Expert consensus on diagnosis and treatment of latent tuberculosis infection in patients with rheumatic diseases

doi:10.19982/j.issn.1000-6621.20220225

Abstract

Abstract:

Rheumatic diseases are autoimmune diseases that occur when an individual’s immune system mistakenly attacks healthy tissues, and are often treated with glucocorticoids, immunosuppressants, biological agents, and small-molecule targeted drugs, etc., which can lead to an increased risk of other autoimmune dysfunctions in patients and the activation of latent tuberculosis infection (LTBI). Therefore, LTBI screening in clinical is essential for patients with rheumatic diseases who meet the screening criteria. This requires greater collaboration and awareness between rheumatologists and tuberculosis physicians, to conduct scientific assessment for patients with rheumatic diseases who need LTBI screening, and to develop preventive treatment guidelines to prevent patients with rheumatic diseases from developing active tuberculosis after LTBI. Therefore, the National Clinical Research Centre for Infectious Disease/The Third People’s Hospital of Shenzhen, Peking University Shenzhen Hospital, Peking Union Medical College Hospital of Chinese Academy of Medical Sciences, Chinese Antituberculosis Association, Editorial Board of Chinese Journal of Antituberculosis and Shenzhen Key Laboratory of Inflammatory and Immune Diseases joint effort in the publication of an expert consensus on the diagnosis and treatment of LTBI in patients with rheumatic diseases. This consensus is based on the epidemiology, evidence-based medicine, and clinical research of rheumatic diseases complicated with LTBI, and has been discussed for many times and reached consensus. It can serve as a reference.

Key words: Rheumatic diseases, Mycobacterium tuberculosis, Infection, Diagnosis, Therapeutic uses

CLC Number:

R593
R52

National Clinical Research Centre for Infectious Disease/The Third People’s Hospital of Shenzhen, Peking University Shenzhen Hospital, Peking Union Medical College Hospital of Chinese Academy of Medical Sciences, Chinese Antituberculosis Association, Editorial Board of Chinese Journal of Antituberculosis, Shenzhen Key Laboratory of Inflammatory and Immune Diseases. Expert consensus on diagnosis and treatment of latent tuberculosis infection in patients with rheumatic diseases[J]. Chinese Journal of Antituberculosis, 2022, 44(9): 869-879. doi: 10.19982/j.issn.1000-6621.20220225

