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Title: Measuring the effect of rotavirus vaccination in primary and secondary care in Merseyside, UK
Author: Hungerford, Daniel J.
ISNI:       0000 0004 7428 6056
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2018
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Prior to the licensing and introduction of rotavirus vaccines in 2006, rotavirus was the most common cause of severe acute gastroenteritis (AGE) in children < 5 years of age, with the majority of disease burden occurring in children under two years of age. In the UK rotavirus was estimated to result in 80,000 general practice (GP) consultations in children < 5 years of age each year, together with 45% of hospitalisations and 20% of emergency department (ED) attendances for AGE. The UK introduced rotavirus vaccination into the routine childhood immunisation programme in July 2013. Whilst rotavirus vaccine impact on severe disease has been well described, uncovering vaccine impact on gastrointestinal (GI) disease outcomes across primary and secondary care is of public health importance; particularly understanding the extent of indirect effect or 'herd' protection. It is also important to ensure vaccine uptake and impact is equitable. As incidence of AGE is highest in the most socioeconomically deprived populations and vaccine uptake is often lower, measuring vaccine impact in relation to socioeconomic deprivation is critical. These themes were addressed through a series of inter-linked studies, for three years post-vaccine introduction (July 2013 to June 2016), in Merseyside, UK. In Merseyside, uptake of first-dose of rotavirus vaccine was 91.4%, and 86.7% for completion of the two dose schedule. Whilst, the risk of non-vaccination was higher in the most socioeconomically deprived populations. At a large acute paediatric hospital, after two seasons post-rotavirus vaccine introduction, laboratory confirmed rotavirus gastroenteritis (RVGE) hospitalisations reduced by 84% in vaccine-eligible children < 2 years of age and 69% in vaccine ineligible children 2-4 years of age. Reductions in both hospital- and community-acquired RVGE was comparable (83%). Interrupted time-series analysis of multiple routine healthcare datasets for three seasons post-vaccine introduction showed that among children < 5 years of age, the incidence of RVGE and AGE hospitalisations decreased by 80% and 44%, respectively, ED attendances fell by 23%, walk-in-centre attendances by 32% and GP consultations by 13%. Vaccine impact was greatest during the rotavirus-season and for vaccine eligible age groups. The rate of hospitalisations averted was higher among infants in the most deprived communities compared to the least deprived. In adults aged 65 years or older, AGE hospitalisations fell by 25%. Analysis of a GP birth cohort of children born between May 2010 and June 2016, demonstrated an overall rotavirus vaccine effectiveness (VE) of 11% against AGE. However, when using established methods to estimate direct and indirect VE, estimates were improbable, suggesting unmeasured confounding, and flawed comparator populations. A novel method using propensity score analysis was developed to deal with these issues through balancing comparator populations. Applying the alternative method produced epidemiologically and biologically plausible direct (8-11%) and indirect (1-4%) estimates of VE against GP consultations for AGE. In summary, rotavirus vaccination reduced healthcare use for multiple GI disease outcomes across the healthcare system. Effects were greatest in infants, for specific rotavirus outcomes, for severe disease, and in the rotavirus season. Furthermore the reduction of GI disease in older populations suggests 'herd' protection. Prioritising vaccine uptake in the most socioeconomically deprived communities is likely to give the greatest health benefit in terms of reducing population disease burden. Finally, a novel approach for measuring VE has been developed to mitigate against unmeasured confounding. This methodology will be valuable for studies using routine healthcare data to measure the broader public health impact of vaccines using syndromic non-specific endpoints.
Supervisor: French, Neil ; Cunliffe, Nigel ; Vivancos, R. ; Read, Jonathan Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral