结核分枝杆菌潜伏性感染诊断的潜在标志物蛋白研究

目的 比较结核分枝杆菌标准株与休眠株蛋白质组差异表达情况,探讨结核潜伏性感染相关的诊断标志物.方法 选取结核分枝杆菌标准株H37 Rv和由标准株诱导的潜伏性感染菌株模型(休眠株)的样本,每个样本各培养3皿.对2组样本中的菌株进行裂解并抽提蛋白,进行同位素标记相对和绝对定量(iTRAQ)检测与分析,获得标准株与休眠菌株中相关蛋白质组的表达数据,并利用蛋白富集、信号通路分析等生物信息学技术将差异蛋白进行分类,进一步确定参与能量代谢通路的相关蛋白.结果 所检测的187个蛋白质中,64个蛋白质具有差异性表达,其中40个蛋白质表达上调,24个蛋白质表达下调.P9WPC9蛋白在休眠菌株与标准株中表达量比较,差异有统计学意义(P＜0.05).结论 P9WPC9蛋白主要参与细菌的能量代谢通路,可能成为结核潜伏性感染的潜在诊断标志物.     

3种检测方法在不同人群结核潜伏性感染诊断中的应用价值

目的研究云南地区不同人群结核潜伏性感染(LTBI)情况,并对相应的检测方法进行比较。方法采用两种结核分枝杆菌相关γ-干扰素(IFN-γ)检测试剂盒(TB-IGRA和T-SPOT.TB)检测云南地区不同人群[人类免疫缺陷病毒(HIV)感染者/艾滋病(AIDS)患者121例、医务人员63例和健康体检者50例]的结核分枝杆菌抗原特异性IFN-γ反应水平,并同时对各组人群进行结核菌素试验皮试(PPD皮试),比较3种方法的结果差异。结果所有研究对象PPD、T-SPOT.TB及TB-IGRA检测的阳性率分别为24.4%、21.8%、21.8%,差异无统计学意义(χ^2=0.585,P>0.05);应用PPD进行检测,医务人员的阳性率高于HIV感染者/AIDS患者、健康体检者,差异有统计学意义(P<0.05)。结论综合应用T-SPOT.TB、TB-IGRA、PPD能够有效指导不同人群LTBI的早期诊断。     

利福平联合吡嗪酰胺治疗潜伏性结核感染会引发危及生命的严重肝损

20世纪80年代起,由于AIDS流行等原因,结核疫情开始回升。为了降低高危人群中活动性结核菌感染的患病率,医学界建议对高危人群的潜伏性结核感染(latent tuberculo- sis infection,LTBI)进行治疗。     

结核感染T细胞斑点试验在血液病合并结核中的诊断价值

目的评价结核感染T细胞斑点试验（T-SPOT．TB）在血液病合并结核感染患者中的诊断价值。方法应用T-SPOT．TB对2012年3月-2013年4月间收治的82例结核感染待排的血液病患者外周血标本进行检测。结果T．SPOT．TB检测对于血液病患者合并结核感染的阳性检出率为59．09％（13／22）,明显高于结核抗体检测的13．64％（3／22）,P〈0．05。T-SPOT．TB检测血液病患者合并结核感染的灵敏度和特异度分别为59．09％（13／22）、68．33％（41／60）,灵敏度优于结核抗体检测（P〈0．05）。结论T-SPOT．TB检测对于血液病患者合并结核感染具有较大的辅助诊断价值,对于确诊结核感染阳性患者的诊断价值大于确诊结核感染阴性患者的诊断价值,临床上可作为血液病患者合并菌阴结核感染的辅助诊断。     

结核感染T细胞检测在结核病诊断中的临床意义

目的分析结核感染T细胞检测在结核病诊断中的临床意义。方法选取我院2015年3月~2016年4月收治的250例疑似结核病患者,患者均给予结核感染T细胞检测、聚合酶链式反应(PCR)荧光探针检测及涂片抗酸染色检测,比较三种检测方法检出结核病的阳性率。结果 165例患者最后确认为结核病,结核感染T细胞检出的阳性率分别显著高于PCR荧光探针检测和涂片抗酸染色检测(P0.05),且PCR荧光探针检测的阳性率显著高于涂片抗酸染色检测(P0.05)。结论应用结核感染T细胞检测来诊断结核病,能有效提高临床检测阳性率,其具备了临床推广的价值。     

