Effectiveness of pasteurization for the inactivation of H5N1 influenza virus in raw whole milk.

Highly pathogenic avian influenza (HPAI) clade 2.3.4.4b H5Nx viruses continue to cause episodic incursions and have been detected in more than 12 taxonomic orders encompassing more than 80 avian species, terrestrial and marine mammals, including lactating dairy cows. HPAI H5N1 spillover to dairy cattle creates a new interface for human exposure and raises food safety concerns. The presence of H5N1 genetic material in one out of five retail pasteurized milk samples in the USA has prompted the evaluation of the pasteurization processes for the inactivation of influenza viruses. Our study examined whether pasteurization could effectively inactivate HPAI H5N1 spiked into raw whole milk. First, we heated 1 mL of non-homogenized cow milk samples to attain an internal temperature of 63°C or 72°C and spiked with 6.3 log10 EID50 of clade 2.3.4.4b H5N1 virus. Complete inactivation was achieved after incubation of the H5N1 spiked raw milk at 63°C for 30 min. In addition, viral inactivation was observed in seven of eight experimental replicates when treated at 72°C for 15s. In one of the replicates, a 4.44 log10 virus reduction was achieved, which is about 1 log higher than the average viral quantities detected in bulk milk in affected areas. Therefore, we conclude that pasteurization of milk is an effective strategy for mitigation of the risk of human exposure to milk contaminated with H5N1 virus.

Rationale and Design of a Multi-National Study of Physicians' Opinions, Attitudes, and Practices Regarding Influenza Vaccination in Patients with Cardiovascular Diseases: A Mixed Methods Designs. The FLUence Project.

Infections, particularly those involving the respiratory tract, are associated with an increased incidence of cardiovascular events, both de novo and as exacerbations of pre-existing cardiovascular diseases. Influenza vaccination has consistently been shown to reduce the incidence of cardiovascular events. Nonetheless, vaccination rates among adults remain suboptimal, both in the general population and among high-risk individuals. Multiple barriers hinder achieving adequate vaccination rates, with physicians' beliefs and attitudes towards these interventions being crucial. The FLUence project was developed within the framework of the World Heart Federation's Emerging Leaders program, to address this issue. This project has two phases: a global quantitative survey to assess the perceptions, opinions, and attitudes and challenges of physicians worldwide regarding the safety and efficacy of the influenza vaccination use, and a qualitative survey to further investigate the barriers and facilitators of recommending and using this vaccination. The quantitative survey was created and disseminated in five languages (English, Spanish, French, Italian, and Portuguese) to physicians of all specialties who care for adults, with a particular focus on patients with cardiovascular disease. The survey included eight domains with a total of 36 questions with closed options; a Likert scale with five possible answers was used to gauge participants' opinions. To gain deeper insights into the complexities behind the low vaccination rates in adults, the second part of the project comprises a qualitative survey, conducted in the two lower-middle- and upper-middle-income countries: India and Argentina, respectively. These countries were selected because patients with cardiovascular diseases have access to free influenza vaccination in Argentina, whereas patients must pay for the vaccine out of pocket in India. Thus, the FLUence study will provide valuable information to better understand the perceptions and barriers to improving influenza vaccination rates from the perspective of physicians. It is imperative to actively engage all healthcare providers to improve influenza vaccination rates.

Meeting Report From "Correlates of Protection for Next Generation Influenza Vaccines: Lessons Learned From the COVID-19 Pandemic".

BACKGROUND: This report summarizes the discussions and conclusions from the "Correlates of Protection for Next Generation Influenza Vaccines: Lessons Learned from the COVID-19 Pandemic" meeting, which took place in Seattle, USA, from March 1, 2023, to March 3, 2023. CONCLUSIONS: Discussions around influenza virus correlates of protection and their use continued from where the discussion had been left off in 2019. While there was not much progress in the influenza field itself, many lessons learned during the coronavirus disease 2019 (COVID-19) pandemic, especially the importance of mucosal immunity, were discussed and can directly be applied to influenza correlates of protection.

SARS-CoV-2, Tdap, and influenza vaccination during pregnancy from 2019 to 2022 in Ontario, Canada: a population-based retrospective cohort study.

