Positive QuantiFERON-TB Gold In-Tube Results Research Articles

Prevalence and incidence of tuberculosis infection among healthcare workers in chest diseases hospitals, Bangladesh: Putting infection control into context.

Healthcare workers (HCWs) are at increased risk of tuberculosis infection (TBI). We estimated the prevalence and incidence of TBI and risk factors among HCWs in Bangladeshi hospitals to target TB infection prevention and control (IPC) interventions. During 2013-2016, we conducted a longitudinal study among HCWs in four chest disease hospitals. At baseline, we administered a questionnaire on sociodemographic and occupational factors for TB, tuberculin skin tests (TST) in all hospitals, and QuantiFERON ®-TB Gold in-Tube (QFT-GIT) tests in one hospital. We assessed factors associated with baseline TST positivity (induration ≥10mm), TST conversion (induration increase ≥10mm from baseline), baseline QFT-GIT positivity (interferon-gamma ≥0.35 IU/mL), and QFT-GIT conversion (interferon-gamma <0.35 IU/mL to ≥0.35 IU/mL). We included factors with a biologically plausible relationship with TBI identified in prior studies or having an association (p = <0.20) in the bivariate analyses with TST positivity or QFT-GIT positivity in multivariable generalized linear models. The Kaplan-Meier was used to estimate the cumulative TBI incidence rate per 100 person-years. Of the 758 HCWs invited, 732 (97%) consented to participate and 731 completed the one-step TST, 40% had a positive TST result, and 48% had a positive QFT-GIT result. In multivariable models, HCWs years of service 11-20 years had 2.1 (95% CI: 1.5-3.0) times higher odds of being TST-positive and 1.6 (95% CI 1.1-2.5) times higher odds of QFT-GIT-positivity at baseline compared with those working ≤10 years. HCWs working 11-20 years in pulmonary TB ward had 2.0 (95% CI: 1.4-2.9) times higher odds of TST positivity, and those >20 years had 2.5 (95% CI: 1.3-4.9) times higher odds of QFT-GIT-positivity at baseline compared with those working <10 years. TBI incidence was 4.8/100 person-years by TST and 4.2/100 person-years by QFT-GIT. Females had 8.5 (95% CI: 1.5-49.5) times higher odds of TST conversion than males. Prevalent TST and QFT-GIT positivity was associated with an increased number of years working as a healthcare worker and in pulmonary TB wards. The incidence of TBI among HCWs suggests ongoing TB exposure in these facilities and an urgent need for improved TB IPC in chest disease hospitals in Bangladesh.

Host, technical, and environmental factors affecting QuantiFERON-TB Gold In-Tube performance in children below 5 years of age

Interferon-gamma release assays performance can be impaired by host-related, technical and environmental factors, but data in young children are limited. We performed a cross-sectional study of children < 5 years-of-age at risk of tuberculosis (TB), using QuantiFERON-TB Gold In-Tube (QFT-GIT) assays. The impact of the following was evaluated: (i) host-related [age; hematological parameters; erythrocyte sedimentation rate (ESR); C-reactive protein (CRP); and tobacco smoke exposure (TSE) based on serum cotinine concentrations], (ii) technical (pre-analytical delay) and (iii) environmental factors (annual season; monthly temperatures). Of 204 children, 35 (17.2%) were diagnosed with latent TB infection or TB disease. QFT-GIT results were indeterminate in 14 (6.9%) patients. In multivariate analysis, younger age and higher ESR were associated with lower positive control responses (beta: 0.247, p = 0.002 and − 0.204, p = 0.007, respectively), and increasing age was associated with lower rates of indeterminate QFT-GIT results [OR (95% CI) 0.948 (0.903–0.996) per month, p = 0.035]. In children with positive QFT-GIT results, average monthly temperatures correlated with antigen responses (r = 0.453, p = 0.020); also, antigen responses were lower in winter than in other seasons (p = 0.027). Serum cotinine concentrations determined in a subgroup of patients (n = 41) indicated TSE in 36 (88%), positive control responses being lower in children with TSE (p = 0.034). In children < 5 years-of-age, young age, elevated ESR, temperature, annual season and TSE can affect the performance of QFT-GIT assays.

