Influenza In England Research Articles

RWD114 Investigating the Impacts of Comorbid Conditions on Costs and Length of Stay in Secondary Care Among Adults Infected With Influenza in England

The burden of influenza varies across time and is affected by variations in circulating strains, population immunity, vaccination coverage and other risk factors including comorbidities and age. This study explored the impact of the presence of comorbidities on influenza-related hospitalisation costs and length of stay (LOS) in adults.

Optimising age coverage of seasonal influenza vaccination in England: A mathematical and health economic evaluation.

For infectious disease prevention, policy-makers are typically required to base policy decisions in light of operational and monetary restrictions, prohibiting implementation of all candidate interventions. To inform the evidence-base underpinning policy decision making, mathematical and health economic modelling can be a valuable constituent. Applied to England, this study aims to identify the optimal target age groups when extending a seasonal influenza vaccination programme of at-risk individuals to those individuals at low risk of developing complications following infection. To perform this analysis, we utilise an age- and strain-structured transmission model that includes immunity propagation mechanisms which link prior season epidemiological outcomes to immunity at the beginning of the following season. Making use of surveillance data from the past decade in conjunction with our dynamic model, we simulate transmission dynamics of seasonal influenza in England from 2012 to 2018. We infer that modified susceptibility due to natural infection in the previous influenza season is the only immunity propagation mechanism to deliver a non-negligible impact on the transmission dynamics. Further, we discerned case ascertainment to be higher for young infants compared to adults under 65 years old, and uncovered a decrease in case ascertainment as age increased from 65 to 85 years of age. Our health economic appraisal sweeps vaccination age space to determine threshold vaccine dose prices achieving cost-effectiveness under differing paired strategies. In particular, we model offering vaccination to all those low-risk individuals younger than a given age (but no younger than two years old) and all low-risk individuals older than a given age, while maintaining vaccination of at-risk individuals of any age. All posited strategies were deemed cost-effective. In general, the addition of low-risk vaccination programmes whose coverage encompassed children and young adults (aged 20 and below) were highly cost-effective. The inclusion of elder age-groups to the low-risk programme typically lessened the cost-effectiveness. Notably, elderly-centric programmes vaccinating from 65-75 years and above had the least permitted expense per vaccine.

Quantifying the direct secondary health care cost of seasonal influenza in England

BackgroundThe winter pressure often experienced by NHS hospitals in England is considerably contributed to by severe cases of seasonal influenza resulting in hospitalisation. The prevention planning and commissioning of the influenza vaccination programme in the UK does not always involve those who control the hospital budget. The objective of this study was to describe the direct medical costs of secondary care influenza-related hospital admissions across different age groups in England during two consecutive influenza seasons.MethodsThe number of hospital admissions, length of stay, and associated costs were quantified as well as determining the primary costs of influenza-related hospitalisations. Data were extracted from the Hospital Episode Statistics (HES) database between September 2017 to March 2018 and September 2018 to March 2019 in order to incorporate the annual influenza seasons. The use of international classification of disease (ICD)-10 codes were used to identify relevant influenza hospitalisations. Healthcare Resource Group (HRG) codes were used to determine the costs of influenza-related hospitalisations.ResultsDuring the 2017/18 and 2018/19 seasons there were 46,215 and 39,670 influenza-related hospital admissions respectively. This resulted in a hospital cost of £128,153,810 and £99,565,310 across both seasons. Results showed that those in the 65+ year group were associated with the highest hospitalisation costs and proportion of in-hospital deaths. In both influenza seasons, the HRG code WJ06 (Sepsis without Interventions) was found to be associated with the longest average length of stay and cost per admission, whereas PD14 (Paediatric Lower Respiratory Tract Disorders without Acute Bronchiolitis) had the shortest length of stay.ConclusionThis study has shown that influenza-related hospital admissions had a considerable impact on the secondary healthcare system during the 2017/18 and 2018/19 influenza seasons, before taking into account its impact on primary health care.

