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Estimates of global seasonal influenza-associated respiratory mortality: a modelling study.

ABSTRACT: BACKGROUND:Estimates of influenza-associated mortality are important for national and international decision making on public health priorities. Previous estimates of 250?000-500?000 annual influenza deaths are outdated. We updated the estimated number of global annual influenza-associated respiratory deaths using country-specific influenza-associated excess respiratory mortality estimates from 1999-2015. METHODS:We estimated country-specific influenza-associated respiratory excess mortality rates (EMR) for 33 countries using time series log-linear regression models with vital death records and influenza surveillance data. To extrapolate estimates to countries without data, we divided countries into three analytic divisions for three age groups (<65 years, 65-74 years, and ?75 years) using WHO Global Health Estimate (GHE) respiratory infection mortality rates. We calculated mortality rate ratios (MRR) to account for differences in risk of influenza death across countries by comparing GHE respiratory infection mortality rates from countries without EMR estimates with those with estimates. To calculate death estimates for individual countries within each age-specific analytic division, we multiplied randomly selected mean annual EMRs by the country's MRR and population. Global 95% credible interval (CrI) estimates were obtained from the posterior distribution of the sum of country-specific estimates to represent the range of possible influenza-associated deaths in a season or year. We calculated influenza-associated deaths for children younger than 5 years for 92 countries with high rates of mortality due to respiratory infection using the same methods. FINDINGS:EMR-contributing countries represented 57% of the global population. The estimated mean annual influenza-associated respiratory EMR ranged from 0·1 to 6·4 per 100?000 individuals for people younger than 65 years, 2·9 to 44·0 per 100?000 individuals for people aged between 65 and 74 years, and 17·9 to 223·5 per 100?000 for people older than 75 years. We estimated that 291?243-645?832 seasonal influenza-associated respiratory deaths (4·0-8·8 per 100?000 individuals) occur annually. The highest mortality rates were estimated in sub-Saharan Africa (2·8-16·5 per 100?000 individuals), southeast Asia (3·5-9·2 per 100?000 individuals), and among people aged 75 years or older (51·3-99·4 per 100?000 individuals). For 92 countries, we estimated that among children younger than 5 years, 9243-105?690 influenza-associated respiratory deaths occur annually. INTERPRETATION:These global influenza-associated respiratory mortality estimates are higher than previously reported, suggesting that previous estimates might have underestimated disease burden. The contribution of non-respiratory causes of death to global influenza-associated mortality should be investigated. FUNDING:None.

SUBMITTER: Iuliano AD

PROVIDER: S-EPMC5935243 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Estimates of global seasonal influenza-associated respiratory mortality: a modelling study.

Iuliano A Danielle AD Roguski Katherine M KM Chang Howard H HH Muscatello David J DJ Palekar Rakhee R Tempia Stefano S Cohen Cheryl C Gran Jon Michael JM Schanzer Dena D Cowling Benjamin J BJ Wu Peng P Kyncl Jan J Ang Li Wei LW Park Minah M Redlberger-Fritz Monika M Yu Hongjie H Espenhain Laura L Krishnan Anand A Emukule Gideon G van Asten Liselotte L Pereira da Silva Susana S Aungkulanon Suchunya S Buchholz Udo U Widdowson Marc-Alain MA Bresee Joseph S JS

Lancet (London, England) 20171214 10127

<h4>Background</h4>Estimates of influenza-associated mortality are important for national and international decision making on public health priorities. Previous estimates of 250 000-500 000 annual influenza deaths are outdated. We updated the estimated number of global annual influenza-associated respiratory deaths using country-specific influenza-associated excess respiratory mortality estimates from 1999-2015.<h4>Methods</h4>We estimated country-specific influenza-associated respiratory exces ...[more]

PMID: 29248255

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Project description: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.

