Influenza-related Hospitalizations Research Articles

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.

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. 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*). 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. 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.

Impact of influenza related hospitalization in Spain: characteristics and risk factor of mortality during five influenza seasons (2016 to 2021).

Estimating the global influenza burden in terms of hospitalization and death is important for optimizing prevention policies. Identifying risk factors for mortality allows for the design of strategies tailored to groups at the highest risk. This study aims to (a) describe the clinical characteristics of hospitalizations with a diagnosis of influenza over five flu seasons (2016-2017 to 2020-2021), (b) assess the associated morbidity (hospitalization rates and ICU admissions rate), mortality and cost of influenza hospitalizations in different age groups and (c) analyze the risk factors for mortality. This retrospective study included all hospital admissions with a diagnosis of influenza in Spain for five influenza seasons. Data were extracted from the Spanish National Surveillance System for Hospital Data from 1 July 2016 to 30 June 2021. We identified cases coded as having influenza as a primary or secondary diagnosis (International Classification of Diseases, 10th revision, J09-J11). The hospitalization rate was calculated relative to the general population. Independent predictors of mortality were identified using multivariable logistic regression. Over the five seasons, there were 127,160 hospitalizations with a diagnosis of influenza. The mean influenza hospitalization rate varied from 5/100,000 in 2020-2021 (COVID-19 pandemic) to 92.9/100,000 in 2017-2018. The proportion of influenza hospitalizations with ICU admission was 7.4% and was highest in people aged 40-59 years (13.9%). The case fatality rate was 5.8% overall and 9.4% in those aged 80 years or older. Median length of stay was 5 days (and 6 days in the oldest age group). In the multivariable analysis, independent risk factors for mortality were male sex (odds ratio [OR] 1.14, 95% confidence interval [95% CI] 1.08-1.20), age (<5 years: OR 1; 5-19 years: OR 2.02, 95%CI 1.17-3.49; 20-39 years: OR 4.11, 95% CI 2.67-6.32; 40-59 years: OR 8.15, 95% CI 5.60-11.87; 60-79 years: OR 15.10, 95% CI 10.44-21.84; ≥80 years: OR 33.41, 95% CI 23.10-48.34), neurological disorder (OR 1.97, 95% CI 1.83-2.11), heart failure (OR 1.85, 95% CI 1.74-1.96), chronic kidney disease (OR 1.33, 95% CI 1.25-1.41), chronic liver disease (OR 2.95, 95% CI 2.68-3.27), cancer (OR 1.85, 95% CI 1.48-2.24), coinfection with SARS-CoV2 (OR 3.17, 95% CI 2.34-4.28), influenza pneumonia (OR 1.76, 95% CI 1.66-1.86) and admission to intensive care (OR 7.81, 95% CI 7.31-8.36). Influenza entails a major public health burden. People aged over 60-and especially those over 80-show the longest hospital stays. Age is also the most significant risk factor for mortality, along with certain associated comorbidities.

Immunogenicity of Enhanced Influenza Vaccines Against Mismatched Influenza Strains in Older Adults: A Review of Randomized Controlled Trials.

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.

Economic burden and secondary complications of influenza-related hospitalization among adults in the US: a retrospective cohort study

Objective This study aims to describe the healthcare resource utilization (HCRU) and direct medical cost of influenza-related hospitalizations to illustrate the persistent economic burden of influenza among adults in the US. Methods A retrospective cohort study was conducted using the PINC AI Healthcare Database. Adults hospitalized with a diagnosis of influenza between August 1–May 31 from 2016–2023 were identified and stratified by age (18–49, 50–64 and ≥65 years). The index hospitalization was defined as the individual’s first influenza-related hospitalization during each season. Patient demographics, comorbidities, and hospitalization characteristics were assessed during the index hospitalization. Index hospitalization length of stay (LOS), in-hospital mortality, intensive care unit (ICU) admissions, mechanical ventilation (MV) usage, and costs were evaluated overall and by MV usage, ICU admission, and secondary complication status. Pre-index influenza-related outpatient and emergency department (ED) visits (7 days prior) were also evaluated. Results Primarily initiated in the ED, the median LOS for influenza-related hospitalizations was 3–4 days. Inpatient mortality increased with age (2.2–4.4%). Combined mean hospitalization and initial ED visit costs were $12,556–$14,494 (2017/18; high severity season) and $11,384–$12,896 (2022/23; most recent season). Compared to other age groups, adults ≥65 years had higher proportions of hospitalization with no MV or ICU usage. Adults 18–49 years had the highest proportion of ICU admission only, whereas adults 50–64 years had the highest MV usage only and both MV and ICU admission. MV and/or ICU usage was associated with higher hospitalization costs. Increasing proportionally with age, the majority of influenza-related hospitalizations had a secondary complication diagnosis, which were associated with elevated costs. Limitations Analysis of this hospital-based administrative database relied on coding accuracy. Only hospital system-associated outpatient/ED visits were captured; the full scope of HCRU was under-ascertained. Conclusions The economic burden of influenza-related hospitalizations remains substantial, driven by underlying conditions, MV/ICU usage and secondary complications.

Cell-based influenza vaccines: An effective vaccine option for under 60-year-olds.

Seasonal influenza poses a significant burden of disease, affecting not only older adults but also individuals under the age of 60. It carries a high economic burden, mainly driven by influenza-associated productivity losses in the working population. Conventional egg-based influenza vaccines may have reduced effectiveness due to antigen adaptation in eggs. In contrast, cell-based influenza vaccines are less likely to be affected by such antigen adaptation. This review aims to present real-world data (RWD) comparing the effectiveness of quadrivalent cell-based (QIVc) and egg-based (QIVe) influenza vaccines over three consecutive seasons. A comprehensive review was conducted, analyzing RWD from retrospective cohort and case-control studies on the relative vaccine effectiveness (rVE) of QIVc versus QIVe during the 2017/18-2019/20 seasons. This study included six retrospective cohort studies and one case-control study, with a combined total of approximately 29 million participants. A cohort study involving people aged ≥4 years during the 2017/18 season showed a statistically significant rVE of QIVc compared to QIVe in preventing influenza-like illness, with a value of 36.2%. QIVc demonstrated statistically significant superiority over QIVe in preventing outpatient and inpatient medical encounters as observed in two cohort studies conducted during the 2018/19 and 2019/20 seasons. The rVE of QIVc compared to QIVe was found to be 7.6% in individuals aged ≥4 years and 9.5% in individuals aged ≥18 years. Three additional cohort studies conducted between 2017/18-2019/20 reported a statistically significant improvement in rVE (5.3-14.4%) of QIVc compared to QIVe in preventing influenza-related hospitalizations and emergency department visits due to influenza in individuals aged 4-64 years. In a case-control study across all three seasons, QIVc showed statistically significantly higher effectiveness compared to QIVe in preventing test-confirmed influenza, with rVEs of 10.0-14.8%. RWD from the 2017/18-2019/20 seasons demonstrated that QIVc is more effective than QIVe in preventing influenza-related outcomes in individuals aged 4-64 years. Preferential use of cell-based influenza vaccines, as opposed to conventional egg-based vaccines, could reduce the burden of influenza-related symptoms on individuals and alleviate the economic impact on the German population under 60 years of age.

Recombinant or Standard-Dose Influenza Vaccine in Adults under 65 Years of Age

BackgroundQuadrivalent recombinant influenza vaccines contain three times the amount of hemagglutinin protein as standard-dose egg-based vaccines, and the recombinant formulation is not susceptible to antigenic drift during manufacturing. Data are needed on the relative effectiveness of recombinant vaccines as compared with standard-dose vaccines against influenza-related outcomes in adults under the age of 65 years.MethodsIn this cluster-randomized observational study, Kaiser Permanente Northern California facilities routinely administered either a high-dose recombinant influenza vaccine (Flublok Quadrivalent) or one of two standard-dose influenza vaccines during the 2018–2019 and 2019–2020 influenza seasons to adults 50 to 64 years of age (primary age group) and 18 to 49 years of age. Each facility alternated weekly between the two vaccine formulations. The primary outcome was influenza (A or B) confirmed by polymerase-chain-reaction (PCR) testing. Secondary outcomes included influenza A, influenza B, and influenza-related hospitalization outcomes. We used Cox regression analysis to estimate the hazard ratio of the recombinant vaccine as compared with the standard-dose vaccines against each outcome. We calculated the relative vaccine effectiveness as 1 minus the hazard ratio.ResultsThe study population included 1,630,328 vaccinees between the ages of 18 and 64 years (632,962 in the recombinant-vaccine group and 997,366 in the standard-dose group). During this study period, 1386 cases of PCR-confirmed influenza were diagnosed in the recombinant-vaccine group and 2435 cases in the standard-dose group. Among the participants who were 50 to 64 years of age, 559 participants (2.00 cases per 1000) tested positive for influenza in the recombinant-vaccine group as compared with 925 participants (2.34 cases per 1000) in the standard-dose group (relative vaccine effectiveness, 15.3%; 95% confidence interval [CI], 5.9 to 23.8; P=0.002). In the same age group, the relative vaccine effectiveness against influenza A was 15.7% (95% CI, 6.0 to 24.5; P=0.002). The recombinant vaccine was not significantly more protective against influenza-related hospitalization than were the standard-dose vaccines.ConclusionsThe high-dose recombinant vaccine conferred more protection against PCR-confirmed influenza than an egg-based standard-dose vaccine among adults between the ages of 50 and 64 years. (Funded by Sanofi; ClinicalTrials.gov number, NCT03694392.)

Effectiveness of the quadrivalent live attenuated influenza vaccine against influenza-related hospitalisations and morbidity among children aged 2 to 6 years in Denmark: a nationwide cohort study emulating a target trial.

Scant evidence exists on the real-world effectiveness of quadrivalent live attenuated influenza vaccines (LAIV-4) in younger children. We aimed to assess the real-world effectiveness of LAIV-4 against influenza-related hospital contacts and admission and morbidity. Using nationwide Danish health-care registries, we designed a cohort study that emulates a target trial, comparing LAIV-4 to no vaccination in children aged 2-6 years. Eligible children vaccinated from Oct 1, 2021, to Jan 15, 2022, were matched to unvaccinated controls in a 1:1 ratio according to demographic characteristics and risk groups for influenza, and followed-up until May 31, 2022. Primary study outcomes any hospital contact for influenza and influenza-related hospital admissions more than 12 h in duration, while hospital admission for respiratory tract infections, or for wheezing or asthma, and antibiotic prescriptions were evaluated as secondary outcomes. We estimated incidence rate ratios (IRRs) and 95% CIs using Poisson regression for each outcome. Vaccine effectiveness was calculated as 1 - IRR. Among 308 520 Danish children aged 2-6 years, 95 434 vaccinated children were matched with 95 434 unvaccinated children who acted as controls. Receipt of LAIV-4 compared with no vaccination was associated with a reduced IRR of 0·36 (95% CI 0·27 to 0·46) and estimated vaccine effectiveness of 64·3% (53·6 to 72·6) against influenza-related hospital contacts (76 vs 210 events). The corresponding IRR and vaccine effectiveness against influenza-related hospital admissions were 0·63 (0·38 to 1·05) and 36·9% (-5·2 to 62·1; 24 vs 38 events), respectively. LAIV-4 was not associated with reductions in admission rates for respiratory tract infections (IRR 1·14, 95% CI 0·94 to 1·38), wheezing or asthma (1·04, 0·83 to 1·31), or antibiotic prescriptions for respiratory tract infections (0·97, 0·93 to 1·00). Vaccine effectiveness assessed across risk groups for influenza showed similar effectiveness in children with and without coexisting risk factors for severe influenza. LAIV-4 offered moderate protection in younger children against influenza-related hospital contacts during a season dominated by influenza A(H3N2); however vaccination was not associated with reductions in secondary outcomes. This real-world study thereby supports trial evidence of moderate vaccine effectiveness of LAIV-4 against influenza-related outcomes when implementing broad vaccination schedules in younger children. Beckett-Fonden.

Influenza Vaccine Effectiveness Pre-pandemic Among Adults Hospitalized With Congestive Heart Failure or Chronic Obstructive Pulmonary Disease and Older Adults.