Exploiting routinely collected severe case data to monitor and predict influenza outbreaks

BackgroundInfluenza remains a significant burden on health systems. Effective responses rely on the timely understanding of the magnitude and the evolution of an outbreak. For monitoring purposes, data on severe cases of influenza in England are reported weekly to Public Health England. These data are both readily available and have the potential to provide valuable information to estimate and predict the key transmission features of seasonal and pandemic influenza.MethodsWe propose an epidemic model that links the underlying unobserved influenza transmission process to data on severe influenza cases. Within a Bayesian framework, we infer retrospectively the parameters of the epidemic model for each seasonal outbreak from 2012 to 2015, including: the effective reproduction number; the initial susceptibility; the probability of admission to intensive care given infection; and the effect of school closure on transmission. The model is also implemented in real time to assess whether early forecasting of the number of admissions to intensive care is possible.ResultsOur model of admissions data allows reconstruction of the underlying transmission dynamics revealing: increased transmission during the season 2013/14 and a noticeable effect of the Christmas school holiday on disease spread during seasons 2012/13 and 2014/15. When information on the initial immunity of the population is available, forecasts of the number of admissions to intensive care can be substantially improved.ConclusionReadily available severe case data can be effectively used to estimate epidemiological characteristics and to predict the evolution of an epidemic, crucially allowing real-time monitoring of the transmission and severity of the outbreak.

Reasons for non-vaccination: Parental vaccine hesitancy and the childhood influenza vaccination school pilot programme in England

IntroductionIn 2013, the annual influenza immunisation programme in England was extended to children to reduce the burden of influenza, but uptake was sub-optimal at 53.2%. AimTo explore the reasons some parents decided not to vaccinate their child against influenza as part of the pilot programme offered in schools. MethodsCross-sectional qualitative study conducted between February and July 2015. 913 parents whose children were not vaccinated against influenza in the school pilots in West Yorkshire and Greater Manchester, England, were asked to comment on their reasons for non-vaccination and invited to take part in a semi-structured interview. 138 parents returned response forms, of which 38 were eligible and interested in participating and 25 were interviewed. Interview transcripts were coded by theme in NVivo. ResultsA third of parents who returned response forms had either vaccinated their child elsewhere, intended to have them vaccinated, or had not vaccinated them due to medical reasons (valid or perceived). Most interviewees were not convinced of the need to vaccinate their child against influenza. Parents expressed concerns about influenza vaccine effectiveness and vaccine side effects. Several parents interviewed declined the vaccine for faith reasons due to the presence of porcine gelatine in the vaccine. ConclusionsTo significantly decrease the burden of influenza in England, influenza vaccination coverage in children needs to be >60%. Hence, it is important to understand the reasons why parents are not vaccinating their children, and to tailor the communication and immunisation programme accordingly. Our finding that a third of parents, who did not consent to their child being vaccinated as part of the school programme, had actually vaccinated their child elsewhere, intended to have their child vaccinated, or had not vaccinated them due to medical reasons, illustrates the importance of including additional questions or data sources when investigating under-vaccination.

The Relationship Between School Holidays and Transmission of Influenza in England and Wales.

School closure is often considered as an influenza control measure, but its effects on transmission are poorly understood. We used 2 approaches to estimate how school holidays affect the contact parameter (the per capita rate of contact sufficient for infection transmission) for influenza using primary care data from England and Wales (1967-2000). Firstly, we fitted an age-structured susceptible-infectious-recovered model to each year's data to estimate the proportional change in the contact parameter during school holidays as compared with termtime. Secondly, we calculated the percentage difference in the contact parameter between holidays and termtime from weekly values of the contact parameter, estimated directly from simple mass-action models. Estimates were combined using random-effects meta-analysis, where appropriate. From fitting to the data, the difference in the contact parameter among children aged 5-14 years during holidays as compared with termtime ranged from a 36% reduction to a 17% increase; estimates were too heterogeneous for meta-analysis. Based on the simple mass-action model, the contact parameter was 17% (95% confidence interval: 10, 25) lower during holidays than during termtime. Results were robust to the assumed proportions of infections that were reported and individuals who were susceptible when the influenza season started. We conclude that school closure may reduce transmission during influenza outbreaks.

