高危医务人员潜伏性结核感染的实验室检测指标分析

目的通过对结核病高危医务人员的结核菌感染状况进行筛查,以了解分析结核病高危医务人员潜伏性结核感染的现状。方法对高危医务人员组、相关实验室人员组和普通人群对照组分别进行结核菌素试验和γ干扰素释放试验的检测。结果高危医务人员组、相关实验人员组、普通人群对照组之间的结核菌素试验阳性率比较差异无显著性(P0.05);高危医务人员组结核菌素实验的强阳性率显著高于普通人群对照组(P0.05);高危医务人员组和相关实验人员组γ干扰素释放试验的阳性率均显著高于普通人群对照组(P0.05)。结论高危医务人员及相关实验室人员受结核分枝杆菌潜伏感染的危险性高,需要提高认识,预防医院感染。     

关口前移:再谈结核分枝杆菌潜伏感染管理和暴露后干预

关口前移是落实预防为主防控策略的重要举措,除了主动发现和早诊早治以外,针对肺结核患者的密切接触者、HIV感染者等高危人群开展结核分枝杆菌潜伏感染检测和预防性治疗也是实现"终止结核病策略"的重要手段。近些年,我国积极响应世界卫生组织(WHO)号召,在结核病管理工作的关口前移上取得了显著进展:2019年《遏制结核病行动计划(2019—2022年)》提出了结核病筛查的重点人群[1];2020年《中国结核病预防控制工作技术规范(2020版)》明确了结核分枝杆菌潜伏感染预防性治疗的目标人群和技术方案[2]。     

重组结核分枝杆菌感染鉴别用变态反应原研究与应用

<正>自1890年科赫发明用于结核病免疫治疗的结核菌素(tuberculin),1907年奥地利人V.Pirquet将结核菌素作为结核病诊断试剂以来[1],产品也从滤液蛋白粗提物改进为结核分枝杆菌纯蛋白衍生物(purified protein derivative,PPD),在结核菌素用于结核菌素皮肤试验(tuberculin skin test,TST)逾百年后的今天,该类产品依然在结核病辅助诊断、流行病学调查,以及卡介苗接种阳转考核中发挥着巨大作用。随着结核病疫情的变化,早在2002年我国研究者已经发现"靠单纯DOTS的现代结核病控制策略,无法解决已经感染结核分枝杆菌人群发展为     

结核菌素及非典型分枝杆菌素的研究及应用

随着结核病在防治效果上的显著进展,以及非典型分枝杆菌在人群中感染与致病问题日渐突出,在结核病的流行病学调查中,对结核菌素和分枝杆菌素的研究与应用也有了一些新的发展与新的问题,现将了解的一些情况,综述如下。结核菌素的研究与进展结核菌素是结核皮肤试验的抗原物质,早在1890     

结核分枝杆菌潜伏性感染及预防性治疗研究进展的系统评价

目的 描述及评价结核分枝杆菌潜伏性感染及预防性治疗的研究进展。方法 由主题专家和检索人员讨论后确定检索词,共检索7个数据库,3个卫生机构网站和搜索引擎Google Scholar,纳入描述或评价结核分枝杆菌潜伏性感染及预防性治疗的方案、效果等相关的文章,对文章信息进行提取。初检得到573条记录,最终纳入17篇文献,其中纳入文献中有4篇描述了不同国家的结核分枝杆菌感染情况;2篇为美国疾病预防控制中心发布的指南,论述了潜伏感染的诊断标准;11篇对潜伏性感染的预防性治疗方案进行了研究及评价。 结果 美国全人群结核分枝杆菌感染率为4.2%,加拿大不列颠哥伦比亚省非原住民的感染率为14.2%,阿富汗8省调查结果为15.0%,中国2000年全国结核病流行病学抽样调查结果表明,全年龄组结核分枝杆菌感染率为44.5%（美国、加拿大、阿富汗三国以结核菌素皮肤试验硬结平均直径≥10 mm为阳性标准,中国以硬结平均直径≥6 mm为阳性标准）。结核分枝杆菌潜伏性感染者的诊断,依据既往结核病史、结核菌素皮肤试验或γ干扰素释放试验结果、胸部X线检查、体格检查等信息综合考量。结核分枝杆菌潜伏性感染的治疗效果,不同预防性治疗方案的效果差异较大,保护率0%～61%不等,完成率43%～90%不等,不良反应发生率0%～10%不等。结论 尽管结核病控制工作的重点是通过发现和治愈传染源达到控制结核病传播的目的。然而,对结核分枝杆菌潜伏性感染人群开展预防性治疗也将成为一项重要的结核病控制措施。     

