Tuberculous meningitis (TBM) is the most serious form of extrapulmonary tuberculosis (TB) and the most common form of central nervous system TB [1,2]. Although TBM accounts for only 1 % of all TB cases worldwide [3], the mortality rate is 30 %-40 % and the risk of central nervous system sequelae is high [4].

Early diagnosis of TBM is critical for reducing mortality and morbidity [1]. Therefore, since 2013 the WHO recommends the use of GeneXpert MTB/RIF (Xpert; Cepheid, Sunnyvale, CA, USA) and GeneXpert MTB/RIF Ultra (Xpert Ultra), both cartridge-based fully-automated nucleic acid amplification tests (NAATs), in the diagnosis of extra-pulmonary TB, including TBM [5]. As previously reported in a prospective study from Vietnam including 53 HIV negative patients, Xpert had a sensitivity of 27.6 %∼53.1 % and a specificity of 92.6 %∼100.0 % when compared against definite TBM [6]. However, the performance of Xpert was considerably worse for the probable/possible cases of TBM, where the sensitivity dropped to 0 % (0/15). Thus, additional indicators might be needed to improve the diagnosis of TBM using GeneXpert.

Due to the damage of blood-brain barrier leading to increased permeability, the components in the CSF may change in patient with TBM. Biochemical indicators (e.g. CSF lactate and glucose) have been shown valuable in diagnosing TBM and may help to increase the diagnostic accuracy if combined with Xpert [7,8].

To date, previous studies evaluating Xpert have mainly focused on accuracy evaluation and lack the investigation of additional indicators to increase the diagnostic performance. Therefore, we performed a multicentre accuracy study to determine the accuracy of Xpert in TBM diagnosis in China as well as to identify the additional CSF biochemical indicator to improve the diagnosis of TBM.