QuantiFERON®-TB Gold In-Tube test can be used for screening latent tuberculosis before biological treatment in a Bacille Calmette-Guérin (BCG)-vaccinated country: the HUR-BIO single-center real-life results.

The Turkish population is vaccinated with Bacille Calmette-Guérin (BCG), and the BCG vaccination decreases the specificity of the tuberculin skin test (TST). The purpose of this study was to investigate the incidence of active tuberculosis (TBC) among rheumatic patients who were screened only with the QuantiFERON®-TB Gold In-Tube (QFT-GIT) test for latent TBC prior to biological treatment. The Hacettepe University Biological Database (HUR-BIO) was used for latent TBC assessment. Consecutive patients were evaluated from July 2015 to October 2016 by a questionnaire that included the patients' demographic characteristics, treatment history, and symptoms of active TBC. A total of 664 patients were interviewed by physicians. TBC statuses of the 671 non-interviewed patients were checked from the Turkish National Tuberculosis Registry records. Mean TBC incidence per year was calculated for anti-tumor necrosis factor-alpha (TNF-α) agents. A total of 1335 (58.2% female) patients with the mean age of 44.2 ± 12.9years were included. Of the patients, 836 (62.6%) had spondyloarthropathy, 432 (32.4%) had rheumatoid arthritis, and 67 (5%) had other rheumatologic diseases. The total biological drug exposure was 2292 patient-years (2043 patient-years for anti-TNF-α, 249 patient-years for non-TNF-α inhibitors). Positive and indeterminate QFT-GIT results were found in 258 (19.3%) and 23 (1.7%) patients, respectively. The median follow-up time after the onset of biological agent was 19.4months (IQR = 29.5). Pulmonary TBC was found in 3 (0.2%) of the 1335 patients. The annual incidence of TBC was 147/100,000 patient-years for all TNF-α inhibitors (249/100,000 and 123/100,000 patient-years for QFT-GIT-positive and negative patients, respectively). TBC incidence increased by nearly seven times the Turkish national TBC incidence. The QFT-GIT Test appears acceptable to determine latent TBC before biological agent use. Consequently, the QFT-GIT Test can be appropriately used in BCG-vaccinated countries. Key Points • Our study contributes to filling the gap in the literature by reflecting real-life data about TBC frequency after QFT-GIT use in patients receiving biological agents. • The frequency of active TBC will remain within acceptable limits when only QFT-GIT is used in the screening of latent TBC prior to the use of biological agents in a population where the majority are vaccinated with BCG. • Using the QFT-GIT alone for latent TBC screening prior to biologic treatment in countries with high BCG vaccination rates reduces the number of patients needing isoniazid (INH) treatment.

Prevalence of Latent Tuberculosis in the Multiple Sclerosis Clinic and Effect of Multiple Sclerosis Treatment on Tuberculosis Testing.

Patients with a compromised immune system are at risk for converting from latent tuberculosis infection (LTBI) to active tuberculosis (TB) infection. Multiple sclerosis (MS) therapies may put individuals with LTBI at higher risk of TB. Patients at the Beth Israel Deaconess Medical Center MS Clinic were screened for TB as part of routine testing with the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay (Cellestis Ltd) from 2013 to 2017. Patients were tested either before or during immunomodulatory therapy. Four of 222 patients (1.8%; 95% CI, 0.1%-3.6%) had positive QFT-GIT results; three patients had risk factors for TB, having emigrated from TB-endemic countries or worked in the health care industry. Twenty-eight of 222 patients (12.6%) had an indeterminate assay result, and 75.0% of these occurred in patients taking dimethyl fumarate. Fingolimod, natalizumab, or anti-CD20 treatments showed 0% to 7.7% indeterminate results. The prevalence of LTBI was 1.8% in the Beth Israel Deaconess Medical Center MS Clinic. Not all LTBI cases were associated with known risk factors for TB. Screening for LTBI before starting immunosuppressive agents for MS could help prevent activation of TB. Dimethyl fumarate use is associated with indeterminate QFT-GIT results, possibly due to functional effects on lymphocytes and levels of cytokines, such as interferon gamma. In contrast, fingolimod use was rarely associated with indeterminate QFT-GIT results despite a high rate of lymphopenia in virtually all patients.

