QuantiFERON-TB Gold In-Tube Test Results Research Articles

Evaluation of serial QuantiFERON‐TB Gold in tube test results and tuberculosis infection status in patients with psoriasis receiving anti‐IL‐17 treatment (secukinumab and ixekizumab): Real‐world data from a tuberculosis‐endemic country

AbstractBackgroundIn comparison with TNF‐α inhibitors, anti‐IL‐17A agents are considered to have a lower risk of active tuberculosis (TB) or latent TB infection (LTBI) reactivation.MethodsIn this study, we aimed to evaluate the TB infection status and serial QuantiFERON‐TB‐Gold in tube test (QFT) results of psoriasis patients using IL‐17 inhibitors (secukinumab [SEC] and ixekizumab [IXE]) in a real‐world setting from a tuberculosis‐endemic country. Patients who used an anti‐IL‐17 agent for at least 3 months in our follow‐up were included in the study. Patients' clinical and demographic features, baseline QFT results and latest QFT results (if any), and TB infection status were noted from the past medical records.ResultsA total of 717 patients, of whom 333 (46.4%) were female, were included in the study. The cumulative exposure time to an anti‐IL‐17 agent was 14,147 patient‐months, 9743 patient‐months for SEC and 4404 patient‐months for IXE. Also, 459 (SEC = 305/IXE = 154) patients used an anti‐IL‐17 agent for ≥ 12 months. Of these, 125 had positive baseline QFT results. In all, 334 had negative baseline QFT results. The latest QFT result of 309 was also negative (persistent seronegative group). During follow‐up, the QFT results of 10 patients changed from negative to positive (positive seroconversion group). Seven of them were using SEC and three were using IXE, respectively. No case of active TB infection was detected.ConclusionIn our study, the positive seroconversion rate of 10/334 seems high, but this did not translate to active disease. However, closer monitoring may be required, especially in patients with advanced age, the presence of PsA, long disease duration and long anti‐IL‐17 treatment duration.

Psoriasis'te Biyolojik Tedavi Öncesi Latent Tüberküloz Enfeksiyonunun Değerlendirilmesi: Web Tabanlı Yorumlayıcı ile Yeni Bir Tanı Yaklaşımı

Purpose: The use of biological agents, particularly anti-TNF-alpha treatments, is associated with an elevated risk of tuberculosis (TB). Hence, a comprehensive assessment of latent tuberculosis infection (LTBI) before biologic therapies is imperative. The objective of this study was to evaluate the utility of an online tuberculin skin test (TST)/ interferon-γ release assay (IGRA) interpreter (OI-TST/IGRA) in assessing the risk of LTBI prior to initiating biological therapies in psoriasis patients.
 Materials and methods: 116 psoriasis patients who were previously evaluated for TB by a pulmonologist before being treated with a biologic agent were re-evaluated retrospectively with OI-TST/IGRA (tstin3d.com). Mean positive predictive value (PPV), mean annual risk of development of active tuberculosis (ARDATB), and mean cumulative risk of active tuberculosis (CRATB) values were calculated with OI-TST/IGRA and compared with previous results. Chi-square, Fisher-Freeman-Halton exact tests, Cohen's Kappa, and Mann-Whitney U-test were used in comparisons of groups. 
 Results: The PPV of the LTBI-positive group was significantly higher than the LTBI-negative group. The PPV, ARDATB and CRATB values of the TST size of >15 mm group were significantly higher than the TST size of 5-9 mm and TST size of 10-15 mm groups. The PPV, ARDATB, and CRATB values of the QuantiFERON-TB Gold In-tube test (QFT-GIT)-positive group were significantly higher than the QFT-GIT-negative group. And the same values of the chest X-ray (CXR)-positive group were significantly higher than the CXR-negative group. The PPV, ARDATB, and CRATB values were positively correlated with QFT-GIT and CXR results. In addition, the PPV was positively correlated with previous LTBI decisions and TSTs.
 Conclusion: OI-TST/IGRA in which many factors are questioned and PPV, ARDATB, and CRATB values are evaluated together, may be a valuable tool for assessing the risk of active TB in psoriasis patients and preventing overdiagnosis and unnecessary prophylaxis.

