Cost-effectiveness of the adjuvanted quadrivalent influenza vaccine for older adults in South Korea.

South Korea's National Immunization Program administers the quadrivalent influenza vaccine (QIV) to manage seasonal influenza, with a particular focus on the elderly. After reviewing the safety and immune response triggered by the adjuvanted QIV (aQIV) in individuals aged 65 and older, the Ministry of Food and Drug Safety in Korea approved its use. However, the extensive impact of aQIV on public health is yet to be fully understood. This study assessed the cost-effectiveness of replacing QIV with aQIV in South Korean adults aged 65 years and older. A dynamic transmission model, calibrated with national influenza data, was applied to compare the influence of aQIV and QIV on older adults and the broader population throughout a single influenza season. This study considered both the direct and indirect effects of vaccination on the elderly. We derived the incremental cost-effectiveness ratios (ICERs) from quality-adjusted life-years (QALYs) and costs incurred, validated through a probabilistic sensitivity analysis with 5,000 simulations. Findings suggest that transitioning to aQIV from QIV in the elderly would be cost-effective, particularly if aQIV's efficacy reaches or exceeds 56.1%. With an ICER of $29,267/QALY, considerably lower than the $34,998/QALY willingness-to-pay threshold, aQIV presents as a cost-effective option. Thus, implementing aQIV with at least 56.1% efficacy is beneficial from both financial and public health perspectives in mitigating seasonal influenza in South Korea.

Antivirals to prepare for surges in influenza cases: an economic evaluation of baloxavir marboxil for the Netherlands.

OBJECTIVES: We perform a cost-effectiveness analysis (CEA) and budget impact analysis (BIA) of baloxavir marboxil compared to current care in the Netherlands for patients at risk of influenza-related complications, including patients with comorbidities and the elderly. METHODS: In the CEA, a decision tree model was developed to assess the cost-effectiveness of baloxavir marboxil for a cohort of 52-year-olds from a societal perspective. A lifetime horizon was taken by incorporating the quality-adjusted life expectancy. The BIA included different epidemiological scenarios, estimating different plausible epidemiological scenarios for seasonal influenza considering the whole Dutch population with an increased risk of influenza complications. RESULTS: The base-case ICER was estimated to be €8,300 per QALY. At the willingness-to-pay threshold of €20,000 per QALY, the probability of being cost effective was 58%. The base-case expected budget impact was €5.7 million on average per year, ranging from €1.5 million to €10.5 million based on the severity of the influenza epidemic and vaccine effectiveness. CONCLUSION: In the Netherlands, baloxavir is a cost-effective treatment option for seasonal influenza, with a base-case ICER of €8,300 per QALY for the population aged 60 years and over and patients at high risk of influenza-related complications. For a large part, this ICER is driven by the reduction of the illness duration of influenza and productivity gains in the working population.

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.

Regional Disparities in the Uptake of Differentiated Influenza Vaccines in the United States.

Significant racial/ethnic inequities in the uptake of differentiated influenza vaccines (DIVs) have been previously reported, though less is known about regional disparities. We conducted a retrospective longitudinal study (2014/15-2017/18 influenza seasons) among privately insured adults aged 65 + years in the US. The exposure was the beneficiary's area of residence (US Census Bureau division) and the outcome was the type of influenza vaccine: differentiated (high-dose [HDV], adjuvanted, recombinant, and cell-based) versus conventional standard-dose egg-based. Multilevel logistic regression modeling, guided by a causal diagram, was used to assess the influence of socio-demographics, medical, healthcare utilization, community, and vaccinator characteristics in confounding or mediating regional disparities. Among those vaccinated in physician offices, beneficiaries in the East North Central region were twice as likely to receive a DIV vs those in the South Atlantic, whereas those in the East and West South Central were least likely. Disparities became more pronounced in models adjusted for individual and community characteristics, suggesting that crude uptake estimates understate the true magnitude of disparities. A vaccinator's previous HDV use was most influential in explaining regional differences. Similar but less pronounced patterns emerged for vaccinations in pharmacies/facilities. Regional disparities remained even in fully adjusted models, pointing to currently poorly understood factors that may include quality of healthcare, client health literacy and engagement, and other political and cultural factors.

Investigation of barriers to county-level seasonal influenza vaccine uptake among Medicare beneficiaries in the United States - 2018-2019 seasonal influenza season.