Impact of Baseline Tuberculin Skin Test and Isoniazid Chemoprophylaxis on Subsequent Quantiferon-TB Gold In-Tube Performance in Young Children Assessed After Tuberculosis Contact in Catalonia.

We investigated the impact of baseline tuberculin skin tests (TSTs) and preventive isoniazid chemoprophylaxis on subsequent QuantiFERON-TB Gold In-Tube (QFT-GIT) assays performed after a 10- to 12-week window period in 114 children <5 years of age. Previous TSTs and chemoprophylaxis had no impact on the magnitude of subsequent antigen-induced responses in QFT-GIT. Furthermore, previous TSTs did not induce conversion from a negative to a positive QFT-GIT result.

Abnormalities suggestive of latent tuberculosis infection on chest radiography; how specific are they?

BackgroundSeveral radiological features have been reported in association with latent tuberculosis infection (LTBI) but it has not been studied which are specific. The aim of this study was to evaluate allegedly characteristic abnormalities on chest radiography (CXR) in patients with LTBI compared to uninfected controls. MethodsFrom 236 patients tested with QuantiFERON-TB Gold In-Tube (QFT), the CXR was re-evaluated in a blinded fashion for fibrotic scarring, (non-)calcified nodules and pleural thickening. LTBI was defined as presence of a positive QFT result and/or positive tuberculin skin test result stratified by Bacille Calmette-Guérin-vaccination status. ResultsAny predefined abnormality of LTBI was observed in 116/236 (49.2%) patients, the frequency not being different between groups. However, the specificity for LTBI of a fibrotic scar ≥ 2 cm2 was 100% [95% CI: 92.0%–100%] and of a calcified nodule ≥1.5 mm was 95.7% [95% CI: 85.2%–99.5%]. The frequency of non-calcified nodules and pleural thickening did not differ between groups. ConclusionOnly a fibrotic scar ≥ 2 cm2 and/or a calcified nodule ≥1.5 mm were significantly associated with LTBI. This finding is clinically relevant mainly in patients who are at significant risk of TB reactivation and in whom indirect diagnostic tests may be unreliable.

754. Prevalence of Latent Tuberculosis Infection Among Healthcare Workers at a Tertiary Care University Hospital

BackgroundWe investigated the prevalence of latent tuberculosis infection (LTBI) among healthcare workers (HCWs) and analyzed its risk factors in a tertiary care university hospital in South Korea in a population with intermediate tuberculosis (TB) burden.MethodsA standard questionnaire regarding the baseline demographics and risk factors for LTBI was given to each participant. QuantiFERON-TB GOLD In-Tube (QFT-GIT) assay and chest radiography were performed to investigate the rate of LTBI.ResultsA total of 1,429 participants, 213 (14.9%) doctors and 988 (69.1%) nurses and 228 (16.0%) others were enrolled. The mean age of the subjects was 33.0 years old, and 1,175 (82.2%) were female. Of the participants, 94.5% had received BCG vaccine. QFT-GIT assays were positive for 156 subjects (10.9%). Of the 213 doctors, 28 (13.1%) were positive by QFT-GIT, and among the 988 nurses, 94 (9.5%) had positive QFT-GIT results. Experience of working in hospital was significantly associated with positive LTBI test results by QFT-GIT assay. Gender and duration of employment as an HCW were significantly associated with having a positive QFT-GIT result in univariate analyses. In multivariate analyses, duration of employment as an HCW (>15 years) (odds ratio, 1.98; 95% confidence interval, 1.14–3.43) was independently associated with increased risk of a positive QFT-GIT result.ConclusionA high prevalence of LTBI was found among our HCWs. Considering the association between the experience of working in hospital and high risk of LTBI. The risk for tuberculosis infection among HCWs was higher than general population, which suggests that stricter preventive strategies against nosocomial tuberculosis infection should be implemented.Disclosures All authors: No reported disclosures.