Project description:BackgroundSeasonal influenza virus is a common cause of acute lower respiratory infection (ALRI) in young children. In 2008, we estimated that 20 million influenza-virus-associated ALRI and 1 million influenza-virus-associated severe ALRI occurred in children under 5 years globally. Despite this substantial burden, only a few low-income and middle-income countries have adopted routine influenza vaccination policies for children and, where present, these have achieved only low or unknown levels of vaccine uptake. Moreover, the influenza burden might have changed due to the emergence and circulation of influenza A/H1N1pdm09. We aimed to incorporate new data to update estimates of the global number of cases, hospital admissions, and mortality from influenza-virus-associated respiratory infections in children under 5 years in 2018.MethodsWe estimated the regional and global burden of influenza-associated respiratory infections in children under 5 years from a systematic review of 100 studies published between Jan 1, 1995, and Dec 31, 2018, and a further 57 high-quality unpublished studies. We adapted the Newcastle-Ottawa Scale to assess the risk of bias. We estimated incidence and hospitalisation rates of influenza-virus-associated respiratory infections by severity, case ascertainment, region, and age. We estimated in-hospital deaths from influenza virus ALRI by combining hospital admissions and in-hospital case-fatality ratios of influenza virus ALRI. We estimated the upper bound of influenza virus-associated ALRI deaths based on the number of in-hospital deaths, US paediatric influenza-associated death data, and population-based childhood all-cause pneumonia mortality data in six sites in low-income and lower-middle-income countries.FindingsIn 2018, among children under 5 years globally, there were an estimated 109·5 million influenza virus episodes (uncertainty range [UR] 63·1-190·6), 10·1 million influenza-virus-associated ALRI cases (6·8-15·1); 870 000 influenza-virus-associated ALRI hospital admissions (543 000-1 415 000), 15 300 in-hospital deaths (5800-43 800), and up to 34 800 (13 200-97 200) overall influenza-virus-associated ALRI deaths. Influenza virus accounted for 7% of ALRI cases, 5% of ALRI hospital admissions, and 4% of ALRI deaths in children under 5 years. About 23% of the hospital admissions and 36% of the in-hospital deaths were in infants under 6 months. About 82% of the in-hospital deaths occurred in low-income and lower-middle-income countries.InterpretationA large proportion of the influenza-associated burden occurs among young infants and in low-income and lower middle-income countries. Our findings provide new and important evidence for maternal and paediatric influenza immunisation, and should inform future immunisation policy particularly in low-income and middle-income countries.FundingWHO; Bill & Melinda Gates Foundation.

Project description:BackgroundAssessing the mortality impact of the 2009 influenza A H1N1 virus (H1N1pdm09) is essential for optimizing public health responses to future pandemics. The World Health Organization reported 18,631 laboratory-confirmed pandemic deaths, but the total pandemic mortality burden was substantially higher. We estimated the 2009 pandemic mortality burden through statistical modeling of mortality data from multiple countries.Methods and findingsWe obtained weekly virology and underlying cause-of-death mortality time series for 2005-2009 for 20 countries covering ?35% of the world population. We applied a multivariate linear regression model to estimate pandemic respiratory mortality in each collaborating country. We then used these results plus ten country indicators in a multiple imputation model to project the mortality burden in all world countries. Between 123,000 and 203,000 pandemic respiratory deaths were estimated globally for the last 9 mo of 2009. The majority (62%-85%) were attributed to persons under 65 y of age. We observed a striking regional heterogeneity, with almost 20-fold higher mortality in some countries in the Americas than in Europe. The model attributed 148,000-249,000 respiratory deaths to influenza in an average pre-pandemic season, with only 19% in persons <65 y. Limitations include lack of representation of low-income countries among single-country estimates and an inability to study subsequent pandemic waves (2010-2012).ConclusionsWe estimate that 2009 global pandemic respiratory mortality was ?10-fold higher than the World Health Organization's laboratory-confirmed mortality count. Although the pandemic mortality estimate was similar in magnitude to that of seasonal influenza, a marked shift toward mortality among persons <65 y of age occurred, so that many more life-years were lost. The burden varied greatly among countries, corroborating early reports of far greater pandemic severity in the Americas than in Australia, New Zealand, and Europe. A collaborative network to collect and analyze mortality and hospitalization surveillance data is needed to rapidly establish the severity of future pandemics. Please see later in the article for the Editors' Summary.

Project description:BackgroundInfluenza is rarely confirmed with laboratory testing and accurate assessment of the overall burden of influenza is difficult. We used statistical modelling methods to generate updated, granular estimates of the number/rate of influenza-attributable hospitalisations and deaths in the United Kingdom. Such data are needed on a continuing basis to inform on cost-benefit analyses of treatment interventions, including vaccination.MethodsWeekly age specific data on hospital admissions (1997-2009) and on deaths (1997-2009) were obtained from national databases. Virology reports (1996-2009) of influenza and respiratory syncytial virus detections were provided by Public Health England. We used an expanded set of ICD-codes to estimate the burden of illness attributable to influenza which we refer to as 'respiratory disease broadly defined'. These codes were chosen to optimise the balance between sensitivity and specificity. A multiple linear regression model controlled for respiratory syncytial virus circulation, with stratification by age and the presence of comorbid risk status (conditions associated with severe influenza outcomes).ResultsIn the United Kingdom there were 28,516 hospitalisations and 7163 deaths estimated to be attributable to influenza respiratory disease in a mean season, with marked variability between seasons. The highest incidence rates of influenza-attributable hospitalisations and deaths were observed in adults aged 75+ years (252/100,000 and 131/100,000 population, respectively). Influenza B hospitalisations were highest among 5-17 year olds (12/100,000 population). Of all estimated influenza respiratory deaths in 75+ year olds, 50 % occurred out of hospital, and 25 % in 50-64 year olds. Rates of hospitalisations and death due to influenza-attributable respiratory disease were increased in adults identified as at-risk.ConclusionsOur study points to a substantial but highly variable seasonal influenza burden in all age groups, particularly affecting 75+ year olds. Effective influenza prevention or early intervention with anti-viral treatment in this age group may substantially impact the disease burden and associated healthcare costs. The high burden of influenza B hospitalisation among 5-17 year olds supports current United Kingdom vaccine policy to extend quadrivalent seasonal influenza vaccination to this age group.Trial registrationClinicalTrial.gov, NCT01520935.

