Abstract
BackgroundDetermining the etiology of pneumonia is essential to guide public health interventions. Diagnostic test results, including from polymerase chain reaction (PCR) assays of upper respiratory tract specimens, have been used to estimate prevalence of pneumococcal pneumonia. However limitations in test sensitivity and specificity and the specimen types available make establishing a definitive diagnosis challenging. Prevalence estimates for pneumococcal pneumonia could be biased in the absence of a true gold standard reference test for detecting Streptococcus pneumoniae.MethodsWe conducted a case control study to identify etiologies of community acquired pneumonia (CAP) from April 2014 through August 2015 in Thailand. We estimated the prevalence of pneumococcal pneumonia among adults hospitalized for CAP using Bayesian latent class models (BLCMs) incorporating results of real-time polymerase chain reaction (qPCR) testing of upper respiratory tract specimens and a urine antigen test (UAT) from cases and controls. We compared the prevalence estimate to conventional analyses using only UAT as a reference test.ResultsThe estimated prevalence of pneumococcal pneumonia was 8% (95% CI: 5–11%) by conventional analyses. By BLCM, we estimated the prevalence to be 10% (95% CrI: 7–16%) using binary qPCR and UAT results, and 11% (95% CrI: 7–17%) using binary UAT results and qPCR cycle threshold (Ct) values.ConclusionsBLCM suggests a > 25% higher prevalence of pneumococcal pneumonia than estimated by a conventional approach assuming UAT as a gold standard reference test. Higher quantities of pneumococcal DNA in the upper respiratory tract were associated with pneumococcal pneumonia in adults but the addition of a second specific pneumococcal test was required to accurately estimate disease status and prevalence. By incorporating the inherent uncertainty of diagnostic tests, BLCM can obtain more reliable estimates of disease status and improve understanding of underlying etiology.
Highlights
Determining the etiology of pneumonia is essential to guide public health interventions
Among 357 case-patients, 32% (114/357) had a NP/ OP specimen positive for S. pneumoniae by real time polymerase chain reaction (qPCR) compared to 26% (57/217) of controls
Using Bayesian latent class model (BLCM) to integrate results from two independent assays and accounting for imperfect test performance, we found that 11% (95% credible interval (CrI): 7–17%) of community-acquired pneumonia (CAP) among adults in Thailand was associated with pneumococcus, a higher prevalence than previously estimated from a similar population
Summary
Determining the etiology of pneumonia is essential to guide public health interventions. Pneumococcus is among the most important etiologies of hospitalized community-acquired pneumonia (CAP) among adults [3,4,5,6], but demonstrating Streptococcus pneumoniae as the etiology of pneumonia is challenging In part this is because specimens from the site of infection (such as lung aspirates) are rarely collected nowadays for either clinical or research purposes. Latent class models (LCM) can link the latent variable with diagnostic tests results This method has been used to estimate prevalence of pneumococcal pneumonia among adults with CAP in the United States (U.S.) and Kenya, incorporating results from multiple tests including PCR assays conducted on specimens from the upper respiratory tract or lung aspirate [2, 8]. The colonization density of S. pneumoniae has been shown in some but not all previous studies [9,10,11,12,13] to be associated with pneumococcal pneumonia
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