Influenza-attributable Mortality Research Articles

Inference of age-dependent case-fatality ratios for seasonal influenza virus subtypes A(H3N2) and A(H1N1)pdm09 and B lineages using data from the Netherlands.

Despite the known relatively high disease burden of influenza, data are lacking regarding a critical epidemiological indicator, the case-fatality ratio. Our objective was to infer age-group and influenza (sub)type specific values by combining modelled estimates of symptomatic incidence and influenza-attributable mortality. The setting was the Netherlands, 2011/2012 through 2019/2020 seasons. Sentinel surveillance data from general practitioners and laboratory testing were synthesised to supply age-group specific estimates of incidence of symptomatic infection, and ecological additive modelling was used to estimate influenza-attributable deaths. These were combined in an Bayesian inferential framework to estimate case-fatality ratios for influenza A(H3N2), A(H1N1)pdm09 and influenza B, per 5-year age-group. Case-fatality estimates were highest for influenza A(H3N2) followed by influenza B and then A(H1N1)pdm09 and were highest for the 85+ years age-group, at 4.76% (95% credible interval [CrI]: 4.52-5.01%) for A(H3N2), followed by influenza B at 4.08% (95% CrI: 3.77-4.39%) and A(H1N1)pdm09 at 2.51% (95% CrI: 2.09-2.94%). For 55-59 through 85+ years, the case-fatality risk was estimated to double with every 3.7years of age. These estimated case-fatality ratios, per influenza sub(type) and per age-group, constitute valuable information for public health decision-making, for assessing the retrospective and prospective value of preventative interventions such as vaccination and for health economic evaluations.

Global, regional and national estimates of influenza-attributable ischemic heart disease mortality.

Influenza virus infection is associated with incident ischemic heart disease (IHD) events. Here, we estimate the global, regional, and national IHD mortality burden attributable to influenza. We used vital registration data from deaths in adults ≥50 years (13.2 million IHD deaths as underlying cause) to assess the relationship between influenza activity and IHD mortality in a non-linear meta-regression framework from 2010 to 2019. This derived relationship was then used to estimate the global influenza attributable IHD mortality. We estimated the population attributable fraction (PAF) of influenza for IHD deaths based on the relative risk associated with a given level of weekly influenza test positivity rate and multiplied PAFs by IHD mortality from the Global Burden of Disease study. Influenza activity was associated with increased risk of IHD mortality across all countries analyzed. The mean PAF of influenza for IHD mortality was 3.9% (95% uncertainty interval [UI] 2.5-5.3%), ranging from <1% to 10%, depending on country and year. Globally, 299,858 IHD deaths (95% UI 191,216-406,809) in adults ≥50 years could be attributed to influenza, with the highest rates per 100,000 population in the Central Europe, Eastern Europe and Central Asia Region (32.3; 95% UI 20.6-43.8), and in the North Africa and Middle East Region (26.7; 95% UI 17-36.2). Influenza may contribute substantially to the burden of IHD. Our results suggest that if there were no influenza, an average of 4% of IHD deaths globally would not occur. Collaborative study funded by Sanofi Vaccines.

Quadrivalent adjuvanted haemagglutinin nanoparticle influenza vaccine: a step towards better protection of older adults from the constantly mutating H3N2 influenza viruses

