亚临床结核病研究进展

doi:10.19982/j.issn.1000-6621.20230159

摘要/Abstract

摘要：

亚临床结核病是处于结核分枝杆菌潜伏感染与活动性结核病之间的一种疾病状态,早期发现和干预可降低其发展为活动性结核病的风险,对改善预后和阻断其传播有积极意义。作者就目前已报道的亚临床结核病定义、临床特征、传播力、发病机制、生物标志物、筛查和诊断方法等国内外相关研究现状进行综述,旨在明确当前亚临床结核病的研究进展和挑战,为我国加速亚临床结核病相关研究及探索更为有效的结核病防控策略提供新的思考方向。

关键词: 结核, 带病原状态, 疾病特征, 生物学标记, 综述文献(主题)

Abstract:

Subclinical tuberculosis is a disease state between latent tuberculosis infection and active tuberculosis. Early detection and intervention of subclinical tuberculosis patients can reduce the risk of developing into active tuberculosis, improve the prognosis, and block the transmission of tuberculosis. This article reviewed domestic and international research progress of subclinical tuberculosis, including the definition, clinical characteristics, transmissibility, pathogenesis, biomarkers, screening and diagnostic methods, in order to identify the current research progress and challenges of subclinical tuberculosis, and provide novel research ideas to accelerate the research on subclinical tuberculosis and exploring more effective tuberculosis prevention and control strategies in China.

Key words: Tuberculosis, Carrier state, Disease attributes, Biological markers, Review literature as topic

中图分类号:

王涵飞, 赵雁林, 徐彩红. 亚临床结核病研究进展[J]. 中国防痨杂志, 2023, 45(8): 808-813. doi: 10.19982/j.issn.1000-6621.20230159

Wang Hanfei, Zhao Yanlin, Xu Caihong. Research progress of subclinical tuberculosis[J]. Chinese Journal of Antituberculosis, 2023, 45(8): 808-813. doi: 10.19982/j.issn.1000-6621.20230159