Introduction: As most public health decisions are made at the local level, public health interventions implemented at the local level may vary by their own unique circumstances, such as demographic composition or the availability of resources. Our objective is to estimate and characterize county-level flu vaccine uptakes among Medicare-covered adults aged ≥65 years. Methods: The flu vaccine uptake was estimated from Medicare Fee-for-Service claims for those who continuously enrolled during the 2018-2019 flu season. County-level characteristics were obtained from Centers for Disease Control and Prevention (CDC)'s Minority Health Social Vulnerability Index and Behavioral Risk Factor Surveillance System data as well as Health Resources and Services Administration's Area Health Resources File. A generalized linear regression was used to assess the relationship between selected characteristics and uptake. Results: A total of 30,265,047 beneficiaries from 3,125 counties were identified, of which 53% received a flu vaccination during the 2018-2019 flu season. For 3,006 counties with more than 500 Medicare beneficiaries, the mean county-level uptake was estimated to be 47.7%. The mean uptakes in counties designated as a health professional shortage area (HPSA) (42.6% and 48.4%, respectively), were lower than the uptakes for the non-HPSA counties (53.8%). Metro counties (53.2%) showed higher uptakes than non-metro counties (44.2%). Regression analysis results showed that the percent of working adults aged 18-64 years and female were positively associated, while the percent of Black and Hispanic adults were negatively associated. Proportions of persons with limited proficiency of English, college education or above, single parent families, multi-unit housing, and living in group quarters were positively associated and significant. Conclusions: The results confirmed that county-level flu vaccine uptakes are low, reflect persistent racial disparities in vaccine uptake, and that Medicare populations in medically underserved communities with lower socioeconomic status need more attention in improving flu vaccine uptake.

Estimated health and economic impact of using high-dose influenza vaccine on respiratory and circulatory plus respiratory hospitalizations of older adults in Australia.

Background: Standard dose influenza vaccine provides moderate protection from infection, but with lower effectiveness among the elderly. High dose and adjuvanted vaccines (HD-TIV and aTIV) were developed to address this. This study aims to estimate the incremental health and economic impact of using HD-TIV (high dose trivalent vaccine) instead of aTIV (adjuvanted trivalent vaccine) on respiratory and circulatory plus respiratory hospitalizations of older people (≥65 years) in Australia. Methods: This is a modelling study comparing predicted hospitalization outcomes in people receiving HD-TIV or aTIV during an average influenza season in Australia. Hospitalization records of Australian adults ≥65 years of age from 01 April to 30 November during 15 influenza seasons (2002-2017 excluding 2009, which was a pandemic) were extracted from the Australian Institute of Health and Welfare [AIHW] and used to calculate hospitalisation rates during an average season. Relative vaccine effectiveness data for aTIV and HD-TIV were used to estimate morbidity burden related to influenza. Results: Between 2002 and 2017, the average respiratory hospitalization rate among older people during influenza season (April-November) was 3,445/100,000 population-seasons, with an average cost of AU$ 7,175 per admission. The average circulatory plus respiratory hospitalization rate among older Australian people during that time was 10,393/100,000 population-seasons, with an average cost of AU$ 7829 per admission. For older Australians, HD-TIV may avert an additional 6,315-9,410 respiratory admissions each year, with an incremental healthcare cost saving of AU$ 15.9-38.2 million per year compared to aTIV. Similar results were also noted for circulatory plus respiratory hospitalizations. Conclusions: From the modelled estimations, HD-TIV was associated with less economic burden and fewer respiratory, and circulatory plus respiratory hospitalizations than aTIV for older Australians.

Cost-Effectiveness of Vaccination of Older Adults with an MF59®-Adjuvanted Quadrivalent Influenza Vaccine Compared to Standard-Dose and High-Dose Vaccines in Denmark, Norway, and Sweden.

