QuantiFERON-TB Gold In-Tube Test Research Articles

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.

A phase I, open-label trial on the safety and immunogenicity of the adjuvanted tuberculosis subunit vaccine H1/IC31\xae in people living in a TB-endemic area

BackgroundH1/IC31® is a tuberculosis (TB) subunit vaccine candidate consisting of the fusion protein of Ag85B and ESAT-6 (H1) formulated with the IC31® adjuvant. Previous trials have reported on the H1/IC31® vaccine in M. tuberculosis (Mtb)-naïve, BCG-vaccinated and previously Mtb-infected individuals. In this trial, conducted between December 2008 and April 2010, the safety and immunogenicity of H1/IC31® was assessed in participants living in Ethiopia – a highly TB-endemic area.MethodsHealthy male participants aged 18–25 years were recruited into four groups. Participants in group 1 (N = 12) and group 2 (N = 12) were Tuberculin Skin Test (TST) negative and QuantiFERON-TB Gold in-tube test (QFT) negative (Mtb-naïve groups), participants in group 3 (N = 3) were TST positive and QFT negative (BCG group), and participants in group 4 (N = 12) were both TST and QFT positive (Mtb-infected group). H1 vaccine alone (group 1) or H1 formulated with the adjuvant IC31® (groups 2, 3 and 4) was administered intramuscularly on day 0 and day 56. Safety and immunogenicity parameters were evaluated for up to 32 weeks after day 0.ResultsThe H1/IC31®vaccine was safe and generally well tolerated. There was little difference among the four groups, with a tendency towards a higher incidence of adverse events in Mtb-infected compared to Mtb-naïve participants. Two serious adverse events were reported in the Mtb-infected group where a relationship to the vaccine could not be excluded. In both cases the participants recovered without sequelae within 72 h. Immunogenicity assays, evaluated in the 29 participants who received both vaccinations, showed a stronger response to TB antigens in the Mtb-naïve group vaccinated with the adjuvant.ConclusionThe trial confirmed the need for an adjuvant for the vaccine to be immunogenic and highlighted the importance of early phase testing of a novel TB vaccine candidate in TB-endemic areas.Trial registrationClinicalTrials.gov, ID: NCT01049282. Retrospectively registered on 14 January 2010.

A comparison of intradermal test with recombinant tuberculosis allergen (diaskintest) with other immunologic tests in the diagnosis of tuberculosis infection

The WHO strategy for eradication of tuberculosis (TB) by 2035 (The End TB Strategy) is aimed at an early and precise diagnosis and subsequent effective treatment of TB patients. Currently, there is no gold standard for the diagnosis of latent TB infection. This study evaluated the diagnostic capabilities of a new intradermal test using recombinant TB allergen (Diaskintest) compared with tuberculin skin test (TST) and commercial TB interferon-gamma release assays (IGRAs). A post-hoc data analysis that involved examining 860 HIV-negative, bacillus Calmette-Guérin (BCG)-vaccinated persons aged 1-65 years who visited the TB health-care institutions of Saint Petersburg to rule out or confirm an active TB was conducted from 2011 to 2016. A high degree of consistency of the Diaskintest results with the enzyme-linked immunospot and QuantiFERON-TB Gold In-Tube test (ELISPOT and QFT) results was observed in the examined pediatric population (n = 696), with a Diaskintest cutoff ≥5 mm: the kappa consistency indices were 1.000 and 0.937, for ELISPOT and QFT, respectively. A high sensitivity of Diaskintest, comparable with the IGRA tests, was observed in patients with a confirmed TB diagnosis in all age groups. The sensitivity of Diaskintest in patients of the TB/MTB + group aged 18 years and older was 88.7%; of ELISPOT, 90.6%; of QFT, 87.0%. The conducted analysis has shown a high concordance of results of the commercial TB tests in adult HIV-negative patients (n = 164) with a Diaskintest cutoff ≥5 mm: the kappa indices were 0.805 and 0.636 (Diaskintest vs. ELISPOT and QFT, respectively) among BCG-vaccinated people. According to the WHO recommendations, replacing the TST by IGRAs is not recommended as a public health intervention in resource-constrained settings because the IGRA tests are more costly and technically complex to conduct than the TST. Diaskintest has comparable complexity to the TST and its performance is close to that of IGRA in a BCG-vaccinated population. Thus, our study demonstrates that replacing the TST by Diaskintest can be recommended as a public health intervention in resource-constrained and universal BCG vaccination settings.

