Influenza-associated Mortality Research Articles

Influenza-associated excess mortality in the Philippines, 2006-2015.

Influenza-associated mortality has not been quantified in the Philippines. Here, we constructed multiple negative binomial regression models to estimate the overall and age-specific excess mortality rates (EMRs) associated with influenza in the Philippines from 2006 to 2015. The regression analyses used all-cause mortality as the dependent variable and meteorological controls, time, influenza A and B positivity rates (lagged for up to two time periods), and annual and semiannual cyclical seasonality controls as independent variables. The regression models closely matched observed all-cause mortality. Influenza was estimated to account for a mean of 5,347 excess deaths per year (1.1% of annual all-cause deaths) in the Philippines, most of which (67.1%) occurred in adults aged ≥60 years. Influenza A accounted for 85.7% of all estimated excess influenza deaths. The annual estimated influenza-attributable EMR was 5.09 (95% CI: 2.20-5.09) per 100,000 individuals. The EMR was highest for individuals aged ≥60 years (44.63 [95% CI: 4.51-44.69] per 100,000), second highest for children aged less than 5 years (2.14 [95% CI: 0.44-2.19] per 100,000), and lowest for individuals aged 10 to 19 years (0.48 [95% CI: 0.10-0.50] per 100,000). Estimated numbers of excess influenza-associated deaths were considerably higher than the numbers of influenza deaths registered nationally. Our results suggest that influenza causes considerable mortality in the Philippines-to an extent far greater than observed from national statistics-especially among older adults and young children.

Burden of influenza-associated respiratory and circulatory mortality in India, 2010-2013.

BackgroundInfluenza causes substantial morbidity and mortality worldwide, however, reliable burden estimates from developing countries are limited, including India. We aimed to quantify influenza-associated mortality for India utilizing 2010-2013 nationally representative data sources for influenza virus circulation and deaths.MethodsVirological data were obtained from the influenza surveillance network of 10 laboratories led by National Institute of Virology, Pune covering eight states from 2010-2013. Death data were obtained from the nationally representative Sample Registration System for the same time period. Generalized linear regression with negative binomial distribution was used to model weekly respiratory and circulatory deaths by age group and proportion of specimens positive for influenza by subtype; excess deaths above the seasonal baseline were taken as an estimate of influenza-associated mortality counts and rates. Annual excess death rates and the 2011 India Census data were used to estimate national influenza-associated deaths.ResultsEstimated annual influenza-associated respiratory mortality rates were highest for those ≥65 years (51.1, 95% confidence interval (CI) = 9.2-93.0 deaths/100 000 population) followed by those <5 years (9.8, 95% CI = 0-21.8/100 000). Influenza-associated circulatory death rates were also higher among those ≥65 years (71.8, 95% CI = 7.9-135.8/100 000) as compared to those aged <65 years (1.9, 95% CI = 0-4.6/100 000). Across all age groups, a mean of 127 092 (95% CI = 64 046-190,139) annual influenza-associated respiratory and circulatory deaths may occur in India.ConclusionsEstimated influenza-associated mortality in India was high among children <5 years and adults ≥65 years. These estimates may inform strategies for influenza prevention and control in India, such as possible vaccine introduction.

Mortality burden from seasonal influenza in Chongqing, China, 2012–2018

ABSTRACT Purpose To estimate influenza-associated excess mortality rates (EMRs) in Chongqing from 2012 to 2018. Methods We obtained weekly mortality data for all-cause and four underlying causes of death (circulatory and respiratory disease (CRD), pneumonia and influenza (P&I), chronic obstructive pulmonary disease (COPD) and ischemic heart disease (IDH)), and influenza surveillance data, from 2012 to 2018. A negative-binomial regression model was used to estimate influenza-associated EMRs in two age groups (<65 years and ≥65 years). Results It was estimated that an annual average of 10025 influenza-associated deaths occurred in Chongqing, corresponding to 5.2% of all deaths. The average EMR for all-cause death associated with influenza was 33.5 (95% confidence interval (CI): 31.5–35.6) per 100 000 persons, and in separate cause-specific models we attributed 24.7 (95% CI: 23.3–26.0), 0.8 (95% CI: 0.7–0.8), 8.5 (95% CI: 8.1–9.0) and 5.0 (95% CI: 4.7–5.3) per 100 000 persons EMRs to CRD, P&I, COPD and IDH, respectively. The estimated EMR for influenza B virus was 20.6 (95% CI: 20.3–21.0), which was significantly higher than the rates of 5.3 (95% CI: 4.5–6.1) and 7.5 (95% CI: 6.7–8.3) for A(H3N2) and A(H1N1) pdm09 virus, respectively. The estimated EMR was 152.3 (95% CI: 136.1–168.4) for people aged ≥65 years, which was significantly higher than the rate for those aged <65 years (6.8, 95% CI: 6.3–7.2). Conclusions Influenza was associated with substantial EMRs in Chongqing, especially among elderly people. Influenza B virus caused a relatively higher excess mortality impact compared with A(H1N1)pdm09 and A(H3N2). It is advisable to optimize future seasonal influenza vaccine reimbursement policy in Chongqing to curb disease burden.

