Transforming tuberculosis diagnosis with clinical metagenomics: progress and roadblocks

Area of Science:

• Infectious Diseases
• Genomics
• Molecular Diagnostics

Background:

• Tuberculosis (TB) is a major global health threat with diagnostic limitations.
• Traditional methods like acid-fast staining and culture are slow or lack sensitivity.
• Current molecular assays offer rapid detection but limited resistance profiling.

Purpose of the Study:

• To evaluate metagenomic next-generation sequencing (mNGS) as a diagnostic tool for TB.
• To explore mNGS's potential in complex TB cases and for drug resistance prediction.
• To identify barriers and future directions for mNGS in TB management.

Main Methods:

• Review of clinical studies on mNGS for TB diagnosis.
• Analysis of mNGS performance metrics including sensitivity, specificity, and read counts.
• Assessment of mNGS capabilities for pathogen identification and drug resistance profiling.

Main Results:

• mNGS demonstrates moderate to high sensitivity and excellent specificity for TB detection.
• mNGS offers advantages in extra-pulmonary, mixed, and pediatric TB cases.
• Challenges include low read counts, host DNA interference, and limited drug resistance prediction accuracy.

Conclusions:

• mNGS is a valuable culture-independent tool for TB diagnosis, especially in complex scenarios.
• Further optimization, standardization, and integration with conventional methods are needed for routine adoption.
• Addressing cost, workflow complexity, and data interpretation are crucial for future clinical utility.