关口前移:结核潜伏感染及其控制

doi:10.3969/j.issn.1000-6621.2018.08.003

摘要/Abstract

摘要：

全球有近1/4的人群感染结核分枝杆菌,其中5%~10%可能在一生中发生活动性结核病,潜伏感染人群成为一个庞大的潜在患者库。世界卫生组织相继于2015年和2018年发布和更新《结核潜伏感染管理指南》,指导包括中国在内的中高收入、结核病发病率低于100/10万的国家和地区推广高危人群结核潜伏感染检测和预防性治疗。我国结核潜伏感染控制策略的开发应该紧密结合国情和结核病疫情特点,可以借鉴但不能照搬国外方案。准确界定干预目标人群、探索适宜的干预手段、建立科学的管理和评价体系等,都需要系统性的基础研究和临床研究提供技术支撑。以结核潜伏感染干预为手段探索结核病防控的关口前移将是落实“预防为主”综合防治策略的重要举措。

关键词: 分枝杆菌, 结核, 感染控制, 干预性研究, 预防性治疗, 潜伏感染

Abstract:

It was estimated that about a quarter of the global population were latently infected with Mycobacterium tuberculosis, and millions of active tuberculosis (TB) diseases will occur from this reservoir. World Health Organization released guidelines in 2015 and in 2018 respectively, to provide updated consolidated guidance for expanding latent tuberculosis infection (LTBI) management in high-income or upper middle-income countries with an estimated TB incidence rate of less than 100 per 100000 population (including China). The development of the national guidelines should adapt to local epidemiology of TB, the availability of resources, and other determinants. Identifying at-risk populations, exploring appropriate intervention tools, and establishing systematic management system all require technical supports by means of strengthening basic research and clinical research. LTBI management is one of the important tools for moving TB control forward to prevention first.

Key words: Mycobacterium tuberculosis, Infection control, Intervention studies, Preventive treatment, Latent infection

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.1000-6621.2018.08.003

Lei GAO,Qi. JIN. Management of latent tuberculosis infection: moving forward to prevention first[J]. Chinese Journal of Antituberculosis, 2018, 40(8): 791-795. doi: 10.3969/j.issn.1000-6621.2018.08.003