结核感染T细胞酶联免疫斑点试验对结核诊断价值的Meta分析

目的系统评价结核感染T细胞酶联免疫斑点试验（T-SPOT.TB）在结核诊断中的价值。方法通过计算机检索CNKI、万方、维普、生物医学文献数据库、PubMed等数据库,获得关于T-SPOT.TB诊断结核的诊断性试验的文献,提取四格表等信息,采用MetaDisc1.4和Stata12.0软件进行统计学分析。结果共9篇文献纳入,各研究间存在明显阈值效应引起的异质性,拟合SROC曲线,计算AUC=0.95,Q指数为0.89。试剂盒来源是引起阈值效应的可能原因,以Oxford（UK）提供的试剂盒为亚组进行分析,汇总灵敏度和特异度分别为0.91[95%CI（0.87-0.94）],0.91[95%CI（0.87-0.94）],阳性似然比和阴性似然比分别为11.09[95%CI（7.12-17.28）]和0.10[95%CI（0.07-0.15）],诊断比值比（OR）为110.97[95%CI（57.67-213.52）];合并均无显著异质性（I2均〈50%,P均〉0.05）。Begg’s检验发现不存在发表偏倚。结论T-SPOT.TB对诊断结核有较高的诊断效能,可以帮助临床实践。     

利福平联用吡嗪酰胺治疗潜伏性结核有肝毒性高风险

美国田纳西州Vanderbilt大学医学院的Dr．David H Priest报告，即使是间断性用药并进行了仔细监测，但利福平和吡嗪酰胺(RZ)治疗潜伏性结核感染仍存在令人难以接受的发生肝毒性的高风险。     

结核感染T细胞试验在儿童结核病临床诊断中的应用研究

目的对比研究结核感染T细胞试验（T-SPOT.TB）在儿童结核病临床诊断中的应用价值。方法选取2012年3月-12月汕头市结核病防治所门诊和汕头大学医学院第二附属医院儿科就诊的结核病患儿112例、非结核病（有其他肺部疾病）患儿58例、结核病易罹患高危者60例、健康儿童60例,分别进行T-SPOT.TB、结核菌素纯蛋白衍生物皮肤试验（PPD皮试）、结核抗体检测（TB-DOT）、痰涂片抗酸染色、痰结核分枝杆菌培养,比较其灵敏度和特异度。同时对儿童结核病组按痰菌结果、病变部位、免疫状态不同进行分组比较。结果在儿童结核病组,T-SPOT.TB的阳性率为92.9%,高于其他方法,差异有统计学意义（χ^2=9.33,P〈0.01;χ^2=81.71,P〈0.01;χ^2=142.00,P〈0.01;χ^2=101.71,P〈0.01）;在非结核病组,T-SPOT.TB的假阳性率为3.4%,较痰涂片、痰培养稍高,与TB-DOT对比无异,但明显低于PPD的27.6%（χ^2=12.89,P〈0.01）;在结核病易罹患高危组,T-SPOT.TB的检出率为25.0%,高于TB-DOT、痰涂片及痰培养（P〈0.05）;在健康对照组,T-SPOT.TB的特异度为95.0%,高于PPD皮试的71.7%（χ^2=11.76,P〈0.01）。T-SPOT.TB在菌阴和菌阳、肺内和肺外结核、正常免疫和免疫缺陷组均具有良好的灵敏度（P〉0.05）。T-SPOT.TB与PPD皮试结果总符合率为78.6%。结论 T-SPOT.TB在儿童结核病的诊断中具有较高的灵敏度和特异度,且受其他因素影响较小,其结果客观、准确,对儿童结核病的诊断具有较高的临床应用价值。     

