Cost-effectiveness of seasonal influenza vaccination in WHO-defined high-risk populations in Bangladesh.

Background: Bangladesh carries a substantial health and economic burden of seasonal influenza, particularly among the World Health Organization (WHO)-defined high-risk populations. We implemented a modelling study to determine the cost-effectiveness of influenza vaccination in each of five high-risk groups (pregnant women, children under five years of age, adults with underlying health conditions, older adults (≥60 years), and healthcare personnel) to inform policy decisions on risk group prioritisation for influenza vaccination in Bangladesh. Methods: We implemented a Markov decision-analytic model to estimate the impact of influenza vaccination for each target risk group. We obtained model inputs from hospital-based influenza surveillance data, unpublished surveys, and published literature (preferentially from studies in Bangladesh, followed by regional and global ones). We used quality-adjusted life years (QALY) as the health outcome of interest. We also estimated incremental cost-effectiveness ratios (ICERs) for each risk group by comparing the costs and QALY of vaccinating compared to not vaccinating each group, where the ICER represents the additional cost needed to achieve one year of additional QALY from a given intervention. We considered a willingness-to-pay threshold (ICER) of less than one gross domestic product (GDP) per capita as highly cost-effective and of one to three times GDP per capita as cost-effective (per WHO standard). For Bangladesh, this threshold ranges between USD 2462 and USD 7386. Results: The estimated ICERs were USD -99, USD -87, USD -4, USD 792, and USD 229 per QALY gained for healthcare personnel, older adults (≥60), children aged less than five years, adults with comorbid conditions, and pregnant women, respectively. For all risk groups, ICERs were below the WHO willingness-to-pay threshold for Bangladesh. Vaccinating pregnant women and adults with comorbid conditions was highly cost-effective per additional life year gained, while vaccinating healthcare personnel, older adults (≥60), and children under five years were cost-saving per additional life year gained. Conclusions: Influenza vaccination to all target risk groups in Bangladesh would be either cost-saving or cost-effective, per WHO guidelines of GDP-based thresholds.

Cost-consequence analysis of a combined COVID-19/influenza rapid diagnostic test in the Brazilian private healthcare setting.

Combination COVID-19/influenza rapid tests provide a way to quickly and accurately differentiate between the two infections. The goal of this economic evaluation was to assess the cost and health benefits of a combination COVID-19/influenza Rapid Diagnostic Test (RDT) vs. current standard-of-care in the Brazilian private healthcare setting. A dual decision tree model was developed to estimate the impact of rapid differentiation of COVID-19 and influenza in a hypothetical cohort of 1,000 adults with influenza-like illness in an ambulatory healthcare setting. The model compared the use of a combination COVID-19/influenza RDT to Brazil standard diagnostic practice of a COVID-19 RDT and presumptive influenza diagnosis. Different levels of influenza prevalence were modeled with co-infection estimated as a function of the COVID-19 prevalence. Outcomes included accuracy of diagnosis, antiviral prescriptions and healthcare resource use (hospital bed days and ICU occupancy). Depending on influenza prevalence, considering 1,000 patients with influenza-like illness, a combination RDT compared to standard practice was estimated to result in between 88 and 149 fewer missed diagnoses of influenza (including co-infection), 161 to 185 fewer cases of over-diagnosis of influenza; a 24 to 34% reduction in hospital bed days and a 16 to 26% reduction in ICU days. In the base case scenario (20% influenza, 5% COVID-19), the combination RDT was estimated to result in cohort cost savings of $99. Based upon a de novo economic model, this analysis indicates that use of a combination RDT could positively impact influenza antiviral prescriptions and lower healthcare resource use.

The Hospital Burden of Flu in Italy: a retrospective study on administrative data from season 2014-2015 to 2018-2019.