Reconstructing a spatially heterogeneous epidemic: Characterising the geographic spread of 2009 A/H1N1pdm infection in England

Understanding how the geographic distribution of and movements within a population influence the spatial spread of infections is crucial for the design of interventions to curb transmission. Existing knowledge is typically based on results from simulation studies whereas analyses of real data remain sparse. The main difficulty in quantifying the spatial pattern of disease spread is the paucity of available data together with the challenge of incorporating optimally the limited information into models of disease transmission. To address this challenge the role of routine migration on the spatial pattern of infection during the epidemic of 2009 pandemic influenza in England is investigated here through two modelling approaches: parallel-region models, where epidemics in different regions are assumed to occur in isolation with shared characteristics; and meta-region models where inter-region transmission is expressed as a function of the commuter flux between regions. Results highlight that the significantly less computationally demanding parallel-region approach is sufficiently flexible to capture the underlying dynamics. This suggests that inter-region movement is either inaccurately characterized by the available commuting data or insignificant once its initial impact on transmission has subsided.

Extending the elderly- and risk-group programme of vaccination against seasonal influenza in England and Wales: a cost-effectiveness study.

BackgroundThe present study aims to evaluate the cost-effectiveness of extending the pre-2013 influenza immunisation programme for high-risk and elderly individuals to those at low risk of developing complications following infection with seasonal influenza.MethodsWe performed an economic evaluation comparing different extensions of the pre-2013 influenza programme to seven possible age groups of low-risk individuals (aged 2–4 years, 50–64 years, 5–16 years, 2–4 and 50–64 years, 2–16 years, 2–16 and 50–64 years, and 2–64 years). These extensions are evaluated incrementally on four base scenarios (no vaccination, risk group only with coverage as observed between 1995 and 2009, risk group and 65+, and risk group with 75 % coverage and 65+). Impact of vaccination is assessed using a transmission model built and parameterised from a previously published study. The study population is all individuals of all ages in England and Wales representing an average total of 52.6 million people over 14 influenza seasons (1995–2009).ResultsThe influenza programme (risk group and elderly) prior to 2013 is likely to be cost effective (incremental cost effectiveness ratio: 7,475 £/QALY, net benefit: 253 M£ [15–829]). Extension to any one of the low-risk target groups defined earlier is likely to be cost-effective. However, strategies that do not include vaccination of school-aged children are less likely to be cost-effective. The most efficient strategy is extension to the 5–16 year age group while universal vaccination (extension to all low-risk individuals over 2 years) will achieve the highest net benefit. While extension to the 2–16 year age group is likely to be very cost effective, the cost-effectiveness of extensions beyond 2–16 years is very uncertain. Extension to the 5–16 year age group would likely remain cost-effective even without herd immunity effects to other age groups. As our study includes a strong historical component, our results depend on the efficacy of the influenza vaccine remaining at levels similar to the ones achieved in the past over a long-period of time (assumed to vary between 28 % and 70 % depending of the circulating strains and age groups).ConclusionsMaking use of surveillance data from over a decade in conjunction with a dynamic model, we find that vaccination of children in the United Kingdom is likely to be highly cost-effective, not only for their own benefit but also to reduce the disease burden in the rest of the community.

Equine disease surveillance: quarterly summary

Equine influenza in England and ScotlandSignificant numbers of outbreaks of equine herpesvirus 1 neurological disease in the USASummary of surveillance testing, April to June 2014These are among matters discussed in...

The influence of changing host immunity on 1918–19 pandemic dynamics

The sociological and biological factors which gave rise to the three pandemic waves of Spanish influenza in England during 1918–19 are still poorly understood. Symptom reporting data available for a limited set of locations in England indicates that reinfection in multiple waves occurred, suggesting a role for loss of infection-acquired immunity. Here we explore the role that changes in host immunity, driven by a combination of within-host factors and viral evolution, may play in explaining weekly mortality data and wave-by-wave symptomatic attack-rates available for a subset of English cities. Our results indicate that changes in the phenotype of the pandemic virus are likely required to explain the closely spaced waves of infection, but distinguishing between the detailed contributions of viral evolution and changing adaptive immune responses to transmission rates is difficult given the dearth of sero-epidemiological and virological data available even for more contemporary pandemics. We find that a dynamical model in which pre-pandemic protection in older “influenza-experienced” cohorts is lost rapidly prior to the second wave provides the best fit to the mortality and symptom reporting data. Best fitting parameter estimates for such a model indicate that post-infection protection lasted of order months, while other statistical analyses indicate that population-age was inversely correlated with overall mortality during the herald wave. Our results suggest that severe secondary waves of pandemic influenza may be triggered by viral escape from pre-pandemic immunity, and thus that understanding the role of heterosubtypic or cross-protective immune responses to pandemic influenza may be key to controlling the severity of future influenza pandemics.