Figures/Tables 6

References 77

[1]	World Health Organization. Latent tuberculosis infection: updated and consolidated guidelines for programmatic management. Geneva: World Health Organization, 2018.
[2]	World Health Organization. Global tuberculosis report 2021. Geneva: World Health Organization, 2021.
[3]	World Health Organization. Global tuberculosis report 2018. Geneva: World Health Organization, 2018.
[4]	中华人民共和国国家卫生和计划生育委员会. WS 288-2017 肺结核诊断. 2017-11-09.
[5]	Centers for Disease Control and Prevention. LTBI: a guide for primary health care providers-Diagnosis of latent TB infection. Atlanta: Centers for Disease Control and Prevention, 2019.
[6]	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. 中国防痨杂志, 2020, 42(8): 761-768. doi: 10.3969/i.issn.1000-6621.2020.08.001. doi: 10.3969/i.issn.1000-6621.2020.08.001
[7]	Anton C, Machado FD, Ramirez JMA, et al. Latent tuberculosis infection in patients with rheumatic diseases. J Bras Pneumol, 2019, 45(2):e20190023. doi: 10.1590/1806-3713/e201 90023. doi: 10.1590/1806-3713/e201 90023 URL
[8]	Garziera G, Morsch ALB, Otesbelgue F, et al. Latent tuberculosis infection and tuberculosis in patients with rheumatic diseases treated with anti-tumor necrosis factor agents. Clin Rheumatol, 2017, 36(8):1891-1896. doi: 10.1007/s10067-017-3714-6. doi: 10.1007/s10067-017-3714-6 pmid: 28589321
[9]	Long W, Cai F, Wang X, et al. High risk of activation of latent tuberculosis infection in rheumatic disease patients. Infect Dis (Lond), 2020, 52(2):80-86. doi: 10.1080/23744235.2019.1682187. doi: 10.1080/23744235.2019.1682187
[10]	Pettipher C, Benitha R. Tuberculosis in biologic users for rheumatic diseases: results from the South African Biologics Registry (SABIO). Ann Rheum Dis, 2020, 79(2):292-299. doi: 10.1136/annrheumdis-2019-216128. doi: 10.1136/annrheumdis-2019-216128 pmid: 31791950
[11]	Malaviya AN, Aggarwal VK, Rawat R, et al. Screening for latent tuberculosis infection among patients with rheumatoid arthritis in the era of biologics and targeted synthetic disease-modifying anti-rheumatic drugs in India, a high-burden TB country: The importance of Mantoux and Quantiferon-TB Gold tests. Int J Rheum Dis, 2018, 21(8):1563-1571. doi: 10.1111/1756-185X.13261. doi: 10.1111/1756-185X.13261 pmid: 29345081
[12]	Lee J, Kim E, Jang EJ, et al. Efficacy of Treatment for Latent Tuberculosis in Patients Undergoing Treatment with a Tumor Necrosis Factor Antagonist. Ann Am Thorac Soc, 2017, 14(5):690-697. doi: 10.1513/AnnalsATS.201608-647OC. doi: 10.1513/AnnalsATS.201608-647OC URL
[13]	Cuomo G, D’Abrosca V, Iacono D, et al. The conversion rate of tuberculosis screening tests during biological therapies in patients with rheumatoid arthritis. Clin Rheumatol, 2017, 36(2):457-461. doi: 10.1007/s10067-016-3462-z. doi: 10.1007/s10067-016-3462-z URL
[14]	王子浔, 荣兰香, 马淑红, 等. 风湿免疫性疾病患者行T-SPOT.TB检测筛查潜伏性结核感染的价值. 中国实验诊断学, 2017, 21(3):512-514. doi: 10.3969/j.issn.1007-4287.2017.03.047. doi: 10.3969/j.issn.1007-4287.2017.03.047
[15]	黄安芳, 罗妍, 赵毅, 等. 风湿病患者合并潜伏性结核感染的分析. 中华内科杂志, 2016, 55(4):307-310. doi: 10.3760/cma.j.issn.0578-1426.2016.04.012. doi: 10.3760/cma.j.issn.0578-1426.2016.04.012
[16]	邓国防, 王玉香, 陈涛, 等. 风湿免疫性疾病并发结核感染的临床特征分析. 中国防痨杂志, 2018, 40(4):392-396. doi: 10.3969/j.issn.1000-6621.2018.04.009. doi: 10.3969/j.issn.1000-6621.2018.04.009
[17]	刘羽佳, 徐婧, 郭倩, 等. 慢性炎症性关节炎患者潜伏性结核感染的发生率及不同筛查方法的诊断价值. 中华医学杂志, 2019, 99(1): 20-24. doi: 10.3760/cma.j.issn.0376-2491. 2019.01.005. doi: 10.3760/cma.j.issn.0376-2491. 2019.01.005
[18]	中国医学科学院病原生物学研究所, 中国疾病预防控制中心, 中国科学院地理科学与资源研究所. 全国结核分枝杆菌潜伏感染率估算专家共识. 中国防痨杂志, 2022, 44(1): 4-8. doi: 10.19982/j.issn.1000-6621.20210662. doi: 10.19982/j.issn.1000-6621.20210662
[19]	Gao L, Lu W, Bai L, et al. Latent tuberculosis infection in rural China: baseline results of a population-based, multicentre, prospective cohort study. Lancet Infect Dis, 2015, 15(3): 310-319. doi: 10.1016/S1473-3099(14)71085-0. doi: 10.1016/S1473-3099(14)71085-0 URL
[20]	Liu X, Zhang L, Zhang F, et al. Prevalence and Risk Factors of Active Tuberculosis in Patients with Rheumatic Diseases: A Multi-center, Cross-Sectional Study in China. Emerg Microbes Infect, 2021, 10:1-36. doi: 10.1080/22221751.2021.2004864. doi: 10.1080/22221751.2021.2004864 URL
[21]	全国第五次结核病流行病学抽样调查技术指导组, 全国第五次结核病流行病学抽样调查办公室. 2010年全国第五次结核病流行病学抽样调查报告. 中国防痨杂志, 2012, 34(8): 485-508.
[22]	Scrivo R, Armignacco O. Tuberculosis risk and anti-tumour necrosis factor agents in rheumatoid arthritis: a critical appraisal of national registry data. Int J Rheum Dis, 2014, 17(7):716-724. doi: 10.1111/1756-185X.12375. doi: 10.1111/1756-185X.12375 URL
