Evaluation of the Xpert MTB/RIF assay for the diagnosis of pulmonary tuberculosis in a high HIV prevalence setting
Date
2011
Authors
Theron G.
Peter J.
Van Zyl-Smit R.
Mishra H.
Streicher E.
Murray S.
Dawson R.
Whitelaw A.
Hoelscher M.
Sharma S.
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
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.
Description
Keywords
Diagnostics, HIV, PCR, Smear-negative tuberculosis, Tuberculosis, rifampicin, adult, aged, antibiotic resistance, article, bacterial load, bacterium culture, computer program, diagnostic accuracy, diagnostic test accuracy study, female, human, Human immunodeficiency virus infection, Human immunodeficiency virus prevalence, lung tuberculosis, major clinical study, male, microscopy, Mycobacterium tuberculosis, performance, phenotype, polymerase chain reaction, predictive value, priority journal, sensitivity and specificity, smear microscopy, sputum culture, xpert mtb rif diagnostic tool, Adolescent, Adult, Aged, Aged, 80 and over, Antitubercular Agents, Bacterial Proteins, Drug Resistance, Bacterial, Female, HIV Infections, Humans, Male, Middle Aged, Molecular Diagnostic Techniques, Mycobacterium tuberculosis, Polymerase Chain Reaction, Predictive Value of Tests, Prevalence, Rifampin, Sensitivity and Specificity, Tuberculosis, Multidrug-Resistant, Tuberculosis, Pulmonary, Young Adult
Citation
American Journal of Respiratory and Critical Care Medicine
184
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184
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