Mortality Attributable to Influenza and RSV in the U.S.
Mortality Attributable to Influenza and RSV in the U.S.
Background Influenza and respiratory syncytial virus (RSV) cause substantial mortality from respiratory and other causes in the USA, especially among people aged 65 and older.
Objectives We 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.
Methods Influenza- and RSV-associated mortality was assessed from October 1997–March 2009 using multiple linear regression modeling on data obtained from designated government repositories.
Results The 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.
Conclusions Influenza-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.
In the United States, annual wintertime influenza epidemics are associated with substantial numbers of medically attended outpatient visits, hospitalizations, and deaths. Estimates of influenza burden have been instrumental in increasing clinical awareness, informing vaccination policy, and guiding influenza prevention and control strategies. Influenza infections are often clinically under-recognized, not laboratory-confirmed when suspected, or difficult to confirm virologically because the virus is no longer detectable when patients present with complications of influenza (e.g., exacerbations of underlying cardiorespiratory disease). Consequently, conventional observational methods result in significant underestimates of influenza burden. Annual wintertime epidemics of respiratory syncytial virus (RSV) often coincide with influenza epidemics, and directly estimating the burden of RSV has presented the same challenges.
For decades, a variety of statistical multiple regression modeling techniques has been used by the United States (US) Centers for Disease Control and Prevention (CDC) and other groups to indirectly estimate the burden of influenza, including the burden attributable to secondary complications. The incidence of influenza-attributable disease outcomes has typically been estimated by statistically modeling the excess burden of respiratory, cardiorespiratory, or other clinical outcomes recorded during periods of influenza virus circulation over background rates of the same outcomes recorded outside these periods. More recently, modeling techniques that include pathogen-specific virological surveillance data [or International Classification of Disease (ICD)-coded outcomes data] as additional model variables have been used. These models allow for estimation of the burden of disease from multiple pathogens while simultaneously controlling for other potential disease drivers even during periods of influenza virus circulation.
Detailed published estimates of influenza-attributable mortality by age, type, and subtype have not been updated by the CDC for seasons beyond the 2006–2007 influenza season. Because patterns of influenza virus circulation and the number of associated disease outcomes can change from decade to decade, updated burden estimates are needed to characterize changes in epidemiology. In addition, RSV is increasingly recognized as an important illness in elderly and high-risk adults, with a similar burden to non-pandemic influenza A. In designing the present study, we sought to generate updated and granular estimates of influenza- and RSV-attributable mortality in the USA according to six age strata, type, or subtype of influenza virus, and by high or low risk status. Moreover, because modeled excess mortality estimates may be attenuated for highly sensitive and less specific outcomes often used, such as cardiorespiratory mortality, we explored outcomes with a range of sensitivity and specificity. Those included a broader respiratory outcome definition ("respiratory broad") which we hypothesized might provide a better trade-off between the under- or over-estimation of mortality associated with the classical pneumonia and influenza (P&I) or cardiorespiratory definitions, respectively.
Abstract and Introduction
Abstract
Background Influenza and respiratory syncytial virus (RSV) cause substantial mortality from respiratory and other causes in the USA, especially among people aged 65 and older.
Objectives We 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.
Methods Influenza- and RSV-associated mortality was assessed from October 1997–March 2009 using multiple linear regression modeling on data obtained from designated government repositories.
Results The 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.
Conclusions Influenza-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.
Introduction
In the United States, annual wintertime influenza epidemics are associated with substantial numbers of medically attended outpatient visits, hospitalizations, and deaths. Estimates of influenza burden have been instrumental in increasing clinical awareness, informing vaccination policy, and guiding influenza prevention and control strategies. Influenza infections are often clinically under-recognized, not laboratory-confirmed when suspected, or difficult to confirm virologically because the virus is no longer detectable when patients present with complications of influenza (e.g., exacerbations of underlying cardiorespiratory disease). Consequently, conventional observational methods result in significant underestimates of influenza burden. Annual wintertime epidemics of respiratory syncytial virus (RSV) often coincide with influenza epidemics, and directly estimating the burden of RSV has presented the same challenges.
For decades, a variety of statistical multiple regression modeling techniques has been used by the United States (US) Centers for Disease Control and Prevention (CDC) and other groups to indirectly estimate the burden of influenza, including the burden attributable to secondary complications. The incidence of influenza-attributable disease outcomes has typically been estimated by statistically modeling the excess burden of respiratory, cardiorespiratory, or other clinical outcomes recorded during periods of influenza virus circulation over background rates of the same outcomes recorded outside these periods. More recently, modeling techniques that include pathogen-specific virological surveillance data [or International Classification of Disease (ICD)-coded outcomes data] as additional model variables have been used. These models allow for estimation of the burden of disease from multiple pathogens while simultaneously controlling for other potential disease drivers even during periods of influenza virus circulation.
Detailed published estimates of influenza-attributable mortality by age, type, and subtype have not been updated by the CDC for seasons beyond the 2006–2007 influenza season. Because patterns of influenza virus circulation and the number of associated disease outcomes can change from decade to decade, updated burden estimates are needed to characterize changes in epidemiology. In addition, RSV is increasingly recognized as an important illness in elderly and high-risk adults, with a similar burden to non-pandemic influenza A. In designing the present study, we sought to generate updated and granular estimates of influenza- and RSV-attributable mortality in the USA according to six age strata, type, or subtype of influenza virus, and by high or low risk status. Moreover, because modeled excess mortality estimates may be attenuated for highly sensitive and less specific outcomes often used, such as cardiorespiratory mortality, we explored outcomes with a range of sensitivity and specificity. Those included a broader respiratory outcome definition ("respiratory broad") which we hypothesized might provide a better trade-off between the under- or over-estimation of mortality associated with the classical pneumonia and influenza (P&I) or cardiorespiratory definitions, respectively.