Predictors of Discordant Tuberculin Skin Test and QuantiFERON-TB Gold In-tube Results in Eastern China: A Population-based, Cohort Study.

BACKGROUND: Discordance between the QuantiFERON-TB Gold In-tube (QFT) and tuberculin skin test (TST) is not well understood. We aimed to identify the factors that determine discordance between the TST and QFT when compared to either TST+QFT+ or TST-QFT- results in a medium tuberculosis (TB) burden setting. METHODS: We conducted a population-based study in Eastern China and administered TSTs and QFTs to participants. We calculated kappa values while constructing multivariable logistic regression models to evaluate predictors of test discordance. We analyzed the predictive value of discordant and concordant test results for progression to TB over 6 years of follow-up. RESULTS: Overall, 5405 participants were enrolled; 2043 (37.8%) and 1104 (20.4%) were TST and QFT positive, respectively. There was fair agreement between the TST and the QFT (kappa values between 0.30-0.39 at different TST cutoffs). Agreement was lower among participants vaccinated with Bacillus Calmette-Guerin (BCG; κ, 0.17 versus 0.47 in nonvaccinated participants). TST+QFT- results were associated with decreasing age, smoking, undiagnosed diabetes, and BCG vaccination (adjusted odds ratio, 1.45; 95% confidence interval [CI], 1.11-1.90). TST-QFT+ results were associated with increasing age, male sex, smoking, and diagnosed diabetes. Compared to participants with TST-QFT- results, QFT+ and TST+QFT+ participants were 6.3 (95% CI, 1.9-20.4) and 7.5 (95%CI, 2.3-25.1) times more likely to progress to TB, respectively. CONCLUSIONS: In this population-based study of over 5000 participants from a medium TB burden region, the test agreement between QFT and TST was fair overall and we found multiple novel predictors of discordant QFT/TST results. QFT provides a substantial improvement to the TST among these populations and was multi-fold better at predicting progression to TB.

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

INTRODUCTION: We 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). METHODS: We 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. RESULTS: QFT-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. CONCLUSIONS: QFT-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.

Latent Tuberculosis Infection Increases in Kidney Transplantation Recipients Compared With Transplantation Candidates: A Neglected Perspective in Tuberculosis Control.

BACKGROUND: The prevalence and incidence of latent tuberculosis infection (LTBI) in patients with kidney transplantation remain unclear. METHODS: In this prospective study, we enrolled kidney transplantation candidates (KTCs) and recipients (KTRs) from 2014 to 2018. We defined LTBI as a positive result of QuantiFERON-TB Gold In-tube (QFT). We analyzed the predictors for LTBI acquisition and followed up on QFT assay test for 2 years among those initially without LTBI. RESULTS: Of 425 patients enrolled, 305 (71.8%) patients belonged to the KTC group and 120 (28.2%) to the KTR group. The initial QFT showed positive results in 32 (10.5%) and 24 (20.0%) patients in the KTC and KTR groups, respectively (P = .009). The QFT response value in patients with LTBI was higher in the KTR group than in the KTC group (1.85 vs 1.06 IU/mL, P = .046). Multivariate logistic regression showed that old age, absence of bacillus Calmette-Guérin (BCG) scar, presence of donor-specific antibody, and KTR group were independent factors for positive LTBI. For participants with initial negative QFT, positive QFT conversion within a 2-year follow-up was higher after kidney transplantation (20%) than in KTCs (5.5%) (P = .034). CONCLUSIONS: This study is the first cohort to follow up LTBI status in patients with kidney transplantation and shows its higher prevalence and incidence in KTRs. It indicates that surveillance of LTBI after renal transplantation is important. In addition to status of kidney transplantation, old age, no BCG vaccination, and positive donor-specific antibody are also positive predictors for LTBI.

Fourth-Generation QuantiFERON-TB Gold Plus: What Is the Evidence?

