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Economic burden of seasonal influenza in the United States
Abstract
Background:
Seasonal influenza is responsible for a large disease and economic burden. Despite the expanding recommendation of influenza vaccination, influenza has continued to be a major public health concern in the United States (U.S.). To evaluate influenza prevention strategies it is important that policy makers have current estimates of the economic burden of influenza.
Objective:
To provide an updated estimate of the average annual economic burden of seasonal influenza in the U.S. population in the presence of vaccination efforts.
Methods:
We evaluated estimates of age-specific influenza-attributable outcomes (ill-non medically attended, office-based outpatient visit, emergency department visits, hospitalizations and death) and associated productivity loss. Health outcome rates were applied to the 2015 U.S. population and multiplied by the relevant estimated unit costs for each outcome. We evaluated both direct healthcare costs and indirect costs (absenteeism from paid employment) reporting results from both a healthcare system and societal perspective. Results were presented in five age groups (<5 years, 5-17 years, 18-49 years, 50-64 years and ≥65 years of age).
Results:
The estimated average annual total economic burden of influenza to the healthcare system and society was $11.2 billion ($6.3-$25.3 billion). Direct medical costs were estimated to be $3.2 billion ($1.5-$11.7 billion) and indirect costs $8.0 billion ($4.8-$13.6 billion). These total costs were based on the estimated average numbers of (1) ill-non medically attended patients (21.6 million), (2) office-based outpatient visits (3.7 million), (3) emergency department visit (0.65 million) (4) hospitalizations (247.0 thousand), (5) deaths (36.3 thousand) and (6) days of productivity lost (20.1 million).
Conclusions:
This study provides an updated estimate of the total economic burden of influenza in the U.S. Although we found a lower total cost than previously estimated, our results confirm that influenza is responsible for a substantial economic burden in the U.S.
... The Centers for Disease Control and Prevention (CDC) estimates that influenza accounted for 4.3-21 million medical visits, 140,000-810,000 hospitalizations, and 12,000-61,000 deaths annually in the US during the 2010-11 through 2019-20 influenza seasons [1]. In turn, the estimated total economic burden of influenza is substantial at $11.2 billion (ranging from $6.3-$25.3 billion) [2] and as high as $87.1 billion (95% confidence interval [CI], $47.2-$149.5) [3]. ...
... [3]. Direct medical costs have been estimated at $3.2 billion annually, of which 70% ($2.3 billion) is due to hospitalizations [2], despite hospitalization in only 1-2% of medically-attended influenza cases [1]. ...
... Although influenza is generally self-limiting with mild symptoms in healthy individuals [4], certain vulnerable populations are at elevated risk for serious influenza-related medical complications. For example, while the elderly population ≥ 65 years of age has the lowest median incidence of influenza (3.9%) compared to children 0-17 years (9.3%) or adults 18-64 years (8.8%) [5], they account for 50-70% of influenza-related hospitalizations, 70-85% of deaths [6], and 42.7% of direct medical costs [2]. Chronic medical conditions, including pulmonary, cardiovascular, renal, hepatic, and metabolic disorders, have also been identified as predictors of influenza-related complications [7][8][9][10][11][12]. ...
Background:
Seasonal influenza poses a substantial clinical and economic burden in the United States and vulnerable populations, including the elderly and those with comorbidities, are at elevated risk for influenza-related medical complications.
Methods:
We conducted a retrospective cohort study using the IQVIA PharMetrics® Plus claims database in two stages. In Stage 1, we identified patients with evidence of medically-attended influenza during influenza seasons from October 1, 2014 to May 31, 2018 (latest available data for Stage 1) and used a multivariable logistic regression model to identify patient characteristics that predicted 30-day influenza-related hospitalization. The findings from Stage 1 informed high-risk subgroups of interest for Stage 2, where we selected cohorts of influenza patients during influenza seasons from October 1, 2014 to March 1, 2019 and used 1:1 propensity score matching to patients without influenza with similar high-risk characteristics to compare influenza-attributable rates of all-cause hospital and emergency department (ED) visits during follow-up (30-day and in the index influenza season).
Results:
In Stage 1, more than 1.6 million influenza cases were identified, of which 18,509 (1.2%) had a hospitalization. Elderly age was associated with 9 times the odds of hospitalization (≥65 years vs. 5-17 years; OR = 9.4, 95% CI 8.8-10.1) and select comorbidities were associated with 2-3 times the odds of hospitalization. In Stage 2, elderly influenza patients with comorbidities had 3 to 7 times higher 30-day hospitalization rates compared to matched patients without influenza, including patients with congestive heart failure (41.0% vs.7.9%), chronic obstructive pulmonary disease (34.6% vs. 6.1%), coronary artery disease (22.8% vs. 3.8%), and late-stage chronic kidney disease (44.1% vs. 13.1%; all p < 0.05).
Conclusions:
The risk of influenza-related complications is elevated in the elderly, especially those with certain underlying comorbidities, leading to excess healthcare resource utilization. Continued efforts, beyond currently available vaccines, are needed to reduce influenza burden in high-risk populations.
... According to the World Health Organization (WHO), influenza affects one-billion of the world's population each year, resulting in about three-to five-million cases of severe illness and about 290,000 to 650,000 influenza-related respiratory deaths [1]. Annually, in the United States alone, influenza is estimated to cause a total economic burden of $11.2 billion ($6.3-25.3 billion) [2]. Influenza complications can occur mostly among high-risk individuals such as children, the elderly, pregnant and postpartum women up to two weeks after COVID-19 pandemic for the 2021-2022 influenza season. ...
... In a study by Davis and colleagues [41], the most common reason for not receiving the influenza vaccine was not being concerned about the infection. In fact, the substantial healthcare and economic burden resulting from influenza was estimated at an annual sum reaching 25 billion US dollars [2]. As individuals may not be well aware of such a burden, raising awareness and dissemination of knowledge regarding influenza and the key role of vaccination are crucial, especially to the population of university students. ...
Vaccination is the most effective preventative strategy against influenza, yet university students’ influenza vaccination uptake remains low. This study aimed firstly to determine the percentage of university students who were vaccinated for the 2015–2016 influenza season and to identify reasons for non-vaccination, and secondly to examine the impact of external factors (on-campus/online influenza awareness campaigns and COVID-19 pandemic) on their influenza vaccination uptake and attitudes for the 2017–2018 and 2021–2022 influenza seasons. A descriptive study was conducted over three phases for three influenza seasons at a Lebanese university in the Bekaa Region. Based on data collected in 2015–2016, promotional activities were developed and implemented for the other influenza seasons. This study was conducted using an anonymous, self-administered questionnaire by students. The majority of the respondents in the three studies did not receive the influenza vaccine (89.2% in the 2015–2016 study, 87.3% in the 2017–2018 study, and 84.7% in the 2021–2022 study). Among the unvaccinated respondents, the main reason for non-vaccination was that they thought that they did not need it. The primary reason for vaccination among those who were vaccinated was that they believed they were at risk of catching influenza in a 2017–2018 study and due to the COVID-19 pandemic in the 2021–2022 study. As for attitudes towards influenza vaccination post-COVID-19, significant differences were shown among the vaccinated and unvaccinated respondents. The vaccination rates among university students remained low despite of the awareness campaigns and COVID-19 pandemic.
... Seasonal influenza vaccines are the primary means of reducing the global burden of influenza-a disease that annually causes approximately 300,000-650,000 deaths worldwide and substantial economic burden in both low and high income countries [1][2][3][4]. In the US, the estimated total economic burden due to influenza is $11.2 billion, including $3.2 billion in direct healthcare costs and $8.0 billion in lost productivity [2]. ...
... Seasonal influenza vaccines are the primary means of reducing the global burden of influenza-a disease that annually causes approximately 300,000-650,000 deaths worldwide and substantial economic burden in both low and high income countries [1][2][3][4]. In the US, the estimated total economic burden due to influenza is $11.2 billion, including $3.2 billion in direct healthcare costs and $8.0 billion in lost productivity [2]. Studies of influenza vaccine cost effectiveness consistently show savings of $10,000-$50,000 per influenzarelated outcome in middle and high income countries [5]. ...
To ensure that vaccination offers the best protection against an infectious disease, sequence identity between the vaccine and the circulating strain is paramount. During replication of nucleic acid, random mutations occur due to the level of polymerase fidelity. In traditional influenza vaccine manufacture, vaccine viruses are propagated in fertilized chicken eggs, which can result in egg-adaptive mutations in the antigen-encoding genes. Whilst this improves infection and replication in eggs, mutations may reduce the effectiveness of egg-based influenza vaccines against circulating human viruses. In contrast, egg-adaptive mutations are avoided when vaccine viruses are propagated in Madin-Darby canine kidney (MDCK) cell lines during manufacture of cell-based inactivated influenza vaccines. The first mammalian cell-only strain was included in Flucelvax® Quadrivalent in 2017. A sequence analysis of the viruses selected for inclusion in this vaccine (n = 15 vaccine strains, containing both hemagglutinin and neuraminidase) demonstrated that no mutations occur in the antigenic sites of either hemagglutinin or neuraminidase, indicating that cell adaptation does not occur during production of this cell-based vaccine. The development of this now entirely mammalian-based vaccine system, which incorporates both hemagglutinin and neuraminidase, ensures that the significant protective antigens are equivalent to the strains recommended by the World Health Organization (WHO) in both amino acid sequence and glycosylation pattern. The inclusion of both proteins in a vaccine may provide an advantage over recombinant vaccines containing hemagglutinin alone. Findings from real world effectiveness studies support the use of cell-based influenza vaccines.
... For example, a recent study covering data from 2015 in the United States, across all age groups, estimated that direct medical costs amounted to approximately $3.2 billion nationally. 3 The same study showed that influenza has a substantial impact on workplace activity, with 20 million days of productivity lost in the United States during 2015. 3 In 2003, the World Health Organization (WHO) stated that member states should aim to achieve an influenza vaccination coverage rate (VCR) of 75% or higher among older people (defined as those aged ≥65 years in 76% of the responding countries but refers to those aged ≥60 years in Germany) and individuals with chronic illnesses and that this target should be achieved by 2010. 4 This motion was reaffirmed by the European Parliament and extended in a 2009 European Council recommendation, whereby European countries should reach 75% vaccination coverage in older age groups by 2015. ...
... 3 The same study showed that influenza has a substantial impact on workplace activity, with 20 million days of productivity lost in the United States during 2015. 3 In 2003, the World Health Organization (WHO) stated that member states should aim to achieve an influenza vaccination coverage rate (VCR) of 75% or higher among older people (defined as those aged ≥65 years in 76% of the responding countries but refers to those aged ≥60 years in Germany) and individuals with chronic illnesses and that this target should be achieved by 2010. 4 This motion was reaffirmed by the European Parliament and extended in a 2009 European Council recommendation, whereby European countries should reach 75% vaccination coverage in older age groups by 2015. 5 In Germany, the current influenza immunization recommendation issued by the Standing Committee on Vaccination (STIKO) focuses on individuals aged ≥60 years, individuals with underlying chronic conditions, pregnant women, and healthcare workers. ...
Background:
The significant annual burden caused by seasonal influenza has led to global calls for increased influenza vaccination coverage rates (VCRs). We aimed to estimate the proportion of the German population at high risk of serious illness from influenza due to chronic conditions and to estimate age-specific VCRs of people with/without chronic conditions.
Methods:
Using health insurance claims data covering nine influenza seasons (2010-2019), we assessed up to 7 million insured individuals per season across all German regions. Individuals were classified according to age and presence of chronic health conditions. VCRs were estimated using outpatient healthcare utilization documentation.
Results:
In the 2018-2019 influenza season, 47.3% of individuals had ≥1 chronic condition. Most common were circulatory disorders, accounting for more than a third of individuals with ≥1 condition. Prevalence of chronic diseases, and therefore the proportion of high-risk individuals, increased slightly over time across most age groups. A downward trend in influenza VCRs was observed in all age groups until the 2017-2018 season, followed by a noticeable increase in the 2018-2019 season. Highest VCRs occurred among individuals of ≥60 years, with a 38.5% VCR for this age group in the 2018-2019 season. Several factors, including age, chronic condition type, and geographical location, affected VCRs.
Conclusions:
Influenza VCRs in individuals at high risk of severe complications from influenza infection are insufficient. Our results suggest that intensified public health efforts are necessary to reach the World Health Organization vaccination coverage target of 75%.
... Influenza is a global health threat, with outbreaks accounting for 3 to 5 million cases of severe illness and approximately 250,000 deaths every year [1,2]. On top of that, it poses a huge economic burden and contributes to higher medical costs, with the estimated economic burden of seasonal influenza in the United States more than USD 11 billion in 2015 [3]. While not perfect, receiving an up-to-date influenza vaccination against the circulating strains is able to effectively reduce an individual's infection, transmission, and disease severity risk [4]. ...
Several countries are witnessing significant increases in influenza cases and severity. Despite the availability, effectiveness and safety of influenza vaccination, vaccination coverage remains suboptimal globally. In this study, we examined the prevailing negative sentiments related to influenza vaccination via a deep learning analysis of public Twitter posts over the past five years. We extracted original tweets containing the terms ‘flu jab’, ‘#flujab’, ‘flu vaccine’, ‘#fluvaccine’, ‘influenza vaccine’, ‘#influenzavaccine’, ‘influenza jab’, or ‘#influenzajab’, and posted in English from 1 January 2017 to 1 November 2022. We then identified tweets with negative sentiment from individuals, and this was followed by topic modelling using machine learning models and qualitative thematic analysis performed independently by the study investigators. A total of 261,613 tweets were analyzed. Topic modelling and thematic analysis produced five topics grouped under two major themes: (1) criticisms of governmental policies related to influenza vaccination and (2) misinformation related to influenza vaccination. A significant majority of the tweets were centered around perceived influenza vaccine mandates or coercion to vaccinate. Our analysis of temporal trends also showed an increase in the prevalence of negative sentiments related to influenza vaccination from the year 2020 onwards, which possibly coincides with misinformation related to COVID-19 policies and vaccination. There was a typology of misperceptions and misinformation underlying the negative sentiments related to influenza vaccination. Public health communications should be mindful of these findings.