Diabetes and COVID-19.

After the recognition in December 2019 of a cluster of patients with pneumonia of unknown cause in Wuhan caused by the novel coronavirus, CoV-19,1 China and the world have faced the extraordinary challenge of a previously unrecognized viral illness with high infectivity.2 Every year, millions of persons (5%-15% of the world's population) contract influenza,3, 4 causing between 300 000 and 600 000 excess respiratory deaths.5 In China alone, recent estimates put the annual influenza-associated mortality rate at more than 88 000 persons,6 likely in excess of any potential outcome of coronavirus disease 2019 (COVID-19). Regardless of the potential for spread of COVID-19, as with influenza-related mortality,7 diabetes is an important risk factor for adverse outcome. Mortality rates among persons with diabetes in Hong Kong age 75 and over from pneumonia currently exceed mortality rates in this age group from cardiovascular disease and from cancer.8 Similar evidence of risk among persons with diabetes has been reported for the two earlier CoV infections, severe acute respiratory syndrome (SARS) beginning in 2002 and affecting more than 8000 persons, mainly in Asia9, 10 and the Middle East respiratory syndrome (MERS) in 2012 affecting more than 2000 persons, mainly in Saudi Arabia.11 As MERS-CoV binds to the receptor-binding domain of human dipeptidyl peptidase IV (DPP-IV), a transgenic mouse model expressing this DPP-IV receptor on pulmonary alveolar cells has been used to study the effect of diabetes in worsening disease severity, showing an association of diabetes with greater weight loss and greater pulmonary inflammation, with macrophage infiltrates similar to those seen clinically in the disease.12 We acknowledge the frontline medical staff working day and night in China to rescue critical cases and protect the public health. We know that these great efforts are now and will be in the future crucial in overcoming COVID-19. Providing care to people with diabetes is an important part of the effort. The Journal of Diabetes was started more than a decade ago in a spirit of collaboration between East and West addressing the epidemiology, etiology, pathogenesis, management, complications, and prevention of diabetes. The journal is issuing a call for submission of commentaries, original articles, and case reports regarding issues with COVID-19 in patients with diabetes, as well as descriptions of basic aspects of the interrelationships between diabetes and the novel CoV. We hope in this way to support the thousands of Chinese medical workers involving themselves in the care of patients with COVID-19, and we look forward to these efforts helping our goal of eradication of the disease. 从2019年12月在武汉发现一群由新型冠状病毒CoV-19引起的不明原因肺炎患者后, 中国乃至世界都面临着一种前所未见的高传染性病毒的挑战。每年都有数百万人(占世界人口的5%-15%)感染流感, 导致30万至60万人因呼吸系统疾病的额外死亡(excess respiratory deaths)。仅在中国, 最近估计每年与流感相关的死亡超过8.8万人, 很可能超过2019年冠状病毒病(COVID-19)所造成的潜在结果。不论COVID-19传播的潜在性如何, 它就像流感相关死亡一样, 糖尿病是其不良结果的一个重要风险因素。在香港, 75岁及以上糖尿病患者因肺炎而死亡的比率, 目前已超过这个年龄组别的心血管疾病和癌症死亡率。早些时候的两种冠状病毒感染在糖尿病患者中也报告了类似的风险证据:2002年初主要在亚洲的严重急性呼吸综合征(SARS), 它影响了8000多人；2012主要在沙特阿拉伯的中东呼吸综合征(MERS), 影响了2000多人。由于MERS-CoV可以与人二肽基肽酶IV(DPP-IV)的受体结合域结合, 利用在肺泡细胞上表达该DPP-IV受体的转基因小鼠模型研究糖尿病在疾病恶化中的作用, 结果显示糖尿病与体重减轻和更严重的肺部炎症有关, 并且可以看到和临床上相似的巨噬细胞浸润表现。 我们感谢一线医务工作者日以继夜的工作来拯救危重患者以及守护公众健康。我们知道这些努力在现在和将来都对战胜COVID-19至关重要。而为糖尿病患者提供相应治疗和护理也是这些努力中重要的一部分。《Journal of Diabetes》创刊于十多年前, 本着东西方合作的精神, 致力于研究糖尿病的流行病学、病因、发病机制、管理、并发症和预防。杂志呼吁读者投稿关于糖尿病患者感染COVID-19问题的评论、原创文章和病例报告, 以及对糖尿病和新型冠状病毒之间基本相互关系的描述。我们希望通过这种方式支持投身于COVID-19患者的治疗和护理中成千上万的中国医务工作者, 我们也期待着这些努力有助于我们实现根除这种疾病的目标。

