In-Tube Test Research Articles

Comparing the Diagnostic Performance of QuantiFERON-TB Gold Plus to Other Tests of Latent Tuberculosis Infection: A Systematic Review and Meta-analysis.

We conducted a review to compare the sensitivity, specificity, reproducibility, and predictive ability of QuantiFERON-TB Gold Plus (QFT-Plus) with that of QuantiFERON-TB Gold In-Tube (QFT-GIT; QIAGEN, Hilden, Germany) and other latent tuberculosis infection (LTBI) tests. We searched MEDLINE, Embase, Web of Science, and the Cochrane Database of Systematic Reviews from January 2013 through May 2020. We included studies comparing QFT-Plus with at least one other LTBI test. We estimated sensitivity from studies of patients with active tuberculosis, and specificity from studies of healthy individuals with low risk of LTBI. Three independent reviewers evaluated eligibility, extracted data, and assessed risk of bias. Compared with QFT-GIT, the sensitivity of QFT-Plus in patients with active TB was 1.3% higher (95% confidence interval [CI], -0.3% to 2.9%); in 2 studies of patients with very low probability of LTBI, the specificity was 0.9% lower (95% CI, -2.4% to 0.6%). These differences were not statistically significant. The agreement between QFT-Plus and QFT-GIT was high, with a pooled Cohen's kappa statistic of 0.83 (95% CI, 0.79 to 0.88). The reproducibility of QFT-GIT and QFT-Plus was similarly poor. All participants in the studies to estimate sensitivity were aged ≥15 years, and only 6 were people living with human immunodeficiency virus. We found no studies to assess predictive ability. QFT-Plus has diagnostic performance that is very similar to that of QFT-GIT. Further studies are needed to assess the sensitivity of QFT-Plus in immunocompromised patients and younger children before concluding if this new version offers advantages.

CD4 response of QuantiFERON-TB Gold Plus for positive consistency of latent tuberculosis infection in patients on dialysis

A significantly negative reversion in the QuantiFERON-TB Gold In-tube (QFT-GIT) test is reported in patients on dialysis, which makes the results unreliable. The CD4 and CD8 responses of the QFT-Gold plus (QFT-Plus) may have better positive consistency, but this needs to be investigated. We enrolled dialysis patients with baseline positive QFT-GIT0 results and conducted two rounds of follow-up paired QFT-GIT1&2 and QFT-Plus1&2 tests at an interval of 6 months. The positive consistency, concordance, and discordance of the QFT results were analyzed. A total of 236 patients on dialysis were screened, and 73 participants with positive QFT-GIT0 results were enrolled. The baseline QFT-GIT0 response was higher in the 1st QFT-Plus1(+) group than in the QFT-Plus1(−) group, but insignificantly different between the 1st QFT-GIT1(+) and QFT-GIT1(−) groups. The two assays had good correlation when concurrently tested. Fifty-three subjects completed a second round of the QFT-GIT2 and QFT-Plus2. Persistent positivity was higher with the QFT-Plus2 (81.8%) than with the QFT-GIT2 (58.8%, p = 0.040). The QFT-GIT1 and QFT-Plus1 CD4 responses were higher in patients with persistent positivity than in those with negative reversion, whereas the difference of the QFT-Plus TB1 and TB2 data, representative of the CD8 response, were similar between positive persistence and negative reversion. In conclusion, the QFT-Plus provides more reliable positive consistency than does the QFT-GIT. The CD4 interferon-γ response might play a role in maintaining positivity of LTBI.

Prevalence of Latent Tuberculosis Infection Among Non-US-Born Persons by Country of Birth-United States, 2012-2017.

Most tuberculosis (TB) disease in the United States (US) is attributed to reactivation of remotely acquired latent TB infection (LTBI) in non-US-born persons who were likely infected with Mycobacterium tuberculosis in their countries of birth. Information on LTBI prevalence by country of birth could help guide local providers and health departments to scale up the LTBI screening and preventive treatment needed to advance progress toward TB elimination. A total of 13 805 non-US-born persons at high risk of TB infection or progression to TB disease were screened for LTBI at 16 clinical sites located across the United States with a tuberculin skin test, QuantiFERON Gold In-Tube test, and T-SPOT.TB test. Bayesian latent class analysis was applied to test results to estimate LTBI prevalence and associated credible intervals (CrIs) for each country or world region of birth. Among the study population, the estimated LTBI prevalence was 31% (95% CrI, 26%-35%). Country-of-birth-level LTBI prevalence estimates were highest for persons born in Haiti, Peru, Somalia, Ethiopia, Vietnam, and Bhutan, ranging from 42% to 55%. LTBI prevalence estimates were lowest for persons born in Colombia, Malaysia, and Thailand, ranging from 8% to 13%. LTBI prevalence in persons born outside the US varies widely by country. These estimates can help target community outreach efforts to the highest-risk groups.

