Serial QuantiFERON-TB Gold testing in patients with psoriasis treated with ustekinumab.
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ABSTRACT: Background
There is increasing concern about the risk of latent tuberculosis infection (LTBI) reactivation during the use of biologics for psoriasis. Although ustekinumab had been documented with low risk of tuberculosis, the long-term follow-up of LTBI as determined by QuantiFERON-TB Gold (QFT-G) testing in patients treated with ustekinumab is limited.Objectives
This study aims to use serial QFT-G testing as a screening method for detecting LTBI in patients with psoriasis from an intermediate tuberculosis burden country.Methods
This retrospective review investigated 134 psoriatic patients in whom ustekinumab was prescribed for at least one year between 2010 and 2016 in National Taiwan University Hospital. All patients underwent annular QFT-G testing during ustekinumab therapy.Results
Among the 134 enrolled patients, baseline LTBI rate was 13.4% (18/134). Indeterminate QFT-G result was noted in 5.2% (7/134) of patients and 71.4% (5/7) of them turn to be QFT-G negative during the next testing. 81.3% (109/134) of patients had a negative QFT-G at baseline and the seroconversion rate was 7.3% (8/109) in the serial QFT-G. All the patients in the conversion group were referred to a pulmonologist for evaluation and 81.5% (22/27) of them underwent chemoprophylactic therapy while on ustekinumab. No active TB infection was noted during further follow-up with or without chemoprophylaxis.Conclusions
This study revealed that psoriatic patients receiving long-term ustekinumab therapy had a low QFT-G conversion rate (7.3%). The clinical significance of QFT-G conversion remains controversial and needs larger scale trials to investigate.
SUBMITTER: Hsiao CY
PROVIDER: S-EPMC5590912 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionInterferon gamma (IFN-?) release assays, such as QuantiFERON®-TB Gold test (QFT-G) and QuantiFERON®-TB Gold In-Tube test (QFT-GIT) are designed to detect M. tuberculosis (Mtb) infection. Recognition of unusual IFN-? measurements may help indicate inaccurate results.MethodsWe examined QFT-G and QFT-GIT results from subjects who had two or more tests completed. We classified unusual IFN-? measurements as: 1) High Nil Concentration (HNC) when IFN-? concentration in plasma from unstimulated blood exceeded 0.7 IU/mL; 2) Low Mitogen Response (LMR) when Mitogen Response was <0.5 IU/mL; 3) Very Low Mitogen Response (VLMR) when Mitogen Response was ?-0.5 IU/mL; and 4) Very Low Antigen Response (VLAR) when the response to a Mtb antigen was ?-0.35 IU/mL and ?-0.5 times the IFN-? concentration in plasma from unstimulated blood.ResultsAmong 5,309 results from 1,728 subjects, HNC occurred in 234 (4.4%) tests for 162 subjects, LMR in 108 (2.0%) tests for 85 subjects, VLMR in 22 (0.4%) tests for 21 subjects, and VLAR in 41 (0.8%) tests for 39 subjects. QFT-GIT had fewer HNC, VLMR, and VLAR (p?=?0.042, 0.004, and 0.067 respectively); QFT-G had fewer LMR (p?=?0.005). Twenty-four (51.6%) of 47 subjects with positive results and HNC were negative or indeterminate by all other tests. Thirteen (61.9%) of 21 subjects with positive results and LMR were negative or indeterminate by all other tests.ConclusionUnusual IFN-? measurements including HNC, LMR, VLMR, and VLAR were encountered in small numbers, and in most instances were not seen on simultaneously or subsequently performed tests. To avoid erroneous diagnosis of Mtb infection, IGRAs with unusual IFN-? measurements should be repeated with another blood sample and interpreted with caution if they recur.