The Prevalence and Risk Factors of Latent Tuberculosis Infection among Health Care Workers Working in a Tertiary Hospital in South Korea.

BackgroundThe risk of tuberculosis (TB) infection among health care workers (HCWs) is higher than as noted among workers in the general population. The prevalence and risk factors of TB infection among HCWs were assessed in a tertiary hospital in South Korea, resulting in a conclusion of an intermediate TB burden within the country.MethodsThis cross-sectional study enrolled HCWs who underwent a QuantiFERON-TB Gold In-Tube (QFT-GIT) test to detect the presence of a latent TB infection (LTBI), in patients admitted to a tertiary hospital in South Korea in 2017. The departments of the hospital were divided into TB-related and TB-unrelated departments, which were based on the risk of exposure to TB patients. In this sense, the risk factors for LTBI, including current working in the TB-related departments, were analyzed.ResultsIn this case, a total of 499 HCWs (54 doctors, 365 nurses and 80 paramedical personnel) were enrolled in this study. The median age of the subjects was 31 years (range, 20–67 years), 428 (85.8%) were female, and 208 (41.7%) were working in the TB-related departments. The prevalence of LTBI was 15.8% based on the QFT-GIT. Additionally, the prevalence of experience of exposure to pre-treatment TB patents was higher among HCWs working in the TB-related departments, than among HCWs working in the TB-unrelated departments (78.8% vs. 61.9%, p<0.001). However, there was no significant difference in the prevalence of LTBI between the two groups (17.3% vs. 14.8%, p=0.458). On a review of the multivariate analysis, only the factor of age was independently associated with an increased risk of LTBI (p=0.006).ConclusionBroadly speaking, the factor of age was associated with an increased risk of LTBI among the HCWs in South Korea. However, those workers current working in the TB-related departments was not associated with an increased risk of LTBI.

Prevalence and risk factors for latent tuberculosis infection among primary health care workers in Brazil.

Health care workers (HCW) are at increased risk of latent tuberculosis infection (LTBI) from occupational exposure to Mycobacterium tuberculosis. The objective was to determine the prevalence of and risk factors for LTBI among primary HCW in five Brazilian cities. We conducted a cross-sectional study, from 2011 to 2013, among primary HCW, using a structured questionnaire and an evaluated for LTBI using the Quantiferon-TB Gold in-tube test. The magnitude of the associations was assessed using hierarchical logistic regression models. Among 708 HCW, the LTBI prevalence was 27% (n = 196; 95%CI: 24%-31%). We found that the following factors were positively associated with LTBI in primary HCW: age > 50 years (OR = 2.94; 95%CI: 1.44-5.99), absence of a BCG scar (OR = 2.10; 95%CI: 1.28-3.43), self-reported ex-smoker status (OR = 1.80; 95%CI: 1.04-3.11), being a nurse (OR = 2.97; 95%CI: 1.13-7.83), being a nurse technician (OR = 3.10; 95%CI: 1.26-7.60), being a community health agent (OR = 2.60; 95%CI: 1.06-6.40), and irregular use of N95 masks (OR = 2.51; 95%CI: 1.11-5.98). In contrast, HCWs who do not work in health care facilities with a TB control program were less likely to have LTBI (OR = 0.66; 95%CI: 0.45-0.97). This study demonstrated a substantial occupational risk of LTBI among primary HCW in Brazil. The Brazilian TB control program, as well as local programs, need to target these high-risk HCW with education, as well as with better personal protective equipment to prevent acquisition of new TB infection.