Data are limited on influenza vaccine effectiveness (VE) in the prevention of influenza-related hospitalizations in older adults and those with underlying high-risk comorbidities. We conducted a prospective, test-negative, case-control study at 2 US hospitals from October 2018-March 2020 among adults aged ≥50 years hospitalized with acute respiratory illnesses (ARIs) and adults ≥18 years admitted with congestive heart failure (CHF) or chronic obstructive pulmonary disease (COPD) exacerbations. Adults were eligible if they resided in 1 of 8 counties in metropolitan Atlanta, Georgia. Nasopharyngeal and oropharyngeal swabs were tested using BioFire FilmArray (bioMérieux, Inc.) respiratory panel, and standard-of-care molecular results were included when available. Influenza vaccination history was determined from the Georgia vaccine registry and medical records. We used multivariable logistic regression to control for potential confounders and to determine 95% confidence intervals (CIs). Among 3090 eligible adults, 1562 (50.6%) were enrolled. Of the 1515 with influenza vaccination history available, 701 (46.2%) had received vaccination during that season. Influenza was identified in 37 (5.3%) vaccinated versus 78 (9.6%) unvaccinated participants. After adjustment for age, race/ethnicity, immunosuppression, month, and season, pooled VE for any influenza-related hospitalization in the eligible study population was 63.1% (95% CI, 43.8-75.8%). Adjusted VE against influenza-related hospitalization for ARI in adults ≥50 years was 55.9% (29.9-72.3%) and adjusted VE against influenza-related CHF/COPD exacerbation in adults ≥18 years was 80.3% (36.3-93.9%). Influenza vaccination was effective in preventing influenza-related hospitalizations in adults aged ≥50 years and those with CHF/COPD exacerbations during the 2018-2020 seasons.

Estimated Effectiveness of Coadministration of the BNT162b2 BA.4/5 COVID-19 Vaccine With Influenza Vaccine.

No data comparing the estimated effectiveness of coadministering COVID-19 vaccines with seasonal influenza vaccine (SIV) in the community setting exist. To examine the comparative effectiveness associated with coadministering the BNT162b2 BA.4/5 bivalent mRNA COVID-19 vaccine (BNT162b2-biv [Pfizer BioNTech]) and SIV vs giving each vaccine alone. A retrospective comparative effectiveness study evaluated US adults aged 18 years or older enrolled in commercial health insurance or Medicare Advantage plans and vaccinated with BNT162b2-biv only, SIV only, or both on the same day between August 31, 2022, and January 30, 2023. Individuals with monovalent or another brand of mRNA bivalent COVID-19 vaccine were excluded. Same-day coadministration of BNT162b2-biv and SIV; receipt of BNT162b2-biv only (for COVID-19-related outcomes) or SIV only (for influenza-related outcomes) were the comparator groups. For adults aged 65 years or older, only enhanced SIVs were included. COVID-19-related and influenza-related hospitalization, emergency department (ED) or urgent care (UC) encounters, and outpatient visits. Overall, 3 442 996 individuals (57.0% female; mean [SD] age, 65 [16.7] years) were included. A total of 627 735 individuals had BNT162b2-biv and SIV vaccine coadministered, 369 423 had BNT162b2-biv alone, and 2 445 838 had SIV alone. Among those aged 65 years or older (n = 2 210 493; mean [SD] age, 75 [6.7] years; 57.9% female), the coadministration group had a similar incidence of COVID-19-related hospitalization (adjusted hazard ratio [AHR], 1.04; 95% CI, 0.87-1.24) and slightly higher incidence of emergency department or urgent care encounters (AHR, 1.12; 95% CI, 1.02-1.23) and outpatient visits (AHR, 1.06; 95% CI, 1.01-1.11) compared with the BNT162b2-biv-only group. Among individuals aged 18 to 64 years (n = 1 232 503; mean [SD] age, 47 [13.1] years; 55.4% female), the incidence of COVID-19-related outcomes was slightly higher among those who received both vaccines vs BNT162b2-biv alone (AHR point estimate range, 1.14-1.57); however, fewer events overall in this age group resulted in wider CIs. Overall, compared with those who received SIV alone, the coadministration group had a slightly lower incidence of most influenza-related end points (AHR point estimates 0.83-0.93 for those aged ≥65 years vs 0.76-1.08 for those aged 18-64 years). Negative control outcomes suggested residual bias and calibration of COVID-19-related and influenza-related outcomes with negative controls moved all estimates closer to the null, with most CIs crossing 1.00. In this study, coadministration of BNT162b2-biv and SIV was associated with generally similar effectiveness in the community setting against COVID-19-related and SIV-related outcomes compared with giving each vaccine alone and may help improve uptake of both vaccines.