Risk factors of influenza-associated mortality in several countries of the Eastern Mediterranean Region, 2007-2017

Risk factors of influenza-associated mortality in several countries of the Eastern Mediterranean Region, 2007-2017

Cardiovascular-targeted patient education and uptake of influenza vaccination in elderly patients

BackgroundElderly patients are especially vulnerable to influenza and its complications but their vaccination coverage remains unsatisfactory. DesignProspective study of hospitalized or ambulatory patients ≥65 years of age. A questionnaire on influenza vaccination was followed by short physician-administered verbal instruction on risk of 'heart-attack and stroke' following influenza, ameliorated by vaccination. ResultsMost patients (n = 100) had cardiovascular risk-factors, many had prior vascular disease. In 2018, 53 % did not intend to be vaccinated. None were aware of the association between influenza and risk of vascular events but when asked again ≤7 days after the intervention 34/53 (64 %) stated they will shortly get vaccinated. Charts of 27/34 recorded actual influenza vaccination when examined six weeks later (51 % of 'unwilling' patients). Together with the patients already planning to be vaccinated (47 + 27/100) the current target of 70 % vaccinated can be surpassed. ConclusionPending confirmation by a larger RCT, informing elderly patients of the substantial risk of vascular events following influenza and its modification by vaccination may constitute a simple, effective, costless and time-frugal method of changing many patients' often-negative attitudes towards seasonal influenza vaccination. The resulting increased vaccine uptake in vulnerable elderly patients, may improve their influenza-associated morbidity and mortality. Practice implicationsProviders discussing seasonal influenza vaccination with their patients could inform them of the substantially increased risk of myocardial infarction and ischemic stroke associated with acute influenza to overcome vaccine hesitancy.

Influenza in patients with cancer after 2009 pandemic AH1N1: An 8-year follow-up study in Mexico.

BackgroundImmunosupressed patients are at high risk of influenza‐related complications. Influenza AH1N1 has been hypothesized to induce worse outcomes in patients with malignancies, but after the A(H1N1)pdm09 few publications have analyzed the presentation and complications related to influenza afterward.ObjectivesWe aimed to describe the characteristics, risk factors, and outcomes of influenza in an oncologic center after the 2009 pandemic and to compare our case distribution to the National community acquired influenza databases in Mexico and the United States.MethodsWe reviewed the cases of confirmed influenza in patients with cancer from an oncological center in Mexico from April 2009 to April 2017. Data on severity and influenza type, malignancy, comorbidities, and outcomes were recorded. We correlated data between the Centers for Disease Control and Prevention (CDC) in the United States and SISVEFLU (Influenza Surveillance Program) in Mexico.ResultsOne hundred eighty‐eight patients were included; 75 (39.9%) had a solid neoplasm and 113 (60.1%) had hematologic malignancies. AH1N1 was the most frequent influenza type (54.2%). Patients with hematologic malignancies had more pneumonia (55% vs 25%, P < .001), needed more hospitalizations (75% vs 39% P < .001), had higher all‐cause mortality at 30 days (20% vs 9% P = .048) and influenza‐associated mortality (17% vs 7% P = .041). Thirty (16%) patients died within 30 days, and 24 (12.7%) were related to influenza. Influenza type was not associated with worse outcomes. Yearly occurrence of influenza reported by the CDC and SISVEFLU showed a significant correlation (ρ = 0.823, P = .006).ConclusionsAH1N1 was the dominant serotype. Patients with hematologic malignancies had more severe influenza and presented worse outcomes. Annual SISVEFLU and CDC surveillance information showed a similar distribution of cases along time but influenza serotypes did not match for all seasons.