BACKGROUND: Every year in Italy, influenza affects about 4 million people. Almost 5% of them are hospitalised. During peak illness, enormous pressure is placed on healthcare and economic systems. This study aims to quantify the clinical and economic burden of severe influenza during 5 epidemic seasons (2014-2019) from administrative claims data. METHODS: Patients hospitalized with a diagnosis of influenza between October 2014, and April 2019, were analyzed. Clinical characteristics and administrative information were retrieved from health-related Administrative Databases (ADs) of 4 Italian Local Health Units (LHUs). The date of first admission was set as the Index Date (ID). A follow-up period of six months after ID was considered to account for complications and re-hospitalizations, while a lookback period (2 years before ID) was set to assess the prevalence of underlying comorbidities. RESULTS: Out of 2,333 patients with severe influenza, 44.1% were adults ≥ 65, and 25.6% young individuals aged 0-17. 46.8% had comorbidities (i.e., were at risk), mainly cardiovascular and metabolic diseases (45.3%), and chronic conditions (24.7%). The highest hospitalization rates were among the elderly (≥ 75) and the young individuals (0-17), and were 37.6 and 19.5/100,000 inhabitants/year, respectively. The average hospital stay was 8 days (IQR: 14 - 4). It was higher for older individuals (≥ 65 years, 11 days, [17 - 6]) and for those with comorbidities (9 days, [16 - 6]), p-value < 0.001. Similarly, mortality was higher in elderly and those at risk (p-value < 0.001). Respiratory complications occurred in 12.7% of patients, and cardiovascular disorders in 5.9%. Total influenza-related costs were €9.7 million with hospitalization accounting for 95% of them. 47.3% of hospitalization costs were associated with individuals ≥ 65 and 52.9% with patients at risk. The average hospitalisation cost per patient was € 4,007. CONCLUSIONS: This retrospective study showed that during the 2014-2019 influenza seasons in Italy, individuals of extreme ages and those with pre-existing medical conditions, were more likely to be hospitalized with severe influenza. Together with complications and ageing, they worsen patient's outcome and may lead to a prolonged hospitalization, thus increasing healthcare utilization and costs. Our data generate real-world evidence on the burden of influenza, useful to inform public health decision-making.

Subsidy Programs for Seasonal Influenza Vaccination of Children and Pregnant Women in Japanese Municipalities.

In Japan, influenza vaccination is offered to children and pregnant women at clinics or hospitals as an elective, self-funded treatment, as the vaccination is not included in the national vaccination subsidy program. However, some Japanese municipalities offer a discretionary subsidy for seasonal influenza vaccination of children and pregnant women as a local policy. We identified these local subsidy programs during 2019/2020 seasonal influenza season by conducting a cross-sectional survey across Japan. Out of a total of 1741 municipalities, responses were received from 1732; therefore, the response rate was 99.5%. The local influenza vaccine subsidy programs for children were offered in 45.7%, and for pregnant women in 10.2%, of Japanese municipalities. This is the first survey of subsidy programs for pregnant women. While policy diffusion of subsidy programs for children was observed during the 9 years since a previous study, such programs for pregnant women remain limited. Despite many municipalities having subsidy programs, we found that their provision still remains limited when viewed as a whole.

The economic rationale for cell-based influenza vaccines in children and adults: A review of cost-effectiveness analyses.

Seasonal influenza significantly affects both health and economic costs in children and adults. This narrative review summarizes published cost-effectiveness analyses (CEAs) of cell-based influenza vaccines in children and adults <65 years of age, critically assesses the assumptions and approaches used in these analyses, and considers the role of cell-based influenza vaccines for children and adults. CEAs from multiple countries demonstrated the cost-effectiveness of cell-based quadrivalent influenza vaccines (QIVc) compared with egg-based trivalent/quadrivalent influenza vaccines (TIVe/QIVe). CEA findings were consistent across models relying on different relative vaccine effectiveness (rVE) estimate inputs, with the rVE of QIVc versus QIVe ranging from 8.1% to 36.2% in favor of QIVc. Across multiple scenarios and types of analyses, QIVc was consistently cost-effective compared with QIVe, including in children and adults across different regions of the world.

