Effectiveness of influenza vaccine in children in preventing influenza associated hospitalisation, 2018/19, England.

2013/14 saw the start of the introduction of a new live attenuated influenza vaccine (LAIV) programme for children in England. 2018/19 saw co-circulation of both A(H1N1)pdm09 and A(H3N2), when LAIV was offered to all healthy children 2-9 years of age. LAIV effectiveness against influenza hospitalisation is not well described. This paper presents the 2018/19 end-of-season adjusted vaccine effectiveness (aVE) against laboratory confirmed influenza related hospitalisation in children aged 2-17. The test negative case control approach was used to estimate aVE by influenza A subtype and vaccine type. Cases and controls were selected from a sentinel laboratory surveillance system which collates details of individuals tested for influenza with reverse-transcription polymerase chain reaction (RT-PCR) on respiratory samples. Vaccine and clinical history was obtained from general practitioners of study participants. There were 307 hospitalised cases and 679 hospitalised controls. End-of-season influenza aVE was 53.0% (95% CI: 33.3, 66.8) against influenza confirmed hospitalisation; 63.5% (95% CI: 34.4, 79.7) against influenza A(H1N1)pdm09 hospitalisation and 31.1% (95% CI: -53.9, 69.2) against influenza A(H3N2). LAIV aVE was 49.1% (95% CI: 25.9, 65.0) for any influenza and 70.7% (95% CI: 41.8, 85.3) for A(H1N1)pdm09, whereas for those receiving quadrivalent inactivated influenza vaccine (QIV), aVE was 64.4% (95% CI: 29.4, 82.0) and 44.4% (95% CI: -51.9, 79.6) respectively. We provide evidence of overall significant VE for both LAIV and QIV against influenza associated hospitalisation in children 2-17 years of age, most notably against influenza A(H1N1)pdm09, with non-significant protection against A(H3N2).

Influenza vaccine effectiveness against hospitalisation due to laboratory-confirmed influenza in children in England in the 2015-2016 influenza season - a test-negative case-control study.

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.

European all-cause excess and influenza-attributable mortality in the 2017/18 season: should the burden of influenza B be reconsidered?

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.

Assessing the severity of influenza: a role for longitudinal telephone surveys?

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.

Significant spike in excess mortality in England in winter 2014/15 - influenza the likely culprit.

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.

The emergence of enterovirus D68 in England in autumn 2014 and the necessity for reinforcing enterovirus respiratory screening.

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.

Developing a system to estimate the severity of influenza infection in England: findings from a hospital-based surveillance system between 2010/2011 and 2014/2015.

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.

Epidemiology of parainfluenza infection in England and Wales, 1998-2013: any evidence of change?

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 χ 2 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.

Burden of acute respiratory disease of epidemic and pandemic potential in the WHO Eastern Mediterranean Region: A literature review.

There are gaps in the knowledge about the burden of severe respiratory disease in the Eastern Mediterranean Region (EMR). This literature review was therefore conducted to describe the burden of epidemicand pandemic-prone acute respiratory infections (ARI) in the Region which may help in the development of evidence-based disease prevention and control policies. Relevant published and unpublished reports were identified from searches of various databases; 83 documents fulfilled the search criteria. The infections identified included: ARI, avian influenza A(H5N1), influenza A(H1N1)pdm09 and Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Pneumonia and ARIs were leading causes of disease and death in the Region. Influenza A(H1N1) was an important cause of morbidity during the 2009 pandemic. This review provides a descriptive summary of the burden of acute respiratory diseases in the Region, but there still remains a lack of necessary data.