Project description:BackgroundThe 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.MethodsWe 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.FindingsWe 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.InterpretationInfluenza 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.FundingNational 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.

Project description:BackgroundSuicide is one of the leading causes of death in the USA and population risk prediction models can inform decisions on the type, location, and timing of public health interventions. We aimed to develop a prediction model to estimate county-level suicide risk in the USA using population characteristics.MethodsWe obtained data on all deaths by suicide reported to the National Vital Statistics System between Jan 1, 2005, and Dec 31, 2019, and age, sex, race, and county of residence of the decedents were extracted to calculate baseline risk. We also obtained county-level annual measures of socioeconomic predictors of suicide risk (unemployment, weekly wage, poverty prevalence, median household income, and population density) and state-level prevalence of major depressive disorder and firearm ownership from US public sources. We applied conditional autoregressive models, which account for spatiotemporal autocorrelation in response and predictors, to estimate county-level suicide risk.FindingsEstimates derived from conditional autoregressive models were more accurate than from models not adjusted for spatiotemporal autocorrelation. Inclusion of suicide risk and protective covariates further reduced errors. Suicide risk was estimated to increase with each SD increase in firearm ownership (2·8% [95% credible interval (CrI) 1·8 to 3·9]), prevalence of major depressive episode (1·0% [0·4 to 1·5]), and unemployment rate (2·8% [1·9 to 3·8]). Conversely, risk was estimated to decrease by 4·3% (-5·1 to -3·2) for each SD increase in median household income and by 4·3% (-5·8 to -2·5) for each SD increase in population density. An increase in the heterogeneity in county-specific suicide risk was also observed during the study period.InterpretationArea-level characteristics and the conditional autoregressive models can estimate population-level suicide risk. Availability of near real-time situational data are necessary for the translation of these models into a surveillance setting. Monitoring changes in population-level risk of suicide could help public health agencies select and deploy targeted interventions quickly.FundingUS National Institute of Mental Health.

Project description:BackgroundThe COVID-19 pandemic priorities have focused on prevention, detection, and response. Beyond morbidity and mortality, pandemics carry secondary impacts, such as children orphaned or bereft of their caregivers. Such children often face adverse consequences, including poverty, abuse, and institutionalisation. We provide estimates for the magnitude of this problem resulting from COVID-19 and describe the need for resource allocation.MethodsWe used mortality and fertility data to model minimum estimates and rates of COVID-19-associated deaths of primary or secondary caregivers for children younger than 18 years in 21 countries. We considered parents and custodial grandparents as primary caregivers, and co-residing grandparents or older kin (aged 60-84 years) as secondary caregivers. To avoid overcounting, we adjusted for possible clustering of deaths using an estimated secondary attack rate and age-specific infection-fatality ratios for SARS-CoV-2. We used these estimates to model global extrapolations for the number of children who have experienced COVID-19-associated deaths of primary and secondary caregivers.FindingsGlobally, from March 1, 2020, to April 30, 2021, we estimate 1 134 000 children (95% credible interval 884 000-1 185 000) experienced the death of primary caregivers, including at least one parent or custodial grandparent. 1 562 000 children (1 299 000-1 683 000) experienced the death of at least one primary or secondary caregiver. Countries in our study set with primary caregiver death rates of at least one per 1000 children included Peru (10·2 per 1000 children), South Africa (5·1), Mexico (3·5), Brazil (2·4), Colombia (2·3), Iran (1·7), the USA (1·5), Argentina (1·1), and Russia (1·0). Numbers of children orphaned exceeded numbers of deaths among those aged 15-50 years. Between two and five times more children had deceased fathers than deceased mothers.InterpretationOrphanhood and caregiver deaths are a hidden pandemic resulting from COVID-19-associated deaths. Accelerating equitable vaccine delivery is key to prevention. Psychosocial and economic support can help families to nurture children bereft of caregivers and help to ensure that institutionalisation is avoided. These data show the need for an additional pillar of our response: prevent, detect, respond, and care for children.FundingUK Research and Innovation (Global Challenges Research Fund, Engineering and Physical Sciences Research Council, Medical Research Council), UK National Institute for Health Research, US National Institutes of Health, and Imperial College London.

Dataset Information

Estimates of global seasonal influenza-associated respiratory mortality: a modelling study.

Publications

Estimates of global seasonal influenza-associated respiratory mortality: a modelling study.

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