BACKGROUND: Hesitancy about vaccination during pregnancy posed challenges to SARS-CoV-2 vaccination efforts. We aimed to examine rates of SARS-CoV-2 vaccination among Ontario residents who gave birth in early 2022, and to compare rates of SARS-CoV-2 vaccine uptake with rates of tetanus, diphtheria, and pertussis (Tdap) and influenza vaccination during pregnancy in 2019, 2021, and 2022. METHODS: We conducted a population-based retrospective cohort study to describe vaccination rates among pregnant and comparable nonpregnant populations in Ontario using linked administrative data. Provincially insured females who had a live, in-hospital birth from Jan. 1 to Mar. 31 in 2019, 2021, or 2022 were our primary cohort. Using log-binomial regression, we tested associations between SARS-CoV-2 (2022) and Tdap and influenza (2019, 2021, 2022) vaccination status, with birth group and covariates. We compared SARS-CoV-2 vaccination status with the status of a matched cohort of nonpregnant females and conducted subgroup analyses by age and prenatal clinician type. RESULTS: Among birthing people, 78.7% received their first SARS-CoV-2 vaccine dose and 74.2% received a second dose. The rate was significantly higher among nonpregnant comparators (dose 1: relative risk [RR] 0.94, 95% confidence interval [CI] 0.93-0.94; dose 2: RR 0.91, 95% CI 0.90-0.91). However, the rate of SARS-CoV-2 vaccination uptake among birthing people was higher than uptake of Tdap or influenza vaccination. Tetanus, diphtheria, and pertussis vaccination increased over time from 22.2% in 2019 to 32.6% in 2022, and influenza vaccination rose to 35.3% in 2021 but returned to prepandemic levels in 2022 (27.7%). Vaccination rates were lower among pregnant people who were young, multiparous, or residents of rural or economically deprived areas for all 3 vaccines. INTERPRETATION: Rates of SARS-CoV-2 vaccination were lower among pregnant people than among nonpregnant comparators but were higher than rates of routinely recommended Tdap and influenza vaccinations. Pandemic urgency may have overcome a great deal of hesitancy about vaccinating against SARS-CoV-2 during pregnancy in 2022, but uptake of routinely recommended vaccines in pregnancy remains a challenge. TRIAL REGISTRATION: Clinicaltrials.gov, no. NCT05663762.

Epidemiological analysis of influenza vaccination coverage in Pudong New Area, Shanghai (2013-2023): Implications for influenza vaccination strategies.

Seasonal influenza remains a significant public health concern globally, with annual vaccinations as the most effectively preventive measure. This study examines influenza vaccination coverage rates across different age groups in Pudong New Area, Shanghai, China, from 2013 to 2023. This study extracted influenza vaccination data from the Shanghai Immunization Planning Information System (SIPIS) of the Center for Disease Control and Prevention Shanghai's Pudong New Area from 2013 to 2023. The analysis utilized weighted linear regression to compare vaccination rates over the study period. From 2013 to 2023, a cumulative total of 1,421,295 influenza vaccinations were administered in Pudong New Area, with the quadrivalent inactivated influenza vaccines (IIV4) and trivalent inactivated influenza vaccines (IIV3) comprising 56.8% and 42.9%, respectively. The overall average influenza vaccine coverage rate was 2.27% (95% CI: 2.26, 2.28). The 0-4 years group exhibited the highest average annual coverage rate of 22.52% (95% CI: 22.47, 22.57) among different age groups, in stark contrast to that of the 20-24 years age group, which had the lowest at 0.32% (95% CI: 0.31, 0.33). In terms of repeat vaccinations, a significant majority (86.87%) of recipients received only 1-2 doses, while just 13.13% received 3 or more doses. Although influenza vaccination coverage among preschool children in Pudong New Area is relatively high, it falls significantly short of WHO recommendations. Enhance the level of awareness of influenza vaccine among adults and provide a free influenza vaccination strategy for specific groups such as doctors, which is helpful to increase influenza vaccination rates among populations.

Evaluating hand hygiene knowledge, attitudes, and practices among healthcare workers in post-pandemic H1N1 influenza control: a cross-sectional study from China.

