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目的探讨干扰素γ释放试验和结核菌素皮肤试验(PPD)在儿童结核病和潜伏结核感染诊断中的价值。方法检索1990年1月至2011年2月在PUBMED、MEDLINE、OVID、CNKI等数据库发表的有关文献,并追查相关文献的参考文献,对文献按照诊断试验的纳入标准进行筛选。采用敏感度和特异度作为诊断价值的评价指标。采用Meta-Disc1.4软件进行Meta分析。结果 QuantiFERON-TB GoldIn-Tube在确诊结核病和(或)临床诊断结核病患儿中的汇总敏感度为67%,在对照儿童中汇总特异度为91%;T-SPOT.TB在确诊结核病和(或)临床诊断结核病患儿中的汇总敏感度为57%,在对照儿童中汇总特异度为88%;PPD试验在确诊结核病和(或)临床诊断结核病患儿中的汇总敏感度为70%,在对照儿童中汇总特异度为43%。结论 PPD试验因受卡介苗接种的影响,特异度较低;而干扰素γ释放试验因不受卡介苗接种的影响而具有很高的特异度。干扰素γ释放试验可以有效筛查儿童潜伏结核感染,特别是在有卡介苗接种史及活动性密切接触史儿童中。     

免疫缺陷患儿合并结核分枝杆菌感染的临床特征分析

目的 探讨继发性免疫缺陷病（SID）及原发性免疫缺陷病（PID）患儿合并结核分枝杆菌感染的临床特征。方法 回顾性分析合并结核分枝杆菌感染的免疫缺陷患儿（SID组36例、PID组52例）及非免疫缺陷患儿（对照组108例）的临床资料。结果 PID组患儿起病年龄低于对照组和SID组（P < 0.05）,男性比例高于对照组和SID组（P < 0.05）。SID组及PID组患儿其他结核中毒症状（盗汗、消瘦、乏力、食欲下降）及PPD试验阳性率均低于对照组（P < 0.05）,且更易出现肺叶受累≥ 3叶（P < 0.05）。PID患儿更易合并多器官受累（P < 0.05）。SID组肺部粟粒影发生率高于对照组和PID组（P < 0.05）,PID组γ-干扰素释放试验阳性率低于对照组和SID组（P < 0.05）。结核分枝杆菌感染在SID组表现为潜伏结核感染（36.1%）和活动性结核病（63.9%）;在PID组以卡介苗病（90.4%）为主,有2例（3.8%）同时合并结核病。结论 免疫缺陷患儿合并结核分枝杆菌感染的临床症状不典型,易出现播散性感染,PPD试验及γ-干扰素释放试验阳性率较低,容易出现误诊及漏诊。免疫缺陷患儿应常规进行结核相关筛查,早期识别及干预以改善预后。     

免疫缺陷患儿合并结核分枝杆菌感染的临床特征分析

目的 探讨继发性免疫缺陷病（SID）及原发性免疫缺陷病（PID）患儿合并结核分枝杆菌感染的临床特征。方法 回顾性分析合并结核分枝杆菌感染的免疫缺陷患儿（SID组36例、PID组52例）及非免疫缺陷患儿（对照组108例）的临床资料。结果 PID组患儿起病年龄低于对照组和SID组（P < 0.05）,男性比例高于对照组和SID组（P < 0.05）。SID组及PID组患儿其他结核中毒症状（盗汗、消瘦、乏力、食欲下降）及PPD试验阳性率均低于对照组（P < 0.05）,且更易出现肺叶受累≥ 3叶（P < 0.05）。PID患儿更易合并多器官受累（P < 0.05）。SID组肺部粟粒影发生率高于对照组和PID组（P < 0.05）,PID组γ-干扰素释放试验阳性率低于对照组和SID组（P < 0.05）。结核分枝杆菌感染在SID组表现为潜伏结核感染（36.1%）和活动性结核病（63.9%）;在PID组以卡介苗病（90.4%）为主,有2例（3.8%）同时合并结核病。结论 免疫缺陷患儿合并结核分枝杆菌感染的临床症状不典型,易出现播散性感染,PPD试验及γ-干扰素释放试验阳性率较低,容易出现误诊及漏诊。免疫缺陷患儿应常规进行结核相关筛查,早期识别及干预以改善预后。     

