Incidence of Influenza-Related Medical Encounters and the Associated Healthcare Resource Use and Complications Across Adult Age Groups in The United States During the 2015-2020 Influenza Seasons.

BACKGROUND: Research on influenza burden in adults has focused on crude subgroups with cut-points at 65-years, limiting insight into how burden varies with increasing age. This study describes the incidence of influenza-related outpatient visits, emergency room (ER) visits, and hospitalizations, along with healthcare resource use and complications in the aging adult population. METHODS: Individuals ≥18 years of age in the United States were evaluated retrospectively in five seasonal cohorts (2015-2020 seasons) in strata of age with 5-year increments. Person-level electronic medical records linked to pharmacy and medical claims were used to ascertain patient characteristics and outcomes. Influenza-related medical encounters were identified based on diagnostic codes (ICD-10 codes J09*-J11*). RESULTS: Incidence of influenza-related outpatient visits was highest among people aged 18-34 years and declined with increasing age. For ER visits, incidence tended to be elevated for people aged 18-34 years, relatively stable from 35 through 60, and increased rapidly after 60. Hospitalization incidence remained relatively stable until about 50 years of age and then increased with age. One in three patients was diagnosed with pneumonia after hospitalization, regardless of age. Across seasons, age groups, and clinical settings, on average, 40.8% of individuals were prescribed antivirals and 17.2% antibiotics. CONCLUSIONS: Incidence of influenza-related hospitalizations begins to increase around age 50 rather than the more common cut-point of 65, whereas incidence of outpatient visits was highest among younger adults. Influenza infections frequently led to antiviral and antibiotic prescriptions, underscoring the role influenza vaccination can play in combating antimicrobial resistance.

Global analysis of respiratory viral circulation and timing of epidemics in the pre-COVID-19 and COVID-19 pandemic eras, based on data from the Global Influenza Surveillance and Response System (GISRS).

INTRODUCTION: The COVID-19 pandemic significantly changed respiratory viruses' epidemiology due to non-pharmaceutical interventions and possible viral interactions. This study investigates whether the circulation patterns of respiratory viruses have returned to pre-pandemic norms by comparing their peak timing and duration during the first three SARS-CoV-2 seasons to pre-pandemic times. METHODS: GISRS data from 194 countries (2014-2023) was analyzed for epidemic peak timing and duration, focusing on pre-pandemic and pandemic periods across both hemispheres and the intertropical belt. Analysis was restricted to countries meeting specific data thresholds to ensure robustness. RESULTS: In 2022/23, the Northern hemisphere experienced earlier influenza and RSV peaks by 1.9 months (p<0.001). The duration of influenza epidemics increased by 2.2 weeks (p<0.001), with RSV showing a similar trend. The Southern hemisphere's influenza peak shift was not significant (p=0.437). Intertropical regions presented no substantial change in peak timing but experienced a significant reduction in duration for hMPV and adenovirus (7.2 and 6.5 weeks shorter, p<0.001). CONCLUSIONS: The pandemic altered the typical patterns of influenza and RSV, with earlier peaks in 2022 in temperate areas. These findings highlight the importance of robust surveillance data to inform public health strategies on evolving viral dynamics in the years to come.

Relative Effectiveness of the MF59®-Adjuvanted Influenza Vaccine Versus High-Dose and Non-Adjuvanted Influenza Vaccines in Preventing Cardiorespiratory Hospitalizations During the 2019-2020 US Influenza Season.

