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England has recently started a new paediatric influenza vaccine programme using a live-attenuated influenza vaccine (LAIV). There is uncertainty over how well the vaccine protects against more severe end-points. A test-negative case–control study was used to estimate vaccine effectiveness (VE) in vaccine-eligible children aged 2–16 years of age in preventing laboratory-confirmed influenza hospitalisation in England in the 2015–2016 season using a national sentinel laboratory surveillance system. Logistic regression was used to estimate the VE with adjustment for sex, risk-group, age group, region, ethnicity, deprivation and month of sample collection. A total of 977 individuals were included in the study (348 cases and 629 controls). The overall adjusted VE for all study ages and vaccine types was 33.4% (95% confidence interval (CI) 2.3–54.6) after adjusting for age group, sex, index of multiple deprivation, ethnicity, region, sample month and risk group. Risk group was shown to be an important confounder. The adjusted VE for all influenza types for the live-attenuated vaccine was 41.9% (95% CI 7.3–63.6) and 28.8% (95% CI −31.1 to 61.3) for the inactivated vaccine. The study provides evidence of the effectiveness of influenza vaccination in preventing hospitalisation due to laboratory-confirmed influenza in children in 2015–2016 and continues to support the rollout of the LAIV childhood programme.
Influenza and respiratory syncytial virus (RSV) are common causes of respiratory tract infections and place a burden on health services each winter. Systems to describe the timing and intensity of such activity will improve the public health response and deployment of interventions to these pressures. Here we develop early warning and activity intensity thresholds for monitoring influenza and RSV using two novel data sources: general practitioner out-of-hours consultations (GP OOH) and telehealth calls (NHS 111). Moving Epidemic Method (MEM) thresholds were developed for winter 2017–2018. The NHS 111 cold/flu threshold was breached several weeks in advance of other systems. The NHS 111 RSV epidemic threshold was breached in week 41, in advance of RSV laboratory reporting. Combining the use of MEM thresholds with daily monitoring of NHS 111 and GP OOH syndromic surveillance systems provides the potential to alert to threshold breaches in real-time. An advantage of using thresholds across different health systems is the ability to capture a range of healthcare-seeking behaviour, which may reflect differences in disease severity. This study also provides a quantifiable measure of seasonal RSV activity, which contributes to our understanding of RSV activity in advance of the potential introduction of new RSV vaccines.
During the 2009 influenza pandemic, a rapid assessment of disease severity was a challenge as a significant proportion of cases did not seek medical care; care-seeking behaviour changed and the proportion asymptomatic was unknown. A random-digit-dialling telephone survey was undertaken during the 2011/12 winter season in England and Wales to address the feasibility of answering these questions. A proportional quota sampling strategy was employed based on gender, age group, geographical location, employment status and level of education. Households were recruited pre-season and re-contacted immediately following peak seasonal influenza activity. The pre-peak survey was undertaken in October 2011 with 1061 individuals recruited and the post-peak telephone survey in March 2012. Eight hundred and thirty-four of the 1061 (78.6%) participants were successfully re-contacted. Their demographic characteristics compared well to national census data. In total, 8.4% of participants self-reported an influenza-like illness (ILI) in the previous 2 weeks, with 3.2% conforming to the World Health Organization (WHO) ILI case definition. In total, 29.6% of the cases reported consulting their general practitioner. 54.1% of the 1061 participants agreed to be re-contacted about providing biological samples. A population-based cohort was successfully recruited and followed up. Longitudinal survey methodology provides a practical tool to assess disease severity during future pandemics.
