Comparative diagnostic utility of metagenomic next‐generation sequencing, GeneXpert, modified Ziehl–Neelsen staining, and culture using cerebrospinal fluid for tuberculous meningitis: A multi‐center, retrospective study in China

Abstract

Background Early diagnosis of tuberculosis meningitis (TBM) remains a great challenge during clinical practice. The diagnostic efficacies of cerebrospinal fluid (CSF)‐based mycobacterial growth indicator tube (MGIT) culture, modified Ziehl–Neelsen (ZN) staining, Xpert MTB/RIF, and metagenomic next‐generation sequencing (mNGS) for TBM remained elusive. Methods A total of 216 adult patients with suspicious TBM were retrospectively enrolled in this multi‐cohort study. The diagnostic performances for MGIT, modified ZN staining, Xpert MTB/RIF, and mNGS using CSF samples were evaluated. Results Uniform clinical case definition classified 88 (40.7%) out of 216 patients as the definite TBM, 5 (2.3%) patients as probable TBM cases, and 24 (11.1%) patients as possible TBM cases. The sensitivities of MGIT, modified ZN staining, Xpert MTB/RIF, and mNGS for TBM diagnosis against consensus uniform case definition for definite TBM were 25.0%, 76.1%, 73.9%, and 84.1%, respectively. Negative predictive values (NPVs) were 66.0%, 85.9%, 84.8%, and 90.1%, respectively. The sensitivities of MGIT, modified ZN staining, Xpert MTB/RIF, and mNGS for TBM diagnosis against consensus uniform case definition for definite, probable, and possible TBM were 18.8%, 57.3%, 55.5%, and 63.2%, respectively. Negative predictive values (NPVs) were 51.0%, 66.4%, 65.6%, and 69.7%, respectively. mNGS combined with modified ZN stain and Xpert could cover TBM cases against a composite microbiological reference standard, yielding 100% specificity and 100% NPV. Conclusion Metagenomic next‐generation sequencing detected TBM with higher sensitivity than Xpert, ZN staining and MGIT culture, but mNGS cannot be used as a rule‐out test. mNGS combined with Xpert or modified ZN staining could enhance the sensitivity of diagnostic tests for TBM.

Diagnostic efficiency of metagenomic next-generation sequencing for suspected spinal tuberculosis in China: A multicenter prospective study

“…Therefore, the diagnostic capability of T-SPOT.TB was lower than that of mNGS and Xpert. This finding is similar to the reported results ( Zhao et al, 2020 ; Chen et al, 2022 ). The poor specificity of T-SPOT.TB is mainly due to the high latent infection rate of mycobacterium TB in China ( Word Health Organization, 2021 ).…”

“…However, conventional methods also have their own advantages over mNGS; for example, although Xpert has the same ability as mNGS for the diagnosis of spinal TB, it can detect rifampicin-resistant gene mutations and provide guidance for TB treatment plans ( Yu et al, 2021 ). In addition, MGIT 960 and bacterial cultures can be used to conduct drug sensitivity tests on bacteria ( Zhou et al, 2019 ; Chen et al, 2022 ), and the results of drug sensitivity test have important guiding significance for the treatment of clinical spinal infections. Currently, mNGS provides limited information on the drug sensitivity of the detected bacteria, and its ability to detect drug-resistant mutations needs further study.…”

A systematic review and meta-analysis of the diagnostic accuracy of metagenomic next-generation sequencing for diagnosing tuberculous meningitis

“…A total of 693 participants were included in the eight studies, including 348 patients with TBM and 345 non-TBM controls. Of these studies, three were prospective ( 18 , 19 , 21 ) and five were retrospective ( 17 , 20 , 22 – 24 ) in design. The patients were randomly selected in three studies ( 18 , 21 , 22 ) and consecutively selected in five studies ( 17 , 19 , 20 , 23 , 24 ).…”

Evaluation of different diagnostic methods for spinal tuberculosis infection

“…The probability of false positives is significantly reduced. mNGS could be used to improve the sensitivity and timely diagnosis of TBM when combined with Xpert or traditional diagnostic tests [ 28 ].…”