An intercountry comparison of the impact of the paediatric live attenuated influenza vaccine (LAIV) programme across the UK and the Republic of Ireland (ROI), 2010 to 2017.

Background: The universal paediatric live attenuated influenza vaccine (LAIV) programme commenced in the United Kingdom (UK) in 2013/2014. Since 2014/2015, all pre-school and primary school children in Scotland and Northern Ireland have been offered the vaccine. England and Wales incrementally introduced the programme with additional school age cohorts being vaccinated each season. The Republic of Ireland (ROI) had no universal paediatric programme before 2017. We evaluated the potential population impact of vaccinating primary school-aged children across the five countries up to the 2016/2017 influenza season. Methods: We compared rates of primary care influenza-like illness (ILI) consultations, confirmed influenza intensive care unit (ICU) admissions, and all-cause excess mortality using standardised methods. To further quantify the impact, a scoring system was developed where each weekly rate/z-score was scored and summed across each influenza season according to the weekly respective threshold experienced in each country. Results: Results highlight ILI consultation rates in the four seasons' post-programme, breached baseline thresholds once or not at all in Scotland and Northern Ireland; in three out of the four seasons in England and Wales; and in all four seasons in ROI. No differences were observed in the seasons' post-programme introduction between countries in rates of ICU and excess mortality, although reductions in influenza-related mortality were seen. The scoring system also reflected similar results overall. Conclusions: Findings of this study suggest that LAIV vaccination of primary school age children is associated with population-level benefits, particularly in reducing infection incidence in primary care.

Health and economic impact of seasonal influenza mass vaccination strategies in European settings: A mathematical modelling and cost-effectiveness analysis.

INTRODUCTION: Despite seasonal influenza vaccination programmes in most countries targeting individuals aged ≥ 65 (or ≥ 55) years and high risk-groups, significant disease burden remains. We explored the impact and cost-effectiveness of 27 vaccination programmes targeting the elderly and/or children in eight European settings (n = 205.8 million). METHODS: We used an age-structured dynamic-transmission model to infer age- and (sub-)type-specific seasonal influenza virus infections calibrated to England, France, Ireland, Navarra, The Netherlands, Portugal, Scotland, and Spain between 2010/11 and 2017/18. The base-case vaccination scenario consisted of non-adjuvanted, non-high dose trivalent vaccines (TV) and no universal paediatric vaccination. We explored i) moving the elderly to "improved" (i.e., adjuvanted or high-dose) trivalent vaccines (iTV) or non-adjuvanted non-high-dose quadrivalent vaccines (QV); ii) adopting mass paediatric vaccination with TV or QV; and iii) combining the elderly and paediatric strategies. We estimated setting-specific costs and quality-adjusted life years (QALYs) gained from the healthcare perspective, and discounted QALYs at 3.0%. RESULTS: In the elderly, the estimated numbers of infection per 100,000 population are reduced by a median of 261.5 (range across settings: 154.4, 475.7) when moving the elderly to iTV and by 150.8 (77.6, 262.3) when moving them to QV. Through indirect protection, adopting mass paediatric programmes with 25% uptake achieves similar reductions in the elderly of 233.6 using TV (range: 58.9, 425.6) or 266.5 using QV (65.7, 477.9), with substantial health gains from averted infections across ages. At €35,000/QALY gained, moving the elderly to iTV plus adopting mass paediatric QV programmes provides the highest mean net benefits and probabilities of being cost-effective in all settings and paediatric coverage levels. CONCLUSION: Given the direct and indirect protection, and depending on the vaccine prices, model results support a combination of having moved the elderly to an improved vaccine and adopting universal paediatric vaccination programmes across the European settings.

Invasive Group B Streptococcus Disease With Recurrence and in Multiples: Towards a Better Understanding of GBS Late-Onset Sepsis.