QuantiFERON-TB Gold Plus (QFT-Plus) is the latest generation of interferon gamma release assays (IGRAs) to receive approval from the U.S. FDA, replacing its predecessor, QuantiFERON-TB Gold In-Tube (QFT-GIT). The novelty of QFT-Plus is that it elicits a response from CD8 T cells, in addition to CD4 T cells, thus collecting a broader response from T-cell subsets than QFT-GIT. It was developed with the aim to improve the detection of latent tuberculosis infection (LTBI), especially among recently exposed contacts, immunocompromised hosts, and young children. In this minireview, we summarize the performance of QFT-Plus compared with that of QFT-GIT among active tuberculosis (TB) patients (a surrogate for LTBI patients), high-risk populations, and low-risk individuals based on recent publications. Studies comparing QFT-Plus to QFT-GIT currently do not support the superior performance of QFT-Plus in individuals with active TB and LTBI. The difference in sensitivity between QFT-Plus and QFT-GIT in active TB patients was not significant in nearly all studies and ranged from -4.0 to 2.0%. Among high-risk groups, the agreement between QFT-Plus and QFT-GIT was 89.9 to 96.0% (kappa coefficient range, 0.80 to 0.91). The specificity in the low-risk population was slightly lower for QFT-Plus than for QFT-GIT, with the difference ranging from -7.4 to 0%. Further studies are needed to accurately evaluate the sensitivity of QFT-Plus in immunocompromised hosts and children. In addition, further evidence is required to validate a modified interpretation of QFT-Plus for the identification of false-positive results in low-risk health care workers.

Clinical application of QuantiFERON-TB Gold in-tube in the diagnosis and treatment of tuberculosis.

At present, although it has made great progress in the diagnosis and treatment of tuberculosis, tuberculosis is still an important cause of morbidity and mortality. There were approximately 8.6 million new cases of tuberculosis in 2012, and approximately 1.3 million people died from tuberculosis. Early diagnosis and timely treatment are essential for controlling the spread of tuberculosis infection and reducing mortality. Conventional methods of Mycobacterium tuberculosis detection such as acid-fast staining microscopy and tuberculin skin test are widely used, but with low sensitivity or specificity. In recent years, a newly developed quantitative test, γ-interferon release test (IGRA), has been recognized and widely applied to the early diagnosis and monitoring of tuberculosis. QuantiFERON-TB Gold in-tube (QFT-GIT) is one of the mature IGRA methods. This paper summarizes the researches on QFT-GIT in recent years and introduces its principles, methodology, clinical application, and factors of uncertain results for the diagnosis and treatment of tuberculosis.

Treatment of latent tuberculosis infection with short-course regimens in potential living kidney donors.

BACKGROUND: Treatment data for latent tuberculosis infection (LTBI) among potential living kidney donors are scarce. METHODS: This retrospective study was performed to evaluate the prevalence of positive QuantiFERON-TB Gold In-Tube (QFT-GIT) among potential living kidney donors that were screened from 2009 to 2017. We investigated if there was any difference in the time to donation between QFT-GIT-positive and QFT-GIT-negative donors. We assessed the regimens used to treat LTBI and whether the recipients of QFT-GIT-positive donors developed active tuberculosis (TB). RESULTS: Forty out of 427 (9%) potential living kidney donors had a positive QFT-GIT. QFT-GIT-positive donors were as likely as negative donors to undergo donation (30 [75%] vs 315 [81%], P = .33). The time from QFT-GIT testing to donation was longer among QFT-GIT-positive donors (median 221 days [range: 4-1139] vs 86 days [range: 3-1887], P = .001). Twelve-week rifapentine (RPT)/Isoniazid (INH) was the most common treatment used and was not associated with significant adverse reactions. There was a trend toward longer time to donation among QFT-GIT-positive donors who were treated for LTBI compared with QFT-GIT-positive donors who were not (252 days [range: 88-1139] vs 95 days [range: 4-802], P = .05). Twenty-nine recipients of QFT-GIT-positive living kidney donors were evaluated. Eleven of these recipients received kidneys from donors that were not treated for LTBI. Two of these recipients were treated with INH post-transplantation. CONCLUSIONS: The time from QFT-GIT testing to donation was longer among QFT-GIT-positive donors. The short-course regimens appear to be excellent options for LTBI treatment among living kidney donors and avoid delaying organ donation further.

Evaluation of QuantiFERON tuberculosis Gold In-Tube assay for diagnosis of active tuberculosis in children.