[23]	Cantini F, Nannini C, Niccoli L, et al. Guidance for the management of patients with latent tuberculosis infection requiring biologic therapy in rheumatology and dermatology clinical practice. Autoimmun Rev, 2015, 14(6):503-509. doi: 10.1016/j.autrev.2015.01.011. doi: 10.1016/j.autrev.2015.01.011 URL
[24]	Muhammed H, Jain A, Pattanaik SS, et al. Clinical spectrum of active tuberculosis in patients with systemic lupus erythematosus. Rheumatol Int, 2021, 41(12):2185-2193. doi: 10.1007/s00296-021-04933-0. doi: 10.1007/s00296-021-04933-0 pmid: 34191047
[25]	Greenstein L, Makan K, Tikly M. Burden of comorbidities in South Africans with systemic lupus erythematosus. Clin Rheumatol, 2019, 38(8):2077-2082. doi: 10.1007/s10067-019-04511-7. doi: 10.1007/s10067-019-04511-7 pmid: 30963335
[26]	González-Naranjo LA, Coral-Enríquez JA, Restrepo-Escobar M, et al. Factors associated with active tuberculosis in Colombian patients with systemic lupus erythematosus: a case-control study. Clin Rheumatol, 2021, 40(1):181-191. doi: 10.1007/s10067-020-05225-x. doi: 10.1007/s10067-020-05225-x URL
[27]	Lao M, Chen D, Wu X, et al. Active tuberculosis in patients with systemic lupus erythematosus from Southern China: a retrospective study. Clin Rheumatol, 2019, 38(2): 535-543. doi: 10.1007/s10067-018-4303-z. doi: 10.1007/s10067-018-4303-z URL
[28]	Xiao X, Da G, Xie X, et al. Tuberculosis in patients with systemic lupus erythematosus-a 37-year longitudinal survey-based study. J Intern Med, 2021, 290(1): 101-115. doi: 10.1111/joim.13218. doi: 10.1111/joim.13218 pmid: 33259665
[29]	Yang Y, Thumboo J, Tan BH, et al. The risk of tuberculosis in SLE patients from an Asian tertiary hospital. Rheumatol Int, 2017, 37(6): 1027-1033. doi: 10.1007/s00296-017-3696-3. doi: 10.1007/s00296-017-3696-3 URL
[30]	Ciang NC, Chan SCW, Lau CS, et al. Risk of tuberculosis in patients with spondyloarthritis: data from a centralized electronic database in Hong Kong. BMC Musculoskelet Disord, 2020, 21(1): 832. doi: 10.1186/s12891-020-03855-5. doi: 10.1186/s12891-020-03855-5 URL
[31]	de Vries MK, Arkema EV, Jonsson J, et al. Tuberculosis Risk in Ankylosing Spondylitis, Other Spondyloarthritis, and Psoriatic Arthritis in Sweden: A Population-Based Cohort Study. Arthritis Care Res (Hoboken), 2018, 70(10):1563-1567. doi: 10.1002/acr.23487. doi: 10.1002/acr.23487 URL
[32]	Ai JW, Zhang S, Ruan QL, et al. The Risk of Tuberculosis in Patients with Rheumatoid Arthritis Treated with Tumor Necrosis Factor-Antagonist: A Metaanalysis of Both Randomized Controlled Trials and Registry/Cohort Studies. J Rheumatol, 2015, 42(12):2229-2237. doi: 10.3899/jrheum.150057. doi: 10.3899/jrheum.150057 URL
[33]	Lorenzetti R, Zullo A, Ridola L, et al. Higher risk of tuberculosis reactivation when anti-TNF is combined with immunosuppressive agents: a systematic review of randomized controlled trials. Ann Med, 2014, 46(7):547-554. doi: 10.3109/07853890.2014.941919. doi: 10.3109/07853890.2014.941919 pmid: 25105206
[34]	Cantini F, Blandizzi C, Niccoli L, et al. Systematic review on tuberculosis risk in patients with rheumatoid arthritis receiving inhibitors of Janus Kinases. Expert Opin Drug Saf, 2020, 19(7):861-872. doi: 10.1080/14740338.2020.1774550. doi: 10.1080/14740338.2020.1774550 URL
[35]	美国辉瑞制药有限公司. 枸橼酸托法替布片说明书[EB/OL]. [2022-04-28]. https://labeling.pfizer.com/ShowLabeling.aspx?id=14493.
[36]	Goletti D, Petrone L, Ippolito G, et al. Preventive therapy for tuberculosis in rheumatological patients undergoing therapy with biological drugs. Expert Rev Anti Infect Ther, 2018, 16(6):501-512. doi: 10.1080/14787210.2018.1483238. doi: 10.1080/14787210.2018.1483238 pmid: 29848120
[37]	Elewski BE, Baddley JW, Deodhar AA, et al. Association of Secukinumab Treatment With Tuberculosis Reactivation in Patients With Psoriasis, Psoriatic Arthritis, or Ankylosing Spondylitis. JAMA Dermatol, 2021, 157(1):43-51. doi: 10.1001/jamadermatol.2020.3257. doi: 10.1001/jamadermatol.2020.3257 URL
[38]	Cantini F, Niccoli L, Goletti D. Tuberculosis risk in patients treated with non-anti-tumor necrosis factor-α (TNF-α) targeted biologics and recently licensed TNF-α inhibitors: data from clinical trials and national registries. J Rheumatol Suppl, 2014, 91:56-64. doi: 10.3899/jrheum.140103. doi: 10.3899/jrheum.140103