山东省某监狱劳教人员结核病筛查结果分析

目的掌握山东省某监狱某监区劳教人员结核病的传播流行以及潜伏结核感染情况。方法对某监区314名劳教人员进行了结核病筛查,筛查者同时作胸透、HIV试验、结核菌素试验、ELISPOT试验,并对每个人进行了有关资料调查,对筛查人群中有咳嗽咳痰症状者以及已确诊的结核病患者,进行分枝杆菌培养,培养阳性的分枝杆菌进行菌种鉴定和药物敏感试验,结核分枝杆菌进行基因分型。结果314名筛查者HIV结果全部为阴性;3例分枝杆菌培养阳性都是结核分枝杆菌,A患者分离的结核杆菌是非北京家族,B患者和C筛查者分离的结核杆菌是北京家族,菌株成簇,312人同时有2种试验T-SPOT.TB试验阳性率为27.9%,PPD反应硬结平均直径≥10mm,阳性率为81.7%,2种试验结果的符合率为42.3%（95%CI,36.8%～47.8%）。结论以T-SPOT.TB试验结果阳性为结核感染的参考标准,该监区潜伏结核感染率为27.6%（86/312）;结核病患病率为0.93%;结核病人部分是内源性复燃引起,部分是在狱内由于新近感染结核菌而引起,监狱内结核病存在局部范围内的传播,该监区在结核病治疗、预防和控制工作方面需要进一步采取措施。     

中国结核潜伏感染管理需要探索一条适宜高负担国家的新路径

基于国外的成功经验,世界卫生组织号召在全球范围内推广结核潜伏感染高危人群的预防干预,以实现结核病发病率快速下降的目标。但是,目前我国结核病的流行特征还基本不清晰,尚未形成成熟的系统性干预策略。国外研究估计中国约有3.5亿人感染结核分枝杆菌,是全球结核潜伏感染负担最重的国家。中国需要根据国情探索一条适宜高负担国家的结核病防控体系,包括潜伏感染管理。目前我国针对HIV感染者、学生密切接触者、免疫抑制剂使用者等部分高危人群发布了结核潜伏感染检测和(或)预防性治疗相关的工作规范、技术指南和专家共识等.     

重组结核杆菌融合蛋白(EC)临床应用专家共识

中国是结核病高负担国家之一,结核病发病例数与潜伏性结核感染(latent tuberculosis infection,LTBI)人数庞大,给我国结核病防控工作带来了巨大的挑战。有效识别结核病和LTBI对控制结核病疫情有重要意义。菌阴肺结核和LTBI的诊断依赖于结核感染的免疫学诊断方法;现行结核感染免疫学检测方法主要是结核菌素皮肤试验(tuberculin skin test,TST)、γ干扰素释放试验(interferon gamma release assays,IGRA)和抗原抗体检测。在现行的三类方法基础上,研发出了敏感度高、特异度强、试验操作简单、可用于LTBI和结核病诊断的新产品和新技术——重组结核杆菌融合蛋白(EC)[该制品名称是国家药典委员会确定的药品中文通用名称,“EC”为重组融合蛋白“结核分枝杆菌早期分泌性抗原靶6(ESAT-6)和培养滤液蛋白10(CFP-10)”](简称“EC”)。目前,已完成EC的Ⅰ、Ⅱ和Ⅲ期临床试验。其中Ⅲ期临床试验中对1559名健康人群的筛查中发现,EC与IGRA的检测结果具有较高的特异度,且两者之间具有较高的一致性(88.77%);对791例临床诊断为结核病患者的临床研究发现,EC、结核感染T淋巴细胞斑点试验(T-SPOT.TB)、结核菌素纯蛋白衍生物(TB-PPD)检测均具有良好的敏感度,且三者之间具有较高的一致性;对479名未感染结核分枝杆菌人员的研究发现,EC与T-SPOT.TB的两次检测阴性一致率较高(88.20%和93.17%);在卡介苗接种对检测结果影响的研究中发现,EC和T-SPOT.TB基本不受卡介苗的影响;对394例临床诊断非结核性疾病患者的临床研究发现,EC与T-SPOT.TB阴性符合率较高,且一致性较好(87.21%)。基于EC在用于诊断结核感染安全且有效的基础上,EC通过了国家药品监督管理局药品审批而准予上市。经广泛征求有关结核病防控、临床和研究等领域的专家意见,在系统总结相关技术和方法的应用特点的基础上,结合EC的临床试验结果,形成了EC临床应用的专家共识。本共识介绍了EC的临床应用建议,包括使用对象、使用方法、结果判读,以及临床意义和使用范围。     