Group B Streptococcus (GBS) is a common intestinal colonizer during the neonatal period, but also may cause late-onset sepsis or meningitis in up to 0.5% of otherwise healthy colonized infants after day 3 of life. Transmission routes and risk factors of this late-onset form of invasive GBS disease (iGBS) are not fully understood. Cases of iGBS with recurrence (n=25) and those occurring in parallel in twins/triplets (n=32) from the UK and Ireland (national surveillance study 2014/15) and from Germany and Switzerland (retrospective case collection) were analyzed to unravel shared (in affected multiples) or fixed (in recurrent disease) risk factors for GBS disease. The risk of iGBS among infants from multiple births was high (17%), if one infant had already developed GBS disease. The interval of onset of iGBS between siblings was 4.5 days and in recurrent cases 12.5 days. Disturbances of the individual microbiome, including persistence of infectious foci are suggested e.g. by high usage of perinatal antibiotics in mothers of affected multiples, and by the association of an increased risk of recurrence with a short term of antibiotics [aOR 4.2 (1.3-14.2), P=0.02]. Identical GBS serotypes in both recurrent infections and concurrently infected multiples might indicate a failed microbiome integration of GBS strains that are generally regarded as commensals in healthy infants. The dynamics of recurrent GBS infections or concurrent infections in multiples suggest individual patterns of exposure and fluctuations in host immunity, causing failure of natural niche occupation.

Uncovering Infant Group B Streptococcal (GBS) Disease Clusters in the United Kingdom and Ireland Through Genomic Analysis: A Population-based Epidemiological Study.

BACKGROUND: The true frequency of hospital outbreaks of invasive group B streptococcal (iGBS; Streptococcus agalactiae) disease in infants is unknown. We used whole genome sequencing (WGS) of iGBS isolates collected during a period of enhanced surveillance of infant iGBS disease in the UK and Ireland to determine the number of clustered cases. METHODS: Potentially linked iGBS cases from infants with early (<7 days of life) or late-onset (7-89 days) disease were identified from WGS data (HiSeq 2500 platform, Illumina) from clinical sterile site isolates collected between 04/2014 and 04/2015. We assessed time and place of cases to determine a single-nucleotide polymorphism (SNP) difference threshold for clustered cases. Case details were augmented through linkage to national hospital admission data and hospital record review by local microbiologists. RESULTS: Analysis of sequences indicated a cutoff of ≤5 SNP differences to define iGBS clusters. Among 410 infant iGBS isolates, we identified 7 clusters (4 genetically identical pairs with 0 SNP differences, 1 pair with 3 SNP differences, 1 cluster of 4 cases with ≤1 SNP differences) of which 4 clusters were uncovered for the first time. The clusters comprised 16 cases, of which 15 were late-onset (of 192 late-onset cases with sequenced isolates) and 1 an early-onset index case. Serial intervals between cases ranged from 0 to 59 (median 12) days. CONCLUSIONS: Approximately 1 in 12 late-onset infant iGBS cases were part of a hospital cluster. Over half of the clusters were previously undetected, emphasizing the importance of routine submission of iGBS isolates to reference laboratories for cluster identification and genomic confirmation.

Community-Based Antibiotic Prescribing Attributable to Respiratory Syncytial Virus and Other Common Respiratory Viruses in Young Children: A Population-Based Time-series Study of Scottish Children.

BACKGROUND: Inappropriate antibiotic prescribing, such as for viral illness, remains common in primary care. The objective of this study was to estimate the proportion of community-prescribed antibiotics to children aged less than 5 years attributable to common respiratory viruses. METHODS: We fitted time-series negative binomial models to predict weekly antibiotic prescribing rates from positive viral pathogen tests for the period 1 April 2009 through 27 December 2017 using comprehensive, population-based administrative data for all children (<5 years) living in Scotland. Multiple respiratory viral pathogens were considered, including respiratory syncytial virus (RSV), influenza, human metapneumovirus (HMPV), rhinovirus, and human parainfluenza (HPIV) types 1-4. We estimated the proportion of antibiotic prescriptions explained by virus circulation according to type of virus, by age group, presence of high-risk chronic conditions, and antibiotic class. RESULTS: We included data on 6 066 492 antibiotic prescriptions among 452 877 children. The antibiotic-prescribing rate among all Scottish children (<5 years) was 609.7 per 1000 child-years. Our final model included RSV, influenza, HMPV, HPIV-1, and HPIV-3. An estimated 6.9% (95% confidence interval, 5.6-8.3%), 2.4% (1.7-3.1%), and 2.3% (.8-3.9%) of antibiotics were attributable to RSV, influenza, and HMPV, respectively. RSV was consistently associated with the highest proportion of prescribed antibiotics, particularly among children without chronic conditions and for amoxicillin and macrolide prescriptions. CONCLUSIONS: Nearly 14% of antibiotics prescribed to children in this study were estimated to be attributable to common viruses for which antibiotics are not recommended. A future RSV vaccine could substantially reduce unnecessary antibiotic prescribing among children.

