Donovan J, Thu DDA, Phu NH, et al. - Given the possibility of a higher sensitivity of Xpert MTB/RIF Ultra (Xpert Ultra) vs its predecessor, Xpert MTB/RIF (Xpert), researchers here assessed the relative efficacy Xpert Ultra vs Xpert in diagnosing tuberculous meningitis in HIV-uninfected and HIV-infected adults. They conducted a prospective, randomized, diagnostic accuracy study including 205 adults (≥ 16 years) with suspected tuberculous meningitis from a single center in Vietnam and randomizing them to cerebrospinal fluid testing by either Xpert Ultra or Xpert at baseline and, if treated for tuberculous meningitis, after 3–4 weeks of treatment. Outcomes revealed no statistically superior efficacy of Xpert Ultra vs Xpert for the diagnosis of tuberculous meningitis in HIV-uninfected and HIV-infected adults. Tuberculous meningitis could not be ruled out with a negative Xpert Ultra or Xpert test. Findings emphasize the urgent necessity for new diagnostic strategies.