QuantiFERON®-TB Gold In-Tube test can be used for screening latent tuberculosis before biological treatment in a Bacille Calmette-Guérin (BCG)-vaccinated country: the HUR-BIO single-center real-life results.

The Turkish population is vaccinated with Bacille Calmette-Guérin (BCG), and the BCG vaccination decreases the specificity of the tuberculin skin test (TST). The purpose of this study was to investigate the incidence of active tuberculosis (TBC) among rheumatic patients who were screened only with the QuantiFERON®-TB Gold In-Tube (QFT-GIT) test for latent TBC prior to biological treatment. The Hacettepe University Biological Database (HUR-BIO) was used for latent TBC assessment. Consecutive patients were evaluated from July 2015 to October 2016 by a questionnaire that included the patients' demographic characteristics, treatment history, and symptoms of active TBC. A total of 664 patients were interviewed by physicians. TBC statuses of the 671 non-interviewed patients were checked from the Turkish National Tuberculosis Registry records. Mean TBC incidence per year was calculated for anti-tumor necrosis factor-alpha (TNF-α) agents. A total of 1335 (58.2% female) patients with the mean age of 44.2 ± 12.9years were included. Of the patients, 836 (62.6%) had spondyloarthropathy, 432 (32.4%) had rheumatoid arthritis, and 67 (5%) had other rheumatologic diseases. The total biological drug exposure was 2292 patient-years (2043 patient-years for anti-TNF-α, 249 patient-years for non-TNF-α inhibitors). Positive and indeterminate QFT-GIT results were found in 258 (19.3%) and 23 (1.7%) patients, respectively. The median follow-up time after the onset of biological agent was 19.4months (IQR = 29.5). Pulmonary TBC was found in 3 (0.2%) of the 1335 patients. The annual incidence of TBC was 147/100,000 patient-years for all TNF-α inhibitors (249/100,000 and 123/100,000 patient-years for QFT-GIT-positive and negative patients, respectively). TBC incidence increased by nearly seven times the Turkish national TBC incidence. The QFT-GIT Test appears acceptable to determine latent TBC before biological agent use. Consequently, the QFT-GIT Test can be appropriately used in BCG-vaccinated countries. Key Points • Our study contributes to filling the gap in the literature by reflecting real-life data about TBC frequency after QFT-GIT use in patients receiving biological agents. • The frequency of active TBC will remain within acceptable limits when only QFT-GIT is used in the screening of latent TBC prior to the use of biological agents in a population where the majority are vaccinated with BCG. • Using the QFT-GIT alone for latent TBC screening prior to biologic treatment in countries with high BCG vaccination rates reduces the number of patients needing isoniazid (INH) treatment.

BCG Vaccine Protection against TB Infection among Children Older than 5 Years in Close Contact with an Infectious Adult TB Case.

The Bacille Calmette–Guérin (BCG) vaccine has been shown to provide considerable protection against miliary or meningeal tuberculosis (TB), but whether it prevents other forms of disease remains controversial. Recent evidence has shown that the BCG vaccine also provides protection against latent TB infection (LTBI). The aim of the current study was to examine whether BCG has a protective role against LTBI among children in close contact with an adult index case in a low TB endemicity setting with the use of the QuantiFERON-TB Gold In-Tube test (QFT-GIT). A cross-sectional study was conducted over a 10-year period among children referred to our outpatient TB clinic with a history of close contact with an adult with pulmonary TB. All subjects had a QFT-GIT performed. In total, 207 children > 5 to 16 years of age with known recent exposure were enrolled. BCG-vaccinated subjects had a 59% lower risk of presenting with LTBI after close contact with an adult index case compared with unvaccinated subjects (OR = 0.41, 95% CI: 0.23–0.73, p = 0.002). After adjustment for possible confounders, the protective effect of prior BCG immunization was estimated at 68% (OR = 0.32, 95% CI: 0.15–0.66, p = 0.002). Other risk factors for LTBI included a history of migration (OR = 2.27, 95% CI: 1.13–4.53, p = 0.021) and transmission of infection to other exposed child contacts (OR = 4.62, 95% CI: 2.27–9.39, p = 0.001). We were able to determine a strong protective role of BCG vaccination among children older than 5 years, immunized at school entry, who had close contact with an adult infectious TB case.

