Investigation of the cell composition and gene expression in the delayed-type hypersensitivity tuberculin skin test

Dear Editor,The tuberculin skin test(TST)reagents have continuously improved,with the ESAT6-CFP10(EC)test having recently been introduced,but are seldom based on the direction of the delayed-type hypersensitivity(DTH)mechanism.Previous studies only partially showed the infiltration and activation of immune cells and the production of cytokines of the skin induration[1,2],and lack the detailed measurements of cell proportions and gene expression in the DTH response.Therefore,in this study,we revealed the comprehensive characteristics of DTH by single-cell RNA sequencing(scRNA-seq)in the guinea pig tuberculosis(TB)model[Experimental Animal Welfare Ethics Committee,Beijing Tuberculosis and Thoracic Tumor Research Institute(2021-064)].

Performance and correlation of QuantiFERON-TB Gold, T-SPOT.TB and tuberculin skin test in young children with or exposed to tuberculosis

Objective:To evaluate the performance of interferon gamma release assays and tuberculin skin test in Bacillus Calmette-Guerin vaccinated young children.Methods:A cross-sectional study was conducted in healthy children younger than 5 years who were recently diagnosed with tuberculosis or had recent exposure to active tuberculosis.QuantiFERON-TB Gold,T-SPOT.TB and tuberculin skin test were performed in each patient.Results:Of the 60 children,median age 3.3 years,17 had tuberculosis and 43 had recent tuberculosis exposure.Overall,15(25.0%)children had tuberculin skin test reaction≥10 mm;8(13.3%)were positive by QuantiFERON-TB Gold In-Tube test,and 12(20.0%)by T-SPOT.TB.Nineteen(31.7%)children had at least one positive test.There was a moderate agreement between interferon gamma release assays and tuberculin skin test.Conclusions:The positive rates of interferon gamma release assays and tuberculin skin test were low in young children who were infected with tuberculosis,supporting the management strategy of not testing children younger than 5 years.

Performance and correlation of interferon gamma release assays and tuberculin skin test in HIV-infected children and adolescents with immune reconstitution

Objective:To evaluate the performance of interferon gamma release assays and tuberculin skin test in HIV-infected children and adolescents with immune reconstitution.Methods:A cross-sectional study was conducted in HIV-infected patients aged 5-18 years receiving antiretroviral treatment with CD4 T-lymphocytes>25%or>500 cells/mm3 for at least 6 months.QuantiF ERON-TB Gold,T-SPOT.TB,and tuberculin skin test were performed in each patient.Results:A total of 50 patients were enrolled with median age of 13.7 years,CD4 counts of 753(IQR:587-989)cells/mm3.Among 27 patients with tuberculosis(16)or tuberculosis exposure(11),8(29.6%)were positive to at least one test,2(7.4%)were positive QuantiFERON-TB Gold,3(11.1%)positive T-SPOT.TB,and 7(25.9%)had tuberculin skin test≥5 mm.Among 23 patients without history of tuberculosis or exposure,all had negative interferon gamma release assays,while 2(8.7%)had positive tuberculin skin test.Conclusions:All tests had low sensitivity despite immune reconstitution.

Comparison between Quanti-FERON-TB Gold In-Tube test and tuberculin skin test for diagnosis of latent tuberculosis in children: A cross-section study

Objective: To compare Quanti-FERON-TB Gold In-Tube (QFT-GIT) test and tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection in children. Methods: In this cross-sectional study, 64 participants who were between 3 months and 14 years old and had close contact with smear-positive pulmonary tuberculosis were included. Both QFT-GIT test and TST were done and the results were analyzed by SPSS software and Kappa test. Results: The distribution of gender and age according to QFT-GIT and TST results were matched (P>0.05). Overall agreement between QFT-GIT and TST for diagnosis of latent tuberculosis infection in children was 75%. In addition, the contingency coefficient was 0.257, and the Kappa measure of agreement was 0.246 (P=0.034). Conclusions: Compared to TST, QFT-GIT shows no apparent advantage for diagnosis of latent tuberculosis infection in children.