The H3N2 influenza subtype has been highly researched due to its rapid mutational variability, which allows it to escape a preexisting immune response, meaning that the effectiveness of the H3N2 vaccine component has been extremely low over the past few seasons, since the 2014–15 season. 1 Martin ET Cheng C Petrie JG et al. Low influenza vaccine effectiveness against A(H3N2)-associated hospitalizations in 2016–2017 and 2017–2018 of the hospitalized adult influenza vaccine effectiveness network (HAIVEN). J Infect Dis. 2020; 223: 2062-2071 Crossref Scopus (5) Google Scholar It is therefore not surprising that in seasons when the H3N2 virus predominates, many countries have markedly higher mortality rates than in other seasons, especially in older people, owing to their reduced immune functions. 2 Vestergaard LS Nielsen J Krause TG et al. Excess all-cause and influenza-attributable mortality in Europe, December 2016 to February 2017. Euro Surveill. 2017; 2230506 Crossref PubMed Scopus (79) Google Scholar In attempts to overcome the issue of immunosenescence in older adults, new enhanced influenza vaccines are being developed, such as high-dose vaccines or vaccines formulated with potent adjuvants. To some extent, these approaches have helped increase the breadth of antibody immune responses and to stimulate virus-specific T-cell responses, thus improving vaccine effectiveness in the older population. 3 Beran J Reynales H Poder A et al. Prevention of influenza during mismatched seasons in older adults with an MF59-adjuvanted quadrivalent influenza vaccine: a randomised, controlled, multicentre, phase 3 efficacy study. Lancet Infect Dis. 2021; 21: 1027-1037 Summary Full Text Full Text PDF PubMed Scopus (15) Google Scholar , 4 DiazGranados CA Dunning AJ Kimmel M et al. Efficacy of high-dose versus standard-dose influenza vaccine in older adults. N Engl J Med. 2014; 371: 635-645 Crossref PubMed Scopus (495) Google Scholar Comparison of the safety and immunogenicity of a novel Matrix-M-adjuvanted nanoparticle influenza vaccine with a quadrivalent seasonal influenza vaccine in older adults: a phase 3 randomised controlled trialqNIV was well tolerated and produced qualitatively and quantitatively enhanced humoral and cellular immune response in older adults compared with IIV4. qNIV might enhance the effectiveness of seasonal influenza vaccination, and future studies to show clinical efficacy are planned. Full-Text PDF

Estimates of mortality attributable to COVID-19: a statistical model for monitoring COVID-19 and seasonal influenza, Denmark, spring 2020.

BackgroundTimely monitoring of COVID-19 impact on mortality is critical for rapid risk assessment and public health action.AimBuilding upon well-established models to estimate influenza-related mortality, we propose a new statistical Attributable Mortality Model (AttMOMO), which estimates mortality attributable to one or more pathogens simultaneously (e.g. SARS-CoV-2 and seasonal influenza viruses), while adjusting for seasonality and excess temperatures.MethodsData from Nationwide Danish registers from 2014-week(W)W27 to 2020-W22 were used to exemplify utilities of the model, and to estimate COVID-19 and influenza attributable mortality from 2019-W40 to 2020-W20.ResultsSARS-CoV-2 was registered in Denmark from 2020-W09. Mortality attributable to COVID-19 in Denmark increased steeply, and peaked in 2020-W14. As preventive measures and national lockdown were implemented from 2020-W12, the attributable mortality started declining within a few weeks. Mortality attributable to COVID-19 from 2020-W09 to 2020-W20 was estimated to 16.2 (95% confidence interval (CI): 12.0 to 20.4) per 100,000 person-years. The 2019/20 influenza season was mild with few deaths attributable to influenza, 3.2 (95% CI: 1.1 to 5.4) per 100,000 person-years.ConclusionAttMOMO estimates mortality attributable to several pathogens simultaneously, providing a fuller picture of mortality by COVID-19 during the pandemic in the context of other seasonal diseases and mortality patterns. Using Danish data, we show that the model accurately estimates mortality attributable to COVID-19 and influenza, respectively. We propose using standardised indicators for pathogen circulation in the population, to make estimates comparable between countries and applicable for timely monitoring.

Evaluation of influenza vaccination efficacy in reducing influenza-related complications and excess mortality in Northern Italy (2014-2017)

ABSTRACT Objective The main objective of this study was to estimate the efficacy of influenza vaccination in reducing influenza-attributable hospitalization and emergency room (ER) admission for severe complications and influenza-attributable excess mortality in individuals ≥65 years of age. Methods We analyzed the ≥65 years-old community (n = 952,822) afferent to the Brescia (Northern Italy) Health Protection Agency, considered an Italian population reference, to evaluate the efficacy of influenza vaccination (seasons 2014–17) in reducing deaths, ER-admissions, and hospitalizations for influenza-related complications in the elderly. Results A protective effect of influenza vaccination emerged in reducing hospitalization and ER admission for diseases of the respiratory system and for death from all causes in people ≥65 years. The major effect of influenza vaccination was the reduction in risk of death from all causes, increasing with age and comorbidity. Conclusion Influenza vaccination has reduced the number of ER admissions and hospitalizations caused by influenza-related complications and has prevented death among high-risk groups in elderly ≥65 years, resulting in social and public health cost savings. Stronger or new vaccination strategies are needed to improve vaccination rates among the elderly.

