Research progress on prevention and control strategies for latent Mycobacterium tuberculosis infection

doi:10.19983/j.issn.2096-8493.20260125

Abstract

Abstract:

Approximately one quarter of global population, nearly two billion individuals, are infected with Mycobacterium tuberculosis, with latent tuberculosis infection (LTBI) accounting for the majority of cases. However, there are no direct diagnostic methods for LTBI, and the major diagnostic assays like tuberculin skin test (TST) and interferon-gamma release assay (IGRA) have notable limitations. Deficiencies in LTBI screening, strict treatment indications, and poor treatment adherence constitute three major challenges confronting current tuberculosis prevention and control, which severely hamper the effectiveness of disease prevention and management. Therefore, developing additional detection modalities to accurately evaluate infection status and predict disease onset risk, coupled with continuous optimization of therapeutic regimens to improve treatment adherence, represent the key to breaking through bottlenecks in tuberculosis prevention and control. Based on latest evidence-based medical data and internationally authoritative guidelines, the authors systematically reviewed advances in LTBI diagnosis and management in alignment with the global End TB Strategy, and further discussed clinical implementation and optimized approaches of LTBI prevention and control, intending to provide theoretical foundation and practical reference for ending global tuberculosis epidemic.

Key words: Mycobacterium tuberculosis, Infections, Protective agents, Review literature as topic

CLC Number:

R52
R183.3

Jiang Ping, Li Tianju, Kang Guanghong, Xiang Mingque. Research progress on prevention and control strategies for latent Mycobacterium tuberculosis infection[J]. Journal of Tuberculosis and Lung Disease, 2026, 7(5): 679-686. doi: 10.19983/j.issn.2096-8493.20260125

