Screening of latent tuberculosis infection by interferon-γ release assays in rheumatic patients: a systemic review and meta-analysis

The aim of this study is to assess the diagnostic value of interferon-γ release assays (IGRAs) for latent tuberculosis infection (LTBI) in patients with rheumatic disease before receiving biologic agents. MEDLINE and EMBASE databases were used for searching studies concerning the evaluation on the performance of IGRAs [QuantiFERON-TB Gold (QFT-G), QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB] in rheumatic patients before biological therapy. After assessing the quality of all studies included in the review, we summarized the results in subgroups using forest plots and calculated pooled estimates if applicable. The search identified 11 studies with a total sample size of 1940 individuals. Compared with the tuberculin skin test (TST), the pooled agreements in QFT-G/GIT and T-SPOT.TB were 72 % (95 % confidence interval (CI) 65, 78 %) and 75 % (95 % CI 67, 83 %), respectively. BCG vaccination was positively correlated with positive rates of TST (pooled odds ratio (OR) 1.64, 95 % CI 1.06, 2.53). Compared with TST, IGRAs were better associated with the presentence of one or more tuberculosis (TB) risk factors. Neither steroid nor disease-modifying anti-rheumatic drugs (DMARDs) significantly affect positive IGRA results. In contrast, TST positivity was significantly impacted by the use of steroid (pooled OR 0.45, 95 % CI 0.30, 0.69), but less significantly by the use of DMARDs (pooled OR 0.78, 95 % CI 0.50, 1.21). In conclusion, in rheumatic patients with previous BCG vaccination or currently on steroid therapy, IGRAs would be the better choice to identify LTBI by decreasing the false-positivity and false-negativity rate compared with conventional TST.     

Contribution of Interferon gamma release assays testing to the diagnosis of latent tuberculosis infection in HIV-infected patients: A comparison of QuantiFERON-TB gold in tube, T-SPOT.TB and tuberculin skin test

ABSTRACT: BACKGROUND: Diagnosis and treatment of latent tuberculosis infection (LTBI) is the most effective strategy to control tuberculosis (TB) among patients with HIV infection. The tuberculin skin test (TST) was the only available method to identify LTBI. The aim of the present work was to evaluate the usefulness of the interferon-gamma release assays (IGRAs): QuantiFERONtuberculosis (TB) Gold-In-Tube test (QFG) and T-SPOT.TB for the diagnosis of LTBI in a diverse cohort of HIV-infected patients. METHODS: A prospective study was carried out in consecutive patients cared for in a single institution in Spain from January 2009 to October 2010. IGRAS and tuberculin skin test (TST) were performed simultaneously. TST induration [greater than or equal to] 5 mm was considered positive. RESULTS: QFG, T-SPOT.TB and TST were performed in 373 subjects. Median CD4 cell count was 470/mul with a median nadir of 150/mul. TST, QFG and T-SPOT.TB were positive in 13.3%, 7.5% and 18.5% cases respectively. Among 277 patients with neither past or current TB nor previous treatment for LTBI and who had TST results, a positive TST result was obtained in 20 (7.2%) cases. When adding QFG results to TST, there were a total of 26 (8.6%) diagnoses of LTBI. When the results of both IGRAs were added, the number of diagnoses increased to 54 (17.9%) (incremental difference: 10.7% [95% confidence interval [CI]:5.3-16.2%] [p <0.001]), and when both IGRAs were added, the number of diagnoses reached 56 (18.5%) (incremental difference: 11.3% [95% CI:5.7%-16.9%] [p < 0.001]). Patients with a CD4 cell count greater than 500 cells/mul and prior stay in prison were more likely to have a diagnosis of LTBI by TST and/or QFG and/or T-SPOT.TB (adjusted odds ratio [aOR]: 3.76; 95% CI, 1.4 - 9.89; and aOR: 3.3; 95% CI, 1.3 - 8.3, respectively). CONCLUSIONS: IGRAs were more sensitive than TST for diagnosis of M. tuberculosis infection in HIVinfected patients. Dual sequential testing with TST and IGRAs may be the optimal approach for LTBI screening in this population.     

