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

doi:10.1016/j.ijtb.2018.02.011

Abstract

Highlights

Tuberculous meningitis is the second most common cause of adult meningitis in Africa.1–4 Meningitis from tuberculosis leads to fatality in more than 50% of cases, in large part due to difficulty and delay in diagnosis.5 Cerebrospinal fluid (CSF) smear microscopy for acid-fast bacilli has poor sensitivity (≤15%) in routine care.5 mycobacterial culture has higher sensitivity (50–60%), culture is too slow to be clinically useful.5In 2013, WHO endorsed the Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA, USA) as the preferred initial test to investigate tuberculous meningitis after a systematic review of 13 studies.6–8 The Xpert is cartridge-based fullyautomated PCR test
Added value of this study To our knowledge, we present the first evaluation of the diagnostic performance of Xpert Ultra in the diagnosis of tuberculous meningitis
Of 221 HIV-infected people presenting with suspected meningitis between Feb 27, 2015, and Nov 7, 2016, 129 participants underwent tuberculous testing with Xpert, culture, and Xpert Ultra on centrifuged cerebrospinal fluid (CSF)

Summary

Introduction

Tuberculous meningitis is the second most common cause of adult meningitis in Africa. Meningitis from tuberculosis leads to fatality in more than 50% of cases, in large part due to difficulty and delay in diagnosis. Cerebrospinal fluid (CSF) smear microscopy for acid-fast bacilli has poor sensitivity (≤15%) in routine care. mycobacterial culture has higher sensitivity (50–60%), culture is too slow to be clinically useful.5In 2013, WHO endorsed the Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA, USA) as the preferred initial test to investigate tuberculous meningitis after a systematic review of 13 studies. The Xpert is cartridge-based fullyautomated PCR test. In 2013, WHO endorsed the Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA, USA) as the preferred initial test to investigate tuberculous meningitis after a systematic review of 13 studies.. The first reported 67% sensitivity using Xpert in microbiologically proven tuberculous meningitis in HIV-infected South Africans.. This study initially tested 1 mL of CSF but later found higher sensitivity (82%; 22 of 27 positive cases) when centrifuging 3 mL of CSF.. Sensitivity compared with consensus clinical case definition was only 36%.9,10. The second large cohort study, in Vietnam, measured Xpert against the same clinical case definition and found 59% sensitivity generally using 2 mL or less of centrifuged CSF.. The imperfect sensitivity has meant no test can exclude tuberculous meningitis. The first reported 67% sensitivity using Xpert in microbiologically proven tuberculous meningitis in HIV-infected South Africans. This study initially tested 1 mL of CSF but later found higher sensitivity (82%; 22 of 27 positive cases) when centrifuging 3 mL of CSF. Sensitivity compared with consensus clinical case definition was only 36%.9,10 The second large cohort study, in Vietnam, measured Xpert against the same clinical case definition and found 59% sensitivity generally using 2 mL or less of centrifuged CSF. A third Ugandan study reported 28% sensitivity with 2 mL of uncentrifuged CSF and 72% sensitivity when centrifuging a median volume of 6 mL (IQR 4–10) with Xpert. the imperfect sensitivity has meant no test can exclude tuberculous meningitis.

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