Diagnostic accuracy of quantitative PCR (Xpert MTB/RIF) for tuberculous meningitis in a high burden setting: a prospective study

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dc.contributor.authorPatel, Vinod Ben_ZA
dc.contributor.authorTheron, Granten_ZA
dc.contributor.authorLenders, Lauraen_ZA
dc.contributor.authorMatinyena, Brianen_ZA
dc.contributor.authorConnolly, Cathyen_ZA
dc.contributor.authorSingh, Raveshen_ZA
dc.contributor.authorCoovadia, Yacooben_ZA
dc.contributor.authorNdung'u, Thumbien_ZA
dc.contributor.authorDheda, Keertanen_ZA
dc.date.accessioned2016-01-11T06:51:26Z
dc.date.available2016-01-11T06:51:26Z
dc.date.issued2013en_ZA
dc.description.abstractBackground: Tuberculous meningitis (TBM) is difficult to diagnose promptly. The utility of the Xpert MTB/RIF test for the diagnosis of TBM remains unclear, and the effect of host- and sample-related factors on test performance is unknown. This study sought to evaluate the sensitivity and specificity of Xpert MTB/RIF for the diagnosis of TBM. Methods and Findings: 235 South-African patients with a meningeal-like illness were categorised as having definite (culture or Amplicor PCR positive), probable (anti-TBM treatment initiated but microbiological confirmation lacking), or non-TBM. Xpert MTB/RIF accuracy was evaluated using 1 ml of uncentrifuged and, when available, 3 ml of centrifuged cerebrospinal fluid (CSF). To evaluate the incremental value of MTB/RIF over a clinically based diagnosis, test accuracy was compared to a clinical score (CS) derived using basic clinical and laboratory information. Of 204 evaluable patients (of whom 87% were HIV-infected), 59 had definite TBM, 64 probable TBM, and 81 non-TBM. Overall sensitivity and specificity (95% CI) were 62% (48%–75%) and 95% (87%–99%), respectively. The sensitivity of Xpert MTB/RIF was significantly better than that of smear microscopy (62% versus 12%; p = 0.001) and significantly better than that of the CS (62% versus 30%; p = 0.001; C statistic 85% [79%–92%]). Xpert MTB/RIF sensitivity was higher when centrifuged versus uncentrifuged samples were used (82% [62%–94%] versus 47% [31%–61%]; p = 0.004). The combination of CS and Xpert MTB/RIF (Xpert MTB/RIF performed if CS<8) performed as well as Xpert MTB/RIF alone but with a ∼10% reduction in test usage. This overall pattern of results remained unchanged when the definite and probable TBM groups were combined. Xpert MTB/RIF was not useful in identifying TBM among HIV-uninfected individuals, although the sample was small. There was no evidence of PCR inhibition, and the limit of detection was ∼80 colony forming units per millilitre. Study limitations included a predominantly HIV-infected cohort and the limited number of culture-positive CSF samples. Conclusions: Xpert MTB/RIF may be a good rule-in test for the diagnosis of TBM in HIV-infected individuals from a tuberculosis-endemic setting, particularly when a centrifuged CSF pellet is used. Further studies are required to confirm these findings in different settings.en_ZA
dc.identifier.apacitationPatel, V. B., Theron, G., Lenders, L., Matinyena, B., Connolly, C., Singh, R., ... Dheda, K. (2013). Diagnostic accuracy of quantitative PCR (Xpert MTB/RIF) for tuberculous meningitis in a high burden setting: a prospective study. <i>PLOS Medicince</i>, http://hdl.handle.net/11427/16241en_ZA
dc.identifier.chicagocitationPatel, Vinod B, Grant Theron, Laura Lenders, Brian Matinyena, Cathy Connolly, Ravesh Singh, Yacoob Coovadia, Thumbi Ndung'u, and Keertan Dheda "Diagnostic accuracy of quantitative PCR (Xpert MTB/RIF) for tuberculous meningitis in a high burden setting: a prospective study." <i>PLOS Medicince</i> (2013) http://hdl.handle.net/11427/16241en_ZA
dc.identifier.citationPatel, V. B., Theron, G., Lenders, L., Matinyena, B., Connolly, C., Singh, R., ... & Dheda, K. (2013). Diagnostic accuracy of quantitative PCR (Xpert MTB/RIF) for tuberculous meningitis in a high burden setting: a prospective study. PLoS Med, 10(10), e1001536. doi:10.1371/journal.pmed.1001536en_ZA
