结核病学科建设:从临床资源型向医学科研型转化

doi:10.19982/j.issn.1000-6621.20230353

摘要/Abstract

摘要：

目前,全球结核病的诊断、治疗和预防已经取得了长足的进展,但依然任重道远。近年来,通过大规模人群队列和生物样本库资源广泛搭建,促使疾病研究和科研转化持续突破,诊断技术和药物开发思路与审批标准也开始发生转变,相关产品陆续进入临床应用,提高了疾病精准预防、诊断和治疗水平。结核病学科建设正在从临床资源型向医学科研型转化。笔者从结核病诊疗现状提出目前面临的困境,详细阐述基于精准医学概念的结核病防治理念,强调医学科研型转化在结核病精准诊治中的作用及重视临床医学和公共卫生双轴转化路径。最后提出,在结核病医学科研转化之路上,需重视综合型、创新型、高层次复合型医学人才培养,并建立相关的政策保障制度,引导精准医学和医学科研转化相关领域及产业的全面有序发展。

关键词: 结核, 学科间信息交流, 队列研究

Abstract:

Currently, great progress has been made in tuberculosis (TB) diagnosis, treatment and prevention; however, there is still a long way to go. In recent years, large-scale cohort studies and biological sample library resources have led to continuous breakthroughs in disease research and TB-related translational medicine. Diagnostic technology and drug development ideas and approval standards have also begun to change, and related products have gradually been applied in clinic, improving the level of precise prevention, diagnosis, and treatment. In this review, we present the current dilemma based on the current situation of TB diagnosis and treatment, elaborate the concept TB prevention and treatment based on the concept of precision medicine, emphasize the role of medical research-based transformation in the accurate diagnosis and treatment of TB, as well as the dual-path transformation of clinical medicine and public health. Finally, on the road to TB translational medicine, it is proposed that, attention should be paid to the cultivation of comprehensive, innovative and high-level medical talents, and establish a policy-oriented guarantee system to guide the orderly development of precision medicine and medical research transformation.

Key words: Tuberculosis, Interdisciplinary communication, Cohort studies

中图分类号:

王瑾, 卢水华. 结核病学科建设:从临床资源型向医学科研型转化[J]. 中国防痨杂志, 2023, 45(12): 1125-1130. doi: 10.19982/j.issn.1000-6621.20230353

Wang Jin, Lu Shuihua. Discipline construction of tuberculosis: from clinical resources to medical research-based translational medicine[J]. Chinese Journal of Antituberculosis, 2023, 45(12): 1125-1130. doi: 10.19982/j.issn.1000-6621.20230353