Cost effectiveness of quadrivalent influenza vaccines in the elderly population of Malaysia

The economic burden of influenza is a significant issue within healthcare system, related to higher medical costs particularly among the elderly. Yet, influenza vaccination rates in the elderly in Malaysia were considerably low as it is not part of Malaysia’s national immunization program, with substantial mortality and morbidity consequences. Therefore, we conducted a cost-effectiveness analysis of quadrivalent influenza vaccine (QIV) for the elderly in Malaysia compared with the current no-vaccination policy. A static cost-utility model, with a lifetime horizon based on age, was used for the analysis to assess the cost-effectiveness and health outcomes associated with QIV. Univariate and probabilistic sensitivity analyses were performed to test the effects of variations in the parameters. The use of QIV in Malaysia’s elderly population would prevent 66,326 potential influenza cases and 888 potential deaths among the elderly, leading to 10,048 potential quality-adjusted life years (QALYs) gained. The QIV would also save over USD 4.4 million currently spent on influenza-related hospitalizations and reduce productivity losses by approximately USD 21.6 million. The ICER per QALY gained from a third-party payer’s perspective would be USD 2216, which is lower than the country’s gross domestic product per capita. A QIV-based vaccination program in the elderly was found to be highly cost-effective, therefore would reduce the financial burden of managing influenza and reduce pre-mature death related to this disease.

Web-based intervention for improving influenza vaccination in pregnant women: a cost-effectiveness analysis

ABSTRACT A website with vaccine information and interactive social media was reported to improve maternal influenza vaccine uptake. This study aimed to evaluate cost-effectiveness of a web-based intervention on influenza vaccine uptake among pregnant women from the perspective of US healthcare providers. A one-year decision-analytic model estimated outcomes in a hypothetical cohort of pregnant women with: (1) website with vaccine information and interactive social media (intervention group), and (2) usual care (usual care group). Primary measures included influenza infection, influenza-related hospitalization, mortality, direct medical cost, and quality-adjusted life-year (QALY) loss. In base-case analysis, intervention group reduced cost (by USD28), infection (by 28 per 1,000 pregnant women), hospitalization (by 1.226 per 1,000 pregnant women), mortality (by 0.0036 per 1,000 pregnant women), and saved 0.000305 QALYs versus usual care group. Relative improvement of vaccine uptake by the intervention and number of pregnant women in the healthcare system were two influential factors identified in deterministic sensitivity analysis. The intervention was cost-effective in 99.5% of 10,000 Monte Carlo simulations (at willingness-to-pay threshold 50,000 USD/QALY). A website with vaccine information and interactive social media to promote influenza vaccination for pregnant women appears to reduce direct medical costs and gain QALYs from the perspective of US healthcare providers.

Vaccine Effectiveness of Cell-Based Quadrivalent Influenza Vaccine in Children: A Narrative Review.

Cell-based manufacturing of seasonal influenza vaccines eliminates the risk of egg-adaptation of candidate vaccine viruses, potentially increasing vaccine effectiveness (VE). We present an overview of published data reporting the VE and cost-effectiveness of a cell-based quadrivalent influenza vaccine (QIVc) in preventing influenza-related outcomes in the pediatric population. We identified 16 clinical studies that included data on the VE of a QIVc or the relative VE (rVE) of a QIVc versus an egg-based QIV (QIVe) in children and/or adolescents, 11 of which presented estimates specifically for the pediatric age group. Of these, two studies reported rVE against hospitalizations. Point estimates of rVE varied from 2.1% to 33.0%, with studies reporting significant benefits of using a QIVc against influenza-related, pneumonia, asthma, and all-cause hospitalization. Four studies reported rVE against influenza-related medical encounters, with point estimates against non-strain specific encounters ranging from 3.9% to 18.8% across seasons. One study evaluated rVE against any influenza, with variable results by strain. The other four studies presented VE data against laboratory-confirmed influenza. Three health economics studies focusing on a pediatric population also found the use of QIVc to be cost-effective or cost-saving. Overall, using a QIVc is effective in pediatric patients, with evidence of incremental benefits over using a QIVe in preventing hospitalizations and influenza-related medical encounters in nearly all published studies.

Cost-effectiveness of seasonal influenza vaccination of children in China: a modeling analysis

