Effects of high-dose versus standard-dose quadrivalent influenza vaccine among patients with diabetes: A post-hoc analysis of the DANFLU-1 trial.

AIM: High-dose quadrivalent influenza vaccine (QIV-HD) has been shown to be more effective than standard-dose (QIV-SD) in reducing influenza infection, but whether diabetes status affects relative vaccine effectiveness (rVE) is unknown. We aimed to assess rVE on change in glycated haemoglobin [HbA1c (∆HbA1c)], incident diabetes, total all-cause hospitalizations (first + recurrent), and a composite of all-cause mortality and hospitalization for pneumonia or influenza. METHODS: DANFLU-1 was a pragmatic, open-label trial randomizing adults (65-79 years) 1:1 to QIV-HD or QIV-SD during the 2021/22 influenza season. Cox proportional hazards regression was used to estimate rVE against incident diabetes and the composite endpoint, negative binomial regression to estimate rVE against all-cause hospitalizations, and ANCOVA when assessing rVE against ∆HbA1c. RESULTS: Of the 12 477 participants, 1162 (9.3%) had diabetes at baseline. QIV-HD, compared with QIV-SD, was associated with a reduction in the rate of all-cause hospitalizations irrespective of diabetes [overall: 647 vs. 742 events, incidence rate ratio (IRR): 0.87, 95% CI (0.76-0.99); diabetes: 93 vs. 118 events, IRR: 0.80, 95% CI (0.55-1.15); without diabetes: 554 vs. 624 events, IRR: 0.88, 95% CI (0.76-1.01), pinteraction = 0.62]. Among those with diabetes, QIV-HD was associated with a lower risk of the composite outcome [2 vs. 11 events, HR: 0.18, 95% CI (0.04-0.83)] but had no effect on ∆HbA1c; QIV-HD adjusted mean difference: ∆ + 0.2 mmol/mol, 95% CI (-0.9 to 1.2). QIV-HD did not affect the risk of incident diabetes [HR 1.18, 95% CI (0.94-1.47)]. CONCLUSIONS: In this post-hoc analysis, QIV-HD versus QIV-SD was associated with an increased rVE against the composite of all-cause death and hospitalization for pneumonia/influenza, and the all-cause hospitalization rate irrespective of diabetes status.

Severity of Respiratory Syncytial Virus vs COVID-19 and Influenza Among Hospitalized US Adults.

Importance: On June 21, 2023, the Centers for Disease Control and Prevention recommended the first respiratory syncytial virus (RSV) vaccines for adults aged 60 years and older using shared clinical decision-making. Understanding the severity of RSV disease in adults can help guide this clinical decision-making. Objective: To describe disease severity among adults hospitalized with RSV and compare it with the severity of COVID-19 and influenza disease by vaccination status. Design, Setting, and Participants: In this cohort study, adults aged 18 years and older admitted to the hospital with acute respiratory illness and laboratory-confirmed RSV, SARS-CoV-2, or influenza infection were prospectively enrolled from 25 hospitals in 20 US states from February 1, 2022, to May 31, 2023. Clinical data during each patient's hospitalization were collected using standardized forms. Data were analyzed from August to October 2023. Exposures: RSV, SARS-CoV-2, or influenza infection. Main Outcomes and Measures: Using multivariable logistic regression, severity of RSV disease was compared with COVID-19 and influenza severity, by COVID-19 and influenza vaccination status, for a range of clinical outcomes, including the composite of invasive mechanical ventilation (IMV) and in-hospital death. Results: Of 7998 adults (median [IQR] age, 67 [54-78] years; 4047 [50.6%] female) included, 484 (6.1%) were hospitalized with RSV, 6422 (80.3%) were hospitalized with COVID-19, and 1092 (13.7%) were hospitalized with influenza. Among patients with RSV, 58 (12.0%) experienced IMV or death, compared with 201 of 1422 unvaccinated patients with COVID-19 (14.1%) and 458 of 5000 vaccinated patients with COVID-19 (9.2%), as well as 72 of 699 unvaccinated patients with influenza (10.3%) and 20 of 393 vaccinated patients with influenza (5.1%). In adjusted analyses, the odds of IMV or in-hospital death were not significantly different among patients hospitalized with RSV and unvaccinated patients hospitalized with COVID-19 (adjusted odds ratio [aOR], 0.82; 95% CI, 0.59-1.13; P = .22) or influenza (aOR, 1.20; 95% CI, 0.82-1.76; P = .35); however, the odds of IMV or death were significantly higher among patients hospitalized with RSV compared with vaccinated patients hospitalized with COVID-19 (aOR, 1.38; 95% CI, 1.02-1.86; P = .03) or influenza disease (aOR, 2.81; 95% CI, 1.62-4.86; P < .001). Conclusions and Relevance: Among adults hospitalized in this US cohort during the 16 months before the first RSV vaccine recommendations, RSV disease was less common but similar in severity compared with COVID-19 or influenza disease among unvaccinated patients and more severe than COVID-19 or influenza disease among vaccinated patients for the most serious outcomes of IMV or death.