What does IGRA testing add to the diagnosis of ocular tuberculosis? A Bayesian latent class analysis

BackgroundTo evaluate the contribution made to the diagnostic work-up for patients with suspected ocular tuberculosis (TB) by QuantiFERON-TB Gold In-Tube (QFT) tests using latent class analysis model.MethodsA single centre retrospective cohort study. A Bayesian latent class model was constructed on the basis of demographics, phenotypes and test results from patients attending a tertiary referral center in the UK. This estimated the probability of ocular TB for each patient in two versions, first with and then without QFT. The estimated probability of ocular TB was compared with treatment failure.ResultsFrom a database of 365 patients with clinical signs suggestive of ocular TB, 267 patients who had QFT and complete data were evaluated. Mean age was 45.0 ± 15.4 years with 141 (52.9%) male and 148 (50.5%) of Asian ethnicity. QFT was positive in 208 (70.1%) patients and ATT was instituted in 145 (49.5%) patients with 100 (34.1%) patients also having concurrent systemic corticosteroid therapy. The best estimate of a QFT level separating TB-positive and TB-negative patients was extremely low. This weak discrimination between TB and non-TB groups was reflected in poor positive and negative predictive values for treatment failure.ConclusionsThe latent class model did not successfully predict treatment failure, despite taking all variables into account. The threshold between TB and non-TB in QFT values was implausibly low and removing QFT from the model made prediction slightly worse. A larger prospective study is required to establish the role of all tests, demographics and phenotypes in diagnosis.

Diagnostic usefulness of the QuantiFERON-TB gold in-tube test (QFT-GIT) for tuberculous vertebral osteomyelitis

Background: Interferon (IFN)-γ-releasing assay for diagnosing tuberculosis (TB) has shown promise; however, there are only a few reports on usefulness of the QuantiFERON-TB Gold In-Tube test (QFT-GIT) for diagnosing TB vertebral osteomyelitis.Methods: All patients presenting at a tertiary hospital between January 2010 and July 2016 with suspected TB vertebral osteomyelitis were retrospectively enrolled to evaluate the diagnostic performance of QFT-GIT. We used QFT-GIT to measure the IFN-γ response to ESAT-6, CFP-10 and TB7.7.Results: A total of 141 patients were enrolled; 32 (23%) were categorized as having confirmed TB, (1%) as probable TB, 14 (10%) as possible TB and 93 (66%) as not TB. Of these, 16 patients with probable and possible TB were excluded from the final analysis. Chronic granulomas with/without necrosis, acid-fast bacilli stain, M. tuberculosis polymerase chain reaction and cultures for M. tuberculosis were positive in 14 (44%), 12 (38%), 22 (69%) and 28 (88%) patients, respectively, among the 32 patients with confirmed TB. The overall sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio for a positive result, and likelihood ratio for a negative result of the QFT-GIT for TB vertebral osteomyelitis were 91% (95% confidence interval [CI], 75–98%), 65% (95% CI, 54–75%), 50% (95% CI, 42–58%), 95% (95% CI, 86–98%), 2.59 (95% CI, 1.89–3.55) and 0.14 (95% CI, 0.05–0.43), respectively.Conclusion: The QFT-GIT appears to be a useful adjunct test for diagnosing TB vertebral osteomyelitis because the negative test results may be useful for excluding a diagnosis of active TB vertebral osteomyelitis.

A multicentre verification study of the QuantiFERON®-TB Gold Plus assay

ObjectivesThe aim of this verification study was to compare the QuantiFERON®-TB Gold Plus (QFT-Plus) to the QuantiFERON®-TB Gold In Tube (QFT-GIT). The new QFT-Plus test contains an extra antigen tube which, according to the manufacturer additionally elicits a CD8+ T-cell response above the CD4+ T-cell response. We assessed the value of this tube in detecting recent latent tuberculosis infections. MethodsBetween May 2015 and December 2016, 1031 subjects underwent QFT-Plus and QFT-GIT test. Overall agreement between both tests and performance for different test indications and/or immune states was assessed. A difference of >0.6 IU/mL interferon-γ release between the two antigen tubes of the QFT-Plus assay was considered a true difference and used as estimation for CD8+ T-cell response. ResultsAnalysis of the QuantiFERON tests resulted in an overall agreement between assays of 95%. Subjects considered to be recently exposed to tuberculosis had significantly more often a true difference in interferon-γ release compared to all other subjects (p = 0.029). ConclusionResults of QFT-Plus are highly comparable to QFT-GIT. Although there is an indication that a true difference in interferon-γ release between the antigen tubes is associated with recent latent tuberculosis infection, the QFT-Plus could not be used to exclude recent exposure.