Improving the estimation of tuberculosis infection prevalence using T-cell-based assay and mixture models

BACKGROUND: The prevalence of latent tuberculosis infection (LTBI) is traditionally estimated using the tuberculin skin test (TST). Highly specific blood-based interferon-gamma release assays (IGRAs) are now available and could enhance the estimation of LTBI prevalence in combination with model-based methods. DESIGN: We compared conventional and model-based methods for estimating LTBI prevalence among 719 Indian health care workers who underwent both TST and QuantiFERON-TB Gold In-Tube (QFT-G). In addition to using standard cut-off points on TST and QFT-G, Bayesian mixture model analyses were performed with: 1) continuous TST data and 2) categorical data using both TST and QFT-G results in a latent class analysis (LCA), accounting for prior information on sensitivity and specificity. RESULTS: Estimates of LTBI prevalence varied from 33.8% to 60.7%, depending on the method used. The mixture model based on TST alone estimated the prevalence at 36.5% (95%CI 28.5-47.0). When results from both tests were combined using LCA, the prevalence was 45.4% (95%CI 39.5-51.1). The LCA provided additional results on the sensitivity, specificity and predictive values of joint results. CONCLUSION: The availability of novel, specific IGRAs and development of methods such as mixture analyses allow a more realistic and informative approach to prevalence estimation.     

Rapid diagnosis of Mycobacterium tuberculosis infection in children using interferon-gamma release assays (IGRAs)

Diagnosis of tuberculosis (TB) in children by the tuberculin skin test (TST) poses a diagnostic challenge for physicians due to its low specificity and cross-reactivity with nontuberculous mycobacteria and bacille Calmette-Guerin (BCG). Although interferon-gamma release assays (IGRAs) have been shown as novel TST alternatives for diagnosis of latent TB infection (LTBI) in adults, their effectiveness is less clear in children. The present study examined QuantiFERON-TB Gold (QFT-G) responses and IFN-gamma production capacity of TST-positive children, younger children ≤5 years. A total of 517 children of whom 434 were TST positive ranging in age from 1 month to 18 years were evaluated by the QFT-G. Of the 517 children, 434 (84%) were TST positive, 25 (5.8%) of whom were found to be QFT-G positive and 25 (5.4%) with an indeterminate response. Of the 517 children, 355 (68.7%) were previously BCG immunized and 310/355 (87.3%) were TST positive including 18/27 (66.7%) QFT-positive children. Adequate IFN-gamma production by purified TB peptides or mitogen was observed in 92.8% of children, 29.6% of whom were <5 years. This study shows that the QFT-G assay is useful for diagnosis of LTBI. The finding of 5.8% positive QFT-G in 434 TST-positive children underscores the superior specificity of the QFT-G than the TST and its greater cost effectiveness in preventing unnecessary and potentially toxic treatment in children. The study suggests that the majority of positive TST in children represent false-positive reactions and supports the use of IGRAs for diagnosis of LTBI in children, including those <5 years of age.     

Diagnosis of latent tuberculosis infection among HIV discordant partners using interferon gamma release assays

Background

There is limited data on the effect of HIV status and CD4 counts on performance of Interferon-g Release assays (IGRAs) for diagnosis of latent tuberculosis infection (LTBI).

Methods

A cross sectional study was conducted to assess the prevalence of and risk factors for a positive diagnostic test for LTBI, using tuberculin skin test (TST) and IGRAs among HIV-discordant couples in Zambia.

Results

A total of 596 subjects (298 couples) were enrolled. Median CD4 count among HIV positive persons was 388 cells/μl, (range 51-1330). HIV negative persons were more likely than their HIV positive partner, to have a positive diagnostic test for LTBI with TST (203 vs 128), QFT (171 vs 109) and TSPOT (156 vs. 109). On multivariate analysis, HIV negative status was an independent predictor for a positive QFT (OR = 2.22, 95% CI 1.42- 3.46) and TSPOT (OR = 1.79, 95% CI 1.16-2.77). Among HIV positive subjects a CD4 count ≥ 388 cells/μl was associated with a positive TST (OR = 1.76 95% CI 1.10-2.82) and QFT (OR = 1.71 95% CI 1.06-2.77) but not TSPOT (OR = 1.20 95% CI 0.74-1.94).

