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中国防痨杂志 ›› 2020, Vol. 42 ›› Issue (8): 761-768.doi: 10.3969/j.issn.1000-6621.2020.08.001

• 指南·规范·共识 •    下一篇

重组结核杆菌融合蛋白(EC)临床应用专家共识

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   

  • 收稿日期:2020-06-12 出版日期:2020-08-10 发布日期:2020-08-10
  • 基金资助:
    “十三五”重大传染病防治国家科技重大专项(2018ZX10731301);“十三五”重大传染病防治国家科技重大专项(2020ZX09201001-005);“十三五”重大传染病防治国家科技重大专项(2018ZX10103001-001-008);“十三五”重大传染病防治国家科技重大专项(2017ZX10201301-001-003);“十三五”重大传染病防治国家科技重大专项(2017ZX09304009);“十二五”重大传染病防治国家科技重大专项(2014ZX10003002-004);“十二五”重大传染病防治国家科技重大专项(2015ZX09108-003);上海市临床重点专科建设项目(shslczdzk03002)

Expert consensus of clinical application of the recombinant Mycobacterium tuberculosis fusion protein (EC)

Chinese Antituberculosis Association, Schools and Children Branch of the Chinese Antituberculosis Association, Editorial Board of Chinese Journal of Antituberculosis   

  • Received:2020-06-12 Online:2020-08-10 Published:2020-08-10

摘要:

中国是结核病高负担国家之一,结核病发病例数与潜伏性结核感染(latent tuberculosis infection,LTBI)人数庞大,给我国结核病防控工作带来了巨大的挑战。有效识别结核病和LTBI对控制结核病疫情有重要意义。菌阴肺结核和LTBI的诊断依赖于结核感染的免疫学诊断方法;现行结核感染免疫学检测方法主要是结核菌素皮肤试验(tuberculin skin test,TST)、γ干扰素释放试验(interferon gamma release assays,IGRA)和抗原抗体检测。在现行的三类方法基础上,研发出了敏感度高、特异度强、试验操作简单、可用于LTBI和结核病诊断的新产品和新技术——重组结核杆菌融合蛋白(EC)[该制品名称是国家药典委员会确定的药品中文通用名称,“EC”为重组融合蛋白“结核分枝杆菌早期分泌性抗原靶6(ESAT-6)和培养滤液蛋白10(CFP-10)”](简称“EC”)。目前,已完成EC的Ⅰ、Ⅱ和Ⅲ期临床试验。其中Ⅲ期临床试验中对1559名健康人群的筛查中发现,EC与IGRA的检测结果具有较高的特异度,且两者之间具有较高的一致性(88.77%);对791例临床诊断为结核病患者的临床研究发现,EC、结核感染T淋巴细胞斑点试验(T-SPOT.TB)、结核菌素纯蛋白衍生物(TB-PPD)检测均具有良好的敏感度,且三者之间具有较高的一致性;对479名未感染结核分枝杆菌人员的研究发现,EC与T-SPOT.TB的两次检测阴性一致率较高(88.20%和93.17%);在卡介苗接种对检测结果影响的研究中发现,EC和T-SPOT.TB基本不受卡介苗的影响;对394例临床诊断非结核性疾病患者的临床研究发现,EC与T-SPOT.TB阴性符合率较高,且一致性较好(87.21%)。基于EC在用于诊断结核感染安全且有效的基础上,EC通过了国家药品监督管理局药品审批而准予上市。经广泛征求有关结核病防控、临床和研究等领域的专家意见,在系统总结相关技术和方法的应用特点的基础上,结合EC的临床试验结果,形成了EC临床应用的专家共识。本共识介绍了EC的临床应用建议,包括使用对象、使用方法、结果判读,以及临床意义和使用范围。

关键词: 潜伏性结核病, 分枝杆菌感染, 诊断, 鉴别, 重组结核杆菌融合蛋白(EC), 卫生服务使用研究, 总结性报告(主题)

Abstract:

As one of the countries with high burden of tuberculosis worldwide, China possesses a huge number of tuberculosis cases and latent tuberculosis infections (LTBI), which brings great challenges to the prevention and control of tuberculosis. Effective identification of tuberculosis and LTBI is of great significance to control the epidemic situation of tuberculosis. The diagnosis of sputum-negative pulmonary tuberculosis, especially LTBI, depends on the immunological diagnostic method of tuberculosis infection. The current immunological detection methods of tuberculosis infection are mainly tuberculin skin test (TST), interferon-gamma release assays (IGRA) and antigen-antibody detection. On the basis of the current three methods, we have developed new products and techniques for the diagnosis of LTBI and tuberculosis-recombinant Mycobacterium tuberculosis fusion protein (EC) (the product name is the Chinese general name of the drug determined by the State Pharmacopoeia Commission, and “EC” refers to the recombinant fusion protein “Mycobacterium tuberculosis early secretory antigen target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10)”) (short for “EC”), featuring simple operation, high sensitivity and specificity. At present, phase Ⅰ, Ⅱ and Ⅲ clinical trials of EC have been completed. In the screening of 1559 healthy people in the phase Ⅲ clinical trial, it was found that the detection results of EC and IGRA had quite high specificity and consistency(88.77%). The clinical study of 791 patients diagnosed with tuberculosis showed that the detection results of EC, tuberculosis infected T lymphocyte spot test (T-SPOT.TB) and tuberculin pure protein derivative (TB-PPD) had good sensitivity and quite high consistency among them. In the study of 479 patients uninfected Mycobacterium tuberculosis, the negative coincidence rate of EC and T-SPOT.TB was high (reaching 88.20% and 93.17%). In the study of the effect of BCG vaccine on the test results, it was found that EC and T-SPOT.TB were basically not affected by BCG. In the clinical study of 394 patients diagnosed with non-tuberculous diseases, it was found that the negative coincidence rate of EC and T-SPOT.TB was quite high, and the consistency was good (87.21%). Based on the fact that EC is safe and effective in the diagnosis of tuberculosis infection, EC has passed the drug examination and approval of the State Drug Administration and is approved to be listed on the market. After extensively soliciting the opinions of experts in the fields of tuberculosis prevention and control, clinical and research and combining with the clinical trial results of EC, the expert consensus on the clinical application of EC has been formed on the basis of systematically summarizing the application characteristics of relevant technologies and methods. This consensus introduces the recommendations for the clinical application of EC, including the target users, method of application, the interpretation of the results, as well as the clinical significance and scope of use.

Key words: Latent tuberculosis, Mycobacterium infections, Diagnosis, differential, Recombinant Mycobacterium tuberculosis fusion protein (EC), Marketing of health services, Consensus development conferences as topic