title: Assessment of serosurveys for H5N1.
abstract: BACKGROUND
  It has been suggested that the true case-fatality rate of human H5N1 influenza infection is appreciably less than the figure of approximately 60% that is based on official World Health Organization (WHO)-confirmed case reports because asymptomatic cases may have been missed. A number of seroepidemiologic studies have been conducted in an attempt to identify such missed cases.
  
  
  METHODS
  We conducted a comprehensive literature review of all English-language H5N1 human serology surveys with detailed attention to laboratory methodology used (including whether investigators used criteria set by the WHO to define positive cases), laboratory controls used, and the clades/genotypes involved.
  
  
  RESULTS
  Twenty-nine studies were included in the analysis. Few reported using unexposed control groups and one-third did not apply WHO criteria. Of studies that used WHO criteria, only 4 found any seropositive results to clades/genotypes of H5N1 that are currently circulating. No studies reported seropositive results to the clade 2/genotype Z viruses that have spread throughout Eurasia and Africa.
  
  
  CONCLUSIONS
  This review suggests that the frequency of positive H5 serology results is likely to be low; therefore, it is essential that future studies adhere to WHO criteria and include unexposed controls in their laboratory assays to limit the likelihood of false-positive results.
authors: Center for Biosecurity, University of Pittsburgh Medical Center, Baltimore, MD 21202, USA. etoner@upmcbiosecurity.org
authors: Eric S
authors: ES
authors: Toner
authors: Amesh A
authors: AA
authors: Adalja
authors: Jennifer B
authors: JB
authors: Nuzzo
authors: Thomas V
authors: TV
authors: Inglesby
authors: Donald A
authors: DA
authors: Henderson
authors: Donald S
authors: DS
authors: Burke
mesh_terms: D014943:Global Health; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000453:epidemiology* / Q000401:mortality / Q000821:virology*; D016036:Seroepidemiologic Studies; D016019:Survival Analysis
references: PLoS One. 2011 Apr 29;6(4):e14809
references: 21559080
references: Vaccine. 2009 Dec 11;28(2):398-402
references: 19853073
references: Emerg Infect Dis. 2008 Mar;14(3):499-501
references: 18325273
references: PLoS One. 2009 Nov 23;4(11):e7948
references: 19956765
references: Emerg Infect Dis. 2009 May;15(5):756-60
references: 19402962
references: J Infect Dis. 2000 Jan;181(1):344-8
references: 10608786
references: Cell Res. 2010 Jan;20(1):51-61
references: 19884910
references: J Infect Dis. 2009 Jun 15;199(12):1744-52
references: 19416078
references: Biosecur Bioterror. 2012 Jun;10(2):237-40
references: 22394305
references: Scand J Infect Dis. 2011 Mar;43(3):216-20
references: 21142624
references: Science. 2012 Mar 23;335(6075):1463
references: 22362880
references: Epidemiol Infect. 2010 Sep;138(9):1274-80
references: 20092669
references: Chin Med J (Engl). 2008 Oct 20;121(20):2050-3
references: 19080274
references: PLoS One. 2012;7(8):e43948
references: 22928049
references: Emerg Infect Dis. 2012 Jun;18(6):986-8
references: 22607722
references: Lancet. 2008 Apr 26;371(9622):1427-34
references: 18400288
references: PLoS One. 2011 Jan 24;6(1):e14582
references: 21283678
references: Clin Infect Dis. 2005 Jan 15;40(2):e16-8
references: 15655735
references: Influenza Other Respir Viruses. 2012 Jan;6(1):1-5
references: 22035148
references: J Infect Dis. 2002 Apr 15;185(8):1005-10
references: 11930308
references: Influenza Other Respir Viruses. 2009 May;3(3):81-9
references: 19459276
references: N Engl J Med. 2009 Jun 11;360(24):2583-4
references: 19516044
references: MMWR Morb Mortal Wkly Rep. 1998 Jan 9;46(52-53):1245-7
references: 9436713
references: BMC Infect Dis. 2009 Oct 18;9:170
references: 19835632
references: Emerg Infect Dis. 2006 Nov;12(11):1773-5
references: 17283635
references: J Infect Dis. 2007 Dec 1;196(11):1685-91
references: 18008254
references: Nature. 2004 Jul 8;430(6996):209-13
references: 15241415
references: Epidemiol Infect. 2010 Feb;138(2):210-3
references: 19765331
references: Southeast Asian J Trop Med Public Health. 2010 Sep;41(5):1095-103
references: 21073030
references: J Infect Dis. 2012 Jan 1;205(1):20-7
references: 22080094
references: mBio. 2012 Feb 24;3(2):e00045-12
references: 22366820
references: Emerg Infect Dis. 2009 Aug;15(8):1252-9
references: 19751587
references: Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8950-5
references: 12077307
references: Emerg Infect Dis. 2006 Oct;12(10):1542-7
references: 17176569
references: J Clin Virol. 2010 Jun;48(2):123-6
references: 20356781
references: Science. 2012 Jun 22;336(6088):1506; author reply 1506
references: 22723396
references: Emerg Infect Dis. 2005 Jul;11(7):1158-9
references: 16032802
references: J Infect Dis. 2011 Apr 15;203(8):1054-62
references: 21450995
references: Clin Infect Dis. 2011 Oct;53(8):e107-16
references: 21921216
references: Int J Infect Dis. 2009 Mar;13(2):261-5
references: 18922718
references: J Infect Dis. 1999 Dec;180(6):1763-70
references: 10558929
references: BMC Infect Dis. 2012 Apr 18;12:93
references: 22512873
references: Emerg Infect Dis. 2005 Feb;11(2):210-5
references: 15752437
references: PLoS One. 2009 Dec 29;4(12):e8452
references: 20041114