QuantiFERON-TB Gold Research Articles

Comparison of interferon-gamma production between TB1 and TB2 tubes of QuantiFERON-TB Gold Plus: a meta-analysis.

CD8 T-cells play an important role in interferon-gamma (IFN-γ) production as a host defense against tuberculosis (TB) infection. Therefore, QuantiFERON-TB Gold Plus (QFT-Plus) was developed by adding a TB2 tube beside the TB1 tube. This study aimed to compare and analyze the difference in IFN-γ production between the two tubes in general and specific populations. PubMed, Web of Science, and EBSCO were searched for studies reporting IFN-γ production levels in the TB1 and TB2 tubes. Statistical analysis was performed using RevMan 5.3. A total of 17 studies met the inclusion criteria. The IFN-γ production in the TB2 tube was statistically higher than that in the TB1 tube (mean difference (MD)=0.02, 95 % confidence interval (95 % CI): 0.01-0.03). Further subgroup analysis in specific populations revealed that the MD of IFN-γ production between the TB2 and TB1 tubes was significantly higher in active TB subjects than in latent TB infection (LTBI) subjects (MD=1.13, 95 % CI: 0.49-1.77, and MD=0.30, 95 % CI: 0.00-0.60, respectively). A similar finding was found in immune-mediated inflammatory disease subjects, but not statistically significant. Interestingly, IFN-γ production capacity was lower in active TB subjects than in LTBI subjects in each of the TB1 and TB2 tubes. This study is the first to systematically compare IFN-γ production between the TB1 and TB2 tubes. The IFN-γ production was higher in the TB2 tube than in the TB1 tube, representing the host's CD8 T-cell response magnitude to TB infection.

Determining the Need for Additional Testing With Quantiferon TB Gold in Patients With Positive Tuberculin Skin Tests and a History of BCG Vaccination.

To determine if the QuantiFERON-TB Gold (QFT) testing can be obviated for the diagnosis of latent tuberculosis infection (LTBI) in patients with a positive tuberculin skin test (TST) and a history of Bacillus Calmette-Guerin (BCG)vaccination by identifying high-risk features in patients with positive TST and a history of BCG vaccination who are associated with positive QFT. Retrospective chart review was done for 76 adult patients by dividing them into two groups. Group 1 consisted of true positive TST patients who had BCG vaccination and were positive for QFT. Group 2 consisted of false positive TST patients who had BCG vaccination but were negative for QFT. The two groups were compared to determine if the high-risk features of TST induration diameter of 15mm and more, TST induration of 20mm and more, recent immigration to the US, the advanced age of more than 65 years, country of origin with high TB burden, known exposure to active TB, and smoking history were more prevalent in Group 1 compared to Group 2. Group 1 had 23 patients and Group 2 had 53 patients. Group 1 had a higher prevalence of patients with PPD induration of more than 10mm than Group 2, which was statistically significant with a P value of 0.03. Other risk factors of advanced age, exposure to active TB and smoking did not show statistically significant differences between Groups 1 and 2. Conclusion:This study also confirms that if the TST induration is more than 10mm in patients with a history of BCG vaccination, the TST induration is likely because of LTBI and is less likely because of cross-reaction with BCG vaccination.

Mycobacterial-specific secretion of cytokines and chemokines in healthcare workers with apparent resistance to infection with Mycobacterium tuberculosis.

