Diagnostic accuracy of the Xpert MTB/RIF assay for extrapulmonary and pulmonary tuberculosis when testing non-respiratory samples: a systematic review.

BACKGROUND: Although the evidence base regarding the use of the Xpert MTB/RIF assay for diagnosis of pulmonary tuberculosis (TB) when testing respiratory samples is well established, the evidence base for its diagnostic accuracy for extrapulmonary and sputum-scarce pulmonary TB when testing non-respiratory samples is less clearly defined. METHODS: A systematic literature search of 7 electronic databases (Medline, EMBASE, ISI Web of Science, BIOSIS, Global Health Database, Scopus and Cochrane Database) was conducted to identify studies of the diagnostic accuracy of the Xpert assay when testing non-respiratory samples compared with a culture-based reference standard. Data were extracted and study quality was assessed using the QUADAS-2 tool. Sensitivities and specificities were calculated on a per-sample basis, stratified by sample type and smear microscopy status and summarised using forest plots. Pooled estimates were calculated for groups with sufficient data. RESULTS: Twenty-seven studies with a total of 6,026 non-respiratory samples were included. Among the 23 studies comparing Xpert and culture done on the same samples, sensitivity was very heterogeneous with a median sensitivity of 0.83 (IQR, 0.68-0.94) whereas specificities were typically very high (median, 0.98; IQR, 0.89-1.00). The pooled summary estimates of sensitivity when testing smear-positive and smear-negative samples were 0.95 (95% CI 0.91-1.00) and 0.69 (95% CI 0.60-0.80), respectively. Pooled summary estimates of sensitivity varied substantially between sample types: lymph node tissue, 0.96 (95% CI, 0.72-0.99); tissue samples of all types, 0.88 (95% CI, 0.76-0.94); pleural fluid, 0.34 (95% CI, 0.24-0.44); gastric aspirates for diagnosis of sputum-scarce pulmonary TB, 0.78 (IQR, 0.68 - 0.85). Median sensitivities when testing cerebrospinal fluid and non-pleural serous fluid samples were 0.85 (IQR, 0.75-1.00) and 0.67 (IQR, 0.00-1.00), respectively. CONCLUSION: Xpert detects with high specificity the vast majority of EPTB cases with smear-positive non-respiratory samples and approximately two-thirds of those with smear-negative samples. Xpert is a useful rule-in diagnostic test for EPTB, especially when testing cerebrospinal fluid and tissue samples. In addition, it has a high sensitivity for detecting pulmonary TB when using gastric aspirate samples. These findings support recent WHO guidelines regarding the use of Xpert for TB diagnosis from non-respiratory samples

Availability and use of molecular microbiological and immunological tests for the diagnosis of tuberculosis in europe

INTRODUCTION Currently only limited data exist regarding the availability and clinical use of molecular and immunological tests for tuberculosis (TB) in the European setting. METHODS Web-based survey of Paediatric-Tuberculosis-Network-European-Trialsgroup (ptbnet) and Tuberculosis-Network-European-Trialsgroup (TBnet) members conducted June to December 2013. Both networks comprise clinicians, microbiologists, epidemiologists and researchers predominately based in Europe. RESULTS 191 healthcare professionals from 31 European countries participated. Overall, 26.8% of respondents did not have access to the Xpert MTB/RIF assay; only 44.6% had access to the assay in-house. However, a substantial proportion had access to other commercial and/or non-commercial PCR-based assays for TB (68.8% and 31.8%, respectively). Only 6.4% did not have access to any PCR-based assays for TB. A large proportion of participants with access to the Xpert MTB/RIF assay had used it for the analysis of non-respiratory samples [pleural fluid: 36.5%, gastric aspirates: 34.7%, cerebrospinal fluid: 34.7%, stool samples: 4.3%, blood/serum: 2.6%, 'other samples' (which included biopsy/tissue samples, lymph node aspirates, joint aspirates and urine samples): 16.5%]. Regarding interferon-gamma release assays, a greater proportion of respondents had access to the QuantiFERON-TB Gold assay (84.7%) than to the T-SPOT.TB assay (52.2%). CONCLUSIONS Both immunological and molecular TB tests are widely available across Europe. The QuantiFERON-TB Gold assay is more widely used than the T-SPOT.TB assay, which may reflect the difficulties of integrating an ELISPOT assay into the routine laboratory setting. Although Xpert MTB/RIF assays are optimised and solely licensed for the analysis of sputum samples, in clinical practice they are commonly used for non-respiratory samples. Further research is needed to establish how current molecular TB tests impact on patient care and outcome in the routine clinical setting