Understanding the burden of respiratory pathogens on health care is key to improving public health emergency response and interventions. In temperate regions, there is a large seasonal rise in influenza and other respiratory pathogens. We have examined the associations between individual pathogens and reported respiratory tract infections to estimate attributable burden. We used multiple linear regression to model the relationship between doctor consultation data and laboratory samples from week 3 2011 until week 37 2015. We fitted separate models for consultation data with in-hours and out-of-hours doctor services, stratified by different age bands. The best fitting all ages models (R2 > 80%) for consultation data resulted in the greatest burden being associated with influenza followed by respiratory syncytial virus (RSV). For models of adult age bands, there were significant associations between consultation data and invasive Streptococcus pneumoniae. There were also smaller numbers of consultations significantly associated with rhinovirus, parainfluenza, and human metapneumovirus. We estimate that a general practice with 10 000 patients would have seen an additional 18 respiratory tract infection consultations per winter week of which six had influenza and four had RSV. Our results are important for the planning of health care services to minimise the impact of winter pressures.
• Respiratory pathogen incidence explains over 80% of seasonal variation in respiratory consultation data.
• Influenza and RSV are associated with the biggest seasonal rises in respiratory consultation counts.
• A third of consultation counts associated with respiratory pathogens were due to influenza.
Significant increases in excess all-cause mortality, particularly in the elderly, were observed during the winter of 2014/15 in England. With influenza A(H3N2) the dominant circulating influenza A subtype, this paper determines the contribution of influenza to this excess controlling for weather. A standardised multivariable Poisson regression model was employed with weekly all-cause deaths the dependent variable for the period 2008–2015. Adjusting for extreme temperature, a total of 26 542 (95% CI 25 301–27 804) deaths in 65+ and 1942 (95% CI 1834–2052) in 15–64-year-olds were associated with influenza from week 40, 2014 to week 20, 2015. This is compatible with the circulation of influenza A(H3N2). It is the largest estimated number of influenza-related deaths in England since prior to 2008/09. The findings highlight the potential health impact of influenza and the important role of the annual influenza vaccination programme that is required to protect the population including the elderly, who are vulnerable to a severe outcome.
In autumn 2014, enterovirus D68 (EV-D68) cases presenting with severe respiratory or neurological disease were described in countries worldwide. To describe the epidemiology and virological characteristics of EV-D68 in England, we collected clinical information on laboratory-confirmed EV-D68 cases detected in secondary care (hospitals), between September 2014 and January 2015. In primary care (general practitioners), respiratory swabs collected (September 2013–January 2015) from patients presenting with influenza-like illness were tested for EV-D68. In secondary care 55 EV-D68 cases were detected. Among those, 45 cases had clinical information available and 89% (40/45) presented with severe respiratory symptoms. Detection of EV-D68 among patients in primary care increased from 0.4% (4/1074; 95% CI 0.1–1.0) (September 2013–January 2014) to 0.8% (11/1359; 95% CI 0.4–1.5) (September 2014–January 2015). Characterization of EV-D68 strains circulating in England since 2012 and up to winter 2014/2015 indicated that those strains were genetically similar to those detected in 2014 in USA. We recommend reinforcing enterovirus surveillance through screening respiratory samples of suspected cases.
The UK Severe Influenza Surveillance System (USISS) was established following the 2009 influenza pandemic to monitor severe seasonal influenza. This article describes the severity of influenza observed in five post-2009 pandemic seasons in England. Two key measures were used to assess severity: impact measured through the cumulative incidence of laboratory-confirmed hospitalised influenza and case severity through the proportion of confirmed hospitalised cases admitted into intensive care units (ICU)/high dependency units (HDU). The impact of influenza varied by subtype and age group across the five seasons with the highest crude cumulative hospitalisation incidence for influenza A/H1N1pdm09 cases in 2010/2011 and in 0–4 year olds each season for all-subtypes. Case severity also varied by subtype and season with a higher hospitalisation: ICU ratio for A/H1N1pdm09 and older age groups (older than 45 years). The USISS system provides a tool for measuring severity of influenza each year. Such seasonal surveillance can provide robust baseline estimates to allow for rapid assessment of the severity of seasonal and emerging influenza viruses.
