PDF(1050 KB)
重组结核分枝杆菌融合蛋白与结核菌素皮肤试验在学校结核病接触者筛查中的比较分析
谢添, 王萌, 胡嘉, 袁志平, 冯德安, 易红秀, 卢雄
安徽预防医学杂志 ›› 2026, Vol. 32 ›› Issue (2) : 137-141.
PDF(1050 KB)
PDF(1050 KB)
重组结核分枝杆菌融合蛋白与结核菌素皮肤试验在学校结核病接触者筛查中的比较分析
Comparative analysis of recombinant Mycobacterium tuberculosis fusion protein skin test and tuberculin skin test in screening for tuberculosis contacts in schools
目的 比较重组结核分枝杆菌融合蛋白（recombinant Mycobacterium tuberculosis fusion protein, EC）皮肤试验与结核菌素皮肤试验（tuberculin skin test, TST）在学校结核病接触者中筛查预防性干预指征阳性人群（EC皮肤试验阳性或TST强阳性）的效果，为优化学校结核病防控措施提供参考。方法 选择2022年7月至2023年6月赣州市信丰县和于都县学校结核病患者的接触者作为研究对象，采用同体双臂法同步进行EC皮肤试验和TST，分析两种方法筛查结果的一致性及其影响因素。结果 共纳入1 503例接触者，EC皮肤试验阳性率为5.26%（79/1 503），TST强阳性率6.92%（104/1 503），差异无统计学意义（χ2=3.637, P=0.057）。两种方法结果一致率为94.88%（1 426/1 503，Kappa=0.553）；不一致77人（EC+&TST-：26人；EC-&TST+：51人），差异有统计学意义（χ2配对=7.481，P=0.006）。多因素逐步回归分析显示，不一致率随年龄增长而上升（aOR=1.063，95%CI：1.041~1.086）；初中（aOR=14.911，95%CI：2.978~74.667）、职业中专/高中（aOR=13.609，95%CI：3.130~59.170）和接触病原学阴性患者（aOR=2.212 ，95%CI：1.262~3.879）的不一致风险更高。TST的局部不良反应发生率（2.53%）高于EC皮肤试验（1.46%），差异有统计学意义（χ2配对=5.921，P=0.015）。结论 EC皮肤试验与TST在学校结核病接触者筛查中总体效能相近，但个体层面存在差异，其不一致性受年龄、学校类型和指示病例病原学结果影响。建议对初中及以上学段学生和病原学阴性患者的接触者优先选择EC皮肤试验进行筛查。
Objective To compare the efficacy of recombinant Mycobacterium tuberculosis fusion protein (EC) skin test and tuberculin skin test (TST) in screening tuberculosis contacts in schools with positive preventive intervention indications (EC skin test positive or TST strongly positive), so as to provide reference for optimizing tuberculosis prevention and control measures in schools. Methods Contacts of pulmonary tuberculosis patients in schools of Xinfeng County and Yudu County of Ganzhou from July 2022 to June 2023 were selected as the research subjects. EC skin test and TST were conducted simultaneously by using the simultaneous bilateral arms method. The consistency of the screening results of the two methods and the influencing factors were analyzed. Results A total of 1 503 contacts were included. The EC skin test positive rate was 5.26% (79/1 503), and the TST strongly positive rate was 6.92% (104/1 503), with no statistically significant difference (χ²=3.637, P=0.057). The consistency rate between the two methods was 94.88% (1 426/1 503, Kappa=0.553). There were 77 inconsistent cases (EC+ & TST-: 26 cases; EC- & TST+: 51 cases), the difference was statistically significant (McNemar’s χ2=7.481, P=0.006). Multivariate stepwise regression analysis showed that the discordance rate increased with age (aOR=1.063, 95% CI: 1.041-1.086). The risk of discordance was higher for individuals from junior high school (aOR=14.911, 95% CI: 2.978-74.667), vocational secondary/high school (aOR=13.609, 95% CI: 3.130-59.170), and contacts of patients with negative etiological results (aOR=2.212, 95% CI: 1.262-3.879). The incidence rate of local adverse reactions in TST (2.53%) was higher than that in EC skin test (1.46%), and the difference was statistically significant (McNemar’s χ2= 5.921, P=0.015). Conclusion EC skin test and TST exhibit similar overall efficacy in screening school-based tuberculosis contacts, but inter-individual discrepancies exist. The inconsistency is influenced by age, school type, and the etiological results of the index case. It is recommended to prioritize EC skin test for screening contacts who are junior high school students or above, faculty members, and contacts of patients with negative etiological results.