Pharmacoeconomic study of anti-influenza virus drugs in Japan based on a network meta-analysis.

BACKGROUND: An analysis was conducted in Japan to determine the most cost-effective neuraminidase inhibitor for the treatment of influenza virus infections from the healthcare payer's standpoint. OBJECTIVE: This study reanalysed the findings of a previous study that had some limitations (no probabilistic sensitivity analysis and quality of life scores measured by the EQ-5D-3L instead of the EQ-5D-5L) and used a decision tree model with only three health conditions. METHODS: This study incorporated new data from a network meta-analysis study into the first examination. The second examination involved constructing a new decision tree model encompassing seven health conditions and identifying costs, which consisted of medical costs and drug prices based on the 2020 version of the Japanese medical fee index. Effectiveness outcomes were measured using EQ-5D-5L questionnaires for adult patients with a history of influenza virus infections within a 14-day time horizon. Deterministic and probabilistic sensitivity analyses were performed to examine the uncertainty. RESULTS: In the first examination, the base-case cost-effectiveness analysis confirmed that oseltamivir outperformed laninamivir, zanamivir and peramivir, making it the most cost-effective neuraminidase inhibitor. The second examination revealed that oseltamivir dominated the other agents. Both deterministic and probabilistic sensitivity analyses showed robust results that validated oseltamivir as the most cost effective among the four neuraminidase inhibitors. CONCLUSIONS: This study thus reaffirms oseltamivir's position as the most cost-effective neuraminidase inhibitor for the treatment of influenza virus infections in Japan from the perspective of healthcare payment. These findings can help decision makers and healthcare providers in Japan.

Epidemiological and health economic implications of symptom propagation in respiratory pathogens: A mathematical modelling investigation.

BACKGROUND: Respiratory pathogens inflict a substantial burden on public health and the economy. Although the severity of symptoms caused by these pathogens can vary from asymptomatic to fatal, the factors that determine symptom severity are not fully understood. Correlations in symptoms between infector-infectee pairs, for which evidence is accumulating, can generate large-scale clusters of severe infections that could be devastating to those most at risk, whilst also conceivably leading to chains of mild or asymptomatic infections that generate widespread immunity with minimal cost to public health. Although this effect could be harnessed to amplify the impact of interventions that reduce symptom severity, the mechanistic representation of symptom propagation within mathematical and health economic modelling of respiratory diseases is understudied. METHODS AND FINDINGS: We propose a novel framework for incorporating different levels of symptom propagation into models of infectious disease transmission via a single parameter, α. Varying α tunes the model from having no symptom propagation (α = 0, as typically assumed) to one where symptoms always propagate (α = 1). For parameters corresponding to three respiratory pathogens-seasonal influenza, pandemic influenza and SARS-CoV-2-we explored how symptom propagation impacted the relative epidemiological and health-economic performance of three interventions, conceptualised as vaccines with different actions: symptom-attenuating (labelled SA), infection-blocking (IB) and infection-blocking admitting only mild breakthrough infections (IB_MB). In the absence of interventions, with fixed underlying epidemiological parameters, stronger symptom propagation increased the proportion of cases that were severe. For SA and IB_MB, interventions were more effective at reducing prevalence (all infections and severe cases) for higher strengths of symptom propagation. For IB, symptom propagation had no impact on effectiveness, and for seasonal influenza this intervention type was more effective than SA at reducing severe infections for all strengths of symptom propagation. For pandemic influenza and SARS-CoV-2, at low intervention uptake, SA was more effective than IB for all levels of symptom propagation; for high uptake, SA only became more effective under strong symptom propagation. Health economic assessments found that, for SA-type interventions, the amount one could spend on control whilst maintaining a cost-effective intervention (termed threshold unit intervention cost) was very sensitive to the strength of symptom propagation. CONCLUSIONS: Overall, the preferred intervention type depended on the combination of the strength of symptom propagation and uptake. Given the importance of determining robust public health responses, we highlight the need to gather further data on symptom propagation, with our modelling framework acting as a template for future analysis.