... Prior to the COVID-19 pandemic, seasonal influenza represented the highest burden in terms of both incidence and cost among all preventable diseases [7][8][9]. According to a study, in 2015, within the United States seasonal influenza resulted in an estimated economic burden of $11.2 billion, of which, $8.0 billion were accounted toward indirect costs [10]. Noteworthy, the annual economic burden of non-influenza viral RTIs was accounted for a much higher cost of $40 billion [11]. ...
Respiratory tract infections (RTIs) are one of the main causes of hospitalization and mortality causing substantial economic burden to healthcare systems globally. As opposed to the previous belief that respiratory infections are caused by a single pathogen, studies have shown that most RTIs are a result of a combination of bacterial and/or viral pathogens infecting the host. The clinical manifestation of RTIs is very similar (i.e., syndrome), often showing Influenza-like illness (ILI) symptoms. While COVID-19 has dominated ILI over the past few years, there are many other pathogens that are responsible for ILI. In addition, it is not uncommon to have coinfections with multiple pathogens in patients presenting with ILI and that such coinfections can even exacerbate the disease severity of RTIs. Therefore, an insight into coinfections can help with accurate disease prognosis, patient care management and outcomes. The goal of this study was to identify the different organisms in symptomatic patients presenting with ILI.
... 1,2 In the United States, the average socio-economic loss attributable to influenza was $11.2 billion in 2015. 3 Globally, annual influenza-related respiratory mortality in 2002-2011 (excluding the 2009 pandemic year) was estimated as 5.9 per 100,000 individuals overall and 53.7 per 100,000 elderly individuals. 4 Numerous studies have investigated mortality burden attributable to seasonal influenza using number of deaths and influenza cases from surveillance data per time interval. ...
... A 2018 study by Putri et al attributes the economic burden of influenza to outpatient visits, emergency department visits, hospitalizations, death, and loss of productivity, for an estimated loss of USD 11.2 billion annually. 22 Due to the well-known clinical and monetary impact of influenza infection and CVD, multiple analyses have been performed to delineate the potential benefit of influenza vaccination in patients with CVD. Udell et al demonstrated improved cardiovascular outcomes with influenza vaccination in a meta-analysis of 6 randomized trials. ...
Influenza vaccination has shown great promise in terms of its cardioprotective effects. The aim of our analysis is to provide evidence regarding the protective effects of influenza vaccination in patients with cardiovascular disease. We conducted a systematic literature search to identify trials assessing the cardiovascular outcomes of influenza vaccination. Summary effects were calculated using a DerSimonian and Laird fixed effects and random effects model as odds ratio with 95% confidence intervals (CIs) for all the clinical endpoints. Fifteen studies with a total of 745,001 patients were included in our analysis. There was lower rates of all-cause mortality [odds ratio (OR) = 0.74, 95% CI 0.64-0.86], cardiovascular death (OR = 0.73, 95% CI 0.59-0.92), and stroke (OR = 0.71, 95% CI 0.57-0.89) in patients who received the influenza vaccine compared to placebo. There was no significant statistical difference in rates of myocardial infarction (OR = 0.91, 95% CI 0.69-1.21) or heart failure hospitalizations (OR = 1.06, 95% CI 0.85-1.31) in the 2 cohorts. In patients with cardiovascular disease, influenza vaccination is associated with lower all-cause mortality, cardiovascular death, and stroke.
... Worldwide, seasonal influenza epidemics of variable severity cause an enormous socioeconomic burden. [1][2][3] Indeed, during the winter months, seasonal influenza can infect up to 20% of the population and cause substantial morbidity, mortality and economic and social disruption. 4 For instance, in Europe, each year 4-50 million symptomatic infections occur and 15,000-70,000 citizens die of influenza-related complications. ...
In accordance with European directives, each year the enhanced safety surveillance (ESS) of seasonal influenza vaccines should be conducted in order to detect any potential increase in reactogenicity when the vaccine composition is updated or a new formulation becomes available. The objective of this passive ESS (EPSS) was to assess the frequency of spontaneously reported adverse events (AEs) following vaccination with the 2021/22 formulation of the MF59-adjuvanted quadrivalent influenza vaccine (aQIV) among older adults in Italy through the collection of data within a short time period (start of seasonal influenza vaccination) in order to monitor the reactogenicity of aQIV early in the season. All AEs reported within seven days following vaccination were analyzed by type and seriousness. In all, 1,059 vaccination cards were distributed to individuals aged ≥65 years. Only one, non-serious, spontaneous individual case safety report was submitted, yielding an overall rate of 0.9 per 1,000 doses administered. This report consisted of a reactogenic AE of pyrexia. The EPSS confirmed that the reactogenicity profile of aQIV was consistent with the known safety profile of the previous trivalent formulation. These optimal safety data could bolster public confidence in influenza vaccination and help to improve vaccination coverage.
... Low influenza vaccination uptake contributed to an estimated 785,000 excess cases and up to 105,000 influenza-associated hospitalizations annually that could have been prevented by vaccination (CDC, 2020;Hughes et al., 2020). These cases add strain on hospital systems (Putri, Muscatello, Stockwell, & Newall, 2018) and result in disproportionate morbidity and mortality to pregnant people (Thompson et al., 2019) and people with chronic health conditions (Bekkat-Berkani et al., 2017;Colquhoun, Nicholson, Botha, & Raymond, 1997). Influenza vaccination coverage was lowest among young adults compared to older age groups: 37.7% for adults 18-49 years of age, 54.2% for adults 50-64 years of age and 75.2% for adults aged 65 years and above in the 2020-2021 influenza season (CDC, 2018;2021a). ...
Seasonal influenza vaccination rates remain low, and contribute to preventable influenza cases, hospitalizations, and deaths in the US. While numerous interventions have been implemented to increase vaccine uptake, there is a need to determine which interventions contribute most to vaccine willingness, particularly among age groups with vaccination rates that have plateaued at suboptimal levels. This study aimed to quantify the relative effect of multiple interventions on vaccine willingness to receive influenza vaccine in three age groups using a series of hypothetical situations with different behavioral interventions. We assessed the relative impact of four categories of interventions: source of vaccine messages, type of vaccination messages, vaccination incentives, and ease of vaccine access using a discrete choice experiment. Within each category, we investigated the role of four different attributes to measure their relative contribution to willingness to be vaccinated by removing one option from each of the intervention categories. Among the 1,763 Minnesota residents who volunteered for our study, participants expressed vaccine willingness in over 80% of the scenarios presented. Easy access to drop-in vaccination sites had the greatest impact on vaccine willingness in all age groups. Among the younger age group, small financial incentives also contributed to high vaccine willingness. Our results suggest that public health programs and vaccination campaigns may improve their chances of successfully increasing vaccine willingness if they offer interventions preferred by adults, including facilitating convenient access to vaccination and offering small monetary incentives, particularly for young adults.
... While swine usually experience mild infection and low mortality [169,170], in humans it can vary between mild to severe symptoms and mortality can be high depending on strain and susceptibility [171], with an estimated average of 650,000 deaths worldwide every year [172]. Morbidity can be high in both species, with a high disease burden observed in humans, estimated in an annual economic cost of US $11.2 billion [173]. The financial consequences of influenza in the pig industry are difficult to determine. ...
The advantages of skin-based vaccination include induction of strong immunity, dose-sparing, and ease of administration. Several technologies for skin-based immunisation in humans are being developed to maximise these key advantages. This route is more conventionally used in veterinary medicine. Skin-based vaccination of pigs is of high relevance due to their anatomical, physiological, and immunological similarities to humans, as well as being a source of zoonotic diseases and their livestock value. We conducted a systematic mapping review, focusing on vaccine-induced immunity and safety after the skin immunisation of pigs. Veterinary vaccines, specifically anti-viral vaccines, predominated in the literature. The safe and potent skin administration to pigs of adjuvanted vaccines, particularly emulsions, are frequently documented. Multiple methods of skin immunisation exist; however, there is a lack of consistent terminology and accurate descriptions of the route and device. Antibody responses, compared to other immune correlates, are most frequently reported. There is a lack of research on the underlying mechanisms of action and breadth of responses. Nevertheless, encouraging results, both in safety and immunogenicity, were observed after skin vaccination that were often comparable to or superior the intramuscular route. Further research in this area will underlie the development of enhanced skin vaccine strategies for pigs, other animals and humans.
... ca tử vong và hơn 200.000 ca nhập viện. Chi phí kinh tế y tế cho điều trị và chăm sóc bệnh nhân mắc cúm mùa của quốc gia này trung bình hàng năm là hơn 11 tỷ đô la [10]. ...
Đặt vấn đề: Nhiều nhân viên y tế (NVYT) còn ngần ngại tiêm ngừa vắc xin virus cúm mùa mặc dù NVYT là đối tượng nguy cơ cao do môi trường làm việc thường xuyên tiếp xúc với mầm bệnh. Mục tiêu nghiên cứu: Xác định tỷ lệ các rào cản và một số yếu tố liên quan đến các rào cản chấp nhận tiêm ngừa vắc xin virus cúm mùa ở nhóm đối tượng nhân viên y tế (NVYT). Đối tượng và phương pháp nghiên cứu: Nghiên cứu mô tả cắt ngang trên 706 nhân viên y tế tại 14 cơ sở y tế trên địa bàn thành phố Cần Thơ năm 2020. Kết quả: Nghiên cứu cho thấy rào cản ảnh hưởng tiêm ngừa vắc xin chủ yếu liên quan đến lo ngại về hiệu quả của vắc xin, giá thành vắc xin, tác dụng phụ của vắc xin và nguồn gốc của vắc xin. Có mối liên quan có ý nghĩa thống kê (p<0,05) giữa các rào cản trong chấp nhận tiêm ngừa virus cúm mùa ở NVYT khác nhau dựa trên các đặc điểm như nhóm tuổi, tình trạng hôn nhân, nơi công tác, đơn vị công tác, lĩnh vực, thâm niên, tiền sử từng mắc cúm mùa nặng, tần suất mắc cúm mùa và loại vắc xin đã tiêm ngừa trước đó. Kết luận: Vẫn còn phần lớn các rào cản ảnh hưởng đến quyết định chấp nhận tiêm ngừa vắc xin cúm mùa. Cần có hệ thống các biện pháp can thiệp phù hợp cho từng nhóm rào cản để gia tăng tỷ lệ tiêm chủng ở nhóm nhân viên y tế.
... The Centers for Disease Control and Prevention (CDC) estimates that the influenza virus infected nearly 40 million people in the United States (US) during the 2019-2020 season, causing 400,000 hospitalizations and over 20,000 deaths [1]. The estimated economic burden of influenza to the US health care system is USD 11.2 billion annually [2]. The influenza vaccine is the most effective form of protection against the virus, its complications, and associated costs [3]. ...
Few studies have investigated the relationship between influenza vaccination and health care access. Furthermore, despite the well-documented disparities in vaccine coverage for communities of color, few studies have examined how experiences of discrimination may influence vaccine uptake. To fill this gap in the literature, this study examined associations between 5-year influenza vaccination rates and sociodemographic characteristics, health care access, and racial discrimination. Age, race/ethnicity, education, health care coverage, primary care provider, no medical care due to cost, and routine doctor checkups were significant correlates of 5-year influenza vaccination. In contrast to previous studies, discrimination scores were not a significant correlate of regular influenza vaccination. Respondents who reported forgoing care due to cost were less likely to report vaccination every year out of the last 5 years compared to all of the less frequent categories combined, demonstrating a more complex association between sometimes not being able to afford medical care and influenza vaccination. Future research should examine the relationship between influenza vaccination uptake, racial discrimination, and forgone care due to cost to enhance resources and messaging for influenza vaccination uptake.
... A recent European Parliament resolution states that respiratory infectious diseases still represent a considerable threat to society, with a huge burden in terms of human life and economy [1]. For example, the cost of influenza in US prior to the COVID-19 pandemic was estimated in 11.2 USD billion annually, with 3.7 million outpatient visits, 247,000 hospital admissions, 36,300 deaths and more than twenty million working days lost [2]. ...
Hexedra+® is a nasal spray containing hydroxypropyl methylcellulose, beta-cyclodextrin, and usnic acid. It has been developed with the aim of reducing the risk of transmission of airborne viral infections, with particular reference to influenza and COVID-19. As part of the preclinical development of the product, we carried out a study on thirty male Wistar rats divided into three study groups and treated with Hexedra+, an alternative formulation containing a double concentration of usnic acid (0.015% instead of 0.0075%) or saline solution. Products were administered at the dose of 30 μL into each nostril, three times a day for seven consecutive days by means of a micropipette. By the end of the treatment period, no significant changes were observed in body weight. Histological examination of nasal mucosa and soft organs did not show any significant difference in the three study groups. Serum transaminase level remained in the normal limit in all the animals treated. The serum level of usnic acid was measured in order to assess the absorption of the molecule through the nasal mucosa. By the end of the study period, the usnic acid serum level was negligible in all the animals treated. In conclusion, the safety profile of Hexedra+ appears favorable in the animal model studied.
... Approximately two-thirds of influenza-related deaths were among those aged 65 years or older [10]. In 2015, the economic burden of seasonal-influenza-associated healthcare services in the United States Vaccines 2023, 11, 353 2 of 11 was estimated to be over USD 11 billion [11]. In China, the annual cost related to seasonal influenza was approximately 4 billion U.S. dollars [12]. ...