Indications, Interpretation and Clinical Consequences of Tuberculin Skin Tests in Resource Limited Settings

Objective: to evaluate the policy of TST testing in Suriname. As there is no gold standard to diagnose latent tuberculosis infection (LTBI), the tuberculin skin test (TST) is used to diagnose LTBI. However, internationally, the cut-off values of the TST are not uniform and depend on local tuberculosis (TB) epidemiology and guidelines for test initiation. In Suriname, where currently several indications exist for TSTs, cut-off values are set at 5 mm or 10 mm, depending on the age and/or medical history of the patient. LTBI classification is performed by pulmonologists primarily based on the American Thoracic Society targeted TB testing guidelines. Method: retrospective analysis of outpatient TST data between 2011 and 2019 from Suriname’s sole pulmonary medicine clinic. Result: 1373 patients were evaluated. 590 patients were from the screening group of whom 253 had a positive TST result, 46 of whom were classified as LTBI. In the contact tracing group of 649 patients, 616 had a positive TST, 352 of whom were classified as LTBI. In the medical condition group of 134 patients, 96 had a positive TST, 38 of whom were classified as LTBI. Eventually, positive TST results were found for 965 tested patients: 436 patients were classified as LTBI and 529 non-LTBI patients were not prescribed chemoprophylaxis. None of the non-LTBI TST-positive patients were diagnosed with active TB, including 174 patients with a TST result of 15 mm or greater and in need of IPT, but not prescribed by judgement of the pulmonologist or because of loss to follow-up. Conclusion: the overrepresentation of positive TST results in Suriname is attributable to stringent cut-off values, especially among patients who do not disclose TB risk factors. In our opinion the TST cut-off value for such patients in Suriname and other similar settings could be set at 15 mm. We also promote that for all patients with a TST result of 15 mm or greater, offering IPT should be considered (after excluding active TB).

基于两种方法筛查常州市高校学生结核潜伏感染结果比较

目的了解常州地区高校学生结核潜伏感染现状,比较结核分枝杆菌素释放试验(tuberculosis skin test,TST)和结核分枝杆菌特异性细胞免疫反应(QuantiFERON-TB Gold In-tube,QFT)检测2种方法一致性。方法2020年采用整群抽样方法,选取常州市两所高校共625名学生进行TST和QFT检测,并进行为期2年的结核病病例监测。结果625名学生中,筛查出结核潜伏感染118人,检出率为18.88%(95%CI:15.94%~21.82%);其中单TST检测阳性率为15.20%,单QFT检测阳性率为10.72%,双阳性率为7.04%。以TST硬结直径≥5 mm为阳性判断标准时,两种检测方法的一致性为中等(Kappa值=0.48,P<0.01);以≥10 mm、≥15mm为阳性判断标准时两种方法一致性均较差(Kappa值=0.33、0.21,P值均<0.01)。筛查出结核潜伏感染118名学生中,参与预防性服药39名(占33.05%)。2年随访确诊为活动性结核病3例,2年累计发病率为0.48%。结论建议在TST硬结直径≥10 mm学生中加做QFT试验,且对单纯TST强阳性或QFT阳性学生采取预防性服药措施,有结核病接触史学生应作为结核筛查和预防性服药重点人群。

基于改进YOLOv5的人体结核菌素试验后皮下硬块检测算法研究

针对传统皮下硬块检测方法精度低、计算速度慢等问题,提出了一种基于改进YOLOv5的皮下硬块目标检测算法。首先,将YOLOv5模型的主干网络CSPDarknet53进行改进,引入Faster模块来替换其中的C3模块。其次,利用模型剪枝在保证整个模型性能的同时减轻其计算复杂度。最后,引入Wise-IoU来进一步提升网络的回归性能。实验结果表明,基于改进YOLOv5的皮下硬块目标检测算法相比于原始的YOLOv5,准确率提升了1.2%,参数量减少了77.7%,整个算法更加轻量化,有效提高了算法对于皮下硬块的检测精度,减少了计算参数量,提升了算法的运行速度。

