Parents' and guardians' views on the acceptability of a future COVID-19 vaccine: A multi-methods study in England.

BACKGROUND: The availability of a COVID-19 vaccine has been heralded as key to controlling the COVID-19 pandemic. COVID-19 vaccination programme success will rely on public willingness to be vaccinated. METHODS: We used a multi-methods approach - involving an online cross-sectional survey and semi-structured interviews - to investigate parents' and guardians' views on the acceptability of a future COVID-19 vaccine. 1252 parents and guardians (aged 16 + years) who reported living in England with a child aged 18 months or under completed the survey. Nineteen survey participants were interviewed. FINDINGS: Most survey participants reported they would likely accept a COVID-19 vaccine for themselves (Definitely 55.8%; Unsure but leaning towards yes 34.3%) and their child/children (Definitely 48.2%; Unsure but leaning towards yes 40.9%). Less than 4% of survey participants reported that they would definitely not accept a COVID-19 vaccine. Survey participants were more likely to accept a COVID-19 vaccine for themselves than their child/children. Participants that self-reported as Black, Asian, Chinese, Mixed or Other ethnicity were almost 3 times more likely to reject a COVID-19 vaccine for themselves and their children than White British, White Irish and White Other participants. Survey participants from lower-income households were also more likely to reject a COVID-19 vaccine. In open-text survey responses and interviews, self-protection from COVID-19 was reported as the main reason for vaccine acceptance. Common concerns identified in open-text responses and interviews were around COVID-19 vaccine safety and effectiveness, mostly prompted by the newness and rapid development of the vaccine. CONCLUSION: Information on how COVID-19 vaccines are developed and tested, including their safety and efficacy, must be communicated clearly to the public. To prevent inequalities in uptake, it is crucial to understand and address factors that may affect COVID-19 vaccine acceptability in ethnic minority and lower-income groups who are disproportionately affected by COVID-19

Effectiveness of herpes zoster vaccination in an older United Kingdom population.

BACKGROUND: Vaccination against herpes zoster was introduced in the United Kingdom in 2013 for individuals aged 70 years, with a phased catch-up campaign for 71-79 year olds. Vaccine introduction has resulted in a marked fall in incident herpes zoster and in post-herpetic neuralgia (PHN), but formal evaluation of vaccine effectiveness is needed. METHODS: In a population-based cohort study of older individuals born between 1933 and 1946, we used linked UK anonymised primary care health records for the first three years of the vaccination programme (01/09/2013-31/08/2016) and multivariable Poisson regression to obtain incidence rates and vaccine effectiveness (VE) against zoster and PHN. RESULTS: Among 516,547 individuals, 21% were vaccinated. Incidence of zoster was 3.15/1000 person-years in vaccinees and 8.80/1000 person-years in unvaccinated individuals. After adjustment, VE was 64% (95%CI = 60-68%) against incident zoster and 81% (95%CI = 61-91%) against PHN, with very similar VE estimates in the routine and catch-up cohorts. VE against zoster was lower in those with a previous history of zoster: 47% (95%CI = 31-58%) versus 64% (95%CI = 60-68%) in those without previous zoster. There was evidence of waning VE over time, from 69% (95%CI = 65-74%) in the first year after vaccination to 45% (95%CI = 29-57%) by the third year. CONCLUSION: This first formal assessment of VE in the UK zoster vaccination programme demonstrates good effectiveness of zoster vaccine, and very good protection against PHN. The findings provide evidence that VE is similar across the age groups targeted for vaccination in the UK, and on duration of protection of the vaccine in public health use. The study provides key information for decision-makers about the future direction of UK zoster vaccination programme, indicating that the live zoster vaccine may be more cost-effective than estimated previously. It also supports efforts to communicate the benefits of zoster vaccination to address the declining coverage observed across the UK

Safety of inadvertent administration of live zoster vaccine to immunosuppressed individuals in a UK-based observational cohort analysis.