| S-EPMC3110578 | biostudies-literature
Project description:QuantiFERON-TB Gold Plus (QFT-Plus) is a new-generation QuantiFERON-TB Gold In-Tube (QFT-GIT) assay which has two antigen-coated tubes called TB1, which contains long peptides derived from ESAT-6 and CFP-10, and TB2, which contains the same components as TB1 and additional short peptides which potentially stimulate CD8+ T cells through the presentation of major histocompatibility complex class I. This is the first study to compare QFT-Plus and QFT-GIT for use in the diagnosis of latent tuberculosis infection (LTBI) among immunocompromised patients in the Republic of Korea. Among 317 consecutive patients who underwent screening for LTBI before solid organ or hematopoietic stem cell transplantation and tumor necrosis factor alpha inhibitor treatment, LTBI was identified in 92 (29.0%) and 88 (27.8%) patients by QFT-GIT and QFT-Plus, respectively. The rate of concordance between QFT-GIT and QFT-Plus was 93.7% (? value, 0.860), and the indeterminate rate (3.2%) was similar between QFT-GIT and QFT-Plus. Of 20 (6.3%) samples with discordant results, 11 (55.0%) and 7 (35.0%) were positive by QFT-GIT alone and QFT-Plus alone, respectively, and 2 (15.0%) were indeterminate by each assay. The interferon gamma level in samples with discordant results ranged from 0.39 to 1.10 IU/ml, except for one sample, in which the gamma interferon level was 2.97 IU/ml only in TB2. Conclusively, there was a high degree of agreement between the results of QFT-GIT and QFT-Plus for the screening of immunocompromised patients for LTBI. The reactivity in TB2 contributed substantially to the difference between QFT-GIT and QFT-Plus, particularly in solid organ transplant candidates. The significance of the discrete responses in TB1 and TB2 of QFT-Plus needs to be explored further by means of an immunological and clinical approach in different patient groups and clinical settings.
| S-EPMC6204680 | biostudies-literature
Project description:ObjectivesTo assess associations between disease severity in index TB patients and QuantiFERON-TB Gold Plus (QFT-Plus) results in contacts, and predictors for QFT-Plus conversion in contacts over 6-12 months.MethodsTB patients (n = 295) and the contacts (n = 1051) were enrolled during 2018-2021 with QFT-Plus performed at baseline and months 6 and 12. A strong CD8 response was defined as TB2 interferon gamma (IFN-γ) response minus TB1 >0.6 IU/ml and stringent conversion as change from QFT-plus negative to high-positive QFT-Plus (TB1 or TB2 IFN-γ responses >0.7 IU/ml).ResultsContacts with index TB patients with sputum smear >1+ was associated with positive QFT-Plus compared to those without (p < 0.001). Contacts with index TB patients with bilateral lung disease were more likely to have strong CD8 responses than those without (p = 0.038). QFT-Plus stringent conversion occurred in 9.7% of contacts over 6-12 months. A TB1 IFN-γ response ≥0.03 IU/ml combined with a TB2 ≥0.06 IU/ml was predictive of a 19-fold increased risk for QFT-Plus stringent conversion in contacts (odd ratio 19.565 [8.484-45.116], p < 0.001).ConclusionBacterial burden and bilateral lung disease of index TB patients were associated with positive QFT-Plus and strong CD8 responses in contacts. TB1 and TB2 IFN-γ responses were synergistically predictive of stringent conversion in contacts.
| S-EPMC10604336 | biostudies-literature
Project description:BackgroundWe investigated changes in the interferon-γ levels before and after treatment of latent tuberculosis infection (LTBI) using QuantiFERON-TB Gold Plus (QFT-Plus) and QuantiFERON-TB Gold In-Tube (QFT-GIT) assays. The objective was to assess whether QFT-Plus could serve as a biomarker of LTBI treatment response.MethodsWe prospectively enrolled 44 individuals whose baseline QFT-GIT and QFT-Plus showed positive results at a tertiary referral center in South Korea between March 2017 and March 2018. The results of the QFT-Plus assay were defined as positive if either or both of the antigen tubes (TB1 and/or TB2) were positive. After LTBI treatment, both tests were repeated.ResultsThe mean age of the participants was 47.6 years. The QFT-GIT and QFT-Plus assays revealed positive results in 42/44 (95.5%) and 41/44 (93.2%) participants after LTBI treatment, showing overall agreement of 93.2%, with a Cohen's kappa value of 0.37 (fair agreement). The differences between pre- and post-LTBI treatment interferon-γ levels were measured using the QFT-GIT and QFT-Plus assays. No significant differences were noted among the 3 values: the median difference in interferon-γ value with QFT-GIT, QFT-Plus TB1, and QFT-Plus TB2 was 0.211 IU/mL (IQR, -0.337-3.347), 0.025 IU/mL (IQR, -0.338-1.368), and 0.180 IU/mL (IQR, -0.490-2.278), respectively (P = 0.401).ConclusionThe change in interferon-γ levels before and after LTBI treatment measured using the QFT-Plus assay showed a similar trend to that of the QFT-GIT assay. Considering that the QFT-GIT assay is not a useful biomarker of LTBI treatment response, QFT-Plus also appears not to be useful for this purpose.