BACKGROUND: Adults ≥ 65 years of age have suboptimal influenza vaccination responses compared to younger adults due to age-related immunosenescence. Two vaccines were specifically developed to enhance protection: MF59-adjuvanted trivalent influenza vaccine (aIIV3) and high-dose egg-based trivalent influenza vaccine (HD-IIV3e). METHODS: In a retrospective cohort study conducted using US electronic medical records linked to claims data during the 2019-2020 influenza season, we compared the relative vaccine effectiveness (rVE) of aIIV3 with HD-IIV3e and a standard-dose non-adjuvanted egg-based quadrivalent inactivated influenza vaccine (IIV4e) for the prevention of cardiorespiratory hospitalizations, including influenza hospitalizations. We evaluated outcomes in the "any" diagnosis position and the "admitting" position on the claim. A doubly robust methodology using inverse probability of treatment weighting and logistic regression was used to adjust for covariate imbalance. rVE was calculated as 100 * (1 - ORadjusted). RESULTS: The study included 4,299,594 adults ≥ 65 years of age who received aIIV3, HD-IIV3e, or IIV4e. Overall, aIIV3 was associated with lower proportions of cardiorespiratory hospitalizations with diagnoses in any position compared to HD-IIV3e (rVE = 3.9% [95% CI, 2.7-5.0]) or IIV4e (9.0% [95% CI, 7.7-10.4]). Specifically, aIIV3 was more effective compared with HD-IIV3e and IIV4e in preventing influenza hospitalizations (HD-IIV3e: 9.7% [95% CI, 1.9-17.0]; IIV4e: 25.3% [95% CI, 17.7-32.2]). Consistent trends were observed for admitting diagnoses. CONCLUSION: Relative to both HD-IIV3e and IIV4e, aIIV3 provided improved protection from cardiorespiratory or influenza hospitalizations.

Influenza burden averted with a cell-based quadrivalent seasonal influenza vaccine compared with egg-based quadrivalent seasonal influenza vaccine.

BACKGROUND: Cell-based quadrivalent inactivated influenza vaccines (IIV4c) avoid egg-adaptive mutations found in egg-based production, improving vaccine effectiveness (VE). Studies demonstrate improved VE for IIV4c relative to egg-based quadrivalent inactivated influenza vaccines (IIV4). RESEARCH DESIGN AND METHODS: We built on a static compartmental model developed by the CDC to estimate the influenza burden in persons 0-64 years that would be additionally averted by vaccination with IIV4c vs. IIV4. Model inputs were based on published data from 2017-2018, 2018-2019, and 2019-2020 Northern Hemisphere influenza seasons for the US. RESULTS: Over 3 influenza seasons, relative to IIV4, IIV4c would avert 31-39% more symptomatic cases, 29-40% more outpatient visits, 29-38% more hospitalizations and ICU admissions, and 34-49% more deaths vs. IIV4. In a deterministic sensitivity analysis, the main drivers were the relative VE of IIV4c vs. IIV4 in the 2017-2018 season and influenza burden estimates for the 2018-2019 and 2019-2020 seasons. Probabilistic sensitivity analysis showed that the interquartile range of symptomatic cases was ± 13% of baseline in 2017-2018, ±8% in 2018-2019, and ± 7% in 2019-2020. CONCLUSIONS: IIV4c prevented significantly more symptomatic cases, outpatient visits, hospitalizations, and deaths than IIV4 in persons aged 0-64 years over 3 influenza seasons.

Co-Administration of Influenza and COVID-19 Vaccines: Policy Review and Vaccination Coverage Trends in the European Union, UK, US, and Canada between 2019 and 2023.

Recommending co-administration of influenza and COVID-19 vaccines has emerged as a strategy to enhance vaccination coverage. This study describes the policy on co-administration and uptake of influenza and COVID-19 vaccination in Europe, the United Kingdom, the United States, and Canada between 2019 and 2023. We collected co-administration policy data from governmental websites, national health organizations, and newspapers. Influenza vaccination coverage among persons ≥65 years and COVID-19 vaccination coverage rates among persons ≥60 years or the general population were collected using national databases, the ECDC database, or ourworldindata.org between 2019 and 2023. Descriptive analyses were used. We collected data from 30/32 (94%) countries on vaccination policy in seasons 2021-2022 and 2022-2023, with most countries (25/30 to 30/30) having policies recommending co-administration. For influenza vaccination coverage, we collected data from 29/32 (91%, 2019-2020), 28/32 (88%, 2020-2021), 27/32 (84%, 2021-2022), and 6/32 (19%, 2022-2023) countries. COVID-19 vaccination was collected from 32/32 (2020-2021), 31/32 (97%, 2021-2022), and 24/32 (75%, 2022-2023) countries. Influenza vaccination coverage increased from 2019-2020 to 2021-2022. COVID-19 vaccination coverage was higher among countries with higher influenza vaccination coverage. By 2022-2023, all countries included implemented a policy supporting co-administration. A positive correlation existed between higher influenza vaccination coverage and higher COVID-19 vaccination rates.

