Estimating the Burden of Pneumococcal Pneumonia Among Adults: a Systematic Review and Meta-analysis of Diagnostic Techniques

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.

Methods And Findings: 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.

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References

DerSimonian R, Laird N . Meta-analysis in clinical trials. Control Clin Trials. 1986; 7(3):177-88. DOI: 10.1016/0197-2456(86)90046-2. View

Sorde R, Falco V, Lowak M, Domingo E, Ferrer A, Burgos J . Current and potential usefulness of pneumococcal urinary antigen detection in hospitalized patients with community-acquired pneumonia to guide antimicrobial therapy. Arch Intern Med. 2010; 171(2):166-72. DOI: 10.1001/archinternmed.2010.347. View

Watt J, Moisi J, Donaldson R, Reid R, Ferro S, Whitney C . Use of serology and urine antigen detection to estimate the proportion of adult community-acquired pneumonia attributable to Streptococcus pneumoniae. Epidemiol Infect. 2010; 138(12):1796-803. DOI: 10.1017/S0950268810000555. View

Grijalva C, Nuorti J, Arbogast P, Martin S, Edwards K, Griffin M . Decline in pneumonia admissions after routine childhood immunisation with pneumococcal conjugate vaccine in the USA: a time-series analysis. Lancet. 2007; 369(9568):1179-86. DOI: 10.1016/S0140-6736(07)60564-9. View

Johansson N, Kalin M, Tiveljung-Lindell A, Giske C, Hedlund J . Etiology of community-acquired pneumonia: increased microbiological yield with new diagnostic methods. Clin Infect Dis. 2009; 50(2):202-9. PMC: 7107844. DOI: 10.1086/648678. View

Perello R, Miro O, Miro J, Masso E, Sanchez M, Camon S . Urgent pneumococcal urinary antigen, importance in the diagnosis of acquired pneumonia in HIV-1 patients. Eur J Emerg Med. 2010; 18(1):50-4. DOI: 10.1097/MEJ.0b013e32833b4fd0. View

OBrien K, Wolfson L, Watt J, Henkle E, Deloria-Knoll M, McCall N . Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates. Lancet. 2009; 374(9693):893-902. DOI: 10.1016/S0140-6736(09)61204-6. View

Ruiz-Gonzalez A, Falguera M, Nogues A . Is Streptococcus pneumoniae the leading cause of pneumonia of unknown etiology? A microbiologic study of lung aspirates in consecutive patients with community-acquired pneumonia. Am J Med. 1999; 106(4):385-90. DOI: 10.1016/s0002-9343(99)00050-9. View

Murdoch D, Laing R, Mills G, Karalus N, Town G, Mirrett S . Evaluation of a rapid immunochromatographic test for detection of Streptococcus pneumoniae antigen in urine samples from adults with community-acquired pneumonia. J Clin Microbiol. 2001; 39(10):3495-8. PMC: 88378. DOI: 10.1128/JCM.39.10.3495-3498.2001. View

10.

van der Eerden M, Vlaspolder F, de Graaff C, Groot T, Jansen H, Boersma W . Value of intensive diagnostic microbiological investigation in low- and high-risk patients with community-acquired pneumonia. Eur J Clin Microbiol Infect Dis. 2005; 24(4):241-9. DOI: 10.1007/s10096-005-1316-8. View

11.

Marekovic I, Plecko V, Boras Z, Pavlovic L, Budimir A, Bosnjak Z . Evaluation of PCR as rapid microbiological method in diagnosis of pneumococcal pneumonia. Scand J Infect Dis. 2008; 40(10):843-5. DOI: 10.1080/00365540802029581. View

12.

Ehara N, Fukushima K, Kakeya H, Mukae H, Akamatsu S, Kageyama A . A novel method for rapid detection of Streptococcus pneumoniae antigen in sputum and its application in adult respiratory tract infections. J Med Microbiol. 2008; 57(Pt 7):820-826. DOI: 10.1099/jmm.0.47793-0. View

13.

Jokinen J, Scott J . Estimating the proportion of pneumonia attributable to pneumococcus in Kenyan adults: latent class analysis. Epidemiology. 2010; 21(5):719-25. PMC: 2923075. DOI: 10.1097/EDE.0b013e3181e4c4d5. View

14.

Charles P, Whitby M, Fuller A, Stirling R, Wright A, Korman T . The etiology of community-acquired pneumonia in Australia: why penicillin plus doxycycline or a macrolide is the most appropriate therapy. Clin Infect Dis. 2008; 46(10):1513-21. DOI: 10.1086/586749. View

15.

Marshall B, Levy S . Food animals and antimicrobials: impacts on human health. Clin Microbiol Rev. 2011; 24(4):718-33. PMC: 3194830. DOI: 10.1128/CMR.00002-11. View

16.

Matute A, Brouwer W, Hak E, Delgado E, Alonso E, Hoepelman I . Aetiology and resistance patterns of community-acquired pneumonia in León, Nicaragua. Int J Antimicrob Agents. 2006; 28(5):423-7. DOI: 10.1016/j.ijantimicag.2006.07.016. View

17.

Hirschtick R, Glassroth J, Jordan M, Wilcosky T, Wallace J, Kvale P . Bacterial pneumonia in persons infected with the human immunodeficiency virus. Pulmonary Complications of HIV Infection Study Group. N Engl J Med. 1995; 333(13):845-51. DOI: 10.1056/NEJM199509283331305. View

18.

Falguera M, Ruiz-Gonzalez A, Schoenenberger J, Touzon C, Gazquez I, Galindo C . Prospective, randomised study to compare empirical treatment versus targeted treatment on the basis of the urine antigen results in hospitalised patients with community-acquired pneumonia. Thorax. 2009; 65(2):101-6. DOI: 10.1136/thx.2009.118588. View

19.

Marcos M, Jimenez de Anta M, de la Bellacasa J, Gonzalez J, Martinez E, Garcia E . Rapid urinary antigen test for diagnosis of pneumococcal community-acquired pneumonia in adults. Eur Respir J. 2003; 21(2):209-14. DOI: 10.1183/09031936.03.00058802. View

20.

Lauderdale T, Chang F, Ben R, Yin H, Ni Y, Tsai J . Etiology of community acquired pneumonia among adult patients requiring hospitalization in Taiwan. Respir Med. 2005; 99(9):1079-86. DOI: 10.1016/j.rmed.2005.02.026. View