Thiopurines are an independent risk factor for active tuberculosis in inflammatory bowel disease patients

The use of thiopurines is an independent risk factor for active tuberculosis in patients with inflammatory bowel disease.     

Cost-effectiveness of interferon-gamma release assay screening for latent tuberculosis infection treatment in Germany

OBJECTIVES: To assess the cost-effectiveness of the new QuantiFERON-TB Gold In-Tube (QFT-G) [Cellestis; Carnegie, VIC, Australia] assay for screening and treating of persons who have had close contact with tuberculosis (TB) patients and are suspected of having latent tuberculosis infection (LTBI) [hereafter called close-contacts] in Germany. METHODS: The health and economic outcomes of isoniazid treatment of 20-year-old close-contacts were compared in a Markov model over a period of 20 years, using two different cutoff values for the tuberculin skin test (TST), the QFT-G assay alone, or the QFT-G assay as a confirmatory test for the TST results. RESULTS: QFT-G assay-based treatment led to cost savings of $542.9 and 3.8 life-days gained per LTBI case. TST-based treatment at a 10-mm induration size cutoff gained $177.4 and 2.0 life-days gained per test-positive contact. When the cutoff induration size for the TST was reduced to 5 mm, the incremental cost-effectiveness ratio fell below the willingness-to-pay threshold ($30,170 per life-years gained) but resulted in unnecessary treatment of 77% of contacts owing to false-positive TST results. Combination with the 5-mm induration size TST cutoff value compared to the results of the QFT-G assay alone reduced the total costs per 1,000 contacts by 1.8% to $222,869. The number treated to prevent 1 TB case was 22 for the two QFT-G assay-based procedures, 40 for the TST at a cutoff induration size of 10 mm, and 96 for the TST at a cutoff induration size of 5 mm. When the sensitivity rates of the TST and the QFT-G assay were compounded, the QFT-G assay strategy alone was slightly less costly (0.6%) than the two-step approach. CONCLUSIONS: Using the QFT-G assay, but especially combining the QFT-G assay following the TST screening of close-contacts at a cutoff induration size of 5 mm before LTBI treatment is highly cost-effective in reducing the disease burden of TB.     

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.     

Use of interferon-gamma release assay for latent tuberculosis infection screening in older adults exposed to tuberculosis in a nursing home

OBJECTIVES: To assess the additive value of a newly marketed interferon‐gamma release assay, QuantiFERON‐TB Gold In‐Tube (QFT‐GIT), to a single tuberculin skin test (TST) for the detection of latent tuberculosis infection (LTBI) in older adults who have been exposed to TB in a nursing home. DESIGN: Contact tracing included clinical examination, chest radiography, TST, and QFT‐GIT in TST‐negative people (TST<5 mm). SETTING: A private nursing home. PARTICIPANTS: Seventy‐seven individuals (63 elderly residents, 14 young employees) who had been exposed to an active TB case in a private nursing home. MEASUREMENTS: Comparison of TST and QFT‐GIT in older adults who have been exposed to TB. RESULTS: For the TST, the positive response rate was 31.7% (n=20) of elderly residents and 43% (n=6) of staff. Positive QFT‐GIT results were obtained in seven (16.3%) elderly residents with negative TST, six of whom were aged 80 and older. QFT‐GIT increased the percentage of possible LTBI in this group from 31.7% to 42.9%. CONCLUSION: QFT‐GIT has a significant additive value to single TST for detecting LTBI in institutionalized older adults, identifying infected subjects anergic to the TST.     

School based screening for tuberculosis infection in Norway: comparison of positive tuberculin skin test with interferon-gamma release assay

Background

In Norway, screening for tuberculosis infection by tuberculin skin test (TST) has been offered for several decades to all children in 9th grade of school, prior to BCG-vaccination. The incidence of tuberculosis in Norway is low and infection with M. tuberculosis is considered rare. QuantiFERON^®TB Gold (QFT) is a new and specific blood test for tuberculosis infection. So far, there have been few reports of QFT used in screening of predominantly unexposed, healthy, TST-positive children, including first and second generation immigrants. In order to evaluate the current TST screening and BCG-vaccination programme we aimed to (1) measure the prevalence of QFT positivity among TST positive children identified in the school based screening, and (2) measure the association between demographic and clinical risk factors for tuberculosis infection and QFT positivity.