In the fall of 2022, the number of influenza-like illnesses (ILIs) and severe acute respiratory infections (SARIs) in Saudi Arabia had significantly increased compared with the corresponding period in previous years. Concerns regarding the population’s seasonal influenza vaccine (SIV) uptake rates have emerged. In particular, the SIV uptake rates may have dropped post the COVID-19 pandemic compared with rates prior to the COVID-19 era. In this study, we aimed to estimate the prevalence and predictors of SIV uptake in Saudi Arabia post the COVID-19 pandemic. We conducted a cross-sectional study utilizing an online survey platform. We mainly collected sociodemographic information and determined whether the respondent was a healthcare professional or had a chronic disease. The overall SIV uptake prevalence was 31.8%. A lower SIV uptake was observed among those aged 55 years or older, females, residents of the central region, non-health practitioners, and those without chronic diseases. Several factors were associated with SIV uptake. Those aged 35–44 were over three-fold more likely to receive an SIV than those aged 55 years or older (OR: 3.66; 95% CI: 1.33–10.05). In addition, males had 73% higher odds of SIV uptake than females (OR: 1.73; 95% CI: 1.18–2.55). Health practitioners were more likely to receive an SIV than non-health practitioners (OR: 2.11; 95% CI: 1.45–3.06). Similarly, those with chronic diseases had 86% higher odds of SIV uptake than those without chronic diseases (OR: 1.86; 95% CI: 1.18–2.95). These findings can provide insights into the low prevalence and predictors of SIV uptake in Saudi Arabia. Future studies should be conducted to further explore the potential factors associated with such a low prevalence of SIV uptake post COVID-19 in Saudi Arabia.
... They are also responsible for non-human diseases which lead to mortality of livestock and crops (Maksimov et al., 2019;Tomley and Shirley, 2009). RNA viruses both directly and indirectly exert a significant cost on the global economy and public health (Bartsch et al., 2020;Courville et al., 2022;Kolahchi et al., 2021;Putri et al., 2018;Richards et al., 2022). Although the high mutation rate of RNA viruses poses a risk to the human population, they allow us to study the evolutionary processes on a shorter timescale (Moya et al., 2000). ...
Viral infections are common and are particularly problematic in immunocompromised individuals. However, other than for HIV, Hepatitis B, Hepatitis C, Influenza, and more recently SARS-CoV-2, there have been few approved drugs available for treating viral infections. Instead, repurposed drugs are often used, especially at the beginning of the current pandemic, for treating SARS-CoV-2. It remains unclear how these repurposed drugs act on the viral population and whether the suppression of viral load we observe is attributed to the drug or the immune response or a combination of both. The research presented in this thesis primarily focuses on the study of two RNA viruses, SARS-CoV-2 and Norovirus. A mixture of viral load data and viral genomic data were analysed to understand the course of infection within individuals. First, we presented a meta-analysis on SARS-CoV-2 viral load dynamics where we investigated the changes of viral dynamics over time, with and without the presence of antiviral drugs. Then, we presented an evolutionary model used for reconstructing haplotypes in mixed infections. Finally, we demonstrated the use of viral deep sequencing to study the within-host evolution of RNA viruses. We identified mutagenic signatures and consensus level changes associated with antiviral treatments. We developed unique methods to analyse viral sequences which allow us to understand the within-host genomic variations and hence inform our understanding of the heterogeneous efficacy of a drug between patients. Overall, this thesis provides insights into how the efficacy of a drug can be evaluated by monitoring the within-host viral dynamics and evolution.
... Seasonal outbreaks, endemic infections, and suddenly occurring pandemic situations are felt mainly within these two families [8][9][10]. All ages are susceptible to infection with influenza viruses and coronaviruses; however, young children (<5 years) and aged people (>65 years) have the highest incidence rate and may suffer more [11,12]. ...
Influenza is a contagious infection in humans that is caused frequently by low pathogenic seasonal influenza viruses and occasionally by pathogenic avian influenza viruses (AIV) of H5, H7, and H9 subtypes. Recently, the clinical sector in poultry and humans has been confronted with many challenges, including the limited number of antiviral drugs and the rapid evolution of drug-resistant variants. Herein, the anti-influenza activities of various plant-derived phytochemicals were investigated against highly pathogenic avian influenza A/H5N1 virus (HPAIV H5N1) and seasonal low pathogenic human influenza A/H1N1 virus (LPHIV H1N1). Out of the 22 tested phytochemicals, the steroid compounds β-sitosterol and β-sitosterol-O-glucoside have very potent activity against the predefined influenza A viruses (IAV). Both steroids could induce such activity by affecting multiple stages during IAV replication cycles, including viral adsorption and replication with a major and significant impact on the virus directly in a cell-free status "viricidal effect". On a molecular level, several molecular docking studies suggested that β-sitosterol and β-sitosterol-O-glucoside exhibited viricidal effects through blocking active binding sites of the hemagglutinin surface protein, as well as showing inhibitory effects against replication through the binding with influenza neuraminidase activity and blocking the active sites of the M2 proton channel activity. The phytoestrogen β-sitosterol has structural similarity with the active form of the female sex hormone estradiol, and this similarity is likely one of the molecular determinants that enables the phytoestrogen β-sitosterol and its derivative to control IAV infection in vitro. This promising anti-influenza activity of β-sitosterol and its O-glycoside derivative, according to both in vitro and cheminformatics studies, recommend both phytochemicals for further studies going through preclinical and clinical phases as efficient anti-influenza drug candidates.
... These influenza-associated costs include medical care expenses and lost earnings. The estimated economic burden of influenza in the US alone is between 6.3 and 25.3 billion US dollars annually, with the most significant percentage impacting ages 18 to 49 (12). ...
Preventing and controlling influenza virus infection remains a global public health challenge, as it causes seasonal epidemics to unexpected pandemics. These infections are responsible for high morbidity, mortality, and substantial economic impact. Vaccines are the prophylaxis mainstay in the fight against influenza. However, vaccination fails to confer complete protection due to inadequate vaccination coverages, vaccine shortages, and mismatches with circulating strains. Antivirals represent an important prophylactic and therapeutic measure to reduce influenza-associated morbidity and mortality, particularly in high-risk populations. Here, we review current FDA-approved influenza antivirals with their mechanisms of action, and different viral- and host-directed influenza antiviral approaches, including immunomodulatory interventions in clinical development. Furthermore, we also illustrate the potential utility of machine learning in developing next-generation antivirals against influenza.
... Although both influenza A and B cause seasonal epidemics, it is the influenza A that lead to >95% of hospitalization in adults. In the US, influenza causes 140,000 to 710,000 hospitalizations, 12,000 to 52,000 deaths, and about USD 25 billion in economic losses annually [1]. In 2022, the co-administration of COVID-19 vaccines with influenza vaccines [2][3][4][5] and/or pneumococcal vaccines [6] was deployed, with safety fully demonstrated in spite of minimal concerns regarding immunogenicity [7]. ...
Combined (concomitant or synchronous) vaccination is crucial to increasing the compliance rate during mass campaigns by reducing the time to deployment (i [...]
... In addition to the severe burden on people's lives and health, influenza causes huge economic losses to individuals and countries, with indirect economic losses reaching tens of billions of dollars globally each year [14]. China is an influenza-prone region, and most studies on the economic burden associated with influenza have focused on more economically developed regions; for example, Beijing, Shanghai and Tianjin have the highest ILI burden, and Qinghai, Gansu and Ningxia have the lowest ILI burden. ...
Influenza viruses usually cause seasonal influenza epidemics and influenza pandemics, resulting in acute respiratory illness and, in severe cases, multiple organ complications and even death, posing a serious global and human health burden. Compared with other countries, China has a large population base and a large number of influenza cases and deaths. Currently, influenza vaccination remains the most cost-effective and efficient way to prevent and control influenza, which can significantly reduce the risk of influenza virus infection and serious complications. The antigenicity of the influenza vaccine exhibits good protective efficacy when matched to the seasonal epidemic strain. However, when influenza viruses undergo rapid and sustained antigenic drift resulting in a mismatch between the vaccine strain and the epidemic strain, the protective effect is greatly reduced. As a result, the flu vaccine must be reformulated and readministered annually, causing a significant drain on human and financial resources. Therefore, the development of a universal influenza vaccine is necessary for the complete fight against the influenza virus. By statistically analyzing cases related to influenza virus infection and death in China in recent years, this paper describes the existing marketed vaccines, vaccine distribution and vaccination in China and summarizes the candidate immunogens designed based on the structure of influenza virus, hoping to provide ideas for the design and development of new influenza vaccines in the future.
... In the United States, influenza was responsible for about half a million hospitalizations from 2016 to 2017 [5]. As a result, influenza puts an undue burden on the healthcare system, with an estimated median annual cost of $11.2 billion [6]. An epidemiologic study from Olmsted County, Minnesota, in 2000 to 2010, attributed 54% of HF deaths and 63% of HF hospitalizations to non-cardiovascular causes [7]. ...
Introduction:
A sizable proportion of heart failure (HF) admissions is precipitated by respiratory infections. Influenza has been linked to higher rates of HF hospitalizations and in-hospital morbidity and mortality.
Aim/objective:
We aim to describe the in-hospital outcomes of systolic HF vs. diastolic HF admissions with concomitant influenza infection in US hospitalizations from 2016 to 2017. Materials and Methods: We queried the National Inpatient Sample (NIS) from 2016 to 2017 for discharge diagnosis for SHF and DHF and influenza per ICD-10 CM codes. Using binominal logistic regression analysis and adjusting for demographic and comorbid conditions, we compared the outcomes of SHF vs. DHF admissions with concomitant influenza as an independent risk factor for inpatient mortality, acute respiratory failure, ICU admission, assisted ventilation, as well as length of stay, and total hospital costs.
Results:
A total of 7,490,596 HF weighted admissions were analyzed, among which 0.9% had concomitant influenza infection. SHF and DHF admissions with influenza had higher mortality, ICU admission, ventilation assistance, and acute respiratory failure when compared to those without influenza. Among influenza admissions, those with SHF had higher mortality (6.6% vs. 5%, adjusted odds ratio - aOR 1.31, p<0.001) compared to DHF. While intensive care unit (ICU) admission (7.8% vs. 5.2%, aOR 1.30, p<0.001) and ventilation assistance rates (22.1% vs. 18.9%, aOR 1.15, p<0.001) were greater among SHF patients with influenza, acute respiratory failure was more common amongst diastolic HF with influenza (46.6% vs. 51.2%, aOR 0.86, p<0.001). Finally, SHF patients with concomitant influenza had higher inpatient costs ($82,788) when compared to diastolic HF patients ($66,373) and a longer in-hospital stay (7.29 days compared to 6.98 days in the diastolic HF group) p <0.001.
Conclusion:
Concomitant influenza infection in hospitalized patients with HF is associated with higher mortality, ICU admission, and the need for assisted ventilation, especially in those with SHF. A greater emphasis on vaccination against influenza may improve in-patient outcomes among HF patients.
... From 2016 to 2019, the incidence of influenza in China increased from 22.3727/100,000 to 253.3561/100,000, and the mortality rate increased from 0.0041/100,000 to 0.0193/100,000 [6], both morbidity and mortality were on the rise. The influenza epidemic has imposed a great economic and health burden on human beings [7][8][9][10]. For the outbreak of influenza, there are many factors (such as individual genetic differences, changing population demographics, antibiotic resistance and environmental, etc.) [11][12][13][14] can affect the spread and infection of flu, therefore, many researchers have explored and analyzed these factors to prevent and control the influenza in some degree. ...
Humans are susceptible to influenza. The influenza virus spreads quickly and behave seasonally. The seasonality and spread of influenza are often associated with meteorological factors and have spatio-temporal differences. Based on the influenza cases and daily average meteorological factors in Lanzhou from 2014 to 2017, this study firstly aimed to analyze the characteristics of influenza incidence in Lanzhou and the impact of meteorological factors on influenza activities. Then, SARIMA(X) models for the prediction were established. The influenza cases in Lanzhou from 2014 to 2017 was more male than female, and the younger the age, the higher the susceptibility; the epidemic characteristics showed that there is a peak in winter, a secondary peak in spring, and a trough in summer and autumn. The influenza cases in Lanzhou increased with increasing daily pressure, decreasing precipitation, average relative humidity, hours of sunshine, average daily temperature and average daily wind speed. Low temperature was a significant driving factor for the increase of transmission intensity of seasonal influenza. The SARIMAX (1,0,0)(1,0,1)[12] multivariable model with average temperature has better prediction performance than the university model. This model is helpful to establish an early warning system, and provide important evidence for the development of influenza control policies and public health interventions.
... This is perhaps not unexpected, as the estimated average annual total economic burden of e.g. influenza to the healthcare system and society was $11.2 billion ($6.3-$25.3 billion) (Putri et al., 2018). In a Dutch study a meta-analysis was performed on clinical study results from probiotic interventions on constipation in institutionalised elderly people, showing that the constipation-related expenses of an average-sized nursing home with 100 residents and a constipation prevalence of 42%, amounted to approximately €90,000 per year (Flach et al., 2018). ...
... The epidemic and pandemic threat of influenza viruses Influenza viruses cause epidemics and pose pandemic threats. Influenza A and B cause seasonal influenza epidemics in humans, resulting in significant morbidity [3-5 million deaths yearly (1)], mortality [290,000-650,000 deaths (1)], and economic burden [$10-$80 billion yearly in the US (2,3)]. Elderly and immunocompromised individuals are at higher risk of severe influenza A infection, whereas children and adolescents are more susceptible to influenza B (4). ...
Human monoclonal antibodies (hmAbs) that protect against all influenza A and B strains are considered the road to universal influenza vaccines. Based on publicly-available data, we analyze the mechanistic and structural basis of pan-influenza protection by CR9114, a hemagglutinin (HA) stem-reactive antibody that protects against influenza subtypes from groups A1, A2, and B. The mechanistic basis of CR9114’s universal protection is not limited to in vitro neutralization, as CR9114 also protects in vivo from strains that escape its neutralizing activity: some H2 strains and influenza B. Fusion inhibition, viral egress inhibition, and activation of Fc-mediated effector functions are key contributors to CR9114’s universal protection. A comparative analysis of paratopes – between CR9114 (pan-influenza protection) and structurally similar VH1-69 hmAb CR6261 (influenza A1 protection) – pinpoints the structural basis of pan-influenza protection. CR9114’s heterosubtypic binding is conferred by its ability to bind HA with multiple domains: three HCDR loops and FR3. In contrast to other VH1-69 hmAbs, CR9114 uses a long and polar side chain of tyrosine (Y) residues on its HCDR3 for crucial H-bonds with H3, H5, and B HA. The recognition of a highly conserved epitope by CR9114 results in a high genetic barrier for escape by influenza strains. The nested, hierarchical structure of the mutations between the germline ancestor and CR9114 demonstrates that it is the result of a narrow evolutionary pathway within the B cell population. This rare evolutionary pathway indicates an immuno-recessive epitope and limited opportunity for vaccines to induce a polyclonal CR9114-like response.