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.

Public health and economic benefits of seasonal influenza vaccination in risk groups in France, Italy, Spain and the UK: state of play and perspectives.

BACKGROUND: Seasonal influenza epidemics have a substantial public health and economic burden, which can be alleviated through vaccination. The World Health Organization (WHO) recommends a 75% vaccination coverage rate (VCR) in: older adults (aged ≥ 65 years), individuals with chronic conditions, pregnant women, children aged 6-24 months and healthcare workers. However, no European country achieves this target in all risk groups. In this study, potential public health and economic benefits achieved by reaching 75% influenza VCR was estimated in risk groups across four European countries: France, Italy, Spain, and the UK. METHODS: A static epidemiological model was used to estimate the averted public health and economic burden of increasing the 2021/2022 season VCR to 75%, using the efficacy data of standard-dose quadrivalent influenza vaccine. For each country and risk group, the most recent data on population size, VCR, pre-pandemic influenza epidemiology, direct medical costs and absenteeism were identified through a systematic literature review, supplemented by manual searching. Outcomes were: averted influenza cases, general practitioner (GP) visits, hospitalisations, case fatalities, number of days of work lost, direct medical costs and absenteeism-related costs. RESULTS: As of the 2021/2022 season, the UK achieved the highest weighted VCR across risk groups (65%), followed by Spain (47%), France (44%) and Italy (44%). Based on modelling, the 2021/2022 VCR prevented an estimated 1.9 million influenza cases, avoiding 375,200 GP visits, 73,200 hospitalisations and 38,400 deaths. To achieve the WHO 75% VCR target, an additional 24 million at-risk individuals would need to be vaccinated, most of which being older adults and patients with chronic conditions. It was estimated that this could avoid a further 918,200 influenza cases, 332,000 GP visits, 16,300 hospitalisations and 6,300 deaths across the four countries, with older adults accounting for 52% of hospitalisations and 80% of deaths. An additional €84 million in direct medical costs and €79 million in absenteeism costs would be saved in total, with most economic benefits delivered in France. CONCLUSIONS: Older adults represent most vaccine-preventable influenza cases and deaths, followed by individuals with chronic conditions. Health authorities should prioritise vaccinating these populations for maximum public health and economic benefits.

Cost-effectiveness of high-dose influenza vaccination in the Netherlands: Incorporating the impact on both respiratory and cardiovascular hospitalizations.

OBJECTIVES: We assess the cost-effectiveness of switching from standard-dose quadrivalent influenza vaccination (SD-QIV) to high-dose vaccination (HD-QIV) for Dutch adults aged 60 years and older. METHODS: A health-economic model was used to compare the scenario where HD-QIV was implemented compared to the current standard, SD-QIV. This model used a lifetime horizon and assessed the cost-effectiveness from a societal perspective. A recently published meta-analysis was used to incorporate the benefits of HD-QIV, including cardiorespiratory hospitalizations, in analyses considering RCT only or combining RCT and RWE estimates in a scenario analysis. RESULTS: Implementing HD-QIV is cost effective at its list price, with an ICER of €5,400 per QALY gained. The main driver of these results is the prevention of cardiorespiratory hospitalizations. Other public health benefits are the prevention of GP consults and deaths. HD-QIV is highly likely to be cost-effective, reaching a 100% probability of being cost effective at the Dutch willingness-to-pay threshold of €20,000 per QALY. CONCLUSIONS: Implementing HD-QIV for adults aged 60 and over within the existing influenza vaccination campaign is highly cost effective. HD-QIV may support alleviating potential capacity issues in Dutch hospitals in the winter respiratory season.