Background: This study evaluates the knowledge, attitudes, and practices (KAP) of hand hygiene among healthcare workers, crucial for preventing healthcare-associated infections (HAIs) in medical facilities. Methodology: This cross-sectional study assessed hand hygiene KAP among healthcare workers across various settings in Hubei, China utilizing a stratified random sampling approach from, December 25, 2023-to-April 25, 2024. A bilingual electronic survey, adapted from validated tools, was disseminated via email and social media to ensure a broad reach. Participants included diverse healthcare professionals who met specific inclusion criteria. Responses were analyzed using R software, employing descriptive and inferential statistics to identify key predictors of hand hygiene behavior and to confirm the reliability of the survey instrument. Results: The survey of 2,265 healthcare workers revealed that 77% demonstrated comprehensive knowledge of hand hygiene, 80% exhibited positive attitudes, and 94% practiced effective hand hygiene. Notable findings include a significant understanding of hand hygiene's role in preventing respiratory illnesses (58%) and HAIs (41% agreed, 39% unsure). High compliance in practices like washing hands for at least 20 s was evident (84%), though gaps in confidence about hand hygiene techniques were noted (33% confident, 56% unsure). Binary logistic regression analysis indicated that younger healthcare workers (21-30 years) were more likely to exhibit both knowledge (OR = 7.4, 95% CI = 1.44-136, p = 0.059) and positive attitudes (OR = 4.48, 95% CI = 1.73-11.8, p < 0.001) compared to other age groups. Significant associations were found between higher income levels and positive attitudes toward hand hygiene (OR for ≥80,000 = 3.19, 95% CI = 2.05-5.02, p < 0.001), and between knowledge and practices, suggesting that well-informed individuals are more likely to adhere to recommended practices. Conclusion: The findings reveal robust hand hygiene knowledge but uncover critical confidence gaps among healthcare workers, urging immediate, targeted educational interventions to fortify adherence and prevent infection outbreaks.

[Pay more attention to vaccination to protect the health of the elderly].

Vaccination has been implemented as a priority measure to control infectious diseases worldwide. The aging of the global population continues to intensify, and the process and level of aging in China are more prominent. As age increases, the immune function of people gradually declines, and the consequences of infectious diseases such as influenza, pneumococcal disease, and shingles are more severe in the elderly, which can exacerbate existing underlying diseases, leading to higher medical costs. In the process of achieving healthy aging, it is very necessary to protect vulnerable elderly people through vaccination. Despite the undeniable protective effects of the influenza, pneumococcal, and shingles vaccines for the elderly, coupled with excellent safety and significant health economic benefits, the current vaccination rates for these vaccines among the elderly in China remain low. Some factors, such as insufficient awareness of the necessity of vaccination, concerns about vaccine adverse reactions, lack of systematic and effective recommendations, and imperfect accessibility of vaccination services, affect the popularization of preventive vaccination among the elderly in China. This situation urgently calls for the attention of society as a whole, in order to maximize the role of vaccines in safeguarding the health of the elderly.

Smoking and serological response to influenza vaccine.

Cigarette smoking confers additional risk from influenza. This study assessed the effect of smoking on humoral immune response to influenza vaccine. Adults ≥50 y of age were enrolled during the 2011-2016 influenza vaccination seasons in an observational prospective study. Non-fasting whole blood samples for hemagglutination inhibition (HAI) assays were obtained from participants at pre- and 28 d post-clinically administered, trivalent influenza vaccination. Among 273 participants, 133 subjects self-reported as never smokers, 87 as ex-smokers, and 53 as current smokers. Postvaccination geometric mean HAI titers were significantly higher among smokers for A/H1N1 (p = .031) and A/H3N2 (p = .001). Relative to never smokers, smoking was independently related to seroconversion to A/H1N1, A/H3N2 and B. The adjusted odd ratios (ORs) were 5.2 [95% confidence interval (CI), 2.3, 11.5] for seroconversion to A/H1N1, 5.4 (95% CI, 2.4, 12.1) for A/H3N2, and 2.7 (95% CI, 1.3, 5.7) for B. Smoking was also independently related to seroprotection to A/H1N1, A/H3N2 and B. The ORs were 3.6 (95% CI, 1.6, 8.08) for seroprotection to A/H1N1 in smokers, 2.7 (95% CI, 1.14, 6.5) for A/H3N2, and 2.5 (95% CI, 1.1, 5.7) for B. Although the mechanism is unclear, smokers showed a better immune response to influenza vaccination than never smokers and ex-smokers. The results can be used to emphasize the value of influenza vaccination for smokers.