结核病新疫苗研究概况

长期以来,结核病对人类健康构成了严重威胁.随着结核分枝杆菌全基因组测序工作的完成和有效抗原的不断发现,有关结核病新疫苗的研究进展迅速,多种结核病新疫苗已进入临床试验阶段.如何对已接种卡介苗人群、结核分枝杆菌隐性感染人群和免疫缺陷人群进行有效的接种是结核病新疫苗必须解决的问题.基础研究与动物实验、临床试验的相互印证有助于各项研究的深入及结核病新疫苗的改进和择选.     

结核病新疫苗研究概况

长期以来,结核病对人类健康构成了严重威胁.随着结核分枝杆菌全基因组测序工作的完成和有效抗原的不断发现,有关结核病新疫苗的研究进展迅速,多种结核病新疫苗已进入临床试验阶段.如何对已接种卡介苗人群、结核分枝杆菌隐性感染人群和免疫缺陷人群进行有效的接种是结核病新疫苗必须解决的问题.基础研究与动物实验、临床试验的相互印证有助于各项研究的深入及结核病新疫苗的改进和择选.     

结核病新疫苗研究概况

长期以来,结核病对人类健康构成了严重威胁.随着结核分枝杆菌全基因组测序工作的完成和有效抗原的不断发现,有关结核病新疫苗的研究进展迅速,多种结核病新疫苗已进入临床试验阶段.如何对已接种卡介苗人群、结核分枝杆菌隐性感染人群和免疫缺陷人群进行有效的接种是结核病新疫苗必须解决的问题.基础研究与动物实验、临床试验的相互印证有助于各项研究的深入及结核病新疫苗的改进和择选.     

结核病新疫苗研究概况

长期以来,结核病对人类健康构成了严重威胁.随着结核分枝杆菌全基因组测序工作的完成和有效抗原的不断发现,有关结核病新疫苗的研究进展迅速,多种结核病新疫苗已进入临床试验阶段.如何对已接种卡介苗人群、结核分枝杆菌隐性感染人群和免疫缺陷人群进行有效的接种是结核病新疫苗必须解决的问题.基础研究与动物实验、临床试验的相互印证有助于各项研究的深入及结核病新疫苗的改进和择选.     

结核病新疫苗研究概况

长期以来,结核病对人类健康构成了严重威胁.随着结核分枝杆菌全基因组测序工作的完成和有效抗原的不断发现,有关结核病新疫苗的研究进展迅速,多种结核病新疫苗已进入临床试验阶段.如何对已接种卡介苗人群、结核分枝杆菌隐性感染人群和免疫缺陷人群进行有效的接种是结核病新疫苗必须解决的问题.基础研究与动物实验、临床试验的相互印证有助于各项研究的深入及结核病新疫苗的改进和择选.     

结核病新疫苗研究概况

长期以来,结核病对人类健康构成了严重威胁.随着结核分枝杆菌全基因组测序工作的完成和有效抗原的不断发现,有关结核病新疫苗的研究进展迅速,多种结核病新疫苗已进入临床试验阶段.如何对已接种卡介苗人群、结核分枝杆菌隐性感染人群和免疫缺陷人群进行有效的接种是结核病新疫苗必须解决的问题.基础研究与动物实验、临床试验的相互印证有助于各项研究的深入及结核病新疫苗的改进和择选.     

结核病新疫苗研究概况

长期以来,结核病对人类健康构成了严重威胁.随着结核分枝杆菌全基因组测序工作的完成和有效抗原的不断发现,有关结核病新疫苗的研究进展迅速,多种结核病新疫苗已进入临床试验阶段.如何对已接种卡介苗人群、结核分枝杆菌隐性感染人群和免疫缺陷人群进行有效的接种是结核病新疫苗必须解决的问题.基础研究与动物实验、临床试验的相互印证有助于各项研究的深入及结核病新疫苗的改进和择选.     