Factors Influencing False-Negative Results of QuantiFERON-TB Gold In-Tube (QFT-GIT) in Active Tuberculosis and the Desirability of Resetting Cutoffs for Different Populations: A Retrospective Study.

Objectives The value of QuantiFERON-TB Gold In-Tube (QFT-GIT) in the diagnosis of TB varies by population, comorbidities, and other factors. In this study, we aimed to investigate factors that influence false-negative results of QFT-GIT test in the diagnosis of TB as well as the impact of different cutoffs on the diagnostic value. Methods A total of 3562 patients who underwent QFT-GIT tests at Shanghai Pulmonary Hospital were enrolled retrospectively between May 2016 and May 2017. False-negative and false-positive results were analyzed using different clinical stratifications. The optimal cutoff values were established under different clinical conditions. Results Positive QFT-GIT results greatly shortened the time taken to diagnose smear-negative TB. The factors of age, smear and culture results, site of TB, comorbidity with tumors, white blood cell count, neutrophil count, and CD4/CD8 ratio were significantly correlated with false-negative QFT-GIT results (p < 0.05). Personalized cutoff values were established according to different influencing factors. The results showed high consistency between the smear-negative and total populations. Conclusion QFT-GIT can facilitate the early diagnosis of smear-negative TB. The diagnostic performance of the QFT-GIT test in the diagnosis of active TB was shown to be affected by many clinical factors. Personalized cutoff values may have superior value in the identification of active tuberculosis under different conditions.

Interferon-Inducible Protein-10 as a Marker to Detect Latent Tuberculosis Infection in Patients with Inflammatory Rheumatic Diseases.

It is important to identify cases of latent tuberculosis infection (LTBI) who are at risk for tuberculosis (TB) reactivation. We aimed to evaluate the performance of interferon (IFN)-gamma-inducible protein 10 (IP-10) as a marker to detect LTBI in patients with inflammatory rheumatic diseases (IRD). This study comprised 76 consecutive subjects with IRD. Patients with a history of TB or having active TB were excluded. In all patients, IP-10 level was measured and tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube test (QFT-GIT) were performed. Seventy patients with complete test results were analyzed. Twenty-one (30%) QFT-GIT-positive patients were defined as having LTBI. IP-10 yielded 2197 pg/mL cut-off point. At this cut-off point, IP-10 showed 89% specificity with a sensitivity of 91% (AUC: 0.950, 95% CI 0.906–0.994). TST, QFT-GIT, and IP-10 were positive in 77.1%, 30%, and 44.3% of the patients, respectively. Concordance among the results of TST, QFT-GIT, and IP-10 tests was evaluated. Agreement was poor between IP-10 and TST (58.6%, κ = 0.19), whereas it was good between QFT-GIT and IP-10 (84.3%, κ = 0.65). The results of the present study demonstrated that sensitivity and specificity of released IP-10 were as high as those of QFT-GIT in indicating LTBI in IRD patient group.

Comparison of QuantiFERON-TB Gold Plus and QuantiFERON-TB Gold In-Tube tests for patients with active and latent tuberculosis: A prospective cohort study

IntroductionWe aimed to determine the diagnostic performance and clinical value of the QuantiFERON-TB Gold In-Tube (QFT-GIT) and QuantiFERON-TB Gold Plus (QFT-Plus) tests in patients with active tuberculosis (TB) or latent TB infection (LTBI). MethodsWe prospectively enrolled 140 patients, including 63 with active TB and 77 with LTBI, between March 2017 and October 2018. QFT-GIT and QFT-Plus were performed simultaneously in all subjects. ResultsQFT-Plus and QFT-GIT test results showed significant agreement, in both active TB and LTBI patients, in terms of the interferon-γ concentration and interpretation result. QFT-Plus had higher sensitivity than QFT-GIT for predicting active TB (82.5% vs. 77.8%) and showed fewer false-negative and indeterminate results in both active TB and LTBI patients due to its “TB2 tube”. The QFT-Plus TB2-TB1 value was higher in the active TB group than in the LTBI group. The QFT-Plus TB1-Nil and TB2-Nil values were useful in predicting remote LTBI, rather than recent LTBI. ConclusionsQFT-Plus showed good agreement with QFT-GIT in both active TB and LTBI patients, and higher sensitivity for predicting active TB than QFT-GIT. The QFT-Plus TB2 tube results, which reflect CD8+ T cell immunity, may improve predictive accuracy and detection of the immune response associated with active TB and LTBI.

