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

Abstract

ObjectiveMetagenomic 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. MethodsA retrospective analysis was conducted on 51 inpatients with suspected TBM who underwent mNGS and four other tests in cerebrospinal fluid (CSF). ResultsAmong 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). ConclusionCSF 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.