BackgroundChina has a high burden of influenza-associated illness among children. We aimed to evaluate the cost-effectiveness of introducing government-funded influenza vaccination to children in China (fully-funded policy) compared with the status quo (self-paid policy).MethodsA decision tree model was developed to calculate the economic and health outcomes, from a societal perspective, using national- and provincial-level data. The incremental cost-effectiveness ratio (ICER) [incremental costs per quality-adjusted life year (QALY) gained] was used to compare the fully-funded policy with the self-paid policy under the willingness-to-pay threshold equivalent to national and provincial GDP per capita. Sensitivity analyses were performed and various scenarios were explored based on real-world conditions, including incorporating indirect effect into the analysis.ResultsCompared to the self-paid policy, implementation of a fully-funded policy could prevent 1,444,768 [95% uncertainty range (UR): 1,203,446–1,719,761] symptomatic cases, 92,110 (95% UR: 66,953–122,226) influenza-related hospitalizations, and 6494 (95% UR: 4590–8962) influenza-related death per season. The fully-funded policy was cost-effective nationally (7964 USD per QALY gained) and provincially for 13 of 31 provincial-level administrative divisions (PLADs). The probability of a funded vaccination policy being cost-effective was 56.5% nationally, and the probability in 9 of 31 PLADs was above 75%. The result was most sensitive to the symptomatic influenza rate among children under 5 years [ICER ranging from − 25,612 (cost-saving) to 14,532 USD per QALY gained]. The ICER of the fully-funded policy was substantially lower (becoming cost-saving) if the indirect effects of vaccination were considered.ConclusionsIntroducing a government-funded influenza policy for children is cost-effective in China nationally and in many PLADs. PLADs with high symptomatic influenza rate and influenza-associated mortality would benefit the most from a government-funded influenza vaccination program.

Estimating the Burden of Influenza Hospitalizations Across Multiple Seasons Using Capture-Recapture.

Influenza remains an important cause of hospitalizations in the United States. Estimating the number of influenza hospitalizations is vital for public health decision making. Combining existing surveillance systems through capture-recapture methods allows for more comprehensive burden estimations. Data from independent surveillance systems were combined using capture-recapture methods to estimate influenza hospitalization rates for children and adults in Middle Tennessee during consecutive influenza seasons from 2016-2017 through 2019-2020. The Emerging Infections Program (EIP) identified cases through surveillance of laboratory results for hospitalized children and adults. The Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) and New Vaccine Surveillance Network (NVSN) recruited hospitalized patients with respiratory symptoms or fever. Population-based influenza rates and the proportion of cases detected by each surveillance system were calculated. Estimated overall influenza hospitalization rates ranged from 23 influenza-related hospitalizations per 10 000 persons in 2016-2017 to 40 per 10 000 persons in 2017-2018. Adults aged ≥65 years had the highest hospitalization rates across seasons and experienced a rate of 170 hospitalizations per 10 000 persons during the 2017-2018 season. EIP consistently identified a higher proportion of influenza cases for adults and children compared with HAIVEN and NVSN, respectively. Current surveillance systems underestimate the influenza burden. Capture-recapture provides an alternative approach to use data from independent surveillance systems and complement population-based burden estimates.

Vaccine Effectiveness of non-adjuvanted and adjuvanted trivalent inactivated influenza vaccines in the prevention of influenza-related hospitalization in older adults: A pooled analysis from the Serious Outcomes Surveillance (SOS) Network of the Canadian Immunization Research Network (CIRN)

BackgroundInfluenza vaccines prevent influenza-related morbidity and mortality; however, suboptimal vaccine effectiveness (VE) of non-adjuvanted trivalent inactivated influenza vaccine (naTIV) or quadrivalent formulations in older adults prompted the use of enhanced products such as adjuvanted TIV (aTIV). Here, the VE of aTIV is compared to naTIV for preventing influenza-associated hospitalization among older adults. MethodsA test-negative design study was used with pooled data from the 2012 to 2015 influenza seasons. An inverse probability of treatment (IPT)-weighted logistic regression estimated the Odds Ratio (OR) for laboratory-confirmed influenza-associated hospitalization. VE was calculated as (1-OR)*100% with accompanying 95% confidence intervals (CI). ResultsOf 7,101 adults aged ≥ 65, 3,364 received naTIV and 526 received aTIV. The overall VE against influenza hospitalization was 45.9% (95% CI: 40.2%–51.1%) for naTIV and 53.5% (42.8%–62.3%) for aTIV. No statistically significant differences in VE were found between aTIV and naTIV by age group or influenza season, though a trend favoring aTIV over naTIV was noted. Frailty may have impacted VE in aTIV recipients compared to those receiving naTIV, according to an exploratory analysis; VE adjusted by frailty was 59.1% (49.6%–66.8%) for aTIV and 44.8% (39.1%–50.0%) for naTIV. The overall relative VE of aTIV to naTIV against laboratory-confirmed influenza hospital admission was 25% (OR 0.75; 0.61–0.92), demonstrating statistically significant benefit favoring aTIV. ConclusionsAdjusting for frailty, aTIV showed statistically significantly better protection than naTIV against influenza-associated hospitalizations in older adults. In future studies, it is important to consider frailty as a significant confounder of VE.