[39]	Campbell L, Chen C, Bhagat SS, et al. Risk of adverse events including serious infections in rheumatoid arthritis patients treated with tocilizumab: a systematic literature review and meta-analysis of randomized controlled trials. Rheumatology (Oxford), 2011, 50(3):552-562. doi: 10.1093/rheumatology/keq343. doi: 10.1093/rheumatology/keq343 pmid: 21078627
[40]	Koike T, Harigai M, Inokuma S, et al. Effectiveness and safety of tocilizumab: postmarketing surveillance of 7901 patients with rheumatoid arthritis in Japan. J Rheumatol, 2014, 41(1):15-23. doi: 10.3899/jrheum.130466. doi: 10.3899/jrheum.130466 URL
[41]	Lin CT, Huang WN, Hsieh CW, et al. Safety and effectiveness of tocilizumab in treating patients with rheumatoid arthritis-A three-year study in Taiwan. J Microbiol Immunol Infect, 2019, 52(1):141-150. doi: 10.1016/j.jmii.2017.04.002. doi: 10.1016/j.jmii.2017.04.002 URL
[42]	先声药业集团有限公司. 阿巴西普药物说明书[EB/OL].[2022-06-08]. https://packageinserts.bms.com/pi/pi_orencia.pdf.
[43]	Jick SS, Lieberman ES, Rahman MU, et al. Glucocorticoid use, other associated factors, and the risk of tuberculosis. Arthritis Rheum, 2006, 55(1):19-26. doi: 10.1002/art.21705. doi: 10.1002/art.21705 URL
[44]	Brassard P, Lowe AM, Bernatsky S, et al. Rheumatoid arthritis, its treatments, and the risk of tuberculosis in Quebec, Canada. Arthritis Rheum, 2009, 61(3):300-304. doi: 10.1002/art.24476. doi: 10.1002/art.24476 URL
[45]	Cooray S, Zhang H, Breen R, et al. Cerebral tuberculosis in a patient with systemic lupus erythematosus following cyclophosphamide treatment: a case report. Lupus, 2018, 27(4): 670-675. doi: 10.1177/0961203317722849. doi: 10.1177/0961203317722849 pmid: 28764615
[46]	Macauley P, Rapp M, Park S, et al. Miliary Tuberculosis Presenting With Meningitis in a Patient Treated With Mycophenolate for Lupus Nephritis: Challenges in Diagnosis and Review of the Literature. J Investig Med High Impact Case Rep, 2018, 6:2324709618770226. doi: 10.1177/2324709618770226. doi: 10.1177/2324709618770226
[47]	Ting SW, Ting SY, Lin YS, et al. Association between dif-ferent systemic therapies and the risk of tuberculosis in psoriasis patients: A population-based study. Int J Clin Pract, 2021, 75(12):e15006. doi: 10.1111/ijcp.15006. doi: 10.1111/ijcp.15006
[48]	Ha YE, Joo EJ, Park SY, et al. Tacrolimus as a risk factor for tuberculosis and outcome of treatment with rifampicin in solid organ transplant recipients. Transpl Infect Dis, 2012, 14(6):626-634. doi: 10.1111/j.1399-3062.2012.00721.x. doi: 10.1111/j.1399-3062.2012.00721.x pmid: 22372581
[49]	朱翠云. 对人类免疫缺陷病毒感染者潜伏性结核感染的筛查和干预. 上海医药, 2020, 41(11):14-16,20. doi: 10.3969/j.issn.1006-1533.2020.11.005. doi: 10.3969/j.issn.1006-1533.2020.11.005
[50]	Wang L, Turner MO, Elwood RK, et al. A meta-analysis of the effect of Bacille Calmette Guérin vaccination on tuberculin skin test measurements. Thorax, 2002, 57(9):804-809. doi: 10.1136/thorax.57.9.804. doi: 10.1136/thorax.57.9.804 pmid: 12200526
[51]	孟炜丽, 罗萍, 胡京坤, 等. BCG-PPD与TB-PPD皮肤试验在大学生结核病筛查中的差异性分析. 中国防痨杂志, 2014, 36(7):532-536. doi: 10.3969/j.issn.1000-6621.2014.07.005. doi: 10.3969/j.issn.1000-6621.2014.07.005
[52]	Friedman L, Dedicoat M, Davies P. Clinical Tuberculosis. 6th ed. Boca Raton: CRC Press, 2020: 154.
[53]	Aggerbeck H, Ruhwald M, Hoff ST, et al. Interaction between C-Tb and PPD given concomitantly in a split-body randomised controlled trial. Int J Tuberc Lung Dis, 2019, 23(1): 38-44. doi: 10.5588/ijtld.18.0137. doi: 10.5588/ijtld.18.0137 pmid: 30572979
[54]	Abubakar I, Jackson C, Rangaka MX. C-Tb: a latent tuberculosis skin test for the 21st century? Lancet Respir Med, 2017, 5(4):236-237. doi: 10.1016/S2213-2600(17)30012-7. doi: 10.1016/S2213-2600(17)30012-7 pmid: 28159607
[55]	Starshinova A, Dovgalyk I, Malkova A, et al. Recombinant tuberculosis allergen (Diaskintest) in tuberculosis diagnostic in Russia (meta-analysis). Int J Mycobacteriol, 2020, 9(4):335-346. doi: 10.4103/ijmy.ijmy_131_20. doi: 10.4103/ijmy.ijmy_131_20 pmid: 33323648
[56]	潘艳艳, 吴园园, 蔡红娇, 等. 不同的风湿免疫性疾病患者免疫功能差异分析. 当代医学, 2020, 26(19):1-4. doi: 10.3969/j.issn.1009-4393.2020.19.001. doi: 10.3969/j.issn.1009-4393.2020.19.001
[57]	Pang C, Wu Y, Wan C, et al. Accuracy of the Bronchoalveolar Lavage Enzyme-Linked Immunospot Assay for the Diagnosis of Pulmonary Tuberculosis: A Meta-analysis. Medicine (Baltimore), 2016, 95(12):e3183. doi: 10.1097/MD.0000000000003183. doi: 10.1097/MD.0000000000003183 URL
[58]	Pai M, Zwerling A, Menzies D. Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection: an update. Ann Intern Med, 2008, 149(3):177-184. doi: 10.7326/0003-4819-149-3-200808050-00241. doi: 10.7326/0003-4819-149-3-200808050-00241 URL