Contribution of QuantiFERON-TB Gold-in-Tube to the Diagnosis of Mycobacterium tuberculosis Infection in Young Children in a Low TB Prevalence Country.

Introduction: Interferon Gamma Release Assay (IGRA) has proven to be a useful test to evaluate the immune response to Mycobacterium tuberculosis antigens in children over the age of 5 years as an alternative to tuberculin skin testing (TST). Much less is known about its performance in younger children, who are at higher risk for developing tuberculosis (TB) disease after exposure. We aimed to evaluate the accuracy of using IGRA in TB screening in this population.Methods: Children below the age of 5 years at high risk for TB infection were prospectively enrolled, to compare the performance of TST and the QuantiFERON-TB Gold-In-Tube test (QFT). Children were treated in accordance with the diagnosis made at baseline and followed-up for 12 months.Results: We included a total of 60 children of which 97 blood samples were available for analysis. There was 90.72% agreement between TST and QFT (Kappa test 0.59, moderate agreement). With TST as a reference, the QFT positive predictive value was 0.72 and the negative predictive value 0.93. Discordant results were observed with 6% TST+/QFT– paired tests. When we restricted the comparison of TST and QFT to non-BCG-vaccinated children, the degree of agreement was more substantial (95%, Kappa test 0.75) and the negative predictive value was 0.99. We observed 3% discordant TST–/QFT+ results. All children with active TB disease had concordant positive QFT results, with QFT values above 4.00 IU/ml.Conclusion: In a low TB prevalence country, serial testing of QFT was found to produce a moderate agreement with TST results. False positive QFT results would have been eliminated by using a higher cutoff without misdiagnosing the children with TB disease. Some of the false negative QFT results could be explained by false positive TST results on consecutive testing. For now the most prudent approach would be to consider discordant QFT–/TST+ results as false negative QFT results, taking into account the young age of our population and the potential risk for evolution to active TB disease.

Low Indeterminate Rates Associated With Use of the QuantiFERON-TB Gold In-Tube Test in Children With Inflammatory Bowel Disease on Long-term Infliximab.

Tumor necrosis factor alpha (TNF-α) inhibitors are linked with increased risk of reactivation of active tuberculosis. The QuantiFERON-TB Gold In-Tube test is approved for screening latent tuberculosis infection in children and adults. There are limited data on the test performance in children on long-term treatment with TNF-α inhibitors. The objective of this study was to assess the proportion of indeterminate results for the QuantiFERON-TB Gold In-Tube in children with inflammatory bowel disease (IBD) on long-term infliximab treatment and to evaluate the range of interferon-γ responses to mitogen. A single-center prospective study of children 5 to 19 years of age with IBD on long-term infliximab treatment (>3 months). Each child was assessed for tuberculosis exposure risk and had blood drawn for the QuantiFERON-TB Gold In-Tube. Data on the range of interferon-γ responses and final QuantiFERON-TB Gold In-Tube test results were collected. Ninety-three children were included, with a median age of 16 years. The median total duration of infliximab therapy was 34 months (range, 3-119 months). The QuantiFERON-TB Gold In-Tube was indeterminate in 1 patient (1.1%), positive in 2 patients, and negative in 90 patients. The maximum interferon-γ response to mitogen (10 IU/mL) was observed in 82 patients (88%), with only 1 patient having an inadequate response. The proportion of indeterminate results was significantly lower than the prospectively hypothesized rate of 8%, based on prior studies in nonimmunosuppressed patients (P = 0.004). Pediatric patients with IBD on long-term treatment with infliximab had an adequate interferon-γ response to mitogen and a low indeterminate rate when assessed with the QuantiFERON-TB Gold In-Tube test. This study demonstrates a robust interferon gamma response to phytohemagglutinin stimulation in a pediatric population on long-term therapy with infliximab. The QuantiFERON-TB Gold In-Tube test may therefore be useful as a periodic screening tactic for latent TB in children on long-term infliximab therapy.