参考文献 52

[1]	World Health Organization . Global tuberculosis report 2017. Geneva: World Health Organization, 2017.
[2]	Houben RM, Dodd PJ . The Global Burden of Latent Tuberculosis Infection: A Re-estimation Using Mathematical Modelling. PLoS Med, 2016,13(10):e1002152. doi: 10.1371/journal.pmed.1002152 URL
[3]	Comstock GW, Livesay VT, Woolpert SF . The prognosis of a positive tuberculin reaction in childhood and adolescence. Am J Epidemiol, 1974,99(2):131-138. doi: 10.1093/oxfordjournals.aje.a121593 URL pmid: 4810628
[4]	Parfitt CD . Osler’s Influence in the War Against Tuberculosis (The Fifth Osler Oration). Can Med Assoc J, 1942,47(4):293-304.
[5]	Mack U, Migliori GB, Sester M , et al. LTBI: latent tuberculosis infection or lasting immune responses to M. tuberculosis? A TBNET consensus statement. Eur Respir J, 2009,33(5):956-973. doi: 10.1183/09031936.00120908 URL
[6]	Pai M, Behr M . Latent Mycobacterium tuberculosis Infection and Interferon-Gamma Release Assays. Microbiol Spectr, 2016,4(5). doi: 10.1128/microbiolspec.TBTB2-0023-2016.
[7]	World Health Organization . Implementing the END-TB strategy: the essentials. Geneva: World Health Organization, 2015.
[8]	World Health Organization . Guidelines on the management of latent tuberculosis infection. Geneva: World Health Organization, 2015. doi: 10.1136/thoraxjnl-2012-201587 URL pmid: 25973515
[9]	World Health Organization . Latent tuberculosis infection: Updated and consolidated guidelines for programmatic management. Geneva: World Health Organization, 2018.
[10]	Stagg HR, Zenner D, Harris RJ , et al. Treatment of latent tuberculosis infection: a network meta-analysis. Ann Intern Med, 2014,161(6):419-428. doi: 10.1016/j.rmr.2011.07.011 URL
[11]	Modlin RL, Bloom BR . TB or not TB: that is no longer the question. Sci Transl Med, 2013,5(213):213s-216s. doi: 10.1126/scitranslmed.3007402 URL pmid: 24285487
[12]	Marks SM, Taylor Z, Qualls NL , et al. Outcomes of contact investigations of infectious tuberculosis patients. Am J Respir Crit Care Med, 2000,162(6):2033-2038. doi: 10.1164/ajrccm.162.6.2004022 URL pmid: 11112109
[13]	Ewer K, Millington KA, Deeks JJ , et al. Dynamic antigen-specific T-cell responses after point-source exposure to Mycobacterium tuberculosis. Am J Respir Crit Care Med, 2006,174(7):831-839. doi: 10.1164/rccm.200511-1783OC URL
[14]	van Zwanenberg D . The influence of the number of bacilli on the development of tuberculous disease in children. Am Rev Respir Dis, 1960,82:31-44. doi: 10.1164/arrd.1960.82.1.31 URL pmid: 13841166
[15]	Daley CL, Small PM, Schecter GF , et al. An outbreak of tuberculosis with accelerated progression among persons infected with the human immunodeficiency virus. An analysis using restriction-fragment-length polymorphisms. N Engl J Med, 1992,326(4):231-235. doi: 10.1056/NEJM199201233260404 URL
[16]	Keane J, Gershon S, Wise RP , et al. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med, 2001,345(15):1098-1104. doi: 10.1056/NEJMoa011110 URL
[17]	Andrews JR, Noubary F, Walensky RP , et al. Risk of progression to active tuberculosis following reinfection with Mycobacterium tuberculosis. Clin Infect Dis, 2012,54(6):784-791. doi: 10.1093/cid/cir951 URL pmid: 3284215
[18]	Lin PL, Flynn JL . Understanding latent tuberculosis: a mo-ving target. J Immunol, 2010,185(1):15-22. doi: 10.4049/jimmunol.0903856 URL
[19]	Cadena AM, Fortune SM, Flynn JL . Heterogeneity in tuberculosis. Nat Rev Immunol, 2017,17(11):691-702. doi: 10.1038/nri.2017.69 URL
[20]	Dodd CE, Schlesinger LS . New concepts in understanding latent tuberculosis. Curr Opin Infect Dis, 2017,30(3):316-321. doi: 10.1097/QCO.0000000000000367 URL pmid: 28177961
[21]	Esmail H, Barry CE 3rd, Young DB, et al. The ongoing challenge of latent tuberculosis. Philos Trans R Soc Lond B Biol Sci, 2014,369(1645):20130437. doi: 10.1098/rstb.2013.0437 URL pmid: 24821923
[22]	Comstock GW, Baum C, Snider DE Jr . Isoniazid prophylaxis among Alaskan Eskimos: a final report of the bethel isoniazid studies. Am Rev Respir Dis, 1979,119(5):827-830. doi: 10.1164/arrd.1979.119.5.827 URL pmid: 453704
[23]	Doherty TM, Demissie A, Olobo J , et al. Immune responses to the Mycobacterium tuberculosis-specific antigen ESAT-6 signal subclinical infection among contacts of tuberculosis patients. J Clin Microbiol, 2002,40(2):704-706. doi: 10.1128/JCM.40.2.704-706.2002 URL
[24]	Millington KA, Gooding S, Hinks TS , et al. Mycobacterium tuberculosis-specific cellular immune profiles suggest bacillary persistence decades after spontaneous cure in untreated tuberculosis. J Infect Dis, 2010,202(11):1685-1689. doi: 10.1086/653023 URL
[25]	Lenaerts A, Barry CE 3rd, Dartois V, . Heterogeneity in tuberculosis pathology, microenvironments and therapeutic responses. Immunol Rev, 2015,264(1):288-307. doi: 10.1111/imr.12252 URL pmid: 25703567
[26]	Achkar JM, Jenny-Avital ER . Incipient and subclinical tuberculosis: defining early disease states in the context of host immune response. J Infect Dis, 2011,204 Suppl 4: S1179-S1186. doi: 10.1093/infdis/jir451 URL
[27]	Corbett EL, MacPherson P . Tuberculosis screening in high human immunodeficiency virus prevalence settings: turning promise into reality. Int J Tuberc Lung Dis, 2013,17(9):1125-1138. doi: 10.5588/ijtld.13.0117 URL
