Transforming tuberculosis diagnosis with clinical metagenomics: progress and roadblocks.

IF 5.4 2区 医学 Q1 MICROBIOLOGY
Yuqing Chen, Hui Tang, Jieyuan Zheng, Qing Yang, Dongsheng Han
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Abstract

Tuberculosis (TB) remains a leading global infectious killer, yet traditional diagnostic methods are inadequate. Acid-fast staining suffers from low sensitivity, and mycobacterial culture requires prolonged incubation because of the slow growth of Mycobacterium tuberculosis. PCR-based molecular assays allow rapid detection, but their capacity for resistance profiling is limited to a narrow set of mutations. Metagenomic next-generation sequencing (mNGS) has emerged as a promising culture-independent tool for TB detection, enabling broad-spectrum pathogen identification and offering added value in complex scenarios including extra-pulmonary disease, mixed infections, and infections in immunocompromised or pediatric populations. Clinical studies indicate that mNGS achieves moderate to high sensitivity and excellent specificity in the diagnosis of tuberculosis. However, its diagnostic performance is often constrained by low mycobacterial read counts, interference from abundant host nucleic acids, and the inability to distinguish active from latent infection. In addition, the accuracy of drug resistance prediction using mNGS remains limited, and the World Health Organization currently endorses targeted NGS as the preferred sequencing-based approach for resistance profiling. Despite these challenges, mNGS has facilitated novel diagnostic strategies that combine pathogen detection with host-response data, thereby broadening its potential clinical utility. Nevertheless, practical barriers such as high cost, complex laboratory workflows, and difficulties in data interpretation continue to restrict widespread adoption in routine practice. Future efforts should prioritize technical optimization, standardized protocols, and integration with conventional diagnostics to establish cost-effective and clinically meaningful roles for mNGS in TB diagnosis and management.

用临床宏基因组学转变结核病诊断:进展和障碍。
结核病(TB)仍然是全球主要的传染病杀手,但传统的诊断方法并不充分。抗酸染色灵敏度低,而且由于结核分枝杆菌生长缓慢,分枝杆菌培养需要较长时间的孵育。基于聚合酶链反应的分子分析可以快速检测,但其抗性谱分析能力仅限于一组狭窄的突变。新一代宏基因组测序(mNGS)已成为一种很有前景的、不依赖培养的结核病检测工具,可实现广谱病原体鉴定,并在肺外疾病、混合感染以及免疫功能低下人群或儿科人群感染等复杂情况下提供附加价值。临床研究表明,mNGS对肺结核的诊断具有中高灵敏度和极好的特异性。然而,它的诊断性能往往受到分枝杆菌读数低、大量宿主核酸的干扰以及无法区分活动性和潜伏性感染的限制。此外,使用mNGS预测耐药性的准确性仍然有限,世界卫生组织目前认可靶向NGS作为基于测序的耐药性分析方法的首选方法。尽管存在这些挑战,但mNGS促进了将病原体检测与宿主反应数据相结合的新型诊断策略,从而扩大了其潜在的临床用途。然而,诸如高成本、复杂的实验室工作流程和数据解释困难等实际障碍继续限制在日常实践中的广泛采用。未来的工作应优先考虑技术优化、标准化方案和与传统诊断的整合,以建立具有成本效益和临床意义的mgs在结核病诊断和管理中的作用。
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来源期刊
Journal of Clinical Microbiology
Journal of Clinical Microbiology 医学-微生物学
CiteScore
17.10
自引率
4.30%
发文量
347
审稿时长
3 months
期刊介绍: The Journal of Clinical Microbiology® disseminates the latest research concerning the laboratory diagnosis of human and animal infections, along with the laboratory's role in epidemiology and the management of infectious diseases.
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