Mortality attributable to influenza in England and Wales prior to, during and after the 2009 pandemic.

Very different influenza seasons have been observed from 2008/09–2011/12 in England and Wales, with the reported burden varying overall and by age group. The objective of this study was to estimate the impact of influenza on all-cause and cause-specific mortality during this period. Age-specific generalised linear regression models fitted with an identity link were developed, modelling weekly influenza activity through multiplying clinical influenza-like illness consultation rates with proportion of samples positive for influenza A or B. To adjust for confounding factors, a similar activity indicator was calculated for Respiratory Syncytial Virus. Extreme temperature and seasonal trend were controlled for. Following a severe influenza season in 2008/09 in 65+yr olds (estimated excess of 13,058 influenza A all-cause deaths), attributed all-cause mortality was not significant during the 2009 pandemic in this age group and comparatively low levels of influenza A mortality were seen in post-pandemic seasons. The age shift of the burden of seasonal influenza from the elderly to young adults during the pandemic continued into 2010/11; a comparatively larger impact was seen with the same circulating A(H1N1)pdm09 strain, with the burden of influenza A all-cause excess mortality in 15–64 yr olds the largest reported during 2008/09–2011/12 (436 deaths in 15–44 yr olds and 1,274 in 45–64 yr olds). On average, 76% of seasonal influenza A all-age attributable deaths had a cardiovascular or respiratory cause recorded (average of 5,849 influenza A deaths per season), with nearly a quarter reported for other causes (average of 1,770 influenza A deaths per season), highlighting the importance of all-cause as well as cause-specific estimates. No significant influenza B attributable mortality was detected by season, cause or age group. This analysis forms part of the preparatory work to establish a routine mortality monitoring system ahead of introduction of the UK universal childhood seasonal influenza vaccination programme in 2013/14.

The burden of influenza in England by age and clinical risk group: A statistical analysis to inform vaccine policy

To assess the burden of influenza by age and clinical status and use this to inform evaluations of the age and risk-based influenza vaccination policy in the United Kingdom. Weekly laboratory reports for influenza and 7 other respiratory pathogens were extracted from the national database and used in a regression model to estimate the proportion of acute respiratory illness outcomes attributable to each pathogen. Influenza accounted for ∼10% of the attributed respiratory admissions and deaths in hospital. Healthy children under five had the highest influenza admission rate (1.9/1000). The presence of co-morbidities increased the admission rate by 5.7 fold for 5-14 year olds (from 0.1 to 0.56/1000), the relative risk declining to 1.8 fold in 65+ year olds (from 0.46 to 0.84/1000). The majority (72%) of influenza-attributable deaths in hospital occurred in 65+ year olds with co-morbidities. Mortality in children under 15 years was low with around 12 influenza-attributable deaths in hospital per year in England; the case fatality rate was substantially higher in risk than non-risk children. Infants under 6 months had the highest consultation and admission rates, around 70/1000 and 3/1000 respectively. Additional strategies are needed to reduce the remaining morbidity and mortality in the high-risk and elderly populations, and to protect healthy children currently not offered the benefits of vaccination.

Effectiveness of seasonal influenza vaccine in preventing medically attended influenza infection in England and Wales during the 2010/2011 season: a primary care-based cohort study