Burden of acute respiratory disease of epidemic and pandemic potential in the WHO Eastern Mediterranean Region: a literature review

There are gaps in the knowledge about the burden of severe respiratory disease in the Eastern Mediterranean Region [EMR]. This literature review was therefore conducted to describe the burden of epidemic- and pandemic-prone acute respiratory infections [ARI] in the Region which may help in the development of evidence-based disease prevention and control policies. Relevant published and unpublished reports were identified from searches of various databases; 83 documents fulfilled the search criteria. The infections identified included: ARI, avian influenza A[H5N1], influenza A[H1N1]pdm09 and Middle East respiratory syndrome coronavirus [MERS-CoV] infection. Pneumonia and ARIs were leading causes of disease and death in the Region. Influenza A[H1N1] was an important cause of morbidity during the 2009 pandemic. This review provides a descriptive summary of the burden of acute respiratory diseases in the Region, but there still remains a lack of necessary data

On observe des lacunes en matière de connaissances concernant la charge des maladies respiratoires sévères dans la Région de la Méditerranée orientale. La présente analyse documentaire détaille la charge des infections respiratoires aiguës [IRA] à potentiel épidémique et pandémique dans la Région, ce qui peut aider à l'élaboration de politiques et programmes de prévention et de lutte contre les maladies reposant sur des données factuelles. Des articles pertinents publiés et non publiés ont été identifiés grâce à des recherches dans différentes bases de données ; 83 documents satisfaisaient à nos critères de recherche. Les infections identifiées comprenaient les infections respiratoires aiguës [IRA], la grippe aviaire A[H5N1], la grippe A[H1N1]pdm09 et l'infection par le coronavirus du syndrome respiratoire du Moyen-Orient [MERS-CoV]. La pneumonie et les IRA constituaient les principales causes de morbidité et de mortalité dans la Région. La grippe A[H1N1] était une cause importante de morbidité durant la pandémie de 2009. Cette analyse fournit un résumé descriptif de la charge des maladies respiratoires aiguës dans la Région mais il existe toujours une lacune concernant les donneés nécessaires à cet égard

Burden of acute respiratory disease of epidemic and pandemic potential in the WHO Eastern Mediterranean Region: A literature review

There are gaps in the knowledge about the burden of severe respiratory disease in the Eastern Mediterranean Region [EMR]. This literature review was therefore conducted to describe the burden of epidemic- and pandemic-prone acute respiratory infections [ARI] in the Region which may help in the development of evidence-based disease prevention and control policies. Relevant published and unpublished reports were identified from searches of various databases; 83 documents fulfilled the search criteria. The infections identified included: ARI, avian influenza A[H5N1], influenza A[H1N1]pdm09 and Middle East respiratory syndrome coronavirus [MERS-CoV] infection. Pneumonia and ARIs were leading causes of disease and death in the Region. Influenza A[H1N1] was an important cause of morbidity during the 2009 pandemic. This review provides a descriptive summary of the burden of acute respiratory diseases in the Region, but there still remains a lack of necessary data

On observe des lacunes en matière de connaissances concernant la charge des maladies respiratoires sévères dans la Région de la Méditerranée orientale. La présente analyse documentaire détaille la charge des infections respiratoires aiguës [IRA] à potentiel épidémique et pandémique dans la Région, ce qui peut aider à l'élaboration de politiques et programmes de prévention et de lutte contre les maladies reposant sur des données factuelles. Des articles pertinents publiés et non publiés ont été identifiés grâce à des recherches dans différentes bases de données ; 83 documents satisfaisaient à nos critères de recherche. Les infections identifiées comprenaient les infections respiratoires aiguës [IRA], la grippe aviaire A[H5N1], la grippe A[H1N1]pdm09 et l'infection par le coronavirus du syndrome respiratoire du Moyen-Orient [MERS-CoV]. La pneumonie et les IRA constituaient les principales causes de morbidité et de mortalité dans la Région. La grippe A[H1N1] était une cause importante de morbidité durant la pandémie de 2009. Cette analyse fournit un résumé descriptif de la charge des maladies respiratoires aiguës dans la Région mais il existe toujours une lacune concernant les donneés nécessaires à cet égard

Ethnicity, deprivation and mortality due to 2009 pandemic influenza A(H1N1) in England during the 2009/2010 pandemic and the first post-pandemic season.

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.

