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Assessment of the sensitivity and specificity of Xpert MTB/RIF assay as an early sputum biomarker of response to tuberculosis treatment

Research output: Contribution to journalArticle

Author(s)

Sven Olaf Friedrich, Andrea Rachow, Elmar Saathoff, Kasha Singh, Chacha D Mangu, Rodney Dawson, Patrick Phillips, Amour Venter, Anna Bateson, Catharina C Boehme, Norbert Heinrich, Robert Hunt, Martin J Boeree, Alimudden Zumla, Timothy D McHugh, Stephen Henry Gillespie, Andreas Diacon, Michael Hoelscher

School/Research organisations

Abstract

Background
An accurate biomarker for monitoring response to treatment of pulmonary tuberculosis is urgently needed. The Xpert® MTB/RIF assay is a commercially available real-time PCR that detects Mycobacterium tuberculosis-specific DNA sequences in sputum samples.
Methods
Sputum samples from 221 patients with smear-positive tuberculosis enrolled in a multi-centre randomized clinical trial of anti-tuberculosis treatment were analysed weekly (weeks 0 to 8), then at weeks 12, 17, 22, 26 after treatment initiation. The Xpert® MTB/RIF results over time were compared with the results of standard smear and culture methods.
Findings
Xpert® MTB/RIF positivity rates declined slower than those of standard methods. At week 8, smear, solid culture, liquid culture, and the Xpert® MTB/RIF were positive in 29·2%, 26·3%, 42·1% and 84·1%, respectively, and at 26 weeks in 5·0%, 2·5%, 4·1%, and 26·5%, respectively. The decline of quantitative M. tuberculosis DNA detection via the Xpert® MTB/RIF correlated with smear grades
(rho=-0·74; P<0·01), solid culture grades (rho=-0·73; P<0·01), and liquid culture time to positivity (rho=0·73; P<0·01). Compared to combined binary smear and culture results as reference standard, the Xpert® MTB/RIF assay had high sensitivity (97·0%) but poor specificity (48·6%).
Interpretation
Quantitative Xpert® MTB/RIF readouts correlate well with M tuberculosis smear and culture results during anti-tuberculosis treatment. The poor specificity precludes the use of Xpert® MTB/RIF assay as a biomarker for tuberculosis treatment monitoring.
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Details

Original languageEnglish
Pages (from-to)462-470
Number of pages9
JournalThe Lancet Respiratory Medicine
Volume1
Issue number6
Early online date1 Jul 2013
DOIs
Publication statusPublished - 2013

    Research areas

  • Tuberculosis, Biomarker, Mycobacterium tuberculosis, Sputum, Xpert® MTB/RIF assay, Clinical trials, Tuberculosis drugs, Smear microscopy, Culture

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