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Background: The 2022/23 influenza season in the United Kingdom saw the return of influenza to prepandemic levels following two seasons with low influenza activity. The early season was dominated by A(H3N2), with cocirculation of A(H1N1), reaching a peak late December 2022, while influenza B circulated at low levels during the latter part of the season. From September to March 2022/23, influenza vaccines were offered, free of charge, to all aged 2–13 (and 14–15 in Scotland and Wales), adults up to 49 years of age with clinical risk conditions and adults aged 50 and above across the mainland United Kingdom. Methods: End‐of‐season adjusted vaccine effectiveness (VE) estimates against sentinel primary‐care attendance for influenza‐like illness, where influenza infection was laboratory confirmed, were calculated using the test negative design, adjusting for potential confounders. Methods: Results In the mainland United Kingdom, end‐of‐season VE against all laboratory‐confirmed influenza for all those > 65 years of age, most of whom received adjuvanted quadrivalent vaccines, was 30% (95% CI: −6% to 54%). VE for those aged 18–64, who largely received cell‐based vaccines, was 47% (95% CI: 37%–56%). Overall VE for 2–17 year olds, predominantly receiving live attenuated vaccines, was 66% (95% CI: 53%–76%). Conclusion: The paper provides evidence of moderate influenza VE in 2022/23. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Antigenic drift is a major driver of viral evolution and a primary reason why influenza vaccines must be reformulated annually. Mismatch between vaccine and circulating viral strains negatively affects vaccine effectiveness and often contributes to higher rates of influenza‐related hospitalizations and deaths, particularly in years dominated by A(H3N2). Several countries recommend enhanced influenza vaccines for older adults, who are at the highest risk of severe influenza complications and mortality. The immunogenicity of enhanced vaccines against heterologous A(H3N2) strains has been examined in nine studies to date. In six studies, an enhanced, licensed MF59‐adjuvanted trivalent inactivated influenza vaccine (aIIV3) consistently increased heterologous antibody titers relative to standard influenza vaccine, with evidence of a broad heterologous immune response across multiple genetic clades. In one study, licensed high‐dose trivalent inactivated influenza vaccine (HD‐IIV3) also induced higher heterologous antibody titers than standard influenza vaccine. In a study comparing a higher dose licensed quadrivalent recombinant influenza vaccine (RIV4) with HD‐IIV3 and aIIV3, no significant differences in antibody titers against a heterologous strain were observed, although seroconversion rates were higher with RIV4 versus comparators. With the unmet medical need for improved influenza vaccines, the paucity of studies especially with enhanced vaccines covering mismatched strains highlights a need for further investigation of cross‐protection in older adults. [ABSTRACT FROM AUTHOR]

Introduction: In 2013, the United Kingdom began to roll‐out a universal annual influenza vaccination program for children. An important component of any new vaccination program is measuring its effectiveness. Live‐attenuated influenza vaccines (LAIVs) have since shown mixed results with vaccine effectiveness (VE) varying across seasons and countries elsewhere. This study aims to assess the effectiveness of influenza vaccination in children against severe disease during the first three seasons of the LAIV program in England. Methods: Using the screening method, LAIV vaccination coverage in children hospitalized with laboratory‐confirmed influenza infection was compared with vaccination coverage in 2–6‐year‐olds in the general population to estimate VE in 2013/14–2015/16. Results: The overall LAIV VE, adjusted for age group, week/month and geographical area, for all influenza types pooled over the three influenza seasons was 50.1% (95% confidence interval [CI] 31.2, 63.8). By age, there was evidence of protection against hospitalization from influenza vaccination in both the pre‐school (2–4‐year‐olds) (48.1%, 95% CI 27.2, 63.1) and school‐aged children (5–6‐year‐olds) (62.6%, 95% CI 2.6, 85.6) over the three seasons. Conclusion: LAIV vaccination in children provided moderate annual protection against laboratory‐confirmed influenza‐related hospitalization in England over the three influenza seasons. This study contributes further to the limited literature to date on influenza VE against severe disease in children. [ABSTRACT FROM AUTHOR]