重组结核分枝杆菌融合蛋白 / 结核菌素皮肤试验 / 学校结核病 / 接触者 / 结核感染
Recombinant Mycobacterium tuberculosis fusion protein / Tuberculin skin test / School tuberculosis / Contacts / Tuberculosis infection
| [1] |
World Health Organization. WHO consolidated guidelines on tuberculosis module 1: prevention: tuberculosis preventive treatment. Geneva:World Health Organization, 2020.
|
| [2] |
高磊, 张慧, 胡茂桂. 全国结核分枝杆菌潜伏感染率估算专家共识[J]. 中国防痨杂志, 2022, 44(1):4-8.
|
| [3] |
李果, 庞先琼, 徐华, 等. 潜伏性结核感染诊治进展[J]. 中国防痨杂志, 2021, 43(1):91-95.
|
| [4] |
马艳, 陆伟, 成诗明. 结核分枝杆菌潜伏感染现状及防控对策[J]. 解放军医学杂志, 2023, 48(6):634-642.
|
| [5] |
吴弟梅, 阳萍. 结核病检查方法的研究进展[J]. 国际检验医学杂志, 2025, 36(1):106-107.
|
| [6] |
Identification and treatment of latent tuberculosis infection (LTBI) can substantially reduce the risk of developing active disease. However, there is no diagnostic gold standard for LTBI. Two tests are available for identification of LTBI: the tuberculin skin test (TST) and the gamma interferon (IFN-γ) release assay (IGRA). Evidence suggests that both TST and IGRA are acceptable but imperfect tests. They represent indirect markers of Mycobacterium tuberculosis exposure and indicate a cellular immune response to M. tuberculosis. Neither test can accurately differentiate between LTBI and active TB, distinguish reactivation from reinfection, or resolve the various stages within the spectrum of M. tuberculosis infection. Both TST and IGRA have reduced sensitivity in immunocompromised patients and have low predictive value for progression to active TB. To maximize the positive predictive value of existing tests, LTBI screening should be reserved for those who are at sufficiently high risk of progressing to disease. Such high-risk individuals may be identifiable by using multivariable risk prediction models that incorporate test results with risk factors and using serial testing to resolve underlying phenotypes. In the longer term, basic research is necessary to identify highly predictive biomarkers.
|
| [7] |
Interferon-γ release assays (IGRAs) are now established for the immunodiagnosis of latent infection with Mycobacterium tuberculosis in many countries. However, the role of IGRAs for the diagnosis of active tuberculosis (TB) remains unclear. Following preferred reporting items for systematic reviews and meta-analyses (PRISMA) and quality assessment of diagnostic accuracy studies (QUADAS) guidelines, we searched PubMed, EMBASE and Cochrane databases to identify studies published in January 2001-November 2009 that evaluated the evidence of using QuantiFERON-TB® Gold in-tube (QFT-G-IT) and T-SPOT.TB® directly on blood or extrasanguinous specimens for the diagnosis of active TB. The literature search yielded 844 studies and 27 met the inclusion criteria. In blood and extrasanguinous fluids, the pooled sensitivity for the diagnosis of active TB was 80% (95% CI 75-84%) and 48% (95% CI 39-58%) for QFT-G-IT, and 81% (95% CI 78-84%) and 88% (confirmed and unconfirmed cases) (95% CI 82-92%) for T-SPOT.TB®, respectively. In blood and extrasanguinous fluids, the pooled specificity was 79% (95% CI 75-82%) and 82% (95% CI 70-91%) for QFT-G-IT, and 59% (95% CI 56-62%) and 82% (95% CI 78-86%) for T-SPOT.TB®, respectively. Although the diagnostic sensitivities of both IGRAs were higher than that of tuberculin skin tests, it was still not high enough to use as a rule out test for TB. Positive evidence for the use of IGRAs in compartments other than blood will require more independent and carefully designed prospective studies.