Currently, diagnosis of latent TB infection (LTBI) is based on the secretion of IFN-γ in response to Mycobacterium tuberculosis (Mtb) antigens, the absence of which is regarded as no infection. Some individuals appear to resist Mtb infection despite sustained exposure (resisters). In this study, we aimed to assess cytokines, chemokines and antibodies that may be associated with resistance to Mtb infection. We hypothesized that there may be an alternative immune response to Mtb exposure in the absence of IFN-γ in resisters. We enrolled HIV-uninfected healthcare workers who had worked in high TB-exposure environments for 5 years or longer. We screened them for LTBI using the tuberculin skin test and the QuantiFERON-TB Gold Plus assay. We performed multiplex Luminex to measure concentrations of T cell-associated cytokines and chemokines as well as total antibodies in plasma collected from unstimulated fresh whole blood and supernatants from QuantiFERON-TB Gold Plus tubes following incubation of whole blood for 16-24 hours with ESAT6/CFP10 peptides. Samples from 78 individuals were analyzed: 33 resisters (TST<10mm; IGRA<0.35 IU/mL), 33 with LTBI (TST≥10mm and IGRA≥0.35 IU/mL) and 12 discordant (TST=0mm; IGRA≥1.0 IU/mL). There were no differences in concentrations of cytokines and chemokines in plasma between the different groups. Resisters had significantly lower concentrations of IFN-γ, IL-2, TNF-α, MIP-1α, MIP-1β, ITAC, IL-13 and GM-CSF in supernatants compared with LTBI group. There were no significant differences in the concentrations in supernatants of IL-10, IL-1β, IL-17A, IL-21, IL-23, MIP-3α, IL-4, IL-5, IL-6, IL-7, IL-8, Fractalkine and IL-12p70 between the groups. We observed that resisters had similar concentrations of total antibodies (IgG1, IgG2, IgG3, IgG4, IgA, and IgM) in plasma and supernatants compared to the LTBI and discordant groups. Resistance to Mtb infection despite sustained exposure is associated with lower Mtb-specific secretion of Th1-associated cytokines and chemokines. However, resisters showed secreted concentrations after Mtb stimulation of total antibodies and cytokines/chemokines associated with innate and Th17 immune responses similar to those with Mtb infection. This suggests an ability to mount non-IFN-γ immune responses to Mtb in apparent resisters.

Performance of two interferon-gamma release assays for tuberculosis infection screening in Kawasaki children before immunosuppressive therapy.

We aimed to compare QuantiFERON-TB Gold In-Tube (QFT-GIT) and X.DOT-TB for screening latent tuberculosis infection (LTBI) in kawasaki patients, and to identify the risk factors associated with indeterminate IGRA results. We conducted a retrospective study on children with KD, who were screened for mycobacterium tuberculosis (Mtb) infection by either ELISA-based QFT-GIT or ELISPOT-based X.DOT-TB tests, admitted in Department of Cardiology, Beijing Children's Hospital from July 2019 to April 2022. A total of 1327 cases were included. Among them, 932 cases were tested by QFT-GIT and 395 cases by X.DOT-TB. The positive rate of children was 0.1% and 0.2%, and the indeterminate rate was 68.2% and 6.1% for QFT-GIT and X.DOT-TB, respectively. Patients with hypoproteinemia had a higher risk of indeterminate X.DOT-TB result. Female, critical ill, shock or hypoproteinemia presented statistically significant associations with an increased risk of indeterminate QFT-GIT result. High-dose of IVIG inhibited the release of IFN-γ by more than 90%, which might account for the high indeterminate incidence. It is recommended to perform X.DOT-TB rather than QFT-GIT to screen LTBI in patients with high level of the mitogen that can inhibit IFN-γ release. For KD children with positive IGRA results, it has a higher risk of activation TB infection when treated with immunosuppressive therapy in the future. Children with KD aged <5 years old had higher frequency of indeterminate IGRA results.

Inflated Gamma Interferon Response with QuantiFERON-TB Gold Plus Using the Automated Liaison XL Analyzer: a Testing Algorithm To Mitigate False-Positive Results in Low-Incidence Settings.

