner6, Marc Van Ranst7, Malcolm Taylor8, Mihai Craiu9, Valtyr Thors10, Simon Kroll11, Anna Odone12, Irene Rivero–Calle13
1Professor Emeritus of Virology and Paediatrics, Director of Vaccine Research Center, Finland, 2Professor of Paediatrics at Clinic of Paediatrics, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Lithuania, 3Professor of Preventive Medicine at School of Medicine, Charles University, Prague, Czech Republic, 4Associate Professor of Pediatrics, University of Split, School of Medicine, Croatia, 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, Department Chair of the Department of Microbiology, Immunology and Transplantation, Head of the Laboratory of Clinical and Epidemiological Virology, Rega Institute for Medical Research, Belgium, 8General Secretary Coalition for Life-Course Immunisation (CLCI), United Kingdom, 9Professor of Pediatrics, Carol Davila University of Medicine Bucharest, Romania, 10Lead for paediatric infectious diseases at the Children's Hospital Reykjavik, and adjunct lecturer at the University of Iceland, Iceland, 11Professor of Paediatrics and Molecular Infectious Diseases, Imperial College and St Mary's Hospital, Member of the UK Health Protection Agency Meningococcus Forum, United Kingdom, 12Associate Professor of Public Health - Director of the School of Public Health, Vita-Salute San Raffaele University Milan, Italy, 13Consultant in Pediatrics and Pediatric Infectious Diseases, University Clinical Hospital of Santiago de Compostela, Spain
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 goals is to promote a LifeCourse approach to vaccines.
Most notably, EIP believes that the following barriers remain: 1) Policy discrepancies - Heterogeneous national vaccination policies. Differences in approach, prioritisation and decision making processes. 2) Overarching barriers - Lack of policies to increase vaccines 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 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 of doing so.
One of the Expert Working Groups was tasked to look at Rotavirus Vaccinations. The Working Group's discussions are set within the context of the increasing importance of rotavirus vaccination, as severe gastroenteritis can cause significant direct costs, indirect costs and societal impacts associated with infection. However, despite the clear evidence for implementing rotavirus vaccinations, not all countries have implemented a common strategy to address this issue.
The Working Group gathered pediatricians and infectious disease experts from many countries across Europe to share their knowledge and expertise, trying to outline a common point of view and implement a universal vaccination strategy, with a focus on overcoming the obstacle of perceived cost-effectiveness of implementation in countries across Europe.
The following report summarises the invited expert's briefings, discussions, and proposed action plans that were debated during the proceedings of the Policy Focus Group focused on Rotavirus Vaccinations and what should change to increase uptake across Europe.
Working Group Briefing
Prof. Timo Vesikari — Professor Emeritus of Virology and Paediatrics, Director of Vaccine Research Center, FinlandProf. Vesikari started the Working Group by pointing out that although Finland was one of the first countries to implement vaccination against rotavirus, they did not find any serotype-specific or associated protection. With this in mind, he suggested that all rotavirus vaccines follow the same pattern, function and mechanism — genotype-independent protection — and consequently he cannot find any important differences between the two vaccines currently available.1 2
Prof. Vesikari then made a historic reference to Germany and the UK working together to promote rotavirus vaccination across Europe, which worked as an application of the domino theory. However, he acknowledged that each country is a separate case and cannot be easily influenced, as each carries its own ideas and beliefs. He made it very clear that we cannot eliminate rotavirus from circulation and can only protect against severe rotavirus disease3, because there will always be a reservoir of the virus in the elderly and some outbreaks at schools due to susceptible children. He then examined rotavirus vaccination policy in Finland, commenting on low hospitalization rates, very high coverage rates, high effectiveness and a good vaccine 4-9 years after implementation of the program.4
Prof. Vesikari went on to mention a significant reduction, by one third, in celiac disease with rotavirus vaccination, counting as an additional argument in favor of vaccination.5 He concluded that all children should enjoy the benefits of this vaccine, and that a parenteral vaccine bypassing the gut may be manufactured in the future, but until then the oral vaccine will continue for many years to come.
During the discussion that followed, Prof. Vesikari underlined the importance of the domino theory as a universal human reaction to a certain extent, not linked specifically to rotavirus. He also stated that he is against health economics and, despite hospitalization care costing a great deal, his main reason for being pro-rotavirus vaccination is medical — namely, not letting children fall ill.
Working Group Briefing
Prof. Vytautas Usonis — Professor of Paediatrics at Clinic of Paediatrics, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, LithuaniaFollowing Prof. Vesikari's evaluation of the latest evidence, the Working Group invited Prof. Usonis to examine the cost effectiveness of implementing a universal rotavirus vaccination policy.