Impact of Choice of Test for Latent Tuberculosis Infection on Treatment Acceptance and Completion.

Objective:The aim of this study is to assess whether choice of test for tuberculosis (TB) infection affects decisions to accept and complete treatment among contacts to TB cases.Methods:Retrospective study is conducted in which TB contacts, ⩾15 years old during 2005 and 2009, were tested for infection with either a tuberculin skin test (TST) or an interferon-gamma release assay test, the QuantiFERON-TB Gold In-Tube (QFT-GIT).Results:Of 658 persons with valid test results, 185 (28%) had positive results, including 128 of 406 (32%) who had TST and 57 of 252 (23%) who received QFT-GIT. Treatment acceptance was 43 of 57 (75%) among QFT-GIT-positive and 97 of 128 (76%) among TST-positive persons (risk ratio [RR] = 1.0, 95% confidence interval [CI], 0.83-1.2). Treatment completion was 56% among QFT-GIT-positive (32 of 57) and 59% (75 of 128) among TST-positive persons (RR = 0.96, 95% CI, 0.73-1.26).Discussion:Our study showed no difference in proportions of TB contacts ⩾15 years old with positive TST results who accepted or completed LTBI treatment compared with those with positive QFT-GIT results. Future studies should include high-risk persons with no known TB exposure, who constitute the main reservoir for TB cases in the United States.

The QuantiFERON-TB Gold In-Tube Assay in Neuro-Ophthalmology

Although QuantiFERON-TB Gold In-Tube (QFT-GIT) testing is regularly used to detect infection with Mycobacterium tuberculosis, its utility in a patient population with a low risk for tuberculosis (TB) has been questioned. The following is a cohort study analyzing the efficacy of QFT-GIT testing as a method for detection of active TB disease in low-risk individuals in a neuro-ophthalmologic setting. Ninety-nine patients from 2 neuro-ophthalmology centers were identified as having undergone QFT-GIT testing between January 2012 and February 2016. Patients were divided into groups of negative, indeterminate, and positive QFT-GIT results. Records of patients with positive QFT-GIT results were reviewed for development of latent or active TB, as determined by clinical, bacteriologic, and/or radiographic evidence. Of the 99 cases reviewed, 18 patients had positive QFT-GIT tests. Of these 18 cases, 12 had documentation of chest radiographs or computed tomography which showed no evidence for either active TB or pulmonary latent TB infection (LTBI). Four had chest imaging which was indicative of possible LTBI. None of these 18 patients had symptoms of active TB and none developed active TB within the follow-up period. Based on our results, we conclude that routine testing with QFT-GIT in a low-risk cohort did not diagnose active TB infection. We do not recommend routine QFT-GIT testing for TB low-risk individuals, as discerned through patient and exposure history, ocular examination, and clinical judgment, in neuro-ophthalmology practice.

Risk of Tuberculosis Among Patients on Dialysis: The Predictive Value of Serial Interferon-Gamma Release Assay.

Patients on long-term dialysis are at high risk for tuberculosis (TB). Although latent tuberculosis infection (LTBI) is good target for TB eradication, interferon-gamma release assay-defined LTBI has a high proportion of negative conversion and lacks active TB correlation among patients on dialysis.Patients on long-term dialysis were screened in multiple centers in Taiwan. QuantiFERON-TB Gold In-tube (QFT-GIT) was used to define LTBI and was performed thrice at 6-month intervals. The primary outcome was active TB diagnosed after LTBI screening. The incidence and predictive value of QFT-GIT were analyzed.The 940 dialysis patients enrolled had an average age of 59.3 years. The initial QFT-GIT results were positive in 193, including 49.6% with persistent positive results on second check. In an average follow-up period of 3 years, 7 patients had TB. Three (319.1 per 100,000 person-yrs) and 4 (141.8 per 100,000 person-yrs) of them were prevalent and incident TB cases, respectively. Persistent positive QFT-GIT for 2 and 3 times correlated with increased hazard ratio for TB (14.44 and 20.29, respectively) compared with a single positive result (hazard ratio 10.38). Among those with 3 positive QFT-GIT results, TB development rate was 4.5% and incidence rate was 1352.3 per 100,000 person-years. In contrast, none of the incident TB occurred in those with initial positive and then negative conversion of QFT-GIT.In an area of intermediate TB incidence, dialysis patients have high TB risk. LTBI status is a good predictor of TB development, especially for those with more than 1 positive result. After excluding prevalent TB cases, serial follow-up of LTBI may narrow the target population to reduce treatment costs.