... Since the clinical symptoms of COVID-19 are similar to those of seasonal influenza [3], co-circulation of influenza would place a greater burden on healthcare workers. In addition to public health concerns, seasonal influenza is estimated to be responsible for a substantial economic burden [4]. Therefore, the prevention of seasonal influenza would contribute to both public health and the economy. ...
Seasonal influenza is a major upper respiratory tract infection occurring in winter. Vaccination is the best method for preventing this infection. We conducted two randomized, double-blind, placebo-controlled trials to examine whether consumption of yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1, which has been reported to reduce the risk of catching the common cold, augments serum antibody titers against seasonal influenza vaccines. In the first trial, which included university students, serum antibody titers against influenza A (H3N2) and B viruses were significantly higher in the yogurt group than in the placebo group. According to the guidelines established by the European Medicines Agency (EMA) for the assessment of vaccines, the seroconversion rate and mean geometric increase of influenza A (H3N2) and seroprotection of influenza B met the criteria only in the yogurt group. In the second trial, which included healthy adults, serum antibody titers against influenza A (H1N1) and B viruses were significantly higher in the yogurt group than in the placebo group. The seroconversion rate and mean geometric increase of influenza B met the EMA criteria only in the yogurt group. Furthermore, the cumulative days of ill health, such as throat complaints, upper respiratory inflammation, and cold, were significantly lower in the yogurt group than in the placebo group. Therefore, daily intake of yogurt fermented with L. bulgaricus OLL1073R-1 could reduce the duration of symptoms caused by respiratory infections and act as a mucosal adjuvant enhancing acquired immune responses against vaccines, leading to the improvement of public health.
... In the US alone, it was estimated that during the 2019-2020 flu season, influenza caused 38 million illnesses, 40,000 hospitalizations, and 22,000 deaths. Moreover, estimates of the economic burden of influenza to the healthcare system and society in the US reach USD 11.2 billion annually [81]. ...
A vital function of the immune system is the modulation of an evolving immune response. It is responsible for guarding against a wide variety of pathogens as well as the establishment of memory responses to some future hostile encounters. Simultaneously, it maintains self-tolerance and minimizes collateral tissue damage at sites of inflammation. In recent years, the regulation of T-cell responses to foreign or self-protein antigens and maintenance of balance between T-cell subsets have been linked to a distinct class of cell surface and extracellular components, the immune checkpoint molecules. The fact that both cancer and viral infections exploit similar, if not the same, immune checkpoint molecules to escape the host immune response highlights the need to study the impact of immune checkpoint blockade on viral infections. More importantly, the process through which immune checkpoint blockade completely changed the way we approach cancer could be the key to decipher the potential role of immunotherapy in the therapeutic algorithm of viral infections. This review focuses on the effect of programmed cell death protein 1/programmed death-ligand 1 blockade on the outcome of viral infections in cancer patients as well as the potential benefit from the incorporation of immune checkpoint inhibitors (ICIs) in treatment of viral infections.
... Between 1999 and 2019, influenza and pneumonia was the ninth leading cause of death in the United States [1], with an estimated annual burden of $11.2 billion [2]. Further, individuals who are Black, American Indian or Alaskan Native, or Hispanic experience disparate rates of hospitalization due to influenza among all age groups compared to individuals who are White [3]. ...
Context
Influenza-related hospitalization and mortality disproportionately affects the Hispanic population in the United States. Among other medical conditions in addition to influenza, Spanish-preferring Hispanics may be more affected than those who speak English.
Objectives
The purpose of this study was to compare seasonal influenza vaccine uptake rates between Spanish-and English-preferring Hispanic US adults from 2017 to 2020.
Methods
For this cross-sectional study, we extracted data from the Behavioral Risk Factor Surveillance System (BRFSS) from the 2017 through 2020 cycles. We calculated the population prevalence of individuals getting influenza vaccines per year, and among subpopulations based on language spoken, age, and sex. We then utilized chi-squared tests of independence to discover possible associations between these subpopulations per year. An alpha level of 0.05 was utilized in this study. Respondents were included if they identified as Hispanic, responded to questions regarding influenza vaccine uptake, and were grouped by the language of the survey returned, age, and sex.
Results
Our results show that self-identified Hispanic individuals who were English-preferring had greater seasonal influenza vaccine uptake rates in the latter 2 years of our study for both sexes in the younger age group. Hispanic individuals over the age of 65 years (n=11,328) were much more likely to have received an influenza vaccine compared to younger individuals (n=34,109). In 2018, Spanish-preferring women over age 65 years (n=677) were more likely to have received a vaccine over English-preferring women (n=772).
Conclusions
Our findings showed that disparities exist between English- and Spanish-preferring Hispanic individuals and age groups. Language barriers may play a role in receiving influenza vaccines. The incorporation of medical translators may assist in reducing these disparities in influenza-related healthcare expenses, overall morbidity, and mortality.
... In the United States, the annual economic burden of respiratory tract infections caused by viruses is in the order of $$50 billion. 1,2 Rhinoviruses are one of several virus groups that cause respiratory tract infections and have been implicated in the etiology of about 50% of asthma and chronic obstructive pulmonary disease exacerbations. 3 Rhinoviruses consist of over 160 genotypes grouped into three species (Rhinovirus A, Rhinovirus B, and Rhinovirus C) in genus Enterovirus, family Picornaviridae. The positive-sense, single-stranded, $7.2 kb RNA genome of rhinoviruses encodes a large polyprotein that is autocatalytically cleaved into 11 proteins; four (VP1-VP4) and seven (2A-2C, 3A-3D) structural (or capsid) and nonstructural proteins, respectively. ...
We determine the presence and diversity of rhinoviruses in nasopharyngeal swab samples from 248 individuals who presented with influenza-like illness (ILI) at a university clinic in the Southwest United States between October 1, 2020 and March 31, 2021. We identify at least 13 rhinovirus genotypes (A11, A22, A23, A25, A67, A101, B6, B79, C1, C17, C36, and C56, as well a new genotype [AZ88**]) and 16 variants that contributed to the burden of ILI in the community. We also describe the complete capsid protein gene of a member (AZ88**) of an unassigned rhinovirus A genotype.
... A recent meta-analysis calculated the influenza attack rate among unvaccinated individuals, and found that 22.5% of child < 18 years old and 10.7% of adults were influenza positive 5 . Due to influenza, the estimated average annual total economic burden was $11.1 billion in the United Stats 6 . To minimized this health and economic burden, vaccination remains the best strategy for preventing the spread of seasonal influenza. ...
In February each year, World Health Organization (WHO) recommends candidate vaccine viruses for the forthcoming northern hemisphere (NH) season; however, the influenza season in the temperate zone of NH begins in October. During egg- or cell culture-propagation, the vaccine viruses become too old to confer the highest match with the latest strains, impacting vaccine effectiveness. Therefore, an alternative strategy like mRNA-based vaccine using the most recent strains should be considered. We analyzed influenza A subtype H3N2 strains circulating in NH during the last 10 years (2009–2020). Phylogenetic analysis revealed multiple clades of influenza strains circulating every season, which had substantial mismatches with WHO-recommended vaccine strains. The clustering pattern suggests that influenza A subtype H3N2 strains are not fixed to the specific geographical region but circulate globally in the same season. By analyzing 39 seasons from eight NH countries with the highest vaccine coverage, we also provide evidence that the influenza A, subtype H3N2 strains from South and Southeast Asia, including Bangladesh, had the highest genetic proximity to the NH strains. Furthermore, insilico analysis showed minimal effect on the Bangladeshi HA protein structure, indicating the stability of Bangladeshi strains. Therefore, we propose that Bangladeshi influenza strains represent genetic makeup that may better fit and serve as the most suitable candidate vaccine viruses for the forthcoming NH season.
Objective:
To investigate how sociodemographic and medical care access variables are associated with influenza vaccine uptake among pregnant women in the USA.
Methods:
This is an observational study using 2015-2019 data from the US Behavioral Risk Factor Surveillance System. Pregnant women aged 18-49 years were included. Weighted χ2 tests and weighted logistic regression models were performed using the software SAS.
Results:
A total of 9149 pregnant women were included, of whom 39.9% received the influenza vaccine. Age, income, education and race/ethnicity were significantly associated with influenza vaccination. The following medical access factors were associated with a higher likelihood of receiving the influenza vaccine: having insurance (odds ratio [OR] 1.43, 95% confidence interval [CI] 1.04-1.97), having had a checkup in the past year (OR 1.69, 95% CI 1.40-2.03), and having a primary care provider (OR 1.45, 95% CI 1.18-1.78). In subgroup analysis by race/ethnicity, non-Hispanic black women had the least difference in influenza vaccine uptake between those with medical care access and those without.
Conclusion:
Our findings suggest that the influenza vaccine uptake level was far from optimal among pregnant women. Influenza vaccine uptake was associated with social demographics and medical care access among pregnant women.
Influenza and air pollution each pose significant health risks with global economic consequences. Their shared etiological pathways present a case of compounding health risk via interacting externalities. Using instrumental variables based on changing wind direction, we show that increased levels of contemporaneous pollution increase influenza hospitalizations. We exploit random variation in effectiveness of the influenza vaccine as an additional instrument to show that vaccine protection neutralizes this relationship. Thus, pollution control and vaccination campaigns jointly provide greater returns than those implied by addressing either in isolation. We show the importance of this consideration in addressing observed gaps in influenza incidence by race. (JEL D62, I12, J15, Q51, Q53)
We have developed an influenza hemagglutinin (HA) pseudotype (PV) library encompassing all influenza A (IAV) subtypes from HA1-HA18, influenza B (IBV) subtypes (both lineages), representative influenza C (ICV), and influenza D (IDV) viruses. These influenza HA (or hemagglutinin-esterase fusion (HEF) for ICV and IDV) pseudotypes have been used in a pseudotype microneutralization assay (pMN), an optimized luciferase reporter assay, that is highly sensitive and specific for detecting neutralizing antibodies against influenza viruses. This has been an invaluable tool in detecting the humoral immune response against specific hemagglutinin or hemagglutinin-esterase fusion proteins for IAV to IDV in serum samples and for screening antibodies for their neutralizing abilities. Additionally, we have also produced influenza neuraminidase (NA) pseudotypes for IAV N1-N9 subtypes and IBV lineages. We have utilized these NA-PV as surrogate antigens in in vitro assays to assess vaccine immunogenicity. These NA PV have been employed as the source of neuraminidase enzyme activity in a pseudotype enzyme-linked lectin assay (pELLA) that is able to measure neuraminidase inhibition (NI) titers of reference antisera, monoclonal antibodies, and postvaccination sera. Here we show the production of influenza HA, HEF, and NA PV and their employment as substitutes for wild-type viruses in influenza serological and neutralization assays. We also introduce AutoPlate, an easily accessible web app that can analyze data from pMN and pELLA quickly and efficiently, plotting inhibition curves and calculating half-maximal concentration (IC50) neutralizing antibody titers. These serological techniques coupled with user-friendly analysis tools are faster, safer, inexpensive alternatives to classical influenza assays while also offering the reliability and reproducibility to advance influenza research and make it more accessible to laboratories around the world.
Background:
Seasonal influenza is associated with significant healthcare resource utilization. An estimated 490,000 hospitalizations and 34,000 deaths were attributed to influenza during the 2018-2019 season. Despite robust influenza vaccination programs in both the inpatient and outpatient setting, the emergency department (ED) represents a missed opportunity to vaccinate patients at high risk for influenza who do not have access to routine preventive care. Feasibility and implementation of ED-based influenza vaccination programs have been previously described but have stopped short of describing the predicted health resource impact. The goal of our study was to describe the potential impact of an influenza vaccination program in an urban adult emergency department population using historic patient data.
Methods:
This was a retrospective study of all encounters within a tertiary care hospital-based ED and three freestanding EDs during influenza season (defined as October 1 - April 30) over a two-years, 2018-2020. Data was obtained from the electronic medical record (EPIC®). All ED encounters during the study period were screened for inclusion using ICD 10 codes. Patients with a confirmed positive influenza test and no documented influenza vaccine for the current season were reviewed for any ED encounter at least 14 days prior to the influenza-positive encounter and during the concurrent influenza season. These ED visits were deemed a missed opportunity to provide vaccination and potentially prevent the influenza-positive encounter. Healthcare resource utilization, including subsequent ED encounters and inpatient admissions, were evaluated for patients with a missed vaccination opportunity.
Results:
A total of 116,140 ED encounters occurred during the study and were screened for inclusion. Of these, 2115 were influenza-positive encounters, which represented 1963 unique patients. There were 418 patients (21.3%) that had a missed opportunity to be vaccinated during an ED encounter at least 14 days prior to the influenza-positive encounter. Of those with a missed vaccination opportunity, 60 patients (14.4%) had subsequent influenza-related encounters, including 69 ED visits and 7 inpatient admissions.
Conclusion:
Patients presenting to the ED with influenza frequently had opportunities to be vaccinated during prior ED encounters. An ED-based influenza vaccination program could potentially reduce influenza-related burden on healthcare resources by preventing future influenza-related ED encounters and hospitalizations.