OBJECTIVES: To investigate the safety of live attenuated varicella zoster vaccination when administered to immunosuppressed individuals. DESIGN: Prospective observational cohort study. SETTING: The study used anonymised data from the Clinical Practice Research Datalink (CPRD), comprising a representative sample of routinely collected primary care data in England between 2013 and 2017 and and linked Hospital Episode Statistics data. PARTICIPANTS: 168 767 individuals age-eligible for varicella zoster vaccination registered at a general practice in England contributing data to CPRD. MAIN OUTCOME MEASURES: Electronic health records indicating immunosuppression, zoster vaccination, diagnoses of specific varicella-zoster virus (VZV)-related disease and non-specific rash/encephalitis compatible with VZV-related disease. RESULTS: Between 1 September 2013 and 31 August 2017, a period of immunosuppression was identified for 9093/168 767 (5.4%; 95% CI: 5.3%-5.5%) individuals age-eligible for zoster vaccination. The overall rate of vaccination while immunosuppressed was 1742/5251 (33.2 per 100 adjusted person years at risk; 95% CI: 31.9%-34.5%). Follow-up of the 1742 individuals who were inadvertently vaccinated while immunosuppressed identified only two cases of VZV-related disease within 8 weeks of vaccination (0.1%; 95% CI: 0.01%-0.4%), both primary care diagnoses of 'shingles', neither with a related hospital admission. CONCLUSIONS: Despite evidence of inadvertent vaccination of immunosuppressed individuals with live zoster vaccination, there is a lack of evidence of severe consequences including hospitalisation. This should reassure primary care staff and encourage vaccination of mildly immunosuppressed individuals who do not meet current thresholds for contraindication. These findings support a review of the extent to which live zoster vaccination is contraindicated among the immunosuppressed

The risk of non-specific hospitalised infections following MMR vaccination given with and without inactivated vaccines in the second year of life. Comparative self-controlled case-series study in England.

Observational cohort studies in high-income settings have suggested that vaccination order may affect children's subsequent risk of a heterologous infection, with live vaccines reducing and inactivated vaccines (given on their own or with a live vaccine), increasing the risk. We used the self-controlled case-series method, which automatically controls for the individual level confounding to which such cohort studies are prone, to test this hypothesis. We compared the relative incidence (RI) of infections post-vaccination in two calendar periods in England; in Period 1 (September 2002-August 2006) live measles, mumps, rubella (MMR) vaccine was given on its own and in Period 2 (September 2006-April 2010) inactivated vaccines (7-valent pneumococcal conjugate vaccine (PCV7) and sometimes the combined Haemophilus influenzae type b/meningococcal group C vaccine (Hib-MenC)) were given concomitantly with MMR. Admissions for an infection of the upper or lower respiratory tract, gastrointestinal system or other site in children aged 11-23?months were selected from the Hospital Episode Statistics database in England and linked to child health immunisation histories. The analysis included a total of 24,144 infections in 21,067 children in Period 1 and 36,880 in 31,616 children in Period 2. The RI of admission for any infection in Period 1 was 1.00 (95% confidence interval 0.95-1.06) compared with 0.95 (95% confidence interval 0.90-1.00) in Period 2. Comparing the two periods showed no evidence of a difference in the relative incidence estimates with a ratio of RI of 0.94 (95% confidence interval 0.87-1.02), RIs within 90?days of vaccination were 0.94 (0.91-0.97) in Period 1 and 0.94 (0.91-0.97) in Period 2, consistent with a temporary healthy vaccinee effect. In conclusion, we found no evidence to support the hypothesis that there is a reduction in heterologous infections after MMR on its own or an increase after MMR given concomitantly with an inactivated vaccine

Impact of the national rotavirus vaccination programme on acute gastroenteritis in England and associated costs averted.