QuantiFERON-TB Gold In-Tube assay for screening arthritis patients for latent tuberculosis infection before starting anti-tumor necrosis factor treatment.

BackgroundPatients undergoing anti-tumor necrosis factor (TNF) treatment are at an increased risk of reactivating a latent tuberculosis infection (LTBI). This study evaluated the effectiveness of the QuantiFERON-TB Gold In-Tube (QFT) assay for diagnosing LTBI in arthritis patients undergoing anti-TNF treatment.MethodsWe enrolled 342 consecutive patients from August 2007 to October 2013: 176 (51.5%) patients with ankylosing spondylitis and 166 (48.5%) with rheumatoid arthritis. Screening tests included tuberculin skin test (TST) and QFT assay. Positive QFT results, regardless of TST results, were considered an indicator for LTBI treatment.ResultsBacillus Calmette-Guérin scars were found in 236 (69.0%) patients. Of 342 patients, TST and QFT were positive in 122 (35.7%) and 103 (30.1%) patients, respectively, and discordant in 101 (29.5%) patients. During a median follow-up duration of 41.7 months, five patients (1.5%) developed TB in a median of 20.8 months after initiation of anti-TNF treatment (428/100,000 person-years). TB did not occur in 62 TST+/QFT+ patients who received LTBI treatment. Of 41 TST−/QFT+ patients who received LTBI treatment, one (2.4%) developed TB 20.5 months after starting anti-TNF treatment (705/100,000 person-years). Of 60 TST+/QFT− patients who did not receive LTBI treatment, two (3.3%) developed TB 20.8 and 22.0 months after starting anti-TNF treatment (871/100,000 person-years). Of 179 TST−/QFT− patients, two (1.1%) developed TB 7.2 and 22.7 months, respectively, after initiating anti-TNF treatment (341/100,000 person-years). TB incidence rate during the follow-up period did not differ among TST−/QFT+, TST+/QFT−, and TST−/QFT− patients (P = 0.661).ConclusionQFT might be used instead of TST for diagnosing LTBI in patients before starting anti-TNF therapy in countries, such as Korea, where the TB prevalence is intermediate and the BCG vaccination is mandatory at birth. In the absence of a true gold standard test for LTBI, however, there is still a risk of TB development during anti-TNF treatment.

Diagnosis of latent tuberculosis infection before initiation of anti-tumor necrosis factor therapy using both tuberculin skin test and QuantiFERON-TB Gold In Tube assay.

Reactivation of latent tuberculosis infection (LTBI) is an important complication in patients treated with tumor necrosis factor-alpha (TNF-α) blocking agents. However, the best method for LTBI detection before initiation of anti-TNF therapy remains to be determined. From January 2010 to August 2013, anti-TNF therapy was initiated in 426 patients with immune-mediated inflammatory diseases (IMIDs). Tuberculin skin test (TST) and Quantiferon-TB Gold In Tube (QFT-GIT) assay were performed before starting anti-TNF treatment. LTBI was defined as a positive TST (induration ≥ 10 mm) or as a positive QFT-GIT result. Patients were followed up until December 2013. The positive TST and QFT-GIT rates were 22.3% (95/426) and 16.0% (68/426), respectively, yielding a total of 27.0% (115/426) of positive LTBI results. LTBI treatment was initiated in 25.1% (107/426) and was completed in 100% (107/107) of patients. During a median 294 days of follow-up, active TB occurred in 1.4% (6/426) of the patients with negative TST and QFT-GIT results at baseline. The either test positive strategy, using both TST and QFT-GIT assay, is acceptable for LTBI screening before commencing anti-TNF therapy in patients with IMIDs.

