title: Estimating the burden of pneumococcal pneumonia among adults: a systematic review and meta-analysis of diagnostic techniques.
abstract: BACKGROUND
  Pneumococcal pneumonia causes significant morbidity and mortality among adults. Given limitations of diagnostic tests for non-bacteremic pneumococcal pneumonia, most studies report the incidence of bacteremic or invasive pneumococcal disease (IPD), and thus, grossly underestimate the pneumococcal pneumonia burden. We aimed to develop a conceptual and quantitative strategy to estimate the non-bacteremic disease burden among adults with community-acquired pneumonia (CAP) using systematic study methods and the availability of a urine antigen assay.
  
  
  RESULTS
  We performed a systematic literature review of studies providing information on the relative yield of various diagnostic assays (BinaxNOW® S. pneumoniae urine antigen test (UAT) with blood and/or sputum culture) in diagnosing pneumococcal pneumonia. We estimated the proportion of pneumococcal pneumonia that is bacteremic, the proportion of CAP attributable to pneumococcus, and the additional contribution of the Binax UAT beyond conventional diagnostic techniques, using random effects meta-analytic methods and bootstrapping. We included 35 studies in the analysis, predominantly from developed countries. The estimated proportion of pneumococcal pneumonia that is bacteremic was 24.8% (95% CI: 21.3%, 28.9%). The estimated proportion of CAP attributable to pneumococcus was 27.3% (95% CI: 23.9%, 31.1%). The Binax UAT diagnosed an additional 11.4% (95% CI: 9.6, 13.6%) of CAP beyond conventional techniques. We were limited by the fact that not all patients underwent all diagnostic tests and by the sensitivity and specificity of the diagnostic tests themselves. We address these resulting biases and provide a range of plausible values in order to estimate the burden of pneumococcal pneumonia among adults.
  
  
  CONCLUSIONS
  Estimating the adult burden of pneumococcal disease from bacteremic pneumococcal pneumonia data alone significantly underestimates the true burden of disease in adults. For every case of bacteremic pneumococcal pneumonia, we estimate that there are at least 3 additional cases of non-bacteremic pneumococcal pneumonia.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America. said.maria@gmail.com
authors.forename: Maria A
authors.initials: MA
authors.lastname: Said
authors.forename: Hope L
authors.initials: HL
authors.lastname: Johnson
authors.forename: Bareng A S
authors.initials: BA
authors.lastname: Nonyane
authors.forename: Maria
authors.initials: M
authors.lastname: Deloria-Knoll
authors.forename: Katherine L
authors.initials: KL
authors.lastname: O'Brien
authors.forename: Felipe
authors.initials: F
authors.lastname: Andreo
authors.forename: Bojana
authors.initials: B
authors.lastname: Beovic
authors.forename: Silvia
authors.initials: S
authors.lastname: Blanco
authors.forename: Wim G
authors.initials: WG
authors.lastname: Boersma
authors.forename: David R
authors.initials: DR
authors.lastname: Boulware
authors.forename: Jay C
authors.initials: JC
authors.lastname: Butler
authors.forename: Jordi
authors.initials: J
authors.lastname: Carratalà
authors.forename: Feng-Yee
authors.initials: FY
authors.lastname: Chang
authors.forename: Patrick G P
authors.initials: PG
authors.lastname: Charles
authors.forename: Alejandro A
authors.initials: AA
authors.lastname: Diaz
authors.forename: Jose
authors.initials: J
authors.lastname: Domínguez
authors.forename: Naomi
authors.initials: N
authors.lastname: Ehara
authors.forename: Henrik
authors.initials: H
authors.lastname: Endeman
authors.forename: Vicenç
authors.initials: V
authors.lastname: Falcó
authors.forename: Miquel
authors.initials: M
authors.lastname: Falguera