The experience of point-of-care testing for influenza in Scotland in 2017/18 and 2018/19 - no gain without pain.

BackgroundDuring the 2017/18 and 2018/19 influenza seasons, molecular amplification-based point-of-care tests (mPOCT) were introduced in Scotland to aid triaging respiratory patients for hospital admission, yet communication of results to national surveillance was unaccounted for.AimThis retrospective study aims to describe steps taken to capture mPOCT data and assess impact on influenza surveillance.MethodsQuestionnaires determined mPOCT usage in 2017/18 and 2018/19. Searches of the Electronic Communication of Surveillance in Scotland (ECOSS) database were performed and compared with information stored in laboratory information management systems. Effect of incomplete data on surveillance was determined by comparing routine against enhanced data and assessing changes in influenza activity levels determined by the moving epidemic method.ResultsThe number of areas employing mPOCT increased over the two seasons (6/14 in 2017/18 and 8/14 in 2018/19). Analysis of a small number of areas (n = 3) showed capture of positive mPOCT results in ECOSS improved between seasons and remained high (> 94%). However, capture of negative results was incomplete. Despite small discrepancies in weekly activity assessments, routine data were able to identify trend, start, peak and end of both influenza seasons.ConclusionThis study has shown an improvement in capture of data from influenza mPOCT and has highlighted issues that need to be addressed for results to be accurately captured in national surveillance. With the clear benefit to patient management we suggest careful consideration should be given to the connectivity aspects of the technology in order to ensure minimal impact on national surveillance.

Implementation of the United Kingdom's childhood influenza national vaccination programme: A review of clinical impact and lessons learned over six influenza seasons.

In 2012, the Joint Committee on Vaccination and Immunisation recommended that the United Kingdom's (UK) National Vaccination Programme (NVP) for influenza was extended to include healthy children and adolescents aged 2 to <17 years. Previously, the UK's NVP focused on seasonal vaccination of the elderly and people (including children) with underlying health conditions that put them at high risk of hospitalisation if they contracted influenza. The extension of the UK's programme began in the 2013/14 influenza season through the vaccination of children aged 2-3 years in primary care across England and the devolved administrations of Scotland, Wales, and Northern Ireland. School-aged children were generally vaccinated in a school setting, with several implementation pilots in England and Scotland. Due to the scale of the programme, it has been phased in over several years and expanded to include broader childhood age groups. This article reviews the experiences from the implementation of the UK's childhood influenza NVP over the first six influenza seasons (between 2013/14 and 2018/19) from the perspectives of England, Scotland, Wales, and Northern Ireland. The processes used to deliver the vaccination programme in general practice and the school-based setting are described in terms of governance, contracting, workforce management, communication, administrative tasks, vaccination sessions, vaccine supply and distribution, and surveillance. In addition, the available evidence regarding the clinical impact of the UK's childhood influenza NVP over the first six influenza seasons is reviewed. We also share lessons learned from the programme and recommendations to provide guidance to other countries looking to implement childhood influenza vaccination programmes.

End of season influenza vaccine effectiveness in primary care in adults and children in the United Kingdom in 2018/19.

2018/19 was the first season of introduction of a newly licensed adjuvanted influenza vaccine (aTIV) for adults aged 65 years and over and the sixth season in the roll-out of a childhood influenza vaccination programme with a quadrivalent live attenuated influenza vaccine (LAIV). The season saw mainly A(H1N1)pdm09 and latterly A(H3N2) circulation. End-of-season adjusted vaccine effectiveness (aVE) estimates against laboratory confirmed influenza infection in primary care were calculated using the test negative case control method adjusting for key confounders. End-of-season aVE was 44.3% (95% CI: 26.8, 57.7) against all laboratory-confirmed influenza; 45.7% (95% CI: 26.0, 60.1) against influenza A(H1N1)pdm09 and 35.1% (95% CI: -3.7,59.3) against A(H3N2). Overall aVE was 49.9% (95%CI: -13.7, 77.9) for all those ≥ 65 years of age and 62.0% (95% CI: 3.4, 85.0) for those who received aTIV. Overall aVE for 2-17 year olds receiving LAIV was 48.6% (95% CI: -4.4, 74.7). The paper provides evidence of overall significant influenza VE in 2018/19, most notably against influenza A(H1N1)pdm09, however, as seen in 2017/18, there was reduced, non-significant VE against A(H3N2). aTIV provided significant protection for those 65 years of age and over.