A human monoclonal antibody targeting the monomeric N6 neuraminidase confers protection against avian H5N6 influenza virus infection.

The influenza neuraminidase (NA) is a potential target for the development of a next-generation influenza vaccine, but its antigenicity is not well understood. Here, we isolate an anti-N6 human monoclonal antibody, named 18_14D, from an H5N6 avian influenza virus (AIV) infected patient. The antibody weakly inhibits enzymatic activity but confers protection in female mice, mainly via ADCC function. The cryo-EM structure shows that 18_14D binds to a unique epitope on the lateral surface of the N6 tetramer, preventing the formation of tightly closed NA tetramers. These findings contribute to the molecular understanding of protective immune responses to NA of AIVs in humans and open an avenue for the rational design of NA-based vaccines.

Out of focus but still relevant? Influenza-related resource utilization and vaccination coverage gaps in adults below 60 years of age with underlying conditions: an analysis of 2016-2024 real-world data in Germany.

BACKGROUND: In 2003, the WHO aimed for a 75% or higher influenza vaccination rate among at-risk populations. However, this target was achieved in a few groups during selected seasons in some European countries, and never in Germany. Adults with underlying conditions (UCs) are a critical negleted group for influenza vaccination. This study aimed to identify data gaps in influenza burden and vaccination coverage among adults under 60 with UCs in Germany and bridge these gaps using real-world data. MATERIAL AND METHODS: We conducted systematic research and analyses using German administrative and claims databases from June 2016 to April 2024. We report on epidemiology, direct care costs, indirect costs from work incapacity, vaccination coverage rates, and describe data gaps. RESULTS: Influenza data for high-risk populations are limited. Comprehensive data on influenza epidemiology and vaccination coverage rates (VCR) is available, though with a delay in data availability. Before and after the pandemic, individuals aged 50-59 had the highest rates of influenza-related hospitalization and ICU admission compared to younger age groups. Across all age groups and seasons, individuals with UC experienced higher rates of medically attended influenza cases, hospitalizations, and healthcare costs, with those aged 35-59 being particularly vulnerable. Vaccine coverage was higher in adults aged 35-59 compared to those aged 18-24, and in females compared to males. LIMITATIONS: Discrepancies of vaccination status, limited data availability, and variations among the extent of UCs. CONCLUSION: In Germany, recent policy measures have mainly targeted those aged 60 and above. While this elderly population experiences the highest disease-related impact, influenza can also lead to substantial healthcare resource utilization (HCRU) and costs in younger populations with chronic UCs; Facilitating vaccination access for this group, such as through pharmacies, is essential. Definition of quantifiable vaccination targets and measures to increase vaccination rates based on these targets are required.

The research analysed real-world data on the impact of influenza among adults under 60 years old with underlying medical conditions in Germany. The key findings include: Low vaccination rates: The flu vaccination rate among adults with underlying conditions, such as asthma, diabetes, and heart disease, is low.High disease burden: This group has a significantly higher risk of severe influenza complications, experiencing notable rates of illness, hospitalization, and healthcare costs due to the flu. Given the high disease burden and low vaccine coverage, there is a need for improved public health strategies to increase flu vaccine access and uptake among this vulnerable population. These findings contribute to growing evidence supporting the importance of influenza vaccination for adults with underlying medical conditions. The insights provided can inform policymakers, healthcare providers, and public health officials working to improve vaccination rates and protect the health of these vulnerable populations.

Protecting the elderly from influenza in the context of immune system senescence. Elderly aged 65 and over are vulnerable to influenza and its associated complications.: Position paper by the Romanian Society of Gerontology and Geriatrics.