|
| [8] |
杨蕾, 韦芬, 张凯, 等. 重组结核杆菌融合蛋白(EC)的稳定性与有效性研究[J]. 中国防痨杂志, 2020, 42(8):799-806.
|
| [9] |
马艳, 陆伟, 高磊, 等. 终止结核病流行须加强结核分枝杆菌潜伏感染高危人群筛查和预防性治疗的管理[J]. 中国防痨杂志, 2022, 44(3):209-214.
|
| [10] |
徐春华, 朱士玉, 胡屹, 等. 重组结核杆菌融合蛋白在肺结核密切接触者中筛查结核分枝杆菌感染效果分析[J]. 中国防痨杂志, 2024, 46(8):897-902.
|
| [11] |
苏倩, 汪清雅, 张婷, 等. 重组结核分枝杆菌融合蛋白皮肤试验与TST在学校结核潜伏感染筛查中的比较[J]. 中国感染控制杂志, 2023, 22(5):547-551.
|
| [12] |
中华人民共和国国家卫生健康委员会办公厅, 中华人民共和国教育部办公厅. 关于印发中国学校结核病防控指南的通知:国卫办疾控函〔2020〕910号[A/OL]. (2020-10-16)[2025-06-26]. https://www.nhc.gov.cn/wjw/c100175/202012/49e493a557a04db5918b5a16706b8445.shtml.
|
| [13] |
卢水华, 陆伟. 新型结核菌素皮肤试验使用手册[M]. 北京: 人民卫生出版社, 2021:50.
|
| [14] |
成诗明, 王国治, 王黎霞, 等. 结核菌素皮肤试验使用指导手册[M]. 北京: 人民卫生出版社, 2019:56.
|
| [15] |
赵雁林, 陈明亭. 中国结核病防治工作技术指南[M]. 北京: 人民卫生出版社, 2021:156.
|
| [16] |
贺晨耘, 姜虹. 两种皮试试剂在肺结核密切接触者筛查中的应用研究[J]. 安徽预防医学杂志, 2024, 30(5):356-360.
|
| [17] |
倪晓凤, 刁莎, 何思颐, 等. 重组结核杆菌融合蛋白的临床综合评价[J]. 中国药房, 2023, 34(4):391-396.
|
| [18] |
程晓, 陈哲, 焦雪峰, 等. 重组结核杆菌融合蛋白(EC)用于诊断结核分枝杆菌感染的有效性和安全性系统评价[J]. 中国防痨杂志, 2022, 44(9):917-926.