Effectiveness of financial incentives on influenza vaccination among older adults in China: a randomized clinical trial.

OBJECTIVES: To investigate the short-term and long-term effectiveness of different levels of financial incentives on increasing the willingness to vaccinate and vaccine uptake. METHODS: A randomized controlled trial was conducted to investigate the effectiveness of financial incentives of three groups with monetary incentives (CNY 20, CNY 40, and CNY 60; 1 CNY = 0.13 EUR) vs. a control group-CNY 0-on influenza vaccine uptake among 720 older adults (≥60 years) in Beijing, China. The primary outcome was vaccine uptake, and the secondary outcomes were intention to vaccinate and length of time to immunization. RESULTS: Financial incentive significantly promoted higher intention to influenza vaccination (120/178 [67.42%] vs. 442/542 [81.55%]; Relative Risk [RR], 1.21; 95% CI, 1.02-1.42) and higher vaccination participation (74/178 [41.57%] vs. 316/542 [58.30%]; RR, 1.39; 95% CI, 1.10-1.75). CNY 60 had the largest impact on the intention to vaccinate (15.00% vs. 13.48% and 13.90%) and vaccination uptake (19.42% vs. 14.05% and 16.67%) compared with CNY 20 and CNY 40. Time to vaccination was significantly lower among participants receiving incentives than those without ([37.21 days; 95% CI, 34.33-39.99] vs. [48.27 days; 95% CI, 43.47-53.07]; Hazard Ratio [HR] 1.57, 95% CI 1.22-2.03). We found no long-term influence of financial incentives on vaccination decisions in the following year (217/542, 40.04% vs. 65/178, 36.52%; RR 1.08, 95% CI 0.82-1.42). DISCUSSION: Our study suggests that modest financial incentives will boost short-term influenza vaccination rates and shorten the length of time to immunization in China. No one single-time financial incentive had a long-term effect on future vaccination behaviours or helped establish regular vaccination behaviours.

The Cost of Seasonal Influenza: A Systematic Literature Review on the Humanistic and Economic Burden of Influenza in Older (≥ 65 Years Old) Adults.

INTRODUCTION: Adults aged ≥ 65 years contribute a large proportion of influenza-related hospitalizations and deaths due to increased risk of complications, which result in high medical costs and reduced health-related quality of life (HRQoL). Although seasonal influenza vaccines are recommended for older adults, the effectiveness of current vaccines is dependent on several factors including strain matching and recipient demographic factors. This systemic literature review aimed to explore the economic and humanistic burden of influenza in adults aged ≥ 65 years. METHODS: An electronic database search was conducted to identify studies assessing the economic and humanistic burden of influenza, including influenza symptoms that impact the HRQoL and patient-related outcomes in adults aged ≥ 65 years. Studies were to be published in English and conducted in Germany, France, Spain, and Italy, the UK, USA, Canada, China, Japan, Brazil, Saudi Arabia, and South Africa. RESULTS: Thirty-eight studies reported on the economic and humanistic burden of influenza in adults aged ≥ 65 years. Higher direct costs were reported for people at increased risk of influenza-related complications compared to those at low risk. Lower influenza-related total costs were found in those vaccinated with adjuvanted inactivated trivalent influenza vaccine (aTIV) compared to high-dose trivalent influenza vaccine (TIV-HD). Older age was associated with an increased occurrence and longer duration of certain influenza symptoms. CONCLUSION: Despite the limited data identified, results show that influenza exerts a high humanistic and economic burden in older adults. Further research is required to confirm findings and to identify the unmet needs of current vaccines.

Socioeconomic impacts of airborne and droplet-borne infectious diseases on industries: a systematic review.