The Liaison XL chemiluminescence immunoassay (CLIA) analyzer allows total automation of gamma interferon (IFN-γ) measurement for the QuantiFERON-TB Gold Plus assay (QFT-Plus) that is used to diagnose Mycobacterium tuberculosis infection. To evaluate CLIA accuracy, plasma samples from 278 patients undergoing QFT-Plus testing were first tested with an enzyme-linked immunosorbent assay (ELISA; 150 negatives and 128 positives) and subsequently with the CLIA. Three strategies to mitigate false-positive CLIA results were investigated in 220 samples with borderline-negative ELISA results (TB1 and/or TB2, 0.1 to 0.34 IU/mL). The Bland-Altman plot of difference versus average of the two IFN-γ measurements in the Nil and antigen (TB1 and TB2) tubes showed higher IFN-γ measurements across the range of values with the CLIA than with the ELISA. Bias was 0.21 IU/mL (standard deviation, 0.61; 95% confidence interval [CI], -1.0 to 1.41). Linear regression of difference versus average had a slope of 0.08 (95% CI, 0.05 to 0.10), which was significantly nonzero (P < 0.0001). The CLIA had positive and negative percent agreement levels with the ELISA of 91.7% (121/132) and 95.2% (139/146), respectively. In borderline-negative samples tested with ELISA, CLIA was positive in 42.7% (94/220). CLIA with a standard curve resulted in 36.4% (80/220) positivity. Retesting CLIA false positives (TB1 or TB2 range, 0 to ≤1.3 IU/mL) with ELISA reduced false positives by 84.3% (59/70). Retesting with CLIA reduced the false-positive rate by 10.4% (8/77). Implementing the Liaison CLIA for QFT-Plus in low-incidence settings risks falsely elevating conversion rates and overburdening clinics and overtreating patients. Confirming borderline positives with ELISA is a viable strategy to mitigate false-positive CLIA results.

Prevalence and predictors of tuberculosis infection among people living with HIV in a high tuberculosis burden context

BackgroundTuberculosis (TB) disease is the leading cause of mortality among people living with HIV (PLHIV). Interferon-gamma release assays (IGRAs) are approved for TB infection ascertainment. However, current IGRA data on...

Evaluation of the Diagnostic Efficacy of EC-Test for Latent Tuberculosis Infection in Ambulatory People Living with HIV.

Latent tuberculosis infection (LTBI) co-infected with human immunodeficiency virus (HIV) is more likely to develop into active tuberculosis (ATB), recombinant Mycobacterium tuberculosis fusion protein (ESAT6/CFP10, EC) Test is a latest developed method for LTBI. Compared with the interferon γ release test assays (IGRAs), the diagnostic performance of EC-Test to LTBI screening in HIV needs to be evaluated. A population-based multicenter prospective study was conducted in Guangxi Province, China. The baseline data was collected and LTBI were measured by QuantiFERON-TB Gold In-Tube (QFT-GIT), EC-Test and T-cell spot of the TB assay (T-SPOT.TB). A total of 1478 patients were enrolled. when taking T-SPOT.TB as reference, the value of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and consistency that EC-Test to diagnosis LTBI in HIV is 40.42%, 97.98%, 85.26%, 85.04% and 85.06% respectively; when taking QFT-GIT as reference, the value is 36.00%, 92.57%, 55.10%, 85.09% and 81.13%, respectively. When the CD4+ <200 /μl, the accuracy of EC-Test to T-SPOT.TB and QFT-GIT were 87.12% and 88.89%, respectively; when the 200 ≤ CD4+ ≤ 500 /μl, the accuracy of EC-Test were 86.20% and 83.18%, respectively; when the CD4+ >500/μl, the accuracy of EC-Test were 84.29% and 77.94%, respectively. The incidence of adverse reactions in EC-Test is 34.23% and the serious adverse reactions is 1.15%. EC-Test has good consistency compared with IGRAs in detecting LTBI in HIV no matter in different immunosuppression status or different regions, and the safety of EC-Test is also well, suitable for LTBI screening in HIV in high prevalence settings.

Quantiferon TB Gold conversion in the medical staff caring to COVID-19 patients: Two Case Reports

Quantiferon TB Gold conversion in the medical staff caring to COVID-19 patients: Two Case Reports

Discrepancy between Mtb-specific IFN-γ and IgG responses in HIV-positive people with low CD4 counts.

