Title: Maintaining public confidence and informing vaccine policy: Using clinical and sero-epidemiological data to predict risk of rotavirus disease in older children and adults in the UK
Funder: Department of Health and Social Care

Abstract: Understanding how immunity to rotavirus and the risk of disease changes as vaccinated children ageBackgroundIn July 2013 the UK introduced rotavirus vaccination for infants at 8 and 12 weeks of age. Before this, rotavirus was estimated to be responsible for 80,000 GP consultations and 45% of acute gastroenteritis hospitalisations in children under 5 years old.Early impact studies have shown reduced incidence of rotavirus hospitalisations and healthcare use for acute gastroenteritis in children since vaccine introduction. However, the long-term impact of vaccination is not fully understood. This is crucial in the assessment of any vaccine programme. To achieve this aim, we need to understand rotavirus transmission, herd immunity, and changes in infection risk that occur as vaccinated cohorts age.I hypothesise that in the UK, rotavirus disease burden will shift from being endemic in young children to epidemic in older children and adults as a consequence of infant vaccination.Objectives To evaluate the impact of rotavirus vaccine 7-years after introduction. To assess how vaccination changes immunity in children as they age. To understand and predict changes in the epidemiology of rotavirus infection from childhood to adulthood. MethodsMy fellowship will be split into three workstreams:One: Epidemiological study Vaccine impact and effectiveness in England will be assessed 7-years post-vaccine introduction using large anonymised databases of laboratory-confirmed rotavirus infections, hospital admissions, emergency department attendances, and GP consultations for acute gastroenteritis. Novel methods employing interrupted time-series analysis will be used to assess vaccine impact across all outcome measures, in the context of vaccine uptake and socioeconomic deprivation.Two: Seroepidemiology For the first time in the England, rotavirus serology will allow us to assess changes in the force of infection with rotavirus over time, pre- and post-vaccine introduction. Using a collection of serum samples representative of the general population of England, rotavirus-specific IgG and IgA titres will be measured using enzyme-linked immunosorbent assays and titres will be compared between the pre- and post-vaccine age-groups.Three: Mathematical models I will modify previously developed mathematical models describing the transmission dynamics of rotavirus strains by fitting these to laboratory-confirmed rotavirus cases in England and the serological analysis from workstream two. The fitted models will be used to generate testable hypotheses regarding changes in the age and strain distribution of rotavirus cases following vaccine introduction, at different levels of vaccine uptake and socioeconomic strata. Model predictions will be validated by using the observed data.Summary of BenefitsBy understanding changes in rotavirus epidemiology we can assess whether a booster dose of vaccine may be needed. Data from this study will enable us to understand the economics and social cost of rotavirus disease, including that borne by parents/carers identified through the consultation group. The long-term analysis of equitability of vaccine uptake and impact will inform public health efforts to efficiently target vaccine promotion. To summarise, these data will have implications for clinical management, diagnostics, health protection preparedness and economics, and will support vaccine programme policy and public confidence in the vaccine programme.

Lay abstract: Rotavirus infection can result in severe diarrhoea. By the age of 5 years most children have had at least one severe rotavirus infection. The protection that results from this means that later infections are mild or have no symptoms. So older children and adults do not normally get diarrhoea even if they get re-infected.In 2013 rotavirus vaccination was introduced for babies in the UK. Since then more than nine out of ten babies have been vaccinated. We already know that rotavirus vaccination greatly reduces diarrhoea in young children. What we don't know is whether like immunity from natural infection, this protection lasts from childhood into adulthood and whether the benefits are shared equally across communities. My previous work has shown that in disadvantaged communities where rates of severe diarrhoea are highest, fewer babies are vaccinated.Research over a lifetime is expensive, but looking at information we already have can help. Using existing data for England and novel statistical methods, this study will predict the risk of rotavirus illness in children as they get older and move into adulthood. It will also describe these changes in relation to existing health inequalities.Change of rotavirus disease patterns due to vaccination will have implications for how we diagnose and prevent rotavirus infection. This will require review of the best time to vaccinate and the cost-effectiveness of vaccination.Research PlanThe aim of my fellowship is to use statistics to predict how vaccination protects people from rotavirus disease from birth to adulthood.I will do this in three ways:a) Building on my previous work, I will assess whether the vaccine has affected the number of people getting diarrhoea, and which type of rotavirus caused their illness for up to 7-years after vaccine introduction. To do this, anonymised healthcare data will be used. The link between vaccine impact, number of people vaccinated and health inequalities will also be investigated.b) Using blood samples previously stored, I will assess the level of immune protection against rotavirus. I will compare immunity in different age groups before and after vaccine introduction. This will help me to understand whether immunity produced from rotavirus vaccination is different to that following natural infection.c) Mathematical models will be used to predict the impact rotavirus vaccination of infants has on children as they get older. Mathematical models can use information we have to predict what might happen. The information from a) and b) will be used to further develop existing models. This will allow us to predict how rotavirus disease patterns may change in the long-term after vaccination, and whether this may vary in disadvantaged communities.I have had discussions with parents/carers from a range of backgrounds about the benefits of vaccination. They have said that these benefits included less pressure on the NHS, reducing the burden/distress of caring for poorly children and less time-off work. Parents/carers had concerns about whether vaccines provided good protection. They also wanted access to basic statistics on vaccine effects. The knowledge gained from this study will help inform parents of the long-term effects of rotavirus vaccination. Including, how it impacts their children's health and the likely social and financial impact on their families.A parent/carer consultation group will be formed for my fellowship. It will include parents/carers who were involved in the above discussions and parents of children who have had rotavirus. This group will meet three times; once early on to discuss the research plan and the implications of the research and later for collaboration on dissemination of outcomes. This is critical because to maintain vaccine confidence, information must be correctly communicated.

Research activity codes: 3.4 VACCINES
Health categories: INFECTION