Factors That Contribute to Indeterminate Results From the QuantiFERON-TB Gold In-Tube Test in Patients With Inflammatory Bowel Disease

The QuantiFERON-Tuberculosis Gold In-Tube (QFT-GIT) (QIAGEN Group, Hilden, Germany) test is widely used to screen for latent Mycobacterium tuberculosis infection in patients with inflammatory bowel diseases (IBD) before treatment with a tumor necrosis factor antagonist. The test frequently produces indeterminate results, prompting additional testing. We evaluated factors associated with indeterminate results from the QFT-GIT test among patients with IBD. We conducted a case-control study among eligible adults with QFT-GIT test results and a concomitant diagnosis of IBD receiving care at a tertiary referral center from 2011 through 2013. We compared patients with IBD with indeterminate and determinate (positive or negative) results from the QFT-GIT test. We collected data on patient demographics, clinical features, laboratory parameters, and medication use from medical charts. We calculated odds ratios (OR) and 95% CIs using multivariate logistic regression models. A total of 400 patients with IBD (265 Crohn's disease and 135 ulcerative colitis) were included in the final analyses. Indeterminate results were noted in 11.5% of patients. At the time of testing, a higher proportion of patients with indeterminate results from the QFT-GIT test wereon systemic corticosteroid therapy (60.9% vs 30.5% of patients with conclusive test results; P < .001), had levels of C-reactive protein above 0.8 mg (62.2% vs 39.9% of patients with clear test results; P= .005), had an erythrocyte sedimentation rate above 15 mm/h (55.6% vs 35.8% of patients with clear test results; P= .01), had serum levels of albumin below 3.5 g/dL (33.3% vs 6.3% of patients with clear test results; P < .001), and had low levels of hemoglobin (52.2% vs 28.3% of patients with clear test results; P= .001). In multivariable analysis, corticosteroid use (adjusted OR, 2.92; 95% CI, 1.44-5.88; P= .003) and serum levels of albumin below 3.5 g/dL (adjusted OR, 3.62; 95% CI, 1.36-9.60; P= .009) were independently associated with increased risk of indeterminate QFT-GIT test results. We did not identify a dose-related effect with corticosteroid therapy and the odds of indeterminate QFT-GIT test results. In a case-control study of patients with IBD, we associated systemic corticosteroid therapy and low levels of albumin with an increased likelihood of having indeterminate QFT-GIT test result.

Use of QuantiFERON®-TB Gold in-tube culture supernatants for measurement of antibody responses.

QuantiFERON®-TB Gold in-tube (QFT-GIT) supernatants may be important samples for use in assessment of anti-tuberculosis (TB) antibodies when only limited volumes of blood can be collected and when a combination of antibody and cytokine measurements are required. These analytes, when used together, may also have the potential to differentiate active pulmonary TB (APTB) from latent TB infection (LTBI). However, few studies have explored the use of QFT-GIT supernatants for investigations of antibody responses. This study determined the correlation and agreement between anti-CFP-10 and anti-ESAT-6 antibody concentrations in QFT-GIT nil supernatant and serum pairs from 68 TB household contacts. We also explored the ability of Mycobacterium tuberculosis (M.tb) specific antibodies, or ratios of antibody to interferon gamma (IFN-γ) in QFT-GIT supernatants, to differentiate 97 APTB cases from 58 individuals with LTBI. Sputum smear microscopy was used to define APTB, whereas the QFT-GIT and tuberculin skin test were used to define LTBI. There were strong and statistically significant correlations between anti-CFP-10 and anti-ESAT-6 antibodies in unstimulated QFT-GIT supernatants and sera (r = 0.89; p<0.0001 for both), and no significant differences in antibody concentration between them. Anti-CFP-10 & anti-ESAT-6 antibodies differentiated APTB from LTBI with sensitivities of 88.7% & 71.1% and specificities of 41.4% & 51.7% respectively. Anti-CFP-10 antibody/M.tb specific IFN-γ and anti-ESAT-6 antibody/M.tb specific IFN-γ ratios had sensitivities of 48.5% & 54.6% and specificities of 89.7% and 75.9% respectively. We conclude that QFT-GIT nil supernatants may be used in the place of sera when measuring antibody responses, reducing blood volumes needed for such investigations. Antibodies in QFT-GIT nil supernatants on their own discriminate APTB from LTBI with high sensitivity but have poor specificity, whereas the reverse is true when antibodies are used in combination with M.tb specific cytokines. Further antibody and antibody/cytokine combinations need to be explored to achieve better diagnostic accuracy.