Effectiveness of Cell-Based Quadrivalent Seasonal Influenza Vaccine: A Systematic Review and Meta-Analysis.

Cell-based seasonal influenza vaccine viruses may more closely match recommended vaccine strains than egg-based options. We sought to evaluate the effectiveness of seasonal cell-based quadrivalent influenza vaccine (QIVc), as reported in the published literature. A systematic literature review was conducted (PROSPERO CRD42020160851) to identify publications reporting on the effectiveness of QIVc in persons aged ≥6 months relative to no vaccination or to standard-dose, egg-based quadrivalent or trivalent influenza vaccines (QIVe/TIVe). Publications from between 1 January 2016 and 25 February 2022 were considered. The review identified 18 relevant publications spanning three influenza seasons from the 2017-2020 period, with an overall pooled relative vaccine effectiveness (rVE) of 8.4% (95% CI, 6.5-10.2%) for QIVc vs. QIVe/TIVe. Among persons aged 4-64 years, the pooled rVE was 16.2% (95% CI, 7.6-24.8%) for 2017-2018, 6.1% (4.9-7.3%) for 2018-2019, and 10.1% (6.3-14.0%) for 2019-2020. For adults aged ≥65 years, the pooled rVE was 9.9% (95% CI, 6.9-12.9%) in the egg-adapted 2017-2018 season, whereas there was no significant difference in 2018-2019. For persons aged 4-64 years, QIVc was consistently more effective than QIVe/TIVe over the three influenza seasons. For persons aged ≥65 years, protection with QIVc was greater than QIVe or TIVe during the 2017-2018 season and comparable in 2018-2019.

Epidemiology and Burden of Influenza in Children 0-14 Years Over Ten Consecutive Seasons in Italy.

BACKGROUND: In Europe, influenza vaccination coverage in the pediatric population is low. This study describes the influenza incidence and associated healthcare utilization in the pediatric population in Italy. METHODS: Deidentified data from electronic medical records for children 0-14 years old seen by >150 family pediatricians in the Pedianet network in Italy were evaluated for 10 influenza seasons spanning 2010-2020. Incidence of influenza (cases per 1000 person-months), related sequelae and associated healthcare resource use were determined using diagnostic, prescription and medical examination data. RESULTS: Over 10 seasons, an average of 8892 influenza cases (range, 4700-12,419; total 88,921) were diagnosed in a cohort of 1,432,384 children 0-14 years of age. Influenza vaccination coverage was 3.6% among children with an influenza diagnosis and 6.8% among children without. Influenza-related healthcare resource utilization included 1.58 family pediatrician visits per influenza episode and 220 ED and 111 hospital admissions, with the highest resource usage among children 1-4 years and lowest among children <6 months old. The most common influenza complications were acute otitis media (2.9% of influenza cases) and pneumonia (0.5%). Antibiotics were prescribed in 38.7% of influenza cases; no antiviral agents were prescribed. One intensive care unit admission and 2 cases requiring ventilatory support were documented. No influenza-related deaths were reported. CONCLUSION: Pediatric influenza vaccination was low despite the burden and healthcare use related to seasonal influenza in the pediatric population during a 10-year period in Italy.

