Influenza vaccine effectiveness among healthcare workers in comparison to hospitalized patients: A 2004-2009 case-test, negative-control, prospective study

Abstract Background Non-egg-based influenza vaccine manufacturing reduces egg adaptation and therefore has the potential to increase vaccine effectiveness. This study evaluated whether the cell-based quadrivalent influenza vaccine (QIVc) improved relative vaccine effectiveness (rVE) compared to standard-dose egg-based quadrivalent influenza vaccine (QIVe-SD) in the reduction of influenza-related and respiratory-related hospitalizations/emergency room (ER) visits among subjects 4-64 years old during the 2019/20 influenza season. Methods A retrospective analysis was conducted among subjects 4-64 years old vaccinated with QIVc or QIVe-SD using administrative claims data in the United States of America (U.S.) (IQVIA PharMetrics® Plus). Inverse probability of treatment weighting (IPTW) was used to adjust for baseline confounders. Post-IPTW, the number of events and rates (per 1,000 vaccinated subject-seasons) of influenza-related hospitalizations/ER visits, respiratory-related hospitalizations/ER visits and all-cause hospitalizations were assessed. Poisson regression was used to estimate adjusted rVE. To avoid any influenza outcome misclassification with COVID-19 infection, the study period ended March 7,2020. A sub-analysis for a high-risk subgroup was conducted. Urinary tract infection (UTI) hospitalization was assessed as a negative control endpoint. Results During the 2019/20 influenza season, 1,150,134 QIVc and 3,924,819 QIVe-SD recipients were identified post-IPTW. Overall adjusted analyses (4-64 years old) found that QIVc was associated with a significantly higher rVE compared to QIVe-SD against influenza-related hospitalizations/ER visits (5.3% [95% CI: 0.5%-9.9%]), all-cause hospitalizations (14.5% [95% CI: 13.1%-15.8%]) and any respiratory-related hospitalization/ER visit (8.2% [95% CI: 6.5%-9.8%]). A similar trend was seen for the high-risk subgroup; for instance, rVE for QIVc compared to QIVe-SD against influenza-related hospitalizations/ER visits was 10.5% [95% CI: 2.9%-17.4%]. No effect was identified for the negative control outcome. Conclusion QIVc was significantly more effective in preventing influenza-related and respiratory-related hospitalizations/ER visits, as well as all-cause hospitalizations, compared to QIVe-SD. Disclosures Stephen I. Pelton, MD, Seqirus (Consultant) Maarten Postma, Dr., Seqirus (Consultant) Victoria Divino, PhD, Seqirus (Consultant) Joaquin F. Mould-Quevedo, PhD, Seqirus (Employee) Ruthwik Anupindi, PhD, Seqirus (Consultant) Mitchell DeKoven, PhD, Seqirus (Consultant) myron J. levin, MD, GSK group of companies (Employee, Research Grant or Support)

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Incorporating Real-time Influenza Detection Into the Test-negative Design for Estimating Influenza Vaccine Effectiveness: The Real-time Test-negative Design (rtTND)

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1453 ◽

2020 ◽

Author(s):

Leora R Feldstein ◽

Wesley H Self ◽

Jill M Ferdinands ◽

Adrienne G Randolph ◽

Michael Aboodi ◽

...

Keyword(s):

Influenza Vaccine ◽

Real Time ◽

Negative Control ◽

Vaccine Effectiveness ◽

Eligibility Criteria ◽

The Real ◽

Advantages And Disadvantages ◽

Time Test ◽

Study Sites ◽

Negative Controls

Abstract With rapid and accurate molecular influenza testing now widely available in clinical settings, influenza vaccine effectiveness (VE) studies can prospectively select participants for enrollment based on real-time results rather than enrolling all eligible patients regardless of influenza status, as in the traditional test-negative design (TND). Thus, we explore advantages and disadvantages of modifying the TND for estimating VE by using real-time, clinically available viral testing results paired with acute respiratory infection eligibility criteria for identifying influenza cases and test-negative controls prior to enrollment. This modification, which we have called the real-time test-negative design (rtTND), has the potential to improve influenza VE studies by optimizing the case-to-test-negative control ratio, more accurately classifying influenza status, improving study efficiency, reducing study cost, and increasing study power to adequately estimate VE. Important considerations for limiting biases in the rtTND include the need for comprehensive clinical influenza testing at study sites and accurate influenza tests.

