【文献汇编】NGS助力终结结核病

2024-03-22 16:36:25 Illumina因美纳（中国）科学器材有限公司

结核病是全球十大死因之一，每年夺走100多万人的生命。根据联合国可持续发展目标（Sustainable Development Goals, SDG），结核病不仅是一个严重的健康问题，还与消除贫困密切相关¹。

近期发表的🔗《Financial Burden of Tuberculosis Patients—China, 2020》，评估了2020年中国结核病患者的经济负担，包括直接成本、间接成本和总成本，并探讨当前结核病护理政策和方案是否足以减轻这一负担²。

中国是世界上结核病高负担国家之一，在许多结核病负担指数上排名世界第三。国家结核病控制战略旨在建立一个协作网络，并将结核病治疗纳入医疗系统。根据世界卫生组织的全球结核病报告，预计2022年中国将新增748000例结核病病例，发病率为每10万人52例。遏制结核病仍然是一个巨大的挑战，需要中国采取全面的控制策略¹。

2024年2月8日发表的🔗《Roadmap for ending TB in China by 2035: The challenges and strategies 》，作者讨论了中国结核病预防和控制面临的挑战，并提出了终结结核病的具体措施。其中，文中重点提到需要进一步改善诊断技术、发展更有效的疫苗、确保全民获得治疗、提高医疗系统和政策的协调性，以及加强科研和实证研究，特别是在结核病诊断、药物耐药性、疫苗研发等领域。

下一代测序技术（Next Generation Sequencing, NGS）在结核病防控的多个领域发挥重要作用，2024年3月20日WHO刚更新了《WHO consolidated guidelines on tuberculosis: Module 3: Diagnosis - Rapid diagnostics for tuberculosis detection, third edition》以及《WHO operational handbook on tuberculosis. Module 3: Diagnosis - Rapid diagnostics for tuberculosis detection, third edition》，其中新增靶向下一代测序（Targeted next-generation sequencing, tNGS）部分，并推荐使用tNGS来检测对一些一线和二线抗结核药物的耐药性，而不是基于培养的表型药物敏感性测试^3,4。

下面以2023-2024年WHO与国家疾控发表的部分文章进行介绍：（文章最后有部分文献原文下载）

一、病原体检测与表征

High diversity of clinicalMycobacterium intracellularein China revealed by whole genome sequencing ⁵

全基因组测序揭示中国临床胞内分枝杆菌的高度多样性

The effect ofM. tuberculosislineage on clinical phenotype⁶

结核分枝杆菌谱系对临床表型的影响

Mycobacterium paragordonaeis an emerging pathogen in human pulmonary disease: clinical features, antimicrobial susceptibility testing and outcomes⁷

Mycobacterium paragordonae是人类肺部疾病中的新兴病原体：临床特征、抗菌素敏感性测试及预后

二、耐药检测与表征

世界卫生组织《结核分枝杆菌耐药相关基因突变目录（第2版）》解读⁸

Genome-wide association studies of globalMycobacterium tuberculosisresistance to 13 antimicrobials in 10,228 genomes identify new resistance mechanisms ⁹

全球范围内对13种抗生素耐药的10228个结核分枝杆菌基因组的全基因组关联研究识别出新的耐药机制

Quantitative measurement of antibiotic resistance inMycobacterium tuberculosisreveals genetic determinants of resistance and susceptibility in a target gene approach¹⁰

结核分枝杆菌抗生素耐药性的定量测量揭示在靶基因方法中耐药性和易感性的遗传决定因素

Identification and drug susceptibility testing of the subspecies ofMycobacterium avium complexclinical isolates in China¹¹

中国大陆临床分离的鸟分枝杆菌复合群亚种的鉴定和药物敏感性测试

Insight into the drug-resistant characteristics and genetic diversity of multidrug-resistantMycobacterium tuberculosisin China¹²

中国耐多药结核分枝杆菌耐药性特征及遗传多样性研究

Use of targeted next-generation sequencing to detect drug-resistant tuberculosis: rapid communication, July 2023 （WHO）¹³

使用靶向下一代测序技术检测耐药结核病：2023年7月快速通讯（WHO）

三、了解传播途径

Transmission and Drug Resistance Genotype of Multidrug-Resistant or Rifampicin-ResistantMycobacterium tuberculosisin Chongqing, China¹⁴

中国重庆多药耐药或利福平耐药结核分枝杆菌的传播和耐药基因型

The Recent Transmission and Associated Risk Factor ofMycobacterium tuberculosisin Golmud City, China¹⁵

中国格尔木市结核分枝杆菌的近期传播及相关风险因素

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参考文献：

Feng, Q. et al. Roadmap for ending TB in China by 2035: The challenges and strategies. Biosci Trends, doi:10.5582/bst.2023.01325 (2024).
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Global Tuberculosis Programme (GTB). WHO consolidated guidelines on tuberculosis. Module 3: Diagnosis – Rapid diagnostics for tuberculosis detection, third edition. 20 March 2024. ISBN: 9789240089488
Global Tuberculosis Programme (GTB). WHO operational handbood on tuberculosis. Module 3: Diagnosis – Rapid diagnostics for tuberculosis detection, third edition. 20 March 2024. ISBN: 9789240089501
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裴少君，欧喜超. 世界卫生组织《结核分枝杆菌耐药相关基因突变目录（第2版）》解读. 中国防痨杂志, 2024, 46(3): 260-266. doi:10.19982/j.issn.1000-6621.20230450
The CRyPTIC Consortium. Genome-wide association studies of global Mycobacterium tuberculosis resistance to 13 antimicrobials in 10,228 genomes identify new resistance mechanisms. PLoS Biol 20, e3001755, doi:10.1371/journal.pbio.3001755 (2022).
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WHO. Use of targeted next-generation sequencing to detect drug-resistant tuberculosis: rapid communication, July 2023 (2023).[1] ISBN: 978-92-4-007637-2
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Song, Z. et al. The Recent Transmission and Associated Risk Factor of Mycobacterium tuberculosis in Golmud City, China. Infect Drug Resist 17, 417-425, doi:10.2147/IDR.S437026 (2024).