[59]	Metcalfe JZ, Everett CK, Steingart KR, et al. Interferon-γ release assays for active pulmonary tuberculosis diagnosis in adults in low- and middle-income countries: systematic review and meta-analysis. J Infect Dis, 2011, 204 Suppl 4(Suppl 4):S1120-S1129. doi: 10.1093/infdis/jir410. doi: 10.1093/infdis/jir410
[60]	Barcellini L, Borroni E, Brown J, et al. First evaluation of QuantiFERON-TB Gold Plus performance in contact screening. Eur Respir J, 2016, 48(5):1411-1419. doi: 10.1183/13993003.00510-2016. doi: 10.1183/13993003.00510-2016 pmid: 27390280
[61]	中华医学会结核病学分会. 非结核分枝杆菌病诊断与治疗指南(2020年版). 中华结核和呼吸杂志, 2020, 43(11):918-946. doi: 10.3760/cma.j.cn112147-20200508-00570. doi: 10.3760/cma.j.cn112147-20200508-00570
[62]	Kim CH, Lim JK, Yoo SS, et al. Diagnostic performance of the QuantiFERON-TB Gold In-Tube assay and factors associated with nonpositive results in patients with miliary tuberculosis. Clin Infect Dis, 2014, 58(7):986-989. doi: 10.1093/cid/ciu045. doi: 10.1093/cid/ciu045 URL
[63]	中华医学会结核病学分会. 结核分枝杆菌γ-干扰素释放试验及临床应用专家意见(2021年版). 中华结核和呼吸杂志, 2022, 45(2):143-150. doi: 10.3760/cma.j.cn112147-20211110-00794. doi: 10.3760/cma.j.cn112147-20211110-00794
[64]	Behar SM, Shin DS, Maier A, et al. Use of the T-SPOT.TB assay to detect latent tuberculosis infection among rheumatic disease patients on immunosuppressive therapy. J Rheumatol, 2009, 36(3):546-551. doi: 10.3899/jrheum.080854. doi: 10.3899/jrheum.080854 URL
[65]	Pyo J, Cho SK, Kim D, et al. Systemic review: agreement between the latent tuberculosis screening tests among patients with rheumatic diseases. Korean J Intern Med, 2018, 33(6):1241-1251. doi: 10.3904/kjim.2016.222. doi: 10.3904/kjim.2016.222 URL
[66]	Ruan Q, Zhang S, Ai J, et al. Screening of latent tuberculosis infection by interferon-γ release assays in rheumatic patients: a systemic review and meta-analysis. Clin Rheumatol, 2016, 35(2):417-425. doi: 10.1007/s10067-014-2817-6. doi: 10.1007/s10067-014-2817-6 URL
[67]	World Health Organization. Guidelines on the Management of Latent Tuberculosis Infection. Geneva: World Health Organization, 2015.
[68]	Wang PH, Lin CH, Chang TH, et al. Chest roentgenography is complementary to interferon-gamma release assay in latent tuberculosis infection screening of rheumatic patients. BMC Pulm Med, 2020, 20(1):232. doi: 10.1186/s12890-020-01274-9. doi: 10.1186/s12890-020-01274-9 URL
[69]	中华医学会结核病学分会. 肺结核诊断和治疗指南. 中国实用乡村医生杂志, 2013, 20(2):7-11. doi: 10.3969/j.issn.1672-7185.2013.02.005. doi: 10.3969/j.issn.1672-7185.2013.02.005
[70]	Badje A, Moh R, Gabillard D, et al. Effect of isoniazid preventive therapy on risk of death in west African, HIV-infected adults with high CD4 cell counts: long-term follow-up of the Temprano ANRS 12136 trial. Lancet Glob Health, 2017, 5(11):e1080-e1089. doi: 10.1016/S2214-109X(17)30372-8. doi: 10.1016/S2214-109X(17)30372-8
[71]	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. doi: 10.3969/j.issn.1000-6621.2021.09.004
[72]	Health Protection Surveillance Centre. Guidelines on the Prevention and Control of Tuberculosis in Ireland, 2010-Amended 2014. Dublin: Health Protection Surveillance Centre, 2014:41-42.
[73]	Singh JA, Furst DE, Bharat A, et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken), 2012, 64(5):625-639. doi: 10.1002/acr.21641. doi: 10.1002/acr.21641 URL
[74]	Sterling TR, Njie G, Zenner D, et al. Guidelines for the Treatment of Latent Tuberculosis Infection: Recommendations from the National Tuberculosis Controllers Association and CDC, 2020. MMWR Recomm Rep, 2020, 69(1):1-11. doi: 10.15585/mmwr.rr6901a1. doi: 10.15585/mmwr.rr6901a1
[75]	Sterling TR, Villarino ME, Borisov AS, et al. Three months of rifapentine and isoniazid for latent tuberculosis infection. N Engl J Med, 2011, 365(23):2155-2166. doi: 10.1056/NEJMoa1104875. doi: 10.1056/NEJMoa1104875 URL
[76]	Villarino ME, Scott NA, Weis SE, et al. Treatment for preventing tuberculosis in children and adolescents: a randomized clinical trial of a 3-month, 12-dose regimen of a combination of rifapentine and isoniazid. JAMA Pediatr, 2015, 169(3):247-255. doi: 10.1001/jamapediatrics.2014.3158. doi: 10.1001/jamapediatrics.2014.3158 pmid: 25580725
[77]	中华医学会结核病学分会儿童结核病专业委员会, 国家儿童医学中心, 首都医科大学附属北京儿童医院, 等. 儿童结核分枝杆菌潜伏感染筛查和预防性治疗专家共识. 中华结核和呼吸杂志, 2020, 43(4):345-349. doi: 10.3760/cma.j.cn112147-20200106-00006. doi: 10.3760/cma.j.cn112147-20200106-00006