BACKGROUND: Introduction of infant oral rotavirus vaccination in the UK in July 2013 has resulted in decreased hospitalisations and Emergency Department (ED) visits for acute gastroenteritis (AGE), for both adults and children. We investigated reductions in AGE incidence seen in primary care in the two years after vaccine introduction, and estimated the healthcare costs averted across healthcare settings in the first year of the vaccination programme. METHODS: We used primary care data from the Clinical Practice Research Datalink and age-stratified time-series analyses to derive adjusted incidence rate ratios (IRRa) for AGE in the first two years of the post-vaccination era (July 2013-April 2015) compared to the pre-vaccination era (July 2008-June 2013). We estimated cases averted among children aged <5years in the first year of the vaccination programme by comparing observed numbers of AGE cases in 2013-2014 to numbers predicted from the time-series models. We then estimated the healthcare costs averted for general practice consultations, ED visits and hospitalisations. RESULTS: In general practice, AGE rates in infants (the target group for vaccination) decreased by 15% overall after vaccine introduction (IRRa=0.85; 95%CI=0.76-0.95), and by 41% in the months of historically high rotavirus circulation (IRRa=0.59; 95%CI=0.53-0.66). Rates also decreased in other young children and to a lesser degree in older individuals, indicating herd immunity. Across all three settings (general practice, EDs, and hospitalisations) an estimated 87,376 (95% prediction interval: 62,588-113,561) AGE visits by children aged <5years were averted in 2013-14, associated with an estimated £12.5million (9,209-16,198) reduction in healthcare costs. CONCLUSIONS: The marked decreases in the general practice AGE burden after rotavirus vaccine introduction mirror decreases seen in other UK healthcare settings. Overall, these decreases are associated with substantial averted healthcare costs

Early impact of the coronavirus disease (COVID-19) pandemic and physical distancing measures on routine childhood vaccinations in England, January to April 2020.

Using electronic health records, we assessed the early impact of coronavirus disease (COVID-19) on routine childhood vaccination in England by 26 April 2020. Measles-mumps-rubella vaccination counts fell from February 2020, and in the 3 weeks after introduction of physical distancing measures were 19.8% lower (95% confidence interval: -20.7 to -18.9) than the same period in 2019, before improving in mid-April. A gradual decline in hexavalent vaccination counts throughout 2020 was not accentuated by physical distancing

Social determinants of pertussis and influenza vaccine uptake in pregnancy: a national cohort study in England using electronic health records.

OBJECTIVE: To examine the social determinants of influenza and pertussis vaccine uptake among pregnant women in England. DESIGN: Nationwide population-based cohort study. SETTING: The study used anonymised primary care data from the Clinical Practice Research Datalink and linked Hospital Episode Statistics secondary care data. PARTICIPANTS: Pregnant women eligible for pertussis (2012-2015, n=68 090) or influenza (2010/2011-2015/2016, n=152 132) vaccination in England. MAIN OUTCOME MEASURES: Influenza and pertussis vaccine uptake. RESULTS: Vaccine uptake was 67.3% for pertussis and 39.1% for influenza. Uptake of both vaccines varied by region, with the lowest uptakes in London and the North East. Lower vaccine uptake was associated with greater deprivation: almost 10% lower in the most deprived quintiles compared with the least deprived for influenza (34.5% vs 44.0%), and almost 20% lower for pertussis (57.7% vs 76.0%). Lower uptake for both vaccines was also associated with non-white ethnicity (lowest among women of black ethnicity), maternal age under 20 years and a greater number of children in the household. The associations between all social factors and vaccine uptake were broadly unchanged in fully adjusted models, suggesting the social determinants of uptake were largely independent of one another. Among 3111 women vaccinated against pertussis in their first eligible pregnancy and pregnant again, 1234 (40%) were not vaccinated in their second eligible pregnancy. CONCLUSIONS: Targeting promotional campaigns to pregnant women who are younger, of non-white ethnicity, with more children, living in areas of greater deprivation or the London or North East regions, has potential to reduce vaccine-preventable disease among infants and pregnant women, and to reduce health inequalities. Vaccination promotion needs to be sustained across successive pregnancies. Further research is needed into whether the effectiveness of vaccine promotion strategies may vary according to social factors

Zoster vaccination inequalities: A population based cohort study using linked data from the UK Clinical Practice Research Datalink.