Figures/Tables 2

References 45

[1]	屈燕, 李涛, 马文斌, 等. 世界卫生组织《2025年全球结核病报告》解读[J]. 结核与肺部疾病杂志, 2025, 6(6): 613-623. doi:10.19983/j.issn.2096-8493.20250178.
[2]	Houben R M, Dodd P J. The Global Burden of Latent Tuberculosis Infection: A Re-estimation Using Mathematical Modelling[J]. PLoS Med, 2016, 13(10):e1002152. doi:10.1371/journal.pmed.1002152.
[3]	World Health Organization. Global tuberculosis report 2020[R]. Geneva: World Health Organization, 2020.
[4]	World Health Organization. Global tuberculosis report 2023[R]. Geneva: World Health Organization, 2023.
[5]	Getahun H, Matteelli A, Chaisson R E, et al. Latent Mycobacterium tuberculosis infection[J]. N Engl J Med, 2015, 372(22):2127-2135. doi:10.1056/NEJMra1405427.
[6]	高磊, 金奇. 关口前移:结核潜伏感染及其控制[J]. 中国防痨杂志, 2018, 40(8):791-795. doi:10.3969/j.issn.1000-6621.2018.08.00.
[7]	中华人民共和国国家卫生和计划生育委员会. WS 196-2017结核病分类[J]. 结核与肺部疾病杂志, 2024, 5 (4): 379-380. doi:10.19983/j.issn.2096-8493.2024055.
[8]	中国防痨协会, 中国防痨协会学校与儿童结核病防治专业分会, 《中国防痨杂志》编辑委员会. 重组结核杆菌融合蛋白(EC)临床应用专家共识[J]. 中国防痨杂志, 2020, 42 (8): 761-768. doi:10.3969/j.issn.1000-6621.2020.08.001.
[9]	中国防痨协会. 高危人群结核分枝杆菌潜伏感染检测及预防性治疗专家共识[J]. 中国防痨杂志, 2021, 43 (9): 874-878. doi:10.3969/j.issn.1000-6621.2021.09.004.
[10]	高磊, 权竹声, 成君, 等. 结核分枝杆菌感染检测两步法在学校结核病控制工作中的应用探讨[J]. 中华预防医学杂志, 2020, 54(4):385-391. doi:10.3760/cma.j.cn112150-20191204-00909.
[11]	Mahon J, Beale S, Holmes H, et al. A systematic review of cost-utility analyses of screening methods in latent tuberculosis infection in high-risk populations[J]. BMC Pulm Med, 2022, 22(1):375. doi:10.1186/s12890-022-02149-x. pmid: 36199061
[12]	Rakotosamimanana N, Richard V, Raharimanga V. Biomarkers for risk of developing active tuberculosis in contacts of TB patients: a prospective cohort study[J]. Eur Respir J, 2015, 46(4):1095-1103. doi:10.1183/13993003.00263-2015. pmid: 26250497
[13]	Zak D E, Penn-Nicholson A, Scriba T J. ACS and GC6-74 cohort study groups. A blood RNA signature for tuberculosis disease risk: a prospective cohort study[J]. Lancet, 2016, 387(10035):2312-2322. doi:10.1016/S0140-6736(15)01316-1. pmid: 27017310
[14]	Warsinske H C, Rao A M, Moreira F M F. Assessment of Validity of a Blood-Based 3-Gene Signature Score for Progression and Diagnosis of Tuberculosis, Disease Severity, and Treatment Response[J]. JAMA Netw Open, 2018, 1(6):e183779. doi:10.1001/jamanetworkopen.2018.3779.
[15]	Sabir N, Hussain T, Shah S Z A. New Avenues for Diagnosis and Host-Directed Therapy[J]. Front Microbiol, 2018, 9:602. doi:10.3389/fmicb.2018.00602.
[16]	Meier N R, Jacobsen M, Ottenhoff T H M. A Systematic Review on Novel Mycobacterium tuberculosis Antigens and Their Discriminatory Potential for the Diagnosis of Latent and Active Tuberculosis[J]. Front Immunol, 2018, 9:2476. doi:10.3389/fimmu.2018.02476.
[17]	Kumar S K, Arya S, Aggarwal A, et al. Immune responses to Mycobacterium tuberculosis membrane-associated antigens including alpha crystallin can potentially discriminate between latent infection and active tuberculosis disease[J]. PLoS One, 2020, 15:e228359. doi:10.1371/journal.pone.0228359.
[18]	Carranza C, Pedraza-Sanchez S. Diagnosis for Latent Tuberculosis Infection: New Alternatives[J]. Front Immunol, 2020, 11:2006. doi:10.3389/fimmu.2020.02006. pmid: 33013856
[19]	李志丽, 刘宇红. 《世界卫生组织结核病整合指南模块6:结核病及其共患病-HIV》解读[J]. 中国防痨杂志, 2024, 46 (8): 869-873. doi:10.19982/j.issn.1000-6621.20240225.
[20]	Ford N, Matteelli A, Shubber Z. TB as a cause of hospitalization and in-hospital mortality among people living with HIV worldwide: a systematic review and meta-analysis[J]. J Int AIDS Soc, 2016, 19(1):20714. doi:10.7448/IAS.19.1.20714. pmid: 26765347
[21]	刘儒卓, 苏容, 李东民. HIV与结核分枝杆菌合并感染现状及影响因素的研究进展[J]. 中华流行病学杂志, 2025, 46 (1): 166-174. doi:10.3760/cma.j.cn112338-20240806-00478.
[22]	Zhang C Y, Zhao F, Xia Y Y. Prevalence and risk factors of active pulmonary tuberculosis among elderly people in China: a population based cross-sectional study[J]. Infect Dis Poverty, 2019, 8(1):7. doi:10.1186/s40249-019-0515-y.
[23]	World Health Organization. WHO consolidated guidelines on tuberculosis: tuberculosis preventive treatment: Module 1: prevention[R]. Geneva: World Health Organization, 2020.
