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Published on: August 29, 2025
Metagenomic next-generation sequencing for tuberculosis diagnosis: enhanced performance and cost-effectiveness
Xiaoli Zhou1, Guo Wei2, Tiange Song1
1Department of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Microbiology Spectrum
|July 29, 2026
Summary
Metagenomic next-generation sequencing (mNGS) shows high specificity for diagnosing tuberculosis (TB). A sequential approach using mNGS after conventional tests improves diagnostic accuracy and becomes cost-effective with increased healthcare investment.
Area of Science:
- Clinical microbiology and infectious diseases.
- Genomic medicine and diagnostics.
- Health economics and outcomes research.
Background:
- Metagenomic next-generation sequencing (mNGS) is an emerging tool for diagnosing complex infections like tuberculosis (TB).
- Previous research primarily focused on case-specific applications of mNGS in TB diagnosis, lacking systematic evaluation.
- A comprehensive assessment of mNGS's diagnostic performance and cost-effectiveness compared to established methods is needed.
Purpose of the Study:
- To systematically evaluate the diagnostic performance and cost-effectiveness of mNGS for TB diagnosis in a large real-world cohort.
- To compare mNGS against six conventional TB diagnostic assays: tuberculosis IgG antibody, TB interferon-γ release assay (TB-IGRA), TB-DNA, Xpert MTB/RIF (Xpert), culture, and acid-fast bacilli staining (AFS).
- To assess the utility of a sequential diagnostic strategy involving mNGS.
Main Methods:
- Retrospective observational study analyzing 16,776 results from 3,757 patients with suspected TB infection.
- Comparison of diagnostic metrics (sensitivity, specificity, accuracy, AUC) against a composite reference standard.
- Microbial composition analysis and cost-utility analysis of mNGS strategies.
Main Results:
- mNGS exhibited the highest specificity (100%), accuracy (72.3%), and AUC (0.795) among the seven assays.
- Sequential use of mNGS after WHO-recommended tests (Xpert/Culture/AFS) significantly improved diagnostic performance (sensitivity 70.4%, AUC 0.823).
- The sequential mNGS strategy demonstrated cost-effectiveness at higher willingness-to-pay thresholds (>200,000 RMB per correct diagnosis).
Conclusions:
- mNGS offers superior specificity for diagnosing TB, particularly in challenging cases.
- A sequential strategy utilizing mNGS for conventional-test-negative patients enhances diagnostic performance.
- This sequential approach is cost-effective at higher healthcare investment levels, supporting its integration into TB diagnostic algorithms.
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