Tuberculosis examination using whole blood interferon-gamma release assay among health care workers in a Japanese hospital without tuberculosis-specific wards

Occupational latent tuberculosis infection (LTBI) among health care workers (HCWs) is an important public health issue. The objective of this study is to assess prevalence and risk factors of LTBI among Japanese HCWs by Quantiferon-TB Gold in Tube (QFT-GIT) and the structured questionnaire. This is a cross-sectional study involving HCWs from a hospital without tuberculosis-specific wards, receiving QFT-GIT for LTBI screening. We reviewed medical records of HCWs and questioned HCWs about exposure to M. tuberculosis and employment length in health care industries. 165 HCWs, approximately 80% of the total hospital staff, were enrolled in this study.18 out of 165 subjects had positive results, suggesting LTBI prevalence rate of 11%. Multiple regression analysis revealed a significant association between the positive or intermediate QFT-GIT results and history of contact investigation for tuberculosis. QFT-GIT positivity rate among HCWs is higher than among general population in Japan.

Predictive factors for tuberculosis in patients with a TB-PCR-negative bronchial aspirate

Pulmonary tuberculosis (PTB), with a tuberculosis (TB)-polymerase chain reaction (PCR)-negative bronchial aspirate (BA), but a positive culture result is often encountered in clinical practice. However, limited data are available concerning clinical judgment in patients with suspected PTB and a TB-PCR-negative BA pending culture results. The present study aimed to identify predictors for PTB in patients with a TB-PCR-negative BA. A retrospective study was conducted on patients who had undergone a bronchoscopy because of suspected PTB. Clinical, laboratory, and computed tomography (CT) findings were investigated in PTB patients with TB-PCR-negative but positive culture BA results, and non-PTB patients with a radiographic lesion comparable to the former. Of 250 patients screened, 31 (12 %) were diagnosed with PTB by positive culture results only. Of these 31 patients, 30 (97 %) had a lesion within one-third of the hemithorax as determined by chest radiography. In the final analysis of 30 PTB and 65 non-PTB patients with comparable radiographic lesions, a positive QuantiFERON-TB Gold In-Tube (QFT) result was independently associated with an increased risk of a positive TB culture. CT findings of consolidation were a negative predictor for PTB. Patients with a negative QFT result and consolidation had a negative predictive value of 95 % for PTB, while patients with a positive QFT result and nodular CT abnormalities without consolidation had a positive predictive value of 86 % for PTB. The simple combination of CT findings of consolidation and QFT test results may help clinicians to refine decision-making in patients with a TB-PCR-negative BA.

Prevalence of Latent Tuberculosis Infection among Health Care Workers in South Korea: A Multicenter Study

BackgroundWe investigated the prevalence of latent tuberculosis infection (LTBI) among the health care workers (HCWs) and analyzed its risk factors in South Korea.MethodsA standard questionnaire regarding the baseline demographics and risk factors for LTBI was given to each participant and tuberculin skin test (TST), QuantiFERON-TB GOLD In-Tube (QFT-GIT) assay, and chest radiography were performed.ResultsA total of 493 participants, 152 (30.8%) doctors and 341 (69.2%) nurses were enrolled in eight tertiary referral hospitals. The mean age of the subjects was 30.6 years old, and 383 (77.7%) were female. Of the 152 doctors, 63 (41.4%) and 36 (23.7%) were positive by TST and by QTF-GIT, respectively, and among the 341 nurses, 119 (34.9%) and 49 (14.4%) had positive TST and QFT-GIT results, respectively. Overall, the agreement between the two tests was 0.22 by the chance corrected proportional agreement rate (kappa coefficient) in 493 subjects. Experience of working in tuberculosis (TB)-related departments was significantly associated with positive LTBI test results by QFT-GIT assay, not by TST. In multivariate analysis, only age was independently associated with increased risk of a positive TST result, while age and experience of working in TB-related departments (odds ratio, 2.29; 95% confidence interval, 1.01-5.12) were independently associated with increased risk of a positive QFT-GIT result.ConclusionA high prevalence of LTBI was found among South Korean HCWs. Considering the association between the experience of working in TB-related departments and high risk of LTBI, QFT-GIT may be a better diagnostic test for LTBI than TST in HCWs.