| S-EPMC7297367 | biostudies-literature
Project description: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.
| S-EPMC7448650 | biostudies-literature
Project description:This review summarizes studies evaluating the performance of the QuantiFERON-TB Gold Plus (QFT-Plus) interferon-gamma release assay (IGRA) test for Mycobacterium tuberculosis ( Mtb ) infection in children. Literature searching was conducted using PubMed, MEDLINE and Embase (January 2017 to December 2021) and the terms "children" or "pediatric" and "IGRAs" or "QuantiFERON-TB Gold Plus." Selected studies (N = 14; 4646 subjects) enrolled children with Mtb infection, tuberculosis (TB) disease or healthy children with household TB contacts. Agreement between QFT-Plus and tuberculin skin test (TST) (kappa values) ranged from -0.201 (no agreement) to 0.83 (almost perfect agreement). Assay sensitivity of QFT-Plus (against reference standard of microbiologically confirmed TB disease) was 54.5%-87.3%, with no reported difference in children less than 5 versus greater than or equal to 5 years of age. In individuals less than or equal to 18 years of age, the rate of indeterminate results was 0%-33.3% (2.6% in children <2 years). IGRAs may overcome the limitations of TST in young, Bacillus Calmette-Guérin-vaccinated children.
| S-EPMC10097492 | biostudies-literature
Project description:BackgroundThe QuantiFERON®-TB Gold In-Tube test (QFT-GIT) is a viable alternative to the tuberculin skin test (TST) for detecting Mycobacterium tuberculosis infection. However, within-subject variability may limit test utility. To assess variability, we compared results from the same subjects when QFT-GIT enzyme-linked immunosorbent assays (ELISAs) were performed in different laboratories.MethodsSubjects were recruited at two sites and blood was tested in three labs. Two labs used the same type of automated ELISA workstation, 8-point calibration curves, and electronic data transfer. The third lab used a different automated ELISA workstation, 4-point calibration curves, and manual data entry. Variability was assessed by interpretation agreement and comparison of interferon-? (IFN-?) measurements. Data for subjects with discordant interpretations or discrepancies in TB Response >0.05 IU/mL were verified or corrected, and variability was reassessed using a reconciled dataset.ResultsNinety-seven subjects had results from three labs. Eleven (11.3%) had discordant interpretations and 72 (74.2%) had discrepancies >0.05 IU/mL using unreconciled results. After correction of manual data entry errors for 9 subjects, and exclusion of 6 subjects due to methodological errors, 7 (7.7%) subjects were discordant. Of these, 6 (85.7%) had all TB Responses within 0.25 IU/mL of the manufacturer's recommended cutoff. Non-uniform error of measurement was observed, with greater variation in higher IFN-? measurements. Within-subject standard deviation for TB Response was as high as 0.16 IU/mL, and limits of agreement ranged from -0.46 to 0.43 IU/mL for subjects with mean TB Response within 0.25 IU/mL of the cutoff.ConclusionGreater interlaboratory variability was associated with manual data entry and higher IFN-? measurements. Manual data entry should be avoided. Because variability in measuring TB Response may affect interpretation, especially near the cutoff, consideration should be given to developing a range of values near the cutoff to be interpreted as "borderline," rather than negative or positive.
| S-EPMC3435391 | biostudies-literature
Project description:The fourth-generation QuantiFERON test for tuberculosis infection, QuantiFERON-TB Gold Plus (QFT-Plus) has replaced the earlier version, QuantiFERON-TB Gold In-Tube (QFT-GIT). A clinical need exists for information about agreement between QFT-Plus and other tests. We conducted this study to assess agreement of test results for QFT-Plus with those of QuantiFERON-TB Gold In-Tube (QFT-GIT), T-SPOT.TB (T-SPOT), and the tuberculin skin test (TST). Persons at high risk of latent tuberculosis infection (LTBI) and/or progression to tuberculosis (TB) disease were enrolled at the 10 sites of the Tuberculosis Epidemiologic Studies Consortium from October 2016 through May 2017; each participant received all four tests. Cohen's kappa (κ) and Wilcoxon signed-rank test compared qualitative and quantitative results of QFT-Plus with the other tests. Test results for 506 participants showed 94% agreement between QFT-Plus and QFT-GIT, with 19% positive and 75% negative results. When the tests disagreed, it was most often in the direction of QFT-GIT negative/QFT-Plus positive. QFT-Plus had similar concordance as QFT-GIT with TST (77% and 77%, respectively) and T-SPOT (92% and 91%, respectively). The study showed high agreement between QFT-GIT and QFT-Plus in a direct comparison. Both tests had similar agreement with TST and T-SPOT.
