Value of Next-generation Sequencing Combined with GeneXpert MTB/RIF in Early Diagnosis of Tuberculous Meningitis

Le ZHANG; Jiawei XIA; Depan CHEN; Haiwen LI; Bin BAI; Yatao YANG; Xiang LI; Kaiyi ZHANG

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Le ZHANG, Jiawei XIA, Depan CHEN, Haiwen LI, Bin BAI, Yatao YANG, Xiang LI, Kaiyi ZHANG. Value of Next-generation Sequencing Combined with GeneXpert MTB/RIF in Early Diagnosis of Tuberculous Meningitis[J]. Journal of Kunming Medical University.

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Value of Next-generation Sequencing Combined with GeneXpert MTB/RIF in Early Diagnosis of Tuberculous Meningitis

The Third People’s Hospital of Kunming/ Yunnan Clinical Medical Center for Infectious Diseases，Kunming Yunnan 650041，China

Received Date: 2026-01-22
Available Online: 2026-06-04

Abstract

Abstract

Objective To evaluate the clinical application value of metagenomic next-generation sequencing （mNGS） combined with GeneXpert MTB/RIF （Mycobacterium tuberculosis/rifampicin resistance gene detection） in the early diagnosis of tuberculous meningitis （TBM）. Methods A total of 73 patients clinically suspected of TBM who visited Kunming Third People’ s Hospital from January 2022 to June 2024 were enrolled. Cerebrospinal fluid specimens were collected for mNGS, GeneXpert MTB/RIF, Mycobacterium tuberculosis smear microscopy, culture, and PCR testing. The sensitivity, specificity, and concordance rate of each detection method were calculated. Appropriate statistical methods were used to comprehensively evaluate the diagnostic value of each method. Results （1） Among 73 clinically suspected TBM patients, 65 were diagnosed with TBM （45 confirmed bacteriologically, 20 diagnosed clinically）; and 8 had non-tuberculous meningitis. （2） Using the 65 diagnosed TBM cases as the reference standard, the sensitivity, specificity, and consistency of mNGS+GeneXpert for TBM diagnosis were 86.1%（95%CI: 75.6～92.5）, 100.0%（95%CI: 67.4～100.0）, and 87.7%（95%CI: 77.7～93.6）, respectively. The sensitivity and concordance rate of mNGS+GeneXpert were higher than those of mNGS alone [60% （95%CI: 47.9～71.0） , 64.4% （95%CI: 52.9～74.4）]and GeneXpert alone [38.5% （95%CI: 27.4～50.8）, 45.2% （95%CI: 34.2～56.6）]. Regarding sensitivity, P-values for all three detection methods were <0.05. （3） Using 45 bacteriologically confirmed TBM cases as the reference standard, mNGS combined with GeneXpert showed the highest sensitivity of 93.3% （95%CI: 81.7～97.7）, and the highest consistency rate was 76.7% （95%CI: 65.7～85.1）. （4） Comparative analysis of mNGS+GeneXpert with mNGS and GeneXpert alone showed statistically significant differences （P < 0.001）. Conclusion Metagenomic next-generation sequencing combined with GeneXpert MTB/RIF showed high sensitivity and specificity in the early diagnosis of tuberculous meningitis, significantly improving diagnostic efficiency, and can provide clinicians with rapid and accurate etiological diagnostic evidence.
- Tuberculous meningitis,
- Metagenomic next-generation sequencing,
- GeneXpert MTB/RIF,
- Diagnostic efficacy

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