Additional Burden Averted in the United States From Use of MF59-Adjuvanted Seasonal Influenza Vaccine Compared With Standard Seasonal Influenza Vaccine Among Adults ≥65 Years.

Background: The MF59-adjuvanted trivalent inactivated influenza vaccine (aIIV3) is designed to overcome immunosenescence and enhance vaccine responses in older adults. We expanded on the Centers for Disease Control and Prevention (CDC) modeling method to estimate the number of additional influenza-related outcomes averted with aIIV3 versus generic quadrivalent inactivated influenza vaccine (IIV4) in adults ≥65 years over 3 influenza seasons (2017-2018 to 2019-2020) in the United States. Methods: A static compartmental model was developed based on an existing CDC model with 2 previously recommended calculation methods that increased the accuracy of the model in providing estimates of burden averted. Model inputs included vaccine effectiveness, vaccine coverage, population counts, and disease burden estimates. Additional burden averted (symptomatic cases, outpatient visits, hospitalizations, intensive care unit [ICU] admissions, and deaths) was expressed as total incremental cases averted between the vaccines. Sensitivity analyses tested the resilience of the model results to uncertainties in model inputs. Results: The model estimated that vaccination with aIIV3 versus IIV4 would avert 2.24 times as many symptomatic cases, outpatient visits, hospitalizations, ICU stays, and deaths during 2017-2018; the burden averted in 2018-2019 and 2019-2020 with aIIV3 would be 3.44 and 1.72 times that averted with IIV4, respectively. Disease burden estimates and relative vaccine effectiveness of aIIV3 had the greatest impact on model estimates. Conclusions: Over 3 influenza seasons, the model estimated that aIIV3 was more effective than IIV4 in averting influenza-related outcomes, preventing 1.72 to 3.44 times as many influenza illnesses with proportionate decreases in related healthcare use and complications.

Relative Effectiveness of the Cell-Based Quadrivalent Influenza Vaccine in Preventing Cardiorespiratory Hospitalizations in Adults Aged 18-64 Years During the 2019-2020 US Influenza Season.

Background: The mammalian cell-based quadrivalent inactivated influenza vaccine (IIV4c) has advantages over egg-based quadrivalent inactivated influenza vaccine (IIV4e), as production using cell-derived candidate viruses eliminates the opportunity for egg adaptation. This study estimated the relative vaccine effectiveness (rVE) of IIV4c versus IIV4e in preventing cardiorespiratory hospitalizations during the 2019-2020 US influenza season. Methods: We conducted a retrospective cohort study using electronic medical records linked to claims data of US individuals aged 18-64 years. We assessed rVE against cardiorespiratory hospitalizations and against subcategories of this outcome, including influenza, pneumonia, myocardial infarction and ischemic stroke, and respiratory hospitalizations. We used a doubly robust inverse probability of treatment weighting and logistic regression model to obtain odds ratios (ORs; odds of outcome among IIV4c recipients/odds of outcome among IIV4e recipients) adjusted for age, sex, race, ethnicity, geographic region, vaccination week, health status, frailty, and healthcare resource utilization. rVE was calculated as 100(1 - ORadjusted). Results: In total, 1 491 097 individuals (25.2%) received IIV4c, and 4 414 758 (74.8%) received IIV4e. IIV4c was associated with lower odds of cardiorespiratory (rVE, 2.5% [95% confidence interval, 0.9%-4.1%]), respiratory (3.7% [1.5%-5.8%]), and influenza (9.3% [0.4%-17.3%]) hospitalizations among adults 18-64 years of age. No difference was observed for the other outcomes. Conclusions: This real-world study conducted for the 2019-2020 season demonstrated that vaccination with IIV4c was associated with fewer cardiorespiratory, respiratory, and influenza hospitalizations compared with IIV4e.

Influenza Vaccine Uptake in the United States before and during the COVID-19 Pandemic.