图/表 1

参考文献 40

[1]	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(Suppl 4):S1179-S1186. doi:10.1093/infdis/jir451. doi: 10.1093/infdis/jir451
[2]	李蒙, 高谦. 结核病自然史的阶段划分及其诊断的现状与展望. 中国防痨杂志, 2021, 43(11):1125-1131. doi:10.3969/j.issn.1000-6621.2021.11.005. doi: 10.3969/j.issn.1000-6621.2021.11.005
[3]	Drain PK, Bajema KL, Dowdy D, et al. Incipient and Subclinical Tuberculosis:a Clinical Review of Early Stages and Progression of Infection. Clin Microbiol Rev, 2018, 31(4):e00021-18. doi:10.1128/CMR.00021-18. doi: 10.1128/CMR.00021-18
[4]	Kendall EA, Shrestha S, Dowdy DW. The Epidemiological Importance of Subclinical Tuberculosis. A Critical Reappraisal. Am J Respir Crit Care Med, 2021, 203(2):168-174. doi:10.1164/rccm.202006-2394PP. doi: 10.1164/rccm.202006-2394PP URL
[5]	Frascella B, Richards AS, Sossen B, et al. Subclinical tuberculosis disease-a review and analysis of prevalence surveys to inform definitions,burden,associations,and screening methodology. Clin Infect Dis, 2021, 73(3):e830-e841. doi:10.1093/cid/ciaa1402. doi: 10.1093/cid/ciaa1402
[6]	Esmail H, Dodd PJ, Houben RMGJ. Tuberculosis transmission during the subclinical period: could unrelated cough play a part? Lancet Respir Med, 2018, 6(4):244-246. doi:10.1016/S2213-2600(18)30105-X. doi: 10.1016/S2213-2600(18)30105-X pmid: 29595504
[7]	Stiehm RH. Subclinical Pulmonary Tuberculosis:A Presentation of Forty Cases. Minerva Chirurgica, 1940, 13(12):2285. doi:10.7326/0003-4819-13-12-2285. doi: 10.7326/0003-4819-13-12-2285
[8]	Pierce CW. Subclinical Tuberculosis:Some Flies in the Ointment. Am J Respir Crit Care Med, 2021, 203(10):1327-1328. doi:10.1164/rccm.202101-0227LE. doi: 10.1164/rccm.202101-0227LE URL
[9]	Hoa NB, Sy DN, Nhung NV, et al. National survey of tuberculosis prevalence in Viet Nam. Bull World Health Organ, 2010, 88(4):273-280. doi:10.2471/BLT.09.067801. doi: 10.2471/BLT.09.067801 URL
[10]	A study of the characteristics and course of sputum smear-negative pulmonary tuberculosis. Tubercle, 1981, 62(3):155-167. doi:10.1016/0041-3879(81)90001-5. doi: 10.1016/0041-3879(81)90001-5 pmid: 7032018
[11]	Dorman SE, Schumacher SG, Alland D, et al. Xpert MTB/RIF Ultra for detection of Mycobacterium tuberculosis and rifampicin resistance:a prospective multicentre diagnostic accuracy study. Lancet Infect Dis, 2018, 18(1):76-84. doi:10.1016/S1473-3099(17)30691-6. doi: S1473-3099(17)30691-6 pmid: 29198911
[12]	Frascella B, Richards AS, Sossen B, et al. Subclinical Tuberculosis Disease-A Review and Analysis of Prevalence Surveys to Inform Definitions,Burden, Associations, and Screening Methodology. Clin Infect Dis, 2021, 73(3):e830-e841. doi:10.1093/cid/ciaa1402. doi: 10.1093/cid/ciaa1402
[13]	梁尔敏. 亚临床结核病患者的免疫学特征及其与结核分枝杆菌基因型相关性研究. 苏州:苏州大学, 2021. doi:10.27351/d.cnki.gszhu.2021.001879. doi: 10.27351/d.cnki.gszhu.2021.001879
[14]	Mtei L, Matee M, Herfort O, et al. High rates of clinical and subclinical tuberculosis among HIV-infected ambulatory subjects in Tanzania. Clin Infect Dis, 2005, 40(10):1500-1507. doi:10.1086/429825. doi: 10.1086/429825 pmid: 15844073
[15]	Tang P, Liang E, Zhang X, et al. Prevalence and Risk Factors of Subclinical Tuberculosis in a Low-Incidence Setting in China. Front Microbiol, 2022, 12:731532. doi:10.3389/fmicb.2021.731532. doi: 10.3389/fmicb.2021.731532
[16]	Min J, Chung C, Jung SS, et al. Clinical profiles of subclinical disease among pulmonary tuberculosis patients:a prospective cohort study in South Korea. BMC Pulm Med, 2020, 20(1):316. doi:10.1186/s12890-020-01351-z. doi: 10.1186/s12890-020-01351-z
[17]	Stuck L, van Haaster AC, Kapata-Chanda P, et al. How “Subclinical” is Subclinical Tuberculosis? An Analysis of National Prevalence Survey Data from Zambia. Clin Infect Dis, 2022, 75(5):842-848. doi:10.1093/cid/ciab1050. doi: 10.1093/cid/ciab1050 URL
[18]	Behr MA, Warren SA, Salamon H, et al. Transmission of Mycobacterium tuberculosis from patients smear-negative for acid-fast bacilli. Lancet, 1999, 353(9151):444-449. doi:10.1016/s0140-6736(98)03406-0. doi: 10.1016/s0140-6736(98)03406-0 pmid: 9989714
[19]	Xu Y, Cancino-Muñoz I, Torres-Puente M, et al. High-resolution mapping of tuberculosis transmission: Whole genome sequencing and phylogenetic modelling of a cohort from Valencia Region, Spain. PLoS Med, 2019, 16(10):e1002961. doi:10.1371/journal.pmed.1002961. doi: 10.1371/journal.pmed.1002961
[20]	Houben RMGJ, Esmail H, Emery JC, et al. Spotting the old foe—revisiting the case definition for TB. Lancet Respir Med, 2019, 7(3):199-201. doi:10.1016/S2213-2600(19)30038-4. doi: 10.1016/S2213-2600(19)30038-4
