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中国防痨杂志 ›› 2018, Vol. 40 ›› Issue (9): 924-931.doi: 10.3969/j.issn.1000-6621.2018.09.004

• 论著 • 上一篇    下一篇

两种检测技术在不同危险因素等级儿童中筛查潜伏性结核感染的结果分析

祁雪,王亚翠,郭雅洁,马琦,陈玉莹,孙琳(),申阿东()   

  1. 100045 首都医科大学附属北京儿童医院呼吸感染疾病研究室 北京市儿科研究所 儿科学国家重点学科 教育部儿科重大疾病研究重点实验室 儿童呼吸道感染性疾病研究北京市重点实验室
  • 收稿日期:2018-07-16 出版日期:2018-09-10 发布日期:2018-10-17
  • 通信作者: 孙琳,申阿东 E-mail:chinatka@163.com;shenad16@hotmail.com
  • 基金资助:
    国家自然科学基金(81571950);首都卫生发展科研专项(2016-1-2092);“十三五”国家科技重大专项(2018ZX10103001)

Analysis of the results of two detection methods for screening latent tuberculosis infection in children with different risk levels

Xue QI,Ya-cui WANG,Ya-jie GUO,Qi MA,Yu-ying CHEN,Lin SUN(),A-dong SHEN()   

  1. Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics (Capital Medical University), Ministry of Education, Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, Beijing 100045, China
  • Received:2018-07-16 Online:2018-09-10 Published:2018-10-17
  • Contact: Lin SUN,A-dong SHEN E-mail:chinatka@163.com;shenad16@hotmail.com

摘要:

目的 评价结核菌素皮肤试验(tuberculin skin test, TST)和γ干扰素释放试验(interferon-gamma release assay, IGRA)在具有不同危险因素等级儿童中检测潜伏性结核感染(latent tuberculosis infection,LTBI)的应用价值。方法 收集2013—2015年首都医科大学附属北京儿童医院收治的有与活动性结核病患者接触史的965例患儿的相关资料,排除经病原学确诊或临床诊断为活动性结核病的451例患儿和根据病史及影像学检查诊断为非活动性结核病的31例患儿,最终纳入483例患儿进行TST和IGRA两种检测方法筛查LTBI的研究与分析。以密切接触、年龄<5岁、无卡介苗接种卡痕(简称“卡痕”)作为危险因素,根据其存在危险因素多少划分危险因素等级,具有0、1、2、3个危险因素者分别归为Ⅰ级(218例)、Ⅱ级(210例)、Ⅲ级(54例)、Ⅳ级(1例,纳入Ⅲ级中分析)。采用卡方检验分析TST和IGRA在上述人群中的检测阳性率差异,并进行其阳性结果相关的单因素分析,均以P<0.05为差异有统计学意义;两种检测方法的一致性分析采用Kappa检验。结果 483例患儿均进行了IGRA筛查检测,阳性率为2.48%(12/483),危险因素等级Ⅰ、Ⅱ、Ⅲ级患儿检测的阳性率分别为2.29%(5/218)、2.38%(5/210)和3.64%(2/55),差异无统计学意义(χ 2=0.459,P=0.795);369例患儿进行了TST检测,阳性率为11.38%(42/369),危险因素等级Ⅰ、Ⅱ、Ⅲ级患儿检测的阳性率分别为9.36%(16/171)、12.74%(20/157)和14.63%(6/41),差异无统计学意义(χ 2=1.412,P=0.494);二者联合(TST+IGRA)检测任一阳性的阳性率为9.11%(44/483), 危险因素等级Ⅰ、Ⅱ、Ⅲ级患儿检测的阳性率分别为7.34%(16/218)、9.52%(20/210)、14.55%(8/55),差异无统计学意义(χ 2=2.832,P=0.243)。3种筛查方法的阳性率在风险等级Ⅰ级和Ⅱ级组中差异均有统计学意义(χ 2=7.861,P=0.020;χ 2=13.318,P=0.001)。患儿与结核病患者密切接触史是TST和IGRA两种方法阳性结果的相关因素,与结核病患者密切接触的患儿TST(25.26%,24/95)或IGRA(5.00%,6/120)检测的阳性率均高于非密切接触患儿[分别为6.57%(18/274)、1.65%(6/363)],差异均有统计学意义[χ 2=21.131,P<0.05,OR(95%CI)=4.329(2.232~8.396);χ 2=4.291,P=0.038,OR(95%CI)=3.186(1.006~10.096)]。TST和IGRA两种方法检测的总体一致性较差,Kappa值为0.346。 结论 在有结核病密切接触史的儿童中,危险因素等级越高,发生LTBI的风险越高,是儿童发生LTBI的高危险因素。由于TST和IGRA两种检测方法的一致性较差,为避免漏诊,建议在暴露后危险因素等级高的儿童中同时使用两种方法筛查LTBI。