Impact of the interferon-γ release assay and glomerular filtration rate on the estimation of active tuberculosis risk before bronchoscopic examinations: a retrospective pilot study.

BackgroundBronchoscopic examinations are vital to diagnose pulmonary diseases. However, as coughing is triggered during and after the procedure, it is imperative to take measures against nosocomial infections, especially for airborne infections like tuberculosis (TB). The interferon-γ release assay (IGRA) has recently been established as a method to evaluate the infection status of TB. We aimed to ascertain the efficacy of IGRA and clinical findings in estimating the prevalence of active TB before bronchoscopy.MethodsWe obtained IGRA results from 136 inpatients using a QuantiFERON-TB Gold In-Tube test. Bronchoscopy samples were cultured in Mycobacteria Growth indicator tubes and 2% Ogawa solid medium. We evaluated the adjusted effects of multiple clinical variables on active TB status using a logistic regression model. In addition, multiple variables were converted into a decision tree to predict active TB.ResultsFive (3.7%) patients were diagnosed with culture-positive TB, two of whom were simultaneously diagnosed with non-small-cell lung carcinoma or small-cell lung carcinoma. The multivariate analysis suggested the probability of predicting active TB using the IGRA [odds ratio (OR), 72.7; 95% confidence interval (CI), 3.169–1668; P=0.007] and decreased estimated glomerular filtration rate (eGFR) (OR, 0.937; 95% CI, 0.882–0.996; P=0.038) in patients undergoing bronchoscopy. A decision tree validated the use of these two variables to predict active TB.ConclusionsIGRA test results are useful for predicting active TB before bronchoscopy. This strategy could identify patients who require antibiotic therapy to prevent TB or who are in the active phase of TB.

PREVALENCE OF LATENT TB AMONG US ADULTS WITH CHRONIC HEPATITIS B VIRUS: A RETROSPECTIVE STUDY OF THE NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY

SESSION TITLE: Chest Infections Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Tuberculosis (TB) and hepatitis B virus infection (HBV) are treatable, communicable diseases that can exist as chronic, asymptomatic infections with a significant global burden. Guidelines recommend screening TB patients for HBV if they have risk factors prior to initiating tuberculosis therapy. However, there are no clear general guidelines regarding TB screening among patients with chronic HBV or vice versa, and rates of co-infection with latent TB (LTBI) and HBV have not been well described. We aim to evaluate prevalence ratios of LTBI and HBV co-infection among U.S. adults using a large population-based database. METHODS: Using the National Health and Nutrition Examination Survey (NHANES), a cross-sectional, stratified, multistage probability sample of the U.S. population, we retrospectively evaluated the prevalence of LTBI and HBV co-infection among adults age 20 and older for the 1990-2000 and 2011-2012 cycles. LTBI was assessed using NHANES data reported for the tuberculin skin test (TST). Data for the QuantiFERON-TB Gold In-Tube test (QFT-GIT) was reported for the 2011-2012 cycle only. The presence/absence of HBV was analyzed using the hepatitis B surface antigen (HBsAg) test result. Observations with missing data were excluded from this study. Between-group comparisons used chi-squared testing with a statistical significance set at a two-tailed p<0.05. RESULTS: Overall prevalence of LTBI was 4.2%, HBV was 0.3% and prevalence of LTBI and HBV coinfection was low (0.03%). Prevalence of LTBI was higher among individuals with HBV compared to those without HBV (15.3% [95% CI 6.6-31.7%] vs. 4.3% [95% CI 3.5-5.2%] respectively, p=0.004). LTBI increased among those with HBV (6.8% [95% CI 1.4-27.1%] in 1999-2000 to 21.9% [95% CI 8.0-47.6%] in 2011-2012; p=0.16), while it remained stable among those without HBV (4.3% [95% CI 3.5-5.4%] in 1999-2000 to 4.2% [95% CI 3.0-5.8%] in 2012-2012; p=0.89). TB prevalence based on the QFT-GIT was 22.7% (95% CI 11.5-40.0) in 2011-2012. In NHANES, among the subset of patients with LTBI, prevalence of HBV showed a non-significant increase (0.4% [95% CI 0.1-1.7%] in 1999-2000 to 1.4% [95% CI 0.5-3.8%] in 2011-2012; p=0.12). CONCLUSIONS: This study is one of the first to describe TB and HBV co-infection prevalence rates using U.S. population-based data. In 2011-2012, prevalence of LTBI was 3.6 times higher among individuals with HBV compared to those without, which may reflect the importance of shared risk factors in affecting disease epidemiology. CLINICAL IMPLICATIONS: This study highlights the high prevalence of TB among chronic HBV patients, which may help guide screening practices and may suggest a potential role for co-screening for TB and HBV among these high-risk patients with shared risk factors. This is particularly important given the potential impact of HBV co-infection on the risk of drug-induced liver injury related to anti-tuberculosis therapies. DISCLOSURES: No relevant relationships by Amit Chitnis, source=Web Response No relevant relationships by Grishma Hirode, source=Web Response No relevant relationships by Ashley Hubbard, source=Web Response No relevant relationships by Robert Wong, source=Web Response