[24]	Jeon C Y, Murray M B. Diabetes mellitus increases the risk of active tuberculosis: a systematic review of 13 observational studies[J]. PLoS Medicine, 2008, 5(7):e152. doi:10.1371/journal.pmed.0050152.
[25]	钱梦妮, 陆霓虹, 杜映荣. 糖尿病合并结核分枝杆菌潜伏感染影响因素的Meta分析[J]. 结核与肺部疾病杂志, 2026, 7 (2): 203-210. doi:10.19983/j.issn.2096-8493.20250136.
[26]	Zhou G, Guo X, Cai S. Diabetes mellitus and latent tuberculosis infection: an updated meta-analysis and systematic review[J]. BMC Infect Dis, 2023, 23(1):770. doi:10.1186/s12879-023-08775-y. pmid: 37940866
[27]	高磊, 张慧, 胡茂桂, 等. 基于多中心调查数据和空间统计模型的全国结核分枝杆菌潜伏感染率估算[J]. 中国防痨杂志, 2022, 44 (1): 54-59. doi:10.19982/j.issn.1000-6621.2022.01.005.
[28]	丁立, 陈惠丽, 刘泽霞, 等. 结核分枝杆菌感染高危人群潜伏结核感染筛查及危险因素分析[J]. 中国热带医学, 2015, 15(5):555-557. doi:10.13604/j.cnki.46-1064/r.2015.05.01.
[29]	游继存, 田磊, 汪玲燕, 等. 1007例糖尿病患者结核分枝杆菌潜伏感染现状及相关因素分析[J]. 中国防痨杂志, 2026, 48(7):965-971. doi:10.19982/j.issn.1000-6621.20260050.
[30]	中华人民共和国国家卫生健康委员会. 中国结核病预防控制工作技术规范(2020年版)[Z]. 国卫办疾控函〔2020〕279号. 2020-04-02.
[31]	World Health Organization. WHO consolidated guidelines on tuberculosis: Module 1: Prevention-Tuberculosis preventive treatment, second edition[R]. Geneva: World Health Organi-zation, 2024.
[32]	Huynh G H, Klein D J, Chin D P. Tuberculosis control strategies to reach the 2035 global targets in China: the role of changing demographics and reactivation disease[J]. BMC Med, 2015, 13:88. doi:10.1186/s12916-015-0341-4. pmid: 25896465
[33]	张璇. 糖尿病患者结核潜伏感染影响因素分析及其向活动性肺结核转化的预测模型研究[D]. 大理: 大理大学, 2025. doi:10.27811/d.cnki.gdixy.2025.000745.
[34]	Golub J E, Cohn S, Saraceni V. Long-term protection from isoniazid preventive therapy for tuberculosis in HIV-infected patients in a medium-burden tuberculosis setting: the TB/HIV in Rio (THRio) study[J]. Clin Infect Dis, 2015, 60(4):639-45. doi:10.1093/cid/ciu849. pmid: 25365974
[35]	Chakaya J, Petersen E, Nantanda R, et al. The WHO Global Tuberculosis 2021 Report-not so good news and turning the tide back to End TB[J]. Int J Infect Dis, 2022, 124 (Suppl 1):S26-S29. doi:10.1016/j.ijid.2022.03.011.
[36]	Menzies D, Adjobimey M, Ruslami R, et al. Four months of rifampin or nine months of isoniazid for latent tuberculosis in adults[J]. N Engl J Med, 2018, 379(5):440-453. doi:10.1056/NEJMoa1714283.
[37]	中华医学会结核病学分会, 《中华结核和呼吸杂志》编辑委员会. 抗结核药所致药物性肝损伤诊断与处理专家建议[J]. 中华结核和呼吸杂志, 2013, 36(10): 732-736. doi:10.3760/cma.j.issn.1001-0939.2013.10.007.
[38]	Chung S J, Byeon S J, Choi J H. Analysis of Adverse Drug Reactions to First-Line Anti-Tuberculosis Drugs Using the Korea Adverse Event Reporting System[J]. J Korean Med Sci, 2022, 37(16):e128. doi:10.3346/jkms.2022.37.e128. pmid: 35470602
[39]	Resende L S, Santos-Neto E T. Risk factors associated with adverse reactions to antituberculosis drugs[J]. J Bras Pneumol, 2015, 41(1):77-89. doi:10.1590/S1806-37132015000100010. pmid: 25750677
[40]	王欣, 邓丰业, 孙玉林, 等. 新型抗结核药物制剂研究进展[J]. 中国现代应用药学, 2023, 40 (11): 1578-1584. doi:10.13748/j.cnki.issn1007-7693.20221800.
[41]	方刚, 顾小燕, 尹小芳. 母牛分枝杆菌菌苗辅助抗结核方案治疗肺结核对患者免疫功能及疾病转归的影响[J]. 中国临床研究, 2020, 33 (4): 501-504. doi:10.13429/j.cnki.cjcr.2020.04.017.
[42]	Vilaplana C, Montané E, Pinto S, et al. Double-blind, randomized, placebo-controlled Phase I Clinical Trial of the therapeutical antituberculous vaccine RUTI[J]. Vaccine, 2010, 28(4):1106-1116. doi:10.1016/j.vaccine.2009.09.134. pmid: 19853680
[43]	Prabowo S A, Painter H, Zelmer A, et al. RUTI Vaccination Enhances Inhibition of Mycobacterial Growth ex vivo and Induces a Shift of Monocyte Phenotype in Mice[J]. Front Immunol, 2019, 10:894. doi:10.3389/fimmu.2019.00894. pmid: 31114572
[44]	Russo G, Sgroi G, Parasiliti Palumbo G A, et al. Moving forward through the in silico modeling of tuberculosis: a further step with UISS-TB[J]. BMC Bioinformatics, 2020, 21(Suppl 17):458. doi:10.1186/s12859-020-03762-5. pmid: 33308139
[45]	Nell A S, D’lom E, Bouic P, et al. Safety, tolerability, and immunogenicity of the novel antituberculous vaccine RUTI: randomized, placebo-controlled phase Ⅱ clinical trial in patients with latent tuberculosis infection[J]. PLoS One, 2014, 9(2):e89612. doi:10.1371/journal.pone.0089612.