Methods

This cross-sectional multi-centre study was conducted during the school year 2005–6 and the TST positive children were recruited from seven public hospitals covering rural and urban areas in Norway. Participation included a QFT test and a questionnaire regarding demographic and clinical risk factors for latent infection. All positive QFT results were confirmed by re-analysis of the same plasma sample. If the confirmatory test was negative the result was reported as non-conclusive and the participant was offered a new test.

Results

Among 511 TST positive children only 9% (44) had a confirmed positive QFT result. QFT positivity was associated with larger TST induration, origin outside Western countries and known exposure to tuberculosis. Most children (79%) had TST reactions in the range of 6–14 mm; 5% of these were QFT positive. Discrepant results between the tests were common even for TST reactions above 15 mm, as only 22 % had a positive QFT.

Conclusion

The results support the assumption that factors other than tuberculosis infection are widely contributing to positive TST results in this group and indicate the improved specificity of QFT for latent tuberculosis. Our study suggests a very low prevalence of latent tuberculosis infection among 9th grade school children in Norway. The result will inform the discussion in Norway of the usefulness of the current TST screening and BCG-policy.

     

Tuberculosis screening among HIV-infected patients: tuberculin skin test vs. interferon-gamma release assay

National guidelines recommend screening for latent tuberculosis infection (LTBI) in all HIV-infected patients. Thus, the objective of this study was to measure protocol adherence to national guidelines regarding LTBI screening for HIV-infected patients entering care at an urban primary care clinic specializing in HIV care, identify clinical and other characteristics associated with adherence, and determine whether transitioning from the tuberculin skin test (TST) to the interferon-gamma release assay (IGRA) improved adherence. We conducted a retrospective study using protocol adherence to LTBI screening guidelines within twelve months of entering care at an HIV clinic as the primary outcome. Successful protocol adherence was defined as the placement and reading of a TST, performance of an IGRA, or a note in study clinic records documenting prior testing or treatment for tuberculosis in an outside setting. Multivariable modified Poisson regression models were used in analyses. Overall, 32% (n?=?118/372) of patients received LTBI screening within twelve months of entering care. Protocol adherence to LTBI screening guidelines increased from 28% to 37% following the transition from TST to IGRA screening. IGRA screening [adjusted prevalence ratio: 1.45, 95% confidence limits: (1.07, 1.96)], male sex [1.47 (1.05, 2.07)], transfer patient status [1.51 (1.05, 2.18)], and greater than one year of clinic attendance [1.62 (1.06, 2.48)] were independently associated with protocol adherence. Among patients without prior LTBI screening or treatment, patients entering the clinic in 2013 under the IGRA screening protocol were more likely to be screened for LTBI compared to patients entering under the TST screening protocol (34.3% vs. 9.7%, p?相似文献   

结核分枝杆菌感染T细胞斑点试验对淋巴结结核的辅助诊断价值研究

目的 探讨评价结核分枝杆菌感染T细胞斑点试验（T-SPOT.TB）对淋巴结结核的辅助诊断价值.方法 本研究募集北京胸科医院2011年7月至2013年12月收治住院的淋巴结肿大患者185例,最终分为确诊结核性淋巴结组（51例）、非结核性淋巴结疾病组（105例）,其余诊断不明确或临床诊断淋巴结结核患者予以剔除.所有患者均行外周血T-SPOT.TB及免疫印迹法检测结核分枝杆菌抗体.采用SPSS 17.0进行统计学分析,非正态分布的计量资料数据用中位数（上下四分位数）[M（P25,P75）]表示,两组间斑点形成个数（SFCs）数据比较采用Mann WhitneyU检验,组间样本率的比较采用x2检验,以P＜0.05为差异具有统计学意义.结果 T-SPOT.TB和免疫印迹法检测结核分枝杆菌抗体的敏感度分别为92.2％（47/51）和60.8％（31/51）,特异度分别为79.0％（83/105）和77.1％（81/105）,T-SPOT.TB敏感度显著高于免疫印迹法检测结核分枝杆菌抗体方法,差异有统计学意义（x2=13.95,P＜0.01）.结核分枝杆菌特异抗原刺激下结核性淋巴结组SFCs中位数为242个（57,621个）/106外周血单个核细胞（PBMCs）,非结核性淋巴结疾病组SFCs中位数为0个（0,20个）/106 PBMCs,结核性淋巴结组SFCs数量显著高于非结核性淋巴结疾病组,应用Mann Whitney U检验,两组间差异具有统计学意义（U=472.0,P＜0.01）.在T-SPOT.TB结果阳性的69例患者中,47例结核性淋巴结患者SFCs的M（P25,P75）为280个（98,684个）/106 PBMCs,显著高于对照组22例非结核性淋巴结疾病患者SFCs的M（P25,P75）52个（35,93个）/106 PBMCs（U=146.5,P＜0.01）.结论 T-SPOT.TB方法在淋巴结结核的诊断中有着较高的敏感度,有可能成为淋巴结结核辅助诊断的一项重要手段.     