证据级别	具体描述	研究类型	表达字母
高级证据	非常确信真实的效应值接近效应估计,未来研究几乎不可能改变现有评价结果的可信度	随机对照试验;质量升高二级的观察性研究	A
中级证据	对效应估计值我们有中等程度的信心:真实值有可能接近估计值,但仍存在二者大小相同的可能性;未来研究可能对现有评估有重要影响,可能改变评价结果的可信度	质量降低一级的随机对照试验;质量升高一级的观察性研究	B
低级证据	我们对效应估计值的确信程度有限:真实值可能与估计值大不相同;未来研究很有可能对现有评估有重要影响,改变评估结果可信度的可能性较大	质量降低二级的随机对照试验;观察性研究	C
极低级证据	我们对效应估计值几乎没有信心:真实值很可能与估计值大不相同;任何评估都很不确定	质量降低三级的随机对照试验;质量降低一级的观察性研究;系列病例观察;个案报道	D

证据质量	推荐强度	具体描述	表达数字
高级证据	支持使用某项干预措施的强推荐	评价者确信干预措施利大于弊	1
中级证据	支持使用某项干预措施的弱推荐	利弊不确定或无论高低质量的证据均显示利弊相当	2
低级证据	反对使用某项干预措施的弱推荐		2
极低级证据	反对使用某项干预措施的强推荐	评价者确信干预措施弊大于利	1