预防护理人员院内结核感染

近年来结核病的死灰复燃直接威胁着医务人员特别是护理人员的健康,对结核的感染现状、护理人员结核发病情况,引起护理人员结核感染的原因及其预防措施进行了综述。     

Adherence to latent tuberculosis infection therapy among latino immigrants

BACKGROUND: One third of the world population is infected with Mycobacterium tuberculosis. In the United States, a key component for eliminating tuberculosis (TB) is treating latent TB infection (LTBI) in high-risk persons such as immigrants. OBJECTIVE: Examine the prevalence of adherence to LTBI therapy and the influence of basic conditioning factors on adherence among Latino immigrants, guided by Orem's Self-Care Deficit Theory. Adherence was treated as a health deviation self-care requisite; the self-care practice of taking daily medication for 9 months is essential to LTBI adherence. Conditioning factors include gender, age, sociocultural factors, environment, and health state. DESIGN: Exploratory, cross-sectional. SAMPLE: Nonprobability sample (n=53) of Latino immigrants attending an urban public health clinic in the Washington, DC metropolitan area. METHODS: Participants completed a brief questionnaire documenting selected conditioning factors, and 9-month adherence to LTBI therapy was determined from their medical records. RESULTS: Adherence dropped from 98% in month 2 to 72% at 9 months. The mean number of months adherent was 7.4. Adherence was not significantly associated with gender, country of origin, languages spoken, age, education, or years in the United States. Adherence was slightly lower (t=2.059, p=.059) in persons who knew someone with TB. CONCLUSIONS: Nurses should emphasize the importance of adherence for the full 9 months to this population.     

Treatment of tuberculosis infection in children

Introduction: Identifying and treating children with tuberculosis (TB) infection in both low and high-TB burden settings will decrease the incidence of TB disease worldwide.

Areas covered: This review covers each of the available TB infection treatment options for children based on effectiveness, safety, tolerability and treatment completion rates. Six to 9 months of daily administered isoniazid is no longer the treatment of choice for many children with TB infection. Shorter, rifamycin based, TB infection treatment regimens are effective, safe and easier for children to complete. Fluroquinolone-based regimens are recommended for the treatment of children infected by a source case with drug-resistant TB. Directly observed therapy (DOT) programs improve childhood TB infection treatment completion rates.

Expert commentary: As shorter, rifamycin-based, TB infection treatment regimens offer superior treatment success rate in both adults and children; the widespread use of these regimens has huge potential to decrease the burden of TB disease worldwide. The implementation of these programs will involve improving patient access to the medications, decreasing their cost to the patient, and the use of novel electronic methods to document patient treatment completion.     

Screening and treatment of latent tuberculosis infection among HIV-infected patients in resource-rich settings

Current international guidelines recommend screening and treatment of latent tuberculosis (TB) infection in HIV-infected patients in all settings. The main factors affecting the risk of TB in HIV-infected patients include the level of immunosuppression, coverage of antiretroviral therapy and local TB burden. In resource-rich settings where antiretroviral therapy is more accessible and HIV-infected patients are expected to be diagnosed at an earlier stage, local TB burden remains a key factor on their risk of TB. This article reviewed the epidemiology of latent TB infection among the adult HIV-infected patients, and the use and benefit of screening and treatment of latent TB infection in resource-rich settings in the past decade. While such practice should be continued in countries with medium or high TB burden, targeted screening and treatment only for HIV-infected patients with additional risk factors for TB might be a more practical option in resource-rich countries with low TB burden.     

Optimizing the management of children with latent tuberculosis infection

Introduction: The management of latent tuberculosis (LTBI) in children represents an important issue for paediatricians because of the disease burden, the lack of a gold standard for the diagnosis and the high annual risk of progression to active disease.

Areas covered: A review of English language articles on LTBI in children, published between the 1st of January 2010 and the 1st of July 2016, was conducted using multiple keywords and standardized terminology in PubMed database. This review provides an updated overview of the available tests for LTBI diagnosis in children, management strategies and treatment options.

Expert commentary: Two tests are available for LTBI diagnosis: tuberculin skin test and interferon-gamma release assays, both with a suboptimal specificity and sensitivity, and both with the lack of capability in distinguishing between infection and disease. Several new markers have been identified but further studies are needed. Among all treatment regimes, because of the high safety and efficacy profile showed and to avoid the poor completion rate, the treatment with a three-month course of isoniazid and rifampicin is currently recommended. New vaccines are needed because of the spread of the disease despite BCG vaccination in high risk countries. Currently, 15 new vaccines are in the pipeline.     

