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Lancet Respir Med. 2013 Aug;1(6):462-70. doi: 10.1016/S2213-2600(13)70119-X. Epub 2013 Jul 1.

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

Author information

1
Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
2
National Institute of Medical Research-Mbeya Medical Research Centre, Mbeya, Tanzania; Division of Infectious Diseases and Tropical Medicine, Medical Centre of the University of Munich (LMU), Munich, Germany; DZIF German Centre for Infection Research, Munich, Germany.
3
Division of Infectious Diseases and Tropical Medicine, Medical Centre of the University of Munich (LMU), Munich, Germany.
4
Centre for Clinical Microbiology, Division of Infection and Immunity, University College London, London, UK.
5
National Institute of Medical Research-Mbeya Medical Research Centre, Mbeya, Tanzania.
6
Division of Pulmonology, Department of Medicine, University of Cape Town Lung Institute, Groote Schuur Hospital, Cape Town, South Africa.
7
Medical Research Centre (MRC) Clinical Trials Unit, London, UK.
8
MRC Centre for Molecular and Cellular Biology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
9
Foundation of Innovative New Diagnostics, Geneva, Switzerland.
10
Radboud University Nijmegen Medical Centre/UCCZ Dekkerswald, Nijmegen.
11
University of St Andrews School of Medicine, North Haugh, St Andrews, Scotland, UK. Electronic address: shg3@st-andrews.ac.uk.
12
Division of Infectious Diseases and Tropical Medicine, Medical Centre of the University of Munich (LMU), Munich, Germany; DZIF German Centre for Infection Research, Munich, Germany.

Abstract

BACKGROUND:

An accurate biomarker is urgently needed to monitor the response to treatment in patients with pulmonary tuberculosis. The Xpert MTB/RIF assay is a commercially available real-time PCR that can be used to detect Mycobacterium-tuberculosis-specific DNA sequences in sputum samples. We therefore evaluated this assay with serial sputum samples obtained over 26 weeks from patients undergoing treatment for tuberculosis.

METHODS:

We analysed sputum samples from 221 patients with smear-positive tuberculosis enrolled at two sites (Cape Town, South Africa, and Mbeya, Tanzania) of a multicentre randomised clinical trial REMoxTB of antituberculosis treatment on a weekly basis (weeks 0 to 8), then at weeks 12, 17, 22, and 26 after treatment initiation. The Xpert MTB/RIF results over time were compared with the results of standard smear microscopy and culture methods.

FINDINGS:

We obtained and analysed 2741 sputum samples from 221 patients. The reduction in positivity rates with Xpert MTB/RIF were slower than those with the standard methods. At week 8, positive results were obtained for 62 (29%) of 212 sputum samples with smear microscopy, 46 (26%) of 175 with solid culture (Löwenstein-Jensen medium), 77 (42%) of 183 with liquid culture (Bactec MGIT960 system), and 174 (84%) of 207 with Xpert MTB/RIF; at 26 weeks, positive results were obtained for ten (5%) of 199, four (3%) of 157, seven (4%) of 169, and 22 (27%) of 83 sputum samples, respectively. The reduction in detection of quantitative M tuberculosis DNA with Xpert MTB/RIF correlated with smear grades (ρ=-0·74; p<0·0001), solid culture grades (ρ=-0·73; p<0·0001), and time to liquid culture positivity (ρ=0·73; p<0·0001). Compared with the combined binary smear and culture results as a reference standard, the Xpert MTB/RIF assay had high sensitivity (97·0%, 95% CI 95·8-97·9), but poor specificity (48·6%, 45·0-52·2).

INTERPRETATION:

The poor specificity precludes the use of the Xpert MTB/RIF assay as a biomarker for monitoring tuberculosis treatment, and should not replace standard smear microscopy and culture.

FUNDING:

Global Alliance for TB Drug Development, Bill & Melinda Gates Foundation, UK Medical Research Council, German Ministry of Science and Technology.

PMID:
24429244
DOI:
10.1016/S2213-2600(13)70119-X
[Indexed for MEDLINE]
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