Individuals aged 65 years and above are at increased risk of complications and death from influenza compared with any other age group. Enhanced vaccines, as the MF59®-adjuvanted quadrivalent influenza vaccine (aQIV) and the high-dose quadrivalent influenza vaccine (HD-QIV), provide increased protection for older adults in comparison to the traditional standard-dose quadrivalent influenza vaccines (SD-QIV). This study aimed to assess the cost-effectiveness of aQIV compared to SD-QIV and HD-QIV in Denmark, Norway, and Sweden for adults aged ≥65 years. A static decision tree model was used to evaluate costs and outcomes of different vaccination strategies from healthcare payer and societal perspectives. This model projects that compared to SD-QIV, vaccination with aQIV could prevent a combined total of 18,772 symptomatic influenza infections, 925 hospitalizations, and 161 deaths in one influenza season across the three countries. From a healthcare payer perspective, the incremental costs per quality adjusted life year (QALY) gained with aQIV versus SD-QIV were EUR 10,170/QALY in Denmark, EUR 12,515/QALY in Norway, and EUR 9894/QALY in Sweden. The aQIV was cost saving compared with HD-QIV. This study found that introducing aQIV to the entire population aged ≥65 years may contribute to reducing the disease and economic burden associated with influenza in these countries.

Establishing Pandemic Influenza Severity Assessment (PISA) parameters and thresholds for Canada's FluWatch program.

Background: The World Health Organization (WHO) developed a structured framework to enable countries to rapidly assess the severity of an influenza pandemic. This framework, the Pandemic Influenza Severity Assessment (PISA), is intended to be performed weekly during seasonal epidemics so that assessing influenza severity during a pandemic can be done with greater ease and efficiency. Objective: Using influenza surveillance indicators within Canada's FluWatch program from seasons 2014-2015 to 2018-2019, national PISA thresholds were developed and assessed against seasonal data for seasons 2019-2020 to June of 2022-2023. Outcomes: Canada developed thresholds for each required indicator (transmissibility, seriousness of disease and impact) for multiple WHO-recommended parameters. The thresholds were assessed against four seasons, and it was determined that there was a good agreement between the PISA assessments and the characterization of the season by FluWatch epidemiologists. Conclusion: With confidence in the validity of the PISA thresholds, the FluWatch program will begin to share PISA assessments weekly through the FluWatch report in the 2023-2024 seasons to help characterize influenza activity in Canada and inform responses to the seasonal influenza epidemic.

What explains racial/ethnic inequities in the uptake of differentiated influenza vaccines?

We investigated the role of individual, community and vaccinator characteristics in mediating racial/ethnic disparities in the uptake of differentiated influenza vaccines (DIVs; including high-dose, adjuvanted, recombinant and cell-based vaccines). We included privately-insured (commercial and Medicare Advantage) ≥65 years-old community-dwelling health plan beneficiaries in the US with >1 year of continuous coverage and who received ≥1 influenza vaccine during the study period (July 2014-June 2018). Of 2.8 million distinct vaccination claims, 60% were for DIVs; lower if received in physician offices (49%) compared to pharmacies/facilities (74%). Among those vaccinated in physician offices, non-whites had lower odds of receiving a DIV if they lived in a non-minority county (0.77;95%CI 0.75-0.80) and even lower odds if they lived in a minority county (0.62;0.60-0.63). Differences in education, household income, medical history, community and vaccinator characteristics did not fully explain the disparities. Similar patterns emerged for vaccinations in pharmacies/facilities, although disparities disappeared altogether after controlling for socio-economic and vaccinator characteristics. When vaccinated in physician offices, minority county residents were less likely to receive a DIV, especially for non-whites (0.72;0.67-0.78). These disparities disappeared for whites, but not for non-whites, after controlling for community and vaccinator characteristics. We found an alarming level of inequity in DIV vaccine uptake among fully insured older adults that could not be fully explained by differences in sociodemographic, medical, community, and vaccinator characteristics. New strategies are urgently needed to address these inequities.

Cost-utility analysis of increasing uptake of universal seasonal quadrivalent influenza vaccine (QIV) in children aged 6 months and older in Germany.

Seasonal influenza causes many cases and related deaths in Europe annually, despite ongoing vaccination programs for older adults and people at high-risk of complications. Children have the highest risk of infection and play a key role in disease transmission. Our cost-utility analysis, based on a dynamic transmission model, estimated the impact of increasing the current vaccination coverage with inactivated quadrivalent influenza vaccine in Germany to all (healthy and high-risk) children under 5 years of age (40% uptake), or under 18 years (40% uptake), or only high-risk children under 18 years (90% uptake). Eight influenza complications were modeled, hospitalization and death rates were based on age and risk status. All three vaccination strategies provided more health benefits than the existing vaccination situation, reducing influenza cases, complications, hospitalizations and deaths across the entire population. The strategy targeting all children under 5 years was highly cost-effective (€6/quality-adjusted life-year gained, payer perspective). The other strategies were cost saving from the payer and societal perspectives. The vaccination strategy targeting all children under 18 years was estimated to provide the most health benefits (preventing on average 1.66 million cases, 179,000 complications, 14,000 hospitalizations and 3,600 deaths due to influenza annually) and the most cost savings (annually €20.5 million and €731.3 million from payer and societal perspectives, respectively). Our analysis provides policy decision-makers with evidence supporting strategies to expand childhood influenza vaccination, to directly protect children, and indirectly all other unvaccinated age groups, in order to reduce the humanistic and economic burden on healthcare systems and society.