Interferon-γ (+874 T/A) and interleukin-10 (−1082 G/A) genes polymorphisms are associated with active tuberculosis in the Algerian population of Oran's city

Background and aimsPolymorphisms within genes encoding the cytokines involved in anti-tuberculosis immunity have been widely studied and sometimes associated with an increased risk of developing the active form of tuberculosis (TB). This study analyzes for the first time the impact of two polymorphisms, namely IFNG+874 T/A and IL10-1082 G/A, in the Algerian population where tuberculosis is moderately endemic. MethodsThis case–control study included 104 healthy controls and 141 active TB patients: 75 extrapulmonary (EPTB) and 66 pulmonary (PTB). They were all genotyped by refractory mutational system-PCR amplification. In order to measure the functional impact of IFNG+874 T/A on the production rate of IFN-γ, 43 patients performed a QuantiFERON®Gold In-tube test. ResultsThe IFNG+874 AA genotype was associated with a higher risk of developing EPTB (OR = 2.52; 95%CI = 1.23–5.18; p = 0.012) while the IFNG+874 TA genotype was associated with a greater protection (OR = 0.34, 95%CI = 0.16–0.74; p = 0.006) which was further characterized by a high production of IFN-γ (p = 0.001). Similarly, the allele A of SNP IL10-1082 G/A, especially in its homozygous form (AA), were overrepresented in PTB patients (p = 0.010 and 0.019, respectively). The combination of both susceptibility genotypes (AA/AA) was strongly associated with risk of development of active TB (OR = 8.58; 95% C.I = 1.95–37.70, p = 0.004). This susceptibility combination was only significant in men regarding PTB (OR = 11.05; 95% C.I = 1.32–92.72, p = 0.027). Additionally, IFNG+874 TA and IL10-1082G∗ genotypes combination was mostly encountered in men controls and conferred the highest protection rate against EPTB (OR = 0.25; 95% C.I = 0.08–0.76, p = 0.015). ConclusionThese two cytokines genes polymorphisms are associated with active TB susceptibility in the Algerian population. They act synergistically in terms of protection and susceptibility regarding the two forms of the disease. Moreover, these associations were more marked among males suggesting a potential role of gender.

Serological and molecular evidence of Mycobacterium bovis in dairy cattle and dairy farm workers under the intensive dairy production system in Egypt.