Virus-virus interactions impact the population dynamics of influenza and the common cold.

The human respiratory tract hosts a diverse community of cocirculating viruses that are responsible for acute respiratory infections. This shared niche provides the opportunity for virus-virus interactions which have the potential to affect individual infection risks and in turn influence dynamics of infection at population scales. However, quantitative evidence for interactions has lacked suitable data and appropriate analytical tools. Here, we expose and quantify interactions among respiratory viruses using bespoke analyses of infection time series at the population scale and coinfections at the individual host scale. We analyzed diagnostic data from 44,230 cases of respiratory illness that were tested for 11 taxonomically broad groups of respiratory viruses over 9 y. Key to our analyses was accounting for alternative drivers of correlated infection frequency, such as age and seasonal dependencies in infection risk, allowing us to obtain strong support for the existence of negative interactions between influenza and noninfluenza viruses and positive interactions among noninfluenza viruses. In mathematical simulations that mimic 2-pathogen dynamics, we show that transient immune-mediated interference can cause a relatively ubiquitous common cold-like virus to diminish during peak activity of a seasonal virus, supporting the potential role of innate immunity in driving the asynchronous circulation of influenza A and rhinovirus. These findings have important implications for understanding the linked epidemiological dynamics of viral respiratory infections, an important step towards improved accuracy of disease forecasting models and evaluation of disease control interventions.

Estimation of temporal covariances in pathogen dynamics using Bayesian multivariate autoregressive models.

It is well recognised that animal and plant pathogens form complex ecological communities of interacting organisms within their hosts, and there is growing interest in the health implications of such pathogen interactions. Although community ecology approaches have been used to identify pathogen interactions at the within-host scale, methodologies enabling robust identification of interactions from population-scale data such as that available from health authorities are lacking. To address this gap, we developed a statistical framework that jointly identifies interactions between multiple viruses from contemporaneous non-stationary infection time series. Our conceptual approach is derived from a Bayesian multivariate disease mapping framework. Importantly, our approach captures within- and between-year dependencies in infection risk while controlling for confounding factors such as seasonality, demographics and infection frequencies, allowing genuine pathogen interactions to be distinguished from simple correlations. We validated our framework using a broad range of synthetic data. We then applied it to diagnostic data available for five respiratory viruses co-circulating in a major urban population between 2005 and 2013: adenovirus, human coronavirus, human metapneumovirus, influenza B virus and respiratory syncytial virus. We found positive and negative covariances indicative of epidemiological interactions among specific virus pairs. This statistical framework enables a community ecology perspective to be applied to infectious disease epidemiology with important utility for public health planning and preparedness.

End of season influenza vaccine effectiveness in adults and children in the United Kingdom in 2017/18.