What is the context? Every winter, millions of people in Europe become ill due to influenza (flu), and some need to be hospitalized for complications that can sometimes lead to death.While mainly older adults and people with chronic illness are at higher risk of complications from influenza, children have the highest risk of infection and of transmitting the disease.Current vaccination policies in Europe, including Germany, target older adults and high-risk populations (pregnant women, children and other age groups with chronic diseases).What is new? This analysis simulates the effects of expanding current German vaccination programs in high-risk children to include healthy children, and of increasing vaccination coverage rates, for direct protection against infection, and to reduce the disease transmission in the rest of the population.We modeled three vaccination strategies: vaccinating 40% of all (healthy and high- risk) children under 5 years old;vaccinating 40% of all (healthy and high-risk) children under 18 years old;vaccinating 90% of high-risk children under 18 years old.What is the impact? All three strategies resulted in health gains, as more influenza cases, complications and deaths were prevented in all age groups of the population compared to the current situation.The strategies targeting both healthy and high-risk children provided the greatest health benefits. In particular, a vaccination policy targeting all children under 18 years old was predicted to provide the most health benefits as well as the highest cost savings: the increased costs of vaccination were more than offset by the savings in disease management costs as a result of having fewer influenza patients.Vaccinating healthy children against influenza is expected to significantly reduce the disease burden in the total population while saving costs, due to reduced transmission of the disease.

Geographically dependent individual-level models for infectious diseases transmission.

Infectious disease models can be of great use for understanding the underlying mechanisms that influence the spread of diseases and predicting future disease progression. Modeling has been increasingly used to evaluate the potential impact of different control measures and to guide public health policy decisions. In recent years, there has been rapid progress in developing spatio-temporal modeling of infectious diseases and an example of such recent developments is the discrete-time individual-level models (ILMs). These models are well developed and provide a common framework for modeling many disease systems; however, they assume the probability of disease transmission between two individuals depends only on their spatial separation and not on their spatial locations. In cases where spatial location itself is important for understanding the spread of emerging infectious diseases and identifying their causes, it would be beneficial to incorporate the effect of spatial location in the model. In this study, we thus generalize the ILMs to a new class of geographically dependent ILMs, to allow for the evaluation of the effect of spatially varying risk factors (e.g., education, social deprivation, environmental), as well as unobserved spatial structure, upon the transmission of infectious disease. Specifically, we consider a conditional autoregressive (CAR) model to capture the effects of unobserved spatially structured latent covariates or measurement error. This results in flexible infectious disease models that can be used for formulating etiological hypotheses and identifying geographical regions of unusually high risk to formulate preventive action. The reliability of these models is investigated on a combination of simulated epidemic data and Alberta seasonal influenza outbreak data ($2009$). This new class of models is fitted to data within a Bayesian statistical framework using Markov chain Monte Carlo methods.

Barriers and activities to implementing or expanding influenza vaccination programs in low- and middle-income countries: A global survey.

INTRODUCTION: Despite considerable global burden of influenza, few low- and middle-income countries (LMICs) have national influenza vaccination programs. This report provides a systematic assessment of barriers to and activities that support initiating or expanding influenza vaccination programs from the perspective of in-country public health officials. METHODS: Public health officials in LMICs were sent a web-based survey to provide information on barriers and activities to initiating, expanding, or maintaining national influenza vaccination programs. The survey primarily included Likert-scale questions asking respondents to rank barriers and activities in five categories. RESULTS: Of 109 eligible countries, 62% participated. Barriers to influenza vaccination programs included lack of data on cost-effectiveness of influenza vaccination programs (87%) and on influenza disease burden (84%), competing health priorities (80%), lack of public perceived risk from influenza (79%), need for better risk communication tools (77%), lack of financial support for influenza vaccine programs (75%), a requirement to use only WHO-prequalified vaccines (62%), and young children require two vaccine doses (60%). Activities for advancing influenza vaccination programs included educating healthcare workers (97%) and decision-makers (91%) on the benefits of influenza vaccination, better estimates of influenza disease burden (91%) and cost of influenza vaccination programs (89%), simplifying vaccine introduction by focusing on selected high-risk groups (82%), developing tools to prioritize target populations (80%), improving availability of influenza diagnostic testing (79%), and developing collaborations with neighboring countries for vaccine procurement (74%) and regulatory approval (73%). Responses varied by country region and income status. CONCLUSIONS: Local governments and key international stakeholders can use the results of this survey to improve influenza vaccination programs in LMICs, which is a critical component of global pandemic preparedness for influenza and other pathogens such as coronaviruses. Additionally, strategies to improve global influenza vaccination coverage should be tailored to country income level and geographic location.