QuantiFERON-TB Gold In-Tube Test in the Diagnosis of Latent Tuberculosis Infection in Arthritis Patients Treated with Tumor Necrosis Factor Antagonists.

The aim of this study was to investigate the role of the QuantiFERON-TB Gold In-Tube test (QFT-GIT) in detecting latent tuberculosis in immunocompromised patients before introducing tumor necrosis factor (TNF-α) antagonists. The study included 300 subjects of similar age. The study group comprised of 150 QuantiFERON (QFT) positive subjects with rheumatoid arthritis, Crohn's disease, ulcerative colitis, ankylosing spondylitis and psoriatic arthritis, while control group comprised of 150 QFT negative respondents with the same diseases. Exhaustive medical history was documented for all patients. Screening tests were performed including QFT-GIT, tuberculin skin test (TST), chest radiography and detection of Mycobacterium tuberculosisin sputum culture 2 times. A positive QFT-GIT test result, regardless of TST result, was considered as an indication for latent tuberculosis infection (LTBI) treatment. Results of this study showed good correlation between the conclusive results of QFT-GIT and TST. All study group patients had normal clinical findings, normal radiologic findings and negative results of sputum microbiological analysis during the course of prophylaxis and after its completion and during the course of biological therapy. Conversion of positive QFT-GIT test to negative was observed in 4% of study group patients, while QFT negative respondents remained negative. There was a statistically significant positive correlation between QFTGIT, TST results and patient age, smoking habit and contact with tuberculosis. Study results showed that along with good clinical evaluation and detailed medical history, it is important to conduct testing in order to avoid disease progression or unnecessary isoniazid prophylaxis.

Multidrug-resistant tuberculosis outbreak in an Italian prison: tolerance of pyrazinamide plus levofloxacin prophylaxis and serial interferon gamma release assays.

The optimal treatment for latent tuberculosis infection (LTBI) in subjects exposed to multidrug-resistant (MDR) tuberculosis (TB) remains unclear, and the change in response of the QuantiFERON-TB Gold In-Tube (QTB-IT) test during and after treatment is unknown. Between May 2010 and August 2010, 39 prisoners at the ‘Casa Circondariale’ of Modena, Italy, were exposed to a patient with active pulmonary MDR TB. All contacts were tested with the tuberculin skin test and QTB-IT. Upon exclusion of active TB, subjects positive to both tests were offered 6 months' treatment with pyrazinamide (PZA) and levofloxacin (LVX). QTB-IT testing was repeated at 3 and 6 months after initial testing in all subjects who were offered LTBI treatment. Seventeen (43.5%) of 39 subjects tested positive to both tuberculin skin test and QTB-IT test, and 12 (70.5%) agreed to receive therapy with PZA and LVX at standard doses. Only five (41.6%) of 12 subjects completed 6 months' treatment. Reasons for discontinuation were asymptomatic hepatitis, gastritis and diarrhoea. The QTB-IT values decreased in all subjects who completed the treatment, in two (33%) of six of those who received treatment for less than 3 months and in one (50%) of two patients who discontinued therapy after 3 months. The QTB-IT test results never turned negative. Despite the small number of subjects, the study confirmed that PZA plus LVX is a poorly tolerated option for MDR LTBI treatment. We observed a large degree of variation in the results of the QTB-IT test results among participants. The study confirmed that the interferon gamma release assay is not a reliable tool for monitoring the treatment of MDR LTBI in clinical practice.

Performance of Interferon-Gamma and IP-10 Release Assays for Diagnosing Latent Tuberculosis Infections in Patients with Concurrent Malaria in Tanzania.