肺结核患者家庭内学生密切接触者结核分枝杆菌感染状况调查

目的:分析肺结核患者家庭内学生密切接触者结核分枝杆菌感染状况及其影响因素。方法:以2021年1月1日至12月31日在江苏省宝应县和张家港市、湖北省宜都市、重庆市彭水苗族土家族自治县和云南省昭通市昭阳区5个县(区)登记的活动性肺结核患者家庭内学生密切接触者为研究对象,开展结核菌素皮肤试验(tuberculin skin test,TST),调查人口学特征,并通过全民健康保障信息化工程疾病预防控制信息系统收集其指示病例的基本信息和诊断信息,分析结核分枝杆菌感染的相关因素。结果:477例指示病例共有686名家庭内学生密切接触者,TST检测总体接受率为92.27%(633/686),各县(区)之间的接受率差异有统计学意义(χ^(2)=57.781,P<0.001),以宝应县为最高(100.00%,35/35)。家庭内学生密切接触者总体感染率为14.85%(94/633,95%CI:11.85%~17.85%),强阳性率为5.06%(32/633),各县(区)之间的差异均有统计学意义(χ^(2)=35.800,P<0.001;Fisher确切概率法,P=0.029)。单因素分析结果显示,≥15岁年龄组[23.47%(23/98);95%CI:13.88%~33.06%]、就读于高中及以上学校[26.09%(18/69);95%CI:14.04%~38.14%]、住在宜都市[33.33%(28/84);95%CI:20.99%~45.68%]、指示病例诊断延迟[18.37%(52/283);95%CI:13.38%~23.37%]的家庭内学生密切接触者感染率更高;多因素logistic回归分析显示,在调整混杂因素后,指示病例诊断延迟的家庭内学生密切接触者的感染风险是指示病例无诊断延迟者的1.586倍(95%CI:1.016~2.476)。结论:活动性肺结核患者家庭内学生密切接触者的结核分枝杆菌感染率较高,尤其是指示病例诊断延迟的家庭内学生密切接触者,应及时开展筛查并采取后续干预措施。

2022年贵州省新生入学肺结核筛查情况分析

目的对入学新生进行肺结核筛查结果进行分析,为贵州省学校结核病防控工作提供一定的基础数据和参考依据。方法对2022年贵州省入学新生开展肺结核筛查。筛查内容有症状筛查(肺结核密切接触史、肺结核可疑症状)、结核菌素皮肤试验(PPD试验)/重组结核杆菌融合蛋白试验(EC试验)、胸部X线片3种,根据不同年级采取不同筛查方法。采用构成比、百分率、千分率等进行描述性分析。结果2022年贵州省共有7651所学校的1675408名新生参加了入学肺结核筛查。肺结核密切接触史率、可疑症状率分别为1.64‰、1.26‰;PDD强阳性率为2.02%、EC阳性率为4.26%;肺结核检出率为16.43/10万,不同办学单位(χ^(2)=9.069,P=0.003)、不同寄宿类型(χ^(2)=92.747,P<0.001)和不同学校类型(P=0.003)的活动性肺结核检出率差异均有统计学意义。结论新生入学肺结核筛查工作对于学校肺结核疫情防控和降低学生肺结核患病水平具有重要意义;要进一步加强对新生的肺结核的健康教育,提升自我防护意识。

中国肾移植受者结核病临床诊疗指南(2023版)

本指南旨在为肾移植受者结核病的临床管理提供全面而实用的指导。首先,概述了肾移植受者结核病的特殊性,强调了其高发生率及临床表现的多样性。为了更好地理解患者的病情,建议在移植前进行结核病相关的评估,并注意移植术后对结核病的监测。在诊断方面,详细介绍了目前常用的结核病诊断方法,并提供了在肾移植受者中的适用性评估。在确诊后,讨论了在免疫抑制药应用的背景下,如何平衡结核病治疗和排斥反应的策略,并关注了潜在的药物相互作用。预防方面,强调了在肾移植前对结核病的筛查。本指南旨在提高医务人员对肾移植受者结核病管理的认知,促进更有效的临床实践,提高受者的生活质量。