BackgroundIn the United Kingdom (UK), in recent influenza seasons, children are offered a quadrivalent live attenuated influenza vaccine (LAIV4), and eligible adults mainly trivalent inactivated vaccine (TIV).AimTo estimate the UK end-of-season 2017/18 adjusted vaccine effectiveness (aVE) and the seroprevalence in England of antibodies against influenza viruses cultured in eggs or tissue.MethodsThis observational study employed the test-negative case-control approach to estimate aVE in primary care. The population-based seroprevalence survey used residual age-stratified samples.ResultsInfluenza viruses A(H3N2) (particularly subgroup 3C.2a2) and B (mainly B/Yamagata/16/88-lineage, similar to the quadrivalent vaccine B-virus component but mismatched to TIV) dominated. All-age aVE was 15% (95% confidence interval (CI): -6.3 to 32) against all influenza; -16.4% (95% CI: -59.3 to 14.9) against A(H3N2); 24.7% (95% CI: 1.1 to 42.7) against B and 66.3% (95% CI: 33.4 to 82.9) against A(H1N1)pdm09. For 2-17 year olds, LAIV4 aVE was 26.9% (95% CI: -32.6 to 59.7) against all influenza; -75.5% (95% CI: -289.6 to 21) against A(H3N2); 60.8% (95% CI: 8.2 to 83.3) against B and 90.3% (95% CI: 16.4 to 98.9) against A(H1N1)pdm09. For ≥ 18 year olds, TIV aVE against influenza B was 1.9% (95% CI: -63.6 to 41.2). The 2017 seroprevalence of antibody recognising tissue-grown A(H3N2) virus was significantly lower than that recognising egg-grown virus in all groups except 15-24 year olds.ConclusionsOverall aVE was low driven by no effectiveness against A(H3N2) possibly related to vaccine virus egg-adaption and a new A(H3N2) subgroup emergence. The TIV was not effective against influenza B. LAIV4 against influenza B and A(H1N1)pdm09 was effective.

Modelling the population effectiveness of the national seasonal influenza vaccination programme in Scotland: The impact of targeting all individuals aged 65 years and over.

BACKGROUND: For the last 17 years, the UK has employed a routine influenza vaccination programme with the aim of reducing the spread of seasonal influenza. In mid-2000, the programme moved from a purely risk-based approach to a risk and age group-targeted approach with all those aged 65+ years being included. To date, there has been no assessment of the population effectiveness of this age-targeted policy in Scotland. OBJECTIVES: Statistical modelling techniques were used to determine what impact the routine vaccination of those aged 65+ years has had on influenza-related morbidity and mortality in Scotland. METHODS: Two Poisson regression models were developed using weekly counts of all-cause mortality, cause-specific mortality and emergency hospitalisations for the period 1981-2012, one using week-in-year and the other using temperature to capture the seasonal variability in mortality/hospitalisations. These models were used to determine the number of excess deaths/hospitalisations associated with the introduction of the local risk and age-based vaccination programme in 2000. RESULTS: Routinely vaccinating those aged 65+ years is associated with a reduction in excess all-cause mortality, cardiovascular and COPD-related mortality and COPD-related hospitalisations. Our analysis suggests that using the week-in-year model, on average, 732 (95% CI 66-1398) deaths from all causes, 248 (95% CI 10-486) cardiovascular-related deaths, 123 (95% CI 28-218) COPD-related deaths and 425 (95% CI 258-592) COPD-related hospitalisations have been prevented each flu season among the those aged 65+. Similar results were found using the temperature model. There was no evidence to suggest that the change in policy was associated with reductions in influenza/pneumonia-related mortality or influenza/cardiovascular-related hospitalisations. CONCLUSIONS: Routinely vaccinating those aged 65+ years appears to have reduced influenza-related morbidity and mortality in Scotland. With the childhood vaccination programme well underway, these data provide an importance benchmark which can be used to accurately assess the impact of this new seasonal influenza vaccination programme.

Group B streptococcal disease in UK and Irish infants younger than 90 days, 2014-15: a prospective surveillance study.

BACKGROUND: Group B streptococcus is a leading cause of serious infection in young infants in many countries worldwide. We aimed to define the burden and clinical features of invasive group B streptococcal disease in infants younger than 90 days in the UK and Ireland, together with the characteristics of disease-causing isolates. METHODS: Prospective, active national surveillance of invasive group B streptococcal disease in infants younger than 90 days was done from April 1, 2014, to April 30, 2015, through the British Paediatric Surveillance Unit, microbiology reference laboratories, and national public health agencies in the UK and Ireland. Early onset was defined as disease in the first 6 days of life and late onset was defined as 7-89 days of life. Incidence was calculated using livebirths in 2014 (after adjustment for the 13-month surveillance period). Isolates were characterised by serotyping, multilocus sequence typing, and antimicrobial susceptibility testing. FINDINGS: 856 cases of group B streptococcus were identified in 2014-15, an incidence of 0·94 per 1000 livebirths (95% CI 0·88-1·00). Incidence for early-onset disease (n=517) was 0·57 per 1000 livebirths (95% CI 0·52-0·62), and for late-onset disease (n=339) was 0·37 per 1000 livebirths (0·33-0·41). 53 infants died (case fatality rate 6·2%), of whom 27 had early-onset disease (case fatality rate 5·2%) and 26 had late-onset disease (case fatality rate 7·7%). The predominant serotypes were III (241 [60%] of 402 serotyped isolates) and Ia (69 [17%]); five serotypes (Ia, Ib, II, III, V) accounted for 377 (94%) of all serotyped isolates. INTERPRETATION: The incidence of invasive infant group B streptococcal disease in the UK and Ireland has increased since a comparable study done in 2000-01. The burden of early-onset disease has not declined despite the introduction of national prevention guidelines. New strategies for prevention are required. FUNDING: Meningitis Now.