Background: We describe the epidemiology and clinical features of Kenyan patients hospitalized with laboratory‐confirmed influenza compared with those testing negative and discuss the potential contribution of severe acute respiratory illness (SARI) surveillance in monitoring a broader range of respiratory pathogens. Methods: We described demographic and clinical characteristics of SARI cases among children (<18 years) and adults, separately. We compared disease severity (clinical features and treatment) of hospitalized influenza positive versus negative cases and explored independent predictors of death among SARI cases using a multivariable logistic regression model. Results: From January 2014 to December 2018, 11,166 persons were hospitalized with SARI and overall positivity for influenza was ~10%. There were 10,742 (96%) children (<18 years)—median age of 1 year, interquartile range (IQR = 6 months, 2 years). Only 424 (4%) of the SARI cases were adults (≥18 years), with median age of 38 years (IQR 28 years, 52 years). There was no difference in disease severity comparing influenza positive and negative cases among children. Children hospitalized with SARI who had an underlying illness had greater odds of in‐hospital death compared with those without (adjusted odds ratio 2.11 95% CI 1.09–4.07). No further analysis was done among adults due to the small sample size. Conclusion: Kenya's sentinel surveillance for SARI mainly captures data on younger children. Hospital‐based platforms designed to monitor influenza viruses and associated disease burden may be adapted and expanded to other respiratory viruses to inform public health interventions. Efforts should be made to capture adults as part of routine respiratory surveillance. [ABSTRACT FROM AUTHOR]

Background: Accurate population estimates of disease incidence and burden are needed to set appropriate public health policy. The capture–recapture (C‐R) method combines data from multiple sources to provide better estimates than is possible using single sources. Methods: Data were derived from clinical virology test results and from an influenza vaccine effectiveness study from seasons 2016–2017 to 2018–2019. The Petersen C‐R method was used to estimate the population size of influenza cases; these estimates were then used to calculate adult influenza hospitalization burden using a Centers for Disease Control and Prevention (CDC) multiplier method. Results: Over all seasons, 343 influenza cases were reported in the clinical database, and 313 in the research database. Fifty‐nine cases (17%) reported in the clinical database were not captured in the research database, and 29 (9%) cases in the research database were not captured in the clinical database. Influenza hospitalizations were higher among vaccinated (58%) than the unvaccinated (35%) in the current season and were similar among unvaccinated (51%) and vaccinated (49%) in the previous year. Completeness of the influenza hospitalization capture was estimated to be 76%. The incidence rates for influenza hospitalizations varied by age and season and averaged 307–309 cases/100,000 adult population annually. Conclusion: Using C‐R methods with more than one database, along with a multiplier method with adjustments improves the population estimates of influenza disease burden compared with relying on a single‐data source. [ABSTRACT FROM AUTHOR]