Influenza viruses are responsible for significant morbidity and mortality worldwide in winter seasonal outbreaks and in flu pandemics. Influenza viruses have a high rate of evolution, requiring annual vaccine updates and severely diminishing the effectiveness of the available antivirals. Identifying novel viral targets and developing new effective antivirals is an urgent need. One of the most promising new targets for influenza antiviral therapy is non-structural protein 1 (NS1), a highly conserved protein exclusively expressed in virus-infected cells that mediates essential functions in virus replication and pathogenesis. Interaction of NS1 with the host proteins PI3K and TRIM25 is paramount for NS1’s role in infection and pathogenesis by promoting viral replication through the inhibition of apoptosis and suppressing interferon production, respectively. We, therefore, conducted an analysis of the druggability of this viral protein by performing molecular dynamics simulations on full-length NS1 coupled with ligand pocket detection. We identified several druggable pockets that are partially conserved throughout most of the simulation time. Moreover, we found out that some of these druggable pockets co-localize with the most stable binding regions of the protein–protein interaction (PPI) sites of NS1 with PI3K and TRIM25, which suggests that these NS1 druggable pockets are promising new targets for antiviral development.
Objective:
This study aimed to explore the association between air pollutants and outpatient visits for influenza-like illnesses (ILI) under the coronavirus disease 2019 (COVID-19) stage in the sub-center of Beijing.
Methods:
The data on ILI in the sub-center of Beijing from 1 January 2018 to 31 December 2020 were obtained from the Beijing Influenza Surveillance Network. A generalized additive Poisson model was applied to examine the associations between the concentrations of air pollutants and daily outpatient visits for ILI when controlling meteorological factors and temporal trend.
Results:
A total of 171,943 ILI patients were included. In the pre-COVID-19 stage, an increased risk of ILI outpatient visits was associated to a high air quality index (AQI) and the high concentrations of particulate matter less than 2.5 (PM2.5 ), particulate matter 10 (PM10 ), sulphur dioxide (SO2 ), nitrogen dioxide (NO2 ), and carbon monoxide (CO), and a low concentration of ozone (O3 ) on lag0 day and lag1 day, while a higher increased risk of ILI outpatient visits was observed by the air pollutants in the COVID-19 stage on lag0 day. Except for PM10， the concentrations of other air pollutants on lag1 day were not significantly associated with an increased risk of ILI outpatient visits during the COVID-19 stage.
Conclusion:
The findings that air pollutants had enhanced immediate effects and diminished lag-effects on the risk of ILI outpatient visits during the COVID-19 pandemic, which is important for the development of public health and environmental governance strategies. This article is protected by copyright. All rights reserved.
Using weekly-level influenza case data from all 47 prefectures in Japan alongside data from Nippon Professional Baseball (NPB) league from 1999 to 2018, we examine the effect of hosting games on local influenza transmission. The results highlight that during the flu season, for every NPB game held at its home ballpark, there is an average increase of 0.18 cases per sentinel medical institution (SMI) between that week and the following week. The effects are robust to different specifications and placebo tests. This translates to about a 0.1% increase in the number of cases during the overlap of NPB and flu seasons.
Background:
Vitamin D plays an essential role in immune responses to infections. However, the association between serum 25(OH)D concentrations and respiratory infection remains unclear.
Objectives:
The current study aimed to examine the association between serum 25(OH)D concentrations and respiratory infection among the United States adults.
Methods:
This cross-sectional study used data from the NHANES 2001-2014. Serum 25(OH)D concentrations were measured by radioimmunoassay or liquid chromatography-tandem mass spectrometry and were classified as ≥75.0 nmol/L (sufficiency), 50.0-74.9 nmol/L (insufficiency), 30.0-49.9 nmol/L (moderate deficiency), and <30 nmol/L (severe deficiency). The respiratory infections included self-reported head or chest cold as well as influenza, pneumonia, or ear infection within the last 30 d. The associations between serum 25(OH)D concentrations and respiratory infections were examined using weighted logistic regression models. Data are presented as ORs and 95% CIs.
Results:
This study included 31,466 United States adults ≥20 y of age (47.1 y, 55.5% women) with a mean serum 25(OH)D concentration of 66.2 nmol/L. After adjusting for sociodemographic characteristics, season of examination, lifestyle and dietary factors, and body mass index, compared with participants with a serum 25(OH)D concentration ≥75.0 nmol/L, those with a serum 25(OH)D concentration <30 nmol/L had higher risk of head or chest cold (OR: 1.17; 95% CI: 1.01, 1.36) and other respiratory diseases, including influenza, pneumonia, and ear infections (OR: 1.84; 95% CI: 1.35, 2.51). In the stratification analyses, lower serum 25(OH)D concentrations were associated with a higher risk of head or chest cold in obese adults but not in nonobese adults.
Conclusions:
Serum 25(OH)D concentrations are inversely associated with respiratory infection occurrence among United States adults. This finding may shed light on the protective effect of vitamin D on the respiratory health.
CD8 memory T cells are generated during primary infection with intracellular pathogens, such as viruses. These cells play an important role in the protection of the host upon re-infection with the same pathogen. In this study, we compare CD8 memory T cell receptor (TCR) beta repertoires directly ex vivo for two common human viruses, influenza A virus (IAV), an RNA virus that frequently re-infects due to a high rate of genetic mutation, and Epstein-Barr virus (EBV), a DNA virus, which persists in B cells for life, in the 95% of people that become infected. In cross-sectional and longitudinal studies of EBV seropositive, HLA-A2+, young (18-22 years), middle age (25-59 years), and older (>60 years) donors, we demonstrate that CD8 memory TCR repertoires to three immunodominant epitopes, known to have cross-reactive responses, IAV-M158-66 (M1), EBV-BMLF1280-288 (BM), and EBV-BRLF109-117 (BR) co-evolve as individuals age. Cross-sectional studies showed that IAV-M1- and both EBV-specific repertoires narrowed their TRBV usage with increasing age manifesting to different degrees for each epitope. In fact, narrowing of EBV-BM and EBV-BR-specific TRBV family usage correlated with increasing age. IAV-M1-specific TRBV usage was significantly narrowed by middle-age. There was evidence that TRBV usage was changing with increasing age. For instance, IAV-M1-specific dominant BV19 usage appeared to become bimodal showing either high or low frequency of usage in the older age group, while BV30 usage frequency directly correlated with age. For the EBV epitope-specific responses there was preferential usage of particular TRBV and changes in the hierarchy of BV family usage in the different age groups. There appeared to be focusing of the TRBV repertoire by all 3 epitopes to three common BV in the older donors, which would be consistent with retention of cross-reactive TCR suggesting co-evolution. Longitudinal studies tracking two donors over 14-15 years (middle age to older) showed that there were continuous modulations in the TCR repertoire of IAV-M1, EBV-BM and EBV-BR-specific responses over time. There was evidence that acute IAV infection could contribute to these changes in TCR repertoire. This could be occurring by the TCR cross-reactivity that is known to exist between these 3 epitopes, and which appeared to be enhanced during acute IAV infection based on increased usage of common shared TRBV. These studies suggest that virus-specific TCR repertoires change over time as individuals age leading to narrowing of the repertoire favoring retention of potentially cross-reactive TCR.
Background
Seasonal influenza vaccines protect against three (trivalent influenza vaccine, IIV3) or four (quadrivalent influenza vaccine, IIV4) viruses. IIV4 costs more than IIV3, and there is a tradeoff between incremental cost and protection. This is especially the case in low- and middle-income countries (LMICs) with limited budgets; previous reviews have not identified studies of IIV4-IIV3 comparisons in LMICs. We summarized the literature that compared health and economic outcomes of IIV4 and IIV3, focused on LMICs.
Methods
We systematically searched five databases for articles published before October 6, 2021 that modeled health or economic effects of IIV4 vs. IIV3. We abstracted data and compared findings among countries and models.
Results
Thirty-eight studies fit our selection criteria, ten included LMICs. Most studies (n=31) reported that IIV4 was cost-saving or cost-effective when compared to IIV3; we observed no difference in health or economic outcomes between LMICs and other countries. Based on cost differences of influenza vaccines, only one study compared coverage of IIV3 with IIV4 and reported that the maximum IIV4 price that would still yield greater public health impact than IIV3 was 13-22% higher than IIV3.
Conclusion
When vaccination coverage with IIV4 and IIV3 is the same, IIV4 tends to be not only more effective, but more cost-effective than IIV3, even with relatively high price differences between vaccine types. Alternatively, where funding is limited as in most LMICs, higher vaccine coverage can be achieved with IIV3 compared to IIV4, which could result in more favorable health and economic outcomes.
Influenza infection imparts an age-related increase in mortality and morbidity. The most effective countermeasure is vaccination; however, vaccines offer modest protection in older adults. To investigate how aging impacts the memory B cell response, we track hemagglutinin-specific B cells by indexed flow sorting and single-cell RNA sequencing (scRNA-seq) in 20 healthy adults that were administered the trivalent influenza vaccine. We demonstrate age-related skewing in the memory B cell compartment 6 weeks after vaccination, with younger adults developing hemagglutinin-specific memory B cells with an FcRL5⁺ “atypical” phenotype, showing evidence of somatic hypermutation and positive selection, which happened to a lesser extent in older persons. We use publicly available scRNA-seq from paired human lymph node and blood samples to corroborate that FcRL5⁺ atypical memory B cells can derive from germinal center (GC) precursors. Together, this study shows that the aged human GC reaction and memory B cell response following vaccination is defective.
Influenza is a highly contagious disease that is responsible for significant morbidity and mortality worldwide. Influenza A viruses (IAVs) have the ability to cross interspecies barriers from avian carriers and then rapidly circulate among and infect crowded livestock creating a breeding ground for the emergence of zoonotic viruses with epidemic and pandemic potential. They are susceptible to antigenic shift and drift and hence are the cause of recurring major epidemics and pandemics. Intensive animal farming creates conditions for the emergence and amplification of epidemics because of the physical and genetic proximity of the billions of animals, often in frail health, raised indoors every year. In particular, because swine and poultry are susceptible to infection with both avian and human influenza viruses, novel influenza viruses can be generated by reassortment of influenza viral segments. These are then transmitted via farm workers into the human population. Increased globalization is a significant factor in the worldwide spread of human influenza viruses that spillover from poultry and swine. The efficacy of influenza vaccination as a public health measure is limited by both the efficacy of the vaccine, which needs to be reformulated biannually, and the degree of public access to the vaccine. The most effective public health prophylaxis would therefore be to encourage less consumption of animal products, thus reducing the need for intensive animal agriculture. This will cut the link in the chain of emergence of influenza viruses into the human population, while at the same time, improving public health more directly.
Background:
Seasonal influenza annually causes significant morbidity and mortality, and unpredictable respiratory virus zoonoses, such as the current COVID-19 pandemic, can threaten the health and lives of millions more. Molecular iodine (I2 ) is a broad-spectrum, pathogen-nonspecific antiseptic agent that has demonstrated antimicrobial activity against a wide range of bacteria, virus, and fungi.
Methods:
We investigated a commercially available antiseptic, a non-irritating formulation of iodine (5% povidone-iodine) with a film-forming agent that extends the duration of the iodine's antimicrobial activity, for its ability to prevent influenza virus transmission between infected and susceptible animals in the guinea pig model of influenza virus transmission.
Results:
We observed that a once-daily topical application of this long-lasting antiseptic to the nares of either the infected virus-donor guinea pig or the susceptible virus-recipient guinea pig, or to the nares of both animals, prior to virus inoculation effectively reduced transmission of a highly transmissible influenza A virus, even when the donor and recipient guinea pigs shared the same cage. Daily treatment of the recipient guinea pig starting 1 day after initial exposure to an infected donor guinea pig in the same cage was similarly effective in preventing detectable influenza virus infection in the recipient animal.
Conclusions:
We conclude that a daily application of this antiseptic formulation is efficacious in reducing the transmission of influenza A virus in the guinea pig model, and further study in this and other preclinical models is warranted.
Influenza viruses cause respiratory infections in humans with high morbidity and mortality rates. Neuraminidase inhibitors such as oseltamivir and peramivir are the most commonly used drugs for influenza virus infections. However, the emergence of resistant viruses necessitates the urgent need to develop next-generation anti-influenza drugs. Soybean (Glycine max L. Merr.) is widely cultivated and used as food worldwide. In addition, soybean has long been used as a nutritional supplement and herbal medicine. However, the potential anti-influenza properties of the soybean cultivar "GL 2626/96″ (SG2626) are yet to be investigated. Herein, we determined whether the ethanolic extract of SG2626 (SG2626E) has anti-viral activity through performing SG2626E pre-, co-, and post-treatment assays, using the influenza green fluorescent protein (GFP)-tagged influenza A/PR/8/34 (A/PR/8/34-GFP) virus. SG2626E showed anti-influenza virus activity in pre- and co-treated cells in a dose-dependent manner, but not in post-treated cells. SG2626E imparted a considerable inhibitory effect on influenza A virus (IAV) infection through blocking viral attachment. SG2626E inhibited the activity of viral hemagglutinin, but not viral neuraminidase of the IAV. SG2626E inhibited IAV infection by reducing intracellular calcium levels in infected human lung epithelial A549 cells. Additionally, SG2626E reduced body weight loss, decreased mortality, and increased the survival rate through reducing viral replication in the lungs of IAV-infected mice. Overall, these results suggest that SG2626E inhibits IAV infection and is a potential novel anti-influenza agent.
Background:
The cost of influenza and other respiratory virus infections should be determined to analyze the real burden of these diseases. We aimed to investigate the clinical outcomes and cost of illness due to respiratory virus infections in hospitalized adult patients.
Methods:
Hospitalized patients who had nasal swab sampling for a suspected viral infection between 1 August 2018 to 31 March 2019 were included. Outcome variables were oxygen requirement, mechanical ventilation need, intensive care unit admission and cost.
Results:
At least one viral pathogen was detected in 125 (47.7%) of 262 patients who were included in the study. Fifty-five (20.9%) of the patients were infected with influenza. Influenza-positive patients had higher rates for respiratory support, intensive care unit admission and mortality compared to all other patients. The average cost of hospitalization per person was 2,879.76 USD in the influenza-negative group, while the same cost was 3,274.03 USD in the influenza-positive group. Although all of the vaccinated influenza-positive patients needed oxygen support, neither of them required invasive mechanical ventilation or intensive care unit admission. The average hospitalization cost per person was 779.70 USD in the vaccinated group compared to 3,762.01 USD in the unvaccinated group. Disease-related direct cost of influenza in the community was estimated as 22,776,075.61 USD in the 18-65 years of age group and 15,756,120.02 USD in the 65 years of age and over group per year.
