title: Case fatality risk of influenza A (H1N1pdm09): a systematic review.
abstract: 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.
authors.affiliation: 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.
authors.forename: Jessica Y
authors.initials: JY
authors.lastname: Wong
authors.forename: Heath
authors.initials: H
authors.lastname: Kelly
authors.forename: Dennis K M
authors.initials: DK
authors.lastname: Ip
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Wu
authors.forename: Gabriel M
authors.initials: GM
authors.lastname: Leung
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Cowling
mesh_terms: D014943:Global Health; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype; D007251:Influenza, Human / Q000401:mortality*; D058873:Pandemics; D012306:Risk
references.citation: Gac Sanit. 2011 Jul-Aug;25(4):296-302
references.pmid: 21543138
references.citation: BMC Infect Dis. 2013 Jan 07;13:6
references.pmid: 23289407
references.citation: Science. 2009 Jun 19;324(5934):1557-61
references.pmid: 19433588
references.citation: Epidemiology. 2012 Jul;23(4):531-42
references.pmid: 22561117
references.citation: PLoS One. 2010 Mar 25;5(3):e9880
references.pmid: 20360868
references.citation: PLoS Med. 2009 Dec;6(12):e1000207
references.pmid: 19997612
references.citation: Euro Surveill. 2009 Jul 02;14(26):
references.pmid: 19573509
references.citation: Expert Rev Respir Med. 2010 Jun;4(3):329-38
references.pmid: 20524916
references.citation: PLoS Med. 2011 May;8(5):e1000436
references.pmid: 21629683
references.citation: Lancet Infect Dis. 2012 Sep;12(9):687-95
references.pmid: 22738893
references.citation: PLoS One. 2012;7(2):e31800
references.pmid: 22363739
references.citation: J Clin Epidemiol. 2009 Oct;62(10):1006-12
references.pmid: 19631508
references.citation: PLoS Curr. 2012 Feb 24;4:RRN1306
references.pmid: 22485199
references.citation: Arch Intern Med. 2005 Feb 14;165(3):265-72
references.pmid: 15710788
references.citation: Nat Commun. 2013;4:1418
references.pmid: 23361009
references.citation: PLoS One. 2013;8(1):e54786
references.pmid: 23355899
references.citation: Stat Med. 2002 Jun 15;21(11):1539-58
references.pmid: 12111919
references.citation: CMAJ. 2010 Feb 9;182(2):131-6
references.pmid: 19959592
references.citation: Am J Public Health. 2009 Oct;99 Suppl 2:S225-30
references.pmid: 19797736
references.citation: Euro Surveill. 2010 Oct 07;15(40):
references.pmid: 20946757
references.citation: Euro Surveill. 2009 Aug 20;14(33):
references.pmid: 19712643
references.citation: PLoS One. 2010 May 07;5(5):e10540
references.pmid: 20479875
references.citation: Euro Surveill. 2010 Dec 09;15(49):
references.pmid: 21163179
references.citation: Am J Epidemiol. 2013 Apr 15;177(8):834-40
references.pmid: 23459950
references.citation: Lancet Infect Dis. 2012 Nov;12(11):845-50
references.pmid: 23041199
references.citation: Lancet Infect Dis. 2010 Jul;10(7):443-4
references.pmid: 20610325
references.citation: J Korean Med Sci. 2011 Jan;26(1):22-7
references.pmid: 21218025
references.citation: J Postgrad Med. 2013 Jan-Mar;59(1):9-14
references.pmid: 23525052
references.citation: PLoS Med. 2011 Jun;8(6):e1000442
references.pmid: 21713000
references.citation: Euro Surveill. 2010 May 20;15(20):
references.pmid: 20504388
references.citation: Lancet. 2009 Dec 19;374(9707):2072-2079
references.pmid: 19913290