Objective: To examine a robust relative risk (RR) estimation for survey data analysis with ideal inferential properties under various model assumptions. Data sources: We employed secondary data from the Household Component of the 2000–2016 US Medical Expenditure Panel Survey (MEPS). Study design: We investigate a broad range of data‐balancing techniques by implementing influence function (IF) methods, which allows us to easily estimate the variability for the RR estimates in the complex survey setting. We conduct a simulation study of seasonal influenza vaccine effectiveness to evaluate these approaches and discuss techniques that show robust inferential performance across model assumptions. Data collection/Extraction methods: Demographic information, vaccine status, and self‐administered questionnaire surveys were obtained from the longitudinal data files. We linked this information with medical condition files and medical event to extract the disease type and associated expenditures for each medical visit. We excluded individuals who were 18 years or younger at the beginning of each panel. Principal findings: Under various model assumptions, the IF methods show robust inferential performance when the data‐balancing procedures are incorporated. Once IF methods and data‐balancing techniques are implemented, contingency table‐based RR estimation yields a comparable result to the generalized linear model approach. We demonstrate the applicability of the proposed methods for complex survey data using 2000–2016 MEPS data. When employing these methods, we find a significant, negative association between vaccine effectiveness (VE) estimates and influenza‐incurred expenditures. Conclusions: We describe and demonstrate a robust method for RR estimation and relevant inferences for influenza vaccine effectiveness using MEPS data. The proposed method is flexible and can be extended to weighted data for survey data analysis. Hence, these methods have great potential for health services research, especially when data are nonexperimental and imbalanced. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Adults with cardiopulmonary conditions may be at increased risk of influenza and respiratory syncytial virus (RSV) infection, but it is not well‐established and few data are available from middle‐income countries. Methods: Using data from a prospective cohort study of influenza vaccine effectiveness, we estimated and compared the incidences of influenza and RSV between community‐dwelling Thai adults aged ≥ 65 years with and without cardiopulmonary conditions. During May 2015‐May 2017, older adults in a rural province in Thailand were followed‐up with weekly surveillance for acute respiratory illness (ARI), defined broadly as new onset or worsening of cough with or without fever, and hospitalized ARI. When ill, nasal self‐swabs and/or nasopharyngeal swabs were collected for reverse‐transcription polymerase chain reaction testing. We used Poisson regression to calculate incidence rate ratios (IRR), adjusting for age, sex, current smoking, number of hospital visits, weekly influenza activity, and influenza vaccination. Results: Overall, 3220 adults with a median age of 71 years (IQR 68‐76) were enrolled; 1324 (41.1%) were male; and 313 (9.7%) had ≥1 underlying cardiopulmonary condition, most commonly chronic obstructive pulmonary disease (131; 41.2%) or asthma (73; 23.3%). Participants with cardiopulmonary conditions had higher incidences of ARI, influenza, and RSV than those without (Adjusted IRR: 1.84, 95% CI 1.64‐2.07; 1.86, 95% CI 1.07‐3.26; 2.04, 95% CI 1.11‐3.76, respectively). Conclusion: Older adults in rural Thailand with cardiopulmonary conditions have increased rates of ARI, influenza, and RSV infections. Our findings support efforts to ensure this population has access to influenza vaccines and other respiratory illness prevention measures. [ABSTRACT FROM AUTHOR]

Systematic reviews and meta‐analyses confirm that influenza vaccination reduces the risk of influenza illness by between about 40% and 60% in seasons when circulating influenza stains are well matched to vaccine strains. Influenza vaccine effectiveness (IVE) estimates, however, are often discordant and a source of confusion for decision makers. IVE assessments are increasingly publicized and are often used by policy makers to make decisions about the value of seasonal influenza vaccination. But there is limited guidance on how IVE should be interpreted or used to inform policy. There are several limitations to the use of IVE for decision‐making: (a) IVE studies have methodological issues that often complicate the interpretation of their value; and (b) the full impact of vaccination will almost always be greater than the impact assessed by a point estimate of IVE in specific populations or settings. Understanding the strengths and weaknesses of study methodologies and the fundamental limitations of IVE estimates is important for the accuracy of interpretations and support of policy makers' decisions. Here, we review a comprehensive set of issues that need to be considered when interpreting IVE and determining the full benefits of influenza vaccination. We propose that published IVE values should be assessed using an evaluative framework that includes influenza‐specific outcomes, types of VE study design, and confounders, among other factors. Better interpretation of IVE will improve the broader assessment of the value of influenza vaccination and ultimately optimize the public health benefits in seasonal influenza vaccination. [ABSTRACT FROM AUTHOR]

Keywords: influenza; systematic review; vaccines EN influenza systematic review vaccines 828 829 2 10/27/21 20211101 NES 211101 CONFLICT OF INTEREST BLC and RS were employed by Sinai Health which received funding from Seqirus for this review. 3 Gasparini R, Amicizia D, Lai PL, Rossi S, Panatto D. Effectiveness of adjuvanted seasonal influenza vaccines (Inflexal V and Fluad) in preventing hospitalization for influenza and pneumonia in the elderly: a matched case-control study. Similarly, the original pooled estimate for the relative VE of aTIV versus TIV for the influenza-related medical encounters (13.9% [4.2, 23.5]) did not change considerably when Mannino et al. was removed in a post hoc analysis (13.0% [2.9, 23.0]). [Extracted from the article]