Estimated hospitalisations attributable to seasonal and pandemic influenza in Australia: 2001- 2013.

BackgroundInfluenza continues to cause seasonal epidemics and pandemics in humans. The burden of influenza is underestimated by traditional laboratory-based surveillance, and modelled estimates are required for influenza-attributable morbidity and mortality. We aimed to estimate the influenza-attributable hospitalisation in Australia, by influenza type.MethodsA generalised-additive regression model was used to estimate type- and age-specific influenza-attributable hospitalisation rates per 100,000 population by principal diagnosis in Australia, from 2001 through 2013. Weekly counts of laboratory-confirmed influenza notifications and by type, influenza A and B were used as covariates in the model. Main principal diagnosis categories of interest were influenza and pneumonia and respiratory admissions. A smoothing spline was used to control for unmeasured time varying factors. Results for 2009, in which the pandemic influenza A(H1N1)pdm09 virus circulated, were not included in annual averages and are reported separately.ResultsDuring the study period, the estimated annual average, all-age, annual respiratory hospitalisation rates attributable to seasonal influenza type A, B and total influenza were 45.4 (95% CI: 34.9, 55.9), 32.6 (95% CI: 22.8, 42.4), and 76.9 (95% CI: 73.6, 80.2) per 100,000 population, respectively. During 2009, the estimated total pandemic influenza-attributable, all-age, respiratory hospitalisation rate was 56.1 (95% CI: 47.4, 64.9) per 100,000. Older adults (≥85 years of age) experienced the highest influenza-attributable hospitalisation rates for both seasonal and 2009 pandemic influenza. Collinearity between influenza A and B time series in some years limited the ability of the model to resolve differences in influenza attribution between the two virus types.ConclusionBoth seasonal and pandemic influenza caused considerable morbidity in Australia during the years studied, particularly among older adults. The pandemic hospitalisation rate in 2009 was lower than the average overall annual rate for seasonal influenza, but young to middle aged adults experience a hospitalisation rate similar to that of severe seasonal influenza.

Investigating the impact of influenza on excess mortality in all ages in Italy during recent seasons (2013/14–2016/17 seasons)

ObjectivesIn recent years, Italy has been registering peaks in death rates, particularly among the elderly during the winter season. Influenza epidemics have been indicated as one of the potential determinants of such an excess. The objective of our study was to estimate the influenza-attributable contribution to excess mortality during the influenza seasons from 2013/14 to 2016/17 in Italy. MethodsWe used the EuroMomo and the FluMomo methods to estimate the annual trend of influenza-attributable excess death rate by age group. Population data were provided by the National Institute of Statistics, data on influenza like illness and confirmed influenza cases were provided by the National Institutes of Health. As an indicator of weekly influenza activity (IA) we adopted the Goldstein index, which is the product of the percentage of patients seen with influenza-like illness (ILI) and percentage of influenza-positive specimens, in a given week. ResultsWe estimated excess deaths of 7,027, 20,259, 15,801 and 24,981 attributable to influenza epidemics in the 2013/14, 2014/15, 2015/16 and 2016/17, respectively, using the Goldstein index. The average annual mortality excess rate per 100,000 ranged from 11.6 to 41.2 with most of the influenza-associated deaths per year registered among the elderly. However children less than 5 years old also reported a relevant influenza attributable excess death rate in the 2014/15 and 2016/17 seasons (1.05/100,000 and 1.54/100,000 respectively). ConclusionsOver 68,000 deaths were attributable to influenza epidemics in the study period. The observed excess of deaths is not completely unexpected, given the high number of fragile very old subjects living in Italy. In conclusion, the unpredictability of the influenza virus continues to present a major challenge to health professionals and policy makers. Nonetheless, vaccination remains the most effective means for reducing the burden of influenza, and efforts to increase vaccine coverage and the introduction of new vaccine strategies (such as vaccinating healthy children) should be considered to reduce the influenza attributable excess mortality experienced in Italy and in Europe in the last seasons.

