Could Xpert MTB/RIF help identify tuberculous meningitis?

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Tuberculous meningitis (TBM) is difficult to diagnose promptly. The usefulness of Xpert MTB/RIF for diagnosing TBM and the effects of host- and sample-related factors on its performance were unclear. The researchers set out to evaluate the test’s sensitivity and specificity.

They categorized 235 South African patients with a meningeal-like illness as having definite TBM (positive culture or Amplicor PCR), probable TBM (anti-TBM treatment started without microbiological confirmation), or non-TBM. They assessed Xpert MTB/RIF accuracy using 1 ml of uncentrifuged cerebrospinal fluid (CSF) and, when available, 3 ml of centrifuged CSF. To assess its added value over clinical diagnosis, they compared its accuracy with a clinical score (CS) based on basic clinical and laboratory information.

Of 204 evaluable patients, 87% were HIV-infected; 59 had definite TBM, 64 had probable TBM, and 81 had non-TBM. Overall sensitivity was 62% (95% confidence interval [CI] 48%–75%) and specificity was 95% (95% CI 87%–99%). Xpert MTB/RIF sensitivity was significantly higher than smear microscopy sensitivity (62% versus 12%; p = 0.001) and CS sensitivity (62% versus 30%; p = 0.001; C statistic 85% [79%–92%]). Sensitivity was higher with centrifuged than uncentrifuged samples (82% [62%–94%] versus 47% [31%–61%]; p = 0.004).

Combining CS and Xpert MTB/RIF—performing Xpert MTB/RIF if CS was below 8—performed as well as Xpert MTB/RIF alone while reducing test usage by approximately 10%. The overall pattern remained unchanged when the definite and probable TBM groups were combined. Xpert MTB/RIF was not useful for identifying TBM among HIV-uninfected individuals, although that sample was small. There was no evidence of PCR inhibition, and the detection limit was approximately 80 colony-forming units per millilitre.

Limitations included a predominantly HIV-infected cohort and a limited number of culture-positive CSF samples. The researchers concluded that Xpert MTB/RIF may be a good rule-in test for TBM in HIV-infected individuals in a tuberculosis-endemic setting, particularly when a centrifuged CSF pellet is used. Further studies are needed to confirm the findings in different settings. The abstract points readers to an Editors’ Summary later in the article.