全国结核分枝杆菌潜伏感染率估算专家共识

针对结核分枝杆菌潜伏感染高危人群开展预防性治疗是降低结核病发病率的直接手段,也是实现终结结核病流行(End TB)全球战略目标的重要组成部分。作为结核病高负担国家,我国如何通过开展结核分枝杆菌潜伏感染人群的预防干预,实现结核病发病率快速下降的目标,值得探讨。其中,准确掌握我国的结核分枝杆菌潜伏感染负担和流行特征是讨论策略可行性和科学性的前提。在缺乏全国范围的结核分枝杆菌潜伏感染流行病学调查的背景下,中国医学科学院病原生物学研究所和中国疾病预防控制中心联合中国科学院地理科学与资源研究所,以全国结核病报告发病率为辅助变量,利用多中心的基于γ-干扰素释放试验检测的结核分枝杆菌潜伏感染流行病学调查数据和小样本空间统计模型,开展了全国结核分枝杆菌潜伏感染率的估算。结果显示,2013年我国5周岁及以上人群结核分枝杆菌潜伏感染率为18.1%(95%CI:13.7%~22.4%);15周岁及以上人群结核分枝杆菌潜伏感染率为20.3%(95%CI:15.6%~25.1%),呈现随着年龄升高而增长的趋势,同年龄段内男性高于女性。领域内专家针对估算结果进行了广泛论证并形成了《全国结核分枝杆菌潜伏感染率估算专家共识》,以供我国结核病防治工作者借鉴和参考。     

儿童结核病的实验室诊断现状与进展

儿童结核病是全球结核病防控工作的重要组成部分,诊断儿童结核病主要依靠实验室检查结果,但由于儿童结核病本身和标本的特殊性,实验室准确、快速地诊断儿童结核病仍面临挑战。病原学诊断作为儿童结核病诊断的金标准,其敏感度不佳;以超敏结核分枝杆菌和利福平耐药基因检测(Xpert MTB/RIF Ultra)为代表的新型分子生物学检测技术因其较高的敏感度和较短的检测时间有其应用前景;结核菌素皮肤试验(TST)被WHO推荐用于中低收入国家;直接抗原检测技术在少菌、肺外结核标本中敏感度高,在儿童结核病的检测中具有独特价值;其他免疫学新方法对于区分潜伏和活动性结核感染方面具有重要意义;此外,目前已有检测结核分枝杆菌感染后基因表达、蛋白质产生和生物标志物变化的新方法投入研究。留取多份标本或不同标本类型、不同检测方法联合检测有助于提高儿童结核病的检出率。提高结核病在现有方法和非侵入性、易获取标本中的检出率,以及评估新的生物标志物和新技术的适用性是未来儿童结核病实验室诊断研究的方向。     

Suttons’s Law: Local Immunodiagnosis of Tuberculosis

Recently, important advances have been made in the immunodiagnosis of tuberculosis. New T cell interferon-γ release assays (TIGRA) are more specific and more sensitive than the tuberculin skin test (TST) for the diagnosis of Mycobacterium tuberculosis (MTB) infection. However, like the TST, TIGRA are unable to distinguish between active tuberculosis (TB), latent TB infection (LTBI) and treated TB if performed on blood mononuclear cells alone. In active TB, MTB-specific T cells are actively recruited to the site of infection and can rapidly be identified in extrasanguinous fluids, such as pleural effusions, ascites, cerebrospinal fluid, and in bronchoalveolar lavages. This review summarizes recent findings comparing systemic and local immune responses against MTB. Although bacteriological and histological methods have the highest specificity for TB in terms of diagnosing active TB and the number of TB patients in whom extrapulmonary TIGRAs have been evaluated is still limited, a comparison of local and systemic MTB-specific immune responses is a promising technique to rapidly distinguish active TB from latent MTB infection in routine clinical practice.     

Innate and adaptive immune responses during acute M. tuberculosis infection in adult household contacts in Kampala, Uganda

Contacts of active pulmonary tuberculosis (TB) patients are at risk for Mycobacterium tuberculosis (MTB) infection. Because most infections are controlled, studies during MTB infection provide insight into protective immunity. We compared immune responses of adult household contacts that did and did not convert the tuberculin skin test (TST). Innate and adaptive immune responses were measured by whole blood assay. Responses of TST converters (TSTC) were compared with persistently TST negative contacts (PTST-) and contacts who were TST+ at baseline (TST+). TLR-2, TLR-4, and IFN-γR responses to IFN-γ did not differ between the groups, nor did γδ T cell responses. T cell responses to MTB antigens differed markedly among TSTC, PTST-, and TST+ contacts. Thus, no differences in innate responses were found among the three household contact groups. However, adaptive T cell responses to MTB antigens did differ before and during MTB infection among PTST-, TSTC, and TST+ contacts.     