2021年泽普县15岁以下中学入学新生结核病感染情况分析

目的:了解泽普县15岁以下中学入学新生结核病感染现状,为学校结核病防控工作提供科学依据。方法:对2021年泽普县15岁以下中学入学新生进行结核菌素试验,对检测结果进行分析,并采用logistic回归模型进行影响因素分析。结果:结核菌素试验阳性率为5.47%(248/4531)。其中,一般阳性率为3.38%(153/4531),中度阳性率为1.50%(68/4531),强阳性率为0.60%(27/4531)。不同年级新生结核菌素试验阳性率和强阳性率比较,差异有统计学意义(χ^(2)值分别为31.74、20.26,P<0.05);不同民族新生结核菌素试验阳性率比较,差异有统计学意义(χ^(2)=37.83,P<0.05);农村新生和城镇新生结核菌素试验阳性率比较,差异有统计学意义(χ^(2)=17.42,P<0.05)。多因素logistic回归分析结果显示,高一年级(OR=3.43)、汉族(OR=2.46)和城镇(OR=1.69)是入学新生结核感染的主要因素。结论:开展结核菌素试验可以了解新生结核病感染现况,识别学生感染结核病的主要因素,从而有针对性地采取防控措施,防止结核病在校园内传播流行。

化学免疫分析结核γ-干扰素释放试验在肺结核诊断中的价值探究

目的 分析化学免疫分析结核γ-干扰素释放试验在肺结核诊断中应用的价值。方法 选取2020年1月—2023年4月江苏省淮安市楚州中医院接受检查的109例疑似肺结核患者作为研究对象,全部研究对象均行结核菌素皮肤试验和化学免疫分析结核γ-干扰素释放试验,将抗酸染色试验的结果为金标准,比较两种检测方式在肺结核诊断中的应用结果及诊断效能。结果 结核γ-干扰素释放试验在肺结核诊断中真阳性例数多于结核菌素皮肤试验。化学免疫分析结核γ-干扰素释放试验的灵敏度(94.74%)和准确度(93.58%)高于结核菌素皮肤试验的84.21%、81.65%,差异有统计学意义(χ^(2)=5.588,7.144,P均<0.05)。结论 在肺结核疾病诊断中,应用化学免疫分析结核γ-干扰素释放试验具有较高价值,诊断结果与金标准较为接近,诊断效能较高。

肺结核密切接触者结核分枝杆菌潜伏感染情况及影响因素分析

目的:分析肺结核密切接触者结核分枝杆菌潜伏感染(latent tuberculosis infection,LTBI)情况及影响因素。方法:以苏州地区张家港市2021年1月1日至12月31日期间登记管理的肺结核患者(76例)及其密切接触者(498名)为研究对象,调查研究对象人口学特征和接触方式等信息,采用结核菌素皮肤试验判定LTBI者。应用非条件的Binary Logistic逐步回归模型筛选肺结核密切接触者发生LTBI的影响因素,绘制森林图。结果:498名肺结核密切接触者中,LTBI者179例,潜伏感染率为35.94%。病原学阳性患者密切接触者LTBI发生率(37.64%,172/457)明显高于病原学阴性者(17.07%,7/41),差异有统计学意义(χ^(2)=6.910,P<0.001)。多因素分析显示,以年龄最低三分位(<20岁)为参考,肺结核密切接触者(20~39岁和≥40岁)发生LTBI风险的OR(95%CI)值分别为1.768(1.132~2.763)和2.020(1.093~3.733),呈现随年龄增加,感染风险上升的趋势(χ_(趋势)^(2)=15.743,P<0.001);社会密切接触者发生LTBI的风险是家庭密切接触者的2.892(95%CI:1.673~4.999)倍。结论:苏州地区张家港市肺结核密切接触者LTBI发生率较高,病原学阳性患者密切接触者、年龄≥40岁密切接触者和社会密切接触者是发生LTBI的高风险人群,应进行针对性开展预防性服药干预。

Latent tuberculosis infection in health-care workers in the government sector in Brunei Darussalam:A cross-sectional study

Objective:Health-care workers(HCWs)are known to be at high risk for occupational biological hazards,and this includes exposure to mycobacterium tuberculosis(TB)which can result in either active or latent TB infection(LTBI).This study aims to provide an overview of the incidence of LTBI among HCWs in Brunei Darussalam,to examine associated risk factors,and to evaluate LTBI treatment compliance.Materials and Methods:This is a retrospective cross-sectional study which was conducted using data from January 2018 to December 2021,on notified cases of LTBI in HCWs which identified 115 cases.Demographic data,underlying medical conditions,and compliance to treatment were assessed through reviews of their electronic health records.Results:The incidence of LBTI was 14.6/year/1000 HCWs.The incidence rate reached a high of 24.6/1000 in 2020,and majority of cases were in the older age groups.There was good treatment acceptance and compliance(82.6%),and this was observed to be significantly higher in females than males(P=0.02).Conclusion:This study showed an average incidence of LTBI of 14.6/1000 HCWs over 4 years and high LTBI treatment acceptance(82.6%)and compliance.Emphasis on infection prevention and control measures in health-care settings and actions to increase awareness of LTBI are crucial interventions toward reducing the burden of LTBI.