Impact of health education on promoting influenza vaccination health literacy in primary school students: a cluster randomised controlled trial protocol.

INTRODUCTION: Influenza is a major public health threat, and vaccination is the most effective prevention method. However, vaccination coverage remains suboptimal. Low health literacy regarding influenza vaccination may contribute to vaccine hesitancy. This study aims to evaluate the effect of health education interventions on influenza vaccination rates and health literacy. METHODS AND ANALYSIS: This cluster randomised controlled trial will enrol 3036 students in grades 4-5 from 20 primary schools in Dongguan City, China. Schools will be randomised to an intervention group receiving influenza vaccination health education or a control group receiving routine health education. The primary outcome is the influenza vaccination rate. Secondary outcomes include health literacy levels, influenza diagnosis rate, influenza-like illness incidence and vaccine protection rate. Data will be collected through questionnaires, influenza surveillance and self-reports at baseline and study conclusion. ETHICS AND DISSEMINATION: Ethical approval has been sought from the Ethics Committee of the School of Public Health, Sun Yat-sen University. Findings from the study will be made accessible to both peer-reviewed journals and key stakeholders. TRIAL REGISTRATION NUMBER: NCT06048406.

Stroke Risk After COVID-19 Bivalent Vaccination Among US Older Adults.

Importance: In January 2023, the US Centers for Disease Control and Prevention and the US Food and Drug Administration noted a safety concern for ischemic stroke among adults aged 65 years or older who received the Pfizer-BioNTech BNT162b2; WT/OMI BA.4/BA.5 COVID-19 bivalent vaccine. Objective: To evaluate stroke risk after administration of (1) either brand of the COVID-19 bivalent vaccine, (2) either brand of the COVID-19 bivalent plus a high-dose or adjuvanted influenza vaccine on the same day (concomitant administration), and (3) a high-dose or adjuvanted influenza vaccine. Design, Setting, and Participants: Self-controlled case series including 11 001 Medicare beneficiaries aged 65 years or older who experienced stroke after receiving either brand of the COVID-19 bivalent vaccine (among 5 397 278 vaccinated individuals). The study period was August 31, 2022, through February 4, 2023. Exposures: Receipt of (1) either brand of the COVID-19 bivalent vaccine (primary) or (2) a high-dose or adjuvanted influenza vaccine (secondary). Main Outcomes and Measures: Stroke risk (nonhemorrhagic stroke, transient ischemic attack, combined outcome of nonhemorrhagic stroke or transient ischemic attack, or hemorrhagic stroke) during the 1- to 21-day or 22- to 42-day risk window after vaccination vs the 43- to 90-day control window. Results: There were 5 397 278 Medicare beneficiaries who received either brand of the COVID-19 bivalent vaccine (median age, 74 years [IQR, 70-80 years]; 56% were women). Among the 11 001 beneficiaries who experienced stroke after receiving either brand of the COVID-19 bivalent vaccine, there were no statistically significant associations between either brand of the COVID-19 bivalent vaccine and the outcomes of nonhemorrhagic stroke, transient ischemic attack, nonhemorrhagic stroke or transient ischemic attack, or hemorrhagic stroke during the 1- to 21-day or 22- to 42-day risk window vs the 43- to 90-day control window (incidence rate ratio [IRR] range, 0.72-1.12). Among the 4596 beneficiaries who experienced stroke after concomitant administration of either brand of the COVID-19 bivalent vaccine plus a high-dose or adjuvanted influenza vaccine, there was a statistically significant association between vaccination and nonhemorrhagic stroke during the 22- to 42-day risk window for the Pfizer-BioNTech BNT162b2; WT/OMI BA.4/BA.5 COVID-19 bivalent vaccine (IRR, 1.20 [95% CI, 1.01-1.42]; risk difference/100 000 doses, 3.13 [95% CI, 0.05-6.22]) and a statistically significant association between vaccination and transient ischemic attack during the 1- to 21-day risk window for the Moderna mRNA-1273.222 COVID-19 bivalent vaccine (IRR, 1.35 [95% CI, 1.06-1.74]; risk difference/100 000 doses, 3.33 [95% CI, 0.46-6.20]). Among the 21 345 beneficiaries who experienced stroke after administration of a high-dose or adjuvanted influenza vaccine, there was a statistically significant association between vaccination and nonhemorrhagic stroke during the 22- to 42-day risk window (IRR, 1.09 [95% CI, 1.02-1.17]; risk difference/100 000 doses, 1.65 [95% CI, 0.43-2.87]). Conclusions and Relevance: Among Medicare beneficiaries aged 65 years or older who experienced stroke after receiving either brand of the COVID-19 bivalent vaccine, there was no evidence of a significantly elevated risk for stroke during the days immediately after vaccination.