Tuberculosis (TB) is a leading infectious cause of death worldwide and treating latent TB infection (LTBI) with TB preventative therapy is a global priority. This study aimed to measure interferon gamma (IFN-γ) release assay (IGRA) positivity (the current reference standard for LTBI diagnosis) and Mtb-specific IgG antibodies in otherwise healthy adults without HIV and those living with HIV (PLWH). One-hundred and eighteen adults (65 without HIV and 53 antiretroviral-naïve PLWH), from a peri-urban setting in KwaZulu-Natal, South Africa were enrolled. IFN-γ released following stimulation with ESAT-6/CFP-10 peptides and plasma IgG antibodies specific for multiple Mtb antigens were measured using the QuantiFERON-TB Gold Plus (QFT) and customized Luminex assays, respectively. The relationships between QFT status, relative concentrations of anti-Mtb IgG, HIV-status, sex, age and CD4 count were analysed. Older age, male sex and higher CD4 count were independently associated with QFT positivity (p=0.045, 0.05 and 0.002 respectively). There was no difference in QFT status between people with and without HIV infection (58% and 65% respectively, p=0.06), but within CD4 count quartiles, people with HIV had higher QFT positivity than people without HIV (p=0.008 (2nd quartile), <0.0001 (3rd quartile)). Concentrations of Mtb-specific IFN-γ were lowest, and relative concentrations of Mtb-specific IgGs were highest in PLWH in the lowest CD4 quartile. These results suggest that the QFT assay underestimates LTBI among immunosuppressed people with HIV and Mtb-specific IgG may be a useful alternative biomarker for Mtb infection. Further evaluation of how Mtb-specific antibodies can be leveraged to improve LTBI diagnosis is warranted, particularly in HIV-endemic areas. NIH, AHRI, SHIP: SA-MRC and SANTHE.

Do the drug doses of conventional synthetic DMARDs used for the treatment of biologic/targeted-synthetic DMARDs naive rheumatoid arthritis patients affect QuantiFERON-TB Gold Plus test results?

We aimed to obtain the effects of immunosuppressive doses on the QuantiFERON-TB Gold Plus (QFT-Plus) test results in Rheumatoid Arthritis (RA) patients. Besides this, the impact of the TB2 tube in QFT-Plus test was also investigated. This study included RA patients registered to HURBIO and were screened via QFT-Plus test for latent tuberculosis between January 2018 and March 2021, before the initiation of treatment of biologic/targeted-synthetic disease modifying anti-rheumatismal drugs (b/ts-DMARDs). Patients using methotrexate ≥ 10mg or leflunomide (any dose) or steroids (≥ 7.5mg prednisolone) at the time of QFT-Plus test were classified as the "high dose" group and the rest of the patients constituted the "low dose" group. The study included 534 RA patients; 353 [66.1%] in the high-dose group and 181 [33.9%] in the low-dose group. While QFT-Plus test was positive in 10.5% (37/353) patients in the high-dose group, it was positive in 20.4% (37/181) patients in the low-dose group (p < 0.001). The percentage of QFT-Plus indeterminate results were similar (around 2%) in both groups. The contribution of the TB2 tube to QFT-Plus test positivity was 6.89%. During a median (inter-quartile range) follow-up period of 23 (7-38) months under treatment of b/ts-DMARDs, latent TB reactivation was not observed. Primer active tuberculosis disease developed in two patients. Positive test results of Interferon-Gamma Release Assays (IGRAs) could decrease as immunosuppressive treatment doses increase in patients with RA and addition of the TB2 tube could increase test sensitivity.

Latent Mycobacterial fortuitum infection presenting as ocular sarcoidosis

A 62-year-old lady presented with bilateral granulomatous uveitis and cystoid macular edema. A diagnosis of ocular sarcoidosis was made (revised International Workshop on Ocular Sarcoidosis [IWOS] criteria) on the basis of lymphopenia, negative Mantoux, and QuantiFERON TB gold tests. Enlarged mediastinal lymph nodes, subpleural nodules, and nodular interstitial thickening were seen on high-resolution computed tomography (HRCT) thorax. Non-necrotizing granulomato us inflammation, negative for mycobacteria on staining and GeneXpert, was noted on endobronchial ultrasound-guided transbronchial lymph node aspiration (EBUS-TBNA). However, culture grew Mycobacterium fortuitum after 3 weeks. This case highlights a rare presentation of latent M. fortuitum infection presenting as ocular sarcoidosis, speculating the coexistence of two diseases in an individual, one possibly triggering the other.