Inclusion of Safety-Related Issues in Economic Evaluations for Seasonal Influenza Vaccines: A Systematic Review.

(1) Background: Vaccines for seasonal influenza are a good preventive and cost-effective strategy. However, it is unknown if and how these economic evaluations include the adverse events following immunization (AEFI), and what the impact of such inclusion is on the health economic outcomes. (2) Methods: We searched the literature, up to January 2020, to identify economic evaluations of seasonal influenza vaccines that considered AEFIs. The review protocol was published in PROSPERO (CDR42017058523). (3) Results: A total of 52 economic evaluations considered AEFI-related parameters in their analyses, reflecting 16% of the economic evaluations on seasonal influenza vaccines in the initial study selection. Most studies used the societal perspective (64%) and evaluated vaccination of children (37%). Where considered, studies included direct medical costs of AEFIs (90%), indirect costs (27%), and disutilities/quality-adjusted life years loss due to AEFIs (37%). The majority of these studies accounted for the effects of the costs of AEFI on cost-effectiveness for Guillain-Barré syndrome. In those papers allowing cost share estimation, direct medical cost of AFEIs was less than 2% of total direct costs. (4) Conclusions: Although the overall impact of AEFIs on the cost-effectiveness outcomes was found to be low, we urge their inclusion in economic evaluations of seasonal influenza vaccines to reflect comprehensive reports for the decision makers and end-users of the vaccination strategies.

Cost Utility of Switching From Trivalent to Quadrivalent Influenza Vaccine in Turkey.

OBJECTIVES: Trivalent influenza vaccines (TIVs) are widely used but protect against only 1 of the 2 co-circulating influenza B virus lineages. Quadrivalent influenza vaccines (QIVs) include a B strain from each lineage to overcome mismatches. The main objective of this study was to determine the cost-utility and budget impact of switching from vaccination with TIV to QIV in the population recommended for influenza vaccination in Turkey. METHODS: A static cohort cost-effectiveness model was developed to predict influenza-related costs and outcomes under a QIV versus a TIV program during an influenza season. The model was informed by data from Turkey on influenza strain distribution, influenza-attributable outcomes, and associated costs over the seasons 2010/2011 to 2016/2017. The effectiveness of each strategy was measured through quality-adjusted life-years (QALYs), and comparisons were based on the incremental cost-effectiveness ratio. RESULTS: In an average influenza season, the model showed that switching from TIV to QIV would prevent an additional 15 092 cases of influenza, 6311 general practitioner visits, 94 hospitalizations, 13 deaths, and gain 440 QALYs. From the societal perspective, this amounted to total cost savings of international dollars (I$) 1102 710 (US$388 643). The incremental cost-effectiveness ratio when using QIV over TIV was I$55 248/QALY gained. Switching to QIV is mostly cost-effective among older adults with I$36 413.38/QALY. Sensitivity analysis showed that vaccine effectiveness, B strain mismatch, and influenza visits highly impact the cost-effectiveness results. CONCLUSION: Switching from TIV to QIV is likely to be cost-effective in Turkey, yet highly dependent on the severity of the influenza season, B strain epidemiology, and vaccine effectiveness.

Assessment of the benefits of seasonal influenza vaccination: Elements of a framework to interpret estimates of vaccine effectiveness and support robust decision-making and communication.

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

Epidemiology and burden of illness of seasonal influenza among the elderly in Japan: A systematic literature review and vaccine effectiveness meta-analysis.