[Which vaccines for COPD patients?] / Quels vaccins pour les patients atteints de BPCO ?

WHICH VACCINES FOR COPD PATIENTS? Patients with chronic obstructive pulmonary disease (COPD) are at high risk of bacterial or viral respiratory infections, which can worsen their symptoms and trigger respiratory exacerbations. Vaccines are recommended in accordance with the vaccine recommendation calendar. Seasonal influenza vaccination is recommended every year. Pneumococcal vaccination is renewed every 5 years, according to a schedule adapted to previous vaccination status. The SARS-Cov2 vaccine is administered according to current recommendations that evolves with the virus circulation. Certain populations are also vaccinated against pertussis and shingles.

QUELS VACCINS POUR LES PATIENTS ATTEINTS DE BPCO ? Les patients atteints de bronchopneumopathie chronique obstructive (BPCO) sont à haut risque d'infections respiratoires bactériennes ou virales, sources de majoration des symptômes et d'exacerbations respiratoires. La vaccination par le vaccin antigrippal saisonnier leur est recommandée tous les ans. La vaccination antipneumococcique est renouvelée tous les cinq ans selon un schéma adapté au statut vaccinal antérieur. Le vaccin anti-SARS-CoV-2 est quant à lui administré selon des recommandations évolutives en fonction du développement de la circulation du virus. Enfin, certains patients bénéficient des vaccins contre la coqueluche et le zona.

County-Level Factors Associated With Influenza and COVID-19 Vaccination in Indiana, 2020‒2022.

Objectives. To assess COVID-19 and influenza vaccination rates across Indiana's 92 counties and identify county-level factors associated with vaccination. Methods. We analyzed county-level data on adult COVID-19 vaccination from the Indiana vaccine registry and 2021 adult influenza vaccination from the Centers for Disease Control and Prevention. We used multiple linear regression (MLR) to determine county-level predictors of vaccinations. Results. COVID-19 vaccination ranged from 31.2% to 87.6% (mean = 58.0%); influenza vaccination ranged from 33.7% to 53.1% (mean = 42.9%). In MLR, COVID-19 vaccination was significantly associated with primary care providers per capita (b = 0.04; 95% confidence interval [CI] = 0.02, 0.05), median household income (b = 0.23; 95% CI = 0.12, 0.34), percentage Medicare enrollees with a mammogram (b = 0.29; 95% CI = 0.08, 0.51), percentage uninsured (b = -1.22; 95% CI = -1.57, -0.87), percentage African American (b = 0.31; 95% CI = 0.19, 0.42), percentage female (b = -0.97; 95% CI = -1.79, ‒0.15), and percentage who smoke (b = -0.75; 95% CI = -1.26, -0.23). Influenza vaccination was significantly associated with percentage uninsured (b = 0.71; 95% CI = 0.22, 1.21), percentage African American (b = -0.07; 95% CI = -0.13, -0.01), percentage Hispanic (b = -0.28; 95% CI = -0.40, -0.17), percentage who smoke (b = -0.85; 95% CI = -1.06, -0.64), and percentage who completed high school (b = 0.54; 95% CI = 0.21, 0.87). The MLR models explained 86.7% (COVID-19) and 70.2% (influenza) of the variance. Conclusions. Factors associated with COVID-19 and influenza vaccinations varied. Variables reflecting access to care (e.g., insurance) and higher risk of severe disease (e.g., smoking) are notable. Programs to improve access and target high-risk populations may improve vaccination rates. (Am J Public Health. 2024;114(4):415-423. https://doi.org/10.2105/AJPH.2023.307553).