Investigation of False-Positive Results Given by the QuantiFERON-TB Gold In-Tube Assay

We investigated a sudden increase in the rate of positive QuantiFERON-TB Gold In-Tube results from 10% to 31% at a U.S. academic institution. Direct comparison of the TB antigen tubes with tubes from a different lot number identified that a potential problem with the TB antigen vials in a certain tube lot was the likely cause of the elevated positive rate. The underlying defect remains unknown. This finding warrants refinement of quality control programs by the manufacturer and users.

Identifying predictors of interferon-γ release assay results in pediatric latent tuberculosis: a protective role of bacillus Calmette-Guerin?: a pTB-NET collaborative study.

Interferon-γ (IFN-γ) release assays are widely used to diagnose latent infection with Mycobacterium tuberculosis in adults, but their performance in children remains incompletely evaluated to date. To investigate factors influencing results of IFN-γ release assays in children using a large European data set. The Pediatric Tuberculosis Network European Trials group pooled and analyzed data from five sites across Europe comprising 1,128 children who were all investigated for latent tuberculosis infection by tuberculin skin test and at least one IFN-γ release assay. Multivariate analyses examined age, bacillus Calmette-Guérin (BCG) vaccination status, and sex as predictor variables of results. Subgroup analyses included children who were household contacts. A total of 1,093 children had a QuantiFERON-TB Gold In-Tube assay and 382 had a T-SPOT.TB IFN-γ release assay. Age was positively correlated with a positive blood result (QuantiFERON-TB Gold In-Tube: odds ratio [OR], 1.08 per year increasing age [P < 0.0001]; T-SPOT.TB: OR, 1.14 per year increasing age [P < 0.001]). A positive QuantiFERON-TB Gold In-Tube result was shown by 5.5% of children with a tuberculin skin test result less than 5 mm, by 14.8% if less than 10 mm, and by 20.2% if less than 15 mm. Prior BCG vaccination was associated with a negative IFN-γ release assay result (QuantiFERON-TB Gold In-Tube: OR, 0.41 [P < 0.001]; T-SPOT.TB: OR, 0.41 [P < 0.001]). Young age was a predictor of indeterminate IFN-γ release assay results, but indeterminate rates were low (3.6% in children < 5 yr, 1% in children > 5 yr). Our data show that BCG vaccination may be effective in protecting children against Mycobacterium tuberculosis infection. To restrict use of IFN-γ release assays to children with positive skin tests risks underestimating latent infection.

Association of the level of IFN- produced by T cells in response to Mycobacterium tuberculosis-specific antigens with the size of skin test indurations among individuals with latent tuberculosis in a highly tuberculosis-endemic setting

There is growing evidence showing the potential of T-cell-based gamma interferon (IFN-γ) release assays (IGRAs) for predicting the risk of progression of Mycobacterium tuberculosis (Mtb) infection, though there is little information from tuberculosis (TB)-endemic settings. In this study, we assessed the association between the level of IFN-γ produced by T cells in response to Mtb-specific antigens and the size of skin test indurations in 505 adult individuals who were screened for latent tuberculosis infection (LTBI) using the QuantiFERON-TB Gold In Tube (QFTGIT) assay and tuberculin skin test (TST). There was a strong positive correlation between the level of IFN-γ induced by the specific antigens and the diameter of the skin indurations (Spearman's rho = 0.6, P < 0.001). Body mass index and parasitic infection were not associated with the level of IFN-γ production or the TST reaction. In linear regression analysis, the size of the skin test indurations was significantly associated with the mean level of IFN-γ [coefficient, 0.65; 95% confidence interval (CI), 0.47 to 0.82, P < 0.001]. Similarly, results from logistic regression analysis demonstrated that individuals who had skin test indurations ≥ 10 mm were 6.82 times more likely than individuals who had skin test indurations < 10 mm to have high levels of IFN-γ (i.e. positive QFTGIT result) (adjusted odd ratio = 6.82; 95% CI, 3.67 to 12.69, P < 0.001). In conclusion, the results of this study could provide indirect evidence for the prognostic use of the QFTGIT assay for progression of Mtb infection, though prospective follow-up studies are needed to provide direct evidence.