Uptake and effectiveness of influenza vaccine in those aged 65 years and older in the United Kingdom, influenza seasons 2010/11 to 2016/17.

BackgroundIn 2016/17, seasonal influenza vaccine was less effective in those aged 65 years and older in the United Kingdom. We describe the uptake, influenza-associated mortality and adjusted vaccine effectiveness (aVE) in this age group over influenza seasons 2010/11-2016/17. Methods: Vaccine uptake in 2016/17 and five previous seasons were measured using a sentinel general practitioners cohort in England; the test-negative case-control design was used to estimate pooled aVE by subtype and age group against laboratory-confirmed influenza in primary care from 2010-2017. Results: Vaccine uptake was 64% in 65-69-year-olds, 74% in 70-74-year-olds and 80% in those aged 75 and older. Overall aVE was 32.5% (95% CI: 11.6 to 48.5); aVE by sub-type was 60.8% (95% CI: 33.9 to 76.7) and 50.0% (95% CI: 21.6 to 68.1) against influenza A(H1N1)pdm09 and influenza B, respectively, but only 5.6% (95% CI: - 39.2 to 35.9) against A(H3N2). Against all laboratory-confirmed influenza aVE was 45.2% (95% CI: 25.1 to 60.0) in 65-74 year olds; - 26.2% (95% CI: - 149.3 to 36.0) in 75-84 year olds and - 3.2% (95% CI: - 237.8 to 68.5) in those aged 85 years and older. Influenza-attributable mortality was highest in seasons dominated by A(H3N2). Conclusions: Vaccine uptake with non-adjuvanted, normal-dose vaccines remained high, with evidence of effectiveness against influenza A(H1N1)pdm09 and B, though poor against A(H3N2), particularly in those aged 75 years and older. Forthcoming availability of newly licensed vaccines with wider use of antivirals can potentially further improve prevention and control of influenza in this group.

Moving epidemic method (MEM) applied to virology data as a novel real time tool to predict peak in seasonal influenza healthcare utilisation. The Scottish experience of the 2017/18 season to date.

Scotland observed an unusual influenza A(H3N2)-dominated 2017/18 influenza season with healthcare services under significant pressure. We report the application of the moving epidemic method (MEM) to virology data as a tool to predict the influenza peak activity period and peak week of swab positivity in the current season. This novel MEM application has been successful locally and is believed to be of potential use to other countries for healthcare planning and building wider community resilience.

Genome sequence analysis of emm89 Streptococcus pyogenes strains causing infections in Scotland, 2010-2016.

PURPOSE: Strains of type emm89 Streptococcus pyogenes have recently increased in frequency as a cause of human infections in several countries in Europe and North America. This increase has been molecular epidemiologically linked with the emergence of a new genetically distinct clone, designated clade 3. We sought to extend our understanding of this epidemic behavior by the genetic characterization of type emm89 strains responsible in recent years for an increased frequency of infections in Scotland. METHODOLOGY: We sequenced the genomes of a retrospective cohort of 122 emm89 strains recovered from patients with invasive and noninvasive infections throughout Scotland during 2010 to 2016. RESULTS: All but one of the 122 emm89 infection isolates are of the recently emerged epidemic clade 3 clonal lineage. The Scotland isolates are closely related to and not genetically distinct from recent emm89 strains from England, they constitute a single genetic population. CONCLUSIONS: The clade 3 clone causes virtually all-contemporary emm89 infections in Scotland. These findings add Scotland to a growing list of countries of Europe and North America where, by whole genome sequencing, emm89 clade 3 strains have been demonstrated to be the cause of an ongoing epidemic of invasive infections and to be genetically related due to descent from a recent common progenitor.