[28]	Golub JE, Mohan CI, Comstock GW , et al. Active case finding of tuberculosis: historical perspective and future prospects. Int J Tuberc Lung Dis, 2005,9(11):1183-1203.
[29]	Wood R, Middelkoop K, Myer L , et al. Undiagnosed tuberculosis in a community with high HIV prevalence: implications for tuberculosis control. Am J Respir Crit Care Med, 2007,175(1):87-93. URL pmid: 16973982
[30]	Berry MP, Graham CM, McNab FW, et al. An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis. Nature, 2010,466(7309):973-977. doi: 10.1038/nature09247 URL pmid: 20725040
[31]	Esmail H, Lai RP, Lesosky M , et al. Characterization of progressive HIV-associated tuberculosis using 2-deoxy-2-[ ¹⁸F]fluoro-D-glucose positron emission and computed tomography . Nat Med, 2016,22(10):1090-1093. doi: 10.1038/nm.4161 URL
[32]	Lin PL, Rodgers M, Smith L , et al. Quantitative comparison of active and latent tuberculosis in the cynomolgus macaque model. Infect Immun, 2009,77(10):4631-4642. doi: 10.1128/IAI.00592-09 URL pmid: 19620341
[33]	Barry CE 3rd, Boshoff HI, Dartois V , et al. The spectrum of latent tuberculosis: rethinking the biology and intervention strategies. Nat Rev Microbiol, 2009,7(12):845-855. doi: 10.1038/nrmicro2236 URL pmid: 19855401
[34]	Gideon HP, Flynn JL . Latent tuberculosis: what the host “sees”. Immunol Res, 2011,50(2/3):202-212. doi: 10.1007/s12026-011-8229-7 URL pmid: 21717066
[35]	Halliday A, Whitworth H, Kottoor SH , et al. Stratification of Latent Mycobacterium tuberculosis Infection by Cellular Immune Profiling. J Infect Dis, 2017,215(9):1480-1487. doi: 10.1093/infdis/jix107 URL pmid: 28329119
[36]	Young DB, Gideon HP, Wilkinson RJ . Eliminating latent tuberculosis. Trends Microbiol, 2009,17(5):183-188. doi: 10.1016/j.tim.2009.02.005 URL
[37]	Dutta NK, Karakousis PC . Latent tuberculosis infection: myths, models, and molecular mechanisms. Microbiol Mol Biol Rev, 2014,78(3):343-371. doi: 10.1128/MMBR.00010-14 URL pmid: 25184558
[38]	Salgame P, Geadas C, Collins L , et al. Latent tuberculosis infection——Revisiting and revising concepts. Tuberculosis (Edinb), 2015,95(4):373-384. doi: 10.1016/j.tube.2015.04.003 URL pmid: 26038289
[39]	van Rie A, Warren R, Richardson M , et al. Exogenous reinfection as a cause of recurrent tuberculosis after curative treatment. N Engl J Med, 1999,341(16):1174-1179. doi: 10.1056/NEJM199910143411602 URL pmid: 10519895
[40]	Lillebaek T, Dirksen A, Vynnycky E , et al. Stability of DNA patterns and evidence of Mycobacterium tuberculosis reactivation occurring decades after the initial infection. J Infect Dis, 2003,188(7):1032-1039. doi: 10.1086/jid.2003.188.issue-7 URL
[41]	Akolo C, Adetifa I, Shepperd S , et al.Treatment of latent tuberculosis infection in HIV infected persons. Cochrane Database Syst Rev, 2010, ( 1): CD000171. doi: 10.1002/14651858.CD000171.pub3 URL pmid: 14973947
[42]	Hermans SM, Grant AD, Chihota V , et al. The timing of tuberculosis after isoniazid preventive therapy among gold miners in South Africa: a prospective cohort study. BMC Med, 2016,14:45. doi: 10.1186/s12916-016-0589-3 URL
[43]	Churchyard GJ, Fielding KL, Grant AD . A trial of mass isoniazid preventive therapy for tuberculosis control. N Engl J Med, 2014,370(17):1662-1663. doi: 10.1056/NEJMc1402073#SA2 URL pmid: 24450889
[44]	Hamada Y, Sidibe A, Matteelli A , et al. Policies and practices on the programmatic management of latent tuberculous infection: global survey. Int J Tuberc Lung Dis, 2016,20(12):1566-1571. doi: 10.5588/ijtld.16.0241 URL
[45]	Eastment MC, McClintock AH, McKinney CM, et al . Factors That Influence Treatment Completion for Latent Tuberculosis Infection. J Am Board Fam Med, 2017,30(4):520-527. doi: 10.3122/jabfm.2017.04.170070 URL pmid: 28720633
[46]	Alsdurf H, Hill PC, Matteelli A , et al. The cascade of care in diagnosis and treatment of latent tuberculosis infection: a systematic review and meta-analysis. Lancet Infect Dis, 2016,16(11):1269-1278. doi: 10.1016/S1473-3099(16)30216-X URL
[47]	Arangalage D, Delyon J, Lermuzeaux M , et al. Survival After Fulminant Myocarditis Induced by Immune-Checkpoint Inhibitors. Ann Intern Med, 2017,167(9):683-684. doi: 10.7326/L17-0396 URL pmid: 28869988
[48]	Wallis RS, Kim P, Cole S , et al. Tuberculosis biomarkers discovery: developments, needs, and challenges. Lancet Infect Dis, 2013,13(4):362-372. doi: 10.1016/S1473-3099(13)70034-3 URL pmid: 23531389
[49]	Petruccioli E, Scriba TJ, Petrone L , et al. Correlates of tuberculosis risk: predictive biomarkers for progression to active tuberculosis. Eur Respir J, 2016,48(6):1751-1763. doi: 10.1183/13993003.01012-2016 URL pmid: 27836953
[50]	Ruhwald M, Aggerbeck H, Gallardo RV , et al. Safety and efficacy of the C-Tb skin test to diagnose Mycobacterium tuberculosis infection, compared with an interferon γ release assay and the tuberculin skin test: a phase 3, double-blind, randomi-sed, controlled trial. Lancet Respir Med, 2017,5(4):259-268. doi: 10.1016/S2213-2600(16)30436-2 URL
[51]	Zenner D, Beer N, Harris RJ , et al. Treatment of Latent Tuberculosis Infection: An Updated Network Meta-analysis. Ann Intern Med, 2017,167(4):248-255. doi: 10.7326/M17-0609 URL
[52]	LoBue PA, Mermin JH . Latent tuberculosis infection: the final frontier of tuberculosis elimination in the USA. Lancet Infect Dis, 2017,17(10):e327-e333. doi: 10.1016/S1473-3099(17)30248-7 URL