图/表 1

参考文献 26

[1]	World Health Organization. Global tuberculosis report 2022. Geneva: World Health Organization, 2022.
[2]	卢水华. 关注结核病共患病已成为公共卫生的需要. 结核与肺部疾病杂志, 2022, 3(4): 255-260. doi:10.19983/j.issn.2096-8493.20220107.
[3]	Lange C, Aaby P, Behr MA, et al. 100 years of Mycobacterium bovis bacille Calmette-Guérin. Lancet Infect Dis, 2022, 22(1): e2-e12. doi:10.1016/S1473-3099(21)00403-5.
[4]	Abubakar I, Pimpin L, Ariti C, et al. Systematic review and meta-analysis of the current evidence on the duration of protection by bacille Calmette-Guérin vaccination against tuberculosis. Health Technol Assess, 2013, 17(37): 1-372, v-vi. doi:10.3310/hta17370. pmid: 24021245
[5]	Nguipdop-Djomo P, Heldal E, Rodrigues LC, et al. Duration of BCG protection against tuberculosis and change in effectiveness with time since vaccination in Norway: a retrospective population-based cohort study. Lancet Infect Dis, 2016, 16(2): 219-226. doi:10.1016/S1473-3099(15)00400-4. pmid: 26603173
[6]	National Research Council US Committee on A Framework for Developing a New Taxonomy of Disease. Toward Precision Medicine:Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease. Washington (DC): National Academies Press (US), 2011.
[7]	Turnbull C, Scott RH, Thomas E, et al. The 100000 Genomes Project: bringing whole genome sequencing to the NHS. BMJ, 2018, 361: k1687. doi:10.1136/bmj.k1687.
[8]	All of Us Research Program Investigators, Denny JC, Rutter JL, et al. The “All of Us” Research Program. N Engl J Med, 2019, 381(7): 668-676. doi:10.1056/NEJMsr1809937.
[9]	Kaiser J. NIH’s ‘precision nutrition’ bet aims for individualized diets. Science, 2021, 371(6529): 552. doi:10.1126/science.371.6529.552.
[10]	Denny JC, Collins FS. Precision medicine in 2030-seven ways to transform healthcare. Cell, 2021, 184(6): 1415-1419. doi:10.1016/j.cell.2021.01.015. pmid: 33740447
[11]	CRyPTIC Consortium and the 100,000 Genomes Project, Allix-Béguec C, Arandjelovic I, et al. Prediction of Susceptibility to First-Line Tuberculosis Drugs by DNA Sequencing. N Engl J Med, 2018, 379(15):1403-1415. doi:10.1056/NEJMoa1800474.
[12]	The CRyPTIC Consortium. A data compendium associating the genomes of 12,289 Mycobacterium tuberculosis isolates with quantitative resistance phenotypes to 13 antibiotics. PLoS Biol, 2022, 20(8): e3001721. doi:10.1371/journal.pbio.3001721.
[13]	Huang H, Wang C, Rubelt F, et al. Analyzing the Mycobacterium tuberculosis immune response by T-cell receptor clustering with GLIPH2 and genome-wide antigen screening. Nat Biotechnol, 2020, 38(10): 1194-1202. doi:10.1038/s41587-020-0505-4.
[14]	Chen JX, Han YS, Zhang SQ, et al. Novel therapeutic evaluation biomarkers of lipid metabolism targets in uncomplicated pulmonary tuberculosis patients. Signal Transduct Target Ther, 2021, 6(1): 22. doi:10.1038/s41392-020-00427-w.
[15]	Cliff JM, Lee JS, Constantinou N, et al. Distinct phases of blood gene expression pattern through tuberculosis treatment reflect modulation of the humoral immune response. J Infect Dis, 2013, 207(1): 18-29. doi:10.1093/infdis/jis499. pmid: 22872737
[16]	DiNardo AR, Gandhi T, Heyckendorf J, et al. Gene expression signatures identify biologically and clinically distinct tuberculosis endotypes. Eur Respir J, 2022, 60(3): 2102263. doi:10.1183/13993003.02263-2021.
[17]	Heyckendorf J, Marwitz S, Reimann M, et al. Prediction of anti-tuberculosis treatment duration based on a 22-gene transcriptomic model. Eur Respir J, 2021, 58(3): 2003492. doi:10.1183/13993003.03492-2020.
[18]	Mulenga H, Musvosvi M, Mendelsohn SC, et al. Longitudinal Dynamics of a Blood Transcriptomic Signature of Tuberculosis. Am J Respir Crit Care Med, 2021, 204(12): 1463-1472. doi:10.1164/rccm.202103-0548OC.
[19]	Turner CT, Gupta RK, Tsaliki E, et al. Blood transcriptional biomarkers for active pulmonary tuberculosis in a high-burden setting: a prospective, observational, diagnostic accuracy study. Lancet Respir Med, 2020, 8(4): 407-419. doi:10.1016/S2213-2600(19)30469-2. pmid: 32178775
[20]	van Doorn CLR, Eckold C, Ronacher K, et al. Transcriptional profiles predict treatment outcome in patients with tuberculosis and diabetes at diagnosis and at two weeks after initiation of anti-tuberculosis treatment. EBioMedicine, 2022, 82:104173. doi:10.1016/j.ebiom.2022.104173.
[21]	Scriba TJ, Fiore-Gartland A, Penn-Nicholson A, et al. Biomarker-guided tuberculosis preventive therapy (CORTIS): a randomised controlled trial. Lancet Infect Dis, 2021, 21(3): 354-365. doi:10.1016/S1473-3099(20)30914-2. pmid: 33508224
[22]	Marakalala MJ, Raju RM, Sharma K, et al. Inflammatory signaling in human tuberculosis granulomas is spatially orga-nized. Nat Med, 2016, 22(5):531-538. doi:10.1038/nm.4073.
[23]	Huang Z, LaCourse SM, Kay AW, et al. CRISPR detection of circulating cell-free Mycobacterium tuberculosis DNA in adults and children, including children with HIV: a molecular diagnostics study. Lancet Microbe, 2022, 3(7): e482-e492. doi:10.1016/S2666-5247(22)00087-8. pmid: 35659882
[24]	Wallis RS, Ginindza S, Beattie T, et al. Adjunctive host-directed therapies for pulmonary tuberculosis: a prospective, open-label, phase 2, randomised controlled trial. Lancet Respir Med, 2021, 9(8): 897-908. doi:10.1016/S2213-2600(20)30448-3. pmid: 33740465
[25]	Marks GB, Nguyen NV, Nguyen PTB, et al. Community-wide Screening for Tuberculosis in a High-Prevalence Setting. N Engl J Med, 2019, 381(14): 1347-1357. doi:10.1056/NEJMoa1902129.
[26]	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. 中国防痨杂志, 2021, 43(9):874-878. doi:10.3969/j.issn.1000-6621.2021.09.004.