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

Richard Meldau; Philippa Randall; Anil Pooran; Jason Limberis; Edson Makambwa; Muhammed Dhansay; Aliasgar Esmail; Keertan Dheda

doi:10.1128/JCM.00614-19

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

J Clin Microbiol. 2019 Aug 26;57(9):e00614-19. doi: 10.1128/JCM.00614-19. Print 2019 Sep.

Authors

Richard Meldau¹, Philippa Randall¹, Anil Pooran¹, Jason Limberis¹, Edson Makambwa¹, Muhammed Dhansay¹, Aliasgar Esmail¹, Keertan Dheda^{2

3}

Affiliations

¹ Centre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and UCT Lung Institute & South African MRC/UCT Centre for the Study of Antimicrobial Resistance, University of Cape Town, Cape Town, South Africa.
² Centre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and UCT Lung Institute & South African MRC/UCT Centre for the Study of Antimicrobial Resistance, University of Cape Town, Cape Town, South Africa keertan.dheda@uct.ac.za.
³ Faculty of Infectious and Tropical Diseases, Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom.

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.

Keywords: IRISA-TB; Mycobacterium tuberculosis; ULTRA; Xpert MTB/RIF; adenosine deaminase; interferon gamma.

Publication types

Evaluation Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Bacteriological Techniques / methods*
Female
Humans
Male
Middle Aged
Molecular Diagnostic Techniques / methods*
Pleural Effusion / microbiology*
Prospective Studies
Sensitivity and Specificity
Time Factors
Tuberculosis, Pleural / diagnosis*