The COVID-19 pandemic, along with disruptions to routine medical care, brought renewed urgency to public health messaging about the importance of influenza vaccination. This retrospective cohort study used a database of linked claims and electronic medical record data to evaluate clinical and demographic characteristics and influenza vaccination history associated with changes in influenza vaccine uptake following the start of the COVID-19 pandemic. Influenza vaccine uptake was examined in six seasons (2015−2016 through 2020−2021). Individuals were grouped by vaccination history in the five seasons before 2020−2021. Characteristics of 2020−2021 vaccinated vs. unvaccinated individuals were compared, stratified by vaccination history. Overall influenza vaccination uptake was highest in 2020−2021 (35.4%), following a trend of increasing uptake since 2016−2017 (31.4%). Uptake in 2020−2021 was observed in all age groups except ≥65 years, and the increase was particularly notable in individuals <18 years. In the previous five seasons, individuals ≤17 and >65 years, White, and Asian individuals were most likely, while 18-to-49-year-olds and those with fewer comorbidities were least likely, to be consistently vaccinated. Influenza vaccination status in 2020−2021 aligned with vaccination history; few differences in patient characteristics (age, comorbidities, state of residence) were observed when stratified by vaccination history.

The value of public-private collaborative real-world evidence platforms to monitor vaccine performance post authorization: DRIVE - a European initiative.

INTRODUCTION: Fighting pandemics requires an established infrastructure for pandemic preparedness, with existing, sustainable platforms ready to be activated. This includes platforms for disease surveillance, virus circulation, and vaccine performance monitoring based on Real-World data, to complement clinical trial evidence. AREAS COVERED: Because of its complexity, this can best be done by combining efforts between public and private sectors, developing a multi-stakeholder approach. Public-Private-Partnerships increasingly play a critical role in combating infectious diseases but are still looked at with hesitancy. The Development of Robust and Innovative Vaccine Effectiveness (DRIVE) project, which established a platform for measuring brand-specific influenza vaccine effectiveness in Europe, exemplifies how to build a collaborative platform with transparent governance, state-of-the-art methodology, and a large network of participating sites. Lessons learned from DRIVE have been cardinal to set up COVIDRIVE, a platform for brand-specific COVID-19 vaccine effectiveness monitoring. EXPERT OPINION: The DRIVE partners propose that a debate on the benefits of Public-Private-Partnership-generated real-world evidence for vaccine effectiveness monitoring should be pursued to clarify roles and responsibilities, set up expectations, and decide the future environment for vaccine monitoring in Europe. In parallel, the driving factors behind PPP hesitancy should be studied.

Relative Vaccine Effectiveness of Adjuvanted Trivalent Influenza Vaccine over Three Consecutive Influenza Seasons in the United States.

Traditional influenza vaccines may be less immunogenic in adults ≥65 years of age due to immunosenescence. Two influenza vaccines-MF59®-adjuvanted trivalent inactivated influenza vaccine (aIIV3) and high-dose influenza vaccine (HD-IIV3)-were developed to overcome this problem. We summarize estimates of the relative vaccine effectiveness (rVE) of aIIV3 vs. HD-IIV3 and aIIV3 vs. standard, egg-based quadrivalent influenza vaccines (IIV4e) during the 2017-2018, 2018-2019, and 2019-2020 US influenza seasons using the same underlying electronic medical record and linked claims dataset for all three seasons. The primary outcome was influenza-related medical encounters (IRMEs), defined by diagnostic codes specific to influenza (ICD J09*-J11*). rVE was estimated using propensity score methods adjusting for demographics and health status. rVE estimates demonstrated consistent benefit for aIIV3 over IIV4e in the overall and at-risk populations. Relative to HD-IIV3, aIIV3 provided improved benefit in the overall study population and comparable benefit in the at-risk population across each season.

Review of Analyses Estimating Relative Vaccine Effectiveness of Cell-Based Quadrivalent Influenza Vaccine in Three Consecutive US Influenza Seasons.