γ-干扰素释放试验在抗酸杆菌涂片阴性肺结核患者诊断中的应用价值研究

目的:研究γ-干扰素释放试验(IGRAs)在抗酸杆菌涂片阴性肺结核患者临床诊断中的应用价值。方法:回顾性分析2017年1月—2018年12月于广西壮族自治区南溪山医院行IGRAs与纤维支气管镜灌洗或刷检标本抗酸杆菌阴性患者320例的临床资料,根据患者是否患有肺结核分为两组,将纤维支气管镜标本涂片阴性肺结核患者178例纳入肺结核组,肺炎、肺癌等疾病患者142例纳入其他肺部疾病组。比较两组患者ICRAs与结核菌素皮肤试验(TST)检测结果,比较两种检查的诊断价值。结果:肺结核组患者IGRAs与TST阳性率均高于其他肺部疾病组,差异有统计学意义(P<0.001)。IGRAs对抗酸杆菌涂片阴性肺结核诊断的敏感度、特异度、阳性预测值及阴性预测值均高于TST,差异有统计学意义(P<0.05)。结论:抗酸杆菌涂片阴性肺结核患者IGRAs与TST阳性检出率均高于其他肺部疾病患者,但IGRAs具有更高敏感度、特异度、阳性预测值与阴性预测值,诊断价值较高。

重组结核杆菌融合蛋白皮肤试验在肾透析患者诊断结核潜伏感染的应用价值

目的 评估重组结核杆菌融合蛋白(ESAT6-CFP10,EC)皮肤试验在肾透析患者中诊断结核潜伏感染的价值。方法 纳入某医院67例肾透析患者,同时接受结核菌素试验(the tuberculin skin test, TST)和γ-干扰素释放实验(interferon gamma release assay, IGRA),并以TST和Quanti FERON-TBgold(QFT,种IGRA方法)作为参照标准,衡量EC皮肤试验的灵敏度和特异度。结果 67例肾透析患者中,EC皮肤试验、TST、QFT阳性率分别为11.3%(7/62)、25.8%(16/62)、22.4%(15/67),差异无统计学意义(χ^(2)=4.051,P=0.105)。分别以TST、QFT、TST&QFT为参照标准,EC皮肤试验灵敏度分别为31.3%(95%CI:11.0%~58.7%)、50.0%(95%CI:23.0%~77.0%)、83.3%(95%CI:35.9%~99.6%),特异度分别为95.7%(95%CI:85.2%~99.5%)、100.0%(95%CI:92.6%~100.0%)、96.4%(95%CI:87.7%~99.6%)。结论 EC皮肤试验在肾透析患者中的结核潜伏感染诊断价值低于QFT,推荐使用QFT。

重组结核分枝杆菌融合蛋白皮肤试验与TST在学校结核潜伏感染筛查中的比较

目的 比较重组结核分枝杆菌融合蛋白皮肤试验(EC)与结核菌素皮肤试验(TST)两种检测方法的筛查效能及成本效益,探讨更适合学校结核潜伏感染的筛查方法。方法 选取2021年9月重庆市某中学高一新生共计283名,采用整群随机抽样方法分为EC组(138名)和TST组(145名),分别于左前臂皮内注射0.1 mL EC或0.1 mL TST,观察注射72 h后皮肤反应。皮肤试验前采集283名学生的静脉血,进行体外γ-干扰素释放试验(IGRA)检测,以IGRA检测结果为标准,分别计算EC、TST试验结果的灵敏度、特异度、漏诊率、一致率,并分析三者的成本效益。结果 EC的灵敏度、特异度、漏诊率、一致率分别为54.55%、93.70%、45.45%、90.58%;TST的灵敏度、特异度、漏诊率、一致率分别为61.11%、81.10%、38.89%、78.62%。每检出1例结核分枝杆菌感染者,TST、EC、IGRA的检测成本分别为124.29、492.86、4 879.31元。结论 EC与IGRA检测结果一致性较好,较TST的特异度和一致率更高,检测成本效益较高,简便易行,有望成为学校结核分枝杆菌潜伏感染新的筛查方法。