酶联免疫斑点法诊断结核感染的阈值

目的：分析确定本实验室条件下酶联免疫斑点法（enzyme-linked immunospot assay,ELISPOT）诊断结核感染的阈值以及活动性结核与非活动性结核外周血 ELISPOT 分界阈值。方法对确诊为活动性结核病患者、经有效抗结核治疗后非活动性结核患者和健康者进行 ELISPOT 检测。结果以早期分泌抗原靶6000蛋白（early secretary antigenic target 6000 protein,ESAT-6）作为刺激源时,外周血 ELISPOT 诊断结核感染的阈值为26斑点形成细胞（SFCs）／106,敏感度90．3％,特异度88．7％,阳性预测值82．3％,阴性预测值94．0％;以培养滤液10000蛋白（culture filtrate protein,CFP-10）作为刺激源时诊断阈值为18 SFCs／106,敏感度80．6％,特异度86．8％,阳性预测值78．1％,阴性预测值88．4％,两种抗原 ELISPOT 斑点形成细胞之和为441 SFCs／106时,其诊断活动性结核感染敏感度为87．1％,特异度为80．6％。结论在本实验室条件下 ESAT-6-ELISPOT 诊断结核感染的阈值为26 SFCs／106, CFP-10-ELISPOT 诊断结核感染的阈值为18 SFCs／106,该阈值诊断结核感染的敏感度较高,但特异度较结核低流行国家偏低;以 ESAT-6和 CFP-10两种抗原 ELISPOT 斑点形成细胞之和441 SFCs／106作为鉴别活动性结核与非活动性结核的阈值,可以为临床工作提供参考。     

A proteomics approach to the identification of plasma biomarkers for latent tuberculosis infection

A proteomic analysis was performed to screen the potential latent tuberculosis infection (LTBI) biomarkers. A training set of spectra was used to generate diagnostic models, and a blind testing set was used to determine the accuracy of the models. Candidate peptides were identified using nano-liquid chromatography-electrospray ionization–tandem mass spectrometry. Based on the training set results, 3 diagnostic models recognized LTBI subjects with good cross-validation accuracy. In the blind testing set, LTBI subjects could be identified with sensitivities and specificities of 85.20% to 88.90% and 85.7% to 100%, respectively. Additionally, 14 potential LTBI biomarkers were identified, and all proteins were identified for the first time through proteomics in the plasma of healthy, latently infected individuals. In all, proteomic pattern analyses can increase the accuracy of LTBI diagnosis, and the data presented here provide novel insights into potential mechanisms involved in LTBI.     

Is interleukin-2 an optimal marker for diagnosing tuberculosis infection? A systematic review and meta-analysis

Abstract

Background

Latent tuberculosis infection (LTBI) is a huge reservoir for the deadlier TB disease. Accurate identification of LTBI is a key strategy to eliminate TB. Therefore, a systematic review and meta-analysis approach was used to assess diagnostic potential of IL-2 for LTBI.     

结核感染T细胞斑点试验诊断肺结核临床价值探讨

目的对比结核感染T细胞斑点试验(T-SPOT.TB)、皮肤结核菌素试验、结核抗体和痰液或肺泡灌洗液涂片4种方法诊断肺结核的结果,选择临床最有价值的诊断方法。方法选择湖北省襄阳市中医院2010年12月至2012年12月非结核呼吸系统疾病患者48例和同期明确诊断为结核的患者42例为研究对象。对所有患者进行T-SPOT.TB、皮肤结核菌素试验、结核抗体和痰液或肺泡灌洗液涂片,计算并比较各种检查阳性率、敏感度和特异性。结果 T-SPOT.TB的结核抗体敏感性和特异性均高于皮肤结核菌素和痰液及肺泡灌洗液涂片,且具体数值相同;通过两两比较发现,T-SPOT.TB的阳性率均明显高于其他3种试验方法(P<0.05)。结论 T-SPOT.TB诊断结核具有很好的稳定性,值得临床推广使用。