A multicenter evaluation of tuberculin skin test positivity and conversion among health care workers in Brazilian hospitals.

SETTING: Four general Brazilian hospitals. OBJECTIVE: To assess the occupational risk of Mycobacterium tuberculosis (TB) in participating hospitals. DESIGN: In phase one of this longitudinal study, a cross-sectional survey documented baseline tuberculin skin test (TST) positivity rates. In phase two, TST conversion rates were evaluated in participants with an initial negative two-step TST. TST conversion data were analyzed to determine risk factors for TB infection using an increase of > or = 10 mm compared to baseline TST. RESULTS: The initial TST positivity rate was 63.1%; the follow-up TST conversion rate was 10.7 per 1000 person-months (p-m). Hospital of employment, recent bacille Calmette-Guerin (BCG) vaccination, nosocomial TB exposure, and employment as a nurse were independent risk factors for TST conversion. Hospitals without TB infection control measures had higher conversion rates than those with control measures (16.0 vs. 7.8/ 1000 p-m, P < 0.001). CONCLUSIONS: This study indicates an important occupational risk of infection in health care settings with a high TB incidence. Longitudinal TST studies are a valuable tool to assess the occupational risk of TB, even in BCG-vaccinated populations, and should be used to direct limited resources for infection control.     

Comparison of the Interferon-Gamma Release Assay With the Traditional Methods for Detecting Mycobacterium tuberculosis Infection in Children

The purpose of the article is to compare the whole blood interferon-γ release assay (IGRA) with the traditional methods for detecting Mycobacterium tuberculosis (MTB) infection in children.Fifteen childhood patients with tuberculosis and 15 healthy children were recruited. Sputa samples and venous blood were collected, and according to different procedures, IGRA, sputum smear, colloidal gold assay (CGA), fluorescence quantitation polymerase chain reaction (FQ-PCR), and tuberculosis skin test (TST) were, respectively, performed. Thirty healthy children vaccinated with Bacillus Calmette–Guérin (BCG) were also recruited, and the comparative test was carried out between IGRA and TST.In all of 15 childhood patients with TB, the positive rates were 86.7%, 20.0%, 26.7%, 40%, and 66.7% in IGRA, sputum smear, CGA, FQ-PCR, and TST, respectively. In the children vaccinated with BCG, the positive rate of IGRA was significantly lower than that of TST (6.7% vs 76.7%). From high to low, the specificities of the five methods were sputum smear (100%), IGRA (86.7%), FQ-PCR (86.7%), TST (40%), and CGA (26.7%). Although the specificities of sputum smear and FQ-PCR were more than or equal to that of IGRA, the relative sensitivities limited their applications in populations of children.IGRA is a sensitive and specific method, and could be taken as a first choice for detecting MTB infection in populations of children.     

Use of an interferon-gamma release assay to diagnose latent tuberculosis infection in foreign-born patients

BACKGROUND: The tuberculin skin test (TST) has a low specificity in the setting of bacille Calmette-Guérin (BCG) vaccination. Interferon-gamma release assays (IGRAs) appear to be more specific but have not been validated in this population under routine clinical conditions. We sought to validate the routine clinical use of the T-SPOT.TB test (Oxford Immunotec; Oxford, UK), an IGRA, in a predominantly foreign-born population with a high rate of BCG vaccination. METHODS: We compared the TST and the T-SPOT.TB test in 96 subjects at a New York City Department of Health tuberculosis clinic. We aimed to determine which test better predicted being a close contact of a case of active tuberculosis, a surrogate for latent tuberculosis infection. RESULTS: A positive T-SPOT.TB test result was strongly associated with being a close contact of a case of active tuberculosis after adjustment for potential confounders (adjusted odds ratio, 2.9; 95% confidence interval, 1.1 to 7.3; p = 0.03). A positive TST result was associated with being a contact only in subjects without BCG vaccination (p = 0.02). The T-SPOT.TB test was more specific for being a close contact than the TST (p < 0.001). Specificity in BCG-vaccinated subjects was 3% for the TST compared with 70% for the T-SPOT.TB test (p < 0.001). CONCLUSIONS: The T-SPOT.TB test is superior in routine clinical use to the TST for identifying high-risk individuals among foreign-born populations with high rates of BCG vaccination.     