We employed a combination of diagnostic tests including single cervical tuberculin test (SCT), rapid lateral-flow test (RT), TB-Feron, conventional PCR and culture to investigate the prevalence of Mycobacterium bovis infections in dairy cattle under the intensive dairy production system in Egypt. In total, 2710 dairy cows from 11 herds in six Governorates were tested by SCT and 444 (16·4%) were TB reactors. Only 65 cows responded to M. bovis antigen by RT and TB-Feron. A postmortem examination showed that 49 (75·4%) of slaughtered cows have visible lesions. Testing of 215 out 444 SCT reactor cows by culture and PCR using blood and milk samples revealed that M. bovis were more frequently identified in the blood (6·1-20·5%) than milk (2·3-5·6%) samples. Additionally, in this study, we investigated the prevalence and potential risk factors associated with M. bovis infection in dairy farm workers. Overall, 100 dairy farm workers were tested using QuantiFERON-TB Gold In-Tube test to detect Mycobacterium tuberculosis complex (MTC) and 35 (35%) were positive. In all, 23 (23%) of MTC positive were M. bovis positive using PCR. Mycobacterium bovis positive cases were associated with workers who had respiratory signs and did not wash or disinfect their hands after handling cows. The prevalence of M. bovis in dairy cows and dairy farm workers under the intensive dairy production system in Egypt is high. It is therefore essential to disseminate effective prevention and control measures to prevent the spread of M. bovis between dairy cows and dairy workers. This study revealed that the use of RT or TB-Feron as an ancillary test of SCT reactor cows resulted in a significant reduction in the SCT false-positive slaughtered cows. A high prevalence of M. bovis infection among farm workers provides evidence of occupational risk in the intensive dairy production system in Egypt.

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

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. 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. 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. 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.

Adherence to nine-month isoniazid for latent tuberculosis infection in healthcare workers: a prospective study in a tertiary hospital

Poor adherence to medication can lead to treatment failure in healthcare workers (HWCs) with latent tuberculosis infection (LTBI) who are at high risk of developing active tuberculosis. However, the factors associated with non-completion of nine-month LTBI treatment with isoniazid (9 H) have not been well studied. We investigated the completion rate and factors affecting adherence to LTBI treatment with 9 H among HCWs. A prospective cohort study of 114 HCWs who were diagnosed with LTBI by QuantiFERON-TB Gold In-Tube tests were performed in a single university hospital between June 2016 and December 2017. All patients received the 9 H LTBI treatment. At each visit, treatment adherence and development of adverse reactions to isoniazid were evaluated via a standard questionnaire. To evaluate the impact of the severity of hepatotoxicity on non-completion of LTBI treatment, we classified hepatotoxicity into two groups: severe hepatotoxicity was defined as alanine aminotransferase >3.0 times the upper normal limit (UNL) with symptoms or = 5.0 times the UNL. Mild hepatotoxicity was defined as alanine aminotransferase>UNL, but not meet the definition of severe hepatotoxicity. Overall, 71 HCWs (62.3%) completed LTBI treatment with 9 H while 43 HCWs (37.7%) discontinued their treatment. Most discontinuation (81.4%, 35/43) occurred during the first three months of treatment. There were no significant differences in age, sex, occupation, or comorbidities between the HCWs who completed and those who discontinued LTBI treatment. However, HCWs who discontinued LTBI treatment had more hepatotoxicity than those who completed treatment (44.2% vs. 11.3%, P < 0.001). Cox proportional hazard analysis revealed that hepatotoxicity is the only factor significantly associated with discontinuation of 9 H LTBI treatment (unadjusted HR = 2.89, 95% CI = 1.62–5.46). In multivariable analysis, not only severe hepatotoxicity (adjusted HR = 7.99, 95% CI = 3.05–20.94) but also mild hepatotoxicity was significantly associated with discontinuation of LTBI treatment (adjusted HR = 2.34, 95% CI = 1.05–5.21). The completion rate of 9 H LTBI treatment was 62.3% among HCWs. While age, sex, occupation, and pretreatment comorbidities were not associated with treatment completion, isoniazid-induced hepatotoxicity significantly affected adherence.