Flucast: A Real-Time Tool to Predict Severity of an Influenza Season

BackgroundInfluenza causes serious illness requiring annual health system surge capacity, yet annual seasonal variation makes it difficult to forecast and plan for the severity of an upcoming season. Research shows that hospital and health system stakeholders indicate a preference for forecasting tools that are easy to use and understand to assist with surge capacity planning for influenza.ObjectiveThis study aimed to develop a simple risk prediction tool, Flucast, to predict the severity of an emerging influenza season.MethodsStudy data were obtained from the National Notifiable Diseases Surveillance System and Australian Influenza Surveillance Reports from the Department of Health, Australia. We tested Flucast using retrospective seasonal data for 11 Australian influenza seasons. We compared five different models using parameters known early in the season that may be associated with the severity of the season. To calibrate the tool, the resulting estimates of seasonal severity were validated against independent reports of influenza-attributable morbidity and mortality. The model with the highest predictive accuracy against retrospective seasonal activity was chosen as a best-fit model to develop the Flucast tool. The tool was prospectively tested against the 2018 and the emerging 2019 influenza season.ResultsThe Flucast tool predicted the severity of all retrospectively studied years correctly for influenza seasonal activity in Australia. With the use of real-time data, the tool provided a reasonable early prediction of a low to moderate season for the 2018 and severe seasonal activity for the upcoming 2019 season. The tool meets stakeholder preferences for simplicity and ease of use to assist with surge capacity planning.ConclusionsThe Flucast tool may be useful to inform future health system influenza preparedness planning, surge capacity, and intervention programs in real time, and can be adapted for different settings and geographic locations.

Mortality attributable to seasonal influenza in Greece, 2013 to 2017: variation by type/subtype and age, and a possible harvesting effect.

IntroductionEstimating the contribution of influenza to excess mortality in the population presents substantial methodological challenges.AimIn a modelling study we combined environmental, epidemiological and laboratory surveillance data to estimate influenza-attributable mortality in Greece, over four seasons (2013/14 to 2016/17), specifically addressing the lag dimension and the confounding effect of temperature.MethodsAssociations of influenza type/subtype-specific incidence proxies and of daily mean temperature with mortality were estimated with a distributed-lag nonlinear model with 30 days of maximum lag, separately by age group (all ages, 15–64 and ≥ 65 years old). Total and weekly deaths attributable to influenza and cold temperatures were calculated.ResultsOverall influenza-attributable mortality was 23.6 deaths per 100,000 population per year (95% confidence interval (CI): 17.8 to 29.2), and varied greatly between seasons, by influenza type/subtype and by age group, with the vast majority occurring in persons aged ≥ 65 years. Most deaths were attributable to A(H3N2), followed by influenza B. During periods of A(H1N1)pdm09 circulation, weekly attributable mortality to this subtype among people ≥ 65 years old increased rapidly at first, but then fell to zero and even negative, suggesting a mortality displacement (harvesting) effect. Mortality attributable to cold temperatures was much higher than that attributable to influenza.ConclusionsStudies of influenza-attributable mortality need to consider distributed-lag effects, stratify by age group and adjust both for circulating influenza virus types/subtypes and daily mean temperatures, in order to produce reliable estimates. Our approach addresses these issues, is readily applicable in the context of influenza surveillance, and can be useful for other countries.

Assessing optimal use of the standard dose adjuvanted trivalent seasonal influenza vaccine in the elderly