references.citation: PLoS Curr. 2009 Dec 20;1:RRN1139
references.pmid: 20043033
references.citation: PLoS One. 2011;6(9):e24440
references.pmid: 21909433
references.citation: Vaccine. 2010 Mar 11;28(12):2370-84
references.pmid: 20096762
references.citation: BMJ. 2011 Sep 08;343:d5408
references.pmid: 21903689
references.citation: Cell Cycle. 2009 Oct 1;8(19):3057-62
references.pmid: 19755847
references.citation: Am J Epidemiol. 2011 Dec 1;174(11):1307-15
references.pmid: 22025354
references.citation: PLoS One. 2010 Oct 14;5(10):e13211
references.pmid: 20976224
references.citation: Rev Esp Salud Publica. 2011 Jan-Feb;85(1):37-45
references.pmid: 21750841
references.citation: Am J Epidemiol. 2012 Sep 15;176(6):519-26
references.pmid: 22952308
references.citation: PLoS One. 2010 Jul 21;5(7):e11677
references.pmid: 20657738
references.citation: Clin Infect Dis. 2010 Nov 15;51(10):1184-91
references.pmid: 20964521
references.citation: BMC Infect Dis. 2011 Mar 16;11:68
references.pmid: 21410965
references.citation: Jpn J Infect Dis. 2010 Mar;63(2):154-6
references.pmid: 20332587
references.citation: PLoS One. 2009 Aug 31;4(8):e6852
references.pmid: 19718434
references.citation: Bull Soc Pathol Exot. 2011 May;104(2):108-13
references.pmid: 21181328
references.citation: Ann Acad Med Singap. 2010 Apr;39(4):273-10
references.pmid: 20473451
references.citation: Lancet. 2009 Oct 3;374(9696):1209-11
references.pmid: 19679345
references.citation: Lancet. 2010 Nov 27;376(9755):1846-52
references.pmid: 21030071
references.citation: Wkly Epidemiol Rec. 2009 May 22;84(21):185-9
references.pmid: 19462531
references.citation: Euro Surveill. 2011 Feb 10;16(6):
references.pmid: 21329643
references.citation: BMJ. 2009 Jul 14;339:b2840
references.pmid: 19602714
references.citation: Euro Surveill. 2009 Oct 22;14(42):
references.pmid: 19883547
references.citation: N Engl J Med. 2009 Dec 31;361(27):2628-36
references.pmid: 20042754
references.citation: Bull Soc Pathol Exot. 2011 May;104(2):119-24
references.pmid: 21181330
references.citation: Influenza Other Respir Viruses. 2011 Sep;5(5):306-16
references.pmid: 21668690
references.citation: PLoS One. 2011;6(8):e21828
references.pmid: 21850217
references.citation: PLoS Comput Biol. 2011 Feb 10;7(2):e1001076
references.pmid: 21347316
references.citation: PLoS Med. 2010 Jun 01;7(6):e1000275
references.pmid: 20532237
references.citation: BMJ. 2009 Dec 10;339:b5213
references.pmid: 20007665
references.citation: Virol J. 2011 Mar 23;8:133
references.pmid: 21426589
references.citation: PLoS Curr. 2009 Aug 23;1:RRN1010
references.pmid: 20020674
references.citation: J Health Care Poor Underserved. 2011;22(4 Suppl):39-60
references.pmid: 22102305
references.citation: PLoS Med. 2011 Oct;8(10):e1001103
references.pmid: 21990967
references.citation: Epidemics. 2011 Sep;3(3-4):143-51
references.pmid: 22094337
references.citation: Euro Surveill. 2009 Jul 30;14(30):19284
references.pmid: 19643059
references.citation: East Mediterr Health J. 2012 Jan;18(1):31-6
references.pmid: 22360008
references.citation: Euro Surveill. 2009 Aug 27;14(34):
references.pmid: 19712648
references.citation: PLoS One. 2011;6(6):e20593
references.pmid: 21694769
references.citation: PLoS Med. 2011 Jul;8(7):e1001053
references.pmid: 21750667
references.citation: Euro Surveill. 2009 Aug 06;14(31):
references.pmid: 19660247