[21]	McHenry ML, Williams SM, Stein CM. Genetics and evolution of tuberculosis pathogenesis: New perspectives and approaches. Infect Genet Evol, 2020, 81:104204. doi:10.1016/j.meegid.2020.104204. doi: 10.1016/j.meegid.2020.104204 URL
[22]	杜威, 刘春雨, 王路生, 等. 结核病发病机制的研究进展. 中国人兽共患病学报, 2022, 38(3):217-225. doi:10.3760/cma.j.issn.1001-0939.2009.08.020. doi: 10.3760/cma.j.issn.1001-0939.2009.08.020
[23]	马福才, 胡群英, 康龙丽. 潜在肺结核的发病机制和防治措施. 国外医学(医学地理分册), 2014, 35(1):80-84. doi:10.3969/j.issn.1001-8883.2014.01.021. doi: 10.3969/j.issn.1001-8883.2014.01.021
[24]	MacLean E, Broger T, Yerlikaya S, et al. Author correction:A systematic review of biomarkers to detect active tuberculosis. Nat Microbiol, 2019, 4(5):899. doi:10.1038/s41564-019-0452-3. doi: 10.1038/s41564-019-0452-3 pmid: 30976122
[25]	Gong W, Wu X. Differential Diagnosis of Latent Tuberculosis Infection and Active Tuberculosis:A Key to a Successful Tuberculosis Control Strategy. Front Microbiol, 2021, 12:745592. doi:10.3389/fmicb.2021.745592. doi: 10.3389/fmicb.2021.745592 URL
[26]	贾红彦, 董静, 张宗德, 等. 结核分枝杆菌感染的免疫学检测技术研究进展及临床应用现状. 中国防痨杂志, 2022, 44(7):720-726. doi:10.19982/j.issn.1000-6621.20220103. doi: 10.19982/j.issn.1000-6621.20220103
[27]	Riou C, Berkowitz N, Goliath R, et al. Analysis of the Phenotype of Mycobacterium tuberculosis-Specific CD4⁺ T Cells to Discriminate Latent from Active Tuberculosis in HIV-Uninfected and HIV-Infected Individuals. Front Immunol, 2017, 8:968. doi:10.3389/fimmu.2017.00968. doi: 10.3389/fimmu.2017.00968 URL
[28]	La Manna MP, Orlando V, Dieli F, et al. Quantitative and qualitative profiles of circulating monocytes may help identifying tuberculosis infection and disease stages. PLoS One, 2017, 12(2):e0171358. doi:10.1371/journal.pone.0171358. doi: 10.1371/journal.pone.0171358
[29]	Garand M, Goodier M, Owolabi O, et al. Functional and Phenotypic Changes of Natural Killer Cells in Whole Blood during Mycobacterium tuberculosis Infection and Disease. Front Immunol, 2018, 9:257. doi:10.3389/fimmu.2018.00257. doi: 10.3389/fimmu.2018.00257 URL
[30]	Grassi G, Vanini V, De Santis F, et al. PMN-MDSC Frequency Discriminates Active Versus Latent Tuberculosis and Could Play a Role in Counteracting the Immune-Mediated Lung Damage in Active Disease. Front Immunol, 2021, 12:594376. doi:10.3389/fimmu.2021.594376. doi: 10.3389/fimmu.2021.594376 URL
[31]	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. doi: 10.1183/13993003.01012-2016 pmid: 27836953
[32]	Zak DE, Penn-Nicholson A, Scriba TJ, et al. A blood RNA signature for tuberculosis disease risk:a prospective cohort study. Lancet, 2016, 387(10035):2312-2322. doi:10.1016/S0140-6736(15)01316-1. doi: 10.1016/S0140-6736(15)01316-1 URL
[33]	Suliman S, Thompson EG, Sutherland J, et al. Four-Gene Pan-African Blood Signature Predicts Progression to Tuberculosis. Am J Respir Crit Care Med, 2018, 197(9):1198-1208. doi:10.1164/rccm.201711-2340OC. doi: 10.1164/rccm.201711-2340OC URL
[34]	Sivakumaran D, Jenum S, Srivastava A, et al. Host blood-based biosignatures for subclinical TB and incipient TB:A prospective study of adult TB household contacts in Southern India. Front Immunol, 2023, 13:1051963. doi:10.3389/fimmu.2022.1051963. doi: 10.3389/fimmu.2022.1051963
[35]	Burnham P, Dadhania D, Heyang M, et al. Urinary cell-free DNA is a versatile analyte for monitoring infections of the urinary tract. Nat Commun, 2018, 9(1):2412. doi:10.1038/s41467-018-04745-0. doi: 10.1038/s41467-018-04745-0 pmid: 29925834
[36]	Singh KK, Dong Y, Belisle JT, et al. Antigens of Mycobacterium tuberculosis recognized by antibodies during incipient,subclinical tuberculosis. Clin Diagn Lab Immunol, 2005, 12(2):354-358. doi:10.1128/CDLI.12.2.354-358.2005. doi: 10.1128/CDLI.12.2.354-358.2005
[37]	Bekken GK, Ritz C, Selvam S, et al. Identification of subclinical tuberculosis in household contacts using exposure scores and contact investigations. BMC Infect Dis, 2020, 20(1):96. doi:10.1186/s12879-020-4800-y. doi: 10.1186/s12879-020-4800-y pmid: 32005136
[38]	Oni T, Burke R, Tsekela R, et al. High prevalence of subclinical tuberculosis in HIV-1-infected persons without advanced immunodeficiency: implications for TB screening. Thorax, 2011, 66(8):669-673. doi:10.1136/thx.2011.160168. doi: 10.1136/thx.2011.160168 pmid: 21632522
[39]	Hoffmann CJ, Variava E, Rakgokong M, et al. High prevalence of pulmonary tuberculosis but low sensitivity of symptom screening among HIV-infected pregnant women in South Africa. PLoS One, 2013, 8(4):e62211. doi:10.1371/journal.pone.0062211. doi: 10.1371/journal.pone.0062211
[40]	祖筱雯, 法立峰, 徐彩红, 等. 结核分枝杆菌潜伏感染影响因素研究进展. 江苏预防医学, 2021, 32(5):561-563. doi:10.13668/j.issn.1006-9070.2021.05.014. doi: 10.13668/j.issn.1006-9070.2021.05.014