Selection of the cutoff value on tuberculin skin test in diagnosing tuberculosis infection: a population-based cross-sectional study in Eastern China

Objective: To confirm the cutoff induration diameter of tuberculin skin test (TST) so as to decrease the false positive of the TST. Methods: Fasting blood glucose test, TST and Quanti FERON-TB (QFT) Gold In-Tube test were administered to recruit participants at the baseline stage. QFT was used as the gold standard to determine the cutoff of the TST test. Results: Overall, 5 405 participants were enrolled in this study, of whom 1 104 (20.4%) were QFT positive. Among all the 5 405 participants that without stratification, diagnostic value reached the highest when the induration diameter was 10.25 mm with sensitivity and specificity as 0.731 and 0.727, respectively. When the participants were divided into groups as nondiabetics, confirmed diabetics, undiagnosed diabetics, the sensitivities and specificities appeared as 0.701, 0.837, 0.824 and 0.805, 0.821, 0.778 with induration diameters as 11.25 mm, 10.25 mm and 11.25 mm, respectively. Conclusions: Findings of this study confirmed that the specificity of tuberculin test could be significantly improved by using 10-12 mm as the cutoff value for diagnosing the latent tuberculosis infection.

Comparison between Quanti-FERON-TB Gold In-Tube test and tuberculin skin test for diagnosis of latent tuberculosis in children: A cross-section study

Objective: To compare Quanti-FERON-TB Gold In-Tube (QFT- GIT) test and tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection in children. Methods: In this cross-sectional study, 64 participants who were between 3 months and 14 years old and had close contact with smear-positive pulmonary tuberculosis were included. Both QFT- GIT test and TST were done and the results were analyzed by SPSS software and Kappa test. Results: The distribution of gender and age according to QFT-GIT and TST results were matched (P>0.05). Overall agreement between QFT-GIT and TST for diagnosis of latent tuberculosis infection in children was 75%. In addition, the contingency coefficient was 0.257, and the Kappa measure of agreement was 0.246 (P=0.034). Conclusions: Compared to TST, QFT-GIT shows no apparent advantage for diagnosis of latent tuberculosis infection in children.

Introduction of a Borderline Range for the Interpretation of QuantiFERON-TB Gold In-Tube Results in Korean Healthcare Workers

South Korea is the only Organisation for Economic Co-operation and Development (OECD) country with a high incidence of tuberculosis (TB). Healthcare workers (HCWs) have an increased risk of TB infection. QuantiFERON-TB Gold In-Tube (QFT-GIT) testing is performed for occupational health screening to detect latent TB infection (LTBI). We evaluated the introduction of new criteria for borderline ranges for interferon-gamma release assay (IGRA) results in HCWs. The results of QFT-GIT tests in HCWs in 2017 and 2018 were collected, with high-risk HCWs having two serial test results. Existing dichotomous criteria and new criteria with borderline ranges (bor-derline negative [BN], 0.20 - 0.34 IU/mL; borderline positive [BP], 0.35 - 0.99 IU/mL) were applied to each test re-sult. After applying the borderline range, 26.4% of the positive results were classified as BP (4% of total results), while 4.2% of the negative results were classified as BN (3.6% of total results). Among seven HCWs with initial results in the borderline range, two had repeated borderline results while 71.4% had low negative results. We recommend the introduction of borderline ranges in the interpretation of QFT-GIT results to reduce unnecessary TB therapy in HCWs.

Latent tuberculosis infection among patients with type 2 diabetes mellitus

Background Although there is well-proved association between type 2 diabetes mellitus (T2DM) and active tuberculosis, factors involved in the association between T2DM and latent tuberculosis infection (LTBI) are scarcely known. Aim The aim of this study was to study the prevalence and risk factors of LTBI in a cohort of Egyptian adults with T2DM including studying the effect of oral hypoglycemic drugs on this prevalence. Patients and methods All patients with T2DM were recruited from Menoufia University Endocrinology outpatient clinic during the period from June to December 2018. Demographic and clinical data, serum glucose and glycosylated hemoglobin (HbA1c) level, and QuantiFERON-TB Gold In-Tube and tuberculin skin test were assessed. Results In all, 102 patients were recruited, according to the QuantiFERON test; 22 (21.6%) patients were diagnosed with LTBI. Their mean age was 54.91±8.85, mean T2DM duration was 9.82±6.54/year, mean HbA1c% was 10.29±1.59, which is significantly higher than patients without LTBI. Patients on metformin-containing regimens were only 18% (four of 22 cases) among the LTBI patients, and 89.7% of the whole patients with metformin-containing regimen were without LTBI. Multivariant regression showed that age (odds ratio=1.178, P=0.041) and HbA1c% (odds ratio=2.789, P=0.008) were strong predictors for LTBI. Conclusion LTBI is prevalent in patients with T2DM especially among those with older age, longer duration of diabetes mellitus, uncontrolled diabetes mellitus, and on nonmetformin regimens. Age and HbA1c are strong predictors of LTBI in T2DM patients.