An explosive outbreak of Streptococcus pneumoniae serotype-8 infection in a highly vaccinated residential care home, England, summer 2012.

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.

Harmonizing influenza primary-care surveillance in the United Kingdom: piloting two methods to assess the timing and intensity of the seasonal epidemic across several general practice-based surveillance schemes.

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.

Uptake and impact of a new live attenuated influenza vaccine programme in England: early results of a pilot in primary school-age children, 2013/14 influenza season.

As part of the introduction and roll-out of a universal childhood live-attenuated influenza vaccination programme, 4­11 year-olds were vaccinated in seven pilot areas in England in the 2013/14 influenza season. This paper presents the uptake and impact of the programme for a range of disease indicators. End-of-season uptake was defined as the number of children in the target population who received at least one dose of influenza vaccine. Between week 40 2013 and week 15 2014, cumulative disease incidence per 100,000 population (general practitioner consultations for influenza-like illness and laboratory-confirmed influenza hospitalisations), cumulative influenza swab positivity in primary and secondary care and cumulative proportion of emergency department respiratory attendances were calculated. Indicators were compared overall and by age group between pilot and non-pilot areas. Direct impact was defined as reduction in cumulative incidence based on residence in pilot relative to non-pilot areas in 4­11 year-olds. Indirect impact was reduction between pilot and non-pilot areas in <4 year-olds and >11 year-olds. Overall vaccine uptake of 52.5% (104,792/199,475) was achieved. Although influenza activity was low, a consistent, though not statistically significant, decrease in cumulative disease incidence and influenza positivity across different indicators was seen in pilot relative to non-pilot areas in both targeted and non-targeted age groups, except in older age groups, where no difference was observed for secondary care indicators.

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.

Incidence of pertussis in patients of general practitioners in Poland.

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.

Enhanced surveillance and investigation of coronavirus: what is required?

Following the discovery in September 2012 of 2 patients, both with links to the Eastern Mediterranean Region, with serious respiratory illness due to novel coronavirus, all countries have instigated surveillance and laboratory activities to detect further cases, with intensive case-contact investigations undertaken on laboratory confirmation of cases. A total of 30 cases, of whom 18 have died, and at least 3 clusters have been detected to date (1 cluster among health-care workers and another 2 clusters among family members). To date, transmission studies have shown a low risk of onward human transmission, with clinical presentation remaining severe for the majority. Many questions remain including the zoonotic source and geographical extent of infection. Surveillance has been extended to include clusters of cases or health-care workers with severe, undiagnosed respiratory illness regardless of travel history. Environmental studies, on-going surveillance and linked case-contact investigations will provide a critical role in answering some of these issues.

Critical care surveillance: insights into the impact of the 2010/11 influenza season relative to the 2009/10 pandemic season in England.

In 2010/11, the influenza season in England was marked by a relative increase in impact on the population compared to that seen during the 2009/10 pandemic, with the same influenza subtype, A(H1N1)pdm09, circulating. The peaks in critical care bed occupancy in both seasons coincided with peaks in influenza A(H1N1)pdm09 activity, but onset of influenza in 2010/11 additionally coincided with notably cold weather, a comparatively smaller peak in influenza B activity and increased reports of bacterial co-infection. A bigger impact on critical care services was seen across all regions in England in 2010/11, with, compared to 2009/10, a notable age shift in critical care admissions from children to young adults. The peak of respiratory syncytial virus (RSV) activity did not coincide with critical care admissions, and regression analysis suggested only a small proportion of critical care bed days might be attributed to the virus in either season. Differences in antiviral policy and improved overall vaccine uptake in 2010/11 with an influenza A(H1N1)pdm09 strain containing vaccine between seasons are unlikely to explain the change in impact observed between the two seasons. The reasons behind the relative high level of severe disease in the 2010/11 winter are likely to have resulted from a combination of factors, including an age shift in infection, accumulation of susceptible individuals through waning immunity, new susceptible individuals from new births and cold weather. The importance of further development of severe influenza disease surveillance schemes for future seasons is reinforced.