Global mortality associated with seasonal influenza epidemics: New burden estimates and predictors from the GLaMOR Project.

BackgroundUntil recently, the World Health Organization (WHO) estimated the annual mortality burden of influenza to be 250 000 to 500 000 all-cause deaths globally; however, a 2017 study indicated a substantially higher mortality burden, at 290 000-650 000 influenza-associated deaths from respiratory causes alone, and a 2019 study estimated 99 000-200 000 deaths from lower respiratory tract infections directly caused by influenza. Here we revisit global and regional estimates of influenza mortality burden and explore mortality trends over time and geography.MethodsWe compiled influenza-associated excess respiratory mortality estimates for 31 countries representing 5 WHO regions during 2002-2011. From these we extrapolated the influenza burden for all 193 countries of the world using a multiple imputation approach. We then used mixed linear regression models to identify factors associated with high seasonal influenza mortality burden, including influenza types and subtypes, health care and socio-demographic development indicators, and baseline mortality levels.ResultsWe estimated an average of 389 000 (uncertainty range 294 000-518 000) respiratory deaths were associated with influenza globally each year during the study period, corresponding to ~ 2% of all annual respiratory deaths. Of these, 67% were among people 65 years and older. Global burden estimates were robust to the choice of countries included in the extrapolation model. For people <65 years, higher baseline respiratory mortality, lower level of access to health care and seasons dominated by the A(H1N1)pdm09 subtype were associated with higher influenza-associated mortality, while lower level of socio-demographic development and A(H3N2) dominance was associated with higher influenza mortality in adults ≥65 years.ConclusionsOur global estimate of influenza-associated excess respiratory mortality is consistent with the 2017 estimate, despite a different modelling strategy, and the lower 2019 estimate which only captured deaths directly caused by influenza. Our finding that baseline respiratory mortality and access to health care are associated with influenza-related mortality in persons <65 years suggests that health care improvements in low and middle-income countries might substantially reduce seasonal influenza mortality. Our estimates add to the body of evidence on the variation in influenza burden over time and geography, and begin to address the relationship between influenza-associated mortality, health and development.

Letter to the editor: influenza-associated mortality and oseltamivir: beware of misstepping into stepwise procedures.

Letter to the editor: influenza-associated mortality and oseltamivir: beware of misstepping into stepwise procedures.

Off-target effects of an insect cell-expressed influenza HA-pseudotyped Gag-VLP preparation in limiting postinfluenza Staphylococcus aureus infections

Clinical and historical data underscore the ability of influenza viruses to ally with Staphylococcus aureus and predispose the host for secondary bacterial pneumonia, which is a leading cause of influenza-associated mortality. This is fundamental because no vaccine for S. aureus is available and the number of antibiotic-resistant strains is alarmingly rising. Hence, this leaves influenza vaccination the only strategy to prevent postinfluenza staphylococcal infections. In the present work, we assessed the off-target effects of a Tnms42 insect cell-expressed BEI-treated Gag-VLP preparation expressing the HA of A/Puerto Rico/8/1934 (H1N1) in preventing S. aureus superinfection in mice pre-infected with a homologous or heterologous H1N1 viral challenge strain. Our results demonstrate that matched anti-hemagglutinin immunity elicited by a VLP preparation may suffice to prevent morbidity and mortality caused by lethal secondary bacterial infection. This effect was observed even when employing a single low antigen dose of 50 ng HA per animal. However, induction of anti-hemagglutinin immunity alone was not helpful in inhibiting heterologous viral replication and subsequent bacterial infection. Our results indicate the potential of the VLP vaccine approach in terms of immunogenicity but suggest that anti-HA immunity should not be considered as the sole preventive method for combatting influenza and postinfluenza bacterial infections.