BackgroundDespite a long-standing vaccination programme, seasonal influenza remains a major public health problem in England, in particular for the elderly where a significant disease burden remains despite vaccine coverage approaching the WHO target of 75%. The recently licensed adjuvanted trivalent vaccines (TIV-ADJ) have been shown to offer greater protection for the elderly compared to the standard-dose non-adjuvanted trivalent vaccines (TIV), particularly for those individuals 75 years old and above for whom the TIV has limited effectiveness. We assessed the cost-effectiveness of the TIV-ADJ for use in the elderly. MethodsWe used a dynamic SEIR-type transmission model coupled with an economic evaluation framework, estimating the reduction in GP consultations, hospitalisations and influenza-attributable mortality. We assessed the optimal use of the TIV-ADJ by estimating the cost-effectiveness of programmes that used this vaccine in the 65+ and 75+ age groups. FindingsThe use of TIV-ADJ is highly cost-effective for both target age cohorts with incremental cost-effectiveness ratios well below the £20,000 per quality-adjusted life year (QALY) with over 90% probability that the vaccine is cost-effective at a cost-effectiveness threshold of £30,000 per QALY. InterpretationThe increased protection provided across all three influenza vaccine sub-types makes TIV-ADJ a more attractive option than TIV from the perspective of the healthcare provider, driven by the increased efficacy against A(H3N2). When deciding on the optimal use of the newly available vaccine it is important to consider the fact that TIV has very limited effectiveness for the 75+ age group, who would therefore get the greatest benefit from a more effective vaccine. FundingI-MOVE+ project (Integrated Monitoring of Vaccines in Europe) through the European Union’s Horizon 2020 research and innovation programme under grant agreement #634446 and the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Respiratory Infections at Imperial College London in partnership with Public Health England, as well as the NIHR HPRU in Immunisation at the London School of Hygiene and Tropical Medicine.

European all-cause excess and influenza-attributable mortality in the 2017/18 season: should the burden of influenza B be reconsidered?

ObjectivesWeekly monitoring of European all-cause excess mortality, the EuroMOMO network, observed high excess mortality during the influenza B/Yamagata dominated 2017/18 winter season, especially among elderly. We describe all-cause excess and influenza-attributable mortality during the season 2017/18 in Europe. MethodsBased on weekly reporting of mortality from 24 European countries or sub-national regions, representing 60% of the European population excluding the Russian and Turkish parts of Europe, we estimated age stratified all-cause excess morality using the EuroMOMO model. In addition, age stratified all-cause influenza-attributable mortality was estimated using the FluMOMO algorithm, incorporating influenza activity based on clinical and virological surveillance data, and adjusting for extreme temperatures. ResultsExcess mortality was mainly attributable to influenza activity from December 2017 to April 2018, but also due to exceptionally low temperatures in February-March 2018. The pattern and extent of mortality excess was similar to the previous A(H3N2) dominated seasons, 2014/15 and 2016/17. The 2017/18 overall all-cause influenza-attributable mortality was estimated to be 25.4 (95%CI 25.0-25.8) per 100,000 population; 118.2 (116.4-119.9) for persons aged 65. Extending to the European population this translates into over-all 152,000 deaths. ConclusionsThe high mortality among elderly was unexpected in an influenza B dominated season, which commonly are considered to cause mild illness, mainly among children. Even though A(H3N2) also circulated in the 2017/18 season and may have contributed to the excess mortality among the elderly, the common perception of influenza B only having a modest impact on excess mortality in the older population may need to be reconsidered.

Uptake and effectiveness of influenza vaccine in those aged 65 years and older in the United Kingdom, influenza seasons 2010/11 to 2016/17.

BackgroundIn 2016/17, seasonal influenza vaccine was less effective in those aged 65 years and older in the United Kingdom. We describe the uptake, influenza-associated mortality and adjusted vaccine effectiveness (aVE) in this age group over influenza seasons 2010/11–2016/17. Methods: Vaccine uptake in 2016/17 and five previous seasons were measured using a sentinel general practitioners cohort in England; the test-negative case-control design was used to estimate pooled aVE by subtype and age group against laboratory-confirmed influenza in primary care from 2010–2017. Results: Vaccine uptake was 64% in 65–69-year-olds, 74% in 70–74-year-olds and 80% in those aged 75 and older. Overall aVE was 32.5% (95% CI: 11.6 to 48.5); aVE by sub-type was 60.8% (95% CI: 33.9 to 76.7) and 50.0% (95% CI: 21.6 to 68.1) against influenza A(H1N1)pdm09 and influenza B, respectively, but only 5.6% (95% CI: - 39.2 to 35.9) against A(H3N2). Against all laboratory-confirmed influenza aVE was 45.2% (95% CI: 25.1 to 60.0) in 65–74 year olds; - 26.2% (95% CI: - 149.3 to 36.0) in 75–84 year olds and - 3.2% (95% CI: - 237.8 to 68.5) in those aged 85 years and older. Influenza-attributable mortality was highest in seasons dominated by A(H3N2). Conclusions: Vaccine uptake with non-adjuvanted, normal-dose vaccines remained high, with evidence of effectiveness against influenza A(H1N1)pdm09 and B, though poor against A(H3N2), particularly in those aged 75 years and older. Forthcoming availability of newly licensed vaccines with wider use of antivirals can potentially further improve prevention and control of influenza in this group.

