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Case Fatality Risk of Influenza A (H1N1pdm09): A Systematic Review

Wong, Jessica Y.a; Kelly, Heathb,c; Ip, Dennis K. M.a; Wu, Joseph T.a; Leung, Gabriel M.a; Cowling, Benjamin J.a

doi: 10.1097/EDE.0b013e3182a67448
Infectious Diseases

Background: During the 2009 influenza pandemic, uncertainty surrounding the seriousness of human infections with the H1N1pdm09 virus hindered appropriate public health response. One measure of seriousness is the case fatality risk, defined as the probability of mortality among people classified as cases.

Methods: We conducted a systematic review to summarize published estimates of the case fatality risk of the pandemic influenza H1N1pdm09 virus. Only studies that reported population-based estimates were included.

Results: We included 77 estimates of the case fatality risk from 50 published studies, about one-third of which were published within the first 9 months of the pandemic. We identified very substantial heterogeneity in published estimates, ranging from less than 1 to more than 10,000 deaths per 100,000 cases or infections. The choice of case definition in the denominator accounted for substantial heterogeneity, with the higher estimates based on laboratory-confirmed cases (point estimates = 0–13,500 per 100,000 cases) compared with symptomatic cases (point estimates = 0–1,200 per 100,000 cases) or infections (point estimates = 1–10 per 100,000 infections). Risk based on symptomatic cases increased substantially with age.

Conclusions: Our review highlights the difficulty in estimating the seriousness of infection with a novel influenza virus using the case fatality risk. In addition, substantial variability in age-specific estimates complicates the interpretation of the overall case fatality risk and comparisons among populations. A consensus is needed on how to define and measure the seriousness of infection before the next pandemic.

From the aSchool of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China; bVictorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria, Australia; and cNational Centre for Epidemiology and Population Health, Australian National University, Canberra, Australian Capital Territory, Australia.

This work received financial support from the Harvard Center for Communicable Disease Dynamics from the National Institute of General Medical Sciences (grant no. U54 GM088558), the Research Fund for the Control of Infectious Disease, Food and Health Bureau, Government of the Hong Kong SAR (grant no. HK-12-04-02), and the Area of Excellence Scheme of the University Grants Committee of Hong Kong (grant no. AoE/M-12/06).

D.K.M.I. receives research funding from F. Hoffman-La Roche. B.J.C. has received research funding from MedImmune Inc. and consults for Crucell NV. The authors report no other potential conflicts of interest.

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Editors' Note: A commentary on this article appears on page 842.

Correspondence: Benjamin J. Cowling, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong. E-mail:

Received March 4, 2013

Accepted May 21, 2013

© 2013 by Lippincott Williams & Wilkins, Inc