Conclusions

Persons with HIV had significantly fewer positive diagnostic tests for LTBI with TST, QFT and TSPOT. Persons with a CD4 count < 388 cells/μl were less likely to have a positive TST or QFT, but not less likely to have a positive TSPOT. TSPOT may perform better than TST or QFT in HIV positive individuals.

     

Is the T-cell-based interferon-gamma releasing assay feasible for diagnosis of latent tuberculosis infection in an intermediate tuberculosis-burden country?

The diagnosis of active and latent tuberculosis infection (LTBI) remains a challenge, especially in light of the fact that the tuberculin skin test (TST), which has been used to diagnose LTBI for over a century, has many well-known drawbacks. This study aimed to compare the diagnostic performance of the T-cell-based interferon-gamma releasing assay (IGRA) T-SPOT.TB with the TST for the diagnosis of LTBI in an intermediate tuberculosis (TB)-burden country with high BCG coverage. For this purpose, a total of 91 participants, including culture-confirmed TB patients, healthy contacts known to have been exposed to Mycobacterium tuberculosis, and healthy volunteers, selected from a BCG-vaccinated population were recruited. The sensitivities of the T-SPOT.TB and TST were 79.3 and 25.8%, and the specificities were 75.9 and 56.7%, respectively. The negative- and positive-predictive values for T-SPOT.TB and TST were 78.6 and 76.7% and 42.5 and 38.1%, respectively. The diagnostic performance of the TST in LTBI diagnosis is therefore severely diminished in BCG-vaccinated populations, with the sensitivity and specificity of the T-SPOT.TB assay being markedly higher. IGRAs have been reported to have higher diagnostic sensitivity and specificity in low TB-incidence settings than those seen here. Further larger scale studies in high and intermediate TB-incidence settings are therefore warranted.     

Comparison of two interferon-gamma assays and tuberculin skin test for tracing tuberculosis contacts

BACKGROUND: The tuberculin skin test (TST) has low specificity. QuantiFERON-TB Gold (QFT-G) and T-SPOT.TB are based on interferon (IFN)-gamma responses to Mycobacterium tuberculosis-specific antigens. A novel in-tube format of QFT-G (QFT-GIT) offers logistical advantages. OBJECTIVE: To compare TST, QFT-GIT, and T-SPOT.TB in bacillus Calmette-Guérin unvaccinated contacts and correlate results with measures of recent exposure. METHODS: When a supermarket employee with smear-positive tuberculosis had infected most close contacts, a contact investigation among more than 20,000 customers was performed. We recruited subjects randomly on the day of TST administration (n = 469) and subjects with TST of more than 0 mm on the day of TST reading (n = 316). QFT-GIT and T-SPOT.TB were performed. Demographic data and measures of exposure were collected. TST results were analyzed at a cutoff of 10 or 15 mm. Blood tests were interpreted following the manufacturers' criteria and by varying cutoff levels. RESULTS: Among 785 study participants, TST results were associated with age, whereas positive IFN-gamma responses were significantly associated with cumulative shopping time, most markedly for QFT-GIT. Among participants with a TST of 15 mm or greater, sensitivity of QFT-GIT and T-SPOT.TB was 42.2 and 51.3%, respectively. Interassay agreement was 89.6% (kappa = 0.59). By varying cutoff values, agreement between the IFN-gamma assays was optimal at 93.6% (kappa = 0.71) using a cutoff of 0.20 IU/ml for QFT-GIT and 13 spots for T-SPOT.TB. CONCLUSIONS: Blood test results were associated with exposure, whereas the TST was not. A possible lack of sensitivity of IFN-gamma assays in detecting individuals with TST of 15 mm or greater, despite negative bacillus Calmette-Guérin vaccination status, warrants further investigation into alternative cutoff values.     