AIM: Tuberculin skin test (TST) is still used in diagnostic algorithms of childhood tuberculosis (TB). QuantiFERON TB Gold In-Tube assay (QFT-GIT) is an alternative test to TST based on the detection of interferon-gamma release upon in vitro induction of peripheral mononuclear cells by TB antigens. In this study, we aimed to determine the diagnostic value and performance of QFT-GIT for active childhood TB. METHODS: This retrospective study was conducted between January 2005 and December 2011 in three referral hospitals in Turkey with 124 children who were diagnosed with definite active TB. Sensitivity values of TST and QFT-GIT were determined by accepting the microbiological confirmation as the gold standard of diagnosis of TB. RESULTS: In our study, sensitivity of QFT-GIT and TST was found to be 65 and 66% respectively. However, combined usage of QFT-GIT and TST was found to be more sensitive (85%) than TST or QFT-GIT alone (P < 0.0001). Although negative results of QFT-GIT or TST did not exclude the diagnosis of active TB in children, their positivity supported the diagnosis. Specificity could not be measured as only microbiologically confirmed cases of Mycobacterium tuberculosis disease were enrolled in the study. CONCLUSION: Although sensitivities of TST and QFT-GIT are too low to exclude active TB, their positivity supports diagnosis of active TB in children concomitant with signs and symptoms. QFT-GIT and TST should be used together to enhance diagnostic sensitivity and could help exclude a diagnosis of TB if the pretest probability is low.

QuantiFERON-TB Performs Better in Children, Including Infants, than in Adults with Active Tuberculosis: a Multicenter Study.

Immunological tests, including the QuantiFERON-TB Gold In-Tube (QFT-IT) assay, represent an important aid for diagnosing active tuberculosis (TB) and latent TB infections in children, but concerns about their use in children <5 years of age persist. This is a multicenter retrospective study comparing a population of 226 children to 521 adults with pulmonary or extrapulmonary TB. The aim was to evaluate the QFT-IT performance, analyzing both qualitative and quantitative results, according to age, birthplace, and disease localization. Compared to culture, QFT-IT sensitivity was 93.9%, 100%, and 94.4% in children ≤2, 2 to 5, and 5 to 16 years of age, respectively, and was significantly higher than that in adults (81.0%) (P < 0.0001). The rate of indeterminate test results for children (2.2%) was significantly lower than that for adults (5.2%) (P < 0.0001). In children, QFT-IT sensitivity was not affected by disease localization or birthplace (Italy born versus foreign born). Interferon gamma (IFN-γ) values in response to TB antigen and mitogen were significantly higher in children than in adults (TB antigen, median of 10 versus 1.66 IU IFN-γ/ml; mitogen, median of 10 versus 6.70 IU IFN-γ/ml; P < 0.0001). In summary, this study supports the use of QFT-IT as a complementary test for the diagnosis of pediatric TB even under 2 years of age. Our observations could be applicable to the new version of the test, QuantiFERON-TB Gold Plus, which has recently been shown to have similar sensitivity in active TB, although data in children are still lacking.

Evaluation of Standard E TB-Feron Enzyme-Linked Immunosorbent Assay for Diagnosis of Latent Tuberculosis Infection in Health Care Workers.