意见条目	推荐意见	推荐级别及证据级别
1	对拟使用肿瘤坏死因子抑制剂治疗的风湿性疾病患者,建议应常规进行LTBI筛查	1A
2	使用靶向合成改善病情抗风湿药(如托法替布)的患者,建议应常规进行LTBI筛查	1B
3	对拟长期使用中大剂量糖皮质激素者,尤其是系统性红斑狼疮、使用免疫抑制剂、低体质量指数、合并肺间质病变的人群,有条件者建议进行LTBI筛查	1C
4	需长期使用具有结核病活动中高风险的改善病情抗风湿药(如来氟米特、甲氨蝶呤、环孢素、环磷酰胺、吗替麦考酚酯)的风湿性疾病患者,有条件者建议进行LTBI筛查	1D
5	风湿性疾病患者结核菌素皮肤试验硬结平均直径≥10mm的阳性者,或接受免疫抑制治疗时间>1个月、结核菌素皮肤试验硬结平均直径≥5mm的患者,应予以警惕,有条件者建议进一步完善γ-干扰素释放试验检测	2D
6	对风湿性疾病患者而言,γ-干扰素释放试验的准确性优于结核菌素皮肤试验,建议风湿性疾病患者优先应用γ-干扰素释放试验筛查LTBI	1B
7	LTBI目前缺乏诊断的金标准,推荐在有条件时联合应用多种方法进行筛查,比如γ-干扰素释放试验联合结核菌素皮肤试验	2D
8	既往完成规范抗结核治疗5年以内者可不予预防性抗结核治疗,建议此类患者在使用生物制剂的时候首选非肿瘤坏死因子抑制剂	1B
9	若病情允许,建议合并LTBI的风湿性疾病患者在预防性抗结核治疗至少1个月后再启动生物制剂治疗;如病情紧急需要立即启动生物制剂治疗时,建议在充分评估风险后同时启动生物制剂和预防性抗结核治疗	2D
10	异烟肼、利福平单药或联合用药方案原则上均可使用,但建议优先推荐使用3个月异烟肼和利福喷丁(3HP)方案	1A

