Comparative accuracy of pleural fluid unstimulated interferon-gamma and adenosine deaminase for diagnosing pleural tuberculosis: A systematic review and meta-analysis

Abstract

Objective We compared diagnostic accuracy of pleural fluid adenosine deaminase (ADA) and interferon-gamma (IFN-γ) in diagnosing tuberculous pleural effusion (TPE) through systematic review and comparative meta-analysis. Methods We queried PubMed and Embase databases to identify studies providing paired data for sensitivity and specificity of both pleural fluid ADA and IFN-γ for diagnosing TPE. We used hierarchical summary receiver operating characteristic (HSROC) plots and HSROC meta-regression to model individual and comparative diagnostic performance of the two tests. Results We retrieved 376 citations and included 45 datasets from 44 publications (4974 patients) in our review. Summary estimates for sensitivity and specificity for ADA were 0.88 (95% CI 0.85–0.91) and 0.91 (95% CI 0.89–0.92), while for IFN-γ they were 0.91 (95% CI 0.89–0.94) and 0.96 (95% CI 0.94–0.97), respectively. HSROC plots showed consistently greater diagnostic accuracy for IFN-γ over ADA across the entire range of observations. HSROC meta-regression using test-type as covariate yielded a relative diagnostic odds ratio of 2.22 (95% CI 1.68–2.94) in favour of IFN-γ, along with better summary sensitivity and specificity figures. No prespecified subgroup variable significantly influenced the summary diagnostic accuracy estimates. Conclusion Pleural fluid IFN-γ estimation has better diagnostic accuracy than ADA estimation for diagnosis of TPE.

Economic evaluation of microbiological and host biomarker-based tests for the diagnosis of pleural tuberculosis in a high burden setting

“…Studies in the same setting showed that ADA suffered from a sub-optimal specificity at a cut point of 30 IU/litre. In these settings, ADA specificity ranged from ~75% to 90% (6,10,18,23,24). This leads to false positives (in those without TB) and unnecessary initiation of treatment, which contributed to IRISA-TB being more cost effective compared to ADA.…”

“…IRISA-TB was found to be more cost-effective than ADA despite both tests having high sensitivity. Compared to ADA, several studies have shown that unstimulated IFNγ-based assays (including IRISA-TB) has a higher specificity and negative predictive value (6,11,18,22). Studies in the same setting showed that ADA suffered from a sub-optimal specificity at a cut point of 30 IU/litre.…”

“…Only two studies (6,7) were identified where Xpert ULTRA was used for pleural TB diagnosis in a high burden setting, one being in South Africa. There is extensive performance data on the use of ADA for pleural TB diagnosis; estimates used in this model were obtained from a South African study and two recent meta-analyses (6,10,18). Finally, although there are several studies that investigated the performance of unstimulated IFN-γ for pleural TB diagnosis, only two studies evaluated the performance of the IRISA TB format (6,11).…”

Diagnostic accuracy of pleural fluid lactate dehydrogenase to adenosine deaminase ratio for tuberculous pleural effusion: an analysis of two cohorts

“…Previous studies usually adopt 35 U/L as a threshold for TPE diagnosis [ 12 , 15 ], which was also endorsed by the guideline [ 17 ]. Therefore, we used this threshold to determine the sensitivity and specificity of ADA in this study.…”

“…Adenosine deaminase (ADA) is the most studied among all available PF biomarkers. According to the published meta-analyses, PF ADA has a sensitivity of 90% and specificity of 92% [ 15 , 16 ]. Although PF ADA is not the gold standard test for the diagnosis of TPE, it is recommended as a ‘rule out’ test in countries with a low prevalence of TB, according to the British Thoracic Society Pleural Disease Guideline [ 17 ].…”