γ-干扰素释放分析T-SPOT.TB在结核性疾病中的诊断价值

目的评价γ-干扰素释放分析T-SPOT.TB检测在结核性疾病中的诊断价值。方法采用T-SPOT.TB试剂盒对疑诊或待排结核患者外周血中释放γ-干扰素的结核分枝杆菌特异性T淋巴细胞进行检测。结果γ-干扰素释放分析T-SPOT.TB检测在结核性疾病阳性检出率为83.3%(20/24),明显高于结核菌素试验(tuberculin skin test,TST)的41.7%(10/24)、涂片找抗酸杆菌的26.7%(4/15)、分枝杆菌分离培养的22.2%(2/9),差异有统计学意义(P<0.05)。γ-干扰素释放分析T-SPOT.TB检测诊断结核性疾病敏感性、特异性分别为83.3%、96.4%,显著优于结核菌素试验。结论γ-干扰素释放分析T-SPOT.TB检测是诊断结核的快速敏感方法,在结核性疾病诊断中有重要价值。     

抗原刺激后外周血单个核细胞γ干扰素释放反应在结核分枝杆菌感染和结核病诊断中的意义

目的 探讨3种结核分枝杆菌抗原刺激后外周血单个核细胞（PBMC）γ干扰素（IFN-γ）释放反应对结核性感染和结核病的诊断意义。方法 获取活动性结核病患者（结核组，57例）、肺癌患者（肺癌组，29例）和健康人（健康对照组，27名）外周血单个核细胞。分别将结核分枝杆菌纯蛋白衍生物（PPD）、结核分枝杆菌早期分泌抗原靶6000蛋白（ESAT6）和38000抗原与PBMC共培养5d，采用酶联免疫吸附测定（ELISA）法检测培养上清液中IFN-γ浓度。比较3种抗原PBMC IFN-γ释放水平和PPD皮试（TST）结果。结果 （1）健康对照组：TST反应与BCG接种史及排菌患者接触密切程度经Logistic回归分析显示均呈正相关（P=0．047和P=0．041）；以ESAT6为抗原的PBMC IFN-γ释放水平与结核病患者接触密切程度相关（P=0．005），而与BCG接种史无明显相关性。（2）3组间TST结果差异无显著性。（3）以38000抗原刺激后IFN-1释放水平为观察指标，经受试者操作特性（ROC）曲线分析获得最佳域值为1000pg／ml，以此判断38000抗原刺激后IFN-γ释放水平诊断结核病敏感性为64．9％，特异性为89．3％，准确性为77．0％，阳性预测值为86．0％，阴性预测值为71．0％。结论 ESAT6抗原的IFN-γ释放反应对结核分枝杆菌感染的诊断意义优于TST，38000抗原刺激后IFN-γ释放反应对结核病的临床诊断有辅助意义。     

The Luebeck interview for psychosocial screening in patients with inflammatory bowel disease

BACKGROUND: Psychosocial factors play an important role in the course of inflammatory bowel disease (IBD). However, a simple, valid psychosocial screening instrument that is suitable for short patient-physician contacts does not exist. Therefore, the Luebeck semistructured Interview for Psychosocial Screening was developed as a rating tool for psychosocial stress in IBD patients (LIPS-IBD). METHOD: The entire interview requires approximately 10 minutes. Interrater reliability was tested. Depression, anxiety, social support, impact of the disease, global level of psychosocial stress, and demand for psychosocial support were rated in 92 patients with IBD on 5 point Likert scales. Patients from the in- and out-patient clinic for gastroenterology were included. In addition, patients filled out self-report questionnaires regarding depression, anxiety, social support, and impact of the disease. Indices of disease activity (Colitis Activity Index, Crohn's Disease Activity Index) were recorded. RESULTS: Both patients and physicians found the interview feasible. Reliability was good, with interrater reliability ranging from .76 to .94. Convergence with self-report instruments was also high (r = .5-.6). Ratings of depression and impact of the disease were correlated with indices of disease activity. DISCUSSION: LIPS helps to identify patients with high levels of psychosocial stress and provide them with more detailed psychologic assessments. It was found to be a suitable instrument for daily clinical routine. It is potentially a valuable screening tool to obtain reliable, valid, and useful information in daily practice in IBD treatment settings.     