Effectiveness of the combination of a whole-blood interferon-gamma assay and the tuberculin skin test in detecting latent tuberculosis infection in rheumatoid arthritis patients receiving adalimumab therapy

OBJECTIVE: To investigate QuantiFERON-tuberculosis Gold (QFT-G) assay and tuberculin skin test (TST) for latent tuberculosis (TB) infection (LTBI) in patients with rheumatoid arthritis (RA) treated with adalimumab. METHODS: We prospectively followed up 43 RA patients who received adalimumab therapy and underwent serial TSTs and QFT-G assays. TST was performed using Mantoux method and QFT-G assay was examined by measuring interferon-gamma levels in whole blood samples that were incubated with early secretary antigenic target-6 and culture filtrate protein 10. RESULTS: Before starting adalimumab therapy, 8 RA patients (18.6%) had positive and 35 (81.4%) had negative TST results. All 8 RA patients with positive TST results were diagnosed as LTBI and received isoniazid prophylaxis (INHP) 1 month before starting adalimumab therapy. None of these 8 RA patients developed active TB 2 years after completing INHP. A high rate (10 [37.0%] patients) of TST conversion was observed among 27 patients who had completed 12-month adalimumab therapy. Of these 10 patients with TST conversion, 2 patients had positive QFT-G results and 1 developed active TB disease. Among 17 RA patients who did not have TST conversion after 12-month adalimumab therapy, 1 patient who had a positive QFT-G result developed active TB disease. Of all 43 RA patients who received adalimumab therapy, 4 (9.3%) developed active TB after starting adalimumab therapy. CONCLUSION: The application of TST for detecting LTBI is limited in RA patients by the frequent presence of anergy. Combined QFT-G assay and TST can aid in detecting LTBI in RA patients receiving adalimumab therapy.     

Contribution of a IFN-gamma assay in contact tracing for tuberculosis in a low-incidence, high immigration area

AIMS OF STUDY: to analyse, in contacts exposed to smear+/culture + (S+/C+) or S-/C+ TB, most of whom are foreign-born: 1) correlation between T-SPOT.TB IFN-gamma release assay (Oxford Immunotec, UK), TST and exposure scores; 2) agreement between T-SPOT.TB and TST in Bacillus of Calmette-Guérin (BCG) vaccinated and non-vaccinated subjects, and 3) impact of results of T-SPOT.TB on diagnosis and treatment for latent tuberculosis infection (LTBI). PATIENTS AND METHODS: TST and T-SPOT.TB were performed in 295 contacts (74% foreign-born) 8-12 weeks after exposure. Contacts completed five exposure scores. Data were analysed according to most recent US (ATS/CDC), British (NICE) and Swiss guidelines. RESULTS: T-SPOT.TB was positive in 115 (39%) and indeterminate in 15 subjects (5.1%). Neither TST, nor T-SPOT.TB was significantly related to exposure scores or infectiousness of the index case. In multivariate analysis, incidence of TB in country of origin was the strongest predictor of result of TST or T-SPOT.TB. Agreement between TST and T-SPOT.TB (kappa: 0.19-0.27) was low but improved in non BCG-vaccinated subjects (kappa: 0.28-0.47). According to guidelines referred to, 10-24% of subjects screened were T-SPOT.TB+/TST-: the prognosis of this group is yet undetermined. Another 10-27% were T-SPOT.TB-/TST+: present guidelines recommend withholding treatment for LTBI in these subjects although longitudinal data are still scarce. CONCLUSIONS: The lack of a relationship between T-SPOT.TB and exposure scores probably results from both the variability inherent to the design of this study (ie, multiple contact investigations, exposure in different settings) and limits in the performance of the IGRA tested. Longitudinal data are needed to clarify the risk of TB in T-SPOT.TB+/TST- individuals. Unreliability of diagnosis of LTBI in spite of the present use of IGRA in algorithms is illustrated by the wide variations in identification of LTBI according to different guidelines referred to.     

