Diagnostic Performance of Xpert MTB/RIF in Tuberculous Pleural Effusion: Systematic Review and Meta-analysis

Abstract

A systematic review investigating the role of Xpert MTB/RIF in the diagnosis of tuberculous pleural effusion (TPE) was conducted. The pooled sensitivities and specificities of Xpert MTB/RIF were 51.4% and 98.6%, respectively, with culture used as a reference standard and 22.7% and 99.8%, respectively, with a composite reference standard (CRS) used as the benchmark. Xpert MTB/RIF has low sensitivity but excellent specificity in the diagnosis of TPE.T uberculous pleural effusion (TPE) is the second most common site of extrapulmonary tuberculosis (EPTB) (1). Currently, the best tool for diagnosing TPE is a thoracoscopic pleural biopsy, an invasive procedure, with sensitivity ranging from 93 to 100% (2-5). The most widely used diagnostic test for TPE is the pleural fluid adenosine deaminase (ADA) level, which has variable sensitivity ranging from 47 to 100% (6). The sensitivities of pleural fluid microscopy and culture in TPE are about 10% and 20%, respectively (5, 7, 8). The absence of a simple reference standard makes the treatment of TPE empirical (nonmicrobiological) in most circumstances.Xpert MTB/RIF (GeneXpert) has not only high sensitivity and specificity in smear-positive pulmonary tuberculosis (TB) (98% and 98%, respectively) but also reasonable diagnostic performance in smear-negative pulmonary tuberculosis (67% and 99%, respectively) (9). However, a recent meta-analysis reported the pooled sensitivity and specificity of GeneXpert in TPE as 46.4% and 99.1%, respectively, compared with those of pleural fluid mycobacterial culture (10). Since then, several new studies evaluating GeneXpert in TPE have been published. Herein, we perform an updated meta-analysis on the role of Xpert MTB/RIF in the diagnosis of TPE.The systematic review was conducted using the standard methodology for systematic reviews of diagnostic test accuracy (see the detailed methodology in the supplemental material) (11,12). Institutional ethics committee approval was not required as this was a systematic review of published data.Our search yielded 155 citations, of which 24 studies (2,486 patients) were included in the current analysis (see Fig. S1 in the supplemental material) (7,8,. There were equal numbers of studies from the developed and the developing countries (see Tables S1 and S2 in the supplemental material) (8, 14, 16-22, 24, 32, 33). Only two studies included children (13,15). Seven studies included people living with HIV infection (8,17,18,(20)(21)(22)27). Twenty-one studies (2,167 patients) and 10 studies (937 patients) used a microbiological standard (mycobacterial culture) (7, 8, 13-16, 19, 20, 22-34) or a composite reference standard (CRS) (7, 14-18, 21, 22, 24, 28), respectively, to assess the diagnostic accuracy of GeneXpert (see Table S3). Seven studies performed Xpert MTB/RIF on frozen pleural fluid (7,15,19,21,23,28,30), while the remaining used fresh samples (see Table S4). Nine studies concentrated the pleural fluid sample by centrifugation before performance of GeneXpert (7, 8, 16-18, 20, 22, 24, 29). The ov...

Thoracoscopic pleural biopsy improves yield of Xpert MTB/RIF for diagnosis of pleural tuberculosis

“…To our knowledge, this is the first study to report the yield of Xpert from thoracoscopic pleural biopsy samples. Sehgal et al . recently published a systemic review and meta‐analysis on the performance of Xpert in the diagnosis of TPE.…”

“…Given the limitations of available tests for the diagnosis of pleural TB, several studies have evaluated the performance of Xpert using pleural fluid as a sample type. Overall, these studies show a sensitivity averaging around 22.7% against a composite reference standard (CRS) . However, the preferred specimen for the diagnosis of pleural TB is pleural tissue.…”

The advantage of PCR for MTB in comparison to ADA in diagnosing tubercular pleural effusion

“…3 The sensitivity of nucleic acid amplification test, Xpert MTB/RIF ranged from (70-100)% in most of the extrapulmonary samples but was much lower around (40-50)% in the pleural fluid. [9][10][11] In our study also the overall sensitivity of PCR for MTB for diagnosis of tubercular pleural effusion has been found to be 51.1% which is low. CB-NAAT has also been shown to be useful in diagnosing abdominal tuberculosis and meningeal tuberculosis.…”

Diagnosis of opportunistic infections

“…Children Overall PTB (sputum): n=12 studies, Smear Positive PTB: n=6 studies, Smear Negative PTB: n=7 studies, Overall Gastic Lavage: n=7 studies [37]. EPTB Overall EPTB: n=36 studies [38]; Lymph Node Tissue/Aspirate: n=18 studies [39], n= 1 HIV positive cohort [40]; CFS(TBM): n=18 studies [39], n=1 HIV positive cohort, mixed CSF samples [41], n=1 HIV positive cohort, centrifuged CSF [42]; Pleural fluid: n=24 studies [43], n=1 high TB-HIV prevalence cohort [44]; Urine: n=1 hospitalised, HIV positive cohort [45]. …”