Department of Infectious Diseases Immunology, Statens Serum Institut, Copenhagen, Denmark.
Department of Vaccine Development, Statens Serum Institut, Copenhagen, Denmark.
Lancet Respir Med. 2017 Apr;5(4):259-268. doi: 10.1016/S2213-2600(16)30436-2. Epub 2017 Feb 1.
Targeted screening and treatment of Mycobacterium tuberculosis infection substantially reduces the risk of developing active tuberculosis. C-Tb (Statens Serum Institute, Copenhagen, Denmark) is a novel specific skin test based on ESAT-6 and CFP10 antigens. We investigated the safety and diagnostic potential of C-Tb compared with established tests in the contact-tracing setting.
Negative controls, close contacts, occasional contacts, and patients with active pulmonary tuberculosis were enrolled at 13 centres in Spain. We compared C-Tb with the QuantiFERON-TB Gold In-Tube ([QFT] Qiagen, Hilden, Germany) interferon γ release assay (IGRA) and the purified protein derivative (PPD) RT 23 tuberculin skin test ([TST] Statens Serum Institute). All participants older than 5 years were tested with QFT. Some participants in the negative control group received C-Tb without the TST to test for potential interactions between C-Tb and PPD RT 23. The rest were randomly assigned in blocks of ten and tested with both C-Tb and TST, with five in each block receiving injection of C-Tb in the right arm and the TST in the left arm and five vice versa. The primary and safety analyses were done in all participants randomly assigned to a group who received any test. This trial is registered with ClinicalTrials.gov, number NCT01631266, and with EudraCT, number 2011-005617-36.
From July 24, 2012, to Oct 2, 2014, 979 participants were enrolled, of whom 263 were negative controls, 299 were occasional contacts, 316 were close contacts, and 101 were patients with tuberculosis. 970 (99%) participants completed the trial. Induration sizes were similar for C-Tb and TST, but TST positivity was affected by BCG vaccination status. We found a strong positive trend towards C-Tb test positivity with increasing risk of infection, from 3% in negative controls to 16% in occasional contacts, to 43% in close contacts. C-Tb and QFT results were concordant in 785 (94%) of 834 participants aged 5 years and older, and results did not differ significantly between exposure groups. The safety profile of C-Tb was similar to that for the TST.
C-Tb delivered IGRA-like results in a field-friendly format. Being unaffected by BCG vaccination status, the C-Tb skin test might provide more accurate treatment guidance in settings where the TST is commonly used.
Statens Serum Institut.
针对结核分枝杆菌感染的靶向筛查和治疗可显著降低发展为活动性肺结核的风险。C-Tb（丹麦哥本哈根血清研究所）是一种基于 ESAT-6 和 CFP10 抗原的新型特异性皮肤试验。我们研究了 C-Tb 在接触者追踪环境中与既定检测方法相比的安全性和诊断潜力。
在西班牙的 13 个中心招募了阴性对照、密切接触者、偶然接触者和活动性肺结核患者。我们将 C-Tb 与 QuantiFERON-TB Gold In-Tube（[QFT]Qiagen，德国希尔德斯海姆）干扰素γ释放测定（IGRA）和纯化蛋白衍生物（PPD）RT 23 结核菌素皮肤试验（[TST]丹麦血清研究所）进行了比较。所有年龄大于 5 岁的参与者均接受了 QFT 检测。阴性对照组的一些参与者在未接受 TST 的情况下接受了 C-Tb 检测，以测试 C-Tb 和 PPD RT 23 之间的潜在相互作用。其余参与者按 10 人一组随机分组，并接受 C-Tb 和 TST 检测，每组 5 人在右臂注射 C-Tb，左臂注射 TST，另外 5 人则相反。所有随机分组接受任何检测的参与者均进行了主要和安全性分析。本试验在 ClinicalTrials.gov 注册，编号为 NCT01631266，在 EudraCT 注册，编号为 2011-005617-36。
从 2012 年 7 月 24 日至 2014 年 10 月 2 日，共纳入 979 名参与者，其中 263 名为阴性对照者，299 名为偶然接触者，316 名为密切接触者，101 名为肺结核患者。970（99%）名参与者完成了试验。C-Tb 和 TST 的硬结大小相似，但 TST 的阳性率受卡介苗接种状况的影响。我们发现，随着感染风险的增加，C-Tb 检测的阳性趋势呈强阳性，从阴性对照者的 3%到偶然接触者的 16%，再到密切接触者的 43%。在 834 名年龄大于 5 岁的参与者中，C-Tb 和 QFT 的结果在 785 名（94%）参与者中一致，且结果在不同的暴露组中无显著差异。C-Tb 的安全性与 TST 相似。
C-Tb 以一种便于现场使用的形式提供了类似于 IGRA 的结果。C-Tb 不受卡介苗接种状况的影响，在 TST 常用于的情况下，C-Tb 皮肤试验可能提供更准确的治疗指导。
丹麦血清研究所。