High level of discordant IGRA results in HIV-infected adults and children.

SETTING: Tygerberg district, Western Cape Province, South Africa. OBJECTIVE: To measure the agreement of two interferon-gamma release assays (IGRAs) and the tuberculin skin test (TST) for the detection of Mycobacterium tuberculosis infection in human immunodeficiency virus (HIV) infected adults and children in a setting highly endemic for tuberculosis (TB). DESIGN: Cross-sectional study. RESULTS: In HIV-infected adults (n=20) and children (n=23), tests yielded discordant results, with 61% of individuals testing positive with T-SPOT.TB, 41% with TST and 28% with QuantiFERON TB Gold (QTF). In children, there was poor agreement between the TST and T-SPOT.TB (kappa [kappa]=-0.02), but moderate agreement between the TST and QTF (kappa=0.44). In adults, there was moderate agreement between the TST and T-SPOT.TB (kappa=0.43), and the TST and QTF (kappa = 0.46). In children and adults, there was fair agreement between the T-SPOT.TB and QTF (kappa=0.33). Twenty per cent of adults had >or=1 indeterminate IGRA results. CONCLUSIONS: There is poor to moderate agreement between the TST and IGRAs in HIV-infected adults and children. T-SPOT.TB may have improved sensitivity for detection of M. tuberculosis infection in HIV-infected individuals compared to the QTF and the TST. In HIV-infected individuals, IGRA test properties are affected by test cut-off point and nil control responses.     

High Prevalence of Latent Tuberculosis Infection in Patients in End-Stage Renal Disease on Hemodialysis: Comparison of QuantiFERON-TB GOLD, ELISPOT, and Tuberculin Skin Test

Abstract Background:   Individuals with end-stage renal disease (ESRD) are 10- to 25-fold more likely than immunocompetent people to develop active tuberculosis (TB) and are candidates for being treated for latent TB infection (LTBI). However, diagnosis using the tuberculin skin test (TST) is doubly difficult due to cutaneous anergy and cross-reactions with Bacille–Calmette–Guérin (BCG) vaccination. Materials and Methods:   This was a prospective, doublematched, cohort study in which 32 ESRD patients and 32 age-matched, healthy controls were enrolled. The TST and two new interferon-γ blood tests, QuantiFERON-TB Gold (QFT-G) and T-SPOT.TB (ELISPOT), were performed. The subjects were followed up 2 years for active TB disease. ELISPOT was done in ESRD patients only. Results:   Compared to the healthy controls, a high prevalence of LTBI was found in the ESRD patients by TST (62.5%, 95% confidence interval [CI] 43.7–78.9), QFT-G (40.0%, 95% CI 22.7–59.4), and ELISPOT (46.9%, 95% CI 29.1–65.3). Agreement was moderate (kappa [κ] = 0.53) for QFT-G and ELISPOT but only slight between TST and QFT-G (κ = 0.25) and fair between TST and ELISPOT (κ = 0.32). ESRD (p = 0.03) and diabetes mellitus (p = 0.04) were significant risk factors for QFT-G positivity on the multivariable analysis. The overall rate of active TB was 1.66 cases per 100 person-years (pys), with the rate higher in patients with ESRD (3.53 per 100 pys) and those with positive (3.40 per 100 pys) and indeterminate QFT results (30.16 per 100 pys), although the difference was not statistically significant. Sensitivity, specificity, and positive and negative predictive values of QFT-G for active TB was 100%, 62.1%, 8.3% and 100%. Conclusion:   This pilot study is the first to compare QFT-G, ELISPOT, and TST in ESRD patients on hemodialysis and demonstrates a high prevalence of LTBI in this population. In our study, the QFT-G was the more accurate method for identifying those truly infected with Mycobacterium tuberculosis, even in BCG-vaccinated individuals. The results of this study have been previously reported in part, in the form of an abstract, at the 46th Annual Meeting of Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), 27–30 September, 2006. San Francisco, USA. Abstract D460: S.S. Lee, Y.Y. Ni, T.S. Huang, K.R. Chou, H.C. Fang, H.C. Tsai, Y.S. Chen, S.R. Wann, H.H. Lin, Y.C. Liu. QuantiFERON-TB GOLD for Diagnosis of Latent Tuberculosis Infection in Patients with End-Stage Renal Disease in Taiwan.     

