Table_1_Evaluation of the specificity of an intradermal test with recombinant tuberculosis allergen in Bacillus Calmette–Guérin-vaccinated healthy volunteers.DOCX

IntroductionThe tuberculin skin test has significant limitations for use in individuals vaccinated with BCG. The presence in the genome of Mycobacterium tuberculosis of the RDI region, which is absent in the genome of Mycobacterium bovis BCG and most non-tuberculous mycobacteria, made it possible to develop new skin tests, which include a skin test with a recombinant tuberculosis allergen [RTA (Diaskintest®, JSC Generium, Russia)]. Diaskintest has shown high diagnostic performance in clinical trials and in conditions of high prevalence of tuberculosis infection. In 2021, the Russia was excluded from the WHO list of high TB burden countries, which makes relevant an assessment of the specificity of the RTA test under conditions of low epidemiologic risk for tuberculosis to confirm the high specificity of the test.
Study objectiveTo assess the specificity of Diaskintest in the regions of the Russian Federation with low epidemiologic risk for tuberculosis.
MethodsA multicenter, open-label, prospective study was conducted, which included 150 healthy volunteers aged 18–30 years old, vaccinated with BCG, who were not at risk of tuberculosis, from regions with low epidemiologic risk (Oryol region, Ryazan region, and Arkhangelsk region). During the study, 4 visits were scheduled for each participant: [Visit 0 (screening), Visit 1, Visit 2 (in 72 h) and Visit 3 (in 28 days)]. All participants, who excluded active and latent tuberculosis infection, underwent a test with RTA. To assess the safety of RTA tests, all systemic and local adverse events that occurred during 28 days were recorded. The trial was filed in the NIH clinical trials database ClinicalTrials.gov (NCT05203068).
ResultsIn individuals with a negative T-SPOT.TB test, the specificity of the RTA test was 97% (95% CI: 92–99%) with a cut-off of >0 mm. The study findings confirm data 2009: 100.00 (95% CI: 94–100). When evaluating the safety of the RTA test during 28 days of follow-up, the participants did not report local and systemic adverse reactions that had a causal relationship with the RTA test.
ConclusionDiaskintest is highly specific and safe, therefore it is a valuable tool as a screening test for early detection of tuberculosis.

引言
结核菌素皮肤试验对于接种卡介苗（Bacillus Calmette-Guérin，简称BCG）的人群存在显著应用局限性。结核分枝杆菌（Mycobacterium tuberculosis）基因组中存在RDI区域，该区域在牛分枝杆菌卡介苗株及多数非结核分枝杆菌的基因组中均不存在，这一发现为新型皮肤试验的研发提供了可能，此类试验包括重组结核变应原皮肤试验[RTA（迪阿金特®，俄罗斯Generium股份公司）]。迪阿金特在临床试验及结核感染高流行场景中展现出优异的诊断效能。2021年，俄罗斯被排除出世界卫生组织（WHO）的结核病高负担国家名单，这使得在结核病流行病学低风险环境下评估RTA试验的特异性以验证其高特异性成为必要。

研究目标
本研究旨在评估俄罗斯联邦结核病流行病学低风险地区中迪阿金特的特异性。

研究方法
本研究为多中心、开放标签的前瞻性研究，共纳入150名年龄18~30岁、接种过卡介苗且无结核感染风险的健康志愿者，招募自结核病流行病学低风险地区（奥廖尔州、梁赞州及阿尔汉格尔斯克州）。每名受试者共安排4次随访：第0次访视（筛查）、第1次访视、第2次访视（接种后72小时）及第3次访视（接种后28天）。所有经排查无活动性及潜伏性结核感染的受试者均接受了RTA试验。为评估RTA试验的安全性，研究人员记录了受试者在接种后28天内发生的所有全身性及局部不良事件。本试验已在美国国立卫生研究院（NIH）临床试验数据库ClinicalTrials.gov注册（注册号：NCT05203068）。

研究结果
在结核感染T细胞检测（T-SPOT.TB）结果为阴性的受试者中，当截断值设定为>0mm时，RTA试验的特异性为97%（95%置信区间：92~99%）。本研究结果验证了2009年的相关数据：100.00（95%置信区间：94~100）。在为期28天的随访安全性评估中，受试者未报告与RTA试验存在因果关联的局部及全身性不良反应。

研究结论
迪阿金特具有优异的特异性与安全性，可作为结核病早期筛查的有效工具。