Predictors of Severity of Influenza-Related Hospitalizations: Results From the Global Influenza Hospital Surveillance Network (GIHSN).

The Global Influenza Hospital Surveillance Network (GIHSN) has since 2012 provided patient-level data on severe influenza-like-illnesses from >100 participating clinical sites worldwide based on a core protocol and consistent case definitions. We used multivariable logistic regression to assess the risk of intensive care unit admission, mechanical ventilation, and in-hospital death among hospitalized patients with influenza and explored the role of patient-level covariates and country income level. The data set included 73 121 patients hospitalized with respiratory illness in 22 countries, including 15 660 with laboratory-confirmed influenza. After adjusting for patient-level covariates we found a 7-fold increase in the risk of influenza-related intensive care unit admission in lower middle-income countries (LMICs), compared with high-income countries (P = .01). The risk of mechanical ventilation and in-hospital death also increased by 4-fold in LMICs, though these differences were not statistically significant. We also find that influenza mortality increased significantly with older age and number of comorbid conditions. Across all severity outcomes studied and after controlling for patient characteristics, infection with influenza A/H1N1pdm09 was more severe than with A/H3N2. Our study provides new information on influenza severity in underresourced populations, particularly those in LMICs.

Attitudes of parents towards influenza vaccine in the Eastern Mediterranean Region: A multilevel analysis

BackgroundSeasonal influenza vaccines (SIVs) can protect against influenza and substantially reduce the risk of influenza-related hospitalizations and fatalities in children. This study aimed to assess parental attitudes towards SIVs in the Eastern Mediterranean region (EMR). MethodsThrough an anonymous online survey conducted in 19 countries in the EMR, parents or caregivers over 18 years who had at least one child above 6 months filled out the Parent Attitudes about Childhood Vaccines questionnaire. As data had two levels; country and individual factors, we utilized multilevel binary logistic regression models. ResultsIn total, 6992 respondents filled out the questionnaire. Of them, 47.4 % were residents of middle-income countries, 72.4 % of the mothers were between 26 and 45 years old, 56.5 % had at least a university degree, and approximately 51.6 % were unemployed. Nearly 50.8 % of the respondents were hesitant to vaccinate their children against seasonal influenza. Parental attitudes towards seasonal influenza vaccination differed significantly between countries, p < 0.001. The main predictors of parental seasonal influenza vaccine hesitancy (VH) were parents vaccination (odds ratio (OR) = 0.42, 95 % CI = 0.32–0.55, p < 0.001)), the mother's education if mother educated vs. who did not receive any education (OR ranged from 0.48 to 0.64, p < 0.05), living in low-income countries (OR = 0.52, 95 % CI = 0.35–0.77, p < 0.01), mountain residence (0.69, 95 % CI = 0.49–0.99, p < 0.05), health workers as a source of information (OR = 0.70, 95 % CI = 0.58–0.85, p < 0.001), children vaccination against COVID-19 (OR = 0.52, 95 % CI = 0.41–0.65, p < 0.001), not receiving routine vaccinations (OR = 1.93, 95 % CI = 1.09–3.44, p = 0.025), and if parents respondents could not remember whether their child had suffered from seasonal influenza in the previous year (OR = 1.57, 95 % CI = 1.33–1.84, p < 0.001). ConclusionA high seasonal influenza VH rate was found in the EMR. Health authorities should implement different interventions targeting the identified modifiable risk factor to increase vaccine uptake among children, especially those at risk of complication from seasonal influenza infection.

Understanding the Global Burden of Influenza in Adults Aged 18-64years: A Systematic Literature Review from 2012 to 2022.