Influenza-associated morbidity and mortality in Tunisia

Abstract Background Influenza is a highly contagious viral infection representing a public health problem worldwide with more than 10% of the population affected each year. In addition, severe complications and deaths may occur especially among high-risk groups. Our objectives was to assess the severity of influenza in Tunisia from 2015 to 2017 and to identify the isolated circulating viruses. Methods Basedon the network of ILI (Influenza-like illness) and SARI (Severe acute respiratory infection) Sentinel Sites and the National Influenza Center, we conducted a descriptive analysis of all data collected from 2015 to 2017. The case definitions of ILI and SARI were those recommended by WHO. Data entry was using Epi-Data and data analysis using SPSS-20. Results The total number of SARI cases during 2016-17 season was 614. The hospitalization rate was 0.7% which was higher than the 2015-16 season (0.19%). The majority of these severe cases were males (60,3%) and the group aged more than 65 years was the most affected. Comorbidities were reported in 58,7% of the cases, especially cardiovascular diseases, obesity and asthma. In 2016-17, the viruses identified in SARI cases were type A(H3N2) (47,7%), type B (40,9%) and type A (H1N1) pmd09 (4%). The lethality rate was lower than in the previous season (0.32% vs 20%) with two deaths reported in February. These deaths were due to virus B and virus AH3N2, comparing to 77% of deaths due to virus A (H1N1) pmd09 the season before. Conclusions Influenza severity vary from a season to another. The 2016-17 season was marked by higher rates of hospitalization but a lower lethality rate. This may be due to a lower circulation of the type A (H1N1) pmd09 virus, which virulence is much discussed. Influenza surveillance remains essential to detect any emerging novel pathogen and to guide decision-makers for future strategies. Key messages Seasonal influenza epidemics continue to have significant morbidity and mortality. Epidemiological and virological surveillance are highly essential for an early detection of epidemics and novel strains.

Influenza-associated mortality in hospital care: a retrospective cohort study of risk factors and impact of oseltamivir in an English teaching hospital, 2016 to 2017.

BackgroundEvidence of an oseltamivir treatment effect on influenza A(H3N2) virus infections in hospitalised patients is incomplete.AimsThis cohort study aimed to evaluate risk factors for death among PCR-confirmed hospitalised cases of seasonal influenza A(H3N2) of all ages and the impact of oseltamivir.MethodsParticipants included all 332 PCR-confirmed influenza A(H3N2) cases diagnosed between 30 August 2016 and 17 March 2017 in an English university teaching Hospital. Oseltamivir treatment effect on odds of inpatient death was assessed by backward stepwise multivariable logistic regression analysis.ResultsThe odds of death were reduced by two thirds (odds ratio (OR): 0.32; 95% confidence interval (CI): 0.11–0.93), in inpatients treated with a standard course of oseltamivir 75 mg two times daily for 5 days – compared with those untreated with oseltamivir, after adjustment for age, sex, current excess alcohol intake, receipt of 2016/17 seasonal influenza vaccine, serum haemoglobin and hospital vs community attribution of acquisition of influenza.ConclusionsOseltamivir treatment given according to National Institutes of Clinical Excellence (NICE); United States Centres for Disease Control and Prevention (CDC); Infectious Diseases Society of America (IDSA) and World Health Organization (WHO) guidelines was shown to be effective in reducing the odds of mortality in inpatients with PCR-confirmed seasonal influenza A(H3N2) after adjustment in a busy routine English hospital setting. Our results highlight the importance of hospitals complying with relevant guidelines for prompt seasonal influenza PCR testing and ensuring standard oseltamivir treatment to all PCR-confirmed cases of seasonal influenza.

1615. Influenza Outbreaks in Long-Term Care Facilities, 2017–2018 Influenza Season, Dallas, Texas

BackgroundHigh rates of influenza-related hospitalizations and deaths occurred in the United States during the 2017–2018 influenza season. A record number of influenza outbreaks were reported in long-term care facilities (LTCF) in Dallas County. Public health surveillance of influenza-related intensive care unit (ICU) admissions and deaths in acute care hospitals improved early identification of outbreaks in LTCFs.MethodsA confirmed LTCF influenza outbreak was defined as at least 1 lab-confirmed influenza case plus at least 1 case of influenza-like illness among residents or staff within 72 hours. Outbreaks were self-reported by facilities or identified by the health department during investigations of ICU hospitalizations and deaths. CDC guidance for influenza outbreak management was provided and daily active surveillance was continued for at least 1 week after the last case was identified. Data collected included: numbers of ill residents and staff, vaccination rates, dates of illness and chemoprophylaxis initiation, hospitalizations and deaths. Fisher exact tests and Chi-square were performed using SAS 9.4.ResultsDuring this influenza season, 32 confirmed influenza outbreaks were identified in Dallas County LTCFs: 17 in skilled nursing facilities (SNF), 13 in assisted-living facilities (ALF) and 2 in hybrid SNF/ALF. The average attack rate in residents was 9.8% (range: 1–35%). Influenza hospitalization rates were higher in ALF compared with SNF outbreaks (OR: 2.2). Influenza-associated mortality rates were higher in ALF compared with SNF (OR: 3.1). Of the 32 outbreaks, 20 (63%) were self-reported by facilities to public health and 12 (38%) were identified through health department review of influenza-associated ICU hospitalizations. Facilities where outbreak cases were identified through public health surveillance of ICU admissions had significantly lower overall attack rates (5.9% vs. 12.1%, P = 0.01) and shorter time to initiation of facility-wide chemoprophylaxis (0.4 vs. 2.4 days, P = 0.05).ConclusionActive surveillance of influenza-associated ICU admissions in acute-care hospitals facilitated the early identification of influenza outbreaks in LTCFs, which was associated with lower overall attack rates and shorter time to initiation of facility-wide chemoprophylaxis.Disclosures All authors: No reported disclosures.