Prof. Usonis fully agreed with Prof. Vesikari that the wellness of children is the most important issue, rather than cost-effectiveness analyses. He outlined the significant burden of rotavirus gastroenteritis in terms of cost and to society, noting that reviews and studies worldwide conclude the costs are extremely high for the community, in both industrialized and developing countries.6 Apart from direct costs, he stressed that indirect costs such as outpatient office visits, home care and lost work hours must also be considered.7
Prof. Usonis suggested that measuring the cost-effectiveness of rotavirus vaccination across different countries is often an impossible task, given huge disparities in vaccination prices, healthcare prices, and available official data — reinforcing that each country is a distinct case. When the same methodology from one setting is applied to a different setting, misleading results are highly likely.8 He concluded that cost-effectiveness estimates should consider at least two distinct groups: industrialized and developing countries.
In the discussion that followed, it was stated that today's health economics should focus not only on the present but on the future, and that vaccination should perhaps be thought of as an investment for years to come.9 It was noted that vaccination would prevent 2.4 million rotavirus deaths and 182 million disability-adjusted life-years (DALYs) in 64 of the 72 GAVI-eligible countries introducing vaccines from 2007 through 2025.10 Applying a baseline scenario with an initial vaccine price of $7 per dose for a 2-dose vaccine, with a gradual decrease from 2012 stabilizing at $1.25 per dose by 2017, vaccination was very cost-effective in all GAVI-eligible countries.
Working Group Briefing
Prof. Roman Prymula — Professor of Preventive Medicine at School of Medicine, Charles University, Prague, Czech RepublicProf. Prymula was invited to brief the Working Group on the perceived low public health priority of protecting against rotavirus compared to other diseases. He began by noting that the rotavirus vaccine is a very significant tool for decreasing the burden of rotavirus disease in society. However, despite its huge potential, the current outlook in Europe is not so optimistic in terms of coverage compared to regions such as Australia and North and South America. Even when ECDC or WHO recommendations are applied, coverage remains quite low and disease burden has not dropped. Every year, rotavirus accounts for 231 deaths, more than 87,000 hospitalizations and almost 700,000 outpatient visits.11 Full reimbursement of vaccines is not the solution either, as coverage rates remain very low even in regions where vaccination is fully supported and reimbursed.
Prof. Prymula presented a recent study requiring data from 80 countries, with only 49 sharing information. It found that several countries have a limited budget for vaccination and immunization, and that in some, politicians along with physicians decide which vaccine will be implemented and which will not.12 13 As a result, the rotavirus burden is often considered less important and gastroenteritis less significant than other threats, which is why it is still excluded from vaccination programs in many countries.
Prof. Prymula concluded that each country should be addressed individually, given significant differences in populations, communities, cultures, priorities and policies. He highlighted the adversities healthcare professionals face when trying to convince parliaments to adopt vaccinations, and noted that convincing parents is often no easier, as a significant part of young parents view many vaccines with skepticism.14
Working Group Briefing
Prof. Irena Bralic — Associate Professor of Pediatrics, University of Split, School of Medicine, CroatiaProf. Bralic was tasked with summarising the arguments for either a universal vaccinations approach or one focused on the vaccination of high-risk groups. She reminded the Group that rotavirus is the most common cause of severe acute gastroenteritis according to the WHO15, and that both monovalent and pentavalent vaccines are particularly effective against rotavirus in children below 5 years of age.16 17 She noted that most international organizations recommend universal rotavirus vaccination, but in Croatia only high-risk groups of children receive the vaccine.
Prof. Bralic explained that rotavirus vaccines can be safely administered to infants living in households with immune-compromised individuals, but monovalent and pentavalent vaccines should not be administered to individuals with SCID, to immunocompromised infants, to infants receiving high doses of corticosteroids, or to infants with primary and acquired immunodeficiencies.18 Implementing universal vaccination in Croatia remains a complex public health, clinical, epidemiological and cost-effectiveness matter. In a meta-analysis of 20 studies, the highest nosocomial rotavirus infection (NRI) incidence rate was found in children less than 2 years old.19 20
During the discussion, Prof. Bralic made clear that she is against the selective approach and that all children should receive what is best for their health — consequently, the best approach is universal rotavirus vaccination. She added that common problems in everyday practice, such as insignificant concerns raised by parents that lead them to avoid immunization, need to be factored into a successful universal immunisation approach.
Dr Gimenez-Sanchez noted that the Spanish Association of Pediatrics has recommended rotavirus vaccination for children for the past 12 years. However, the vaccine was only reimbursed for preterm babies, resulting in an average uptake of 60%, with most parents still paying for the vaccine. He expressed hope this would change, noting pressure is accumulating from parents towards the government, as pediatricians recommend the vaccine while the effects of gastroenteritis in a small baby can be very stressful.
Dr Meszner explained that most children with gastroenteritis are not diagnosed with rotavirus unless hospitalized, representing only the tip of the iceberg. Hungary sees approximately 70,000 cases per year, one third attributed to rotavirus, with intensive care units taking a couple of hundred cases yearly, especially in winter. Most parents know what diarrhea is but are unaware of rotavirus gastroenteritis. Despite a high vaccine cost that parents must fully self-fund, 33.2% of eligible children were vaccinated in Hungary in 2018.