The laboratory diagnosis of latent tuberculosis infection (LTBI) is mainly performed with interferon gamma release assays (IGRAs). We compared the performance of a new enzyme-linked immunosorbent assay (ELISA)-based IGRA, the Standard E TB-Feron ELISA (TBF; SD Biosensor, Gyeonggi-do, Republic of Korea), with that of a widely used assay, the QuantiFERON-TB Gold In-Tube assay (QFT-GIT; Qiagen, Hilden, Germany), in a population of 425 health care workers (HCWs). All HCWs were screened by both assays per the manufacturers' protocols and in a cross-manner, where tube sets from one assay were used with the alternative ELISA. The results were compared both qualitatively and quantitatively. TBF and QFT-GIT identified 11.3% (48/425) and 12.9% (55/425) of the positive samples, respectively. TBF demonstrated 81.6% positive and 97.4% negative percent agreement with QFT-GIT, with a Cohen's kappa value of 0.78 (strong agreement). Discordant results were detected in 20 subjects (4.3%): 13 samples (65.0%) were TBF negative and QFT-GIT positive, 6 samples (30.0%) were TBF positive and QFT-GIT negative, and 1 sample provided TBF and QFT-GIT indeterminate/negative results. We observed a statistically significant degree of correlation between the interferon gamma reactivity between the two assays (Spearman's rho [rs ] value = 0.551, P < 0.01) and between standard assays and cross-manner tests (rs value range, 0.449 to 0.816; P < 0.01 for all combinations). Cross-manner tests also revealed that the ELISA kit of TBF provided higher values for the tube containing the tuberculosis (TB) antigen and the negative-control tube than the ELISA of QFT-GIT under the same conditions (P < 0.01), although these differences disappeared when the value for the negative-control tube was subtracted from that for the TB antigen tube. TBF showed a comparable and acceptable clinical performance in detecting LTBI compared to QFT-GIT. TBF represents a useful alternative tool as an ELISA-based IGRA, especially for large-scale screening for LTBI in HCWs.

QuantiFERON-TB Gold In-Tube test performance in a large pediatric population investigated for suspected tuberculosis infection.

BACKGROUND: The performance of QuantiFERON-TB Gold In-Tube (QTF-IT) in children is under debate, especially in those under 5 years of age. Moreover, interpretation of discordant QFT-IT/Tuberculin-Skin-Test (TST) results remains controversial. This study aims at studying the sensitivity of QFT-IT and TST in children with active TB cases and exploring risk factors associated with discordant TST+/QFT-IT-. METHODS: Children consecutively referred to one single pediatric center between 2010 and 2017 for suspected tuberculosis infection (TB) were enrolled. All children underwent clinical evaluation, TST and QFT-IT. Sensitivity of QFT-IT and TST in active TB cases and risk factors associated with discordant TST+/QFT-IT- results were assessed. Uni- and multi-variate logistic regression analyses were performed. RESULTS: Overall, 4631 children (median age 5.67 years) were enrolled, and 205 active TB cases were diagnosed (83 microbiologically confirmed). A high QFT-IT sensitivity was observed in children between 2 and 4 years of age (95.0%; 95%CI: 85.4-100) and in those between 5 and 18 years (89.1%; 95%CI:79.2-99.2) with microbiologically confirmed active TB. However, sensitivity was suboptimal in children younger than 2 years (84.6%; 95%CI: 65.0-100). Independent risk factors associated with discordant TST+/QFT-IT- results in children with latent tuberculosis infection (LTBI) were previous BCG vaccination (aOR:2.18; 95%CI:1.33-3.58; p = 0.002), age <2 years vs. 5-18 years (aOR:7.54; 95%CI:2.52-22.59; p < 0.0001), age 2-4 years vs. 5-18 years (aOR:4.63; 95%CI:2.66-8.06; p < 0.0001), and investigation for screening rather than for contact with a suspected or confirmed case (aOR:3.58; 95%CI:2.30-5.59; p < 0.0001). CONCLUSION: Our data suggest that QFT-IT might be used as unique assay in children over 2 years of age investigated for recent immigration/adoption screening and in cases of recent low risk TB contact. This approach could considerably reduce the number of children undergoing pharmacological treatment. Conversely, both tests are recommended in cases of strong clinical suspicion or high risk TB contact in children less than 5 years of age, in order to avoid misdiagnosis.

Comparison of the QuantiFERON-TB Gold Plus and QuantiFERON-TB Gold In-Tube Interferon Gamma Release Assays in Patients at Risk for Tuberculosis and in Health Care Workers.

