Document Detail

Evaluation of the Xpert MTB/RIF assay for the diagnosis of pulmonary tuberculosis in a high HIV prevalence setting.
MedLine Citation:
PMID:  21493734     Owner:  NLM     Status:  MEDLINE    
RATIONALE: Xpert MTB/RIF is a novel automated molecular diagnostic recently endorsed by the World Health Organization. However, performance-related data from high HIV prevalence settings are limited.
OBJECTIVES: The impact of sample-related factors on performance and the significance of Xpert MTB/RIF-positive culture-negative discordance remain unclear.
METHODS: Xpert MTB/RIF was evaluated using single archived spot-sputum samples from 496 South African patients with suspected TB. Mycobacterium tuberculosis culture positivity and phenotypic resistance to rifampicin served as reference standards.
MEASUREMENTS AND MAIN RESULTS: Overall, Xpert MTB/RIF detected 95% (95% confidence interval [CI], 88-98%; 89 of 94) of smear-positive culture-positive cases and the specificity was 94% (91-96%; 320 of 339). The sensitivity in smear-negative cases was 55% (35-73%; 12 of 22) when the analysis was restricted to 1 ml of unprocessed sputum and culture time-to-positivity of less than or equal to 28 days. Compared with smear microscopy (n=94), Xpert MTB/RIF detected an additional 17 cases (n=111) representing an 18% (11-27%; 111 vs. 94) relative increase in the rapid TB case detection rate. Moreover, compared with smear microscopy, the inclusion of Xpert MTB/RIF-positive culture-negative TB cases (ruled-in by an alternative diagnostic method) resulted in the detection of a further 16 cases (n=127), thus significantly increasing the rapid TB case detection rate to 35% (95% CI, 26-45%; 94 to 111 vs. 94 to 127; P<0.01), the overall specificity to 99.1% (97-100%; 320 of 323; P<0.001), and sensitivity in smear-negative TB to 60% (P=0.12). Performance strongly correlated with smear status and culture time-to-positivity. In patients infected with HIV compared with patients uninfected with HIV Xpert MTB/RIF showed a trend to reduced sensitivity (P=0.09) and significantly reduced negative predictive value (P=0.01). The negative predictive value for rifampicin resistance was 99.4%.
CONCLUSIONS: XpertMTB/RIF outperformed smear microscopy, established a diagnosis in a significant proportion of patients with smear-negative TB, detected many highly likely TB cases missed by culture, and accurately ruled out rifampicin-resistant TB. Sample-specific factors had limited impact on performance. Performance in patients infected with HIV, especially those with advanced immunosuppression, warrants further study.
Grant Theron; Jonny Peter; Richard van Zyl-Smit; Hridesh Mishra; Elizabeth Streicher; Samuel Murray; Rodney Dawson; Andrew Whitelaw; Michael Hoelscher; Surendra Sharma; Madhukar Pai; Robin Warren; Keertan Dheda
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-04-14
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  184     ISSN:  1535-4970     ISO Abbreviation:  Am. J. Respir. Crit. Care Med.     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-07-08     Completed Date:  2011-09-13     Revised Date:  2012-01-25    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  132-40     Citation Subset:  AIM; IM    
Lung Infection and Immunity Unit, Division of Pulmonology and UCT Lung Institute, Department of Medicine, University of Cape Town, Cape Town, South Africa.
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MeSH Terms
Aged, 80 and over
Antitubercular Agents / pharmacology
Bacterial Proteins / genetics
Drug Resistance, Bacterial
HIV Infections / complications*,  epidemiology
Middle Aged
Molecular Diagnostic Techniques*
Mycobacterium tuberculosis / drug effects,  genetics
Polymerase Chain Reaction
Predictive Value of Tests
Rifampin / pharmacology
Sensitivity and Specificity
Tuberculosis, Multidrug-Resistant / diagnosis
Tuberculosis, Pulmonary / complications*,  diagnosis*
Young Adult
Grant Support
//Canadian Institutes of Health Research
Reg. No./Substance:
0/Antitubercular Agents; 0/Bacterial Proteins; 0/rpoB protein, Mycobacterium tuberculosis; 13292-46-1/Rifampin
Comment In:
Am J Respir Crit Care Med. 2011 Dec 15;184(12):1420; author reply 1420   [PMID:  22174115 ]

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