Influenza affects millions globally each year, often causing severe complications, hospitalizations, and deaths, particularly among the elderly. As the global population ages, infections will pose a growing health risk. Annual vaccination remains the most effective way to prevent influenza and its complications. After the age of 65, people suffering from chronic diseases become the majority of this population category. All the data support that most of the population over 65 years old, whose immune system goes through immunosenescence, presents multimorbidity, requiring age-appropriate anti-influenza protection. The immune response to the traditional influenza vaccine has been proven to be lower in the elderly, highlighting the need for a more immunogenic vaccine specifically tailored to the elderly population group. Therefore, high-dose (HD) influenza vaccines have demonstrated their safety and are more effective in preventing influenza and its associated complications compared to standard-dose (SD) vaccines in the elderly in the context of immunosenescence. These recommendations focus on the safety, effectiveness, and efficacy of HD influenza vaccines, adapted to the elderly and available on the Romanian market, to increase the vaccination rate and, thus, protect against influenza infection and its complications. Therefore, strategies such as increased accessibility and free immunizations, as well as ensuring that flu vaccines for the elderly are prescribed without restrictions based on the number of comorbidities, should be used.

Meeting Report: Controlled Human Influenza Virus Infection Model Studies: Current Status and Future Directions for Innovation.

On November 13-14, 2023, the National Institute of Allergy and Infectious Diseases (NIAID) in partnership with the Task Force for Global Health, Flu Lab, the Canadian Institutes of Health Research, and the Centers for Disease Control and Prevention convened a meeting on controlled human influenza virus infection model (CHIVIM) studies to review the current research landscape of CHIVIM studies and to generate actionable next steps. Presentations and panel discussions highlighted CHIVIM use cases, regulatory and ethical considerations, innovations, networks and standardization, and the utility of using CHIVIM in vaccine development. This report summarizes the presentations, discussions, key takeaways, and future directions for innovations in CHIVIMs. Experts agreed that CHIVIM studies can be valuable for the study of influenza infection, immune response, and transmission. Furthermore, they may have utility in the development of vaccines and other medical countermeasures; however, the use of CHIVIMs to de-risk clinical development of investigational vaccines should employ a cautious approach. Endpoints in CHIVIM studies should be tailored to the specific use case. CHIVIM studies can provide useful supporting data for vaccine licensure but are not required and do not obviate the need for the conduct of field efficacy trials. Future directions in this field include the continued expansion of capacity to conduct CHIVIM studies, development of a broad panel of challenge viruses and assay reagents and standards that can be shared, streamlining of manufacturing processes, the exploration of targeted delivery of virus to the lower respiratory tract, efforts to more closely replicate natural influenza disease in CHIVIM, alignment on a definition of breadth to facilitate development of more broadly protective/universal vaccine approaches, and continued collaboration between stakeholders.

A Rapid Virus-Free Method for Producing Influenza HA Immunogen Needed for Preparation of Influenza Vaccine Potency Antisera Reagents.

BACKGROUND: The potency of inactivated and recombinant influenza vaccines is measured using the single-radial immunodiffusion (SRID) assay. The strain-specific antigen and antibody potency reagents required for the assay are prepared and distributed by regulatory agencies to ensure vaccine standardization, but timely reagent production is always challenging. This poses unique concerns for rapid pandemic responses. Alternative methods have been described for generating strain-specific potency antibody reagents without the need for live influenza virus, but such methods are infrequently used, suggesting the need for additional antigen expression approaches. METHODS: We describe a rapid process using a mammalian expression system to produce recombinant influenza hemagglutinin (rHA). This platform was used to generate rHA from two H5 clade 2.3.4.4 influenza viruses, in both soluble ectodomain or full-length HA forms, and a soluble ectodomain rHA from an influenza H2 virus. RESULTS: The purified rHAs were used as immunogens to produce HA antibody reagents that were tested for suitability in the SRID assay to accurately measure the potency of inactivated pandemic influenza vaccines. Antibody reagents generated to either ectodomain or full-length rHA worked well in the SRID assay and resulted in vaccine potency values equivalent to those generated with standard reference antibodies. CONCLUSIONS: The results demonstrate that rHA produced from a simple mammalian cell transfection method can be used to generate HA antibody suitable for use in the influenza vaccine SRID potency assay and suggest a practical means by which an extensive library of pandemic reagents can easily be prepared in advance of and during an influenza emergency.