Conclusion:
Influenza, compared to other respiratory virus infections, can lead to untoward clinical outcomes and mortality as well as higher direct medical costs in adults. This article is protected by copyright. All rights reserved.
Background:
The objective of this study was to test a novel household-based approach to improve late-season influenza vaccine uptake during the 2020-2021 season, using Epic's MyChart patient portal messages and/or interactive voice response telephone calls.
Methods:
This study was a non-blinded, quality improvement program using a block randomized design conducted among patients from Reliant Medical Group clinics residing in a traditional household (≥2 individuals clinically active in the Reliant system living at the same address). Households were randomized 1:1:1 into intervention arms: non-tailored communication (messaging based on CDC's seasonal influenza vaccination campaign), tailored communication (comprehensive communication including reinforcement of the importance of influenza vaccination for high-risk individuals), and standard-of-care control. Influenza vaccination during the program was captured via medical records, and the odds of vaccination among communication arms versus the control arm were assessed. A survey assessing influenza vaccination drivers was administered using MyChart.
Results:
Influenza vaccination increased by 3.3% during the program period, and no significant differences in vaccination were observed in intervention arms relative to the control arm. Study operationalization faced substantial challenges related to the concurrent COVID-19 pandemic. Compared with vaccinated survey respondents, unvaccinated respondents less frequently reported receiving a recommendation for influenza vaccination from their healthcare provider (15.8% vs. 42.3%, p < 0.001) or awareness that vaccination could protect themselves and higher risk contacts (82.3% vs. 92.6%, p < 0.001).
Conclusions:
No significant effects of the interventions were observed. Survey results highlighted the importance of healthcare provider recommendations and the need for increased education around the benefits of vaccination.
Seasonal influenza epidemics have a substantial public health and economic burden in the United States (US). On average, over 200,000 people are hospitalized and an estimated 23,000 people die from respiratory and circulatory complications associated with seasonal influenza virus infections each year. Annual direct medical costs and indirect productivity costs across the US have been found to average respectively at $10.4 billion and $16.3 billion. The objective of this study was to estimate the economic impact of severe influenza-induced illness on the US Veterans Affairs population. The five-year study period included 2010 through 2014. Influenza-attributed outcomes were estimated with a statistical regression model using observed emergency department (ED) visits, hospitalizations, and deaths from the Veterans Health Administration of the Department of Veterans Affairs (VA) electronic medical records and respiratory viral surveillance data from the Centers for Disease Control and Prevention (CDC). Da
Background:
Although many studies have modelled the national burdens of hospitalizations and deaths due to influenza, few studies have considered the outpatient burden. To fill this gap for the United States (US), we applied traditional statistical modelling approaches to time series derived from large medical claims databases held in the private sector.
Methods:
We accessed ICD-9-coded office visit data extracted from Truven Health Analytics' MarketScan Commercial database covering about one third of the US population <65 years during 2001-2009, and Medicare Supplemental data covering about one fifth of US seniors 65+ during 2006-2009. We extracted weekly time series of visits due to respiratory diagnoses, otitis media (OM), and urinary tract infections (UTI), a "negative control". We used multiple linear regression modelling to estimate age-specific influenza-related excess in office visits.
Results:
In the <65 year age group, in the 8 pre-pandemic seasons studied and for the broadest defined respiratory outcome, the model attributed an average of ~14.5 M (Standard deviation [SD] across seasons 3.9 million) office visits to influenza (rate of 5,581/100,000 population). Of these, ~80 % of visits occurred in the 5-17 and 18-49 age group. In school children aged 5-17 year olds and adult 18-64 year age groups the majority of visits were due to influenza B, while A/H3N2 explained most visits in children <5 year olds. The model further attributed ~2.2 M OM visits (SD across seasons 790,000) annually to influenza, of which 86 % of these occurred in children <18 years; this indicates that 6.4 % of all infants <2 years and 4.9 % of all toddlers aged 2-4 years in the US have an influenza-attributable outpatient visit with an OM diagnosis. In seniors 65 years and older, our model attributed ~0.7 M (SD across seasons 351,000) respiratory visits to influenza (rate of 1,887/100,000 population). The model identified no significant excess UTI (negative control) visits in most seasons.
Conclusions:
This is to our knowledge a first study of the outpatient burden of influenza in the US in a large database. The model estimated that 10 % of all children <18 years and 4 % of the entire population <65 years seek outpatient care for respiratory illness attributable to influenza annually.
Trial registration:
ClinicalTrial.gov, NCT02019732 .
This report updates the 2015-16 recommendations ofthe Advisoiy Committee on Immunization Practices (ACIP) regarding the use of seasonal influenza vaccines (Grohskopf LA, Sokolow LZ, Olsen SJ, Bresee JS, Broder KR, Karron RA. Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices, United States, 2015-16 influenza season. MMWR Morb Mortal Wkly Rep 2015;64:818-25). Routine annual influenza vaccination is recommended for all persons aged months who do not have contraindications. For the 2016-17 influenza season, inactivated influenza vaccines (IIVs) will be available in both trivalent (IIV3) and quadrivalent (IIV4) formulations. Recombinant influenza vaccine (RIV) will be available in a trivalent formulation (RIV3). In light of concerns regarding low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013-14 and 2015-16 seasons, for the 2016-17 season, ACIP makes the interim recommendation that live attenuated influenza vaccine (LAIV4) should not be used. Vaccine virus strains included in the 2016-17 U.S. trivalent influenza vaccines will be an A/California/7/2009 (H1N1) like virus, an A/Hong Kong/4801/2014 (H3N2) like virus, and a B/Brisbane/60/2008 like virus (Victoria lineage). Quadrivalent vaccines will include an additional influenza B virus strain, a B/Phuket/3073/2013 like virus (Yamagata lineage). Recommendations for use of different vaccine types and specific populations are discussed. A licensed, age -appropriate vaccine should be used. No preferential recommendation is made for one influenza vaccine product over another for persons for whom more than one licensed, recommended product is otherwise appropriate. This information is intended for vaccination providers, immunization program personnel, and public health personnel. Information in this report reflects discussions during public meetings ofACIP held on October 21, 2015; February 24, 2016; andJune 22, 2016 These recommendations apply to all licensed influenza vaccines used within Food and DrugAdministration licensed indications, including those licensed after the publication of this report. Updates and other information are available at CDC's influenza website (http://www.cdc.govfflit). Vaccination and health care providers should check CDC's influenza website periodically for additional information.
Background:
Designed to overcome influenza B mismatch, new quadrivalent influenza vaccines (QIVs) contain one additional B strain compared with trivalent influenza vaccines (TIVs).
Objective:
To examine the expected public health impact, budget impact, and incremental cost-effectiveness of QIV versus TIV in the United States.
Methods:
A dynamic transmission model was used to predict the annual incidence of influenza over the 20-year-period of 2014 to 2034 under either a TIV program or a QIV program. A decision tree model was interfaced with the transmission model to estimate the public health impact and the cost-effectiveness of replacing TIV with QIV from a societal perspective. Our models were informed by published data from the United States on influenza complication probabilities and relevant costs. The incremental vaccine price of QIV as compared with that of TIV was set at US $5.40 per dose.
Results:
Over the next 20 years, replacing TIV with QIV may reduce the number of influenza B cases by 27.2% (16.0 million cases), resulting in the prevention of 137,600 hospitalizations and 16,100 deaths and a gain of 212,000 quality-adjusted life-years (QALYs). The net societal budget impact would be US $5.8 billion and the incremental cost-effectiveness ratio US $27,411/QALY gained. In the probabilistic sensitivity analysis, 100% and 96.5% of the simulations fell below US $100,000/QALY and US $50,000/QALY, respectively.
Conclusions:
Introducing QIV into the US immunization program may prevent a substantial number of hospitalizations and deaths. QIV is also expected to be a cost-effective alternative option to TIV.
Purpose:
The objective of the study is to evaluate the effect of antiviral treatment, pre-existing diseases, and sociodemographic factors on the risk of influenza-related complications and healthcare utilization.
Methods:
Case data were obtained from US MarketScan Research Databases. Cases had a clinical diagnosis of influenza between 2006 and 2010 and continuous healthcare insurance from 90 days before to 30 days after diagnosis. Logistic regression models were applied to explore the impact of antiviral treatment on complications and healthcare utilization. Modified generalized estimating equation regression models in propensity score matched samples were used to address the robustness of the study.
Results:
Analyses included 1,557, 437 cases from four influenza seasons. In each season, 34.82%- 43.42% of patients received antiviral treatment, mostly oseltamivir. On average, 1.86% of patients were hospitalized, 9.56% visited the emergency room and 41.14% made ≥2 outpatient visits. The incidence of complications ranged from 17.62 to 19.67 per 100 patient-months. The relative risk of complications was increased in patients aged 0-4 years and those with pre-existing diseases, including asthma, Parkinson's disease, and cystic fibrosis. Overall, patients receiving antiviral treatment had an 11% reduction in the risk of complications. Among oseltamivir-treated patients, the risk of complications was significantly reduced by 81% in those treated ≤two days after diagnosis compared with later. Antiviral treatment significantly reduced the risk of hospitalization, emergency room visits and need for ≥2 outpatient visits by 29%, 24% and 11%, respectively. Propensity score matching method improved the strength of the study.
Conclusions:
Early treatment with antivirals, and specifically oseltamivir, significantly reduced the risk of influenza-related complications and healthcare utilization. However, lacking information about diseases severity and the time from onset of symptoms to fulfillment of a prescription may bias the outcomes.
Background:
Influenza causes significant morbidity and mortality with considerable economic costs, including lost work productivity. Influenza vaccines may reduce the economic burden through primary prevention of influenza and reduction in illness severity.
Methods:
We examined illness severity and work productivity loss among working adults with medically-attended acute respiratory illnesses, and compared outcomes for patients with and without laboratory-confirmed influenza, and by influenza vaccination status among patients with influenza during the 2012-2013 influenza season.
Results:
Illnesses laboratory-confirmed as influenza (i.e. Cases) were subjectively assessed as more severe than illnesses not caused by influenza (i.e. Non-Cases) based on multiple measures, including current health status at study enrollment (<7 days from illness onset), and current activity and sleep quality status relative to usual. Influenza Cases reported missing 45% more work hours (20.5 vs. 15.0, P<.001) than Non-Cases, and subjectively assessed their work productivity as impeded to a greater degree (6.0 vs. 5.4, P<.001). Current health status and current activity relative to usual were subjectively assessed as modestly, but significantly, better for vaccinated influenza Cases compared with unvaccinated Cases; however, no significant modifications of sleep quality, missed work hours, or work productivity loss were noted for vaccinated subjects.
Conclusions:
. Influenza illnesses were more severe and resulted in more missed work hours and productivity loss than illnesses not confirmed as influenza. Modest reductions in illness severity for vaccinated influenza cases were observed. These findings highlight the burden of influenza illnesses and illustrate the importance of laboratory-confirmation of influenza outcomes in evaluations of vaccine effectiveness.
Background
Seasonal influenza causes considerable morbidity and mortality across all age groups, and influenza vaccination was recommended in 2010 for all persons aged 6 months and above. We estimated the averted costs due to influenza vaccination, taking into account the seasonal economic burden of the disease.
Methods
We used recently published values for averted outcomes due to influenza vaccination for influenza seasons 2005-06, 2006-07, 2007-08, and 2008-09, and age cohorts 6 months-4 years, 5-19 years, 20-64 years, and 65 years and above. Costs were calculated according to a payer and societal perspective (in 2009 US$), and took into account medical costs and productivity losses.
Results
When taking into account direct medical costs (payer perspective), influenza vaccination was cost saving only for the older age group (65≥) in seasons 2005-06 and 2007-08. Using the same perspective, influenza vaccination resulted in total costs of $US 1.7 billion (95%CI: $US 0.3–4.0 billion) in 2006-07 and $US 1.8 billion (95%CI: $US 0.1–4.1 billion) in 2008-09. When taking into account a societal perspective (and including the averted lost earnings due to premature death) averted deaths in the older age group influenced the results, resulting in cost savings for all ages combined in season 07-08.
Discussion
Influenza vaccination was cost saving in the older age group (65≥) when taking into account productivity losses and, in some seasons, when taking into account medical costs only. Averted costs vary significantly per season; however, in seasons where the averted burden of deaths is high in the older age group, averted productivity losses due to premature death tilt overall seasonal results towards savings. Indirect vaccination effects and the possibility of diminished case severity due to influenza vaccination were not considered, thus the averted burden due to influenza vaccine may be even greater than reported.
SUMMARY Death certificate reports and laboratory-confirmed influenza deaths probably underestimate paediatric deaths attributable to influenza. Using US mortality data for persons aged <18 years who died during 28 September 2003 to 2 October 2010, we estimated influenza-attributable deaths using a generalized linear regression model based on seasonal covariates, influenza-certified deaths (deaths for which influenza was a reported cause of death), and occurrence during the 2009 pandemic period. Of 32 783 paediatric deaths in the death categories examined, 853 (3%) were influenza-certified. The estimated number of influenza-attributable deaths over the study period was 1·8 [95% confidence interval (CI) 1·3-2·8] times higher than the number of influenza-certified deaths. Influenza-attributable deaths were 2·1 (95% CI 1·5-3·4) times higher than influenza-certified deaths during the non-pandemic period and 1·1 (95% CI 1·0-1·8) times higher during the pandemic. Overall, US paediatric deaths attributable to influenza were almost twice the number reported by death certificate codes in the seasons prior to the 2009 pandemic.