Accuracy of an interferon-gamma release assay to detect active pulmonary and extra-pulmonary tuberculosis.

OBJECTIVE: To examine the performance of an interferon-gamma (IFN-gamma) release assay (QuantiFERON-TB 2G assay [QFT-G]) to detect Mycobacterium tuberculosis infection in a Japanese general hospital, for the diagnosis of active pulmonary tuberculosis (PTB) and extra-pulmonary tuberculosis (EPTB). DESIGN: We prospectively examined the performance of QFT-G in 194 patients suspected of active TB. Diagnosis was confirmed by 1) positive M. tuberculosis cultures, or 2) clinical manifestations or laboratory or pathological findings consistent with active TB and response to specific therapy. RESULTS: Three patients with indeterminate QFT-G results were excluded. Among the remaining 191 patients, 77 had active TB. When the cut-off concentration of IFN-gamma was set at 0.35 IU/ml, as recommended by the manufacturer, the assay was positive in 69 patients and negative in 122. The sensitivity of the assay was 76.6% in all patients, 74.5% in the 47 patients with PTB and 80.0% in the 30 patients with EPTB. The overall specificity of the assay was 91.2%. CONCLUSION: Although the specificity of the QFT-G to detect active TB was high and its sensitivity low, it was as accurate for the detection of active EPTB as for PTB when the 0.35 IU/ml INF-gamma cut-off concentration was used.     

Apolipoprotein A-IV is an independent predictor of disease activity in patients with inflammatory bowel disease

BACKGROUND: ApoA-IV, an apolipoprotein (apo) with antioxidant, antiatherogenic, and antiinflammatory properties, was recently demonstrated to inhibit dextran sulfate sodium (DSS)-induced experimental colitis in mice. We therefore hypothesized that apoA-IV may be associated with disease activity in patients with inflammatory bowel disease (IBD). METHODS: We addressed this question by testing for associations between apoA-IV genotypes, apoA-IV plasma levels, inflammatory parameters, and clinical disease activity in 206 patients with Crohn's disease (CD), 95 subjects with ulcerative colitis (UC), and 157 healthy controls. RESULTS: In CD patients, apoA-IV plasma levels were inversely associated with C-reactive protein (CRP) (P = 0.005) and disease activity (P = 0.01) in univariate analysis. In multiple logistic regression analysis, apoA-IV levels were identified as an independent predictor of elevated CRP (odds ratio [OR] 0.956, 95% confidence interval [CI]: 0.916-0.998, P = 0.04) and active disease (OR 0.957, 95% CI: 0.918-0.998, P = 0.04). In UC patients the apoA-IV gene variant 360 His (P = 0.03) but not apoA-IV levels (P = 0.15) were associated with increased disease activity in univariate analysis. This association, however, was lost in multiple logistic regression analysis (OR 3.435, 95% CI 0.995-11.853, P = 0.05). CONCLUSIONS: To our knowledge, this is the first study to demonstrate an association of apoA-IV with disease activity in patients with CD. Further studies are needed to define the relationship of apoA-IV to IBD.     

Molecular screening for colon cancer in inflammatory bowel disease

Prophylactic colectomy is an established method of bowel cancer prevention in high-risk patients such as familial adenomatosis polyposis coli (FAP) and hereditary non-polyposis colorectal cancer (HNPCC) kindreds, as well as in patients with longstanding ulcerative colitis or Crohn's disease. The decision to perform such a major procedure cannot be made lightly, and issues of timing are important. In inflammatory bowel disease (IBD), the trigger to carry out colectomy usually relates to detection of dysplasia, well recognized to be a premalignant lesion. Screening methods are aimed at detection of precursor lesions or clinically occult malignancies. In current clinical practice, such screening methods are either resource intensive (e.g. colonoscopy and biopsy) or of low sensitivity and specificity (e.g. faecal occult blood testing). We discuss the development of screening techniques based upon molecular technologies and the limitations engendered by our incomplete understanding of the natural history and molecular biology of colorectal neoplasia in IBD.     

Implementation of screening criteria for inflammatory bowel disease in patients with spondyloarthritis and its association with disease and endoscopic activity

Clinical Rheumatology - There is little literature on the implementation of screening criteria for inflammatory bowel disease (IBD) in patients with&nbsp;spondyloarthritis (SpA).&nbsp;This...