The adaptation of influenza seed viruses in egg culture can result in a variable antigenic vaccine match each season. The cell-based quadrivalent inactivated influenza vaccine (IIV4c) contains viruses grown in mammalian cell lines rather than eggs. IIV4c is not subject to egg-adaptive changes and therefore may offer improved protection relative to egg-based vaccines, depending on the degree of match with circulating influenza viruses. We summarize the relative vaccine effectiveness (rVE) of IIV4c versus egg-based quadrivalent influenza vaccines (IIV4e) to prevent influenza-related medical encounters (IRMEs) from three retrospective observational cohort studies conducted during the 2017-2018, 2018-2019, and 2019-2020 US influenza seasons using the same underlying electronic medical record dataset for all three seasons-with the addition of linked medical claims for the latter two seasons. We identified IRMEs using diagnostic codes specific to influenza disease (ICD J09*-J11*) from the records of over 10 million people. We estimated rVE using propensity score methods adjusting for age, sex, race, ethnicity, geographic location, week of vaccination, and health status. Subgroup analyses included specific age groups. IIV4c consistently had higher relative effectiveness than IIV4e across all seasons assessed, which were characterized by different dominant circulating strains and variable antigenic drift or egg adaptation.

Global patterns of seasonal influenza activity, duration of activity and virus (sub)type circulation from 2010 to 2020.

BACKGROUND: Seasonal influenza viruses undergo unpredictable changes, which may lead to antigenic mismatch between circulating and vaccine strains and to a reduced vaccine effectiveness. A continuously updated knowledge of influenza strain circulation and seasonality is essential to optimize the effectiveness of influenza vaccination campaigns. We described the global epidemiology of influenza between the 2009 A(H1N1)p and the 2020 COVID-19 pandemic. METHODS: Influenza virological surveillance data were obtained from the WHO-FluNet database. We determined the median proportion of influenza cases caused by the different influenza virus types, subtypes, and lineages; the typical timing of the epidemic peak; and the median duration of influenza epidemics (applying the annual average percentage method with a 75% threshold). RESULTS: We included over 4.6 million influenza cases from 149 countries. The median proportion of influenza cases caused by type A viruses was 75.5%, highest in the Southern hemisphere (81.6%) and lowest in the intertropical belt (73.0%), and ranged across seasons between 60.9% in 2017 and 88.7% in 2018. Epidemic peaks typically occurred during winter months in Northern and Southern hemisphere countries, while much more variability emerged in tropical countries. Influenza epidemics lasted a median of 25 weeks (range 8-42) in countries lying between 30°N and 26°S, and a median of 9 weeks (range 5-25) in countries outside this latitude range. CONCLUSIONS: This work will establish an important baseline to better understand factors that influence seasonal influenza dynamics and how COVID-19 may have affected seasonal activity and influenza virus types, subtypes, and lineages circulation patterns.

Effectiveness of the MF59-adjuvanted trivalent or quadrivalent seasonal influenza vaccine among adults 65 years of age or older, a systematic review and meta-analysis.