BACKGROUND: Recent pandemics have had far-reaching effects on the world's largest economies and amplified the need to estimate the full extent and range of socioeconomic impacts of infectious diseases outbreaks on multi-sectoral industries. This systematic review aims to evaluate the socioeconomic impacts of airborne and droplet-borne infectious diseases outbreaks on industries. METHODS: A structured, systematic review was performed according to the PRISMA guidelines. Databases of PubMed, Scopus, Web of Science, IDEAS/REPEC, OSHLINE, HSELINE, and NIOSHTIC-2 were reviewed. Study quality appraisal was performed using the Table of Evidence Levels from Cincinnati Children's Hospital Medical Center, Joanna Briggs Institute tools, Mixed Methods Appraisal Tool, and Center of Evidence Based Management case study critical appraisal checklist. Quantitative analysis was not attempted due to the heterogeneity of included studies. A qualitative synthesis of primary studies examining socioeconomic impact of airborne and droplet-borne infectious diseases outbreaks in any industry was performed and a framework based on empirical findings was conceptualized. RESULTS: A total of 55 studies conducted from 1984 to 2021 were included, reporting on 46,813,038 participants working in multiple industries across the globe. The quality of articles were good. On the whole, direct socioeconomic impacts of Coronavirus Disease 2019, influenza, influenza A (H1N1), Severe Acute Respiratory Syndrome, tuberculosis and norovirus outbreaks include increased morbidity, mortality, and health costs. This had then led to indirect impacts including social impacts such as employment crises and reduced workforce size as well as economic impacts such as demand shock, supply chain disruptions, increased supply and production cost, service and business disruptions, and financial and Gross Domestic Product loss, attributable to productivity losses from illnesses as well as national policy responses to contain the diseases. CONCLUSIONS: Evidence suggests that airborne and droplet-borne infectious diseases have inflicted severe socioeconomic costs on regional and global industries. Further research is needed to better understand their long-term socioeconomic impacts to support improved industry preparedness and response capacity for outbreaks. Public and private stakeholders at local, national, and international levels must join forces to ensure informed systems and sector-specific cost-sharing strategies for optimal global health and economic security.

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

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

Correspondence to: Estimating the full health and economic benefits of current and future influenza vaccines.

We recently published an article in BMC Medicine looking at the potential health and economic impact of paediatric vaccination using next-generation influenza vaccines in Kenya: a modelling study. In their commentary on our article, Lafond et al. highlight the potential importance of the wider benefits of vaccination on cost-effectiveness. Whilst we agree with many points raised in the commentary, we think it raises further interesting discussion points, specifically around model complexity, model assumptions and data availability. These points are both relevant to this manuscript but have wider implications for vaccine cost-effectiveness studies.

Estimating the full health and economic benefits of current and future influenza vaccines.

In the dynamic landscape of respiratory virus vaccines, it is crucial to assess the value of novel mRNA and combination influenza/COVID-19 vaccines in low- and middle-income countries. Modeling studies, such as the one conducted by Waterlow et al., provide vital information about the cost-benefit potential of these products compared to currently licensed vaccines. However, this approach only accounts for directly measured medically attended influenza-associated illnesses and has two major limitations. First, this method fails to capture the full disease burden of influenza (including non-respiratory and non-medically attended influenza illnesses), which are particularly important drivers of disease burden in infants and older adults. Second, the model does not describe the ancillary benefits of influenza vaccination such as the attenuation of severe disease, prevention of severe non-respiratory outcomes (e.g., myocardial infarctions), or reduced antibiotic use. To obtain a comprehensive understanding of the benefits of influenza vaccines, we must strive to improve the inputs for future modeling-based evaluations.

Delayed Influenza Treatment in Children With False-Negative Rapid Antigen Test: A Retrospective Single-Center Study in Korea 2016-2019.