Interferon-gamma (IFN-γ) release assays (IGRAs) are used to detect cellular immune recognition of Mycobacterium tuberculosis The chemokine IFN-γ-inducible protein 10 (IP-10) is an alternative diagnostic biomarker to IFN-γ. Several conditions interfere with IGRA test performance. We aimed to assess the possible influence of Plasmodium falciparum infection on the IGRA test QuantiFERON-TB GOLD® In-Tube (QFT) test and an in-house IP-10 release assay. In total, 241 Tanzanian adults were included; 184 patients with uncomplicated malaria (88 human immunodeficiency virus [HIV] coinfected) and 57 HIV-infected patients without malaria infection. Malaria was treated with artemether-lumefantrine (Coartem®). QFT testing was performed before initiation of malaria treatment and at days 7 and 42. In total, 172 patients completed follow-up. IFN-γ and IP-10 was measured in QFT supernatants. We found that during malaria infection IFN-γ and IP-10 levels in the unstimulated samples were elevated, mitogen responsiveness was impaired, and CD4 cell counts were decreased. These alterations reverted after malaria treatment. Concurrent malaria infection did not affect QFT test results, whereas there were more indeterminate IP-10 results during acute malaria infection. We suggest that IGRA and IP-10 release assay results of malaria patients should be interpreted with caution and that testing preferably should be postponed until after malaria treatment.

Association of clinical properties and compatibility of the QuantiFERON-TB Gold In-Tube test with the tuberculin skin test in patients with psoriasis.

Individuals with psoriasis show conflicting responses to the tuberculin skin test (TST), a commonly used screening test for latent tuberculosis infection. An alternative to TST is QuantiFERON-TB Gold In-Tube test (QFT-GIT), an in vitro interferon-gamma release assay. This study aimed to determine the effect of the clinical properties of psoriasis (disease severity and koebnerization status) on TST results and the agreement between the TST and QFT-GIT results in psoriatic patients. One hundred patients with mild to severe psoriasis were enrolled in this prospective cross-sectional study. Psoriasis properties, including disease severity (psoriasis area and severity index score and koebnerization status), latent tuberculosis infection risk factors, and bacillus Calmette-Guérin vaccination history, were recorded. All patients underwent a TST and QFT-GIT. TST positivity cut-off point was ≥10 mm for bacillus Calmette-Guérin-vaccinated patients and ≥5 mm for non-vaccinated patients. Psoriasis area and severity index scores and koebnerization status did not correlate with TST diameters. Only one of the 23 koebnerization-positive patients developed koebnerization in response to TST. QFT-GIT positivity was prominently higher in the TST-positive group, and this was the only factor that differed between the TST-positive and TST-negative groups (P < 0.001). Tuberculin skin test results were not affected by psoriasis severity or koebnerization status. QFT-GIT positivity was prominently higher in the TST-positive group (P < 0.001). Overall agreement between TST and QFT-GIT results was moderate (κ = 0.413). Concurrent negativity (44%) was higher than concurrent positivity (27%).

Factors that Predict Negative Results of QuantiFERON-TB Gold In-Tube Test in Patients with Culture-Confirmed Tuberculosis: A Multicenter Retrospective Cohort Study.

BackgroundInterferon-γ release assays such as the QuantiFERON-TB Gold In-Tube Test (QFT-GIT) are designed to detect Mycobacterium tuberculosis infections, whether latent or manifesting as disease. However, a substantial number of persons with culture-confirmed tuberculosis (TB) have negative QFT-GITs. Information on host factors contributing to false-negative and indeterminate results are limited.MethodsA multicenter retrospective cohort study was performed with 1,264 culture-confirmed TB patients older than 18 years who were subjected to the QFT-GIT at one of the six hospitals between May 2007 and February 2014. Patients with human immunodeficiency virus infection were excluded. Clinical and laboratory data were collected in South Korea.ResultsOf all patients, 87.6% (1,107/1,264) were diagnosed with pulmonary TB and 12.4% (157/1,264) with extrapulmonary TB. The rate of negative results was 14.4% (182/1,264). The following factors were highly correlated with false-negative results in the QFT-GIT: advanced age (age ≥ 65 years, odds ratio [OR] 1.57, 95% confidence interval [CI] 1.03–2.39), bilateral disease as determined by chest radiography (OR 1.75, 95% CI 1.13–2.72), malignancy (OR 2.42, 95% CI 1.30–4.49), and lymphocytopenia (total lymphocyte count < 1.0 × 109/L, OR 1.86, 95% CI 1.21–2.87).ConclusionsConsequently, QFT-GIT results need to be interpreted with caution in patients with these host risk factors such as the elderly, bilateral disease on chest radiography, or malignancy, or lymphocytopenia.