Evaluation of ESAT6-CFP10 Skin Test for Mycobacterium tuberculosis Infection among Persons Living with HIV in China.

Recent global guidelines recommend Mycobacterium tuberculosis antigen-based skin tests, such as the ESAT6-CFP10 (EC) skin test, as acceptable alternatives to the tuberculin skin test (TST) and the QuantiFERON-TB Gold In-Tube test (QFT). However, the diagnostic value of these tests among persons living with HIV (PLHIV) is unknown. We aimed to assess the diagnostic accuracy of the EC among a cohort of PLHIV in China. We recruited PLHIV in Jiangsu Province, China, to assess sensitivity and specificity of the EC test. Participants were tested with the QFT, TST, and EC skin test. Results were stratified by age, M. tuberculosis BCG vaccination, and CD4 count. The sensitivity and specificity of the EC skin test was assessed using distinct cutoffs of the QFT and TST. Of 350 PLHIV enrolled in the study, 58 (16.6%), 89 (25.4%), and 59 (16.9%) tested positive with the EC test, the QFT, and the TST, respectively. Positivity increased with CD4 count; however, these trends were similar across tests. At a 5-mm cutoff, EC skin test specificity was high (99.6%, 95% confidence interval [CI] 95% CI = 97.7 to 100.0); however, sensitivity was moderate (81.4%; 95% CI = 66.6 to 91.6). After stratifying by BCG, the sensitivity and specificity were 86.4% (95% CI = 65.1 to 97.1) and 99.1% (95% CI = 95.0 to 100.0) among vaccinated PLHIV and 76.2% (95% CI = 52.8 to 91.8) and 100.0% (95% CI = 97.2 to 100.0) among unvaccinated PLHIV, respectively. Among PLHIV, the diagnostic value of the EC skin test remained high, regardless of BCG vaccination or CD4 count. The EC skin test performed comparably to TST and may be a valid alternative diagnostic test to use in settings or populations with high HIV prevalence and BCG vaccination. To our knowledge, this is the first study to evaluate the novel ESAT6-CFP10 skin test among PLHIV. Among 350 PLHIV, the test displayed high specificity and sensitivity, a finding which did not markedly differ based on BCG vaccination and CD4 count.

Positive rate and risk factors of latent tuberculosis infection among persons living with HIV in Jiangsu Province, China.

To analyze the latent tuberculosis infection (LTBI) among persons living with HIV(PLWH) in Jiangsu Province, to explore the factors affecting the positive rate of LTBI, and to take appropriate measures to control tuberculosis (TB) infection. A cross-sectional study was conducted among PLWH in Jiangsu Province from June to July 2021. All PLWH in Jiangsu Province were used as the study population. Currently, the diagnosis of LTBI lacks a "gold standard" and can only be assisted by the immunological method. In this study, Tuberculin skin test (TST), ESAT6-CFP10 test (EC), and QuantiFERON-TB gold in-tube (QFT) were used to detect the positive rate of LTBI among PLWH and to analyze their risk factors. A total of 340 prisoners were included, 89.7% were male, the median age was 38 years [Interquartile Range (IQR):32-46 years], these patients were on Antiviral Therapy (ART), and median CD4 counts was 376 (IQR: 261-496), 103 (30.3%) were positive in at least one test, LTBI by TST was 16.5%, LTBI by EC was 15.9%, LTBI by QFT was 26.2%. Univariate analysis showed the results for TST, EC, and QFT were not affected by CD4 counts (p>0.05), and multivariate analysis showed that a history of incarceration was associated with an increased risk of positive TST (adjusted odds ratio [aOR]=1.98;95% CI,1.03-3.82), EC (aOR=2.65;95% CI,1.37-5.12) and QFT (aOR=2.01;95%CI,1.12-3.57), in addition, female gender was associated with increased risk of positive TST (aOR=3.66;95%CI,1.60-8.37) and EC (aOR=3.43;95%CI,1.46-8.07), and contact history of TB patients was associated with increased risk of TST (aOR= 2.54;95%CI,1.23-5.22) and QFT (aOR=2.03;95%CI,1.03-3.99), and ethnic minorities (aOR=0.26;95%CI,0.12-0.57), longer duration of incarceration was associated with an increased risk of positive QFT (aOR=1.12;95%CI,1.02-1.24). Conclusions Female gender, and ethnic minorities, history of incarceration, longer duration of incarceration, and contact history of TB patients are risk factors for LTBI among PLWH in Jiangsu Province, and attention should be paid to TB control in this population.