Adults aged 18-64years comprise most of the working population, meaning that influenza infection can be disruptive, causing prolonged absence from the workplace, and reduced productivity and the ability to care for dependents. Influenza vaccine uptake is relatively low, even among the older adults in this population (i.e., aged 50-64years), reflecting a lack of perceived need for vaccination. This systematic literature review (SLR) aimed to characterize the global burden of influenza in the 18-64years population. An electronic database search was conducted and supplemented with conference and gray literature searches. Eligible studies described at least one of clinical, humanistic, or economic outcomes in adults aged 18-64years and conducted across several global regions. Included studies were published in English, between January 1, 2012, and September 20, 2022. A total of 40 publications were included, with clinical, humanistic, and economic outcomes reported in 39, 5, and 15, respectively. Risk of influenza-associated clinical outcomes were reported to increase with age among the 18-64years population, including hospitalizations (Yamana et al. in Intern Med 60:3401-3408, 2021; Derqui et al. in Influenza Other Respir Viruses 16:862-872, 2022; Fuller et al. in Influenza Other Respir Viruses 16:265-275, 2022; Ortiz et al. in Crit Care Med 42:2325-2332, 2014; Yandrapalli et al. in Ann Transl Med 6:318, 2018; Zimmerman et al. in Influenza Other Respir Viruses 16:1133-1140, 2022). ICU admissions, mortality, ER/outpatient visits, and use of mechanical ventilation were recorded. Adults aged 18-64years with underlying comorbidities were at higher risk of influenza-related hospitalizations, ICU admission, and mortality than otherwise healthy individuals. Length of hospital stay increased with age, although a lack of stratification across other economic outcomes prevented identification of further trends across age groups. High levels of hospitalization and outpatient visits demonstrated a clinical influenza-associated burden on patients and healthcare systems, which is exacerbated by comorbidities. Considering the size and breadth of the general population aged 18-64years, the limited humanistic and economic findings of this SLR likely reflect an underreported burden. Greater investigation into indirect costs and prolonged absenteeism associated with influenza infection is required to fully understand the economic burden in this population.

Vaccine effectiveness of recombinant and standard dose influenza vaccines against influenza related hospitalization using a retrospective test-negative design

BackgroundRelative effectiveness of various vaccine formulations provide important input for vaccine policy decisions and provider purchasing decisions. We used electronic databases to conduct a test-negative case control study to determine relative vaccine effectiveness (rVE) of recombinant influenza vaccine (RIV4) compared with standard dose vaccines (SD-IIV4) against influenza hospitalization. MethodsAdults 18–64 and ≥65 years of age hospitalized in a large U.S. health system (19 hospitals) in 2018–2019 and 2019–2020 who were clinically tested for influenza using reverse transcription polymerase chain reaction (RT-PCR) assays were included. The hospital system electronic medical record (EMR) and the state immunization registry were used to confirm influenza vaccination. Propensity scores with inverse probability weighting were used to adjust for potential confounders and determine rVE. ResultsOf the 14,590 individuals included in the primary analysis, 3,338 were vaccinated with RIV4 and 976 were vaccinated with SD-IIV4, with the balance of 10,276 being unvaccinated. Most participants were white (80 %), most (70 %) had a high-risk condition, just over half were female (54 %) and age 65 years or older (53 %). Overall RIV4 rVE was significant when adjusted for propensity scores with inverse probability weights (rVE = 31; 95 % CI = 11 %, 46 %). Among younger adults (18–64 years-old), overall rVE of RIV4 was significant (rVE = 29; 95 % CI = 4 %, 47 %). ConclusionsOver all adults, both RIV4 and SD-IIV4 were effective against influenza hospitalization, with RIV4 providing better protection compared with SD-IIV4 overall, for females, younger adults, and those with no high-risk conditions.

Cost-effectiveness of the adjuvanted quadrivalent influenza vaccine in the elderly Belgian population

ABSTRACTBackgroundBetween 2015 and 2019, when 62% of Belgian adults aged ≥65 years were vaccinated with standard quadrivalent influenza vaccines, influenza caused an average of 3,905 hospitalizations and 347 premature deaths per year in older adults. The objective of the present analysis was to estimate the cost-effectiveness of the adjuvanted quadrivalent influenza vaccine (aQIV) compared to the standard (SD-QIV) and high-dose (HD-QIV) vaccines in elderly Belgians.Research Design and MethodsThe analysis was based on a static cost-effectiveness model that captured the evolution of patients infected with influenza and was customized with available national data.ResultsVaccinating adults aged ≥65 years with aQIV instead of SD-QIV would decrease the number of hospitalizations by 530 and the number of deaths by 66 in the 2023–2024 influenza season. aQIV was cost-effective compared to SD-QIV with an incremental cost of €15,227/quality-adjusted life year (QALY). aQIV is cost-saving when compared to HD-QIV in the subgroup of institutionalized elderly adults who were granted reimbursement for this vaccine.ConclusionIn a health care system striving to improve the prevention of infectious diseases, a cost-effective vaccine such as aQIV is a key asset to reduce the number of influenza-related hospitalizations and premature deaths in older adults.