Classical and Latent Class Analysis Evaluation of Sputum Polymerase Chain Reaction and Urine Antigen Testing for Diagnosis of Pneumococcal Pneumonia in Adults

Abstract

Diagnosis of pneumococcal pneumonia is complicated by the lack of a diagnostic reference standard that is highly sensitive and specific. Latent class analysis (LCA) is a mathematical technique that relates an unobserved ("latent") infection to multiple diagnostic test results by use of a statistical model. We used classical analysis and LCA to evaluate the sensitivity and specificity of blood culture, sputum Gram stain, sputum polymerase chain reaction (PCR), and urine antigen testing for diagnosing pneumococcal pneumonia among 149 adults with community-acquired pneumonia. On the basis of LCA models, sensitivity of autolysin PCR and pneumolysin PCR was 82% and 89%, respectively, but specificity was low, 38% and 27%, respectively. For urine antigen testing, sensitivity was 77%-78%, and specificity was 67%-71%. Results of the LCA models were comparable with those obtained from classical analysis. LCA may be useful for diagnostic test evaluation and for determining the prevalence of pneumococcal infection in epidemiological studies of community-acquired pneumonia and in vaccine efficacy trials.

Optimal Sampling Sites and Methods for Detection of Pathogens Possibly Causing Community-Acquired Lower Respiratory Tract Infections

“…In a recent study, Butler et al used latent class analysis to determine the sensitivity and specificity of blood cultures (14) and confirmed previous results.…”

“…When a purulent sample was available, the Gram stain gave a presumptive diagnosis in 175/210 cases (80%). The studies by Butler et al and Miyashita et al confirmed these results (14,70).…”

“…In contrast with a widespread opinion, it is now also clear that sputum culture results are convincing when and only when the organism isolated is compatible with the morphology of the organism present in Ͼ90% of leukocytes in the Gram stain (14,35,42,53,85).…”

PCR Using Blood for Diagnosis of Invasive Pneumococcal Disease: Systematic Review and Meta-Analysis

“…The case is especially noteworthy for community-acquired pneumonia (CAP), for which positivity rates are very low and blood cultures cannot be used to direct treatment (3). The results of sputum Gram stain and culture are positive for 31 to 68% and 28 to 86% of patients with pneumococcal pneumonia who can produce sputum, respectively (8,21,43,46,54), while the test for pneumococcal urine antigen is positive for about 70 to 87% of patients (8,22,61,63), with all values being highly dependent on previous antibiotic treatment.Molecular methods for pathogen identification are appealing since, in principle, the results should not depend on the amount of pathogen present in the sample, identification defined by DNA can be highly specific, and noncultivable pathogens can be detected (18,44). The results can be made available within hours of a patient's presentation with an infection, during the time window that allows the direction of early antibiotic treatment.…”

“…The case is especially noteworthy for community-acquired pneumonia (CAP), for which positivity rates are very low and blood cultures cannot be used to direct treatment (3). The results of sputum Gram stain and culture are positive for 31 to 68% and 28 to 86% of patients with pneumococcal pneumonia who can produce sputum, respectively (8,21,43,46,54), while the test for pneumococcal urine antigen is positive for about 70 to 87% of patients (8,22,61,63), with all values being highly dependent on previous antibiotic treatment.…”