Mycobacterium tuberculosis-specific cytokine responses according to HIV status among household contacts of people with TB

Following exposure to Mycobacterium tuberculosis (Mtb), a coordinated host response comprising both pro- and anti-inflammatory cytokines is critical for pathogen control. Although tuberculosis (TB) remains the leading cause of death among people with human immunodeficiency virus (HIV), the impact of HIV infection on Mtb-specific immune responses remains unclear. In this cross-sectional study of TB-exposed household contacts with and without HIV, we collected remaining supernatant from interferon-gamma release assay (IGRA) testing (QuantiFERON-TB Gold Plus [QFT-Plus]) and measured Mtb-specific pro-inflammatory, anti-inflammatory, and regulatory cytokine responses with a multiplex assay of 11 analytes. While people with HIV had lower responses to mitogen stimulation for some cytokines (granulocyte-macrophage colony-stimulating factor [GM-CSF], interleukin [IL]-2, IL-10, IL-17A, IL-22), there was no difference in cytokine levels for people with and without HIV following stimulation with Mtb-specific antigens. Future studies are necessary to explore whether changes in Mtb-specific cytokine responses over time are associated with distinct clinical outcomes following exposure to TB.

Assessing the Prevalence of Latent Tuberculosis by the QuantiFERON-TB Gold Plus Test and Risk Factor Analyses Among Nursing Professionals in a High Burden Setting of Thailand

Assessing the Prevalence of Latent Tuberculosis by the QuantiFERON-TB Gold Plus Test and Risk Factor Analyses Among Nursing Professionals in a High Burden Setting of Thailand

Concurrent syphilis, gonorrhea, and monkeypox: A case report.

Documented cases of monkeypox virus outside of Africa are rare, but as of August 22, 2022, the CDC was tracking 18,101 cases in the United States. Monkeypox rash can easily mimic other sexually transmitted infections, which may occur concurrently. This case report describes a 36-year old Caucasian man who has sex with men. The patient came in for a routine history and physical examination and disclosed a perianal rash. The patient had a medical history significant for undertreated HIV, ankylosing spondylitis, and homelessness. On examination, he had multiple perianal deep-seated ulcers that were swabbed for monkeypox and herpes simplex virus 1 and 2. Samples were also collected for syphilis, chlamydia, and gonorrhea. The swabs were positive for monkeypox and pharyngeal gonorrhea. At subsequent blood draw, he was found to have elevated titers for syphilis and a positive QuantiFERON-TB gold test. In summary, this case is a clear example of an individual with concurrent monkeypox virus and other sexually and nonsexually transmitted infections, highlighting the importance of careful identification of risk factors and testing for monkeypox virus even when the clinical presentation may depict a common sexually transmitted infection, such as the herpes simplex virus.

Latent Tuberculosis Infection Diagnosis Using QuantiFERON-TB Gold Plus Kit Among Correctional Workers: A Cross-Sectional Study in Francisco Beltrão-PR, Brazil.

Correctional workers form a high-priority group for tuberculosis control measures because of their high exposure and risk. This cross-sectional study conducted in April and May 2022 included 71 criminal police officers from the State Penitentiary of Francisco Beltrão-PR, Brazil. Their sociodemographic and laboratory data were collected. Latent tuberculosis infection (LTBI) was assessed using a QuantiFERON-TB Gold Plus in-tube test kit. Binary logistic regression was applied to calculate the odds ratios (ORs) and 95% confidence intervals (CI) of the LTBI predictors. The prevalence of LTBI was 22.6% (95% CI, 12.8-32.2%). Factors associated with LTBI were age > 43 years (OR, 0.18; 95% CI, 0.04-0.70; p < 0.014) and the use of medications (OR, 5.13; 95% CI, 1.40-18.87; p < 0.014). The prevalence was close to that estimated worldwide for LTBI in correctional workers, reinforcing the need for occupational health control measures consisting of regular screening and treatment of positive cases of latent infection among correctional workers to reduce the risk of illness and spread of infection in the penitentiary system and community.

