Diagnostic Accuracy of Metagenomic Next-Generation Sequencing in Sputum-Scarce or Smear-Negative Cases with Suspected Pulmonary Tuberculosis.

Ning Zhu,Shengqing Li,Daibing Zhou,Marcelo A Soares

doi:10.1155/2021/9970817

Abstract

Objective To investigate the diagnostic accuracy of metagenomic next-generation sequencing (mNGS) in bronchoalveolar lavage fluid (BALF) samples or lung biopsy specimens from which suspected pulmonary tuberculosis (PTB) patients have no sputum or negative smear. Materials and Methods Sputum-scarce or smear-negative cases with suspected PTB (n = 107) were analyzed from January 2018 to June 2020. We collected BALF or lung tissue biopsy samples with these cases of suspected TB during hospitalization. The diagnostic accuracy of mNGS for these samples was compared with those of conventional tests or the T-SPOT.TB assay. Results 46 cases of PTB patients and 61 cases of non-PTB patients were finally enrolled and analyzed. mNGS exhibited a sensitivity of 89.13%, which was higher than conventional tests (67.39%) but equivalent to those of the T-SPOT.TB assay alone (76.09%) or T-SPOT.TB assay in combination with conventional tests (91.30%). The specificity of mNGS was 98.36%, similar to conventional tests (95.08%) but significantly higher than those of the T-SPOT.TB assay alone (65.57%) or the T-SPOT.TB assay in combination with conventional tests (63.93%). There was no significant difference in the diagnostic accuracy of mNGS in BALF samples and lung biopsy tissue specimens. Conclusion Our findings demonstrate that mNGS could offer improved detection of Mycobacterium tuberculosis in BALF or lung tissue biopsy samples in sputum-scarce or smear-negative cases with suspected PTB.

Highlights

Tuberculosis remains a major global health problem that causes ill health to millions of people worldwide every year
Since the T-SPOT.TB assay is a commonly used auxiliary assay in the diagnosis of Pulmonary tuberculosis (PTB), and each enrolled patient was subjected to the T-SPOT.TB assay
bronchoalveolar lavage fluid (BALF) or lung tissue specimens were obtained for testing by either conventional tests or metagenomic next-generation sequencing (mNGS)

Summary

Introduction

Tuberculosis remains a major global health problem that causes ill health to millions of people worldwide every year. Left untreated, disseminated tuberculosis, including subclinical PTB [2], is potentially fatal. Early and timely diagnosis of tuberculosis is critical to preventing disease progression and improving prognosis [3]. Standard diagnostic methods for tuberculosis include acid-fast staining, tuberculosis culture, GeneXpert MTB/RIF assay, and T-SPOT.TB assay. The sensitivity of microscopic examination of acid-fast bacilli (AFB) in sputum specimens is 50% or less, AFB staining is still the most widely used rapid diagnostic method for tuberculosis. The World Health Organization (WHO) recommends mycobacterial culture, which exhibits a high sensitivity for detecting M. tb, as the diagnostic gold standard. Due to the slow growth of M. tb, mycobacterial culture cannot meet the clinical needs of the diagnosis and treatment of TB. The T-SPOT.TB assay is an auxiliary assay commonly used in the diagnosis of PTB.

Methods

Results

Conclusion