Estimates of seasonal influenza vaccine effectiveness (VE) are affected by factors such as the strain of the current circulating influenza virus and characteristics of the host. The objective of this study was to provide VE estimates for the 2010/2011 seasonal trivalent influenza vaccine (TIV) in preventing medically attended influenza in England and Wales for the season 2010/2011. A cohort study design was employed using electronic health records extracted from 104 GP practices in the Royal College of General Practitioners (RCGP) primary care sentinel network. Endpoints included influenza-like illness (ILI), lower respiratory tract infection (LTRI) as well as PCR-confirmed influenza from patients swabbed from practices participating in a swabbing scheme. Adjustment was made for age, month, underlying chronic condition, region and number of consultations in the 12months prior to the study period. In addition to the cohort analysis, a nested test-negative case-control analysis (TNCC) was carried out using the swab-negative results as controls. In the cohort analysis, VE against LRTI was -0·5% [95% CI: (-7·0%, 7·5%)], against ILI was 37·8% [95% CI: (32·3%, 43·0%)] and against PCR-confirmed influenza was 50·0% [95% CI:(25·9%, 65·6%)] for type A and 44·4% [95% CI: (10·1%, 65·6%)] for type B. Using the TNCC design, the type A VE was 56·5% [95% CI: (30·4%, 72·7%)] and for type B was 54·0% [95% CI: (21·0%, 73·3%)]. This study shows that the 2010/2011 TIV provided moderate protection against the circulating influenza strains for the 2010/2011 season. It also suggests that VE against the less specific diagnosis of ILI can be found, but less specific endpoints such as LRTI are not useful.

Estimating vaccine effectiveness against severe influenza in England and Scotland 2011/2012: applying the screening method to data from intensive care surveillance systems

Methods for estimating vaccine effectiveness (VE) against severe influenza are not well established. We used the screening method to estimate VE against influenza resulting in intensive care unit (ICU) admission in England and Scotland in 2011/2012. We extracted data on confirmed influenza ICU cases from severe influenza surveillance systems, and obtained their 2011/2012 trivalent influenza vaccine (TIV) status from primary care. We compared case vaccine uptake with population vaccine uptake obtained from routine monitoring systems, adjusting for age group, specific risk group, region and week. Of 60 influenza ICU cases reported, vaccination status was available for 56 (93%). Adjusted VE against ICU admission for those aged ≥ 65 years was -10% [95% confidence interval (CI) -207 to 60], consistent with evidence of poor protection from the 2011/2012 TIV in 2011/2012. Adjusted VE for those aged <65 years in risk groups was -296% (95% CI -930 to -52), suggesting significant residual confounding using the screening method in those subject to selective vaccination.

Socio-economic disparities in mortality due to pandemic influenza in England

This study examines variations in mortality between socio-economic groups due to the pandemic Influenza (H1N1) 2009 virus in England. We established a system to identify all deaths related to pandemic (H1N1) 2009 influenza. We collected the postcode of every individual who died, and through this determined the socio-economic deprivation, urban-rural characteristics and region of their residence. Across England, we were therefore able to examine how mortality rates varied by socio-economic group, between urban and rural areas, and between regions. People in the most deprived quintile of England's population had an age and sex-standardised mortality rate three times that experienced by the least deprived quintile (RR = 3.1, 95% CI 2.2-4.4). Mortality was also higher in urban areas than in rural areas (RR = 1.7, 95% CI 1.2-2.3). Mortality rates were similar between regions of the country. Tackling socio-economic health inequalities is a central concept within public health, but has not always been a part of emergency preparedness plans. These data demonstrate the opportunity to reduce the overall impact and narrow inequalities by considering socio-economic disparities in future pandemic planning.

A New Sentinel Surveillance System for Severe Influenza in England Shows a Shift in Age Distribution of Hospitalised Cases in the Post-Pandemic Period

BackgroundThe World Health Organization and European Centre for Disease Prevention and Control have highlighted the importance of establishing systems to monitor severe influenza. Following the H1N1 (2009) influenza pandemic, a sentinel network of 23 Trusts, the UK Severe Influenza Surveillance System (USISS), was established to monitor hospitalisations due to confirmed seasonal influenza in England. This article presents the results of the first season of operation of USISS in 2010/11.Methodology/Principal FindingsA case was defined as a person hospitalised with confirmed influenza of any type. Weekly aggregate numbers of hospitalised influenza cases, broken down by flu type and level of care, were submitted by participating Trusts. Cases in 2010/11 were compared to cases during the 2009 pandemic in hospitals with available surveillance data for both time periods (n = 19). An unexpected resurgence in seasonal A/H1N1 (2009) influenza activity in England was observed in December 2010 with reports of severe disease. Reported cases over the period of 4 October 2010 to 13 February 2011 were mostly due to influenza A/H1N1 (2009). One thousand and seventy-one cases of influenza A/H1N1 (2009) occurred over this period compared to 409 at the same Trusts over the 2009/10 pandemic period (1 April 2009 to 6 January 2010). Median age of influenza A/H1N1 (2009) cases in 2010/11 was 35 years, compared with 20 years during the pandemic (p = <0.0001).Conclusions/SignificanceThe Health Protection Agency successfully established a sentinel surveillance system for severe influenza in 2010/11, detecting a rise in influenza cases mirroring other surveillance indicators. The data indicate an upward shift in the age-distribution of influenza A/H1N1 (2009) during the 2010/11 influenza season as compared to the 2009/10 pandemic. Systems to enable the ongoing surveillance of severe influenza will be a key component in understanding and responding to the evolving epidemiology of influenza in the post-pandemic era.