The dynamics of QuantiFERON-TB gold in-tube conversion and reversion in a cohort of South African adolescents.

Interferon-γ release assays are used to diagnose tuberculosis infection. In developed countries, high rates of reversion following conversion have been described. To assess QuantiFERON TB Gold In-Tube test (QFT) conversion and reversion dynamics in a tuberculosis-endemic setting. Adolescents aged 12-18 years residing near Cape Town were recruited. Tuberculin skin tests (TSTs) and QFTs were performed at baseline and after 2 years of follow up. Half of the participants had TST and QFT performed at additional time points. Participants were observed for incident tuberculosis disease for up to 5 years. Among 5,357 participants, 2,751 (51.4%) and 2,987 (55.8%) had positive QFT and TST results, respectively, at baseline. Annualized QFT and TST conversion risks were 14.0 and 13.0%, respectively, and reversion risks were 5.1 and 4.1%, respectively. Concordance was excellent for conversions (κ = 0.74), but poor for reversions (κ = 0.12). Among recent QFT converters, the magnitude of the QFT value was strongly inversely associated with risk of reversion (P < 0.0001). When longitudinal QFT data were analyzed in a cross-sectional manner, the annual risk of infection was 7.3%, whereas inclusion of reversions in the analysis showed that the actual risk of infection was 14.0%. Incident tuberculosis was 8-fold higher among QFT reverters than in participants with all negative QFT results (1.47 vs. 0.18 cases/100 person-years, P = 0.011). In this tuberculosis-endemic setting, annual risk of infection was extremely high, whereas QFT and TST conversion concordance was higher and QFT reversion rates were lower than reported in low-burden settings.

Automation of an Interferon-γ Release Assay and Comparison to the Tuberculin Skin Test for Screening Basic Military Trainees forMycobacterium tuberculosisInfection

We automated portions of the QuantiFERON-TB Gold In-Tube test (QFT-GIT) and assessed its quality when performed concurrently with the tuberculin skin test (TST) among U.S. Air Force basic military trainees (BMTs). The volume of blood collected for QFT-GIT was monitored. At least one of the three tubes required for QFT-GIT had blood volume outside the recommended 0.8- to 1.2-mL range for 688 (29.0%) of 2,373 subjects who had their blood collected. Of the 2,124 subjects who had TST and QFT-GIT completed, TST was positive for 0.6%; QFT-GIT was positive for 0.3% and indeterminate for 2.0%. Among 2,081 subjects with completed TST and determinate QFT-GIT results, overall agreement was 99.5% but positive agreement was 5.6%. Specificity among the 1,546 low-risk BMTs was identical (99.7%). Indeterminate QFT-GIT results were 2.7 times more likely when mitogen tubes contained >1.2 mL blood than when containing 0.8- to 1.2-mL blood. Automation can facilitate QFT-GIT completion, especially if the recommended volume of blood is collected. Mycobacterium tuberculosis infection prevalence among BMTs based on TST and QFT-GIT is similar and low. Selectively testing those with significant risk may be more appropriate than universal testing of all recruits.