Estimates of influenza-associated excess mortality by three regression models in Shanxi Province during 2013-2017

Objective: Using three models too estimate excess mortality associated with influenza of Shanxi Province during 2013-2017. Methods: Mortality data and influenza surveillance data of 11 cities of Shanxi Province from the 2013-2014 through 2016-2017 were used to estimate influenza-associated all cause deaths, circulatory and respiratory deaths and respiratory deaths. Three models were used: (i) Serfling regression, (ii)Poisson regression, (iii)General line model. Results: The total reported death cases of all cause were 157 733, annual death cases of all cause were 39 433, among these cases, male cases 93 831 (59.50%), cases above 65 years old 123 931 (78.57%). Annual influenza-associated excess mortality, for all causes, circulatory and respiratory deaths, respiratory deaths were 8.62 deaths per 100 000, 6.33 deaths per 100 000 and 0.68 deaths per 100 000 estimated by Serfling model, respectively; and 21.30 deaths per 100 000, 16.89 deaths per 100 000 and 2.14 deaths per 100 000 estimated by General line model, respectively; and 21.76 deaths per 100 000, 17.03 deaths per 100 000 and 2.05 deaths per 100 000, estimated by Poisson model, respectively. Influenza-related excess mortality was higher in people over 75 years old; influenza-associated excess mortalityfor all causes, circulatory and respiratory deaths, respiratory deaths were 259.67 deaths per 100 000, 229.90 deaths per 100 000 and 32.63 deaths per 100 000, estimated by GLM model, respectively; and 269.49 deaths per 100 000, 233.69 deaths per 100 000 and 31.27 deaths per 100 000, estimated by Poisson model,respectively. Conclusion: Excess mortality associated with influenza mainly caused by A (H3N2), Influenza caused the most associated death amongold people.

247EMF Impaired Human Influenza-Specific CD8+ T Cell Responses During Acute Symptomatic Seasonal Influenza Infection

Human influenza-specific CD8+ T cell responses during acute infection are not well characterized. Robust influenza-specific CD8+ T cell responses during acute infection are important in preventing influenza-associated morbidity and mortality in animal models, especially in animals without pre-existing anti-influenza antibodies. We set out to characterize influenza-specific CD8+ T cell responses in human subjects who presented to the emergency department with acute symptomatic seasonal influenza infection.

Patterns of seasonal and pandemic influenza-associated health care and mortality in Ontario, Canada

BackgroundMathematical and statistical models are used to project the future time course of infectious disease epidemics and the expected future burden on health care systems and economies. Influenza is a particularly important disease in this context because it causes annual epidemics and occasional pandemics. In order to forecast health care utilization during epidemics—and the effects of hospitalizations and deaths on the contact network and, in turn, on transmission dynamics—modellers must make assumptions about the lengths of time between infection, visiting a physician, being admitted to hospital, leaving hospital, and death. More reliable forecasts could be be made if the distributions of times between these types of events (“delay distributions”) were known.MethodsWe estimated delay distributions in the province of Ontario, Canada, between 2006 and 2010. To do so, we used encrypted health insurance numbers to link 1.34 billion health care billing records to 4.27 million hospital inpatient stays. Because the four year period we studied included three typical influenza seasons and the 2009 influenza pandemic, we were able to compare the delay distributions in non-pandemic and pandemic settings. We also estimated conditional probabilities such as the probability of hospitalization within the year if diagnosed with influenza.ResultsIn non-pandemic [pandemic] years, delay distribution medians (inter-quartile ranges) were: Service to Admission 6.3 days (0.1–17.6 days) [2.4 days (-0.3–13.6 days)], Admission to Discharge 3 days (1.4–5.9 days) [2.6 days (1.2–5.1 days)], Admission to Death 5.3 days (2.1–11 days) [6 days (2.6–13.1 days)]. (Service date is defined as the date, within the year, of the first health care billing that included a diagnostic code for influenza-like-illness.) Among individuals diagnosed with either pneumonia or influenza in a given year, 19% [16%] were hospitalized within the year and 3% [2%] died in hospital. Among all individuals who were hospitalized, 10% [12%] were diagnosed with pneumonia or influenza during the year and 5% [5%] died in hospital.ConclusionOur empirical delay distributions and conditional probabilities should help facilitate more accurate forecasts in the future, including improved predictions of hospital bed demands during influenza outbreaks, and the expected effects of hospitalizations on epidemic dynamics.