Is secretion of IFN-gamma in response to Mycobacterium tuberculosis antigens in youngest children sufficient to play a role in TB diagnostics?

To assess whether children ≤5 years of age, produce sufficient amounts of interferon gamma (IFN-ɣ) in response to phytohaemagglutinin (mitogen), and Mycobacterium tuberculosis antigens (TB antigens) in the QuantiFERON-TB Gold in-Tube test (QFT-GIT), (Cellestis Ltd., Australia). Is TB-antigen-induced IFN-ɣ response in children ≤5 years sufficient to consider QFT-GIT a possible tool for TB diagnostics? Study design, patient-subject selection, and methods: We recruited children 0-17 years old suspected of TB infection to this cross-sectional study, in whom QFT-GIT and TST were performed. We analyzed the median IFN-ɣ levels in mitogen and TB antigen tubes in children ≤5 years and >5 years, and the correlation between IFN-ɣ level in both tubes and age. A total of 153 children were enrolled, age median was 7.8 (IQR:8), 45 (29.4%) aged ≤5 years (median 3.4, IQR:1.7), 108 > 5 years (median 10.55, IQR:5.93). In the mitogen tubes, the median IFN-ɣ level was higher in children >5 years (median 17.87, IQR:2.1 vs 16.77, IQR:7.6), but surprisingly in the TB antigen tubes it was higher in the younger group (median 0.12, IQR:0.21vs 0.06, IQR:0.09, P = 0.04). We proved a positive correlation between IFN-ɣ level and age in mitogen tubes (r = 0.18, P = 0.03) and a negative correlation in TB antigen tubes (r = -0.17, P = 0.04). In latent tuberculosis infection patients, the latter correlation was found to be even stronger (r = -0.39, P = 0.01). The youngest children release sufficient amount of IFN-ɣ in response to TB antigens thus QFT-GIT might be a useful tool for TB diagnostics in this age group.

Screening for Latent Tuberculosis Infection in Patients with Hematologic Malignancies Using Interferon-Gamma Release Assays (IGRAS)

Background: The development of interferon-gamma release assays (IGRAs) is important in the diagnosis- of latent tuberculosis infection (LTBI). Objectives: The aim of this study was to evaluate the role of QuantiFERON®-TB Gold In-Tube test (QFT-GIT) in detection of LTBI in patient with hematological malignancy and to identify individuals who are at increased risk for the development of tuberculosis (TB). Methodology: the study was conducted on 52 newly diagnosed patients with hematologic malignancies at National Cancer Institute, Cairo University. The interferone- gamma secreted by T-lymphocytes following stimulation by antigens unique to Mycobacterium tuberculosis was measured. The QFT results were evaluated in relation to different clinical and hematologic parameters and outcome after induction therapy. Results: Nine out of 52 cases (17.5%) were positive for QFT. The patients included were 30 males (58%) and 22 females (42%), with a mean age of 42.75±15.39 years. Out of the 52 patients, 21 (40%) were Leukemic, while 31 patient (60%) had lymphoma. Among the QFT positive cases, 6/9 were lymphoma (67%) and 3/9 were leukemic cases (33%). Manifestations of infection were observed in 13/52 (25%) of cases and 55.5% of positive QFT cases (5/9) while positive chest radiological findings were reported in 44.4% of positive QFT cases (4/9). Lymph node enlargement were reported in 6/9 (66.7%) of QFT positive cases. After induction chemotherapy, 8 patients had an unfavorable outcome, 4 of whom were QFT positive. Conclusion: Interferon-Gamma Release Assays (IGRAs) can aid in diagnosing latent tuberculosis infection in patients with hematologic malignancies. This may prevent the spread of infection and identify who would benefit from treatment of latent TB infection.

Development and Validation of a Novel Prediction Model for Differential Diagnosis Between Crohn's Disease and Intestinal Tuberculosis.