Variability of the QuantiFERON®-TB Gold In-Tube Test Using Automated and Manual Methods

BackgroundThe QuantiFERON®-TB Gold In-Tube test (QFT-GIT) detects Mycobacterium tuberculosis (Mtb) infection by measuring release of interferon gamma (IFN-γ) when T-cells (in heparinized whole blood) are stimulated with specific Mtb antigens. The amount of IFN-γ is determined by enzyme-linked immunosorbent assay (ELISA). Automation of the ELISA method may reduce variability. To assess the impact of ELISA automation, we compared QFT-GIT results and variability when ELISAs were performed manually and with automation.MethodsBlood was collected into two sets of QFT-GIT tubes and processed at the same time. For each set, IFN-γ was measured in automated and manual ELISAs. Variability in interpretations and IFN-γ measurements was assessed between automated (A1 vs. A2) and manual (M1 vs. M2) ELISAs. Variability in IFN-γ measurements was also assessed on separate groups stratified by the mean of the four ELISAs.ResultsSubjects (N = 146) had two automated and two manual ELISAs completed. Overall, interpretations were discordant for 16 (11%) subjects. Excluding one subject with indeterminate results, 7 (4.8%) subjects had discordant automated interpretations and 10 (6.9%) subjects had discordant manual interpretations (p = 0.17). Quantitative variability was not uniform; within-subject variability was greater with higher IFN-γ measurements and with manual ELISAs. For subjects with mean TB Responses ±0.25 IU/mL of the 0.35 IU/mL cutoff, the within-subject standard deviation for two manual tests was 0.27 (CI95 = 0.22–0.37) IU/mL vs. 0.09 (CI95 = 0.07–0.12) IU/mL for two automated tests.ConclusionQFT-GIT ELISA automation may reduce variability near the test cutoff. Methodological differences should be considered when interpreting and using IFN-γ release assays (IGRAs).

Performance of QuantiFERON-TB Gold In-Tube test and Tuberculin Skin Test for diagnosis of latent tuberculosis infection in BCG vaccinated health care workers

BackgroundTuberculin skin test (TST) has been used for years as an aid in diagnosing latent tuberculosis infection (LTBI) but it suffers from a number of well-documented performance and logistic problems. Quantiferon-TB Gold In Tube test (QFT-GIT) has been reported to have better sensitivity and specifity than TST. In this study, it was aimed to compare the performance of a commercial IFN-γ release assay (QFT-GIT) with TST in the diagnosis of HCWs at risk for latent TB infection in BCG vaccinated population.Material/MethodsHundred healthy volunteer health care workers were enrolled. All were subjected to TST and QFT-GIT. Results were compared among Health Care Workers (HCWs) groups in terms of profession, workplace, working duration.ResultsTST is affected by previous BCG vaccinations and number of cases with QFT-GIT positivity is increased in accordance with the TST induration diameter range. QFT-GIT result was negative in 17 of 32 TST positive (≥15 mm) cases and positive in 4 of 61 cases whose TST diameters are between 6–14 mm, that is attritutable to previous BCG vaccination(s). It was negative in all cases with TST diameters between 0–5 mm.HCWs with positive QFT-GIT results were significantly older than the ones with negative results. Furthermore duration of work was significantly longer in QFT-GIT positive than in negative HCWs.ConclusionsThere was a moderate concordance between QFT-GIT and TST, when TST result was defined as positive with a ≥15 mm diameter of induration. We suggest that QFT-GIT can be used as an alternative to TST for detection of LTBI, especially in groups with high risk of LTBI and in population with routine BCG vaccination program.

Effect of micronutrient deficiency on QuantiFERON-TB Gold In-Tube test and tuberculin skin test in diagnosis of childhood intrathoracic tuberculosis

Data on performance of QuantiFERON-TB Gold In-Tube test (QFT) and tuberculin skin test (TST) in children with active tuberculosis from high burden countries in the context of micronutrient deficiency are scarce. The objective of this study was to evaluate the effect of micronutrient deficiency on the performance of TST and QFT in children with intrathoracic tuberculosis. Children with probable intrathoracic tuberculosis underwent TST, QFT, gastric lavages and induced sputum examination for AFB (Acid-Fast Bacilli) smear and culture. Zinc, copper, ferritin and vitamin D were measured on stored serum samples. The study used cross-sectional data at initiation of anti-tubercular therapy. Three hundred and sixty-two children (median age 115.5 months (interquartile range: 73, 144), 200 (55.3%) girls) were enrolled in the study. Microbiological confirmation of tuberculosis could be obtained in 128 patients. TST and QFT were positive in 337 (93%) and 297 (82%) children, respectively. Performance of both the tests was unaffected by weight-for-age and height-for-age 'z-scores' or by serum copper levels. TST was not affected by serum zinc and ferritin levels. Children with negative QFT results had lower mean serum zinc level (P=0.01) and higher ferritin levels (P=0.007) as compared to those with positive test. Higher proportion of children with positive TST were vitamin D deficient/insufficient (P=0.003). Micronutrient status, especially serum levels of zinc, may influence the performance of QFT in children with intrathoracic tuberculosis. Considering the high prevalence of zinc deficiency in developing countries, QFT should be used cautiously for diagnosing tuberculosis.

