Comparison of diagnostic accuracy of the GeneXpert Ultra, and cell-free nucleic acid assay for tuberculous meningitis: a multicenter prospective study

Abstract Design We conducted a prospective, multicenter study to compare the diagnostic accuracy of the GeneXpert MTB/RIF Ultra (Xpert Ultra), and cell-free DNA (cfDNA) assay for tuberculous meningitis (TBM) in China. Methods A prospective cohort study was conducted among individuals with symptoms suggestive of TBM registered in three TB specialised hospitals in China between between June 2018 and January 2019. Results Overall, 84 patients suggestive of TBM were included in our analysis between June 2018 and January 2019. Using microbiological evidence as reference, the sensitivity/specificity for the diagnostic tests were Xpert Ultra 93.3%/100%; cfDNA 93.3%/92.6%; and culture 13.3%/100%. In addition, the sensitivity of culture was 6.7% when using clinical diagnosis criteria as gold standard. Xpert Ultra correctly identified 28 cases as TBM, indicating a sensitivity of 46.7%. Notably, four additional TBM cases were detected by cfDNA compared with Xpert Ultra, yielding an overall sensitivity of 53.3%. Statistical analysis revealed that the sensitivity of Xpert Ultra and cfDNA were significantly higher than that of culture. Conclusions In conclusion, our data demonstrate that Xpert Ultra and cfDNA assay show optimal sensitivity compared with MGIT culture. In addition, there is no significant correlation between bacterial load and TBM severity in our participants.