Limited information on age- and sex-specific estimates of influenza-associated death with different underlying causes is currently available. We regressed weekly age- and sex-specific US mortality outcomes underlying several causes between 1997 and 2007 to incidence proxies for influenza A/H3N2, A/H1N1, and B that combine data on influenzalike illness consultations and respiratory specimen testing, adjusting for seasonal baselines and time trends. Adults older than 75 years of age had the highest average annual rate of influenza-associated mortality, with 141.15 deaths per 100,000 people (95% confidence interval (CI): 118.3, 163.9), whereas children under 18 had the lowest average mortality rate, with 0.41 deaths per 100,000 people (95% CI: 0.23, 0.60). In addition to respiratory and circulatory causes, mortality with underlying cancer, diabetes, renal disease, and Alzheimer disease had a contribution from influenza in adult age groups, whereas mortality with underlying septicemia had a contribution from influenza in children. For adults, within several age groups and for several underlying causes, the rate of influenza-associated mortality was somewhat higher in men than in women. Of note, in men 50-64 years of age, our estimate for the average annual rate of influenza-associated cancer mortality per 100,000 persons (1.90, 95% CI: 1.20, 2.62) is similar to the corresponding rate of influenza-associated respiratory deaths (1.81, 95% CI: 1.42, 2.21). Age, sex, and underlying health conditions should be considered when planning influenza vaccination and treatment strategies.
Objective
To improve the understanding of common health care cost collection, estimation, analysis, and reporting methodologies.Data SourcesOvid MEDLINE (1947 to December 2012), Cochrane Central register of Controlled Trials, Database of Systematic Reviews, Health Technology Assessment, and National Health Service Economic Evaluation Database.Review Methods
This article discusses the following cost collection methods: defining relevant resources, quantification of consumed resources, and resource valuation. It outlines the recommendations for cost reporting in economic evaluations and reviews the techniques on how to handle cost data uncertainty. Last, it discusses the controversial topics of future costs and patient productivity losses.Conclusion
Health care cost collection and estimation can be challenging, and an organized approach is required to optimize accuracy of economic evaluation outcomes.Implications for PracticeUnderstanding health care cost collection and estimation techniques will improve both critical appraisal and development of future economic evaluations.
Productivity costs occur when the productivity of individuals is affected by illness, treatment, disability or premature death. The objective of this paper was to review past and current developments related to the inclusion, identification, measurement and valuation of productivity costs in economic evaluations. The main debates in the theory and practice of economic evaluations of health technologies described in this review have centred on the questions of whether and how to include productivity costs, especially productivity costs related to paid work. The past few decades have seen important progress in this area. There are important sources of productivity costs other than absenteeism (e.g. presenteeism and multiplier effects in co-workers), but their exact influence on costs remains unclear. Different measurement instruments have been developed over the years, but which instrument provides the most accurate estimates has not been established. Several valuation approaches have been proposed. While empirical research suggests that productivity costs are best included in the cost side of the cost-effectiveness ratio, the jury is still out regarding whether the human capital approach or the friction cost approach is the most appropriate valuation method to do so. Despite the progress and the substantial amount of scientific research, a consensus has not been reached on either the inclusion of productivity costs in economic evaluations or the methods used to produce productivity cost estimates. Such a lack of consensus has likely contributed to ignoring productivity costs in actual economic evaluations and is reflected in variations in national health economic guidelines. Further research is needed to lessen the controversy regarding the estimation of health-related productivity costs. More standardization would increase the comparability and credibility of economic evaluations taking a societal perspective.
The primary objective of this study was to assess trends in employer expenditures for both direct medical costs and indirect productivity losses associated with influenza. A retrospective analysis was performed using two of the MarketScan family of databases for 2005-2009. Patients with at least one diagnosis claim for influenza during an influenza season were selected. We estimated seasonal incidence of influenza in the employed population from the MarketScan Commercial Claims and Encounters database. Health care utilization and costs and productivity losses were assessed during the 21-d period following the influenza diagnosis date. Compared with the 2005-2006 season (493 per 100,000 plan members), influenza incidence increased during the 2006-2007 (598 per 100,000 plan members) and 2007-2008 (1,142 per 100,000 plan members) seasons and had a dramatic increase during the pandemic season of 2008-2009 (1,715 per 100,000 plan members) . The total influenza-related employer spending per 100,000 plan members also increased by over 400% during the 2008-2009 influenza season [$623,248; confidence interval (CI]):$601,518-$644,991], compared with 2005-2006 ($145,834; 95% CI: $135,067-$156,603). The primary drivers of the increased costs were emergency room, outpatient and inpatient visits. Total costs associated with influenza-related missed work time per 100,000 plan members increased over 4-fold from $26,479 in the 2005-2006 influenza season to $122,811 in 2008-2009. Overall, as expected, considerably higher direct and indirect costs were observed during the 2008-2009 influenza pandemic season than during other influenza seasons. In recent years, the influenza-related employer burden has increased considerably. In future, employers may need efficient resource allocation in order to address the productivity losses and increasing direct medical costs associated with increased influenza incidence. One of the strategies that employers may consider is increasing influenza vaccination rates among employees, which likely will help lower the influenza incidence and the associated downstream direct and indirect costs.
Age-specific comparisons of influenza and respiratory syncytial virus (RSV) hospitalization rates can inform prevention efforts, including vaccine development plans. Previous US studies have not estimated jointly the burden of these viruses using similar data sources and over many seasons.
We estimated influenza and RSV hospitalizations in 5 age categories (<1, 1-4, 5-49, 50-64, and ≥65 years) with data for 13 states from 1993-1994 through 2007-2008. For each state and age group, we estimated the contribution of influenza and RSV to hospitalizations for respiratory and circulatory disease by using negative binomial regression models that incorporated weekly influenza and RSV surveillance data as covariates.
Mean rates of influenza and RSV hospitalizations were 63.5 (95% confidence interval [CI], 37.5-237) and 55.3 (95% CI, 44.4-107) per 100000 person-years, respectively. The highest hospitalization rates for influenza were among persons aged ≥65 years (309/100000; 95% CI, 186-1100) and those aged <1 year (151/100000; 95% CI, 151-660). For RSV, children aged <1 year had the highest hospitalization rate (2350/100000; 95% CI, 2220-2520) followed by those aged 1-4 years (178/100000; 95% CI, 155-230). Age-standardized annual rates per 100000 person-years varied substantially for influenza (33-100) but less for RSV (42-77).
Overall US hospitalization rates for influenza and RSV are similar; however, their age-specific burdens differ dramatically. Our estimates are consistent with those from previous studies focusing either on influenza or RSV. Our approach provides robust national comparisons of hospitalizations associated with these 2 viral respiratory pathogens by age group and over time.
We estimated the possible effects of the next influenza pandemic in the United States and analyzed the economic impact of vaccine-based interventions. Using death rates, hospitalization data, and outpatient visits, we estimated 89,000 to 207,000 deaths; 314,000 to 734,000 hospitalizations; 18 to 42 million outpatient visits; and 20 to 47 million additional illnesses. Patients at high risk (15% of the population) would account for approximately 84% of all deaths. The estimated economic impact would be US$71.3 to $166.5 billion, excluding disruptions to commerce and society. At $21 per vaccinee, we project a net savings to society if persons in all age groups are vaccinated. At $62 per vaccinee and at gross attack rates of 25%, we project net losses if persons not at high risk for complications are vaccinated. Vaccinating 60% of the population would generate the highest economic returns but may not be possible within the time required for vaccine effectiveness, especially if two doses of vaccine are required.
Respiratory viral infections are responsible for a large number of hospitalizations in the United States each year.
To estimate annual influenza-associated hospitalizations in the United States by hospital discharge category, discharge type, and age group.
National Hospital Discharge Survey (NHDS) data and World Health Organization Collaborating Laboratories influenza surveillance data were used to estimate annual average numbers of hospitalizations associated with the circulation of influenza viruses from the 1979-1980 through the 2000-2001 seasons in the United States using age-specific Poisson regression models.
We estimated influenza-associated hospitalizations for primary and any listed pneumonia and influenza and respiratory and circulatory hospitalizations.
Annual averages of 94,735 (range, 18,908-193,561) primary and 133,900 (range, 30,757-271,529) any listed pneumonia and influenza hospitalizations were associated with influenza virus infections. Annual averages of 226,54 (range, 54,523-430,960) primary and 294,128 (range, 86,494-544,909) any listed respiratory and circulatory hospitalizations were associated with influenza virus infections. Persons 85 years or older had the highest rates of influenza-associated primary respiratory and circulatory hospitalizations (1194.9 per 100,000 persons). Children younger than 5 years (107.9 primary respiratory and circulatory hospitalizations per 100,000 persons) had rates similar to persons aged 50 through 64 years. Estimated rates of influenza-associated hospitalizations were highest during seasons in which A(H3N2) viruses predominated, followed by B and A(H1N1) seasons. After adjusting for the length of each influenza season, influenza-associated primary pneumonia and influenza hospitalizations increased over time among the elderly. There were no significant increases in influenza-associated primary respiratory and circulatory hospitalizations after adjusting for the length of the influenza season.
Significant numbers of influenza-associated hospitalizations in the United States occur among the elderly, and the numbers of these hospitalizations have increased substantially over the last 2 decades due in part to the aging of the population. Children younger than 5 years had rates of influenza-associated hospitalizations similar to those among individuals aged 50 through 64 years. These findings highlight the need for improved influenza prevention efforts for both young and older US residents.
Background:
The seasonal incidence of influenza is often approximated as "5% to 20%".
Methods:
We used two methods to estimate the seasonal incidence of symptomatic influenza in the United States. First, we made a statistical estimate extrapolated from influenza-associated hospitalization rates for 2010-11 to 2015-16, collected as part of national surveillance, covering approximately 9% of the United States, and including the existing mix of vaccinated and unvaccinated persons. Second, we performed a literature search and meta-analysis of published manuscripts that followed cohorts of subjects during 1996-2016 to detect laboratory-confirmed symptomatic influenza among unvaccinated persons; we adjusted this result to the United States median vaccination coverage and effectiveness during 2010-2016.
Results:
The statistical estimate of influenza incidence among all ages ranged from 3.0-11.3% among seasons, with median values of 8.3 (95% confidence interval [CI] 7.3%, 9.7%) for all ages, 9.3% (CI 8.2%, 11.1%) for children <18 years and 8.9% (CI 8.2%, 9.9%) for adults 18-64 years. Corresponding values for the meta-analysis were 7.1% (CI 6.1, 8.1) for all ages, 8.7% (6.6, 10.5) for children, and 5.1% (3.6, 6.6) for adults.
Conclusions:
The two approaches produced comparable results for children and persons of all ages. The statistical estimates are more versatile and permit estimation of season-to-season variation. During 2010-2016, the incidence of symptomatic influenza among vaccinated and unvaccinated United States residents, including both medically attended and non-attended infections, was approximately 8% and varied from 3% to 11% among seasons.
Background:
Immune responses to influenza vaccines decline with age, reducing clinical effectiveness. We compared the effect of the more immunogenic high-dose trivalent influenza vaccine with a standard-dose vaccine to identify the effect on reducing hospital admissions of nursing home residents in the USA.
Methods:
We did a single-blind, pragmatic, comparative effectiveness, cluster-randomised trial with a 2 × 2 factorial design. Medicare-certified nursing homes in the USA located within 50 miles of a Centers for Disease Control and Prevention influenza reporting city were recruited, so long as the facilities were not located in a hospital, had more than 50 long-stay residents, had less than 20% of the population aged under 65 years, and were not already planning to administer the high-dose influenza vaccine to residents. Enrolled nursing homes were randomised to a facility-wide standard of care for the residents of either high dose or standard dose as the vaccine for the 2013-14 influenza season and half of each group were randomly allocated to free vaccines for staff. Individual residents were included in the analysis group if they were aged 65 years or older and were long-stay residents (ie, had been in the facility 90 days or more before commencing the influenza vaccination programme). The analysts and investigators with access to the raw data were masked to study group by coding the groups until after the analyses were complete. The primary outcome was hospital admissions related to pulmonary and influenza-like illness between Nov 1, 2013, and May 31, 2014, identified from Medicare hospital claims available for residents who were without private health insurance (ie, those who were considered Medicare fee-for-service). We obtained data from the Centers for Medicare & Medicaid Services (CMS) and enrolled facilities. The analyses used marginal Poisson and Cox proportional hazards regression, accounting for clustering of residents within homes, on an intention-to-treat basis, adjusting for facility clustering and prespecified covariates. Safety data were voluntarily reported according to the standard of care. This trial is registered with ClinicalTrials.gov, number NCT01815268.
Findings:
823 facilities were recruited to the study between March and August, 2013, to participate in the trial, of which 409 facilities were randomised for residents to receive high-dose vaccine, and 414 facilities for residents to receive standard-dose vaccine. The facilities housed 92 269, of whom 75 917 were aged 65 years or older and 53 008 were also long-stay residents, and 38 256 were matched to Medicare hospital claims as of Nov 1, 2013. Staff vaccination rates did not differ between groups, so analyses focused on the high-dose versus standard-dose vaccine comparison. On the basis of Medicare fee-for-service claims, the incidence of respiratory-related hospital admissions was significantly lower in facilities where residents received high-dose influenza vaccines than in those that received standard-dose influenza vaccines (0·185 per 1000 resident-days or 3·4% over 6 months vs 0·211 per 1000 resident-days or 3·9% over 6 months; unadjusted relative risk of 0·888, 95% CI 0·785-1·005, 0=0·061, and adjusted relative risk 0·873, 0·776-0·982, p=0·023).
Interpretation:
When compared with standard-dose vaccine, high-dose influenza vaccine can reduce risk of respiratory-related hospital admissions from nursing home residents aged 65 years and older.
Funding:
Sanofi Pasteur, Swiftwater, PA, USA.
Background:
There is a paucity of data on the clinical and economic impact of seasonal influenza in children. This study estimated the incidence of diagnosed influenza and related complications, and associated healthcare resource utilization (HRU) and costs in US children.
Methods:
Children ≥6 months and <18 years old diagnosed with influenza using ICD-9 codes and enrolled in a health plan during at least one influenza season between 2010-2014 were matched to similar patients without diagnosed influenza (GSK study identifier: HO-15-15728). Outcomes included incidence of influenza and complications, HRU frequency, and healthcare costs during 21 days of follow-up. Adjusted costs were estimated using generalized linear models.