BACKGROUND: Elderly populations are particularly vulnerable to influenza and often require extensive clinical support. In Japan, nationwide passive surveillance monitors seasonal influenza but does not capture the full disease burden. We synthesized existing evidence on the epidemiology, vaccine effectiveness (VE), and economic burden of seasonal influenza in the elderly population. METHODS: PubMed, EMBASE, and ICHUSHI were searched for articles on seasonal influenza in Japan, published between 1997 and 2018, in English or Japanese. Grey literature was also assessed. A random-effects meta-analysis characterized VE of influenza vaccines among studies reporting this information. RESULTS: Of 1,147 identified articles, 143 met inclusion criteria. Reported incidence rates varied considerably depending on study design, season, study setting and, most importantly, case definition. In nursing homes, the maximum reported attack rate was 55.2% and in the 16 articles reporting mortality rates, case fatality rates varied from 0.009% to 14.3%. Most hospitalizations were in people aged >60; healthcare costs were partially mitigated by vaccine administration. Meta-analysis estimated overall VE of 19.1% (95% CI: 2.3% - 33.0%) with a high proportion of heterogeneity (I2 : 89.1%). There was a trend of lower VE in older people (40.1% [-57.3-77.2] in the <65 group; 12.9% [-8.0-29.8] in those 65; P = .21). CONCLUSIONS: Despite differences between studies that make comparisons challenging, the influenza burden in elderly Japanese is significant. While vaccines are effective, current vaccination programs offer suboptimal protection. Health economic data and cost-effectiveness analyses were limited and represent areas for policy-relevant future research.

Impact of COVID-19 infection control measures on influenza-related outcomes in Hong Kong.

Following the announcement of coronavirus disease 2019 (COVID-19) cases in Wuhan on 31 December 2019, government officials in Hong Kong recommended the wearing of face masks as a public infection control measure against the COVID-19 virus and curtail the impact of the concurrent influenza season. The present study evaluated the influenza-related outcomes between the influenza season 2019 and 2020 in Hong Kong as a result of these infection control measures. A Monte Carlo simulation model was designed to estimate the number of influenza cases, clinic visits, hospitalization, deaths, direct medical cost and disability-adjusted life-years (DALYs) for the season 2018-2019 and 2019-2020 in six age groups: 0-5 years, 6-11 years, 12-17 years, 18-49 years, 50-64 years and ≥65 years in Hong Kong. Model inputs were derived from public data and existing literature. The model findings showed significant reduction in influenza-related cases, clinic visits, hospitalization, and deaths in 2020 versus 2019 (p < 0.05). Influenza-related direct costs in all age-groups were significantly reduced by 56%-82% (p < 0.01) in 2020 versus 2019. DALYs were also significantly decreased by 58%-85% (p < 0.01). The direct cost and DALYs avoided in 2020 was the highest among the age group of 0-5 years with a cost-saving of USD593,763 (95%CI 590,730-596,796) per 10,000 population and a DALY reduction of 57.67 (95%CI 57.54-57.83) per 10,000 population. This study illustrated the reduction of all influenza-related outcome measures in Hong Kong as a result of the implementation of public infection control measures against COVID-19.

Cost-effectiveness of live-attenuated influenza vaccination among school-age children.

The current pediatric vaccination program in England and Wales administers Live-Attenuated Influenza Vaccine (LAIV) to children ages 2-16 years old. Annual administration of LAIV to this age group is costly and poses substantial logistical issues. This study aims to evaluate the cost-effectiveness of prioritizing vaccination to age groups within the 2-16 year old age range to mitigate the operational and resource challenges of the current strategy. We performed economic evaluations comparing the influenza vaccination program from 1995-2013 to seven alternative strategies targeted at low risk individuals along the school age divisions Preschool (2-4 years old), Primary school (5-11 years old), and Secondary school (12-16 years old). These extensions are evaluated incrementally on the status quo scenario (vaccinating subgroups at high risk of influenza-related complications and individuals 65+ years old). Impact of vaccination was assessed using a transmission model from a previously published study and updated with new data. At all levels of coverage, all strategies had a 100% probability of being cost-effective at the current National Health Service threshold, £20,000/QALY gained. The incremental analysis demonstrated vaccinating Primary School children was the most cost-efficient strategy compared incrementally against others with an Incremental Cost-Effectiveness Ratio of £639 spent per QALY gained (Net Benefit: 404 M£ [155, 795]). When coverage was varied between 30%, 55%, and 70% strategies which included Primary school children had a higher probability of being cost-effective at lower willingness-to-pay levels. Although children were the vaccine target the majority of QALY gains occurred in the 25-44 years old and 65+ age groups. Influenza strain A/H3N2 incurred the greatest costs and QALYs lost regardless of which strategy was used. Improvement could be made to the current LAIV pediatric vaccination strategy by eliminating vaccination of 2-4 year olds and focusing on school-based delivery to Primary and Secondary school children in tandem.