BACKGROUND: Standard-dose seasonal influenza vaccines often produce modest immunogenic responses in adults ≥65 years old. MF59 is intended to elicit a greater magnitude and increased breadth of immune response. OBJECTIVE: To determine the effectiveness of seasonal MF59-adjuvanted trivalent/quadrivalent influenza vaccine (aTIV/aQIV) relative to no vaccination or vaccination with standard or high-dose egg-based influenza vaccines among people ≥65 years old. METHODS: Cochrane methodological standards and PRISMA-P guidelines were followed. Real-world evidence from non-interventional studies published in peer-reviewed journals and gray literature from 1997 through to July 15, 2020, including cluster-randomized trials, were eligible. Two reviewers independently extracted data; risk of bias was assessed using the ROBINS-I tool. RESULTS: Twenty-one studies conducted during the 2006/07-2019/20 influenza seasons were included in the qualitative review; 16 in the meta-analyses. Meta-analysis of test-negative studies found that aTIV reduced medical encounters due to lab-confirmed influenza with pooled estimates of 40.7% (95% CI: 21.9, 54.9; I2  = 0%) for non-emergency outpatient visits and 58.5% (40.7, 70.9; I2  = 52.9%) for hospitalized patients. The pooled estimate of VE from case-control studies was 51.3% (39.1, 61.1; I2  = 0%) against influenza- or pneumonia-related hospitalization. The pooled estimates for the relative VE of aTIV for the prevention of influenza-related medical encounters were 13.9% (4.2, 23.5; I2  = 95.9%) compared with TIV, 13.7% (3.1, 24.2; I2  = 98.8%) compared with QIV, and 2.8% (-2.9, 8.5; I2  = 94.5%) compared with HD-TIV. CONCLUSIONS: Among adults ≥65 years, aTIV demonstrated significant absolute VE, improved relative VE compared to non-adjuvanted standard-dose TIV/QIV, and comparable relative VE to high-dose TIV.

Factors driving choices between types and brands of influenza vaccines in general practice in Austria, Italy, Spain and the UK.

Influenza vaccine effectiveness (IVE) assessment is increasingly stratified by vaccine type or brand, such as done by the European network of DRIVE. In 2019/2020, eleven influenza vaccines were licensed in Europe. If more than one vaccine type is recommended or if more than one vaccine brand is available for a specific risk group, it is not clear which factors affect the choice of a specific vaccine (type or brand) by a health practitioner for individual patients. This is important for IVE assessment. A survey tailored to the 2019/20 local vaccine recommendations was conducted among GPs in four European countries (Austria, Italy, Spain, UK) to understand how influenza vaccine is offered to recommended risk groups and, if GPs have a choice between 2 or more vaccines, what factors influence their vaccine choice for patients. Overall, 360 GPs participated. In Austria, Italy and Spain GPs indicated that influenza vaccines are commonly offered when patients present for consultation, whereas in the UK all GPs indicated that all relevant patients are contacted by letter. In Austria and Italy, roughly 80% of GPs had only one vaccine type available for patients <65y. The use of any specific vaccine type in this age group is mostly determined by the availability of specific vaccine type(s) at the clinic. GPs frequently reported availability of more than one vaccine type for patients ≥65y in Austria (45%), Italy (70%) and Spain (79%). In this group, patient characteristics played a role in choice of vaccine, notably older age and presence of (multiple) comorbidities. Knowing that a non-patient related factor usually determines the vaccine type a patient receives in settings where more than one vaccine type is recommended for risk groups <65y, simplifies IVE assessment in this age group. However, patient characteristics need careful consideration when assessing IVE in those ≥65y.

Investigating the procurement system for understanding seasonal influenza vaccine brand availability in Europe.

BACKGROUND: Timely knowledge of which influenza vaccine brands are procured and where is of interest to inform site-selection for brand-specific influenza vaccine effectiveness (VE) studies. Vaccine procurement is a key determinant of brand availability. We therefore sought to understand how the procurement for seasonal influenza vaccine in Europe is organized, how this drives brand availability and how procurement data could enable to determine brand availability pre-season. METHODS: Structured telephone interviews were conducted with 15 experts in 16 European countries between 2017 and 2019 to collect information on the influenza vaccine procurement systems. Sources of (brand-specific) procurement data were identified and assessed on public accessibility. Vaccine type and brand availability and timelines were determined for the 2019-20 season to understand how procurement systems drive brand availability and diversity. RESULTS: Four main types of procurement systems for seasonal influenza vaccination campaigns were identified: national public tenders (Croatia, Denmark, Finland, Ireland, Lithuania, Netherlands, Norway, Scotland, Slovenia), regional public tenders (Italy, Spain, Sweden), direct purchase of vaccines by GPs (England, Wales) or pharmacies (Belgium, France, Germany, Greece) from manufacturers or wholesalers. National public tender outcomes are publicly available and timely; brand availability at clinic level can generally be deduced or narrowed down to two brands. Regional tender outcomes are more difficult to find, known very late or not available. In Italian and Spanish regions tenders may be awarded only a few weeks before the seasonal campaign. No public procurement information is available for countries with direct purchase. CONCLUSION: At the country-level, brand diversity is generally lower for countries with national public tenders than for countries with regional public tenders or direct purchase. In only a few countries, procurement data at the brand level is both publicly available and timely. Therefore the usefulness of procurement data for prospective site-selection for brand-specific VE studies is limited.