The QuantiFERON-TB Gold Plus (QFT-Plus; Qiagen, Germantown, MD) interferon gamma release assay (IGRA) received FDA clearance in 2017 and will replace the prior version of the assay, the QFT-Gold In-Tube (QFT-GIT). Here, we compared performances of the QFT-Plus assay and the QFT-GIT version in a diverse patient population, including patients undergoing evaluation for or follow-up of latent tuberculosis infection (LTBI; n = 39) or active TB infection (n = 3), and in health care workers (HCWs; n = 119) at Mayo Clinic (Rochester, MN). Compared to the QFT-GIT, the QFT-Plus assay showed 91.2% (31/34) positive, 98.4% (124/126) negative, and 96.6% (156/161) overall qualitative agreement among the 161 enrolled subjects, with a Cohen's kappa value of 0.91 (excellent interrater agreement). Among the 28 patients diagnosed with LTBI at the time of enrollment, the QFT-GIT and QFT-Plus assays agreed in 24 (85.7%) patients; in all four discordant patients, the positivity of the QFT-GIT or QFT-Plus IGRA was associated with low-level interferon gamma (IFN-γ) reactivity, ranging from 0.36 IU/ml to 0.66 IU/ml. Additionally, we document a high degree of correlation between IFN-γ levels in the QFT-GIT TB antigen tube and each of the two QFT-Plus TB antigen tubes, as well as between the QFT-Plus TB1 and TB2 tubes (Pearson's correlation coefficients [R] > 0.95). Overall, we show comparable results between the QFT-GIT and QFT-Plus assays in our study population composed of subjects presenting with a diverse spectrum of TB infections. Our findings suggest that the necessary transition to the QFT-Plus assay will be associated with a minimal difference in assay performance characteristics.

QuantiFERON-TB Gold Plus Is a More Sensitive Screening Tool than QuantiFERON-TB Gold In-Tube for Latent Tuberculosis Infection among Older Adults in Long-Term Care Facilities.

We investigated the prevalence of latent tuberculosis infection (LTBI) among the residents in seven long-term care facilities (LTCFs) located in different regions of Taiwan and compared the performance of two interferon gamma release assays, i.e., QuantiFERON-TB Gold In-Tube (QFT-GIT) and QuantiFERON-TB Gold Plus (QFT-Plus) for screening LTBI. We also assessed the diagnostic performance against a composite reference standard (subjects with persistent-positive, transient-positive, and negative results from QFTs during reproducibility analysis were classified as definite, possible, and not LTBI, respectively). Two hundred forty-four residents were enrolled, and 229 subjects were included in the analysis. The median age was 80 years (range, 60 to 102 years old), and 117 (51.1%) were male. Among them, 66 (28.8%) and 74 (32.3%) subjects had positive results from QFT-GIT and QFT-Plus, respectively, and the results for 215 (93.9%) subjects showed agreement. Using the composite reference standard, 66 (28.8%), 11 (4.8%), and 152 (66.4%) were classified as definite, possible, and not LTBI, respectively. For definite LTBI, the sensitivity, specificity, positive predictive value, and negative predictive value of QFT-GIT were 89.4%, 95.7%, 89.4%, and 95.7%, respectively, and those for QFT-Plus were 100.0%, 95.1%, 89.2%, and 100.0%, respectively. The sensitivity of QFT-GIT decreased gradually with patient age. Compared to QFT-GIT, QFT-Plus displayed significantly higher sensitivity (100.0% versus 89.4%, P = 0.013) and similar specificity (95.1% versus 95.7%). In conclusion, a high prevalence of LTBI was found among elders in LTCFs in Taiwan. The new QFT-Plus test demonstrated a higher sensitivity than QFT-GIT in the older adults in LTCFs.

Diagnostic potential of interferon-gamma release assay to detect latent tuberculosis infection in kidney transplant recipients.

BACKGROUND: Latent tuberculosis (TB) infection (LTBI) is screened by using clinical assessment, tuberculin skin test (TST), chest radiography, and recently by interferon-gamma release assays (IGRA). The objective of this study was to evaluate the diagnostic potential of QuantiFERON® -TB Gold In-Tube test (QFT) for diagnosing LTBI in patients planned for kidney transplantation. METHODS: All adult patients with end-stage renal disease, evaluated for kidney transplantation in a referral center from August 2008 till May 2013, were enrolled, after consenting in a prospective, observational, non-interventional study. LTBI diagnosis was conducted by TST, chest x-ray, and clinical assessment, followed by IGRA by QFT. RESULTS: Overall, 278 patients were enrolled and kidney transplantation was performed in 173 patients. Contributed follow-up was 836.5 patient-years, and TB-free transplant duration was 478.5 patient-years. By standard methods, LTBI was diagnosed in 14 patients. Peri-transplant chemoprophylaxis was given to 53 patients, which included recipients of organs from all deceased donors and living donors with LTBI. QFT was positive in 70 patients, negative in 200 patients, and indeterminate in 8 patients. The agreement between LTBI diagnosis using standard methods and IGRA by QFT was poor (kappa: 0.089+0.046, P-value=.017). Twenty-seven of the QFT-positive patients were transplanted and only one was given isoniazid preventive therapy. None of the transplant recipients developed TB after a median follow-up of 25 months (range 2-58 months, mean 27 months). CONCLUSIONS: The agreement of the QFT with standard diagnosis of LTBI in kidney transplant recipients was poor.