关键词: 接触者追踪, 危险因素, 实验室技术和方法, 潜伏性结核病, 多相筛查

Abstract:

Objective Evaluate the value of tuberculin skin test (TST) and interferon-gamma release assay test (IGRA) in screening latent tuberculosis infection (LTBI) among children with different risk levels.Methods Collection of information on 965 children with a history of contact with active tuberculosis (ATB) patients enrolled at Beijing Children’s Hospital from 2013 to 2015, excluding 451 children diagnosed by etiology or clinically as ATB and 31 children diagnosed as inactive tuberculosis based on medical history and imaging examination, 483 children were finally included for the study and analysis of LTBI screening by TST and IGRA. Close contact history, children aged <5 years and no BCG scar were defined as risk factors, and the risk level was classified according to the number of risk factors. Those without the above risk factors were grouped as Grade Ⅰ (218 cases), those with 1, 2 and 3 risk factors were grouped as Ⅱ (210 cases), Ⅲ (54 cases) and Ⅳ (1 case, incorporate Ⅲ), respectively. Chi-square test was used to analyze the positive rates of TST and IGRA, and the univariate analysis related to positive results was conducted, P<0.05 was considered to be statistically significant. Kappa test was used for consistency analysis of the two laboratory techniques.Results All of the 483 children were tested by IGRA, the positive rate was 2.48% (12/483). The positive rates of IGRA in the Ⅰ-Ⅲ group were 2.29% (5/218), 2.38% (5/210), and 3.64% (2/55), respectively, and the difference was not statistically significant (χ 2=0.459, P=0.795). TST was performed in 369 children, the positive rate was 11.38% (42/369), and the positive rates of TST in the Ⅰ-Ⅲ group were 9.36% (16/171), 12.74% (20/157) and 14.63% (6/41), the difference was not statistically significant (χ 2=1.412,P=0.494). The combined detection of the two methods (TST+IGRA) means that the positive rate of either method was 9.11% (44/483), and the positive rates of TST+IGRA in the Ⅰ-Ⅲ group were 7.34% (16/218), 9.52% (20/210), 14.55% (8/55), and the difference was not statistically significant (χ 2=2.832,P=0.243). The positive rates of the three screening methods were statistically significant in the risk grades Ⅰ and Ⅱ (χ 2=7.861,P=0.020;χ 2=13.318,P=0.001). The close contact history with tuberculosis patients had the most significant correlation with the positive results of TST and IGRA. The positive rate of TST (25.26%, 24/95) or IGRA (5.00%, 6/120) in children with close contact with ATB patients was higher than that in non-intimate patients (6.57% (18/274), 1.65% (6/363)), the difference was statistically significant (χ 2=21.131,P=0.000, OR (95%CI)=4.329(2.232-8.396); χ 2=4.291,P=0.038,OR (95%CI)=3.186(1.006-10.096)).The consistency of the two tests was poor and the Kappa value was 0.346.Conclusion Among children with history of exposure to tuberculosis, those at the higher risk levels have the higher risk to develop LTBI, which is a high risk factor for LTBI in children. Due to the poor consistency of the two tests, in order to avoid missed diagnosis, combination use of TST and IGRA for screening LTBI in high-risk children is recommended.

Key words: Contact tracing, Risk factors, Laboratory techniques and procedures, Latent tuberculosis, Multiphasic screening