Combining interferon-γ release assays and metagenomic next-generation sequencing for diagnosis of pulmonary tuberculosis: a retrospective study

BMC Infect Dis. 2024 Nov 18;24(1):1316. doi: 10.1186/s12879-024-10206-5.

Abstract

Background: Rapid diagnosis of pulmonary tuberculosis (PTB) is urgently needed. We aimed to improve diagnosis rates by combining tuberculosis-interferon (IFN)-γ release assays (TB-IGRA) with metagenomic next-generation sequencing (mNGS) for PTB diagnosis.

Methods: A retrospective study of 29 PTB and 32 non-TB patients from our hospital was conducted between October 2022 and June 2023. Samples were processed for TB-IGRA and mNGS tests according to the manufacturer's protocol.

Results: The levels of IFN-γ release in PTB patients were significantly higher than those in non-TB patients (604.15 ± 112.18 pg/mL, and 1.04 ± 0.38 pg/mL, respectively; p < 0.0001). Regarding presenting symptoms or signs, cough and thoracalgia were less common in PTB patients than in non-TB patients (p = 0.001 and p = 0.024, respectively). Total protein and albumin levels in the sera of PTB patients were significantly elevated compared to non-TB patients (p = 0.039 and p = 0.004, respectively). The area under the ROC curve (AUC) for TB-IGRA in PTB diagnosis was 0.939. With an optimal IFN-γ cut-off value of 14.3 pg/mL (Youden's index 0.831), sensitivity was 86.2% and specificity was 96.9%. ROC curve analysis for mNGS and TB-IGRA combined with mNGS showed AUCs of 0.879 and 1, respectively. The AUC of TB-IGRA combined with mNGS was higher than that of TB-IGRA and mNGS alone.

Conclusions: TB-IGRA combined with mNGS may be an effective method for diagnosing tuberculosis, and can be used in the clinical diagnosis of PTB.

Keywords: IFN-γ; Sputum smears; TB-IGRA; Tuberculosis; mNGS.

MeSH terms

  • Adult
  • Aged
  • Female
  • High-Throughput Nucleotide Sequencing* / methods
  • Humans
  • Interferon-gamma / blood
  • Interferon-gamma Release Tests* / methods
  • Male
  • Metagenomics / methods
  • Middle Aged
  • Mycobacterium tuberculosis / genetics
  • ROC Curve
  • Retrospective Studies
  • Sensitivity and Specificity
  • Tuberculosis, Pulmonary* / blood
  • Tuberculosis, Pulmonary* / diagnosis
  • Tuberculosis, Pulmonary* / microbiology

Substances

  • Interferon-gamma