项目	TST	TBST	IGRA
操作方法	前臂皮内注射5U结核菌素纯蛋白衍生物(PPD)—72h后观察皮肤反应	前臂皮内注射重组结核杆菌融合蛋白0.1ml(5U)—48h后观察皮肤反应	静脉血检测
试验设备	不需要仪器设备	不需要仪器设备	设备昂贵
操作特点	简便	简便	复杂
对人员要求	皮肤试验检测	皮肤试验检测	技术要求较高
受BCG干扰;能否区分MTB/NTM	受BCG干扰;不能区分	不受BCG干扰;能区分	不受BCG干扰;能区分
优势	费用低,可大面积筛查	检测准确性提升	特异度提高
劣势	存在主观性;可能为假阴性;受BCG接种的影响,高估实际的感染人数	存在主观性	费用高,不适合大面积筛查;可能为假阴性
预测进展为活动性结核病的能力	低	低	低

与利福平合用的药物	受影响结果
咪达唑仑、三唑仑、辛伐他汀	浓度下降
维拉帕米和大多数二氢吡啶类钙通道拮抗剂	治疗无效
地高辛(通过转运安保P-糖蛋白)	治疗无效
伊曲康唑和酮康唑、伏立康唑	疗效下降
HIV蛋白酶、整合酶抑制剂	疗效下降或无效
美沙酮	出现阿片类药物戒断症状
引起接受免疫抑制药物如接受环孢素治疗	浓度下降,出现急性移植排斥反应
华法林和磺酰脲类(减低CYP 2C底物血药浓度)	疗效下降