Difficultés du diagnostic de la tuberculose chez l’enfant : intérêt du test QuantiFÉRON TB Gold® In-Tube

Diagnosis of childhood tuberculosis (TB), active TB or latent tuberculosis infection (LTBI), is complicated by uncommon clinical, radiological and bacteriological features. The tuberculin skin test (TST) is imperfect: difficulty of the intradermal injection for the child, lack of sensibility and specificity. The stop of the systematic inoculation by the BCG since July 2007, in France, could lead to an increase of the incidence of the childhood TB. It is urgent to find new diagnostic tools: sensitive, specific, fast, of objective reading and little expensive. Interferon-γ assays could be useful but the data are still insufficient in paediatrics and sometimes contradictory. A prospective study which compared the usefulness of QuantiFERON TB Gold^® In-Tube (QFT-IT) assay with TST to detect LTBI or active disease in 51 children was realised in University Hospital of Nancy. This allowed us to confirm interest of QFT-IT; however, surprisingly, very discordant QFT-IT and TST results were obtained (only five children were QFT-IT+/TST+). A high number (14%) of indeterminate QFT-IT occurred, without explanation by pre-analytical or clinical parameters. Further studies are needed to demonstrate the usefulness of this assay in diagnosing LTBI and particularly active TB in children.     

Tuberculin Reactivity in School Age Children; Five-year Follow-up in Iran

Objective

Tuberculosis (TB) is an important infectious disease worldwide. Tuberculin skin test (TST) is the standard test for diagnosis of tuberculosis infection; Bacillus Calmette-Guerin (BCG) vaccination at birth has effects on this test. The aim of this study was to determine the prevalence of positive TST cases among 7- to 11-year-old primary school children and also to follow test-positive individuals for a five-year period.

Methods

TST was performed on 10.184 children aged 7–11 years sampled by cluster random method in Kermanshah, West Iran. Those who had a positive test result (i.e. an induration of ≥15 mm following 72 hours of injecting 0.1 ml of 5 tuberculin units of purified protein derivative from Mycobacterium tuberculosis) were followed for five years to determine the presence of active TB. Also tuberculin positive rates at cut-off points of 10 mm and ≥15 mm for boys and girls and at different ages were derived and compared using the chi-squared test.

Findings

Of 10.184 studied subjects, 830 (8.15%) cases showed positive TST. This rate was 8.7% in boys and 7.8% in girls (P=0.1). A significant linear trend was found between the tuberculin positive rates and age at all cut-off points (P<0.001). No active TB was detected during 5-year follow-up.

Conclusion

The rate of positive TST cases in primary school children in Kermanshah, Iran was 8.15% with no new cases of active tuberculosis detection within five-year follow-up.     

Lack of an inverse association between tuberculosis infection and atopy: By T-cell-based immune assay (RD1–ELISpot)

The association between mycobacterial exposure, vaccination with bacillus Calmette-Guerin (BCG) in early life and atopy remains controversial. Distinguishing between environmental mycobacterial exposure, TB infection and BCG-vaccination is not possible with the tuberculin skin test (TST) but new accurate blood-tests for TB infection present an opportunity to differentiate TB infection from environmental mycobacterial exposure and BCG-vaccination. We used a new blood test in parallel with TST to investigate whether Mycobacterium tuberculosis infection and/or BCG vaccination are associated with development of atopy in children with prior household TB contacts. All children who had contact with adult active pulmonary TB during the last 6 months underwent TST, chest radiography, and RD1–ELISpot assay. The presence of a BCG scar was documented, and assessment of atopy was carried out by International Study of Asthma and Allergies in Childhood questionnaire, allergy skin prick testing (SPT) and evaluation of serum total IgE. Among 361 children enrolled 39 (11%) had a positive SPT, 236 (63%) positive TST, and 189 (52%) positive RD1–ELISpot. The frequency of SPT positivity, ever wheezing, allergic rhinitis, doctor-diagnosed asthma, high serum IgE level, and median total serum IgE levels did not differ significantly different by TST or RD1–ELISpot status. On the other hand, presence of BGC scar was associated with lower median total serum IgE level (p = 0.01) and lower frequency of high IgE (p = 0.003). M. tuberculosis infection whether measured by TST or RD1–ELISpot, was not associated with atopy in children with household TB contact. Presence of a BCG vaccination scar was inversely associated with atopy, as measured by serum IgE.     

