Same-Day Tools, Including Xpert Ultra and IRISA-TB, for Rapid Diagnosis of Pleural Tuberculosis: a Prospective Observational Study

Abstract

The diagnosis of pleural tuberculosis (TB) is problematic. The comparative performance of newer same-day tools for pleural TB, including Xpert MTB/RIF Ultra (ULTRA), has hitherto not been comprehensively studied. Adenosine deaminase (ADA), IRISA-TB (interferon gamma ultrasensitive rapid immunosuspension assay), Xpert MTB/RIF, and ULTRA performance outcomes were evaluated in pleural fluid samples from 149 patients with suspected pleural TB. The reference standard was culture positivity (fluid, biopsy specimen, or sputum) and/or pleural biopsy histopathology (termed definite TB). Those designated as having non-TB were negative by microbiological testing and were not initiated on anti-TB treatment. To determine the effect of sample concentration, 65 samples underwent pelleting by centrifugation, followed by conventional Xpert MTB/RIF and ULTRA. Of the 149 patients, 49 had definite TB, 16 had probable TB (not definite but treated for TB), and 84 had non-TB. ULTRA sensitivity and specificity (95% confidence intervals [CI]) were similar to those of Xpert MTB/RIF [sensitivity, 37.5% (25.3 to 51.2) versus 28.6% (15.9 to 41.2), respectively; specificity, 98.8% (96.5 to 100) versus 98.8% (96.5 to 100), respectively]. Centrifugation did not significantly improve ULTRA sensitivity (29.5% versus 31.3%, respectively). Adenosine deaminase and IRISA-TB sensitivity were 84.4% (73.9 to 95.0) and 89.8% (81.3 to 98.3), respectively. However, IRISA-TB demonstrated significantly better specificity (96.4% versus 87.5% [P = 0.034]), positive predictive value (93.6% versus 80.9 [P = 0.028]), and positive likelihood ratio (25.1 versus 6.8 [P = 0.032]) than ADA. In summary, Xpert ULTRA has poor sensitivity for the diagnosis of pleural TB. Alternative assays (ADA and IRISA-TB) are significantly more sensitive, with IRISA-TB demonstrating a higher specificity and rule-in value than ADA in this high-TB-burden setting where HIV is endemic.

Xpert MTB/RIF ultra for rapid diagnosis of extrapulmonary tuberculosis in a high-income low-tuberculosis prevalence setting

“…When culture is used as reference standard, the reported sensitivity of Ultra varies, but is generally high in lymph node specimens (90-94%) 18,24 , FNAs and tissue samples (87-95%) 18,22 , cerebrospinal fluid (80-100%) 17,18,21,25,29 and pus specimens (65-95%) 18,19 , and lower in pleural fluid samples (48-84%) 18,20,22,23 , which is in line with our findings. Several of the studies also show that Ultra can detect MTC in culture negative specimens from clinically diagnosed TB cases 17,[19][20][21][22][23][24][25]28,29 , thus, contributing to improved diagnosis of TB in samples with a very low bacillary load.…”

“…Several studies have been published on the diagnostic accuracy of Ultra in extrapulmonary specimens 11,14,15,[17][18][19][20][21][22][23][24][25]28,29 . Most of the studies were performed in TB endemic settings 14,17,[19][20][21][22][23][24][25]28,29 , and only three studies have investigated Ultra test performance in low TB prevalence settings 11,15,18 . However, two of these studies were retrospective and performed on selected sample material.…”

“…Most, but not all 28 , 29 , of the studies that investigate Ultra for the diagnosis of EPTB suggest increased sensitivity of Ultra compared to Xpert in different extrapulmonary specimens 11 , 14 , 15 , 17 , 19 – 23 , 25 . When culture is used as reference standard, the reported sensitivity of Ultra varies, but is generally high in lymph node specimens (90–94%) 18 , 24 , FNAs and tissue samples (87–95%) 18 , 22 , cerebrospinal fluid (80–100%) 17 , 18 , 21 , 25 , 29 and pus specimens (65–95%) 18 , 19 , and lower in pleural fluid samples (48–84%) 18 , 20 , 22 , 23 , which is in line with our findings.…”

Performance of Xpert MTB/RIF Ultra for diagnosis of pulmonary and extra-pulmonary tuberculosis, one year of use in a multi-centric hospital laboratory in Brussels, Belgium

“…Pleural TB is the most common cause of pleural effusion in many developing countries and remains a diagnostic challenge due to unreliable laboratory detection test results [ 16 ]. Numerous studies [ 17 – 20 ] reported poor sensitivity (29 to 55%) for testing of pleural effusion specimens. This could be due to very low bacillary load, the presence of inhibitory substance or the use of different gold standards in various studies.…”

Which sample type is better for Xpert MTB/RIF to diagnose adult and pediatric pulmonary tuberculosis?

“…These two changes confer Ultra's lower limit of detection than Xpert MTB/RIF and culture [78]. The following clinical trials have found that improper sample types and poor sample quality still have an adverse influence on the sensitivity of Ultra [79,80]. Obviously, no matter how sensitive the detection method is, choosing proper sample type and ensuring the quality of sample are crucial.…”