Monitorization of tuberculosis screening tests during anti-TNF- and #945; treatment in children with rheumatic diseases

Aim: We aimed to investigate the incidence of latent tuberculosis infection (LTBI) and seroconversion rate of LTBI screening tests under anti-TNF-α treatment, in our pediatric patients with chronic rheumatic diseases.Material and Methods: The data of 47 patients received anti-TNF-α treatment for different chronic rheumatic diseases between May-2015 and May-2018, were reviewed retrospectively. Demographics and clinical findings of the patients, as well as the treatments and their durations, were collected. The tuberculin skin test (TST) and Quantiferon-TB-Gold in-tube (QFT) test results at initiation and one year after the anti-TNF-α treatment were compared. Results: The study group included 38 (80.8%) patients with juvenile idiopathic arthritis, six (12.7%) with idiopathic uveitis, two (4.2%) with Behcet's disease related uveitis and one (2.1%) with juvenile dermatomyositis. For a period at least one year, 33 (70.2%) patients received etanercept, 12 (25.5%) received infliximab and two (4.2%) received adalimumab treatment. Before anti-TNF-α treatment, 31.9% of the patients were diagnosed with LTBI. After one year of treatment, it was found to be increased to 44.6%. During treatment, the seroconversion rate of the screening tests for LTBI was determined to be 12.7% (6/47).Conclusion: The seroconversion rate of screening tests for LTBI was found high in pediatric patients receiving anti-TNF-α treatment. Although the consistency between TST and QFT tests was found weak in our study, the fact that these tests should be used and evaluated together in the follow-up in the light of current guidelines in terms of LTBI and active tuberculosis development, remains still up to date. Further research is need in order for more enlightening data on the risk of LTBI and active tuberculosis in patients under anti-TNF-α treatment.

Diagnostic Potential of a PPE Protein Derived from Mycobacterium tuberculosis Beijing/K Strain.

PurposeThe prevalence of Mycobacterium tuberculosis (M. tb) and the status of M. bovis BCG vaccination may affect host immune responses to M. tb antigens. Understanding of the predominant local M. tb strain and immune signatures induced by its strain-specific antigens may contribute to an improved diagnosis of tuberculosis (TB). The aim of this study was to determine immune responses to M. tb antigen which was identified from the hyper-virulent Beijing/K strain in South Korea.Materials and MethodsPulmonary TB patients (n=52) and healthy subjects (n=92) including individuals with latent TB infection (n=31) were recruited, and QuantiFERON-TB Gold In-Tube tests were performed. The Beijing/K-antigen specific immune signatures were examined by diluted whole blood assays and multiplex bead arrays in a setting where nationwide BCG vaccination is employed.ResultsStatistical analyses demonstrated that three [C-X-C motif chemokine (CXCL10), interleukin (IL)-6, interferon (IFN)-α] of 17 cytokines/chemokines distinguished active cases from healthy controls following stimulation with the Beijing/K-specific antigen. IFN-α also differentiated between active diseases and latent TB infection (p<0.01), and the detection rate of TB was dramatically increased in combination with IL-6 and CXCL10 at the highest levels of specificity (95–100%).ConclusionOur data indicate that immune signatures to the M. tb Beijing/K-specific antigen can provide useful information for improved TB diagnostics. The antigen may be developed as a diagnostic marker or a vaccine candidate, particularly in regions where the M. tb Beijing/K strain is endemic.

Performance and correlation of QuantiFERON-TB Gold, T-SPOT.TB and tuberculin skin test in young children with tuberculosis exposure or tuberculosis disease

Objective: To evaluate the performance of interferon gamma release assays and tuberculin skin test in Bacillus Calmette-Guerin vaccinated young children. Methods: A cross-sectional study was conducted in healthy children younger than 5 years who were recently diagnosed with tuberculosis or had recent exposure to active tuberculosis. QuantiFERON-TB Gold, T-SPOT.TB and tuberculin skin test were performed in each patient. Results: Of the 60 children, median age 3.3 years, 17 had tuberculosis and 43 had recent tuberculosis exposure. Overall, 15 (25.0%) children had tuberculin skin test reaction ≥ 10 mm; 8 (13.3%) were positive by QuantiFERON-TB Gold In-Tube test, and 12 (20.0%) by T-SPOT.TB. Nineteen (31.7%) children had at least one positive test. There was a moderate agreement between interferon gamma release assays and tuberculin skin test. Conclusions: The positive rates of interferon gamma release assays and tuberculin skin test were low in young children who were infected with tuberculosis, supporting the management strategy without testing in children younger than 5 years.