authors.forename: Kiyoyasu
authors.initials: K
authors.lastname: Fukushima
authors.forename: Carolina
authors.initials: C
authors.lastname: Garcia-Vidal
authors.forename: Daniel
authors.initials: D
authors.lastname: Genne
authors.forename: Igor A
authors.initials: IA
authors.lastname: Guchev
authors.forename: Felix
authors.initials: F
authors.lastname: Gutierrez
authors.forename: Susanne S
authors.initials: SS
authors.lastname: Hernes
authors.forename: Andy I M
authors.initials: AI
authors.lastname: Hoepelman
authors.forename: Ulla
authors.initials: U
authors.lastname: Hohenthal
authors.forename: Niclas
authors.initials: N
authors.lastname: Johansson
authors.forename: Vitezslav
authors.initials: V
authors.lastname: Kolek
authors.forename: Roman S
authors.initials: RS
authors.lastname: Kozlov
authors.forename: Tsai-Ling
authors.initials: TL
authors.lastname: Lauderdale
authors.forename: Ivana
authors.initials: I
authors.lastname: Mareković
authors.forename: Mar
authors.initials: M
authors.lastname: Masiá
authors.forename: Matta A
authors.initials: MA
authors.lastname: Matta
authors.forename: Òscar
authors.initials: Ò
authors.lastname: Miró
authors.forename: David R
authors.initials: DR
authors.lastname: Murdoch
authors.forename: Eric
authors.initials: E
authors.lastname: Nuermberger
authors.forename: Richard
authors.initials: R
authors.lastname: Paolini
authors.forename: Rafael
authors.initials: R
authors.lastname: Perelló
authors.forename: Dominic
authors.initials: D
authors.lastname: Snijders
authors.forename: Vanda
authors.initials: V
authors.lastname: Plečko
authors.forename: Roger
authors.initials: R
authors.lastname: Sordé
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Strålin
authors.forename: Menno M
authors.initials: MM
authors.lastname: van der Eerden
authors.forename: Angel
authors.initials: A
authors.lastname: Vila-Corcoles
authors.forename: James P
authors.initials: JP
authors.lastname: Watt
mesh_terms: D000328:Adult; D016470:Bacteremia / Q000175:diagnosis; D017714:Community-Acquired Infections; D006801:Humans; D011018:Pneumonia, Pneumococcal / Q000175:diagnosis* / Q000453:epidemiology; D012680:Sensitivity and Specificity; D013296:Streptococcus pneumoniae / Q000276:immunology / Q000302:isolation & purification
references.citation: Control Clin Trials. 1986 Sep;7(3):177-88
references.pmid: 3802833
references.citation: Arch Intern Med. 2011 Jan 24;171(2):166-72
references.pmid: 20876397
references.citation: Epidemiol Infect. 2010 Dec;138(12):1796-803
references.pmid: 20334727
references.citation: Lancet. 2007 Apr 7;369(9568):1179-86
references.pmid: 17416262
references.citation: Clin Infect Dis. 2010 Jan 15;50(2):202-9
references.pmid: 20014950
references.citation: Eur J Emerg Med. 2011 Feb;18(1):50-4
references.pmid: 20531201
references.citation: Lancet. 2009 Sep 12;374(9693):893-902
references.pmid: 19748398
references.citation: Am J Med. 1999 Apr;106(4):385-90
references.pmid: 10225239
references.citation: J Clin Microbiol. 2001 Oct;39(10):3495-8
references.pmid: 11574562
references.citation: Eur J Clin Microbiol Infect Dis. 2005 Apr;24(4):241-9
references.pmid: 15902529
references.citation: Scand J Infect Dis. 2008;40(10):843-5
references.pmid: 18609214
references.citation: J Med Microbiol. 2008 Jul;57(Pt 7):820-826
references.pmid: 18566139
references.citation: Epidemiology. 2010 Sep;21(5):719-25
references.pmid: 20562627
references.citation: Clin Infect Dis. 2008 May 15;46(10):1513-21
references.pmid: 18419484
references.citation: Clin Microbiol Rev. 2011 Oct;24(4):718-33
references.pmid: 21976606
references.citation: Int J Antimicrob Agents. 2006 Nov;28(5):423-7
references.pmid: 17046211
references.citation: N Engl J Med. 1995 Sep 28;333(13):845-51
references.pmid: 7651475