Years of Life Lost Due to Influenza-Attributable Mortality in Older Adults in the Netherlands: A Competing-Risks Approach.

We estimated the influenza mortality burden in adults aged 60 years or older in the Netherlands in terms of years of life lost, taking into account competing mortality risks. Weekly laboratory surveillance data for influenza and other respiratory pathogens and weekly extreme temperature served as covariates in Poisson regression models fitted to weekly mortality data, specific to age group, for the period 1999-2000 through 2012-2013. Burden for age groups 60-64 years through 85-89 years was computed as years of life lost before age 90 (YLL90), using restricted mean lifetime survival analysis and accounting for competing risks. Influenza-attributable mortality burden was greatest for persons aged 80-84 years, at 914 YLL90 per 100,000 persons (95% uncertainty interval: 867, 963), followed by persons aged 85-89 years (787 YLL90/100,000; 95% uncertainty interval: 741, 834). Ignoring competing mortality risks in the computation of influenza-attributable YLL90 would lead to substantial overestimation of burden, from 3.5% for persons aged 60-64 years to 82% for those aged 80-89 years at death. Failure to account for competing mortality risks has implications for the accuracy of disease-burden estimates, especially among persons aged 80 years or older. Because the mortality burden borne by the elderly is notably high, prevention initiatives may benefit from being redesigned to more effectively prevent infection in the oldest age groups.

Excess all-cause and influenza-attributable mortality in Europe, December 2016 to February 2017

Since December 2016, excess all-cause mortality was observed in many European countries, especially among people aged ≥ 65 years. We estimated all-cause and influenza-attributable mortality in 19 European countries/regions. Excess mortality was primarily explained by circulation of influenza virus A(H3N2). Cold weather snaps contributed in some countries. The pattern was similar to the last major influenza A(H3N2) season in 2014/15 in Europe, although starting earlier in line with the early influenza season start.

Maternal Influenza Immunization and Adverse Birth Outcomes: Using Data and Practice to Inform Theory and Research Design

Maternal influenza immunization can reduce influenza-attributable morbidity and mortality among pregnant women and infants who are too young to be vaccinated. Data from empirical studies also support the hypothesis that immunization can protect the fetus against adverse outcomes if the mother is exposed to influenza. In their theoretical analysis in the Journal, Hutcheon et al. (Am J Epidemiol. 2016;184(3):227–232) critiqued the existing evidence of the fetal benefits of maternal influenza immunization by calculating the sample sizes needed to demonstrate hypothetical reductions in risk and concluded that the benefits observed in empirical studies are likely implausible. However, in their analysis, they did not take into account multiple fundamental characteristics of influenza epidemiology, including the time-variable effects of influenza illness and vaccination during pregnancy, or well-known differences in disease epidemiology between seasons, populations, and geographic regions. Although these and other factors might affect the magnitude of fetal benefit conferred by maternal influenza immunization, studies in which investigators have accounted for influenza circulation have demonstrated a consistent protective effect against a variety of adverse birth outcomes; those studies include the only randomized controlled trial designed a priori and adequately powered to do so. Only a comprehensive and nuanced assessment of the evidence base will allow for effective translation of these data into a global immunization policy.

Seasonal Influenza Infections and Cardiovascular Disease Mortality.