Triton X-100-treated virus-based ELLA demonstrates discordant antigenic evolution of influenza B virus hemagglutinin and neuraminidase.

Neuraminidase (NA)-specific antibodies have been associated with protection against influenza and thus NA is considered a promising target for next-generation vaccines against influenza A (IAV) and B viruses (IBV). NA inhibition (NI) by antibodies is typically assessed using an enzyme-linked lectin assay (ELLA). However, ELLA can be confounded by anti-hemagglutinin (anti-HA) antibodies that block NA by steric hindrance (termed HA interference). Although strategies have been employed to overcome HA interference for IAV, similar approaches have not been assessed for IBV. We found that HA interference is common in ELLA using IBV, rendering the technique unreliable. Anti-HA antibodies were not completely depleted from sera by HA-expressing cell lines, and this approach was of limited utility. In contrast, we find that treatment of virions with Triton X-100, but not Tween-20 or ether, efficiently separates the HA and NA components and overcomes interference caused by anti-HA antibodies. We also characterize a panel of recombinant IBV NA proteins that further validated the results from Triton X-100-treated virus-based ELLA. Using these reagents and assays, we demonstrate discordant antigenic evolution between IBV NA and HA over the last 80 years. This optimized ELLA protocol will facilitate further in-depth serological surveys of IBV immunity as well as antigenic characterization of the IBV NA on a larger scale.IMPORTANCEInfluenza B viruses (IBVs) contribute to annual epidemics and may cause severe disease, especially in children. Consequently, several approaches are being explored to improve vaccine efficacy, including the addition of neuraminidase (NA). Antigen selection and assessment of serological responses will require a reliable serological assay to specifically quantify NA inhibition (NI). Although such assays have been assessed for influenza A viruses (IAVs), this has not been done of influenza B viruses. Our study identifies a readily applicable strategy to measure the inhibitory activity of neuraminidase-specific antibodies against influenza B virus without interference from anti-hemagglutinin (anti-HA) antibodies. This will aid broader serological assessment of influenza B virus-specific antibodies and antigenic characterization of the influenza B virus neuraminidase.

Head-to-head comparison of influenza vaccines in children: a systematic review and meta-analysis.

Although vaccination is considered the most effective weapon against influenza, coverage rates, national vaccination policies, and funding vary largely around the globe. Despite their huge potential for achieving herd immunity, child-focused national vaccination strategies that favor pain-free nasal vaccines are uncommon. CENTRAL, Embase, and MEDLINE were last searched on November 13, 2023. Active-controlled randomized controlled trials comparing the live-attenuated intranasal vaccine with the inactivated intramuscular influenza vaccine in children were included. Event rates of laboratory-confirmed influenza virus infection, all-cause mortality, hospitalization, serious adverse events, adverse events, and financial outcomes were extracted based on the PRISMA 2020 Guideline. PROSPERO: CRD42021285412. Pooled odds ratios (ORs) with 95% confidence intervals (CI) were calculated using the random-effects model when at least three comparable outcomes were available. We found no significant difference between quadrivalent live-attenuated intranasal and trivalent inactivated intramuscular (OR = 1.48; 95% CI 0.49-4.45) or between trivalent live-attenuated intranasal and inactivated intramuscular vaccines (OR = 0.77, CI = 0.44-1.34) regarding their efficacy. However, the subgroup analysis of large, multi-center trials indicated that the trivalent live attenuated intranasal influenza vaccine was superior to the trivalent inactivated intramuscular influenza vaccine (12,154 people, OR = 0.50, CI = 0.28-0.88). Only 23 "vaccine-related serious adverse events" were recorded among 17 833 individuals, with no significant difference between methods. The widespread initiation of pediatric national flu vaccination programs prioritizing the live-attenuated intranasal influenza vaccine would be beneficial. Multi-continent, high-quality studies that include children younger than two years old and those living in subtropical and tropical regions are needed to further enhance our understanding.

Safety of Simultaneous Vaccination With Adjuvanted Zoster Vaccine and Adjuvanted Influenza Vaccine: A Randomized Clinical Trial.