Influenza-associated excess respiratory mortality in China, 2010–15: a population-based study

The estimation of influenza-associated excess mortality in countries can help to improve estimates of the global mortality burden attributable to influenza virus infections. We did a study to estimate the influenza-associated excess respiratory mortality in mainland China for the 2010-11 through 2014-15 seasons. We obtained provincial weekly influenza surveillance data and population mortality data for 161 disease surveillance points in 31 provinces in mainland China from the Chinese Center for Disease Control and Prevention for the years 2005-15. Disease surveillance points with an annual average mortality rate of less than 0·4% between 2005 and 2015 or an annual mortality rate of less than 0·3% in any given years were excluded. We extracted data for respiratory deaths based on codes J00-J99 under the tenth edition of the International Classification of Diseases. Data on respiratory mortality and population were stratified by age group (age <60 years and ≥60 years) and aggregated by province. The overall annual population data of each province and national annual respiratory mortality data were compiled from the China Statistical Yearbook. Influenza surveillance data on weekly proportion of samples testing positive for influenza virus by type or subtype for 31 provinces were extracted from the National Sentinel Hospital-based Influenza Surveillance Network. We estimated influenza-associated excess respiratory mortality rates between the 2010-11 and 2014-15 seasons for 22 provinces with valid data in the country using linear regression models. Extrapolation of excess respiratory mortality rates was done using random-effect meta-regression models for nine provinces without valid data for a direct estimation of the rates. We fitted the linear regression model with the data from 22 of 31 provinces in mainland China, representing 83·0% of the total population. We estimated that an annual mean of 88 100 (95% CI 84 200-92 000) influenza-associated excess respiratory deaths occurred in China in the 5 years studied, corresponding to 8·2% (95% CI 7·9-8·6) of respiratory deaths. The mean excess respiratory mortality rates per 100 000 person-seasons for influenza A(H1N1)pdm09, A(H3N2), and B viruses were 1·6 (95% CI 1·5-1·7), 2·6 (2·4-2·8), and 2·3 (2·1-2·5), respectively. Estimated excess respiratory mortality rates per 100 000 person-seasons were 1·5 (95% CI 1·1-1·9) for individuals younger than 60 years and 38·5 (36·8-40·2) for individuals aged 60 years or older. Approximately 71 000 (95% CI 67 800-74 100) influenza-associated excess respiratory deaths occurred in individuals aged 60 years or older, corresponding to 80% of such deaths. Influenza was associated with substantial excess respiratory mortality in China between 2010-11 and 2014-15 seasons, especially in older adults aged at least 60 years. Continuous and high-quality surveillance data across China are needed to improve the estimation of the disease burden attributable to influenza and the best public health interventions are needed to curb this burden. National Science Fund for Distinguished Young Scholars, National Science and Technology Major Project of China, National Institute of Health Research, the Harvard Center for Communicable Disease Dynamics from the National Institute of General Medical Sciences, and the China-US Collaborative Program on Emerging and Re-emerging Infectious Disease.

Estimating Influenza-associated Mortality in Korea: The 2009-2016 Seasons.