Interventional study to improve pertussis and influenza vaccination uptake in pregnant women.

OBJECTIVES: Pertussis and influenza are endemic infections and associated with relevant morbidity and mortality in newborns and young infants. The Swiss Federal Office of Public Health has recommended influenza vaccination since 2011 and pertussis vaccination in pregnancy (ViP) since 2013 and expanded to repetition in each pregnancy since 2017. ViP is safe and effective in preventing severe diseases, but implementation is a challenge. We hypothesized that the proportion of women receiving ViP is persistently low despite existing national recommendations. Our primary objective was to compare the proportion of pertussis and influenza vaccine recommendations for and its acceptance by pregnant women before and after an information campaign tailored to obstetricians. Secondly, we aimed to identify reasons for missing or declining ViP. STUDY DESIGN: We conducted a prospective, single-center, single-arm implementation study in the maternity ward at the University Women's Hospital Basel. We performed standardized interviews with women hospitalized for postpartum care before (October to December 2019, Phase 1, n = 262) and after an information campaign (October to December 2020, Phase 2, n = 233) and compared categorical variables using chi-squared or Fisher's exact test and continuous variables using Whitney Mann U test. RESULTS: We found no significant differences in the proportion of recommendation for pertussis ViP (80 % vs. 84 %, p = 0.25) and implementation (76 % vs. 78 %, p = 0.63) between Phase 1 and 2. Main reasons for missing or declining vaccinations were lack of recommendation (62.8 %) and safety concerns regarding the unborn child (17.7 %). In contrast, the proportion of recommendation for influenza ViP (45 % vs. 63 %, p < 0.001) and implementation (29 % vs. 43 %, p < 0.001) increased significantly. CONCLUSION: Proactive recommendations by obstetricians play a key role in the implementation of ViP but is still insufficient in our setting. We believe that future efforts should aim to explore possible hurdles that impede recommendations by obstetricians for ViP. The focus should be on the needs and experiences of obstetricians in private practice, but also other health care professionals involved in care of pregnant women. Local campaigns do not seem effective enough, therefore national campaigns with new strategies are desirable.

Quality Improvement Interventions to Enhance Vaccine Uptake in Cancer Patients: A Systematic Review.

INTRODUCTION: Cancer patients, because of their compromised immune responses, face a higher risk of preventable infections, leading to increased morbidity and mortality. Despite this, vaccination rates among these patients are suboptimal, and research on effective interventions to improve vaccination rates is limited. METHODS: We conducted a comprehensive search in PubMed and Cochrane Library for studies investigating quality improvement (QI) interventions targeting vaccine uptake in cancer patients. Two authors independently screened, extracted data, and analyzed studies, resolving any discrepancies through consensus. RESULTS: Thirteen studies met the inclusion criteria, published between 2014 and 2022. Seven studies focused on the influenza vaccine, five on the pneumococcal vaccine, and one on both. Twelve studies used multiple interventions, whereas one used a single intervention. Most interventions aimed to enhance patient and family knowledge and identify eligible patients before their appointments. All studies demonstrated improved vaccine uptake after implementing the interventions. CONCLUSIONS: A variety of QI interventions have effectively increased pneumococcal and influenza vaccine uptake among cancer patients. Future research should address roadblocks to implementation and explore the effect of these interventions on other vaccines.

Optimal timing of influenza vaccination in young children: population based cohort study.

OBJECTIVE: To assess optimal timing of influenza vaccination in young children. DESIGN: Population based cohort study. SETTING: United States. PARTICIPANTS: Commercially insured children aged 2-5 years who were vaccinated against influenza during 2011-18. MAIN OUTCOME MEASURE: Rates of diagnosis of influenza among children who were vaccinated against influenza, by birth month. RESULTS: Overall, 819 223 children aged 2-5 received influenza vaccination. Children vaccinated in November and December were least likely to have a diagnosis of influenza, a finding that may be confounded by unmeasured factors that influence the timing of vaccination and risk of influenza. Vaccination commonly occurred on days of preventive care visits and during birth months. Children born in October were disproportionately vaccinated in October and were, on average, vaccinated later than children born in August and earlier than those born in December. Children born in October had the lowest rate of influenza diagnosis (for example, 2.7% (6016/224 540) versus 3.0% (6462/212 622) for those born in August; adjusted odds ratio 0.88, 95% confidence interval 0.85 to 0.92). CONCLUSIONS: In a quasi-experimental analysis of young children vaccinated against influenza, birth month was associated with the timing of vaccination through its influence on the timing of preventive care visits. Children born in October were most likely to be vaccinated in October and least likely to have a diagnosis of influenza, consistent with recommendations promoting October vaccination.

