title: Mortality attributable to seasonal and pandemic influenza, Australia, 2003 to 2009, using a novel time series smoothing approach.
abstract: BACKGROUND
  Official statistics under-estimate influenza deaths. Time series methods allow the estimation of influenza-attributable mortality. The methods often model background, non-influenza mortality using a cyclic, harmonic regression model based on the Serfling approach. This approach assumes that the seasonal pattern of non-influenza mortality is the same each year, which may not always be accurate.
  
  
  OBJECTIVE
  To estimate Australian seasonal and pandemic influenza-attributable mortality from 2003 to 2009, and to assess a more flexible influenza mortality estimation approach.
  
  
  METHODS
  We used a semi-parametric generalized additive model (GAM) to replace the conventional seasonal harmonic terms with a smoothing spline of time ('spline model') to estimate influenza-attributable respiratory, respiratory and circulatory, and all-cause mortality in persons aged <65 and ≥ 65 years. Influenza A(H1N1)pdm09, seasonal influenza A and B virus laboratory detection time series were used as independent variables. Model fit and estimates were compared with those of a harmonic model.
  
  
  RESULTS
  Compared with the harmonic model, the spline model improved model fit by up to 20%. In <65 year-olds, the estimated respiratory mortality attributable to pandemic influenza A(H1N1)pdm09 was 0.5 (95% confidence interval (CI), 0.3, 0.7) per 100,000; similar to that of the years with the highest seasonal influenza A mortality, 2003 and 2007 (A/H3N2 years). In ≥ 65 year-olds, the highest annual seasonal influenza A mortality estimate was 25.8 (95% CI 22.2, 29.5) per 100,000 in 2003, five-fold higher than the non-statistically significant 2009 pandemic influenza estimate in that age group. Seasonal influenza B mortality estimates were negligible.
  
  
  CONCLUSIONS
  The spline model achieved a better model fit. The study provides additional evidence that seasonal influenza, particularly A/H3N2, remains an important cause of mortality in Australia and that the epidemic of pandemic influenza A (H1N1)pdm09 virus in 2009 did not result in mortality greater than seasonal A/H3N2 influenza mortality, even in younger age groups.
authors.affiliation: School of Public Health and Community Medicine, University of New South Wales, Kensington, New South Wales, Australia. dmusc@doh.health.nsw.gov.au
authors.forename: David J
authors.initials: DJ
authors.lastname: Muscatello
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Newall
authors.forename: Dominic E
authors.initials: DE
authors.lastname: Dwyer
authors.forename: C Raina
authors.initials: CR
authors.lastname: Macintyre
mesh_terms: D000368:Aged; D001315:Australia / Q000453:epidemiology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology*; D053122:Influenza A Virus, H3N2 Subtype / Q000502:physiology*; D007251:Influenza, Human / Q000401:mortality* / Q000821:virology*; D008875:Middle Aged; D015233:Models, Statistical; D058873:Pandemics / Q000706:statistics & numerical data*; D012621:Seasons; D013997:Time Factors