The use of GeneXpert Mycobacterium tuberculosis/rifampicin assay in diagnosis of pulmonary tuberculosis in children

Introduction Rapid diagno sis of tuberculosis (TB) is essential for early disease management. GeneXpert (GX) test is a novel rapid diagnostic modality. In this study, we aimed to evaluate the diagnostic role of GX test in diagnosing pulmonary tuberculosis (PTB) in children as well as detection of rifampicin (RIF) resistance. Patients and methods This was a cross-sectional study that included 80 patients suspected to have PTB based on clinical data together with at least one of the followings: a positive tuberculin skin test or QuantiFERON-TB Gold In-Tube test result, a positive blood TB PCR result, or a positive Ziehl–Neelsen staining result. Results PTB was more common in older females. Extrapulmonary manifestations and hilar lymphadenopathy were more frequent in younger age. Both positive tuberculin skin test and positive GX were more frequent in older age. Positive GX was found in 30 (37.5%) cases, and RIF resistance was detected in two (6.6%) of them. Positive GX results were more frequent in sputum than gastric aspirate samples. Positive GX results were more frequent with absent Bacillus Calmette–Guerin scar, and with hemoptysis, failure to thrive, cavitary lung lesions, and lower mean hemoglobin. Conclusion GX detects many more cases than blood PCR and Ziehl–Neelsen stain. GX had 70% sensitivity and 95% specificity in diagnosing PTB, with overall diagnostic accuracy of 86.67%, with better performance in older children who could expectorate. RIF resistance was ∼6.6%.

Comparison of tuberculin skin test and QuantiFERON-TB Gold In-Tube test in Bacillus Calmette-Guerin-vaccinated children.

Objectives:The aim of this study is to determine the concordance between QuantiFERON-TB Gold In-Tube (QFT-GIT) and tuberculin skin test (TST) in children vaccinated with Bacillus Calmette–Guerin (BCG).Methods:This cross-sectional study was done at a pediatric tertiary care center in 33 BCG-vaccinated children aged 6 months–15 years suspected of Mycobacterium tuberculosis infection or in contact with a patient with open tuberculosis (TB). All patients were tested for TST with purified protein derivative-S 5 tuberculin units and QFT-GIT assays. Concordance was evaluated between TST and QFT assay by kappa coefficient (k). Agreement between the tests was classified into categories: poor if k < 0.20, fair (k = 0.21–0.40), moderate (k = 0.41–0.60), good (k = 0.61–0.80), and very good (k = 0.81–1.00).Results:Both the TST and QFT assay were positive in 13 and negative in eight children, respectively, resulting in an agreement of 63% (κ = 0.31). Eight children were <4 years of age of which only one patient had a positive TST and QFT-GIT, and TST and QFT-GIT were negative in two patients resulting in an agreement of 37.5% (κ = 0.063). Among children 4 years of age and older, 12 patients had a positive TST and QFT-GIT and 6 patients had a negative TST and QFT-GIT resulting in an agreement of 72% (κ = 0.41). Among 12 children who had been in contact with an adult having open TB, both the TST and QFT-GIT were positive in 6 patients and negative in two patients, respectively, resulting in an agreement of 66% (κ = 0.41). TST specificity was only 29.6% with a positive predictive value of 42.4% as compared to QFT-GIT. Among children <4 years of age, TST specificity was only 28.6% with a positive predictive rate of 16.7%, and among children >4 years of age, TST specificity was 50% with a positive predictive value of 66.7%. In patients with contact with a patient having TB, TST specificity was 33.3%. Considering TST of 15 mm and above as positive, TST specificity increased to 63.2% and a positive predictive value was 56.3%.Conclusion:The concordance of TST and QFT-GIT is low in children with previous BCG vaccination and especially in children <4 years of age. QFT-GIT may help to rule out false-positive TST.