Although colonoscopy is useful for differentiating between Crohn's disease (CD) and intestinal tuberculosis (ITB), the technique has limitations. We developed a practical prediction model for differentiating between CD and ITB using laboratory and radiologic parameters and colonoscopic characteristics. We prospectively enrolled 80 patients newly diagnosed with CD (n = 40) and ITB (n = 40). We developed a new prediction score by integrating colonoscopic, laboratory, and radiologic parameters. The score's predictive ability was validated on an additional 37 patients. The accuracy of colonoscopic scoring for differentiation was 81.2% (65/80), with 65.0% sensitivity for CD and 97.5% for ITB. In multivariate analysis, positive IgA and/or IgG anti-Saccharomyces cerevisiae antibody and involvement of the proximal intestine were the independent laboratory and radiologic parameters for CD, and positive QuantiFERON-TB Gold In-Tube Test and typical pulmonary TB findings were the parameters for ITB. A new prediction scoring combining colonoscopic, laboratory, and radiologic factors increased the accuracy of diagnosis from 81.2% to 96.3% (77/80). The CD prediction score (from -2 to 2) estimated the likelihood of CD, from 0.3% for patients scoring -2 to 100% for patients scoring 2. The area under the receiver operating characteristic curve of the score was 0.990 in the development group and 0.981 in the validation group. The new prediction model using a CD prediction score can be useful for calculating the probability of either CD or ITB at initial evaluation (NCT01392365).

Optic disc swelling in a patient with tuberculous meningitis: a diagnostic challenge

We discuss the diagnostic challenge in an adult patient presented with purely ocular symptoms diagnosed with tuberculous meningitis (TBM). A 38-year-old woman presented with bilateral painless blurring of vision. There...

Impact of diabetes mellitus on indeterminate results of the QuantiFERON TB Gold In-Tube test: A propensity score matching analysis.

BackgroundThe sensitivity of interferon-gamma release assays (IGRAs) in the detection of Mycobacterium tuberculosis infection could be affected by conditions of immune dysregulation. For this reason, diabetes mellitus (DM) may increase the frequency of indeterminate results of IGRAs. However, there have been inconsistent reports of role of DM on indeterminate IGRA results.MethodsWe retrospectively reviewed all patients who underwent QuantiFERON-TB Gold In-Tube testing (QFT-GIT) at Chonnam National University Hospital. We collected the clinical and laboratory data of these patients.ResultsOf all 3,391 subjects, 1,265 (37.3%) had a positive QFT-GIT result, 266 (7.8%) had an indeterminate result, and 1,860 (54.9%) had a negative result. The mean age was 54.8 ± 18.1 years and 55.0% of the patients were male. There were 512 (15.1%) patients with DM. Multivariable analysis revealed that systemic corticosteroid use, tuberculosis, lymphocytopenia, low serum albumin, and high serum C-reactive protein (CRP) levels were significantly associated with indeterminate QFT-GIT results. However, DM was not associated with indeterminate QFT-GIT results (adjusted odds ratio, 0.98; 95% confidence interval, 0.69–1.41; P = 0.939). After propensity score matching, DM was not associated with indeterminate results of QFT-GIT.ConclusionIn this large cohort study, DM does not affect the incidence of indeterminate results of QFT-GIT.

Incidence of active tuberculosis in individuals with latent tuberculosis infection in rural China: follow-up results of a population-based, multicentre, prospective cohort study

