Rotavirus is a viral infection which can result in severe diarrhoea. It is the most common cause of diarrhoeal disease in infants and young children. By the age of 3 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 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 dont know is whether like immunity from natural infection, this protection lasts from early years into older childhood, and if vaccination has shifted rotavirus disease from an early childhood severe disease to more episodes of mild-disease across childhood. This study will therefore assess the impact of rotavirus vaccination on acute gastroenteritis GP consultations and hospitalisations in children up to 7 years of age.
Additionally, rotavirus infection has previously been linked to increased risk of autoimmune diseases including type 1 diabetes and coeliac disease. We will therefore also assess the potential effect of rotavirus vaccination on preventing non-acute diarrhoea outcomes, including type 1 diabetes, inflammatory bowel disease and coeliac disease in children.
Aim: To assess the long-term impact of rotavirus vaccination on acute gastroenteritis (AGE) disease and heterologous vaccine effects on type 1 diabetes (T1D), Inflammatory Bowel Disease (IBD) and coeliac disease (CD) in pre-school and primary school children.
Objectives:
To assess whether rotavirus vaccination:
1. has changed the age and severity distribution of AGE in early childhood;
2. has any impact on the prevalence of IBD and CD in children;
3. has any impact on the prevalence of T1D in children.
Design: cohort study
Population: children <7 years of age, born between January 2000 and 31st December 2019.
Exposure: Rotavirus vaccination status.
Primary outcome: CPRD recorded primary care consultations for AGE and Hospital Episode Statistic recorded hospitalisation with AGE.
Secondary outcomes: IBD, CD and diagnosis of T1D.
Confounders and adjusters: DTaP/IPV/Hib/HepB vaccine status, socioeconomic deprivation, geography, GP, comorbidities.
Data analysis:
Outcome measures will be assessed in rotavirus vaccinated and unvaccinated children. A previously validated method will be used to balance comparator populations to account for bias in healthcare-seeking behaviours. We will describe cohort characteristics and compare disease rates in vaccinated and unvaccinated groups.
Primary outcome: Age-stratified disease incidence will be calculated for hospitalisations and GP consultations and compared in vaccinated and unvaccinated populations. Mixture models will be used to compare density of disease episodes by age for a vaccinated vs unvaccinated populations. Flexible parametric survival models will be used to assess differences in time to first event (GP consultation or hospitalisation). Age-stratified interrupted time-series analysis will assess how incidence rates have changed by season post-vaccine introduction.
Secondary outcomes - Flexible parametric survival models will be used to assess the risk of T1D, IBD and CD in a vaccinated and unvaccinated cohort.
Hazard ratios and incidence rate ratios derived from the regression models will be used as a measure of vaccine impact.
Primary care AGE consultations
AGE hospitalisations
Primary care, outpatient and hospitalisation with a diagnosis of IBD
Primary care, outpatient and hospitalisation with a diagnosis of CD
Primary care, outpatient and hospitalisation with a diagnosis of T1D
Daniel Hungerford - Chief Investigator - University of Liverpool
Daniel Hungerford - Corresponding Applicant - University of Liverpool
Aidan Flatt - Collaborator - University of Liverpool
David Taylor-Robinson - Collaborator - University of Liverpool
Kate Fleming - Collaborator - University of Liverpool
Mara Violato - Collaborator - University of Oxford
Miren Iturriza-Gomara - Collaborator - University of Liverpool
Neil French - Collaborator - University of Liverpool
Nigel Cunliffe - Collaborator - University of Liverpool
Roberto Vivancos - Collaborator - Public Health England
Thomas Inns - Collaborator - University of Liverpool
Virginia Pitzer - Collaborator - Yale University
HES Admitted Patient Care;HES Outpatient;Patient Level Index of Multiple Deprivation