Comparison of QuantiFERON-TB Gold With Tuberculin Skin Test for Detection of Latent Tuberculosis Infection Before Kidney Transplantation

IntroductionScreening for latent tuberculosis infection (LTBI) before kidney transplantation (KT) is an indispensable process, purposes of this study were to compare the QuantiFERON-TB Gold In-Tube test (QFT-GIT) with the tuberculin skin test (TST) for screening of LTBI in kidney transplant recipients (KTRs). MethodsWe compared prospectively the results of QFT-GIT with TST in 97 KTRs screened for LTBI between July 2008 and July 2012. Isoniazid (INH) prophylaxis was applied to KTRs with a positive TST or positive QFT-GIT or clinical risk factors for LTBI. Post-transplant tuberculosis (TB) was diagnosed by clinical evidence. ResultsThe mean patients follow-up was 24.6 ± 14.4 months. Positive results on QFT-GIT and TST was obtained among 19 (20.4%) and 12 (12.9%) subjects, respectively, an overall agreement of 79.3% (κ = 0.27, 95% confidence interval [CI] −0.03–0.50; P < .014). The incidence of TB was 0.52 per 100 person-years (95% CI 0.02–3.68). None of the patients in the INH prophylaxis group developed TB, whereas 1 in the no prophylaxis group developed disease at 14 months after KT. Sensitivity of the 2 tests could not be compared because patients who showed positive results on QFT-GIT or TST did not develop TB. The difference of specificity between QFT-GIT (79.3%) and TST (86.9%) was not significant (P = .l67). Abnormal chest radiographs (odds ratio [OR] 27.94, 95% CI 1.22–636.61, P = .037) and positive TST (OR 7.65, 95% CI 1.75–33.30, P = .007) showed significant associations with positive QFT-GIT results. Only positive QFT-GIT (OR 6.03, 95% CI 1.51–24.01, P = .011) showed an association with positive TST results. ConclusionsQFT-GIT and TST for diagnosis of LTBI in KTRs showed reasonable concordance but no superiority of either test.

Factors influencing discordant results of the QuantiFERON-TB Gold In-tube test in patients with active TB

Indeterminate or negative results from the QuantiFERON-TB Gold In-tube test (QFT-GIT) for TB-confirmed patients indicate the lower sensitivity of this method. The aim of this study was to determine the factors associated with indeterminate and negative QFT-GIT results in active TB patients. We analyzed retrospectively the laboratory and clinical data of patients diagnosed with TB between December 2009 and April 2012 at a tertiary university hospital in Seoul, Korea. Among 1301 patients who underwent QFT-GIT, TB-PCR and TB-culture, 168 (12.9%), those with positive TB-PCR or TB-culture were diagnosed with TB. Thirty-nine (23.2%) had indeterminate or negative results by QFT-GIT assay, which did not correlate with positive results of TB-PCR or TB-culture. These patients were older, had lower lymphocyte, total protein and albumin levels, and showed significantly higher CRP levels than the positive group. Multivariate logistic regression analysis showed that the probability of indeterminate and negative QFT-GIT results increased as CRP (odd ratio, 1.069; 95% CI, 1.013-1.127; P = 0.014) or age (1.030, 1.005-1.056, 0.02) increases. When levels of markers of inflammation, such as CRP, are high or the patient is older, QFT-GIT results should be interpreted carefully and correlated with additional tests for TB.

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.