意见条目	专家群体权威系数(0~1)	重要性评价		变异系数 (0~1)
意见条目	专家群体权威系数(0~1)	平均值(0~5)	标准差	变异系数 (0~1)
1	0.92	4.90	0.31	0.06
2	0.89	4.38	0.82	0.19
3	0.84	3.83	0.89	0.23
4	0.81	4.00	0.89	0.22
5	0.86	4.24	0.88	0.20
6	0.88	4.14	0.64	0.15
7	0.88	3.90	0.82	0.21
8	0.82	4.03	0.68	0.17
9	0.87	4.45	0.74	0.17
10	0.83	4.00	0.76	0.19

治疗方案	剂量			用法	疗程
治疗方案	成人	儿童	最大剂量	用法	疗程
异烟肼+利福喷丁每周疗法(3HP)				1次/周	3个月
异烟肼	900mg/次	年龄2~14岁:(1)体质量10~15kg:300mg/次;(2)体质量16~23kg:500mg/次;(3)体质量24~30kg:600mg/次;(4)体质量>31kg:700mg/次年龄>14岁:900mg/次	900mg/次
利福喷丁	900mg/次	年龄2~14岁:(1)体质量10~15kg:300mg/次;(2)体质量16~23kg:450mg/次;(3)体质量24~30kg:600mg/次;(4)体质量>31kg:750mg/次年龄>14岁:900mg/次	900mg/次
利福平单药每日疗法	体质量<50kg:450mg/次;体质量≥50kg:600mg/次	10mg·kg^-1·次^-1	450mg/次	1次/d	4个月
异烟肼+利福平每日疗法				1次/d	3个月
异烟肼	300mg/次	10mg·kg^-1·次^-1	300mg/次
利福平	体质量<50kg:450mg/次;体质量≥50kg:600mg/次	10mg·kg^-1·次^-1	450mg/次
异烟肼单药每日疗法	300mg/次	10mg·kg^-1·次^-1	300mg/次	1次/d	6~9个月