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Multicenter Study
. 2022 Apr;36(4):e24307.
doi: 10.1002/jcla.24307. Epub 2022 Feb 24.

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

Yuxin Chen  1 , Yuqing Wang  2 , Xiaojin Liu  3 , Wen Li  4 , Hongyi Fu  5 , Xinyan Liu  6 , Xun Zhang  7 , Xueqin Zhou  7 , Bingzhou Yang  7 , Jie Yao  2 , Xiaolei Ma  2 , Lijun Han  8 , Huan Li  8 , Liheng Zheng  7
Affiliations
Multicenter Study

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

Yuxin Chen et al. J Clin Lab Anal. 2022 Apr.

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.

Keywords: diagnostic efficacy; metagenomic next-generation sequencing; tuberculous meningitis.

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Conflict of interest statement

The authors declared that they have no potential conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Flow diagram showing the diagnostic outcomes of the study population
FIGURE 2
FIGURE 2
Venn diagram of positive diagnostic tests in the composite microbiological reference standard. The Venn diagram displays 88 participants with microbiological confirmed tuberculous meningitis by either Xpert MTB/RIF, mNGS, or Ziehl–Neelsen staining. mNGS, metagenomic next‐generation sequencing
See this image and copyright information in PMC

References

    1. World Health Organization . Global Tuberculosis Report, 20th ed. Geneva: World Health Organization; 2015.
    1. Seddon JA, Wilkinson R, van Crevel R, Figaji A, Thwaites GE; Tuberculous Meningitis International Research Consortium . Knowledge gaps and research priorities in tuberculous meningitis. Wellcome Open Res. 2019;4:188. - PMC - PubMed
    1. Garcia‐Monco JC. Central nervous system tuberculosis. Neurol Clin. 1999;17(4):737‐759. - PubMed
    1. Gupta R, Talwar P, Talwar P, et al. Diagnostic accuracy of nucleic acid amplification based assays for tuberculous meningitis: a meta‐analysis. J Infect. 2018;77(4):302‐313. - PubMed
    1. Wilkinson RJ, Rohlwink U, Misra UK, et al. Tuberculous meningitis. Nat Rev Neurol. 2017;13(10):581‐598. - PubMed

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