Quality control in QuantiFERON-TB gold in-tube for screening latent tuberculosis infection in health care workers.

QuantiFERON-TB gold in-tube has been used for screening latent tuberculosis infection in newly employed health care workers in Japan. There have been a few studies concerning quality control. We retrospectively analysed QuantiFERON-TB gold in-tube results in a hospital in Japan. Interferon-γ values in three blood collection tubes for QuantiFERON-TB gold in-tube were analysed in association with the positivity rate. The data set consisted of health care workers aged 20-29 years during the 7 years between 2010 and 2016. The yearly QuantiFERON-TB gold in-tube positivity rate was 0.9%, 16.4%, 3.0%, 39.3%, 2.8%, 0.9% and 1.5%, and was extremely high in 2011 and 2013. The interferon-γ values in the tuberculosis antigen tube were elevated in these two years, as indicated by higher median and wider interquartile range. The interferon-γ value in the negative control tube was also higher in 2011. The higher interferon-γ values in collection tubes (tuberculosis antigen tube and/or negative control tube) resulted in higher QuantiFERON-TB gold in-tube positivity rate. The distribution of interferon-γ in tuberculosis antigen tube and negative control tube, as evaluated by median and interquartile range, proved to be an effective index for the quality control of QuantiFERON-TB gold in-tube.

Performance of interferon-γ release assays in the diagnosis of confirmed active tuberculosis in immunocompetent children: a new systematic review and meta-analysis.

BACKGROUND: Tuberculosis (TB) is a global public health problem, causing morbidity and mortality in adults and children. The most reliable diagnostic tools currently available are the in vivo Tuberculin Skin Test (TST) and the ex vivo Interferon-γ release assays (IGRAs). Several clinical, radiological, and bacteriological features make the detection of active (overt disease) TB in children difficult. Although recently developed immunological assays such as QuantiFERON-TB Gold In-Tube (QFT-IT) and T-SPOT®.TB are commonly used to identify active TB in adults, different evidence is required for diagnosis in children. The purpose of this study was to reassess the sensitivity and specificity of IGRAs in detecting microbiologically confirmed active TB in immunocompetent children. METHODS: A systematic review and meta-analysis of studies reporting on the diagnostic accuracy of tests for TB in immunocompetent children aged 0-18 years, with confirmation by positive M. tuberculosis cultures, were undertaken. Electronic databases were searched up to September 2015 and study quality assessment was performed using QUADAS-2. RESULTS: Fifteen studies were included in our meta-analysis. Results showed that there were no significant differences in sensitivity between TST (88.2%, 95% confidence interval [CI] 79.4-94.2%), QFT-IT (89.6%, 95% CI 79.7-95.7%) and T SPOT (88.5%, 95% CI 80.4-94.1%). However, both QFT-IT (95.4%, 95% CI 93.8-96.6%) and T-SPOT (96.8%, 95% CI 94.2-98.5%) have significantly higher specificity than TST (86.3%, 95% CI 83.9-88.6%). CONCLUSIONS: QFT-IT and T-SPOT have higher specificity than TST for detecting active TB cases in immunocompetent children.

QuantiFERON conversion following tuberculin administration is common in HIV infection and relates to baseline response.