A cost-effectiveness analysis of South Africa's seasonal influenza vaccination programme.

BACKGROUND: Seasonal influenza imposes a significant health and economic burden in South Africa, particularly in populations vulnerable to severe consequences of influenza. This study assesses the cost-effectiveness of South Africa's seasonal influenza vaccination strategy, which involves vaccinating vulnerable populations with trivalent inactivated influenza vaccine (TIV) during routine facility visits. Vulnerable populations included in our analysis are persons aged ≥ 65 years; pregnant women; persons living with HIV/AIDS (PLWHA), persons of any age with underlying medical conditions (UMC) and children aged 6-59 months. METHOD: We employed the World Health Organisation's (WHO) Cost Effectiveness Tool for Seasonal Influenza Vaccination (CETSIV), a decision tree model, to evaluate the 2018 seasonal influenza vaccination campaign from a public healthcare provider and societal perspective. CETSIV was populated with existing country-specific demographic, epidemiologic and coverage data to estimate incremental cost-effectiveness ratios (ICERs) by comparing costs and benefits of the influenza vaccination programme to no vaccination. RESULTS: The highest number of clinical events (influenza cases, outpatient visits, hospitalisation and deaths) were averted in PLWHA and persons with other UMCs. Using a cost-effectiveness threshold of US$ 3400 per quality-adjusted life year (QALY), our findings suggest that the vaccination programme is cost-effective for all vulnerable populations except for children aged 6-59 months. ICERs ranged from ~US$ 1 750 /QALY in PLWHA to ~US$ 7500/QALY in children. In probabilistic sensitivity analyses, the vaccination programme was cost-effective in pregnant women, PLWHA, persons with UMCs and persons aged ≥65 years in >80% of simulations. These findings were robust to changes in many model inputs but were most sensitive to uncertainty in estimates of influenza-associated illness burden. CONCLUSION: South Africa's seasonal influenza vaccination strategy of opportunistically targeting vulnerable populations during routine visits is cost-effective. A budget impact analysis will be useful for supporting future expansions of the programme.

Cost effectiveness of trivalent and quadrivalent influenza vaccines in 50- to 64-year-old adults in Korea.

BACKGROUND: Influenza causes severe complications in at-risk populations, resulting in significant morbidity and mortality. Vaccination is the most effective measure to prevent infection and complications caused by seasonal influenza. However, no study has analyzed the cost-effectiveness of influenza vaccines in 50- to 64-year-olds in South Korea. OBJECTIVE: We examined the application of the National Immunization Program (NIP) in 50- to 64-year-olds and compared the cost-effectiveness of quadrivalent influenza vaccine (QIV) with that of trivalent influenza vaccine (TIV) in South Korea. METHODS: One-year static model was assumed by constructing separate decision trees for age subgroups: 50-54, 55-59, and 60-64. Each subgroup was divided into at-risk and not-at-risk groups. Using circulation data from previous studies and Korea Centers for Disease Control and Prevention, we estimated the probabilities of influenza infection, outpatient treatment, hospitalization, and deaths. Medical cost was estimated from 2015 to 2017 National Health Insurance Sharing Service claim data, while productivity losses from work absenteeism or death were estimated from labor and economic surveys of Korean government. Disutility was estimated based on previous studies. RESULTS: Compared with non-vaccination, incremental cost-effectiveness ratios (ICERs) for the 50-54, 55-59, and 60-64 age groups for TIV were US$2010.90, US$2004.58, and US$1865.55, respectively, while for QIV were US$2187.17, US$2190.89, and US$2074.52, respectively. Compared with TIV, ICERs for QIV were US$4445.66, US$4578.06, and US$4751.93, respectively. All the aforementioned ICER values were lower than the 2017 Korean GDP per capita of US$29,742.839. CONCLUSION: Implementing the NIP in the 50- to 64-year-old age group was found to be cost effective. Since both TIV and QIV were cost effective, we recommend QIV as the preferred option, based on its greater protection against Influenza B.