Human parainfluenza virus (HPIV) infections are one of the commonest causes of upper and lower respiratory tract infections. In order to determine if there have been any recent changes in HPIV epidemiology in England and Wales, laboratory surveillance data between 1998 and 2013 were analysed. The UK national laboratory surveillance database, LabBase, and the newly established laboratory-based virological surveillance system, the Respiratory DataMart System (RDMS), were used. Descriptive analysis was performed to examine the distribution of cases by year, age, sex and serotype, and to examine the overall temporal trend using the χ2 test. A random-effects model was also employed to model the number of cases. Sixty-eight per cent of all HPIV detections were due to HPIV type 3 (HPIV-3). HPIV-3 infections were detected all year round but peaked annually between March and June. HPIV-1 and HPIV-2 circulated at lower levels accounting for 20% and 8%, respectively, peaking during the last quarter of the year with a biennial cycle. HPIV-4 was detected in smaller numbers, accounting for only 4% and also mainly observed in the last quarter of the year. However, in recent years, HPIV-4 detection has been reported much more commonly with an increase from 0% in 1998 to 3·7% in 2013. Although an overall higher proportion of HPIV infection was reported in infants (43·0%), a long-term decreasing trend in proportion in infants was observed. An increase was also observed in older age groups. Continuous surveillance will be important in tracking any future changes.
Seasonal respiratory infections place an increased burden on health services annually. We used a sentinel emergency department syndromic surveillance system to understand the factors driving respiratory attendances at emergency departments (EDs) in England. Trends in different respiratory indicators were observed to peak at different points during winter, with further variation observed in the distribution of attendances by age. Multiple linear regression analysis revealed acute respiratory infection and bronchitis/bronchiolitis ED attendances in patients aged 1–4 years were particularly sensitive indicators for increasing respiratory syncytial virus activity. Using near real-time surveillance of respiratory ED attendances may provide early warning of increased winter pressures in EDs, particularly driven by seasonal pathogens. This surveillance may provide additional intelligence about different categories of attendance, highlighting pressures in particular age groups, thereby aiding planning and preparation to respond to acute changes in EDs, and thus the health service in general.
The relationship between risk of death following influenza A(H1N1)pdm09 infection and ethnicity and deprivation during the 2009/2010 pandemic period and the first post-pandemic season of 2010/2011 in England was examined. Poisson regression models were used to estimate the mortality risk, adjusted for age, gender, and place of residence. Those of non-White ethnicity experienced an increased mortality risk compared to White populations during the 2009/2010 pandemic [10·5/1000 vs. 6·0/1000 general population; adjusted risk ratio (RR) 1·84, 95% confidence interval (CI) 1·39-2·54] with the highest risk in those of Pakistani ethnicity. However, no significant difference between ethnicities was observed during the following 2010/2011 season. Persons living in areas with the highest level of deprivation had a significantly higher risk of death (RR 2·08, 95% CI 1·49-2·91) compared to the lowest level for both periods. These results highlight the importance of rapid identification of groups at higher risk of severe disease in the early stages of future pandemics to enable the implementation of optimal prevention and control measures for vulnerable populations.
The aim of the European Sero-Epidemiology Network 2 (ESEN2) project was to estimate age-specific seroprevalence for a number of vaccine-preventable diseases in Europe. To achieve this serosurveys were collected by 22 national laboratories. To adjust for a variety of laboratory methods and assays, all quantitative results were transformed to a reference laboratory's units and were then classified as positive or negative to obtain age-specific seroprevalence. The aim of this study was to assess the value of standardization by comparing the crude and standardized seroprevalence estimates. Seroprevalence was estimated for measles, mumps, rubella, diphtheria, varicella zoster and hepatitis A virus (HAV) and compared before and after serological results had been standardized. The results showed that if no such adjustment had taken place, seroprevalence would have differed by an average of 3·2% (95% bootstrap interval 2·9–3·6) although this percentage varied substantially by antigen. These differences were as high as 16% for some serosurveys (HAV) which means that standardization could have a considerable impact on seroprevalence estimates and should be considered when comparing serosurveys performed in different laboratories using different assay methods.
