Estimating the Burden of Pneumococcal Pneumonia among Adults: A Systematic Review and Meta-Analysis of Diagnostic Techniques

<div><p>Background</p><p>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.</p><p>Methods and Findings</p><p>We performed a systematic literature review of studies providing information on the relative yield of various diagnostic assays (BinaxNOW® <i>S. pneumoniae</i> 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.</p><p>Conclusions</p><p>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.</p></div

Meta-analysis of the association of prior antibiotic use and PSI class on the yield of blood culture, sputum culture, and the Binax UAT.

1<p>Of positive yield; reference is no prior antibiotic use.</p>2<p>Of positive yield; reference is Pneumonia Severity Index class I–III.</p

Meta-analysis of the proportion of pneumococcal pneumonia that is bacteremic and the proportion of CAP attributable to pneumococcus, stratified by severity of disease, prior antibiotic use, and HIV status.

<p>Meta-analysis of the proportion of pneumococcal pneumonia that is bacteremic and the proportion of CAP attributable to pneumococcus, stratified by severity of disease, prior antibiotic use, and HIV status.</p

The relationships between CAP1, non-bacteremic pneumococcal pneumonia, and bacteremic pneumococcal pneumonia.

<p>The relationships between CAP<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0060273#fn2" target="_blank">1</a>, non-bacteremic pneumococcal pneumonia, and bacteremic pneumococcal pneumonia.</p

Studies included in the meta-analysis and their descriptors.

1<p>Only patients with radiographically confirmed pneumonia were included.</p>2<p>All studies were prospective, except #5 and #13.</p>3<p>All studies were included in the analyses of the proportion of pneumococcal pneumonia that is bacteremic and the proportion of CAP attributable to pneumococcus except # 10, #24, and #32, because these did not include blood cultures, #13, because this did not include sputum cultures, and #21 and #25, because even though all three diagnostic tests were done, we did not have sufficient information to determine the overlap in diagnostic yield of the three tests.</p>4<p>The numbers of patients undergoing the test was unknown; thus, the percentage is the number of positive tests among all study participants.</p>5<p>Patients with HIV were excluded if CD4<200.</p>6<p>All specimens were collected within 12 hours of the first dose of antibiotics.</p

Forest plot for the proportion of pneumococcal pneumonia identified as bacteremic, sorted by proportion of study participants who received antecedent antibiotics.

<p>Forest plot for the proportion of pneumococcal pneumonia identified as bacteremic, sorted by proportion of study participants who received antecedent antibiotics.</p

The proportion of community-acquired pneumonia attributable to pneumococcus, according to diagnostic test results, by individual studies3.

<p>The proportion of community-acquired pneumonia attributable to pneumococcus, according to diagnostic test results, by individual studies<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0060273#fn4" target="_blank">3</a>.</p

Flow diagram for the selection of studies.

<p>Flow diagram for the selection of studies.</p

Additional file 1: Table S1. of Arsenic exposure is associated with pediatric pneumonia in rural Bangladesh: a case control study

Case characteristics by presence of convalescent urine sample. (DOC 91 kb