Evaluation of the Xpert MTB/RIF assay for the diagnosis of pulmonary tuberculosis in a high HIV prevalence setting

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dc.contributor.authorTheron G.
dc.contributor.authorPeter J.
dc.contributor.authorVan Zyl-Smit R.
dc.contributor.authorMishra H.
dc.contributor.authorStreicher E.
dc.contributor.authorMurray S.
dc.contributor.authorDawson R.
dc.contributor.authorWhitelaw A.
dc.contributor.authorHoelscher M.
dc.contributor.authorSharma S.
dc.contributor.authorPai M.
dc.contributor.authorWarren R.
dc.contributor.authorDheda K.
dc.date.accessioned2011-10-13T16:58:44Z
dc.date.available2011-10-13T16:58:44Z
dc.date.issued2011
dc.description.abstractRationale: 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.
dc.description.versionArticle
dc.identifier.citationAmerican Journal of Respiratory and Critical Care Medicine
dc.identifier.citation184
dc.identifier.citation1
dc.identifier.citationhttp://www.scopus.com/inward/record.url?eid=2-s2.0-79960509329&partnerID=40&md5=aabaaec9b9db1d97fe8f7f71a72d2231
dc.identifier.issn1073449X
dc.identifier.other10.1164/rccm.201101-0056OC
dc.identifier.urihttp://hdl.handle.net/10019.1/16837
dc.subjectDiagnostics
dc.subjectHIV
dc.subjectPCR
dc.subjectSmear-negative tuberculosis
dc.subjectTuberculosis
dc.subjectrifampicin
dc.subjectadult
dc.subjectaged
dc.subjectantibiotic resistance
dc.subjectarticle
dc.subjectbacterial load
dc.subjectbacterium culture
dc.subjectcomputer program
dc.subjectdiagnostic accuracy
dc.subjectdiagnostic test accuracy study
dc.subjectfemale
dc.subjecthuman
dc.subjectHuman immunodeficiency virus infection
dc.subjectHuman immunodeficiency virus prevalence
dc.subjectlung tuberculosis
dc.subjectmajor clinical study
dc.subjectmale
dc.subjectmicroscopy
dc.subjectMycobacterium tuberculosis
dc.subjectperformance
dc.subjectphenotype
dc.subjectpolymerase chain reaction
dc.subjectpredictive value
dc.subjectpriority journal
dc.subjectsensitivity and specificity
dc.subjectsmear microscopy
dc.subjectsputum culture
dc.subjectxpert mtb rif diagnostic tool
dc.subjectAdolescent
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectAntitubercular Agents
dc.subjectBacterial Proteins
dc.subjectDrug Resistance, Bacterial
dc.subjectFemale
dc.subjectHIV Infections
dc.subjectHumans
dc.subjectMale
dc.subjectMiddle Aged
dc.subjectMolecular Diagnostic Techniques
dc.subjectMycobacterium tuberculosis
dc.subjectPolymerase Chain Reaction
dc.subjectPredictive Value of Tests
dc.subjectPrevalence
dc.subjectRifampin
dc.subjectSensitivity and Specificity
dc.subjectTuberculosis, Multidrug-Resistant
dc.subjectTuberculosis, Pulmonary
dc.subjectYoung Adult
dc.titleEvaluation of the Xpert MTB/RIF assay for the diagnosis of pulmonary tuberculosis in a high HIV prevalence setting
dc.typeArticle
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