OBJECTIVE: To quantify inequalities in zoster vaccine uptake by determining its association with socio-demographic factors: age, gender, ethnicity, immigration status, deprivation (at Lower-layer Super Output Area-level), care home residence and living arrangements. METHOD: This population-based cohort study utilised anonymised primary care electronic health records from England (Clinical Practice Research Datalink) linked to deprivation and hospitalisation data. Data from 35,333 individuals from 277 general practices in England and eligible for zoster vaccination during the two-year period (2013-2015) after vaccine introduction were analysed. Logistic regression was used to obtain adjusted odds ratios (aOR) for the association of socio-demographic factors with zoster vaccine uptake for adults aged 70 years (main target group) and adults aged 79 years (catch-up group). RESULTS: Amongst those eligible for vaccination, 52.4% (n = 18,499) received the vaccine. Socio-demographic factors independently associated with lower zoster vaccine uptake in multivariable analyses were: being older (catch-up group: aged 79 years) aOR = 0.89 (95% confidence interval (CI):0.85-0.93), care home residence (aOR = 0.64 (95%CI: 0.57-0.73)) and living alone (aOR = 0.85 (95%CI: 0.81-0.90)). Uptake decreased with increasing levels of deprivation (p-value for trend<0.0001; aOR most deprived versus least deprived areas = 0.69 (95%CI: 0.64-0.75)). Uptake was also lower amongst those of non-White ethnicities (for example, Black versus White ethnicity: aOR = 0.61 (95%CI: 0.49-0.75)) but was not lower among immigrants after adjusting for ethnicity. Lower uptake was also seen amongst females compared to men in the catch-up group. CONCLUSIONS: Inequalities in zoster vaccine uptake exist in England; with lower uptake among those of non-White ethnicities, and among those living alone, in a care home and in more deprived areas. Tailored interventions to increase uptake in these social groups should assist in realising the aim of mitigating vaccination inequalities. As care home residents are also at higher risk of zoster, improving the uptake of zoster vaccination in this group will also mitigate inequalities in zoster burden

Effectiveness of oral rotavirus vaccination in England against rotavirus-confirmed and all-cause acute gastroenteritis.

BACKGROUND: The monovalent oral rotavirus vaccine Rotarix® was introduced into the UK infant immunisation programme in 2013. We estimated vaccine effectiveness (VE) in the first two years of the programme. METHODS: We used a test-negative case-control design and enhanced national surveillance data for 1869 vaccine-eligible children tested for rotavirus infection to obtain adjusted odds ratios and VE against laboratory-confirmed rotavirus infections. Linked anonymised UK primary care and hospitalisation data from the Clinical Practice Research Datalink (40,723 children) and random-effects Poisson regression were used in a cohort study to estimate VE against all-cause acute gastroenteritis (AGE) and AGE hospitalisations. RESULTS: VE against laboratory-confirmed infection was 69% (95% Confidence Interval: 40-84%) for one dose and 77% (95%CI: 66-85%) for two doses. Two-dose VE in children aged 90% vaccine coverage), explains the lack of VE against all-cause AGE because most AGE in the post-vaccine era would not have been due to rotavirus, although some underestimation of VE could also have occurred due to differential healthcare utilisation by vaccinated and unvaccinated infants. This highlights the importance of using specific vaccine-preventable endpoints for these scenarios

Exome array analysis of adverse reactions to fluoropyrimidine-based therapy for gastrointestinal cancer.

Fluoropyrimidines, including 5-fluororacil (5FU) and its pro-drug Capecitabine, are the common treatment for colorectal, breast, neck and head cancers-either as monotherapy or in combination therapy. Adverse reactions (ADRs) to the treatment are common and often result in treatment discontinuation or dose reduction. Factors contributing to ADRs, including genetic variation, are poorly characterized. We performed exome array analysis to identify genetic variants that contribute to adverse reactions. Our final dataset consisted of 504 European ancestry individuals undergoing fluoropyrimidine-based therapy for gastrointestinal cancer. A subset of 254 of these were treated with Capecitabine. All individuals were genotyped on the Illumina HumanExome Array. Firstly, we performed SNP and gene-level analyses of protein-altering variants on the array to identify novel associations the following ADRs, which were grouped into four phenotypes based on symptoms of diarrhea, mucositis, and neutropenia and hand-and-foot syndrome. Secondly, we performed detailed analyses of the HLA region on the same phenotypes after imputing the HLA alleles and amino acids. No protein-altering variants, or sets of protein-altering variants collapsed into genes, were associated with the main outcomes after Bonferroni correction. We found evidence that the HLA region was enriched for associations with Hand-and-Foot syndrome (p = 0.023), but no specific SNPs or HLA alleles were significant after Bonferroni correction. Larger studies will be required to characterize the genetic contribution to ADRs to 5FU. Future studies that focus on the HLA region are likely to be fruitful