The management of latent Mycobacterium tuberculosis infection is a new priority action for the WHO End Tuberculosis (TB) Strategy. However, national guidelines on latent tuberculosis infection testing and treatment have not yet been developed in China. Here, we present the results from the 2-year follow-up of a study that aimed to track the development of active disease in individuals with latent tuberculosis infection, identify priority populations for latent infection management, and explore the most suitable latent infection diagnostic approach. A population-based multicentre prospective study was done in four sites in rural China, between 2013 and 2015. The baseline survey in 2013 measured the prevalence of latent tuberculosis infection using QuantiFERON-TB Gold In-Tube (QFT) and tuberculin skin test (TST) in eligible participants. During the follow-up phase between 2014-15, we assessed individuals who had tuberculosis infection at baseline (QFT-positivity or TST tuberculin reaction size [induration] of ≥10 mm) for the development of active disease through active case finding. Eligible participants included in follow-up survey had a birth date before June 1, 2008 (5 years or older in 2013), and continuous residence at the study site for 6 months or longer in the past year. Participants with current active tuberculosis at baseline survey were excluded. Between Sept 1, 2013, and Aug 31, 2015, 7505 eligible participants (aged 5 years or older) were included in tuberculosis infection test positive cohorts (4455 were QFT positive, 6404 had TST induration ≥10 mm, and 3354 were positive for both tests) after baseline examination. During the 2-year follow-up period, 84 incident cases of active tuberculosis were diagnosed. Of participants who developed active tuberculosis, 75 were diagnosed with latent infection by QFT, 62 were diagnosed by TST, and 53 were diagnosed by both tests. An incidence rate of 0·87 (95% CI 0·68-1·07) per 100 person-years was observed for individuals who tested positive with QFT, 0·50 (0·38-0·63) per 100 person-years for those who tested positive with TST (p<0·0001), and 0·82 (0·60-1·04) per 100 person-years for those who tested positive with both tests. Male sex and a history of tuberculosis were significantly associated with increased risk of disease development with adjusted hazard ratios of 2·36 (95% CI 1·30-4·30) for male sex and 5·40 (3·34-8·71) for a history of tuberculosis. Our results suggest that high-risk populations in communities in rural China, such as individuals at a high risk of disease reactivation from previous tuberculosis, should be targeted for latent infection screening and treatment with an interferon-γ releasing assay rather than a TST. National Science and Technology Major Project of China, Program for Changjiang Scholars and Innovative Research Team in University of China, CAMS Innovation Fund for Medical Sciences, and Sanming Project of Medicine in Shenzhen.

Mycobacterium tuberculosis infection in systemic lupus erythematosus patients

Aim of the workTo estimate prevalence of tuberculosis (TB) infection in systemic lupus erythematosus (SLE) patients; to study its relation to disease duration, activity, damage and treatment as well as to compare the performance of interferon gamma (IFN-γ) release assay and tuberculin skin test (TST) in detection of TB infection. Patients and methodsThe study enrolled 100 adult SLE patients. Disease activity was assessed using the British Isles Lupus Assessment Group (BILAG) activity index and damage using the Systemic Lupus International Collaborative Clinics damage Index (SLICCDI). Tuberculin skin tests and QuantiFERON-TB GOLD In-Tube (QFT-GIT) test were performed. ResultsThe mean age of the patients was 29.82±7.9years; 90% females and 10% males with a mean disease duration 5.5±5.4years. The BILAG index showing that 30% had category A renal activity and the mean of SLICCDI was 1.4±1.7. All patients were Bacille Calmette-Guérin(BCG) vaccinated; none of them had a previous history or contact to members with TB infection. QFT-GIT was positive in 13 patients and TST was positive in 2 patients. 15 patients were diagnosed as latent tuberculosis infection (LTBI). No patients were identified with active TB and microscopic examination and culture were negative. The agreement between the QFT-GIT and TST was poor. No significant difference between patients with positive and negative QFT-GIT results as regard disease duration, corticosteroids and immunosuppressive drugs used, BILAG, SLICCDI, chest X-ray and laboratory investigations. ConclusionThe prevalence of LTBI in SLE patients in our study was 15% with poor agreement between the QFT-GIT and TST.

Poor predictability of QuantiFERON-TB assay in recipients and donors for tuberculosis development after kidney transplantation in an intermediate-TB-burden country

BackgroundTuberculosis (TB) is a common opportunistic infection after kidney transplantation (KT). The QuantiFERON-TB-Gold In-Tube test (QFT) is widely used for assessing latent TB; however, it is currently unclear whether the pre-KT QFT of the recipient and donor can predict post-KT TB.MethodsWe retrospectively reviewed patients who received KT between January 2009 and December 2015 at Seoul National University Hospital. The QFT was performed in 458 KT recipients and 239 paired living donors, and 138 KT recipients underwent both the QFT and tuberculin skin test (TST). After excluding 12 patients diagnosed as having clinically latent TB, we evaluated whether the QFT of the recipient and donor was predictive for new-onset active TB after KT.ResultsThe QFT was positive in 101 (22.1%) recipients and associated with clinically latent TB before KT (P < 0.05). However, agreement between the TST and QFT was poor (κ = 0.327). Post-KT TB occurred in 1 of 95 recipients with a positive QFT, and 2 cases of TB occurred among 351 patients with a negative or indeterminate QFT. The incidence of TB was 242 cases/100,000 person-years among 446 KT recipients with a median follow-up of 30.2 months. The QFT of recipients could not predict post-KT TB in Poisson regression analysis (relative risk [RR], 1.847; 95% confidence interval [CI], 0.168–20.373; P = 0.616). Of 234 living donor-recipient pairs, the QFT of the recipient (RR, 5.012; 95% CI, 0.301–83.430; P = 0.261) and QFT of the donor (RR, 1.758; 95% CI, 0.106–29.274; P = 0.694) could not predict post-KT TB.ConclusionThe QFT of recipients or living donors pre-KT cannot predict the short-term development of post-KT TB in an intermediate TB-burden country.