references.citation: Thorax. 2010 Feb;65(2):101-6
references.pmid: 19703825
references.citation: Eur Respir J. 2003 Feb;21(2):209-14
references.pmid: 12608431
references.citation: Respir Med. 2005 Sep;99(9):1079-86
references.pmid: 16085210
references.citation: Respir Med. 2006 May;100(5):884-91
references.pmid: 16226441
references.citation: Respir Med. 2001 Jan;95(1):78-82
references.pmid: 11207022
references.citation: PLoS Med. 2009 Jul 21;6(7):e1000100
references.pmid: 19621070
references.citation: N Engl J Med. 1997 Jan 23;336(4):243-50
references.pmid: 8995086
references.citation: J Clin Microbiol. 2003 Jul;41(7):2810-3
references.pmid: 12843005
references.citation: Clin Infect Dis. 2005 Jun 1;40(11):1608-16
references.pmid: 15889358
references.citation: Clin Infect Dis. 2007 Mar 1;44 Suppl 2:S27-72
references.pmid: 17278083
references.citation: Clin Infect Dis. 1998 Apr;26(4):811-38
references.pmid: 9564457
references.citation: JAMA. 2010 Sep 22;304(12):1326; author reply 1326-7
references.pmid: 20858875
references.citation: Thorax. 2009 Oct;64 Suppl 3:iii1-55
references.pmid: 19783532
references.citation: Medicine (Baltimore). 2003 May;82(3):159-69
references.pmid: 12792302
references.citation: Chest. 2007 Mar;131(3):779-787
references.pmid: 17356093
references.citation: JAMA. 1996 Jan 10;275(2):134-41
references.pmid: 8531309
references.citation: Chest. 1999 Jul;116(1):107-14
references.pmid: 10424512
references.citation: Chest. 1988 Jan;93(1):43-8
references.pmid: 3275531
references.citation: Thorax. 2001 Apr;56(4):296-301
references.pmid: 11254821
references.citation: J Infect Dis. 2010 Jan 1;201(1):32-41
references.pmid: 19947881
references.citation: Chest. 1998 Dec;114(6):1588-93
references.pmid: 9872193
references.citation: Scand J Infect Dis. 2008;40(9):715-20
references.pmid: 19086245
references.citation: Chest. 2001 Jan;119(1):243-9
references.pmid: 11157611
references.citation: JAMA. 2000 Apr 19;283(15):2008-12
references.pmid: 10789670
references.citation: JAMA. 1981 Oct 23-30;246(17):1942-8
references.pmid: 7288974
references.citation: Clin Infect Dis. 2009 Aug 1;49(3):409-16
references.pmid: 19555286
references.citation: Scand J Infect Dis. 2005;37(9):657-63
references.pmid: 16126566
references.citation: J Infect Dis. 2003 May 1;187(9):1416-23
references.pmid: 12717623
references.citation: mBio. 2011 Jan 25;2(1):e00309-10
references.pmid: 21264063
references.citation: Scand J Infect Dis. 2008;40(2):131-8
references.pmid: 17852937
references.citation: Clin Infect Dis. 2004 Jan 15;38(2):222-6
references.pmid: 14699454
references.citation: J Chemother. 2006 Oct;18(5):562-4
references.pmid: 17127237
references.citation: Emerg Med J. 2008 Mar;25(3):144-8
references.pmid: 18299361
references.citation: Clin Infect Dis. 2004 Jul 15;39(2):170-2
references.pmid: 15307024
references.citation: Clin Microbiol Infect. 2010 Jul;16(7):909-11
references.pmid: 19681958
references.citation: Lancet. 2003 Dec 13;362(9400):1991-2001
references.pmid: 14683661
references.citation: Ann Intern Med. 1964 May;60:759-76
references.pmid: 14156606
references.citation: Intensive Care Med. 2006 Nov;32(11):1766-72
references.pmid: 16957905
references.citation: J Clin Microbiol. 2004 Aug;42(8):3620-5
references.pmid: 15297507
references.citation: Respiration. 2007;74(4):387-93
references.pmid: 16582535
references.citation: Clin Infect Dis. 2003 Feb 1;36(3):286-92
references.pmid: 12539069
references.citation: Wkly Epidemiol Rec. 2007 Mar 23;82(12):93-104
references.pmid: 17380597
references.citation: Stat Med. 2004 Jun 15;23(11):1663-82
references.pmid: 15160401
references.citation: Eur J Clin Microbiol Infect Dis. 2003 Oct;22(10):584-91
references.pmid: 13680399
references.citation: Am J Respir Crit Care Med. 2010 May 1;181(9):975-82
references.pmid: 20133929