False-positive rifampicin resistance on Xpert? MTB/RIF: case report and clinical implications

The World Health Organization had endorsed Xpert? MTB/RIF (Xpert) as the initial diagnostic for multidrug-resistant tuberculosis (TB) or TB suspects co-infected with the human immunodeficiency virus. We investigated an unexpected case of rifampicin (RMP) resistance on Xpert using repeat Xpert, smear microscopy, MTBDRplus assay, culture, drug susceptibility testing, spoligotyping and rpoB gene sequencing. A false-positive result was most likely, given the wild type rpoB gene sequence and exclusion of both mixed infection and mixture of drug-susceptible and drug-resistant populations. When decentralising Xpert, test performance characteristics need to be understood by health care workers and methods of confirmation of RMP resistance need to be accessible.     

Comparison of T-Cell Interferon-γ Release Assays for Mycobacterium tuberculosis-Specific Antigens in Patients with Active and Latent Tuberculosis

Through the use of QuantiFERON-TB Gold, a commercial IFN-γ assay, we compared differences in quantitative T-cell responses to Mycobacterium tuberculosis (MTB)-specific antigens [QuantiFERON TB-2G (QFT-2G)] between patients with active tuberculosis (TB) disease and those with latent TB infection (LTBI). The patient group consisted of 180 patients with active TB disease (culture-positive for MTB) and 50 screening contacts with LTBI-positive response to the QFT-2G test. We prospectively performed a tuberculin skin test (TST) and a QFT-2G test for all subjects. The median IFN-γ levels upon the application of both antigens, ESAT-6 and CFP-10, were significantly higher in patients with active TB disease than in those with LTBI. A combined positive response to both antigens occurred at a higher rate in patients with active TB disease than in those with LTBI. There were no significant relationships between the quantitative responses of IFN-γ to both antigens and the maximum induration on TST in both patient groups. We demonstrated significant differences in the quantitative responses of IFN-γ to MTB between patients with active TB disease and those with LTBI in this study. However, there was an overlap in the IFN-γ levels between active TB disease and LTBI groups. Therefore, it would be difficult to use the QFT-2G test to completely discriminate active TB disease from LTBI.     

Effect of tuberculin skin testing on a Mycobacterium tuberculosis-specific interferon-gamma assay.

Recently, interferon-gamma release assays (IGRA) for specific diagnosis of Mycobacterium tuberculosis infection have become available. In recent UK tuberculosis (TB) guidelines, it has been advised to screen for latent M. tuberculosis infection using the tuberculin skin test (TST), followed by IGRA if the TST is positive. Since TST can boost immune responses to tuberculin, the present authors evaluated whether TST administration affects the result of QuantiFERON-TB Gold in-tube (QFT-GIT), a whole blood-based IGRA. QFT-GIT was performed on the day of TST administration and the day of reading in 15 TST-negative subjects, 46 TST-positive subjects with recent or remote exposure to M. tuberculosis and five cured TB patients. No systematic boosting of QFT-GIT responses from negative to positive was observed. Only in a few TST-positive persons did TST enhance pre-existing QFT-GIT responses. Screening for latent Mycobacterium tuberculosis infection using tuberculin skin testing followed by interferon-gamma release assays on the day of reading is a reliable approach, as the specificity of QuantiFERON-TB Gold in-tube is not affected by prior tuberculin skin test administration.     

Detection of latent tuberculosis infection in peritoneal dialysis patients: new methods

OBJECTIVE: The risk for tuberculosis (TB) is increased in patients with chronic renal failure and dialysis. Tuberculin skin test (TST) is the classical diagnostic method for screening despite its low sensitivity. New methods based on interferon-gamma have been developed. The aim of this study was to evaluate if Quantiferon? TB-gold In Tube (QFT-GIT) could be useful in the diagnosis of TB infection in patients on peritoneal dialysis (PD). Patients and methods: Fifty-four patients on PD were included in the study. They were evaluated for latent tuberculosis with QFT-GIT, TST and an assessment by an expert pulmonologist using patient's medical history and x-rays. Agreement between test results was determined. Results:The prevalence of a positive TST was 29.6% for the first test and 31.5% for the second (booster effect). A positive chest x-ray increased the rate of detection of patients with latent TB infection up to 42.6% and the expert physician's evaluation to 44.4%. The correlation between QFT-GIT and TST was fair (k=0.36; P=.006), as it was between TST and expert physician's evaluation (k=0.257; P=.06). CONCLUSIONS: According to our experience QFT-GIT represents an important advantage in the diagnosis of latent TB infection in chronic renal failure patients on PD. It may complement but not replace TST.