Importance: Quadrivalent adjuvanted inactivated influenza vaccine (aIIV4) and adjuvanted recombinant zoster vaccine (RZV) contain novel adjuvants. Data are limited on the comparative safety, reactogenicity, and health-related quality of life (HRQOL) effects of the simultaneous administration of these vaccines. Objective: To compare the safety and reactogenicity after simultaneous doses of RZV and aIIV4 administration (opposite arms) with simultaneous doses of RZV with quadrivalent high-dose inactivated influenza vaccine [HD-IIV4]). Design, Setting, and Participants: This randomized blinded clinical trial was conducted during the 2021-2022 and 2022-2023 influenza seasons at 2 centers in the US among community-dwelling adults aged 65 years or older. Analysis was performed on an intention-to-treat basis. Intervention: Simultaneous intramuscular administration of RZV dose 1 and aIIV4 or HD-IIV4 in opposite arms after age stratification (65-69 and ≥70 years) and randomization. Main Outcomes and Measures: The primary outcome was the proportions of participants with 1 or more severe solicited reactions during days 1 to 8, using a noninferiority test (10% noninferiority margin). Additional measures included serious adverse events and adverse events of clinical interest during days 1 to 43 of the study period. Results: A total of 267 adults (median age, 71 years [range, 65-92 years]; 137 men [51.3%]) were randomized; 130 received simultaneous RZV and aIIV4, and 137 received simultaneous RZV and HD-IIV4. The proportion of patients reporting 1 or more severe reactions after simultaneous administration of RZV and aIIV4 (15 of 115 [11.5%]) was noninferior compared with simultaneous RZV and HD-IIV4 (17 of 119 [12.5%]) (absolute difference, -1.0% [95% CI, -8.9% to 7.1%]). There were no significant differences in the number of serious adverse events or adverse events of clinical interest between the groups. Conclusions and Relevance: In this clinical trial of simultaneous doses of RZV and aIIV4 compared with simultaneous doses of RZV and HD-IIV4, overall safety findings were similar between groups. From a safety standpoint, this study supports the simultaneous administration of RZV and aIIV4 among older adults. Trial Registration: ClinicalTrials.gov Identifier: NCT05007041.

Hospitalizations and emergency attendance averted by influenza vaccination in Victoria, Australia, 2017 - 2019.

Seasonal influenza epidemics result in high levels of healthcare utilization. Vaccination is an effective strategy to reduce the influenza-related burden of disease. However, reporting vaccine effectiveness does not convey the population impacts of influenza vaccination. We aimed to calculate the burden of influenza-related hospitalizations and emergency department (ED) attendance averted by influenza vaccination in Victoria, Australia, from 2017 to 2019, and associated economic savings. We applied a compartmental model to hospitalizations and ED attendances with influenza-specific, and pneumonia and influenza (P&I) with the International Classification of Diseases, 10th Revision, Australian Modification (ICD-10-AM) diagnostic codes of J09-J11 and J09-J18, respectively. We estimated an annual average of 7657 (120 per 100000 population) hospitalizations and 20560 (322 per 100000 population) ED attendances over the study period, associated with A$85 million hospital expenditure. We estimated that influenza vaccination averted an annual average of 1182 [range: 556 - 2277] hospitalizations and 3286 [range: 1554 - 6257] ED attendances and reduced the demand for healthcare services at the influenza season peak. This equated to approximately A13 [range: A6 - A25] million of savings over the study period. Calculating the burden averted is feasible in Australia and auseful approach to demonstrate the health and economic benefits of influenza vaccination.

Effectiveness of influenza vaccines in children aged 6 to 59 months: a test-negative case-control study at primary care and hospital level, Spain 2023/24.

During 2023/24, all children aged 6 to 59 months were targeted for seasonal influenza vaccination in Spain nationally. Using a test-negative case-control design with sentinel surveillance data, we estimated adjusted influenza vaccine effectiveness (IVE) against any influenza type to be 70% (95% confidence interval (CI): 51 to 81%) for primary care patients with acute respiratory illness (ARI) and 77% (95% CI: 21 to 93%) for hospitalised patients with severe ARI. In primary care, where most subtyped viruses (61%; 145/237) were A(H1N1), adjusted IVE was 77% (95% CI: 56 to 88%) against A(H1N1)pdm09.