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.     

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.     

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。     

Comparison of the interferon- gamma release assay and the tuberculin skin test for contact investigation of tuberculosis in BCG-vaccinated health care workers

Health care workers are at increased risk of Mycobacterium tuberculosis infection. The tuberculin skin test (TST) is frequently false positive in BCG-vaccinated health care workers. QuantiFERON-TB GOLD (QFT-G) is a sensitive and specific interferon-gamma release assay unaffected by BCG vaccination. This study compared TST and QFT-G in the diagnosis of latent TB infection in BCG-vaccinated health care workers. 39 health care workers exposed to a smear-positive TB patient were enrolled. Initial TST was positive in 33 (84.6%) cases, but only 4 (10.2%) cases using QFT-G. TST conversion occurred in 2/6 (33.3%), compared to 4/32(12.5%), cases using QFT-G. A higher proportion of QFT converters was associated with intimate contact, although not reaching statistical significance. Face-to-face contact >1 h was significantly associated with QFT-G conversion >or=0.7 IU/ml (OR 8.63, 95%CI 1.08-69.07, p=0.04). Agreement between TST and QFT-G was 18.0%, (kappa: -0.03). Concordance between TST and QFT (>or=0.35 IU/ml) conversion was 40.0%(kappa=-0.40), and 60.0%(kappa=0.00) if QFT >or=0.7 IU/ml was used. Agreement increased with increasing TST cut-offs. TST is not useful in contact investigation among BCG-vaccinated health care workers, in an area with intermediate burden of TB. QFT may provide additional information for the diagnosis and strategic management of preventive treatment of LTBI in BCG-vaccinated health care workers in a country with intermediate burden of TB.     

Direct costs of three models for the screening of latent tuberculosis infection.

The aim of the present study was to compare the direct costs of three models for detection of latent tuberculosis infection (LTBI) in routine clinical practice in Switzerland. Comparison of the overall costs of screening for LTBI, including medical and radiological examination, and preventive treatment associated with three screening models was carried out. Model 1 relies only on the tuberculin skin test (TST) according to the current national guidelines, model 2 relies on T-SPOT.TB (Oxford Immunotec, Oxford, UK) only and model 3 relies on TST followed by confirmation of positive results by T-SPOT.TB. Costs were taken directly from the clinic's figures. Clinical assumptions were based on the 267 patients who were referred to the clinic over the study period. Model 3 was found to be the most cost-effective. Using only the skin test (model 1) was the least cost-effective. If only one test for LTBI is to be used, then model 2 (using T-SPOT.TB only) is cheaper than using the TST (model 1). Screening for latent tuberculosis infection by tuberculin skin test followed by confirmation with T-SPOT.TB is less costly than screening with tuberculin skin test alone, as it allows a reduction in the number of people who receive preventive treatment. In groups with a high proportion of negative tuberculin skin tests, screening with T-SPOT.TB test only may be the most cost-effective.     

上海地区四小学高年级学生结核感染率及影响因素的横断面研究

目的 了解上海地区小学生潜伏结核感染的分布情况并分析影响儿童潜伏结核感染的因素.方法 以上海市浦东新区和杨浦区四所小学四、五年级在校学生作为研究对象,问卷调查形式收集研究对象的基本信息和结核感染相关信息,结核感染T细胞斑点试验(T-SPOT.TB)技术了解结核感染情况,单因素和多因素分析研究影响小学生结核感染状况的因素.结果 本研究共纳入小学生472名,其中有卡介苗接种史者439人,占93.0%,与结核患者既往有过接触的学生10人,占2.1%.472名小学生中16人T-SPOT.TB检测阳性,占3.4%,但无结核相关的临床症状和体征,为潜伏结核感染者.接种卡介苗者潜伏结核感染率为2.7%,未接种者为12.1%(OR:6.972,95% CI:1.834～26.500);有结核接触史者潜伏结核感染率为30.0%,无接触史者为2.8%(OR:16.38,95% CI:3.692～72.700).结论 上海市小学高年级学生的潜伏结核感染率为3.4%,卡介苗接种对预防上海学龄儿童潜伏结核感染有保护作用,而日常生活中与结核患者接触增加了儿童潜伏结核感染的危险性.

