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BackgroundThe 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.MethodsPotentially linked iGBS cases from infants with early (ResultsAnalysis 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.ConclusionsApproximately 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.

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 ( Results We included data on 6 066 492 antibiotic prescriptions among 452 877 children. The antibiotic-prescribing rate among all Scottish children ( 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.

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 allcause 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 – 1,398) 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.

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.

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 to17 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.

PurposeStrains 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.MethodologyWe 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.ResultsAll 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.ConclusionsThe 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.

Significance When multiple pathogens cocirculate this can lead to competitive or cooperative forms of pathogen–pathogen interactions. It is believed that such interactions occur among cold and flu viruses, perhaps through broad-acting immunity, resulting in interlinked epidemiological patterns of infection. However, to date, quantitative evidence has been limited. We analyzed a large collection of diagnostic reports collected over multiple years for 11 respiratory viruses. Our analyses provide strong statistical support for the existence of interactions among respiratory viruses. Using computer simulations, we found that very short-lived interferences may explain why common cold infections are less frequent during flu seasons. Improved understanding of how the epidemiology of viral infections is interlinked can help improve disease forecasting and evaluation of disease control interventions., 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.

Introduction The 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.

Background In 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). Aim To 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. Methods This 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. Results Influenza 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. Conclusions Overall 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.

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., Author summary Disease-causing microorganisms, including viruses, bacteria, protozoa and fungi, form complex communities within animals and plants. These microorganisms can coexist harmoniously or even beneficially, or they may competitively interact for host resources. Well-studied examples include interactions between viruses and bacteria in the respiratory tract. Whilst ecological studies have revealed that some pathogens do interact within their hosts, identifying interactions from available population scale data from health authorities is challenging. This is exacerbated by a lack of large-scale data describing the infection patterns of multiple pathogens within single populations over long time frames. Furthermore, methods for evaluating whether infection frequencies of different pathogens fluctuate together or not over time cannot readily account for alternative explanations. For example, human pathogens may have related seasonal patterns depending on the age groups they infect and the weather conditions they survive in, and not because they are interacting. We developed a robust statistical framework to identify pathogen-pathogen interactions from population scale diagnostic data. This framework serves as a crucial step in identifying such important interactions and will guide new studies to elucidate their underpinning mechanisms. This will have important consequences for public health preparedness and the design of effective disease control interventions.

Objectives: Weekly monitoring of European all-cause excess mortality, the EuroMOMO network, observed high excess mortality during the influenza B/Yamagata dominated 2017/18 winter season, especially among elderly. We describe all-cause excess and influenza-attributable mortality during the season 2017/18 in Europe. Methods: Based on weekly reporting of mortality from 24 European countries or sub-national regions, representing 60% of the European population excluding the Russian and Turkish parts of Europe, we estimated age stratified all-cause excess morality using the EuroMOMO model. In addition, age stratified all-cause influenza-attributable mortality was estimated using the FluMOMO algorithm, incorporating influenza activity based on clinical and virological surveillance data, and adjusting for extreme temperatures. Results: Excess mortality was mainly attributable to influenza activity from December 2017 to April 2018, but also due to exceptionally low temperatures in February-March 2018. The pattern and extent of mortality excess was similar to the previous A(H3N2) dominated seasons, 2014/15 and 2016/17. The 2017/18 overall all-cause influenza-attributable mortality was estimated to be 25.4 (95%CI 25.0-25.8) per 100,000 population; 118.2 (116.4-119.9) for persons aged 65. Extending to the European population this translates into over-all 152,000 deaths. Conclusions: The high mortality among elderly was unexpected in an influenza B dominated season, which commonly are considered to cause mild illness, mainly among children. Even though A(H3N2) also circulated in the 2017/18 season and may have contributed to the excess mortality among the elderly, the common perception of influenza B only having a modest impact on excess mortality in the older population may need to be reconsidered. info:eu-repo/semantics/publishedVersion

Background In 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.

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

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. info:eu-repo/semantics/publishedVersion

Summary 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.

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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.

Background Public Health England (PHE) coordinates a suite of real-time national syndromic surveillance systems monitoring general practice, emergency department and remote health advice data. We describe the development and informal evaluation of a new syndromic surveillance system using NHS 111 remote health advice data. Methods NHS 111 syndromic indicators were monitored daily at national and local level. Statistical models were applied to daily data to identify significant exceedances; statistical baselines were developed for each syndrome and area using a multi-level hierarchical mixed effects model. Results Between November 2013 and October 2014, there were on average 19 095 NHS 111 calls each weekday and 43 084 each weekend day in the PHE dataset. There was a predominance of females using the service (57%); highest percentage of calls received was in the age group 1-4 years (14%). This system was used to monitor respiratory and gastrointestinal infections over the winter of 2013-14, the potential public health impact of severe flooding across parts of southern England and poor air quality episodes across England in April 2014. Conclusions This new system complements and supplements the existing PHE syndromic surveillance systems and is now integrated into the routine daily processes that form this national syndromic surveillance service.

Wagner, A P McKenzie, E Robertson, C McMenamin, J Reynolds, A Murdoch, H eng Research Support, Non-U.S. Gov't Sweden 2013/04/19 06:00 Euro Surveill. 2013 Apr 11;18(15):20451.; International audience; Mortality monitoring systems are important for gauging the effect of influenza and other wide ranging health threats. We present the daily all-cause mortality monitoring system routinely used in Scotland, which differs from others by using two different statistical models for calculating expected mortality. The first model is an extended Serfling model, which captures annual seasonality in mortality using sine and cosine terms, and is frequently seen in other systems. Serfling models fit to summer seasonality well, but not to the winter peak. Thus, during the winter, there are frequent 'excesses', higher than expected mortality, making it harder to directly judge if winter mortality is higher than in previous years. The second model, a Generalised Additive Model, resolves this by allowing a more flexible seasonal pattern that includes the winter peak. Thus, excesses under the second model directly indicate if winter mortality is higher than in previous years, useful, for example, in judging if a new strain of seasonal influenza is more likely to produce death than previous ones. As common in all-cause mortality monitoring systems, the Scottish system uses a reporting delay correction: we discuss the difficulties of interpretation when such a correction is used and possible avenues for future work that may address these difficulties.