BACKGROUND: HIV-1 infection impairs tuberculosis (TB) specific immune responses affecting the diagnosis of latent TB. We aimed to (1) determine the proportion of HIV-1-infected adults with a negative QuantiFERON®-TB Gold in-tube (QFT-GIT) and Tuberculin skin testing (TST) that convert to QFT-GIT positive following TST, and (2) evaluate the relationship between conversion and baseline QFT-GIT results. METHODS: HIV-1 infected adults being screened for a TB vaccine study in South Africa underwent QFT-GIT followed by TST. As per protocol, QFT-GIT was repeated if randomization was delayed allowing for evaluation of TST boosting in a proportion of participants. RESULTS: Of the 22 HIV-1 infected, TST and QFT-GIT negative adults (median CD4 477/mm3 IQR 439-621) who had QFT-GIT repeated after median 62 days (IQR 49-70), 40.9 % (95 % CI 18.6-63.2 %) converted. Converters had a significantly greater increase in the background subtracted TB antigen response (TBAg-Nil - all units IU/mL) following TST, 0.82 (IQR 0.39-1.28) vs 0.03 (IQR -0.05-0.06), p = 0.0001. Those who converted also had a significantly higher baseline TBAg-Nil 0.21(IQR 0.17-0.26) vs 0.02(IQR 0.01-0.07), p = 0.002. Converters did not differ with regard to CD4 count or ART status. ROC analysis showed a baseline cut off of 0.15 correctly classified 86.4 % of converters with 88.9 % sensitivity. CONCLUSIONS: Our findings support the possibility that there are 2 distinct groups in an HIV-1 infected population with negative QFT-GIT and TST; a true negative group and a group showing evidence of a weak Mtb specific immune response that boosts significantly following TST resulting in conversion of the test result that may represent false negatives. Further evaluation of whether a lower cut off may improve sensitivity of QFT-GIT in this population is warranted.

Demographics and prevalence of positive QuantiFERON-TB Gold In-Tube test in renal transplant candidates.

BACKGROUND: Latent tuberculosis infection (LTBI) screening prior to solid organ transplantation is standard of care. QuantiFERON-TB Gold In-Tube (QFT-GIT) test is the preferred diagnostic test for renal transplant candidates (RTC). QFT-GIT reversions and the potential delay of living-donor kidney transplantation (LDKT) because of QFT-GIT positivity have not been examined previously in RTC. METHODS: We evaluated the prevalence of positive QFT-GIT in RTC from January 1 through December 31, 2011. In addition, we examined the demographic and renal disease data differences between QFT-GIT-positive and -negative patients, changes in QFT-GIT results, and positive QFT-GIT results reverting to negative. Lastly, we evaluated if QFT-GIT-positive patients were less likely to undergo LDKT within 6 months of QFT-GIT testing. RESULTS: In total, 722 RTC were analyzed, 16% of whom had positive QFT-GIT. The QFT-GIT-positive patients were more likely to be older and foreign-born, P < 0.0001. Haitians had the highest prevalence. Of the 119 QFT-GIT-positive patients, 25% had low/intermediate-positive results and were more likely to revert to negative, compared with patients with high-positive QFT-GIT results (50% vs. 0%, P = 0.01). A trend was seen toward fewer QFT-GIT-positive patients undergoing LDKT, compared with QFT-GIT-negative patients (0% vs. 3%, P = 0.09). CONCLUSIONS: Our high prevalence was likely a result of the high number of foreign-born RTC. Half of our small subset of low/intermediate-positive QFT-GIT patients reverted to negative. QFT-GIT-positive patients were more likely to have their LDKT delayed.

A comparative analysis of two interferon-γ releasing assays to detect past tuberculosis infections in Japanese rheumatoid arthritis patients.

OBJECTIVES: To compare the utility of QuantiFERON-TB Gold in tube (QFT-GIT) and T-SPOT.TB assays to detect past tuberculosis infection in Japanese rheumatoid arthritis patients receiving methotrexate. METHODS: We compared the sensitivities and specificities, the rates of indeterminate results, and the rates of positive results in patients with total and CD4-positive lymphocyte counts of both assays simultaneously performed on 68 rheumatoid arthritis patients receiving methotrexate, in whom 33 had evidence of past tuberculosis infection by chest computed tomography and the other had neither history of tuberculosis exposure nor abnormalities in chest computed tomography. RESULTS: The sensitivities, specificities, and the rates of indeterminate results of QFT-GIT were 21.2%, 100%, and 4.4%, and those of T-SPOT.TB were 21.9%, 100%, and 1.5%, respectively. The overall agreement of both assays was good (κ = 0.68). In patients with past tuberculosis infection, there are significant positive linear trends in positive rates of both assays across ranges of larger numbers of total and CD4-positive lymphocyte counts. CONCLUSIONS: Both assays were equally useful with high specificities, but may falsely identify past tuberculosis infection owing to low sensitivities. In patients with low total and CD4-positive lymphocyte counts, both assays might give higher rates of false negative results.

