Burden and severity of influenza viruses

Abstract

Background: The seriousness of human influenza virus infection, in combination with the transmissibility of the virus, determines the impact that the virus will have in a population. However, the uncertainty surrounding the seriousness and changes in seriousness hindered the calibration of the early public health response.

Methods: I applied statistical models to population-based mortality data and hospitalizations among patients with laboratory-confirmed H1N1pdm09. I estimated the disease burden, retrospectively and prospectively determined seriousness of influenza virus infections including the risk of death on a per-infection basis (IFR) and on a per-hospitalization (HFR) of H1N1pdm09, and investigated changes in seriousness. I used serologic surveillance data to estimate the cumulative incidence of infection in a population, and used it as the denominator of the IFR. I also conducted systematic reviews and meta-analysis to summarize published estimates of the risk of death among cases (CFR) and HFR of the pandemic influenza H1N1pdm09 virus.

Results: I estimated that the first wave of H1N1pdm09 was associated with approximately 232 (95% confidence interval: 136, 328) excess deaths in all ages in Hong Kong, which was around 4 times the observed number of laboratory-confirmed deaths of H1N1pdm09. The point estimates for the IFR and HFR increased substantially with age. I included 77 estimates for the CFR from 50 published studies; whereas I included 187 estimates for the HFR from 184 published studies. The CFR was widely used to assess seriousness but the variation of a ‘case’ varied considerably in the literature. Variability in published estimates of the HFR was much less than variability in the CFR.

Conclusions: Early in the next pandemic, estimation of the HFR, IFR or symptomatic CFR may provide a timely picture of the seriousness of infection, particularly if presented in comparison between two influenza virus infections in the same setting. Ongoing monitoring of mortality and influenza activity could permit identification of changes in seriousness of influenza virus infections.