Abstract：

Objective To investigate the prevalence of latent tuberculosis infection(LTBI),and to identify the risk factors in primary schoolchildren from Shanghai through the population-based field investigation combined with the tuberculosis infection enzyme-linked immunospot assay(T-SPOT.TB)assay.Methods The children in grade 4 and 5 were enrolled from four primary schools in Pudong new district and Yangpu district of Shanghai.Questionnaire interview was applied to investigate the soeiodemographic and clinical information related to LTBI.The T-SPOT.TB assay was used to detect LTBI in the enrolled subjects.Univaitate and multivariate analyses were used to identify the risk factors associated with LTBI among the primary schoolchildren.Results Totally 472 schoolchildren were enrolled in the present study,with 439(93.0%)being vaccinated with bacillus calmette-guerin (BCG) and ten (2.1%) having contact history with tuberculosis (TB) patients.Among the 472 eligible subjects,16(3.4%) children were T-SPOT.TB positive,who had no clinical symptoms andsigns relevant to TB and were defined as LTBI.The LTBI prevalence in BCG vaccinated and unvaccinated children were 2.7% and 12.1%,respectively (OR:6.972;95%CI:1.834-26.500);those in TB contacts and children without TB contact history were 30.0% and 2.8%, respectively (OR: 16. 38; 95% CI: 3. 692-72. 700). Conclusions The prevalence of LTBI among senior schoolchildren in Shanghai is 3.4%. BCG vaccination is protective for children from LTBI, while daily contacts with TB patients increases the risk of LTBI in schoolchildren.     

Interferon-gamma release assays in the detection of latent tuberculosis infection in patients with inflammatory arthritis scheduled for anti-tumour necrosis factor treatment

Biological agents, particularly anti-Tumour Necrosis Factor (TNF)-α agents, have emerged as an effective treatment in patients with chronic inflammatory diseases. An association between anti-TNF-α antibodies and reactivation of latent tuberculosis infection (LTBI) has been established. Appropriate screening for TB infection has become mandatory before starting a treatment based on TNF-α inhibition. The objective was to determine the usefulness of IFN-γ release assays in diagnosing LTBI in patients with inflammatory rheumatic diseases scheduled for anti-TNF-α treatment. The study included 53 individuals with inflammatory rheumatism. All patients had a TST, a chest radiograph, QuantiFERON Gold In-Tube (QFN-G-IT) and T-SPOT.TB. To investigate the influence of non-tuberculous mycobacteria (NTM) infections on non-BCG-vaccinated patients, with a positive TST result and both negative IFN-γ assays, we performed an ex vivo ELISPOT, stimulating the cells separately with NTM sensitins. TST was positive in 7 cases, T-SPOT.TB in 11 and QFN-G-IT in 9 cases. Agreement between TST and T-SPOT.TB and QFN-G-IT was 77.35% (κ = 0.33 and κ = 0.40, respectively), and between both in vitro tests, it was 83.01% (κ = 0.57). Of the three patients with positive TST and negative T-SPOT.TB and QFN-G-IT, one positive ELISPOT result was obtained after stimulation with NTM sensitins. Positive TST, T-SPOT.TB and QFN-G-IT results were not affected by the immunosuppressive therapies. IFN-γ release assays are useful methods for avoiding TST false-positive results, but in those patients with a high risk of developing active TB and in the absence of predictive value studies in this specific kind of population for knowing how safe is the use of IGRAs alone, the combined use of TST and IFN-γ tests should be recommended in order to increase the overall number of LTBI diagnoses.     