Comparison of the 2-step tuberculin skin test and the quantiFERON-TB gold in-tube test for the screening of tuberculosis infection before liver transplantation

The ability of interferon-gamma release assays (IGRAs) to detect latent tuberculosis (TB) infection before liver transplantation (LT)is not well established. The aims of this study were (1) to compare the ability of the tuberculin skin test (TST) and the QuantiFERON-TB Gold In-Tube (QFT-IT) test (a whole-blood IGRA) to diagnose latent TB infections in patients awaiting LT and (2) to correlate the results with the severity of liver disease. We conducted a prospective, cross-sectional study of patients who were evaluated for LT between July 2008 and July 2010. The 95 patients who were included underwent the 2-step TST and the QFT-IT test. The mean Model for End-Stage Liver Disease (MELD) score was 13.8. Forty-four patients (46.3%) had positive TST results, 42 (44.2%) had positive QFT-IT results, and 2 (2.1%) had indeterminate QFT-IT results. Simultaneous TST and QFT-IT testing yielded a positivity rate of 55.8% [95% confidence interval (CI) = 45.3-65.9] with either test, and the 2-step TST yielded a positivity rate of 46.3% (95% CI = 36.1-56.8); the difference was 9.5% (P = 0.004). In an adjusted analysis, the rates for positive TST results were lower in patients with MELD scores > or = 18 [odds ratio (OR) = 0.2, 95% CI = 0.04-0.7], lower in Child-Pugh-Turcotte (CPT) class C patients versus CPT class A patients (OR = 0.1, 95% CI = 0.02-0.6), and higher in males (OR = 6.4, 95% CI = 1.9-22.0). In contrast, only being male (OR = 3.5, 95% CI = 1.1-11.0) was associated with positive QFT-IT results; no association was found with the MELD score (OR = 0.8, 95% CI = 0.2-2.8) or the CPT class (OR = 0.3; 0.05-1.4). In conclusion, the QFT-IT test is better than the TST for detecting latent TB infection in patients with more advanced liver disease. Our results support the regular use of the QFT-IT test for screening patients with end-stage liver disease for latent TB infection before LT.

Clinical applicability of Quantiferon‐TB‐Gold testing in psoriasis patients during long‐term anti‐TNF‐alpha treatment: a prospective, observational study

Psoriasis patients who are treated with tumour necrosis factor (TNF)-alpha antagonists are at increased risk of reactivation of latent tuberculosis infection (LTBI) and should be adequately screened and monitored during active treatment. To evaluate in a prospective study, the performance of Quantiferon-TB-Gold in tube (QFT) in vitro assay compared to the conventional tuberculin skin test (TST) in detecting LTBI among a cohort of non-BCG-vaccinated patients with moderate-to-severe psoriasis during long-term treatment (12 months) with TNF-alpha antagonists. A total of 50 patients underwent QFT and TST testing at baseline and after 6 and 12 months of continuous anti-TNF-alpha treatment. Diagnosis of LTBI was made on the basis of a positive QFT result and negative chest-radiographic and microbiological assays. Patients with LTBI were subjected to standard isoniazid chemoprophylaxis and after 1 month, they resumed anti-TNF-alpha treatment with subsequent QFT and TST testing after 6 months. In all the cases, a follow-up period of 12 months was observed. During the 12-month-study period, 14% of patients presented a QFT conversion. During active anti-TNF-alpha treatment, a QFT conversion was observed in 10% of patients (five cases). Agreement between QFT and TST was moderate (κ=0.408) at screening, good (κ=0.734) after 6 months and fair (κ=0.328) after 12 months of treatment. A total of 18% of patients presented a positive, discordant TST during the study period. A single-test QFT-based screening strategy for LTBI in psoriasis patients receiving long-term anti-TNF-alpha treatment could reduce the incidence of false-positive LTBI cases, preventing unnecessary TB chemoprophylaxis.