Influenza vaccination during the 2021/22 season: A data-linkage test-negative case-control study of effectiveness against influenza requiring emergency care in England and serological analysis of primary care patients.

We present England 2021/22 end-of-season adjusted vaccine effectiveness (aVE) against laboratory confirmed influenza related emergency care use in children aged 1-17 and in adults aged 50+, and serological findings in vaccinated vs unvaccinated adults by hemagglutination inhibition assay. Influenza vaccination has been routinely offered to all children aged 2-10 years and adults aged 65 years + in England. In 2021/22, the offer was extended to children to age 15 years, and adults aged 50-64 years. Influenza activity rose during the latter half of the 2021/22 season, while remaining comparatively low due to COVID-19 pandemic control measures. Influenza A(H3N2) strains predominated. A test negative design was used to estimate aVE by vaccine type. Cases and controls were identified within a sentinel laboratory surveillance system. Vaccine histories were obtained from the National Immunisation Management Service (NIMS), an influenza and COVID-19 vaccine registry. These were linked to emergency department presentations (excluding accidents) with respiratory swabbing ≤ 14 days before or ≤ 7 days after presentation. Amongst adults, 423 positive and 32,917 negative samples were eligible for inclusion, and 145 positive and 6,438 negative samples among children. Those admitted to hospital were further identified. In serology against the circulating A(H3N2) A/Bangladesh/4005/2020-like strain, 61 % of current season adult vaccinees had titres ≥ 1:40 compared to 17 % of those unvaccinated in 2020/21 or 2021/22 (p < 0.001). We found good protection from influenza vaccination against influenza requiring emergency care in children (72.7 % [95 % CI 52.7, 84.3 %]) and modest effectiveness in adults (26.1 % [95 % CI 4.5, 42.8 %]). Adult VE was higher for A(H1N1) (81 % [95 % CI 50, 93 %]) than A(H3N2) (33 % [95 % CI 6, 53 %]). Consistent protection was observable across preschool, primary and secondary school aged children. Imperfect test specificity combined with very low prevalence may have biased estimates towards null. With limited influenza circulation, the study could not determine differences by vaccine types.

The coverage of influenza vaccination and predictors of influenza non-vaccination in Danish cancer patients: A nationwide register-based cohort study.

BACKGROUND: Influenza vaccination is recommended and provided free-of-charge to Danish citizens aged ≥65 years and to individuals with acquired immunodeficiency. We aimed to estimate influenza vaccination coverage and investigate predictors of influenza non-vaccination in Danish cancer patients. METHODS: A nationwide cohort study of all Danish citizens aged ≥18 years with an incident cancer diagnosis between 2002 and 2017. Using national registries, we assessed information on influenza vaccination and potential predictors of influenza non-vaccination. We estimated adjusted prevalence ratios (aPR) of influenza non-vaccination for patients aged <65 years and ≥65 years. RESULTS: We observed 269,863 patients during 840,876 influenza vaccination seasons. The influenza vaccination coverage was 14 % for cancer patients <65 years and 51 % for those ≥65 years. No influenza vaccination in the previous season was associated with non-vaccination in the current season (<65 years: aPR = 2.75, 95 %CI = 2.71-2.80; ≥65 years: aPR = 5.15, 95 %CI = 5.10-5.21). Haematological cancer patients receiving chemotherapy had lower vaccination prevalence compared with those not receiving chemotherapy. CONCLUSIONS: The influenza vaccination coverage was low among cancer patients. Influenza non-vaccination in the previous season was the strongest predictor of not receiving influenza vaccination in the current season. Haematological cancer patients on current chemotherapy had lower vaccination prevalence than those not currently receiving chemotherapy.

Changes of influenza vaccination rate and associated influencing factors after the COVID-19 pandemic in Shanghai, China.