Cardiovascular deaths and influenza epidemics peak during winter in temperate regions. To quantify the temporal association between population increases in seasonal influenza infections and mortality due to cardiovascular causes and to test if influenza incidence indicators are predictive of cardiovascular mortality during the influenza season. Time-series analysis of vital statistics records and emergency department visits in New York City, among cardiovascular deaths that occurred during influenza seasons between January 1, 2006, and December 31, 2012. The 2009 novel influenza A(H1N1) pandemic period was excluded from temporal analyses. Emergency department visits for influenza-like illness, grouped by age (≥0 years and ≥65 years) and scaled by laboratory surveillance data for viral types and subtypes, in the previous 28 days. Mortality due to cardiovascular disease, ischemic heart disease, and myocardial infarction. Among adults 65 years and older, who accounted for 83.0% (73 363 deaths) of nonpandemic cardiovascular mortality during influenza seasons, seasonal average influenza incidence was correlated year to year with excess cardiovascular mortality (Pearson correlation coefficients ≥0.75, P ≤ .05 for 4 different influenza indicators). In daily time-series analyses using 4 different influenza metrics, interquartile range increases in influenza incidence during the previous 21 days were associated with an increase between 2.3% (95% CI, 0.7%-3.9%) and 6.3% (95% CI, 3.7%-8.9%) for cardiovascular disease mortality and between 2.4% (95% CI, 1.1%-3.6%) and 6.9% (95% CI, 4.0%-9.9%) for ischemic heart disease mortality among adults 65 years and older. The associations were most acute and strongest for myocardial infarction mortality, with each interquartile range increase in influenza incidence during the previous 14 days associated with mortality increases between 5.8% (95% CI, 2.5%-9.1%) and 13.1% (95% CI, 5.3%-20.9%). Out-of-sample prediction of cardiovascular mortality among adults 65 years and older during the 2009-2010 influenza season yielded average estimates with 94.0% accuracy using 4 different influenza metrics. Emergency department visits for influenza-like illness were associated with and predictive of cardiovascular disease mortality. Retrospective estimation of influenza-attributable cardiovascular mortality burden combined with accurate and reliable influenza forecasts could predict the timing and burden of seasonal increases in cardiovascular mortality.

Using Laboratory Data to Aid Early Warning in Prospective Influenza Mortality Surveillance

Many countries prospectively monitor influenza-attributable mortality using a variation of the Serfling seasonal time series model. Our aim is to demonstrate use of routine laboratory-confirmed influenza surveillance data to forecast predicted influenza-attributable deaths during the current influenza season. The two models provided a reasonable forecast for 2012. The model forecasts of weekly deaths during 2012 were compared against observed deaths using root mean squared error (RMSE). The results shown that the model including influenza type A and B provided a better fit. Here, we demonstrated a time series model for influenza-attributable mortality surveillance based on laboratory surveillance information.

Abstract P325: Emergency Department Visit Rates for Influenza-like Illness Can be Used to Predict Seasonal Cardiovascular Disease Mortality Rates Among Older Adults

Introduction: In temperate regions, cardiovascular deaths and influenza epidemics peak with regularity during the winter months. Hypothesis: We assessed the hypothesis that population increases in seasonal influenza infections are associated with a rise in mortality due to cardiovascular causes, and that influenza incidence can be used to predict cardiovascular mortality rates during the influenza season. Methods: We used time series regression models, adjusted for season and time trend, to quantify the temporal association between influenza incidence and cardiovascular mortality during the influenza season in New York City. Mortality data on date of death, age, and underlying cause of death were obtained from the New York City Office of Vital Statistics. Daily mortality counts from 2006 to 2012 were aggregated for all cardiovascular causes (International Classification of Diseases, Revision 10 (ICD-10) codes I00-I99), ischemic heart disease (ICD-10 codes I20-I25), and myocardial infarction (ICD-10 code I21). Influenza incidence was represented using four different measures: emergency department visits for influenza-like illness, grouped by age ≥ 0 and age ≥ 65 years, and these same measures scaled by laboratory surveillance data for viral types/sub-types. The 2009 H1N1 pandemic period was excluded from temporal analyses and reserved for out-of-sample prediction. Results: There were 73,384 cardiovascular deaths among adults age ≥ 65 years during the influenza seasons between 2006 and 2012, excluding the 2009 H1N1 pandemic period. Interquartile range increases of the four indicators of influenza incidence in the previous 21 days were associated with increases in cardiovascular mortality of between 2.3% (95% confidence interval (CI): 0.7%, 3.9%) and 6.3% (95% CI: 3.6%, 8.9%), and increases in ischemic heart disease mortality of between 2.4% (95% CI: 1.1%, 3.7%) and 7.0% (95% CI: 4.1%, 10.0%). Associations were most acute and strongest for myocardial infarction mortality, with interquartile range increases for the four influenza indicators during the previous 14 days associated with mortality increases between 5.9% (95% CI: 2.7%, 9.2%) and 12.8% (95% CI: 5.1%, 20.6%). Out-of-sample prediction of cardiovascular mortality among adults age ≥ 65 years during the 2009-2010 influenza season yielded average estimates with 94.4% accuracy. Conclusions: Emergency department visits for influenza-like illness are associated with and predictive of cardiovascular disease mortality in New York City. Retrospective estimation of influenza-attributable cardiovascular mortality burden, combined with accurate and reliable influenza forecasts, could predict the timing and burden of seasonal increases in cardiovascular mortality.