| S-EPMC6813010 | biostudies-literature
Project description:RationaleAlthough IFN-γ release assays (IGRAs) are widely used to screen for Mycobacterium tuberculosis infection in high-income countries, published data on repeatability are limited.ObjectivesTo determine IGRA repeatability.MethodsThe study population included consecutive patients referred to The Methodist Hospital (Houston, TX) between August 1, 2010 and July 31, 2011 for latent tuberculosis (TB) infection screening with an IGRA (QuantiFERON-TB Gold In-Tube; Cellestis, Carnegie, Australia). We performed multiple IGRA tests using leftover stimulated plasma according to a prospectively formulated quality control protocol. We analyzed agreement in interpretation of test results classified according to manufacturer-recommended criteria and repeatability of quantitative TB response.Measurements and main resultsDuring the study period, 1,086 test results were obtained from 543 subjects. Per the manufacturer's cut-point, the result of the second test was discordant from that of the first in 28 (8%) of 366 patients with valid test results, including 13 with an initial negative result and 15 with an initial positive result. Although agreement between repeat test results was high (κ = 0.84; 95% confidence interval, 0.79-0.90), the normal expected range of within-subject variability in TB response on retesting included differences of ± 0.60 IU/ml for all individuals (coefficient of variation, 14%), and ± 0.24 IU/ml (coefficient of variation, 27%) for individuals whose initial TB response was between 0.25 and 0.80 IU/ml.ConclusionsThere is substantial variability in TB response when IGRAs are repeated using the same patient sample. IGRA results should be interpreted cautiously when TB response is near interpretation cut-points.
| S-EPMC3570654 | biostudies-literature
Project description:BackgroundWorld Health Organization (WHO) recommends systematic screening of high-risk populations, including household contacts (HHCs) of adult pulmonary tuberculosis (TB) patients, as a key strategy for elimination of TB. QuantiFERON-TB Gold In-Tube (QFT-GIT) assay and tuberculin skin test (TST) are two commonly used tools for the detection of latent tuberculosis infection (LTBI) but may yield differential results, affecting eligibility for TB preventive therapy.Materials and methodsA prospective cohort study of adult pulmonary TB patients and their HHCs were recruited in 2 cities of India, Pune and Chennai. HHCs underwent QFT-GIT (QIAGEN) and TST (PPD SPAN 2TU/5TU). A positive QFT-GIT was defined as value ?0.35 IU/ml and a positive TST as an induration of ?5 mm. A secondary outcome of TST induration ?10mm was explored. Proportion positive by either or both assays, discordant positives and negatives were calculated; test concordance was assessed using percentage agreement and kappa statistics; and risk factors for concordance and discordance including age categories were assessed using logistic regression. Sensitivity and specificity was estimated by latent class model.ResultsOf 1048 HHCs enrolled, 869 [median (IQR) age: 27 years (15-40)] had both TST and QFT-GIT results available and prevalence of LTBI by QFT-GIT was 54% [95% CI (51, 57)], by TST was 55% [95% CI (52, 58)], by either test was 74% [95% CI (71, 77) and by both tests was 35% [95% CI (31, 38)]. Discordance of TST+/QFT-GIT- was 21% while TST-/QFT-GIT+ was 26%. Poor to fair agreement occurred with TST 5mm or 10mm cutoff (60 and 61% agreement with kappa value of 0.20 and 0.25 respectively). Test agreement varied by age, TST strength and induration cut-off. In multivariate analysis, span PPD was a risk factor for QFT-GIT+ and TST- while absence of BCG scar was for TST+ and QFT-GIT-. Being employed and exposure to TB case outside the household case were associated with positivity by both the tests. Sensitivity of TST and QFT-GIT to diagnose LTBI was 77% and 69%. Probability of having LTBI was >90% when both tests were positive irrespective of exposure gradient.ConclusionPrevalence of LTBI among HHCs of adult pulmonary TB patients in India is very high and varies by test type, age, and exposure gradient. In our high TB burden setting, a strategy to treat all HHCs or a targeted strategy whereby an exposure index is used should be assessed in future preventive therapy and vaccine studies as HHCs have several factors that place them at high risk for progression to TB disease.
| S-EPMC6070176 | biostudies-literature