Diagnostic Accuracy of In-House PCR for Pulmonary Tuberculosis in Smear-Positive Patients: Meta-Analysis and Metaregression

Abstract

In-house PCR (hPCR) could speed differential diagnosis between tuberculosis (TB) and nontuberculous mycobacterial disease in patients with positive smears and pulmonary infiltrates, but its reported accuracy fluctuates across studies. We conducted a systematic review and meta-analysis of hPCR sensitivity and specificity for smear-positive TB diagnosis, using culture as the reference standard. After searching English language studies in MEDLINE and EMBASE, we estimated cumulative accuracy by means of summary receiver operating characteristic analysis. The possible influence of hPCR procedures and study methodological features on accuracy was explored by univariate metaregression, followed by multivariate adjustment of items selected as significant. Thirty-five articles (1991 to 2006) met the inclusion criteria. The pooled estimates of the diagnostic odds ratio, sensitivity, and specificity (random-effect model) were, respectively, 60 (confidence interval [CI], 29 to 123), 0.96 (CI, 0.95 to 0.97), and 0.81 (CI, 0.78 to 0.84), but significant variations (mainly in specificity) limit their clinical applicability. The quality of the reference test, the detection method, and real-time PCR use explained some of the observed heterogeneity. Probably due to the limited study power of our meta-analysis and to the wide differences in both laboratory techniques and methodological quality, only real-time PCR also displayed a positive impact on accuracy in the multivariate model. Currently, hPCR can be confidently used to exclude TB in smear-positive patients, but its low specificity could lead to erroneous initiation of therapy, isolation, and contact investigation. As the inclusion of samples from treated patients could have artificially reduced specificity, future studies should report mycobacterial-culture results for each TB and non-TB sample analyzed.With the continuing expansion of human immunodeficiency virus and other immunosuppressive conditions, tuberculosis (TB), as well as infections caused by nontuberculous mycobacteria (NTM), have increased in many parts of the world. In addition, the spread of tumor necrosis factor alpha-blocking agents has led to high rates of development of both infections among patients affected by inflammatory and autoimmune diseases. Similarities in clinical and radiographic features, particularly in cases of fibrocavitary disease, make differential diagnosis between TB and NTM infection a difficult task. In order to avoid the risk of progressive disease, the initiation of empirical antituberculous therapy has been suggested for patients with both positive acid-fast bacillus smear microscopy (AFB) and nucleic acid amplification tests (NAATs) pending culture results (25).The diagnostic accuracy of NAATs for AFB-positive samples, however, is still unclear. In a previous meta-analysis of commercially based NAATs, we found that their sensitivities and specificities for AFB-positive samples ranged, among different kits, from 0.96 to 0.98 and from 0.71 to 0.96 and that they were considerably inf...

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