In August 2012, an explosive outbreak of severe lower respiratory tract infection (LRTI) due to Streptococcus pneumoniae serotype-8 occurred in a highly vaccinated elderly institutionalized population in England. Fifteen of 23 residents developed LRTI over 4 days (attack rate 65%); 11 had confirmed S. pneumoniae serotype-8 disease, and two died. Following amoxicillin chemoprophylaxis and pneumococcal polysaccharide vaccine (PPV) re-vaccination no further cases occurred in the following 2 months. No association was found between being an outbreak-associated case and age (P = 0·36), underlying comorbidities [relative risk (RR) 0·84 95% confidence interval (CI) 0·34–2·09], or prior receipt of PPV (RR 1·4, 95% CI 0·60–3·33). However, the median number of years since PPV was significantly higher for cases (n = 15, 10·2 years, range 7·3–17·9 years) than non-cases (n = 8, 7·2 years, range 6·8–12·8 years) (P = 0·045), provided evidence of waning immunity. Alternative vaccination strategies should be considered to prevent future S. pneumoniae outbreaks in institutionalized elderly populations.
General Practitioner consultation rates for influenza-like illness (ILI) are monitored through several geographically distinct schemes in the UK, providing early warning to government and health services of community circulation and intensity of activity each winter. Following on from the 2009 pandemic, there has been a harmonization initiative to allow comparison across the distinct existing surveillance schemes each season. The moving epidemic method (MEM), proposed by the European Centre for Disease Prevention and Control for standardizing reporting of ILI rates, was piloted in 2011/12 and 2012/13 along with the previously proposed UK method of empirical percentiles. The MEM resulted in thresholds that were lower than traditional thresholds but more appropriate as indicators of the start of influenza virus circulation. The intensity of the influenza season assessed with the MEM was similar to that reported through the percentile approach. The MEM pre-epidemic threshold has now been adopted for reporting by each country of the UK. Further work will continue to assess intensity of activity and apply standardized methods to other influenza-related data sources.
During 2012 real-time syndromic surveillance formed a key part of the daily public health surveillance for the London Olympic and Paralympic Games. It was vital that these systems were evaluated prior to the Games; in particular what types and scales of incidents could and could not be detected. Different public health scenarios were created covering a range of potential incidents that the Health Protection Agency would require syndromic surveillance to rapidly detect and monitor. For the scenarios considered it is now possible to determine what is likely to be detectable and how incidents are likely to present using the different syndromic systems. Small localized incidents involving food poisoning are most likely to be detected the next day via emergency department surveillance, while a new strain of influenza is more likely to be detected via GP or telephone helpline surveillance, several weeks after the first seed case is introduced.
We estimated the incidence of pertussis in patients consulting general practitioners (GPs). Between July 2009 and April 2011, we conducted a prospective cohort study of patients attending 78 general practices (158 863 persons overall). We included patients aged ⩾3 years, with cough lasting 2–15 weeks, who gave informed consent. GPs interviewed eligible patients, collected a blood specimen, and a nasopharyngeal swab. At follow-up 30–60 days after the initial visit, physicians collected a second blood specimen and conducted patient interview. Cases were confirmed by specific IgA and/or IgG antibody titre exceeding significantly the general population background level or detection of bacterial DNA by real-time PCR. During the study period, 3864 patients with prolonged cough consulted the participating GPs, of those 1852 met the inclusion criteria, 1232 were recruited, and 288 were confirmed as pertussis cases (4% by PCR, 96% by serology). The adjusted incidence rate was 201·1/100 000 person-years [95% confidence interval (CI) 133·9–302·0], ranging from 456·5 (95% CI 239·3–870·8) in the 15–19 years group to 94·0 (95% CI 33·4–264·5) in the 25–29 years group. The reporting ratio was 61, ranging from 4 in those aged 3–5 years, to 167 in those aged 65–69 years. The study confirmed high incidence of pertussis in all age groups in the general population, in particular in adults, not appropriately documented by the existing surveillance system.
