Background Xpert MTB/RIF Ultra (Xpert Ultra) might have higher sensitivity than its predecessor, Xpert MTB/RIF (Xpert), but its role in tuberculous meningitis diagnosis is uncertain. We aimed to compare Xpert Ultra with Xpert for the diagnosis of tuberculous meningitis in HIV-uninfected and HIV-infected adults. Methods In this prospective, randomised, diagnostic accuracy study, adults (≥16 years) with suspected tuberculous meningitis from a single centre in Vietnam were randomly assigned to cerebrospinal fluid testing by either Xpert Ultra or Xpert at baseline and, if treated for tuberculous meningitis, after 3-4 weeks of treatment. Test performance (sensitivity, specificity, and positive and negative predictive values) was calculated for Xpert Ultra and Xpert and compared against clinical and mycobacterial culture reference standards. Analyses were done for all patients and by HIV status.

Modified ZN stain does not improve diagnosis of TBM. Currently available tests are insensitive, but testing large CSF volumes improves performance. New diagnostic tests for TBM are urgently required.

Tuberculous meningitis (TBM) is the most devastating form of tuberculosis (TB) and often causes critical illness with high mortality. A primary management objective is reducing intracranial pressure (ICP), and optimising cerebral perfusion, whilst killing the bacteria and controlling intra-cerebral inflammation. However, the evidence base guiding the care of critically ill patients with TBM is poor and many patients do not have access to neurocritical care units. Invasive ICP monitoring is often unavailable; whilst new non-invasive monitoring techniques show promise, further evidence for their use is required. Optimal management of neurological complications, and of hyponatraemia, which frequently accompanies TBM, is not known. The best supportive care remains uncertain. Recent advances in the field of TBM predominantly focus upon diagnosis, inflammatory processes and anti-TB chemotherapy. Clinical trials are required to provide robust evidence guiding the most effective supportive, therapeutic and neurosurgical interventions in TBM, with proven benefits for morbidity and mortality.