Evaluation of household contacts of children with positive tuberculin skin tests

BACKGROUND: Associate investigation, defined as screening the contacts of children with positive tuberculin skin tests (TST) and normal chest radiographs, has been recommended to improve case finding for active tuberculosis (TB). The success of this strategy has not been adequately studied in either adults or children. METHODS: A 2-year prospective study was conducted wherein 187 children and adolescents with infection caused by Mycobacterium tuberculosis (positive TST and normal chest radiograph) were referred to a TB Screening Clinic. An associate investigation was performed among their 659 household contacts who were interviewed to assess risk factors for TB and screened with TSTs and with chest radiographs when appropriate. RESULTS: No cases of active TB were detected, but 32% of household contacts had TSTs > or = 10 mm and were candidates for preventive therapy. Logistic regression analysis revealed that household contacts with Calmette-Guérin bacillus immunization and foreign birth were 2.26 and 3.92 times more likely (P < 0.001 and 0.002, respectively) to be tuberculin-positive. Univariate analysis of the 187 households revealed that the following risk factors present in a household member were associated with detecting a household contact with a positive TST: Calmette-Guérin bacillus immunization (P = 0.001), foreign birth (P = 0.017) and a history of having hosted foreign visitors (P = 0.032). CONCLUSION: In this Hispanic immigrant population, primarily from the Dominican Republic, screening household contacts of children with positive TSTs did not identify new cases of active TB. However, this strategy did identify household contacts who were eligible for preventive therapy.     

Gruźlica i latentne zakażenie prątkami gruźlicy u dzieci. Zastosowanie testów uwalniania interferonu-γ w identyfikacji latentnego zakażenia prątkami gruźlicy u dzieci

The interferon-γ release assays (IGRAs) were developed for the diagnosis of latent tuberculosis infection. IGRAs are currently used for the diagnosis of latent tuberculosis infection in adults; a lack of evaluated studies in children has led to difficulties in their clinical interpretation. These two blood assays, including the commercially available T-SPOT.TB and QuantiFERON, enable detection of circulating T-cells responsive to specific Mycobacterium tuberculosis antigens. These assays are available for use in Poland. Evaluation of these tests has been hampered by the lack of a gold standard for latent tuberculosis infection (LTBI) and limited pediatric data on their use. They may add sensitivity if used in addition to the tuberculin skin test (TST) in the youngest children. A summary of IGRA and TST, their application to pediatric practice and their benefits and limitations are described in this article.     

结核菌素皮试和全血γ干扰素测定试验的儿童结核感染诊断应用研究

目的 评价结核菌素（PPD）皮试和全血γ干扰素（IFN-γ）测定试验诊断儿童结核病的准确性。方法 选择2006年7月至2010年4月首都医科大学附属北京儿童医院住院临床诊断结核和呼吸系统疾病的患儿为研究对象。根据患儿所暴露的结核感染危险因素分为5组：A组：无结核病密切接触史的非结核病的呼吸系统疾病患儿;B组：有活动性结核病患者密切接触史的非结核病的呼吸系统疾病患儿;C组：无结核病密切接触史的临床诊断结核病患儿;D组：有活动性结核病患者密切接触史的临床诊断结核病患儿;E组：病原学或病理学确诊的活动性结核病患儿。患儿于入院当日行PPD皮试,入院后1~7 d采集外周静脉血行全血IFN-γ测定。以敏感度、特异度、阴性预测值、阳性预测值和似然比评价PPD皮试和全血IFN-γ测定对结核病的诊断价值。结果 125例患儿进入分析。A组40例,B组11例,C组29例,D组27例,E组18例。①PPD皮试取硬结≥10 mm为阳性判断标准时,诊断结核病的敏感度为77.0%,特异度为70.6%;取硬结≥15 mm为阳性判断标准时,诊断结核病的敏感度为50.0%、特异度为80.2%;全血IFN-γ测定的敏感度为85.1%、特异度为94.1%。②PPD皮试取硬结≥10 mm为阳性判断标准诊断结核病时,<3岁患儿PPD皮试的敏感度和特异度均显著低于≥3岁患儿,城区和郊区患儿的敏感度和特异度接近;全血IFN-γ测定诊断结核病的敏感度和特异度在不同年龄、居住地间差异无统计学意义。③全血IFN-γ测定阳性率与结核感染暴露因素的相关性优于PPD皮试（取硬结≥10或15 mm为阳性判断标准时）。结论 潜伏结核感染筛查时以硬结≥15 mm作为PPD皮试阳性判断标准,可提高诊断的特异度;临床疑似结核病的诊断以硬结≥10 mm作为PPD皮试阳性判断标准,可提高诊断的敏感度。全血IFN-γ测定诊断结核病的敏感度和特异度均较好。     

