Prognostic Value of a T-Cell-Based, Interferon-γ Biomarker in Children with Tuberculosis Contact
Prognostic Value of a T-Cell-Based, Interferon-γ Biomarker in Children with Tuberculosis Contact
复制标题
DOI：
10.7326/0003-4819-149-11-200812020-00248
复制
发表时间：
2008-12-02
影响因子：
39.2
通讯作者：
Lalvani, Ajit
中科院分区：
文献类型：
--
作者：
Bakir, Mustafa;Millington, Kerry A.;Lalvani, Ajit
背景资料：酶联免疫斑点（ELISpot）试验是一种越来越广泛使用的、基于T细胞的、γ-干扰素释放试验，用于诊断结核病感染，但阳性结果是否是活动性结核病的预后尚不清楚。目的：确定ELISpot试验结果是否能预测近期结核病暴露者中活动性结核病的发展。设计：2002年10月至2004年4月招募的儿童和青少年结核病接触者的纵向队列研究。背景：土耳其社区接触者调查。患者：908名儿童和青少年最近有家庭结核病暴露。干预：在基线时进行酶联免疫斑点试验，包括早期分泌抗原靶标-6和培养滤液蛋白-10，以及结核菌素皮肤试验。测量：结核菌素皮试和ELISpot结果阳性的接触者进展为活动性结核病的发病率比率，以及比较阳性和阴性检测结果的接触者的相对发病率。根据当地指南，对688名（76%）接触者进行了异烟肼预防性治疗。在1201人年的随访中，15名接触者发展为活动性结核病。在ELISpot结果阳性的381名接触者中，11名在536人-年的随访中发展为活动性结核病（发病率，21/1000人-年[95% CI，10.2 - 36.7/1000人-年]），相对于ELISpot阴性接触者，进展风险增加3- 4倍，具有统计学意义。在550名结核菌素皮肤试验结果阳性的接触者中，12人在722人年的随访中发展为活动性结核病（发病率，17/1000人-年[CI，8.6 - 29.0/1000人-年]）。局限性：15例发病病例中仅3例经培养证实。阳性ELISpot结果预测近期结核病接触者随后发生活动性结核病。尽管ELISpot结果呈阳性的结核病接触者的结核病发病率与结核菌素皮试结果呈阳性的接触者相似，但ELISpot检测可以更有针对性地对更少的接触者进行预防性治疗。
Background: Enzyme-linked immunospot (ELISpot) assay is an increasingly widely used, T-cell-based, interferon-gamma-release assay for diagnosing tuberculosis infection, but whether positive results are prognostic of active tuberculosis is not known.Objective: To determine whether ELISpot results predict the development of active tuberculosis among persons with recent tuberculosis exposure.Design: Longitudinal cohort study of children and adolescents with tuberculosis contact recruited from October 2002 to April 2004.Setting: Community-based contact investigations in Turkey.Patients: 908 children and adolescents with recent household tuberculosis exposure.Intervention: Enzyme-linked immunospot assay, incorporating early secretory antigenic target-6 and culture filtrate protein-10, and tuberculin skin test were done at baseline.Measurements: Incidence rates ratios of progression to active tuberculosis for contacts with positive tuberculin skin test and ELISpot results, and relative incidence rates comparing contacts with positive and negative test results.Results: Isoniazid preventive therapy was given to 688 (76%) contacts according to local guidelines. Fifteen contacts developed active tuberculosis over 1201 person-years of follow-up. Of 381 contacts with positive ELISpot results, 11 developed active tuberculosis over 536 person-years of follow-up ( incidence rate, 21 per 1000 person-years [95% CI, 10.2 to 36.7 per 1000 person-years]), a statistically significant 3- to 4-fold increased risk for progression relative to ELISpot-negative contacts. Of 550 contacts with positive tuberculin skin test results, 12 developed active tuberculosis over 722 person-years of follow-up ( incidence rate, 17 per 1000 person-years [CI, 8.6 to 29.0 per 1000 person-years]).Limitation: Only 3 of the 15 incident cases were confirmed by culture.Conclusion: Positive ELISpot results predict subsequent development of active tuberculosis in recent tuberculosis contacts. Although tuberculosis contacts with positive ELISpot results have an incidence rate of tuberculosis similar to that of contacts with positive tuberculin skin test results, ELISpot testing could allow more focused targeting of preventive therapy to fewer contacts.