Metagenomic Next-Generation Sequencing (mNGS) in cerebrospinal fluid for rapid diagnosis of Tuberculosis meningitis in HIV-negative population

Abstract

Objective: Metagenomic Next-Generation Sequencing (mNGS) has been applied as a novel method of detection pathogens for infectious diseases, but its value in the rapid diagnosis of tuberculous meningitis(TBM)has not been clarified based on large samples.

Methods: A retrospective analysis was conducted on 51 inpatients with suspected TBM who underwent mNGS and four other tests in cerebrospinal fluid (CSF).

Results: Among 51 included patients, 45 cases were diagnosed as TBM (38 definite, 5 probable, 2 possible) and 6 cases as non-TBM. Using final diagnosis as reference standard, the sensitivity, specificity, PPV (positive predictive value), and NPV (negative predictive value) of mNGS in CSF for TBM were 84.44%(38/45, 69.94%-93.01%), 100%(6/6, 51.68%-100%), 100%(40/40, 88.57%-100%) and 46.15%(6/13, 20.40%-73.88%). The diagnostic sensitivity of mNGS(84.4%)was significantly higher than that of AFB (0%, P = 0.000), MGIT960 culture(22.2%, P = 0.000), MTB PCR(24.4%, P = 0.000) and Xpert MTB/RIF(40%, P = 0.000). The ROC curve showed that CSF protein quantification and CSF cell count might be valuable in the prediction of NGS positive detection of MTB (Mycobacterium tuberculosis).

Conclusion: CSF mNGS had high sensitivity, specificity and PPV in the diagnosis of TBM. Patients with a significant increase in CSF cell number and protein quantification might have a higher likelihood of positive MTB detection of NGS.

Keywords: Gene Xpert MTB/RIF assay; Meningitis; Metagenomic Next-Generation Sequencing; Mycobacterium tuberculosis; Rapid diagnosis.