结核菌素皮肤试验、干扰素释放酶联免疫法及核酸分子检测技术在结核病中的诊断价值

目的探讨结核菌素皮肤试验(TST)、干扰素释放酶联免疫法(TB-IGRA)及核酸分子检测(NAT)3种检测方法诊断结核病的价值及差异。方法选取2021年1-12月海口市人民医院(中南大学湘雅医学院附属海口医院)收治的206例疑似结核病患者,206例中确诊为结核病的106例患者为研究组(其中新收治患者17例,治疗1~2个月患者89例),其他肺部疾病患者100例为对照组。两组患者均进行了TST、TB-IGRA及NAT,以临床诊断结果为参考,分析这3种检测方式的临床应用价值。结果研究组3种检测方式阳性率均高于对照组,差异有统计学意义(P<0.05);与TST相比,研究组TB-IGRA、NAT的阳性率更高,对照组TB-IGRA、NAT的阳性率更低,差异有统计学意义(P<0.05);TB-IGRA、NAT检测新收治和治疗1~2个月患者结果无统计学意义(P>0.05);TB-IGRA、NAT符合率、敏感度、特异度、均高于TST检测,差异有统计学意义(P<0.05)。结论TB-IGRA、NAT结核病诊断符合率高,均具有较高的敏感度和特异度。

结核菌素试验对结核杆菌γ-干扰素释放试验检测结果的影响

目的探讨结核菌素试验对结核杆菌γ-干扰素释放试验(IGRAs)检测结果的影响。方法回顾性分析2019年11月至2020年10月于本院确诊为肺结核或者结核性胸膜炎的191例住院患者的临床资料,根据入院前是否行结核菌素试验[结核菌素纯蛋白衍化物(PPD皮试)]分为实验组(n=66)与对照组(n=125),实验组入院前PPD皮试均为强阳性,对照组未行PPD皮试,比较两组IGRAs结果。结果共纳入确诊为结核病的患者191例,其中男120例,女71例;年龄13~84岁,平均(35.97±21.80)岁。实验组IGRAs阳性率为95.45%,高于对照组的70.4%,差异有统计学意义(P<0.05)。结论结核菌素刺激后可能会影响检测结果,增加IGRAs阳性率,建议在临床检测时抽血送检IGRAs后再行结核菌素皮试(TST)。

结核感染T细胞斑点试验对结核性腹膜炎的诊断价值

目的:评价结核感染T细胞斑点试验(T-SPOT.TB)对诊断结核性腹膜炎(tuberculous peritonitis,TBP)的价值。方法:前瞻性纳入疑诊结核性腹膜炎患者50例,进行外周血T-SPOT.TB、结核菌素纯蛋白衍生物(purifiedprotein derivatives of tuberculin,PPD)皮试、血清结核抗体、腹水腺苷脱氨酶(adenosine deaminase,ADA)检测,并比较4种方法的诊断价值。结果:根据诊断及分组标准,最终诊断TBP 24例,非结核性腹膜炎17例,无法确定者9例,外周血T-SPOT.TB、PPD皮试、血清结核抗体、腹水ADA诊断TBP的灵敏度分别是91.7%(22/24),37.5%(9/24),16.7%(4/24),36.4%(8/22);特异度分别是76.5%(13/17),70.0%(7/10),78.6%(11/14),100%(14/14);阳性预测值分别是84.6%(22/26),75.0%(9/12),57.1%(4/7),100.0%(8/8);阴性预测值分别是86.7%(13/15),31.8%(7/22),35.5%(11/31),50.0%(14/28)。T-SPOT.TB灵敏度及阴性预测值与后3种方法比较,差异均有统计学意义(均P<0.05)特异度及阳性预测值与后3种方法比较,差异均无统计学意义(均P>0.05)。结论:外周血T-SPOT.TB对诊断TBP具有较高的灵敏度及阴性预测值,对疑诊结核性腹膜炎的患者进行快速而准确的诊断具有重要的参考价值。