Randomised Clinical Trial Investigating the Specificity of a Novel Skin Test (C-Tb) for Diagnosis of M. tuberculosis Infection
Randomised Clinical Trial Investigating the Specificity of a Novel Skin Test (C-Tb) for Diagnosis of M. tuberculosis Infection
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DOI：
10.1371/journal.pone.0064215
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发表时间：
2013-05-14
期刊：
影响因子：
3.7
通讯作者：
Lewis, David J. M.
中科院分区：
文献类型：
--
作者：
Aggerbeck, Henrik;Giemza, Rafaela;Lewis, David J. M.
背景：结核菌素皮试简单且相对便宜，但 PPD 的特异性受 BCG 疫苗接种的影响。目的：确定乳酸乳球菌中产生的重组 ESAT-6 和 CFP-10 (C-Tb) 的最佳剂量和特异性，用于诊断结核分枝杆菌感染。方法：在剂量探索 I 期试验中，通过 Mantoux 技术将 0.01 或 0.1 μg 保存和未保存的 C-Tb 注射到 38 例患者中。患有活动性结核病的患者和测量的硬结反应。在 151 名未感染者参与的 II 期特异性试验中，将接种 BCG 的参与者 0.1 μg C-Tb 与 2 TU PPD 进行比较。结果：0.1 μg C-Tb 2 天后中位硬结为 15 毫米。苯酚保存不影响响应。 C-Tb 的特异性为 99.3% (95% CI 96-100%)，将硬结 >= 5 mm 作为阳性结果。这高于 PPD 的特异性（63% 使用 5 mm 的截止值或 92% 使用 15 mm 的截止值来调整非特异性 BCG 反应）。 C-Tb 注射后的局部不良反应包括短暂的瘙痒和不适，这是免疫反应的预期组成部分。结论：C-Tb 提供了一种简单方便的皮肤测试，使用不受 BCG 疫苗接种影响的单一通用临界点来诊断结核分枝杆菌感染。
Background: Tuberculin skin testing is simple and relatively inexpensive, but the specificity of PPD is affected by BCG vaccination.Objective: Determine optimal dose and specificity of recombinant ESAT-6 and CFP-10 (C-Tb) produced in Lactococcus lactis for diagnosis of M. tuberculosis infection.Methods: In a dose finding phase I trial 0.01 or 0.1 mu g preserved and unpreserved C-Tb was injected by Mantoux technique in 38 patients with active tuberculosis and induration responses measured. In a phase II specificity trial in 151 uninfected, BCG vaccinated participants 0.1 mu g C-Tb was compared to 2 TU PPD.Results: 0.1 mu g C-Tb gave a median induration of 15 mm after 2 days. Phenol preservation did not affect the response. The specificity of C-Tb was 99.3% (95% CI 96-100%) regarding indurations >= 5 mm as a positive outcome. This was higher than the specificity of PPD (63% using a cut-off of 5 mm or 92% using a cut-off of 15 mm to adjust for non-specific BCG responses). Local adverse reactions following C-Tb injection included transient itching and discomfort as expected components of the immune response.Conclusion: C-Tb offers a simple and convenient skin test to diagnose M. tuberculosis infection using a single, universal cutoff unaffected by BCG vaccination.