The vaccination rate for seasonal influenza remains low in most regions of China. It is essential to understand the factors that associated with the low influenza vaccination rate in various populations after the COVID-19 pandemic. A cross-sectional survey was conducted with residents in Pudong New Area, Shanghai, China. Respondents' vaccination condition during the 2021-2022 flu season and the reasons for receiving or not receiving influenza vaccine were investigated. Binary logistic regression was conducted to explore potential factors influencing vaccination uptake. 2,476 of 14,001 respondents received an influenza vaccine, with a total coverage of 17.68% (95% CI: 17.05%, 18.32%). Children had the highest vaccination coverage (35.68%; 95% CI: 34.02, 37.33), followed by adults (12.75%; 95% CI: 11.91%, 13.58%) and elderly individuals (11.70%, 95% CI: 10.78%, 12.62%). For children, lower household income was an significant promoting factor. For adults, factors significantly associated with vaccination were household income, sex, and education level. For elderly, factors significantly associated with vaccination were household income, education level, living state, and having underlying diseases. (P < .05)The main reason for vaccine hesitancy among children was worried about side effects (21.49%), for adults and elderly was self-rated good health (adults: 37.14%, elderly people: 30.66%). The overall influenza vaccination coverage rate in Shanghai, especially among elderly individuals, is lower than many developed countries. Appropriate strategies and programs targeting different populations need to be implemented to enhance influenza vaccine coverage.

The vaccination rate for seasonal influenza remains low in most regions of China. However, the COVID-19 pandemic has resulted in an increase in public awareness regarding the prevention and control of infectious diseases and changes in people's health behaviors thus may leading to changes in influenza vaccination rates and vaccination willingness. We conducted a survey on the medical service utilization behavior of community residents in Shanghai, the biggest city in eastern China. The vaccination status of respondents during the 2021­2022 flu season and the reasons for receiving or not receiving the vaccine were investigated among 14,001 local residents. The influenza vaccination rate in 2021­2022 season (17.68%) was higher than that in 2018­2019 season (11.8%) in the same area. And this trend was found in population of different age groups. However, the overall influenza vaccination coverage rate in Shanghai is still low, especially among elderly, it remains inadequate to establish an immune barrier and lags behind other developed regions. For children, lower household income was an independent promoting factor. For adults, factors significantly associated with vaccination were  household income, sex, and education level. For elderly, factors significantly associated with vaccination were household income, education level, living state, and having underlying diseases. (P < .05) The main reason for vaccine hesitancy among children was worried about side effects (21.49%), for adults and elderly was self-rated good health (adults: 37.14%,elderly people: 30.66%).Efforts should be made to increase awareness of influenza vaccines according to the characteristics of different population.

Crossprotection induced by virus-like particles containing influenza dual-hemagglutinin and M2 ectodomain.

Aims: To develop an effective universal vaccine against antigenically different influenza viruses. Materials & methods: We generated influenza virus-like particles (VLPs) expressing the H1 and H3 antigens with or without M2e5x. VLP-induced immune responses and crossprotection against H1N1, H3N2 or H5N1 viruses were assessed to evaluate their protective efficacy. Results: H1H3M2e5x immunization elicited higher crossreactive IgG antibodies than H1H3 VLPs. Upon challenge, both VLPs enhanced lung IgG, IgA and germinal center B-cell responses compared with control. While these VLPs conferred protection, H1H3M2e5x showed greater lung viral load reduction than H1H3 VLPs with minimal body weight loss. Conclusion: Utilizing VLPs containing dual-hemagglutinin, along with M2e5x, can be a vaccination strategy for inducing crossprotection against influenza A viruses.

Costs and cost-effectiveness of influenza illness and vaccination in low- and middle-income countries: A systematic review from 2012 to 2022.