ObjectivesEstimating influenza-associated mortality is important since seasonal influenza affects persons of all ages, causing severe illness or death. This study aimed to estimate influenza-associated mortality, considering both periodic changes and age-specific mortality by influenza subtypes.MethodsUsing the Microdata Integrated Service from Statistics Korea, we collected weekly mortality data including cause of death. Laboratory surveillance data of respiratory viruses from 2009 to 2016 were obtained from the Korea Centers for Disease Control and Prevention. After adjusting for the annual age-specific population size, we used a negative binomial regression model by age group and influenza subtype.ResultsOverall, 1 859 890 deaths were observed and the average rate of influenza virus positivity was 14.7% (standard deviation [SD], 5.8), with the following subtype distribution: A(H1N1), 5.0% (SD, 5.8); A(H3N2), 4.4% (SD, 3.4); and B, 5.3% (SD, 3.7). As a result, among individuals under 65 years old, 6774 (0.51%) all-cause deaths, 2521 (3.05%) respiratory or circulatory deaths, and 1048 (18.23%) influenza or pneumonia deaths were estimated. Among those 65 years of age or older, 30 414 (2.27%) all-cause deaths, 16 411 (3.42%) respiratory or circulatory deaths, and 4906 (6.87%) influenza or pneumonia deaths were estimated. Influenza A(H3N2) virus was the major contributor to influenza-associated all-cause and respiratory or circulatory deaths in both age groups. However, influenza A(H1N1) virus–associated influenza or pneumonia deaths were more common in those under 65 years old.ConclusionsInfluenza-associated mortality was substantial during this period, especially in the elderly. By subtype, influenza A(H3N2) virus made the largest contribution to influenza-associated mortality.

Macrophage migration inhibitory factor enhances influenza-associated mortality in mice.

Influenza-associated mortality continues to occur annually despite available antiviral therapies. New therapies that improve host immunity could reduce influenza virus disease burden. Targeting macrophage migration inhibitory factor (MIF) has improved the outcomes of certain inflammatory diseases, but its role in influenza viral infection is unclear. Here, we showed that, during influenza viral infection, Mif-deficient mice have less inflammation, viral load, and mortality compared with WT control mice; conversely, Tg mice, overexpressing Mif in alveolar epithelial cells, had higher inflammation, viral load, and mortality. Antibody-mediated blockade of MIF in WT mice during influenza viral infection improved their survival. Mif-deficient murine lungs showed reduced levels of parkin, a mitophagy protein that negatively regulates antiviral signaling, prior to infection and augmented antiviral type I/III IFN levels in the airspaces after infection as compared with WT lungs. Additionally, in vitro assays with human lung epithelial cells showed that treatment with recombinant human MIF increased the percentage of influenza virus-infected cells. In conclusion, our study reveals that MIF impairs antiviral host immunity and increases inflammation during influenza infection and suggests that targeting MIF could be therapeutically beneficial during influenza viral infection.

Influenza virus infection: an approach to identify predictors for in-hospital and 90-day mortality from patients in Vienna during the season 2017/18.

Seasonal influenza outbreaks are associated with increased mortality and hospitalisation rates. Herein we tried to identify predictors of mortality in hospitalised patients with influenza virus infection. In this exploratory retrospective observational single-centre-study we included all influenza-positive patients older than 18years who were hospitalised and treated at the flu-isolation-ward during the influenza season 2017/18. Diagnosis was based on point-of-care-test with the Alere™ i. First we performed χ2 tests and Mann-Whitney U tests to identify predictors of mortality. Significant variables were used in a stepwise-forward-logistic-regression-model to predict in-hospital and 90-day mortality. Of the 396 patients who tested positive for influenza 96 (24.2%) had influenza A and 300 (75.8%) influenza B. Twenty-two (5.6%) died in hospital and the 90-day mortality rate was 9.4%. In the stepwise logistic regression older age (OR 1.1 per year 95% CI 1.03-1.17), history of atrial fibrillation (OR 5.91 95% CI 1.91-18.34), dementia (OR 3.98 95% CI 1.24-12.78), leucocyte count (OR 1.11 per G/L 95% CI 1.03-1.20), pneumonia (OR 4.39 95% CI 1.44-13.39) and acute heart failure (OR 23.15 95% CI 4.33-123.76) increased the risk of in-hospital mortality. The risk for 90-day mortality was increased by older age (OR 1.04 per year 95% CI 1.01-1.07), history of atrial fibrillation (OR 3.1, 95% CI 1.36-7.05), history of congestive heart failure (OR 4.7 95% CI 1.94-11.48), pneumonia (OR 3.2 95% CI 1.45-6.91) and decreased by statin use (OR 0.28 95% CI 0.10-0.78). Older age, history of atrial fibrillation and pneumonia are associated with increased risk of influenza-associated in-hospital and 90-day mortality. Statin use may decrease 90-day mortality.