Estimating the clinical impact of introducing paediatric influenza vaccination in England and Wales

Influenza causes a significant burden of disease each year in England and Wales, with the young and the elderly suffering the greatest burden. Children are recognised as playing an important role in the dissemination of the influenza virus. This study examines the population impact of implementing a programme of paediatric vaccination. A dynamic transmission model was used to simulate the impact of vaccination programmes with varying levels of coverage across pre-school and school age children. These analyses suggest that vaccinating as few as 50% of 2-18 year olds could result in a substantial reduction in the annual incidence of influenza related morbidity and mortality across the population. Herd immunity may extend this protection to the young and the elderly. It is assumed that such programmes would be implemented in concert with the current strategy of vaccinating the elderly and younger at risk groups with an inactivated vaccine. In England and Wales, paediatric vaccination of two to eighteen year olds reduced the estimated number of general practice consultations, hospitalisations and deaths arising from influenza A and B infections by up to 95%. This translates into an annual average reduction of approximately 52,000, 1500 and 1200 events, respectively. A policy of paediatric vaccination could significantly reduce the clinical burden of influenza in England and Wales, in all age groups, with the added value of herd immunity helping to protect the young and the elderly who are at highest risk of complications.

Mortality due to pandemic (H1N1) 2009 influenza in England: a comparison of the first and second waves

Deaths in England attributable to pandemic (H1N1) 2009 deaths were investigated through a mandatory reporting system. The pandemic came in two waves. The second caused greater population mortality than the first (5·4 vs. 1·6 deaths per million, P<0·001). Mortality was particularly high in those with chronic neurological disease, chronic heart disease and immune suppression (450, 100, and 94 deaths per million, respectively); significantly higher than in those with chronic respiratory disease (39 per million) and those with no risk factors (2·4 per million). Greater mortality in the second wave has been observed in all previous influenza pandemics. This time, the explanation appears to be behavioural. This emphasizes the importance of maintaining public and clinical awareness of risks associated with pandemic influenza beyond the initial high-profile period.

Changes in severity of 2009 pandemic A/H1N1 influenza in England: a Bayesian evidence synthesis

Objective To assess the impact of the 2009 A/H1N1 influenza pandemic in England during the two waves of activity up to end of February 2010 by estimating the probabilities of...

Age-specific incidence of A/H1N1 2009 influenza infection in England from sequential antibody prevalence data using likelihood-based estimation.

Estimating the age-specific incidence of an emerging pathogen is essential for understanding its severity and transmission dynamics. This paper describes a statistical method that uses likelihoods to estimate incidence from sequential serological data. The method requires information on seroconversion intervals and allows integration of information on the temporal distribution of cases from clinical surveillance. Among a family of candidate incidences, a likelihood function is derived by reconstructing the change in seroprevalence from seroconversion following infection and comparing it with the observed sequence of positivity among the samples. This method is applied to derive the cumulative and weekly incidence of A/H1N1 pandemic influenza in England during the second wave using sera taken between September 2009 and February 2010 in four age groups (1–4, 5–14, 15–24, 25–44 years). The highest cumulative incidence was in 5–14 year olds (59%, 95% credible interval (CI): 52%, 68%) followed by 1–4 year olds (49%, 95% CI: 38%, 61%), rates 20 and 40 times higher respectively than estimated from clinical surveillance. The method provides a more accurate and continuous measure of incidence than achieved by comparing prevalence in samples grouped by time period.