BACKGROUND: Historically, lack of data on cost-effectiveness of influenza vaccination has been identified as a barrier to vaccine use in low- and middle-income countries. We conducted a systematic review of economic evaluations describing (1) costs of influenza illness; (2) costs of influenza vaccination programs; and (3) vaccination cost-effectiveness from low- and middle-income countries to assess if gaps persist that could hinder global implementation of influenza vaccination programs. METHODS AND FINDINGS: We performed a systematic search in Medline, Embase, Cochrane Library, CINAHL, and Scopus in January 2022 and October 2023 using a combination of the following key words: "influenza" AND "cost" OR "economic." The search included studies with publication years 2012 through 2022. Studies were eligible if they (1) presented original, peer-reviewed findings on cost of illness, cost of vaccination program, or cost-effectiveness of vaccination for seasonal influenza; and (2) included data for at least 1 low- or middle-income country. We abstracted general study characteristics and data specific to each of the 3 study types. Of 54 included studies, 26 presented data on cost-effectiveness, 24 on cost-of-illness, and 5 on program costs. Represented countries were classified as upper-middle income (UMIC; n = 12), lower-middle income (LMIC; n = 7), and low-income (LIC; n = 3). The most evaluated target groups were children (n = 26 studies), older adults (n = 17), and persons with chronic medical conditions (n = 12); fewer studies evaluated pregnant persons (n = 9), healthcare workers (n = 5), and persons in congregate living settings (n = 1). Costs-of-illness were generally higher in UMICs than in LMICs/LICs; however, the highest national economic burden, as a percent of gross domestic product and national health expenditure, was reported from an LIC. Among studies that evaluated the cost-effectiveness of influenza vaccine introduction, most (88%) interpreted at least 1 scenario per target group as either cost-effective or cost-saving, based on thresholds designated in the study. Key limitations of this work included (1) heterogeneity across included studies; (2) restrictiveness of the inclusion criteria used; and (3) potential for missed influenza burden from use of sentinel surveillance systems. CONCLUSIONS: The 54 studies identified in this review suggest an increased momentum to generate economic evidence about influenza illness and vaccination from low- and middle-income countries during 2012 to 2022. However, given that we observed substantial heterogeneity, continued evaluation of the economic burden of influenza illness and costs/cost-effectiveness of influenza vaccination, particularly in LICs and among underrepresented target groups (e.g., healthcare workers and pregnant persons), is needed. Use of standardized methodology could facilitate pooling across settings and knowledge sharing to strengthen global influenza vaccination programs.

Acceptability, cost-effectiveness, and capacity of a facility-based seasonal influenza vaccination among high-risk groups: a study protocol in selected tertiary care hospitals of Bangladesh.

BACKGROUND: In Bangladesh, seasonal influenza imposes considerable disease and economic burden, especially for those at high-risk of severe disease. The most successful approach for influenza prevention is the administration of a vaccine. Many poor and middle-income nations, including Bangladesh, do not have a national strategy or program in place for seasonal influenza vaccines, despite the World Health Organization's (WHO) advice to prioritize high-risk populations. Additionally, there is a scarcity of substantial data on the cost-effectiveness of seasonal influenza vaccination in these countries. The aim of our study is to determine acceptability, health beliefs, barriers, and intention of receiving influenza vaccine among high-risk populations, assess the cost-effectiveness of implementing a facility-based seasonal influenza vaccination programme, and investigate the required capacity for a potential seasonal influenza vaccination programme. METHODS: We will undertake this study following STROBE guidelines. We will conduct the study in inpatient and outpatient departments of three selected tertiary-level hospitals leveraging the ongoing hospital-based influenza surveillance (HBIS) platform. The study population will include the WHO-defined four high-risk groups excluding healthcare workers: children six months to eight years, pregnant women, elderly ≥ 60 years, and adults with chronic diseases. We will collect quantitative data on participants' acceptability, health beliefs, barriers, and vaccination intentions using the health belief model (HBM) from patients meeting the criteria for high-risk populations attending two public tertiary-level hospitals. In one of the two public tertiary-level hospitals, we will arrange an influenza vaccination campaign before the influenza season, where the vaccine will be offered free of cost to high-risk patients, and in the second hospital, vaccination will not be offered. Both the vaccinated and unvaccinated participants will then be followed-up once a month for one year to record any influenza-like illness, hospitalization, and death. Additional data for objective two will be collected from patients with symptoms of influenza-like illness (ILI) and severe acute respiratory infection (SARI) at one public and one private hospital to determine both direct and indirect costs associated with influenza illness. We will estimate the required number of influenza vaccines, safe injections, and total storage volume utilizing secondary data. We will use a deterministic Markov decision-analytic model to estimate the cost-effectiveness of facility-based influenza vaccination in Bangladesh. DISCUSSION: The results of this study will enable the National Immunization Technical Advisory Group and the Ministry of Health & Family Welfare of Bangladesh to decide what steps to take to develop and implement an influenza vaccination strategy targeting high-risk populations. TRIAL REGISTRATION: The Clinicaltrials.gov registration number is NCT05996549. The registration for the protocol version 2.0 took place in August 2023, with the initial participant being enrolled in March 2022.