QuantiFERON-TB Gold test for screening latent tuberculosis infection in hemodialysis patients

Hemodialysis patients are at increased risk of latent tuberculosis infection (LTBI) compared with the general population. QuantiFERON-TB Gold (QFT-G) for LTBI detection is more promising than tuberculin skin test (TST) in hemodialysis patients. The aim of this study is to determine whether the QFT-G is more sensitive than the TST in hemodialysis patients in LTBI. Eighty nine hemodialysis patients were evaluated for latent tuberculosis infection with the TST and QFT-G. Blood was obtained for QFT-G, and then TST was administered to all patients. Demographic information, laboratory tests, chest radiography results and BCG vaccination status were collected on standardized patient medical files. Forty patients had positive QFT-G results. 56 patients had TST induration above 5 mm, 28 patients above 10 mm. 61 patients had BCG vaccination scar. Statistically significant correlation was detected between TST and QFT-G (p< 0.05). In the BCG non-vaccinated subgroup, TST was positive in 8 (29%) patients and the QFT-G was positive in 11 (39%). Among the 21 non vaccinated patients with results for both tests, the concordance between the TST and QFT-G was 82%, k= 0.61, p= 0.001. We found good agreement between the TST and QFT-G test for LTBI in non vaccinated hemodialysis patients, whereas we found poor agreement in vaccinated patients. Because BCG vaccination is widely used in our country, the QFT-G test might be more useful for the diagnosis of LTBI than TST in hemodialysis patients who are suspected to have LTBI.     

Detection of Mycobacterium tuberculosis infection in United States Navy recruits using the tuberculin skin test or whole-blood interferon-gamma release assays.

BACKGROUND: Military personnel are at risk for acquiring Mycobacterium tuberculosis infection because of activities in close quarters and in regions with a high prevalence of tuberculosis (TB). Accurate tests are needed to avoid unnecessary treatment because of false-positive results and to avoid TB because of false-negative results and failure to diagnose and treat M. tuberculosis infection. We sought to estimate the specificity of the tuberculin skin test (TST) and 2 whole-blood interferon-gamma release assays (QuantiFERON-TB assay [QFT] and QuantiFERON-TB Gold assay [QFT-G]) and to identify factors associated with test discordance. METHODS: A cross-sectional comparison study was performed in which 856 US Navy recruits were tested for M. tuberculosis infection using the TST, QFT, and QFT-G. RESULTS: Among the study subjects, 5.1% of TSTs resulted in an induration > or = 10 mm, and 2.9% of TSTs resulted in an induration > or = 15 mm. Eleven percent of QFT results and 0.6% of QFT-G results were positive. Assuming recruits at low risk for M. tuberculosis exposure were not infected, estimates of TST specificity were 99.1% (95% confidence interval [CI], 98.3%-99.9%) when a 15-mm cutoff value was used and 98.4% (95% CI, 97.3%-99.4%) when a 10-mm cutoff value was used. The estimated QFT specificity was 92.3% (95% CI, 90.0%-94.5%), and the estimated QFT-G specificity was 99.8% (95% CI, 99.5%-100%). Recruits who were born in countries with a high prevalence of TB were 26-40 times more likely to have discordant results involving a positive TST result and a negative QFT-G result than were recruits born in countries with a low prevalence of TB. Nineteen (50%) of 38 recruits with this type of discordant results had a TST induration > or = 15 mm. CONCLUSIONS: The QFT-G and TST are more specific than the QFT. No statistically significant difference in specificity between the QFT-G and TST was found using a 15-mm induration cutoff value. The discordant results observed among recruits with increased risk of M. tuberculosis infection may have been because of lower TST specificity or lower QFT-G sensitivity. Negative QFT-G results for recruits born in countries where TB is highly prevalent and whose TST induration was > or = 15 mm suggest that the QFT-G may be less sensitive than the TST. Additional studies are needed to determine the risk of TB when TST and QFT-G results are discordant.