Xpert Ultra improves TB meningitis detection, does not rule out disease
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In an HIV-positive population, the Xpert MTB/RIF Ultra assay detected tuberculous meningitis with higher sensitivity than the older Xpert assay and a mycobacterial growth indicator tube culture, according to findings published in The Lancet.
However, results also showed that the Xpert Ultra (Cephid) proved an unreliable method of ruling out TB meningitis, meaning that “clinical judgment and novel highly sensitive point-of-care tests are still required,” researchers said.
Fiona V. Cresswell , MBChB, a research fellow at the London School of Hygiene & Tropical Medicine, and colleagues noted that cerebrospinal fluid smear microscopy with Ziehl–Neelsen staining for acid-fast bacilli is the “cheapest and most widely available test for TB meningitis diagnosis,” but it takes a minimum of 2 weeks for results and has only “moderate” sensitivity. Endorsed by WHO, the rapid molecular Xpert MTB/RIF assay was deployed to 130 countries in 2016 at adjusted prices for the diagnosis of TB meningitis, but its sensitivity ranges only from 45% to 67%. Later, an improved version of the assay was developed — the Xpert Ultra — and among its several improvements was a limit of detection of Mycobacterium tuberculosis that was seven times lower than that of its predecessor and the capacity to run five additional tests a day.
Cresswell and colleagues evaluated the performance of the Xpert Ultra assay for TB meningitis diagnosis in a prospective validation study that included 204 adults with suspected meningitis in Uganda from Nov. 25, 2016 to Jan. 24, 2019. The researchers compared its performance with that of the original Xpert test and mycobacterial growth indicator tube (MGIT) culture.
Based on a uniform case definition that classified 51 participants as having probable or definite TB meningitis, the Xpert Ultra had a sensitivity of 76.5% (95% CI, 62.5-87.2) and a negative predictive value of 92.7% (95% CI, 87.6-96.2). Xpert had a 55.6% sensitivity (95% CI, 44-70.4) and a negative predictive value of 85.8% (95% CI, 78.9-91.1). The MGIT culture had a sensitivity of 61.4% (95% CI, 45.5-75.6) and a negative predictive value of 85.2% (95% CI, 77.4-91.1), Cresswell and colleagues wrote.
Using a composite microbiological reference standard, the researchers determined that Xpert Ultra had a sensitivity of 92.9% (95% CI, 80.5-98.5), which was higher than Xpert’s sensitivity of 65.8% (95% CI, 48.6-80.4). However, its sensitivity was not significantly higher than MGIT culture, which stood at 72.2% (95% CI, 55.9-86.2; 27 of 37).
Xpert Ultra detected nine cases of TB meningitis that were missed by both MGIT culture and Xpert, according to Cresswell and colleagues.
Because of its inability to rule out TB meningitis, “clinical judgment and empirical therapy remain important to improve outcomes for patients with tuberculous meningitis,” the authors wrote. “In this exciting era of rapidly evolving molecular diagnostics and biomarkers, the development of a highly sensitive point-of-care test that can facilitate rapid treatment and give clinicians confidence in rationalizing the use of empirical tuberculosis treatment is a realistic goal.” – by Earl Holland Jr.
Disclosures: The authors report no relevant financial disclosures.
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