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Healthcare Workers’ Willingness to Receive Influenza Vaccination in the Context of the COVID-19 Pandemic: A Survey in Southern Italy

Vaccines ◽

10.3390/vaccines9070766 ◽

2021 ◽

Vol 9 (7) ◽

pp. 766

Author(s):

Gabriella Di Giuseppe ◽

Concetta P. Pelullo ◽

Andrea Paolantonio ◽

Giorgia Della Polla ◽

Maria Pavia

Keyword(s):

Side Effects ◽

Influenza Vaccine ◽

Influenza Vaccination ◽

Healthcare Workers ◽

Southern Italy ◽

Hospitalized Patients ◽

Cross Sectional Survey ◽

Enabling Factors ◽

Cross Sectional ◽

To Receive

This cross-sectional survey was designed to evaluate hospital healthcare workers’ (HCWs) willingness to receive the influenza vaccination during the COVID-19 pandemic and to identify the related determinants, since it is plausible that the two epidemics will coexist in future winters. Overall, 68% out of 490 participants expressed their willingness to receive influenza vaccination in the 2020/21 season, with 95% of those ever and 45.8% of those never vaccinated in the previous six influenza seasons. Belief that influenza vaccine is useful in distinguishing influenza symptoms from those of COVID-19 and that the influenza vaccine is useful to prevent influenza in hospital settings, willingness to receive COVID-19 vaccination, having no concern about influenza vaccine side effects, concern about the possibility to transmit influenza to hospitalized patients, and influenza vaccination in previous years were all predictors of willingness to receive influenza vaccination. In the context of the COVID-19 pandemic, a relevant increase in the willingness to undergo influenza vaccination was reported. Therefore, interventions focused primarily on enabling factors are needed to promote the adherence to influenza vaccination in future seasons among HCWs.

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Spotlight influenza: Estimation of influenza vaccine effectiveness in elderly people with assessment of residual confounding by negative control outcomes, Finland, 2012/13 to 2019/20

Eurosurveillance ◽

10.2807/1560-7917.es.2021.26.36.2100054 ◽

2021 ◽

Vol 26 (36) ◽

Author(s):

Ulrike Baum ◽

Sangita Kulathinal ◽

Kari Auranen

Keyword(s):

Influenza Vaccine ◽

Elderly People ◽

Demographic Data ◽

The Elderly ◽

Negative Control ◽

Vaccine Effectiveness ◽

Hazard Ratio ◽

Confounding Bias ◽

Vaccination History ◽

Residual Confounding

Background Cohort studies on vaccine effectiveness are prone to confounding bias if the distribution of risk factors is unbalanced between vaccinated and unvaccinated study subjects. Aim We aimed to estimate influenza vaccine effectiveness in the elderly population in Finland by controlling for a sufficient set of confounders based on routinely available register data. Methods For each of the eight consecutive influenza seasons from 2012/13 through 2019/20, we conducted a cohort study comparing the hazards of laboratory-confirmed influenza in vaccinated and unvaccinated people aged 65–100 years using individual-level medical and demographic data. Vaccine effectiveness was estimated as 1 minus the hazard ratio adjusted for the confounders age, sex, vaccination history, nights hospitalised in the past and presence of underlying chronic conditions. To assess the adequacy of the selected set of confounders, we estimated hazard ratios of off-season hospitalisation for acute respiratory infection as a negative control outcome. Results Each analysed cohort comprised around 1 million subjects, of whom 37% to 49% were vaccinated. Vaccine effectiveness against laboratory-confirmed influenza ranged from 16% (95% confidence interval (CI): 12–19) to 48% (95% CI: 41–54). More than 80% of the laboratory-confirmed cases were hospitalised. The adjusted off-season hazard ratio estimates varied between 1.00 (95% CI: 0.94–1.05) and 1.08 (95% CI: 1.01–1.15), indicating that residual confounding was absent or negligible. Conclusion Seasonal influenza vaccination reduces the hazard of severe influenza disease in vaccinated elderly people. Data about age, sex, vaccination history and utilisation of hospital care proved sufficient to control confounding.

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Influenza Vaccine Effectiveness Against Influenza-Related Mortality in Australian Hospitalized Patients: A Propensity Score Analysis

Clinical Infectious Diseases ◽

10.1093/cid/ciz1238 ◽

2020 ◽

Cited By ~ 1

Author(s):

Monica L Nation ◽

Robert Moss ◽

Matthew J Spittal ◽

Tom Kotsimbos ◽

Paul M Kelly ◽

...