|
| [19] |
This study aimed to evaluate the diagnostic performance of ESAT6-CFP10 (EC) skin test in healthy population and determine the factors influencing the booster effect.We conducted a randomized, double-blind, parallel controlled trial in healthy population. The experiment was divided into two stages. In the first stage, all participants underwent T-SPOT, TB-PPD, and EC tests. In the second stage, to evaluate whether BCG vaccination affected the efficacy of skin tests, the participants with three negative results in the first stage were randomly assigned to the BCG and placebo groups at a ratio of 2:1 and underwent three tests. The positivity rates and concordance of the three tests were calculated in both stages, and a logistic regression model was constructed to determine the factors influencing the booster effect of EC in the second stage. Safety observations were continued until the skin test results were available.In the first stage, 1,564 participants were enrolled in the study. The positivity rates of the T-SPOT, EC, and TB-PPD tests in all the participants were 18.89%, 10.37%, and 53.96%, respectively. The concordance between the EC and T-SPOT tests was 88.97% (kappa = 0.56), and that between the TB-PPD and T-SPOT tests was 58.19% (kappa = 0.20). In the second stage, 585 participants were assigned to the BCG or placebo group. In the BCG group, the positivity rates for the T-SPOT, EC, and TB-PPD tests were 4.76%, 7.30%, and 73.65%, respectively. The concordance between the EC and T-SPOT tests was 94.92% (kappa = 0.55), and that between the TB-PPD and T-SPOT tests was 29.84% (kappa = 0.02). In the placebo group, the positivity rates for the T-SPOT, EC, and TB-PPD tests were 6.88%, 11.88%, and 39.38%, respectively. The concordance between the EC and T-SPOT tests was 91.25% (kappa = 0.49), and that between the TB-PPD and T-SPOT tests was 66.25% (kappa = 0.17). The logistic regression model showed that age ≥ 60 years (odds ratio [OR] = 5.42, 95% confidence interval [CI]: 2.05-14.26) and retest positivity of T-SPOT test (OR = 44.87, 95% CI: 16.58-135.21) were stimulative factors of EC booster effect. Adverse reactions occurred in 168 (10.74%) and 33 participants (5.64%) in the first and second stage, respectively. Most of these were local adverse reactions, including injection site pain, pruritus, and rash.The diagnostic performance of the EC skin test was similar to that of the T-SPOT test in the healthy population and was unaffected by BCG vaccination. The booster effects were more inclined to occur in population with retest positivity of T-SPOT or age ≥ 60 years.NCT02795260, Clinical Study of Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10 on Healthy People Aged 18-65(III-healthy), Registration Date: June 10, 2016.© 2024. The Author(s).
|
| [20] |
李锦成, 王慧, 竺丽梅, 等. 2023年江苏省扬州市17 093名入学新生重组结核杆菌融合蛋白皮肤试验结果与肺结核检出情况分析[J]. 疾病监测, 2024, 39(6):726-731.
|
| [21] |
牟廷梅, 胡启源, 李文, 等. 重组结核杆菌融合蛋白在学生结核病筛查中的应用[J]. 寄生虫病与感染性疾病, 2022, 20(3):166-170.
|
| [22] |
张婷, 杨眉, 吴成果, 等. 重组结核分枝杆菌融合蛋白在学校结核病筛查中的应用[J]. 预防医学情报杂志, 2021, 37(11):1609-1613.
|
| [23] |
张慧, 范明宽. 结核分枝杆菌感染检测技术应用专家共识[J]. 结核与肺部疾病杂志, 2025, 6(4):365-381.
|
| [24] |
许礼发, 侯长浩, 路小欢, 等. 结核病免疫学检测方法的研究进展[J]. 医学动物防制, 2021, 37(2):152-156.
|
| [25] |
董小伟, 郭卉欣, 张晨晨, 等. 结核分枝杆菌感染检测两步法在学校结核病筛查中的应用价值[J]. 中国防痨杂志, 2022, 44(8):802-807.
|
| [26] |
|
| [27] |
卢水华, 陆伟. 重组结核杆菌融合蛋白(EC)临床应用专家共识[J]. 中国防痨杂志, 2020, 42(8):761-768.
|
| [28] |
朱干霖, 徐青, 郭锋, 等. 2019—2022年苏州市高新区学校结核病流行病学特征分析及基于ARIMA模型的趋势预测[J]. 职业与健康, 2024, 40(13):1810-1814.
|
| [29] |
陈同, 贺天锋, 于梅, 等. 浙江省宁波市16 795名入学新生结核菌素试验结果分析[J]. 疾病监测, 2023, 38(9):1043-1047.
|
利益冲突声明 全部作者声明无利益冲突
/
| 〈 |
|
〉 |