Prof. Van Ranst stated that rotavirus vaccination worked remarkably well in Belgium. Uptake rose above 90% very rapidly despite only partial reimbursement when introduced in 2007, with infection cases and hospitalization rates dropping dramatically and the rotavirus season shifting towards spring. He attributed this success to the remarkable readiness of the Minister of Health, vaccine companies and pediatric associations, which were key to how well the vaccination was perceived by parents.
Mr Taylor pointed out that cost-effectiveness analyses are gaining ground in health policy evaluation and implementation, and that healthcare professionals should make good use of social media and other means to strengthen parents' and patients' push towards politicians. In the UK, not everyone agreed with setting the cost-effectiveness concept aside, illustrating the need to return and convince parliaments of the necessity of the vaccination program. Direct costs, indirect costs (both individual and public health) and societal impact must all be taken into consideration. He noted that the benefits of vaccines in terms of improved education, benefit across the whole family rather than just the recipient, and contribution to national economic wellbeing are all sincerely underestimated.
Dr Zsofia Meszner asked about the mechanism responsible for the observed reduction in type 1 diabetes and celiac disease associated with rotavirus vaccination. Prof. Timo Vesikari responded that the mechanism is not yet fully understood and that knowledge is still accumulating in this area.
Dr Mihai Craiu (Professor of Pediatrics, Carol Davila University of Medicine, Bucharest, Romania) pointed out that more and more parents are digitally connected almost all the time, and that a weak government may buckle under that pressure. He suggested keeping things simple and addressing the problem as "diarrhea" rather than "rotavirus vaccination".
Dr Valtyr Thors (Lead for paediatric infectious diseases at the Children's Hospital, Reykjavik, and adjunct lecturer at the University of Iceland) commented that on returning to his country, rotavirus was not thought of as a big problem, but there was no data to support that view. He and his team therefore conducted a 2-year prospective research study alongside a public questionnaire; once completed, the data will be sent directly to policy makers, and he believes uptake will be extremely high in Iceland.
Prof. Simon Kroll (Professor of Paediatrics and Molecular Infectious Diseases, Imperial College and St Mary's Hospital, UK) spoke about the impact of vaccination not only on the recipient but across the whole family, while expressing some doubt over whether vaccination needs to be universal and mandatory or whether a voluntary approach is more beneficial.
Prof. Anna Odone (Associate Professor of Public Health, Director of the School of Public Health, Vita-Salute San Raffaele University, Milan, Italy) spoke on mandatory vaccination in Italy, where rotavirus vaccines are not mandatory. She commented that having some vaccines merely recommended and others mandatory creates more problems than it solves, as parents wonder whether some vaccines are more or less important than others, creating confusion. She asked whether epidemiological data can justify compulsion around rotavirus vaccination; Prof. Vesikari responded that he advocated it should be voluntary, and compared the importance of coverage rate between rotavirus and measles.
Dr Irene Rivero-Calle (Consultant in Pediatrics and Pediatric Infectious Diseases, University Clinical Hospital of Santiago de Compostela, Spain) spoke about WHO surveillance of the rotavirus burden globally, with 61 countries and 131 sentinel sites currently reporting to the network. This provides information on vaccine coverage, seasonality and impact on severe cases, allows cost-effectiveness studies and optimization of vaccination schedules, and addresses questions on vaccine performance, uptake and safety. She suggested these post-commercialization studies can globally promote decision-making on new vaccine introduction, including rotavirus vaccines.
The Working Group was dedicated to rotavirus vaccination, its current uptake rates around Europe, and where barriers to uptake still remain. It was concluded that the vaccine is a very significant tool for decreasing the burden of rotavirus disease in society, where rotavirus is the most common cause of severe acute gastroenteritis.
In particular the Working Group raised the following areas that need to be explored in more detail with necessary actions taken in 2020-21 to achieve increased rotavirus vaccination uptake across Europe, they include:
There is a need to make the public aware that rotavirus vaccines can protect children, the immunocompromised and wider society from the most common cause of severe acute gastroenteritis. Despite rotavirus-associated medical and emergency room visits and hospitalizations being significant across Europe, there is a significant lack of public awareness, while health authorities frequently fail to recognise the need for rotavirus vaccination.
An HCP-led campaign to the general public. An awareness campaign highlighting the expanded spectrum of rotavirus disease in Europe and the effective role universal vaccinations can play, aiming to change public perception.
Improved surveillance and reporting tools are needed to collect evidence on the true disease burden, the circulation of rotavirus genotypes and cost-effectiveness. There is also a need to adopt a harmonised economic evaluation methodology to make the process more comparable and transparent across European countries.
A dedicated expert-led European Working Group convened for countries who want to join together and implement the next wave of rotavirus vaccination programmes.