Burden of Influenza-Related Hospitalizations and Attributable Mortality in Pediatric Acute Lymphoblastic Leukemia.

Influenza can be severe in patients with underlying malignancy; however, the rate of influenza hospitalizations and attributable mortality in children with cancer is unknown. We performed a retrospective cohort study among 10 698 children with new-onset acute lymphoblastic leukemia (ALL) from 41 US children's hospitals between January 1999 and September 2011. Influenza-related hospitalizations were identified using ICD-9 discharge diagnosis codes, excluding hospitalizations during low-prevalence influenza periods. Follow-up was censored at the earliest of 5 events: end of study period, expected end of chemotherapy, last known hospitalization, hematopoietic stem cell transplant, or death. Data were collected on hospitalization characteristics and resource utilization. Hospitalization rates were calculated using season-adjusted person-time. Crude attributable in-hospital mortality was calculated using baseline mortality for noninfluenza hospitalizations during the same period. Subgroup analysis was performed by time from ALL diagnosis and by age category. The rate of influenza-related hospitalizations was 618.3 per 100 000 person-months. Rates were similar by time from ALL diagnosis and across age categories. Overall attributable in-hospital mortality was 1.0% (95% confidence interval [CI], 0.3%-2.3%) and was highest for children <6 months from diagnosis (1.6%; 95% CI, 0.4%-4.5%) and children <2 years of age (6.7%; 95% CI, 1.3%-22.7%). Total length of stay, days of broad-spectrum antibiotic exposure, and duration of intensive care were significantly greater for influenza-related hospitalizations compared with noninfluenza hospitalizations. The burden of influenza-related hospitalizations in children with ALL is high and associated with significantly increased resource utilization and attributable mortality.

Estimates of mortality attributable to influenza and RSV in the United States during 1997-2009 by influenza type or subtype, age, cause of death, and risk status.

BackgroundInfluenza and respiratory syncytial virus (RSV) cause substantial mortality from respiratory and other causes in the USA, especially among people aged 65 and older.ObjectivesWe estimated the influenza-attributable mortality and RSV-attributable mortality in the USA, stratified by age and risk status, using outcome definitions with different sensitivity and specificity.MethodsInfluenza- and RSV-associated mortality was assessed from October 1997–March 2009 using multiple linear regression modeling on data obtained from designated government repositories.ResultsThe main outcomes and measures included mortality outcome definitions—pneumonia and influenza, respiratory broad, and cardiorespiratory disease. A seasonal average of 10 682 (2287–16 363), 19 100 (4862–29 245), and 28 169 (6797–42 316) deaths was attributed to influenza for pneumonia and influenza, respiratory broad, and cardiorespiratory outcome definitions, respectively. Corresponding values for RSV were 6211 (4584–8169), 11 300 (8546–14 244), and 17 199 (13 384–21 891), respectively. A/H3N2 accounted for seasonal average of 71% influenza-attributable deaths; influenza B accounted for most (51–95%) deaths during four seasons. Approximately 70% influenza-attributable deaths occurred in individuals ≥75 years, with increasing mortality for influenza A/H3N2 and B, but not A/H1N1. In children aged 0–4 years, an average of 97 deaths was attributed to influenza (A/H3N2 = 49, B = 33, A/H1N1 = 15) and 165 to respiratory broad outcome definition (RSV). Influenza-attributable mortality was 2·94-fold higher in high-risk individuals.ConclusionsInfluenza-attributable mortality was highest in older and high-risk individuals and mortality in children was higher than reported in passive Centers for Disease Control and Prevention surveillance. Influenza B-attributable mortality was higher than A in four of 12 seasons. Our estimates represent an updated assessment of influenza-attributable mortality in the USA.