Comparison of QuantiFERON-TB Gold In-Tube (QFT-GIT) and tuberculin skin test (TST) for diagnosis of latent tuberculosis in haemodialysis (HD) patients: a meta-analysis of κ estimates.

Diagnosis of latent tuberculosis infection (LTBI) is a concern in haemodialysis (HD) patients. Many studies have compared QuantiFERON-TB Gold In-Tube (QFT-GIT) and tuberculin skin test (TST) for detecting LTBI and reported the κ statistic of agreement between QFT-GIT and TST in HD patients. The present study aimed to systematically review this literature and conduct meta-analysis of individual studies that estimated the κ between QFT-GIT with TST among HD patients. All relevant published studies that were available as full-text were obtained by searching Medline (1950), Web of Sciences (1945), Scopus (1973) through May 2016. The κ was re-estimated from the individual studies and pooled using random effect meta-analysis. Subgroup analysis and meta-regression were applied to evaluate the effect of Bacillus Calmette-Guérin (BCG) vaccination, TST cut-off points, quality of studies, sample size and age on variation of κ estimate. Eight studies involving 901 HD patients were included in meta-analysis. The pooled κ estimate was 0·28 (I 2 = 18·4%, P = 0·239, 95% confidence intervals 0·22-0·34). The discordance of TST-/QFT-GIT+ was more than TST+/QFT-GIT-. History of BCG vaccination, TST cut-off points and age are related to variation of κ estimates. TST and QFT-GIT are not comparable in detecting LTBI in HD patients. The higher TST-/QFT-GIT+ ratio compared with TST+/QFT-GIT- ratio, may indicate the superiority of QFT-GIT over TST for detection LTBI in HD patients.

Use of the QuantiFERON-TB Gold In-Tube Test in the Diagnosis and Monitoring of Treatment Efficacy in Active Pulmonary Tuberculosis.

The value of QuantiFERON in the diagnosis of tuberculosis disease and in the monitoring of the response to anti-tuberculosis treatment is unclear. The aims of this study were to evaluate the accuracy of the QuantiFERON-TB Gold In-Tube (QFT-GIT) test in the diagnosis of tuberculosis and in the monitoring of the response to anti-tuberculosis treatment in patients with active pulmonary tuberculosis (PTB). Between January 2013 and December 2015, 133 cases with active PTB and 133 controls with no mycobacterial infection, matched by age (within 3 years) and by the week that they visited Tainan Chest Hospital, were enrolled in the study. Serial testing by QFT-GIT at baseline and after 2 and 6 months of treatment was performed. At these time points, a comparison of the performance of QFT-GIT with that of sputum culture status among study subjects was conducted. Compared to baseline, 116 (87.2%) cases showed a decreased response, whereas 17 (12.8%) showed persistent or stronger interferon-gamma (IFN-γ) responses at 2 months. PTB patients IFN-γ responses declined significantly from baseline to 2 months (median, 6.32 vs. 4.12; p < 0.005). The sensitivity values of the QFT-GIT test for the detection of pulmonary tuberculosis at cut-off points of 0.35 IU/mL, 0.20 IU/mL, and 0.10 IU/mL were 74.4%, 78.2%, and 80.5%, respectively. The specificity values at cut-off points of 0.35 IU/mL, 0.20 IU/mL, and 0.10 IU/mL were 66.2%, 63.9%, and 57.1%, respectively. Our results support the QFT-GIT assay as a potential tool for diagnosing tuberculosis and for monitoring the efficacy of anti-tuberculosis treatment.