Retrospective Assessment of the Antigenic Similarity of Egg-Propagated and Cell Culture-Propagated Reference Influenza Viruses as Compared with Circulating Viruses across Influenza Seasons 2002-2003 to 2017-2018.

Suboptimal vaccine effectiveness against seasonal influenza is a significant public health concern, partly explained by antigenic differences between vaccine viruses and viruses circulating in the environment. Haemagglutinin mutations within vaccine viruses acquired during serial passage in eggs have been identified as a source of antigenic variation between vaccine and circulating viruses. This study retrospectively compared the antigenic similarity of circulating influenza isolates with egg- and cell-propagated reference viruses to assess any observable trends over a 16-year period. Using annual and interim reports published by the Worldwide Influenza Centre, London, for the 2002-2003 to 2017-2018 influenza seasons, we assessed the proportions of circulating viruses which showed antigenic similarity to reference viruses by season. Egg-propagated reference viruses were well matched against circulating viruses for A/H1N1 and B/Yamagata. However, A/H3N2 and B/Victoria cell-propagated reference viruses appeared to be more antigenically similar to circulating A/H3N2 and B/Victoria viruses than egg-propagated reference viruses. These data support the possibility that A/H3N2 and B/Victoria viruses are relatively more prone to egg-adaptive mutation. Cell-propagated A/H3N2 and B/Victoria reference viruses were more antigenically similar to circulating A/H3N2 and B/Victoria viruses over a 16-year period than were egg-propagated reference viruses.

Enhanced Passive Safety Surveillance (EPSS) confirms an optimal safety profile of the use of MF59® -adjuvanted influenza vaccine in older adults: Results from three consecutive seasons.

BACKGROUND: In Europe, the enhanced safety surveillance (ESS) of seasonal influenza vaccines is mandatory, in order to detect any potential increase in reactogenicity when the vaccine composition is updated. The MF59® -adjuvanted influenza vaccine (Fluad™) is the first and the only licensed adjuvanted seasonal influenza vaccine in Europe. OBJECTIVE: Our objective was to summarize the safety data of Fluad™ over three consecutive seasons. METHODS: A passive approach to ESS (EPSS) was adopted, in which reporting of spontaneous adverse events (AEs) by vaccinees and vaccine exposure was estimated, in order to generate a near real-time reporting rate. EPSS was conducted in Italy during the 2015, 2016, and 2017 influenza seasons in the primary care setting. All AEs reported within 7 days following immunization were analyzed by season, type and seriousness. Fisher's exact test was used to compare frequencies between seasons. RESULTS: Total exposure accounted for approximately 1,000 doses of Fluad™ for each season. A total of 0.5% (2015), 0.7% (2016), and 0.5% (2017) individual case safety reports (ICSRs) were received, corresponding to a total of 9 (2015), 18 (2016), and 12 (2017) spontaneous AEs. The frequencies of AEs of interest were below those expected on the basis of the known safety profile of the vaccine. Most AEs were mild-to-moderate in severity. No between-season difference was found. CONCLUSIONS: Our analyses confirmed that the safety data observed were consistent with the known safety profile of Fluad™, which has been amply established over the last 20 years. No significant changes in the safety profile were observed.