A cost-effectiveness evaluation of latent tuberculosis infection screening of a migrant population in Malaysia

To estimate the costs and benefits of screening for latent tuberculosis infection (LTBI) in a migrant population in Malaysia. An economic model was developed from a Malaysian healthcare perspective to compare QuantiFERON-TB Gold Plus (QuantiFERON) with the tuberculin skin test (TST). A decision tree was used to capture outcomes relating to LTBI screening followed by a Markov model that simulated the lifetime costs and benefits of the patient cohort. The Markov model did not capture the impact of secondary infections. The model included an R shiny interactive interface to allow adaptation to other scenarios and settings. QuantiFERON is both more effective and less costly than TST (dominant). Compared with QuantiFERON, the lifetime risk of developing active TB increases by approximately 40% for TST due to missed LTBI cases during screening (i.e. a higher number of false negative cases for TST). For a migrant population in Malaysia, QuantiFERON is cost-effective when compared with TST. Further research should consider targeted LTBI screening for migrants in Malaysia based on common risk factors.

QuantiFERON-TB Gold Plus: can we stop at three?

Background: QuantiFERON-TB Gold Plus (QFT) (Qiagen) is an indicator of cell-mediated immune response to Mycobacterium tuberculosis specific antigens. The antigen tubes TB1 and TB2 elicits CD4+ T cell response but TB2 has an additional set of peptides which elicits CD8+ T cell response. A sample is positive if either TB1 or TB2 is interpreted as positive. We analysed TB1 and TB2 IFN-γ levels to determine if TB2 (with nil and mitogen tubes) will suffice.

Comparing the diagnostic performance of QuantiFERON-TB Gold Plus with QFT-GIT, T-SPOT.TB and TST: a systematic review and meta-analysis

BackgroundQuantiFERON-TB Gold Plus (QFT-Plus) is an important test that has emerged in recent years for detecting TB infection. We conducted a review to compare the sensitivity, specificity and positive rate of QFT-Plus with that of QuantiFERON-TB Gold In-Tube (QFT-GIT), T-cell spot of tuberculosis assay (T-SPOT.TB) and Tuberculin test (TST).MethodsPubMed and Embase were searched, without language restrictions, from 1 January 2015 to 31 March 2022 using “Mycobacterium tuberculosis Infections” and “QuantiFERON-TB-Plus” as search phrases. We estimated the sensitivity from studies of patients with active tuberculosis, specificity from studies of populations with very low risk of TB exposure, and positive rate from studies of high-risk populations. The methodological quality of the eligible studies was assessed, and a random-effects model meta-analysis was used to determine the risk difference (RD). We assessed the pooled rate by using a random-effects model. This study was registered in PROSPERO (CRD 42021267432).ResultsOf 3996 studies, 83 were eligible for full-text screening and 41 were included in the meta-analysis. In patients with active TB, the sensitivity of QFT-Plus was compared to that of QFT-GIT and T-SPOT.TB, respectively, and no statistically differences were found. In populations with a very low risk of TB exposure, the specificity of QFT-Plus was compared with that of QFT-GTI and T-SPOT.TB, respectively, and no statistically differences were found. Two studies were eligible to compare the specificity of the QFT-Plus test with that of the TST test, and the pooled RD was 0.12 (95% CI 0.02 to 0.22). In high-risk populations, 18 studies were eligible to compare the positive rate of the QFT-Plus test with that of the QFT-GIT test, and the pooled RD was 0.02 (95% CI 0.01 to 0.03). The positive rate of QFT-Plus was compared with that of T-SPOT.TB and TST groups, and no statistically differences were found.ConclusionsThe diagnostic performance of QFT-Plus was similar to that of QFT-GIT and T-SPOT.TB, but was slightly more specific than TST.