High prevalence of latent tuberculosis in hematopoietic stem cell transplant recipients: A First Report

TB is an increasing health problem, and patients undergoing HSCT are more prone to develop tuberculosis. The aim of our study was to evaluate prevalence of latent tuberculosis in HSCT recipients. In this study, 84 patients (2 months to 18 years) who were candidates for HSCT at the referral hospital of Tehran Children's Medical Center were enrolled. The TST and the QFT‐GIT test were performed in all 84 patients, simultaneously. LTBI was considered when one of the tests was positive. Overall, the prevalence of LTBI in HSCT recipients in our study was 12% (10 cases). TST induration ≥5 mm was seen in only three patients (3.5%). Eight patients (9.5%) had a positive result for IGRA test, and 11 of them (13%) had indeterminate QFT‐GIT result. The agreement between the TST results (induration size ≥5 mm) and the QFT‐GIT results was poor (kappa = 0.14). In conclusion, there was a high rate of discordance between TST and IGRA results with many more positive QFT‐GIT tests. However, more studies are needed in this population to determine whether this discordance reflects true infection.     

Drug-resistant tuberculosis: pediatric guidelines

Drug-resistant Mycobacterium tuberculosis (TB) infection represents a serious and growing problem. For patients infected or suspected of being infected with multidrug or extensively drug-resistant TB, several medications have to be given simultaneously for prolonged periods. Here, we review the literature on treatment and monitoring of adverse effects of pediatric drug-resistant TB therapy in a high resource, low TB burden setting.     

Tuberculin skin test positivity in pediatric allogeneic BMT recipients and donors in Turkey

The preliminary study was performed to determine the frequency of tuberculin skin test (TST) positivity among 26 patients and their donors screened by TST to investigate whether tuberculin positivity of a recipient or donor influenced the rate of tuberculosis disease, transplant-related events, and to evaluate the effectiveness of isoniazide (INAH) prophylaxis administered to those with positive TST. The frequency of TST positivity was 23% (n = 6) among recipients and also 23% (n = 6) among donors. Two recipients and five donors with positive TST received INAH prophylaxis for six months. Our use of INAH prophylaxis in transplant patients was very conservative because of the risk of drug interaction. The transplantation procedure was not postponed for either recipient or donor TST positivity. Despite the high frequency of tuberculosis in our country, we have not detected any case of tuberculosis in our center, either among the purified protein derivative-screened (n = 26) or non-screened (n = 128) patients except for disseminated tuberculosis infection because of BCG vaccination in two patients with severe combined immunodeficiency. In conclusion, TST positivity in either recipient or donor may not be a contraindication for bone marrow transplantation and the procedure may not be postponed. Pretransplantation TST screening may be needed in countries where tuberculosis is common in the general population.     

Qualitative evaluation of Tuberculin test responses in childhood Tuberculosis

Objective To study if different forms of clinical presentation of tuberculosis in children are associated with a different type of tuberculin reaction. Methods This cross sectional study, describing Tuberculin skin testing (TST) responses in 268 children (134 cases and 134 controls) less than 12 yr of age was carried out over a period of 18 months at JIPMER, a tertiary care referral hospital in Pondicherry, India. The qualitative and quantitative TST responses in various clinical forms of Tuberculosis were analysed. Results Koch’s and Listeria variants were more common in children with TB Lymphadenitis and Pulmonary TB respectively. 10% of the study children with TB meningitis were tuberculin negative. Conclusion Qualitative TST responses are non-homogeneous among the various clinical types of childhood tuberculosis. They are not a correlate of protective immunity with little or no prognostic significance.