BACKGROUND: We aimed to examine the delay in antiviral initiation in rapid antigen test (RAT) false-negative children with influenza virus infection and to explore the clinical outcomes. We additionally conducted a medical cost-benefit analysis. METHODS: This single-center, retrospective study included children (aged < 10 years) with influenza-like illness (ILI), hospitalized after presenting to the emergency department during three influenza seasons (2016-2019). RAT-false-negativity was defined as RAT-negative and polymerase chain reaction-positive cases. The turnaround time to antiviral treatment (TAT) was from the time when RAT was prescribed to the time when the antiviral was administered. The medical cost analysis by scenarios was also performed. RESULTS: A total of 1,430 patients were included, 7.5% were RAT-positive (n = 107) and 2.4% were RAT-false-negative (n = 20). The median TAT of RAT-false-negative patients was 52.8 hours, significantly longer than that of 4 hours in RAT-positive patients (19.2-100.1, P < 0.001). In the multivariable analysis, TAT of ≥ 24 hours was associated with a risk of severe influenza infection and the need for mechanical ventilation (odds ratio [OR], 6.8, P = 0.009 and OR, 16.2, P = 0.033, respectively). The medical cost varied from $11.7-187.3/ILI patient. CONCLUSION: Antiviral initiation was delayed in RAT-false-negative patients. Our findings support the guideline that children with influenza, suspected of having severe or progressive infection, should be treated immediately.

Impact of Adding Oseltamivir to Usual Care on Quality-Adjusted Life-Years During Influenza-Like Illness.

OBJECTIVES: The ALIC4E trial has shown that oseltamivir reduces recovery time while increasing the risk of nausea. This secondary analysis of the ALIC4E trial aimed to determine the gain in quality-adjusted life-years (QALYs) associated with adding oseltamivir to usual primary care in patients presenting with influenza-like illness (ILI). METHODS: Patients with ILI were recruited during the influenza season (2015-2018) in 15 European countries. Patients were assigned to usual care with or without oseltamivir through stratified randomization (age, severity, comorbidities, and symptom onset). Patients' health status was valued with the EQ-5D and visual analog scale (VAS) for up to 28 days. Average EQ-5D and VAS scores over time were estimated for both treatment groups using one-inflated beta regression in children (<13 years old) and adults (≥13 years old). QALY gain was calculated as the difference between the groups. Sensitivity analysis considered the value set to convert EQ-5D answers to summary scores and the follow-up period. RESULTS: In adults, oseltamivir gained 0.0006 (95% confidence interval 0.0002-0.0010) QALYs, whereas no statistically significant gain was found in children (14-day follow-up, EQ-5D). QALY gains were statistically significant in patients aged ≥65 years, patients without relevant comorbidities, or patients experiencing symptoms for ≤48 hours. Using VAS and accounting for 28-day follow-up resulted in higher QALY gain. CONCLUSIONS: QALY gain owing to oseltamivir is limited compared with other diseases, and its clinical meaningfulness remains to be determined. Further analysis is needed to evaluate whether QALY gain and its impact on ILI treatment cost render oseltamivir cost-effective.

Why Does Influenza Hit the Poor More Than the Rich? A 1931 Social Epidemiology Article That Broke New Ground in the History of Confounding, Mediation, and Interaction.

In 1931, Edgar Sydenstricker, the former statistician of the US Public Health Service, challenged the common belief that the 1918 influenza outbreak had affected "the rich and the poor alike." Using data from 112,317 participants in a 1918 US national survey, he observed that, on the contrary, both morbidity and mortality from the flu had been higher among the poor than among the rich. To explain these differences, Sydenstricker stratified the analyses by 2 measures of affluence collected in the survey: "economic status" (from "very poor" to "well-to-do") and household crowding (i.e., number of people per household room). Economic status was associated with influenza attack rates within categories of crowding, but not the opposite, suggesting that characteristics of poverty other than "household congestion" were the culprit of the poor's higher influenza burden. Attack rate ratios for influenza in infants and older adults were greater for the poor or very poor. Sydenstricker reanalyzed an already 12-year-old data set in the context of the Great Depression to build the evidence base relating poverty to ill health. For this purpose he used a stratification approach to assess confounding, mediation, and interaction before the concepts were formally named.