Keyword(s):

Propensity Score ◽

Influenza Vaccine ◽

Influenza Vaccination ◽

Propensity Score Analysis ◽

Vaccine Effectiveness ◽

Hospitalized Patients ◽

Score Analysis ◽

Influenza Illness ◽

Residual Confounding ◽

Related Mortality

Abstract Background Data on influenza vaccine effectiveness (IVE) against mortality are limited, with no Australian data to guide vaccine uptake. We aimed to assess IVE against influenza-related mortality in Australian hospitalized patients, assess residual confounding in the association between influenza vaccination and mortality, and assess whether influenza vaccination reduces the severity of influenza illness. Methods Data were collected between 2010 and 2017 from a national Australian hospital-based sentinel surveillance system using a case-control design. Adults and children admitted to the 17 study hospitals with acute respiratory symptoms were tested for influenza using nucleic acid testing; all eligible test-positive cases, and a subset of test-negative controls, were included. Propensity score analysis and multivariable logistic regression were used to determine the adjusted odds ratio (aOR) of vaccination, with IVE = 1 – aOR × 100%. Residual confounding was assessed by examining mortality in controls. Results Over 8 seasons, 14038 patients were admitted with laboratory-confirmed influenza. The primary analysis included 9298 cases and 6451 controls, with 194 cases and 136 controls dying during hospitalization. Vaccination was associated with a 31% (95% confidence interval [CI], 3%–51%; P = .033) reduction in influenza-related mortality, with similar estimates in the National Immunisation Program target group. Residual confounding was identified in patients ≥65 years old (aOR, 1.92 [95% CI, 1.06–3.46]; P = .031). There was no evidence that vaccination reduced the severity of influenza illness (aOR, 1.07 [95% CI, .76–1.50]; P = .713). Conclusions Influenza vaccination is associated with a moderate reduction in influenza-related mortality. This finding reinforces the utility of the Australian vaccination program in protecting those most at risk of influenza-related deaths.

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Estimates of 2012/13 influenza vaccine effectiveness using the case test-negative control design with different influenza negative control groups

Vaccine ◽

10.1016/j.vaccine.2014.06.053 ◽

2014 ◽

Vol 32 (35) ◽

pp. 4443-4449 ◽

Cited By ~ 11

Author(s):

Baltazar Nunes ◽

Ausenda Machado ◽

Raquel Guiomar ◽

Pedro Pechirra ◽

Patrícia Conde ◽

...

Keyword(s):

Influenza Vaccine ◽

Control Design ◽

Negative Control ◽

Vaccine Effectiveness ◽

Control Groups

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1715. Influenza-like Illness (ILI) Experience Among Healthcare Workers in Military Treatment Facilities: An Offshoot of the Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD (PAIVED) Study

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1893 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S841-S841

Author(s):

Rhonda Colombo ◽

Stephanie Richard ◽

Christina Schofield ◽

Limone Collins ◽

Anuradha Ganesan ◽

...

Keyword(s):

Influenza Vaccine ◽

Healthcare Workers ◽

Pathogen Detection ◽

Demographic Data ◽

A Priori ◽

Vaccine Effectiveness ◽

Published Data ◽

Respiratory Pathogens ◽

Physically Active ◽

Influenza Like Illness

Abstract Background Healthcare workers (HCWs) are at heightened risk of exposure to respiratory pathogens. There are limited published data on influenza-like illness (ILI) experience among HCWs, and the few available studies were hampered by incomplete vaccination histories. PAIVED, a multicenter, multiservice study assessing influenza vaccine effectiveness in the Department of Defense, provides a unique opportunity to describe ILI experience among vaccinated HCWs compared to vaccinated non-HCWs. Methods PAIVED participants were randomized to receive either egg-based, cell-based, or recombinant-derived influenza vaccine then surveyed weekly for ILI. At enrollment, participants provided key demographic data including whether they were HCWs with direct patient contact. ILI was defined a priori as 1) having cough or sore throat plus 2) feeling feverish/having chills or having body aches/fatigue. Participants with ILI completed a daily symptom diary for seven days and submitted a nasal swab for pathogen detection. Results Of 4433 eligible participants enrolled during the 2019-20 influenza season, 1551 (35%) were HCWs. A higher percentage of HCWs experienced an ILI than non-HCWs (34% vs 26%, p< 0.001). Overall, HCWs were more likely to be female (42% vs 32%), age 25-34 years (39% vs 28%), active-duty military (81% vs 62%), non-smokers (88% vs 75%), and physically active (92% vs 85%). Self-reported race differed between HCWs and non-HCWs; a higher proportion of HCWs identified as White (63% vs 56%) or Asian (8% vs 5%). Similar demographic differences existed among HCWs and non-HCWs with ILI. HCWs were more likely to respond to at least 50% of weekly surveillance messages, irrespective of ILI status. HCWs with ILI had less severe lower respiratory symptoms (p< 0.001) and a shorter duration of illness (12.4±8.1 days vs 13.7±9.0, p=0.005) than non-HCWs. Pathogen data is pending. Conclusion HCWs in PAIVED were more likely to report ILI than their non-HCW counterparts yet tended to have lower illness severity, possibly reflecting a higher level of baseline health or enhanced awareness of early ILI symptoms. The important epidemiologic position HCWs occupy for ILI has been apparent in the COVID-19 pandemic. Exploring ways to mitigate ILI risk in HCWs beyond influenza vaccination is warranted. Disclaimer Disclosures All Authors: No reported disclosures

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