生物标志物类型	生物标志物作用	生物标志物
基于宿主的转录标志物
新型抗原方面	测量结核病不同疾病阶段方面具有很好的鉴别能力	21种潜伏期特定的RD相关抗原
细胞因子方面	鉴别结核感染后所处的不同阶段	γ-干扰素(IFN-γ)、干扰素诱导蛋白10、白细胞介素-2(IL-2),以及包含白细胞介素类、趋化因子等
细胞亚型方面	区分结核感染不同疾病阶段	结核分枝杆菌特异性T细胞亚群的数目和比例,中性粒细胞、循环单核细胞的表达及与淋巴细胞的比值、NKG2C⁺自然杀伤细胞、多形核髓源性抑制细胞等
基因与表达调控方面	预测结核病进展风险	16个基因转录组风险相关标签:ETV7、FCGR1A、FCGR1B、GBP1、GBP2、GBP5、SCARF1、SERPING1、STAT1和TAP1等;RISK4和双转录本C1QC/TRAV27标签
	区分亚临床结核病和早期结核病;鉴别结核病疾病谱不同阶段	11个基因标记,分别为ABLIM2、C20orf197、CTC-543D15.3、CTD-2503O16.3、HLADRB3、METRNL、RAB11B-AS1、RP4-614C10.2、RNA5SP345、RSU1P1和UACA;还鉴定出一种包含b-FGF、IFN-γ、IL-8RA、IL-1、IL-7p12、IL-70、PDGF-BB和VEGF的8蛋白标签
基于病原体的标志物	评价宿主对感染的反应	痕量游离DNA