dc.identifier.ris TY - Journal Article AU - Patel, Vinod B AU - Theron, Grant AU - Lenders, Laura AU - Matinyena, Brian AU - Connolly, Cathy AU - Singh, Ravesh AU - Coovadia, Yacoob AU - Ndung'u, Thumbi AU - Dheda, Keertan AB - Background: Tuberculous meningitis (TBM) is difficult to diagnose promptly. The utility of the Xpert MTB/RIF test for the diagnosis of TBM remains unclear, and the effect of host- and sample-related factors on test performance is unknown. This study sought to evaluate the sensitivity and specificity of Xpert MTB/RIF for the diagnosis of TBM. Methods and Findings: 235 South-African patients with a meningeal-like illness were categorised as having definite (culture or Amplicor PCR positive), probable (anti-TBM treatment initiated but microbiological confirmation lacking), or non-TBM. Xpert MTB/RIF accuracy was evaluated using 1 ml of uncentrifuged and, when available, 3 ml of centrifuged cerebrospinal fluid (CSF). To evaluate the incremental value of MTB/RIF over a clinically based diagnosis, test accuracy was compared to a clinical score (CS) derived using basic clinical and laboratory information. Of 204 evaluable patients (of whom 87% were HIV-infected), 59 had definite TBM, 64 probable TBM, and 81 non-TBM. Overall sensitivity and specificity (95% CI) were 62% (48%–75%) and 95% (87%–99%), respectively. The sensitivity of Xpert MTB/RIF was significantly better than that of smear microscopy (62% versus 12%; p = 0.001) and significantly better than that of the CS (62% versus 30%; p = 0.001; C statistic 85% [79%–92%]). Xpert MTB/RIF sensitivity was higher when centrifuged versus uncentrifuged samples were used (82% [62%–94%] versus 47% [31%–61%]; p = 0.004). The combination of CS and Xpert MTB/RIF (Xpert MTB/RIF performed if CS<8) performed as well as Xpert MTB/RIF alone but with a ∼10% reduction in test usage. This overall pattern of results remained unchanged when the definite and probable TBM groups were combined. Xpert MTB/RIF was not useful in identifying TBM among HIV-uninfected individuals, although the sample was small. There was no evidence of PCR inhibition, and the limit of detection was ∼80 colony forming units per millilitre. Study limitations included a predominantly HIV-infected cohort and the limited number of culture-positive CSF samples. Conclusions: Xpert MTB/RIF may be a good rule-in test for the diagnosis of TBM in HIV-infected individuals from a tuberculosis-endemic setting, particularly when a centrifuged CSF pellet is used. Further studies are required to confirm these findings in different settings. DA - 2013 DB - OpenUCT DO - 10.1371/journal.pmed.1001536 DP - University of Cape Town J1 - PLOS Medicince LK - https://open.uct.ac.za PB - University of Cape Town PY - 2013 T1 - Diagnostic accuracy of quantitative PCR (Xpert MTB/RIF) for tuberculous meningitis in a high burden setting: a prospective study TI - Diagnostic accuracy of quantitative PCR (Xpert MTB/RIF) for tuberculous meningitis in a high burden setting: a prospective study UR - http://hdl.handle.net/11427/16241 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16241
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pmed.1001536
dc.identifier.vancouvercitationPatel VB, Theron G, Lenders L, Matinyena B, Connolly C, Singh R, et al. Diagnostic accuracy of quantitative PCR (Xpert MTB/RIF) for tuberculous meningitis in a high burden setting: a prospective study. PLOS Medicince. 2013; http://hdl.handle.net/11427/16241.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDivision of Pulmonologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2013 Patel et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLOS Medicinceen_ZA
dc.source.urihttp://journals.plos.org/plosmedicineen_ZA
dc.subject.otherMycobacterium tuberculosisen_ZA
dc.subject.otherTuberculosisen_ZA
dc.subject.otherMeningitisen_ZA
dc.subject.otherCerebrospinal fluiden_ZA
dc.subject.otherPolymerase chain reactionen_ZA
dc.subject.otherDiagnostic medicineen_ZA
dc.subject.otherTuberculosis diagnosis and managementen_ZA
dc.subject.otherHIVen_ZA
dc.titleDiagnostic accuracy of quantitative PCR (Xpert MTB/RIF) for tuberculous meningitis in a high burden setting: a prospective studyen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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