Prevention of anti-tumor necrosis factor-associated tuberculosis: a 10-year longitudinal cohort study.

BACKGROUND: The extent to which anti-tumor necrosis factor (TNF)-associated tuberculosis can be prevented is unclear, and there is no established guidance on the optimal screening strategy for latent tuberculosis (LTBI) in patients about to start anti-TNF therapy. We aimed to determine the effectiveness of a comprehensive program for the prevention of anti-TNF-associated tuberculosis, and to evaluate 3 LTBI screening strategies and the need for retesting patients with negative results at baseline. METHODS: In total, 726 patients were screened prior to anti-TNF therapy using 1 of 3 diagnostic strategies over 3 consecutive periods: first, a 2-step tuberculin skin test (TST); second, a 2-step TST plus QuantiFERON-TB Gold In-Tube test (QFT-GIT) (2-step TST/QFT); and third, a single-step TST plus QFT-GIT (TST/QFT). Infected patients were offered preventive therapy. We assessed differences in the incidence of tuberculosis between anti-TNF exposed and nonexposed patients, and between the 3 study periods. RESULTS: Tuberculosis developed during the first year in 2.85 per 1000 exposed patient-years (3/1052 patient-years) and 1.77 per 1000 nonexposed patient-years (1/566 patient-years). No cases occurred beyond the first year of treatment. LTBI diagnoses decreased with the single-step TST/QFT (26.5%) compared with the 2-step TST (42.5%; P < .001) and 2-step TST/QFT (38.5%; P = .02); the incidence of tuberculosis among exposed patients did not change significantly across the 3 periods (2.63/1000, 3.91/1000, and 2.4/1000 patient-years, respectively). CONCLUSIONS: Although anti-TNF-associated tuberculosis can be reduced, some risk remains during the first year of therapy. Neither the 2-step TST nor systematic retesting after negative baseline testing is justified.

Tuberculin skin test and QuantiFERON-TB Gold In-tube Test for latent tuberculosis in Thai HIV-infected adults.

BACKGROUND AND OBJECTIVE: Limited data exist for the performance of QuantiFERON-TB Gold In-tube Test (QFT-IT) in comparison to tuberculin skin test (TST) for detecting latent tuberculosis (LTB) in patients with human immunodeficiency virus (HIV) infection from tuberculosis (TB)-endemic Asia-Pacific countries. METHODS: A cohort study of Thai HIV-infected patients without history of TB or LTB treatment was conducted from March 2012 through March 2013. Each patient underwent simultaneous TST and QFT-IT. RESULTS: Among the 150 enrolled subjects, the median age was 40 years (range 17-65), 53% were male, and the median CD4 count was 367 cells/µL (range 8-1290). Reactive TST and positive QFT-IT were 16% and 13%, respectively, with low concordance between tests (kappa = 0.26); correlation between TST reaction size and level of interferon-γ was moderate (r = 0.34). Independent factors associated with discordant results were long-term smoking (adjusted odds ratio (aOR) 5.74; P = 0.002) for TST-reactive, QFT-IT-negative subjects, and age greater than 52 years (aOR 5.56; P = 0.02) and female gender (aOR 4.40; P = 0.04) for TST non-reactive, QFT-IT-positive subjects. The level of agreement between both tests improved when using a TST cut-off of ≥ 10 mm (kappa = 0.39). CONCLUSIONS: In our setting where QFT-IT is available but has limited use due to cost, TST with a cut-off of 10 mm for reactivity should be the initial LTB test. HIV-infected women and persons older than 52 years with non-reactive TST and long-term smokers with reactive TST may benefit from subsequent QFT-IT.