Results:
Incidence (per 1,000) of influenza was 20.3 (commercially-insured) and 32.6 (Medicaid), with the highest incidence among 6 to 35-month olds (Commercial: 26.8; Medicaid: 47.9). Approximately 12-17% of influenza patients experienced complications, with the 6-35 months group having the highest percentage (25-30%). The 6-35-month-old influenza patients with complications had the highest proportion with hospitalizations (5-6%) and emergency room visits (Commercial: 19%; Medicaid: 36%). Influenza patients with (vs. without) complications had greater adjusted mean influenza-specific costs (Commercial: $1,161 vs. $337; Medicaid: $1,199 vs. $354; p<0.05), and influenza cases (vs. controls) had greater adjusted mean all-cause costs (Commercial: $688 vs. $470; Medicaid: $818 vs. $453; p<0.05).
Conclusions:
Pediatric patients with influenza incurred higher healthcare costs compared with matched controls, and influenza-specific costs were greater among those with complications.
Although researchers have demonstrated that influenza illness has affected societies for many centuries, in more recent decades, the World Health Organization and the Centers for Disease Control and Prevention have developed sophisticated means of tracking the virus' activity around the globe. The importance of tracking influenza activity lies not only in detecting what is circulating in other countries, but also in enabling global manufacturers of vaccine to prepare the appropriate A and B compositions for the impending epidemic. Tracking influenza also allows quantification of its great toll in terms of morbidity and mortality. Influenza has broad societal and financial impact, with as much as $12 to $14 billion in indirect economic impact in the United States annually and a significant increase in physician visits for febrile respiratory illness. For example, during many influenza outbreaks visits to family care physicians and internal medicine specialists earl increase by 150% to 450%. Influenza presents an ongoing public health issue because of the virus' ability to continually reinvent itself. Antigenic drift, caused by subtle changes in influenza's surface proteins, partially accounts for annual epidemic outbreaks of the illness. Antigenic shift that occurs because of major changes in the viral hemagglutinin and sometimes in the neuraminidase, the other surface protein, results in the more widespread and lethal pandemic forms of influenza. Moreover, type A influenza is not an exclusively human infection. By understanding how both of these types of changes occur in waterfowl, the virus' primary nonhuman hosts, scientists can develop both drugs and epidemiological strategies to avert or minimize the most severe effects of influenza.
Since the introduction of pandemic influenza A (H1N1) to the USA in 2009, the Influenza Incidence Surveillance Project has monitored the burden of influenza in the outpatient setting through population-based surveillance.
From Oct 1, 2009, to July 31, 2013, outpatient clinics representing 13 health jurisdictions in the USA reported counts of influenza-like illness (fever including cough or sore throat) and all patient visits by age. During four years, staff at 104 unique clinics (range 35-64 per year) with a combined median population of 368 559 (IQR 352 595-428 286) attended 35 663 patients with influenza-like illness and collected 13 925 respiratory specimens. Clinical data and a respiratory specimen for influenza testing by RT-PCR were collected from the first ten patients presenting with influenza-like illness each week. We calculated the incidence of visits for influenza-like illness using the size of the patient population, and the incidence attributable to influenza was extrapolated from the proportion of patients with positive tests each week.
The site-median peak percentage of specimens positive for influenza ranged from 58·3% to 77·8%. Children aged 2 to 17 years had the highest incidence of influenza-associated visits (range 4·2-28·0 per 1000 people by year), and adults older than 65 years had the lowest (range 0·5-3·5 per 1000 population). Influenza A H3N2, pandemic H1N1, and influenza B equally co-circulated in the first post-pandemic season, whereas H3N2 predominated for the next two seasons. Of patients for whom data was available, influenza vaccination was reported in 3289 (28·7%) of 11 459 patients with influenza-like illness, and antivirals were prescribed to 1644 (13·8%) of 11 953 patients.
Influenza incidence varied with age groups and by season after the pandemic of 2009 influenza A H1N1. High levels of influenza virus circulation, especially in young children, emphasise the need for additional efforts to increase the uptake of influenza vaccines and antivirals.
US Centers for Disease Control and Prevention.
Copyright © 2015 Elsevier Ltd. All rights reserved.
A high-dose trivalent inactivated influenza vaccine was licensed in 2009 by the US Food and Drug Administration (FDA) on the basis of serological criteria. We sought to establish whether high-dose inactivated influenza vaccine was more effective for prevention of influenza-related visits and hospital admissions in US Medicare beneficiaries than was standard-dose inactivated influenza vaccine.
In this retrospective cohort study, we identified Medicare beneficiaries aged 65 years and older who received high-dose or standard-dose inactivated influenza vaccines from community pharmacies that offered both vaccines during the 2012-13 influenza season. Outcomes were defined with billing codes on Medicare claims. The primary outcome was probable influenza infection, defined by receipt of a rapid influenza test followed by dispensing of the neuraminidase inhibitor oseltamivir. The secondary outcome was a hospital or emergency department visit, listing a Medicare billing code for influenza. We estimated relative vaccine effectiveness by comparing outcome rates in Medicare beneficiaries during periods of high influenza circulation. Univariate and multivariate Poisson regression models were used for analyses.
Between Aug 1, 2012 and Jan 31, 2013, we studied 929 730 recipients of high-dose vaccine and 1 615 545 recipients of standard-dose vaccine. Participants enrolled in each cohort were well balanced with respect to age and presence of underlying medical disorders. The high-dose vaccine (1·30 outcomes per 10 000 person-weeks) was 22% (95% CI 15-29) more effective than the standard-dose vaccine (1·01 outcomes per 10 000 person-weeks) for prevention of probable influenza infections (rapid influenza test followed by oseltamivir treatment) and 22% (95% CI 16-27%) more effective for prevention of influenza hospital admissions (0·86 outcomes per 10 000 person-weeks in the high-dose cohort vs 1·10 outcomes per 10 000 person-weeks in the standard-dose cohort).
Our retrospective cohort study in US Medicare beneficiaries shows that, in people 65 years of age and older, high-dose inactivated influenza vaccine was significantly more effective than standard-dose vaccine in prevention of influenza-related medical encounters. Additionally, the large population in our study enabled us to show, for the first time, a significant reduction in influenza-related hospital admissions in high-dose compared to standard-dose vaccine recipients, an outcome not shown in randomised studies. These results provide important new information to be considered by policy makers recommending influenza vaccinations for elderly people.
FDA and the office of the Assistant Secretary of Planning and Evaluation.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Human capital estimates of labor productivity are often used to estimate the economic impact of diseases and injuries that cause incapacitation or death.
Estimates of average hourly, annual, and lifetime economic productivity, both market and household, were calculated in 2007 US dollars for 5-year age groups for men, women, and both sexes in the United States.
Data from the American Time Use Survey were used to estimate hours of paid work and household services and hourly and annual earnings and household productivity. Present values of discounted lifetime earnings were calculated for each age group using the 2004 US life tables and a discount rate of 3% per year and assuming future productivity growth of 1% per year.
The estimates of hours and productivity were calculated using the time diaries of 72,922 persons included in the American Time Use Survey for the years 2003 to 2007.
The present value of lifetime productivity is approximately $1.2 million in 2007 dollars for children under 5 years of age. For adults in their 20s and 30s, it is approximately $1.6 million and then it declines with increasing age. Productivity estimates are higher for males than for females, more for market productivity than for total productivity.
Changes in hours of paid employment and household services can affect economic productivity by age and sex. This is the first publication to include estimates of household services based on contemporary time use data for the US population.
Healthcare delivery in the USA and abroad has changed dramatically over the last several decades. Along with the growth in diagnostic and therapeutic interventions, the costs of healthcare have escalated out of proportion relative to other aspects of the economy. This growth has fostered careful scrutiny of both the effectiveness and efficiency of healthcare delivery. Because of this emphasis on the economics of healthcare, physicians require an understanding not only of the efficacy and clinical utility of their interventions, but also of the relative value in an economic sense of their efforts. In other words, physicians in the modern era must now appreciate the concept of cost-effectiveness. Cost-effectiveness and cost-utility analyses are critical evaluative tools. Explicit data on comparative cost-effectiveness are useful for allocating the increasingly stretched healthcare resources. This article provides a primer for understanding the methods and applications of cost-effectiveness and cost-utility analyses.
This study aimed to compare systematically approaches to estimating influenza-attributable mortality in older Australians. Using monthly age-specific death data together with viral surveillance counts for influenza and respiratory syncytial virus, we explored two of the most frequently used methods of estimating excess influenza-attributable disease: Poisson and Serfling regression models. These approaches produced consistent age and temporal patterns in estimates of influenza-attributable mortality in older Australians but some variation in the magnitude of the disease burden. Of Australians aged >50 years, average annual estimated influenza-attributable deaths (all cause) ranged from 2314 to 3457 for the Serfling and Poisson regression models, respectively. The excess influenza-attributable disease burden was substantial under all approaches.
We measured the relative impact of influenza and respiratory syncytial virus (RSV) infections in young children in terms of emergency department (ED) visits, clinical care requirements, and overall resource use.
Patients who were aged <or=7 years and treated in the ED of a tertiary care pediatric hospital for an acute respiratory infection were enrolled during 2 winter seasons between 2003 and 2005. We quantified health care resource use for children with influenza or RSV infections, and extrapolated results to estimate the national resource use associated with influenza and RSV infections.
Nationally, an estimated 10.2 ED visits per 1000 children were attributable to influenza and 21.5 visits per 1000 to RSV. Children who were aged 0 to 23 months and infected with RSV had the highest rate of ED visits with 64.4 visits per 1000 children. Significantly more children required hospitalization as a result of an RSV infection compared with influenza, with national hospitalization rates of 8.5 and 1.4 per 1000 children, respectively. The total number of workdays missed yearly by caregivers of children who required ED care was 246965 days for influenza infections and 716404 days for RSV infections.
For young children, RSV is associated with higher rates of ED visits, hospitalization, and caregiver resource use than is influenza. Our results provide data on the large number of children who receive outpatient care for influenza and RSV illnesses and serve to inform analyses of prevention programs and treatments for both influenza and RSV disease.
The cost-effectiveness of treating influenzalike illness (ILI) with oseltamivir in the United States was assessed.
A decision-analysis model was developed with a one-year time horizon to assess the cost-effectiveness of oseltamivir compared with usual care from societal and payer perspectives for four patient populations: high-risk adults, healthy adults, elderly adults, and children. The model used efficacy data from oseltamivir clinical trials and other published literature and assumed oseltamivir was effective only in individuals infected with influenza virus not resistant to oseltamivir and treated within 48 hours of symptom onset. Direct medical costs were based on resources used; indirect costs were estimated based on time lost from work due to illness and premature mortality. Base-case estimates were tested in one-way sensitivity and variability analyses.
From a societal perspective, oseltamivir was cost-effective across all populations modeled, with an incremental cost per quality-adjusted life-year gained of $5,388, $6,317, $7,652, and $16,176 for high-risk adults, children, elderly adults, and healthy adults, respectively. Results were similar from a payer perspective. When indirect costs were included (for all populations except elderly adults), oseltamivir was cost saving. In sensitivity analyses, oseltamivir remained cost-effective across all patient populations for all values tested, except the probability of developing influenza-related pneumonia. Variability analyses showed that oseltamivir remained cost-effective under most scenarios tested.
Base-case results and sensitivity analyses from a decision-analysis model found that treatment of ILI with oseltamivir was cost-effective compared with usual care from U.S. payer and societal perspectives in all patient populations studied when only direct costs were considered.
The impact of influenza has been recognized for centuries. Its seasonality in temperate climates has allowed estimates of mortality and severe morbidity, such as hospitalization, to be made statistically, without identifying cases virologically. Most influenza related mortality occurs in older individuals and those with underlying conditions. In addition to those groups, influenza hospitalizations occur in younger children and pregnant women. Morbidity is more difficult to identify and laboratory confirmation is required for precise estimates to be made. Younger individuals experience the highest frequency of illnesses caused by all subtypes. This has resulted in suggested strategies for community control by vaccinating children.
Many respiratory viruses cause morbidity in young children, but a licensed vaccine and effective oral therapy are available
only for influenzavirus. To determine the incidence of laboratory-confirmed influenza illness, we prospectively followed up
1665 healthy children aged <5 years who were enrolled in the Vanderbilt Vaccine Clinic at some point from 1974 through 1999.
Viral cultures were obtained when the children presented with clinical illness. The isolation of influenzavirus was associated
with an estimated 95 health care visits for children with symptoms of influenza, 46 episodes of acute otitis media, and 8
episodes of lower respiratory tract disease per 1000 children yearly. Rates of acute otitis media and lower respiratory tract
disease were highest among children aged <2 years. Hospitalizations associated with culture-positive influenza occurred at
an annual rate of 3–4 per 1000 children aged <2 years. Influenza is associated with substantial morbidity in otherwise healthy
children aged <5 years
The current healthcare environment requires the evaluation of both the costs and benefits of alternative interventions for a given clinical problem. Given the increased interest in the economic evaluation of healthcare interventions, this article briefly defines various forms of economic evaluations and describes some useful steps for conducting appraisals of cost-effectiveness analyses. Studies of competing methods of treatment of abdominal aortic aneurysms greater than 5 cm are used as a clinical example of interest to the readers of this Journal. Rather than actually conducting such an analysis with existing data, we describe the principles for conducting or reviewing an economic analysis with factitious data.
A substantial literature over the past thirty years has evaluated tradeoffs between money and fatality risks. These values in turn serve as estimates of the value of a statistical life. This article reviews more than 60 studies of mortality risk premiums from ten countries and approximately 40 studies that present estimates of injury risk premiums. This critical review examines a variety of econometric issues, the role of unionization in risk premiums, and the effects of age on the value of a statistical life. Our meta-analysis indicates an income elasticity of the value of a statistical life from about 0.5 to 0.6. The paper also presents a detailed discussion of policy applications of these value of a statistical life estimates and related issues, including risk-risk analysis. Copyright 2003 by Kluwer Academic Publishers
Healthcare Cost and Utilization Project (HCUP): 2014 National estimates on hospital use for all patients from the HCUP National Inpatient Sample (NIS). Agency for Healthcare Research and Quality