The West Midlands was the first English region to report sustained community transmission during the ‘containment’ phase of the influenza A(H1N1)pdm09 pandemic in England. To describe the epidemiological experience in the region, West Midlands and national datasets containing laboratory-confirmed A(H1N1)pdm09 virus cases in the region during the ‘containment’ phase were analysed. The region accounts for about 10·5% of England's population, but reported about 42% of all laboratory-confirmed cases. Altogether 3063 cases were reported, with an incidence rate of 56/100 000 population. School-associated cases accounted for 25% of cases. Those aged <20 years, South Asian ethnic groups, and residents of urban and socioeconomically deprived areas were disproportionately affected. Imported cases accounted for 1% of known exposures. Regional R0 central estimates between 1·41 and 1·43 were obtained. The West Midlands experience suggests that interpretation of transmission rates may be affected by complex interactions within and between sub-populations in the region.
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.
An analysis was undertaken to measure age-specific vaccine effectiveness (VE) of 2010/11 trivalent seasonal influenza vaccine (TIV) and monovalent 2009 pandemic influenza vaccine (PIV) administered in 2009/2010. The test-negative case-control study design was employed based on patients consulting primary care. Overall TIV effectiveness, adjusted for age and month, against confirmed influenza A(H1N1)pdm 2009 infection was 56% (95% CI 42–66); age-specific adjusted VE was 87% (95% CI 45–97) in <5-year-olds and 84% (95% CI 27–97) in 5- to 14-year-olds. Adjusted VE for PIV was only 28% (95% CI −6 to 51) overall and 72% (95% CI 15–91) in <5-year-olds. For confirmed influenza B infection, TIV effectiveness was 57% (95% CI 42–68) and in 5- to 14-year-olds 75% (95% CI 32–91). TIV provided moderate protection against the main circulating strains in 2010/2011, with higher protection in children. PIV administered during the previous season provided residual protection after 1 year, particularly in the <5 years age group.
Mumps outbreaks have recently been recorded in a number of highly vaccinated populations. We related seroprevalence, epidemiological and vaccination data from 18 European countries participating in The European Sero-Epidemiology Network (ESEN) to their risk of mumps outbreaks in order to inform vaccination strategies. Samples from national population serum banks were collected, tested for mumps IgG antibodies and standardized for international comparisons. A comparative analysis between countries was undertaken using age-specific mumps seroprevalence data and information on reported mumps incidence, vaccine strains, vaccination programmes and vaccine coverage 5–12 years after sera collection. Mean geometric mumps antibody titres were lower in mumps outbreak countries [odds ratio (OR) 0·09, 95% confidence interval (CI) 0·01–0·71)]. MMR1 vaccine coverage ⩾95% remained protective in a multivariable model (P < 0·001), as did an interval of 4–8 years between doses (OR 0·08, 95% CI 0·01–0·85). Preventing outbreaks and controlling mumps probably requires several elements, including high-coverage vaccination programmes with MMR vaccine with 4–8 years between doses.
Serological surveys for diphtheria were conducted in six European countries including Czech Republic, Hungary, Ireland, Latvia, Luxembourg, Slovakia and one country outside Europe, Israel. For each country, a nationally representative population sample was collected across the entire age range and was tested for antibodies to diphtheria toxin. Although each national laboratory used its preferred assay, the results were all standardized to those of the in vitro neutralization test and expressed in international units (IU) which allowed comparative analyses to be performed. The results showed that increasing age is related to a gradual increase in seronegative subjects (<0·01 IU/ml of diphtheria antitoxin antibodies). This may reflect waning immunity following childhood vaccination without repeated booster vaccinations in adults. Differences in seronegativity were also found according to gender. In subjects aged 1–19 years, geometric mean titres of antitoxin are clearly related to the different vaccination schedules used in the participating countries. Although clinical disease remains rare, the susceptibility to diphtheria observed in these serosurveys highlights the importance of strengthened surveillance.