End-of-season influenza vaccine effectiveness in adults and children, United Kingdom, 2016/17.

IntroductionThe United Kingdom is in the fourth season of introducing a universal childhood influenza vaccine programme. The 2016/17 season saw early influenza A(H3N2) virus circulation with care home outbreaks and increased excess mortality particularly in those 65 years or older. Virus characterisation data indicated emergence of genetic clusters within the A(H3N2) 3C.2a group which the 2016/17 vaccine strain belonged to. Methods: The test-negative case-control (TNCC) design was used to estimate vaccine effectiveness (VE) against laboratory confirmed influenza in primary care. Results: Adjusted end-of-season vaccine effectiveness (aVE) estimates were 39.8% (95% confidence interval (CI): 23.1 to 52.8) against all influenza and 40.6% (95% CI: 19.0 to 56.3) in 18-64-year-olds, but no significant aVE in ≥ 65-year-olds. aVE was 65.8% (95% CI: 30.3 to 83.2) for 2-17-year-olds receiving quadrivalent live attenuated influenza vaccine. Discussion: The findings continue to provide support for the ongoing roll-out of the paediatric vaccine programme, with a need for ongoing evaluation. The importance of effective interventions to protect the ≥ 65-year-olds remains.

Excess all-cause and influenza-attributable mortality in Europe, December 2016 to February 2017.

Since December 2016, excess all-cause mortality was observed in many European countries, especially among people aged ≥ 65 years. We estimated all-cause and influenza-attributable mortality in 19 European countries/regions. Excess mortality was primarily explained by circulation of influenza virus A(H3N2). Cold weather snaps contributed in some countries. The pattern was similar to the last major influenza A(H3N2) season in 2014/15 in Europe, although starting earlier in line with the early influenza season start.

Effectiveness of seasonal influenza vaccine for adults and children in preventing laboratory-confirmed influenza in primary care in the United Kingdom: 2015/16 end-of-season results.

The United Kingdom (UK) is in the third season of introducing universal paediatric influenza vaccination with a quadrivalent live attenuated influenza vaccine (LAIV). The 2015/16 season in the UK was initially dominated by influenza A(H1N1)pdm09 and then influenza of B/Victoria lineage, not contained in that season's adult trivalent inactivated influenza vaccine (IIV). Overall adjusted end-of-season vaccine effectiveness (VE) was 52.4% (95% confidence interval (CI): 41.0-61.6) against influenza-confirmed primary care consultation, 54.5% (95% CI: 41.6-64.5) against influenza A(H1N1)pdm09 and 54.2% (95% CI: 33.1-68.6) against influenza B. In 2-17 year-olds, adjusted VE for LAIV was 57.6% (95% CI: 25.1 to 76.0) against any influenza, 81.4% (95% CI: 39.6-94.3) against influenza B and 41.5% (95% CI: -8.5 to 68.5) against influenza A(H1N1)pdm09. These estimates demonstrate moderate to good levels of protection, particularly against influenza B in children, but relatively less against influenza A(H1N1)pdm09. Despite lineage mismatch in the trivalent IIV, adults younger than 65 years were still protected against influenza B. These results provide reassurance for the UK to continue its influenza immunisation programme planned for 2016/17.

Effectiveness of seasonal influenza vaccine in preventing laboratory-confirmed influenza in primary care in the United Kingdom: 2015/16 mid-season results.

In 2015/16, the influenza season in the United Kingdom was dominated by influenza A(H1N1)pdm09 circulation. Virus characterisation indicated the emergence of genetic clusters, with the majority antigenically similar to the current influenza A(H1N1)pdm09 vaccine strain. Mid-season vaccine effectiveness (VE) estimates show an adjusted VE of 41.5% (95% confidence interval (CI): 3.0-64.7) against influenza-confirmed primary care consultations and of 49.1% (95% CI: 9.3-71.5) against influenza A(H1N1)pdm09. These estimates show levels of protection similar to the 2010/11 season, when this strain was first used in the seasonal vaccine.