Diagnostic Accuracy of Quantitative PCR (Xpert MTB/RIF) for Tuberculous Meningitis in a High Burden Setting: A Prospective Study

Patel, Vinod; Theron, Grant; Lenders, Laura; Matinyena, Brian; Connolly, Cathy; Singh, Ravesh; Coovadia, Yacoob; Ndung’u, Thumbi; Dheda, Keertan

doi:10.1371/journal.pmed.1001536

Cited by 153 publications

(169 citation statements)

References 37 publications

(37 reference statements)

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“…In a predominantly HIV-infected SA TBM cohort study (87% of the 204 participants were HIV-infected), the sensitivity and specificity of Xpert were 67% and 94%, respectively; this analysis included patients with definite TBM (CSF M. tuberculosis culture and/or Amplicor PCR positive), compared with patients with other causes of meningitis as controls. [9] Although the overall sensitivity decreased to 36% when probable TBM was included in the reference standard, using a larger volume (3 mL) of centrifuged CSF compared with 1 mL of neat CSF increased the sensitivity markedly from 26% to 65% in this analysis.…”

Section: Definitive Diagnostic Methodsmentioning

confidence: 67%

The diagnosis and medical management of tuberculous meningitis in adults

Marais

Wilkinson

2014

S Afr Med J

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Section: Definitive Diagnostic Methodsmentioning

confidence: 67%

The diagnosis and medical management of tuberculous meningitis in adults

Marais

Wilkinson

2014

S Afr Med J

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“…Among participants without cryptococcal meningitis (who require large volume lumbar punctures for control of intracranial pressure), testing of at least 6 mL of CSF (median 10 mL [IQR [8][9][10][11][12]) was associated with a tuberculous meningitis diagnosis (19 [26%] of 73) compared with less than 6 mL (4 mL [3-5mL]; 3 [7%] of 43; p=0·014)].…”

Section: Resultsmentioning

confidence: 99%

Diagnostic accuracy of Xpert MTB/RIF Ultra for tuberculous meningitis in HIV-infected adults: A prospective cohort study

2018

Indian Journal of Tuberculosis

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“…Of the two major studies included in the meta-analysis, Patel and colleagues reported 67% sensitivity against microbiologically proven TBM and 36% against consensus clinical case definitions, while Nhu and colleagues showed 59% sensitivity against the same case definitions 10– 12 . Additionally, use of a larger volume of centrifuged CSF improves sensitivity of Xpert 10, 13 . Yet, inadequate negative predictive value means that Xpert cannot substitute for clinical judgement 14 .…”

Section: Introductionmentioning

confidence: 99%

Can improved diagnostics reduce mortality from Tuberculous meningitis? Findings from a 6.5-year cohort in Uganda

Cresswell¹,

Bangdiwala²,

Bahr³

et al. 2018

Wellcome Open Res

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Background: Tuberculous meningitis (TBM) is the second most common cause of meningitis in sub-Saharan Africa and is notoriously difficult to diagnose. We describe the impact of improved TBM diagnostics over 6.5 years at two Ugandan referral hospitals. Methods: Cohort one received cerebrospinal fluid (CSF) smear microscopy only (2010-2013). Cohort two received smear microscopy and Xpert MTB/Rif (Xpert) on 1ml unprocessed CSF at physician discretion (2011-2013). Cohort three received smear microscopy, routine liquid-media culture and Xpert on large volume centrifuged CSF (2013-2017) for all meningitis suspects with a negative CSF cryptococcal antigen. We compared rates of microbiologically confirmed TBM and hospital outcomes over time. Results: 1672 HIV-infected adults presenting with suspected meningitis underwent lumbar puncture, of which 33% (558/1672) had negative CSF cryptococcal antigen and 12% (195/1672) were treated for TB meningitis. Over the study period, microbiological confirmation of TBM increased from 3% to 41% (P<0.01) and there was a decline in in-hospital mortality from 57% to 41% (P=0.27) amongst those with a known outcome. Adjusting for definite TBM diagnosis and antiretroviral therapy use, and using imputed data, assuming 50% of those with an unknown outcome died, the odds of dying were nearly twice as high in cohort one (adjusted odds ratio 1.7, 95% CI 0.7 to 4.4) compared to cohort three. Sensitivity of Xpert was 63% (38/60) and culture was 65% (39/60) against a composite reference standard. Conclusions: As TBM diagnostics have improved, microbiologically-confirmed TBM diagnoses have increased and in-hospital mortality has declined. Yet, mortality due to TB meningitis remains unacceptably high and further measures are needed to improve outcomes from TBM in Uganda.

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Diagnostic Accuracy of Quantitative PCR (Xpert MTB/RIF) for Tuberculous Meningitis in a High Burden Setting: A Prospective Study

Abstract: Vinod Patel and colleagues evaluate the sensitivity and specificity of quantitative PCR using Xpert MTB/RIF for diagnosis of TB meningitis in the high-burden setting of South Africa. Please see later in the article for the Editors' Summary

Cited by 153 publications

References 37 publications

The diagnosis and medical management of tuberculous meningitis in adults

The diagnosis and medical management of tuberculous meningitis in adults

Diagnostic accuracy of Xpert MTB/RIF Ultra for tuberculous meningitis in HIV-infected adults: A prospective cohort study

Can improved diagnostics reduce mortality from Tuberculous meningitis? Findings from a 6.5-year cohort in Uganda

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