Positive Interferon-gamma Release Assay Results Research Articles

Abstract 27 — Prevalence and Management Approach of Latent Tuberculosis Infection in Rheumatology Patients

Prior to immunosuppression, rheumatology patients are routinely screened for latent tuberculosis infection (LTBI) using Interferon-Gamma Release Assays (IGRA). The management of latent and indeterminate IGRA results varied among institutions and long-term outcome data is lacking. We conducted a retrospective study at Tawam Hospital, United Arab Emirates, to examine the frequency and management of positive and indeterminate IGRA results and tuberculosis infection in rheumatic patients. Methods Laboratory records and hospital electronic medical system were used to obtain information about IGRA results over a 12 years period (April 2010-April 2022). Results In our hospital record over a 12-year period, we found a total of 1012 positive and 223 indeterminate IGRA test results. Within the rheumatology department, 123 positive and 39 indeterminate IGRA results were identified. In the indeterminate IGRA group, the majority were female (n=24, 61.5%), UAE nationals (n=22, 56.4%), and had a mean age of 38.6 years. Systemic lupus erythematosus (SLE) was the most prevalent rheumatologic condition (n=21, 53.8%). 33.3% (n=13) were on disease modifying anti-rheumatic drugs (DMARDs) and 66.7% (n=26) were on corticosteroid during IGRA testing. A total of 8 patients (20.5%) received anti-TB medications. In a positive IGRA group, the mean age of 55.7 years and a female-to-male ratio of 3:1. The most common rheumatologic conditions were RA (n=67, 54.4%). Approximately 52.8% (n=65) of patients were on conventional DMARDs, 66.7% (n=26) were on corticosteroids during IGRA testing, and 60% (n=74) received anti-TB medications. Two cases (1.6%) of active TB infections were detected among patients with positive IGRA tests, both of whom were receiving anti-TNFa inhibitor treatment in combination with methotrexate. No cases of active TB infection were observed in the indeterminate IGRA group. Conclusion Tuberculosis risk in positive and indeterminate IGRA results for rheumatological conditions is low. Further multicenter studies are required to analyze patient outcomes and differences in TB-endemic and non-endemic regions.

LTBI-negative close contacts of tuberculosis are more likely to develop the disease: enlightenment and lessons from a cluster outbreak.

Tuberculosis (TB) prevention and control among groups living together, such as students, workers, older adults in nursing homes, and prisoners, present many challenges due to their particular age and environmental factors, which can make them more susceptible to TB clusters with significant societal impact. This study aimed to evaluate a TB cluster outbreak epidemic in a university and provide suggestions for improving TB control strategies for groups living together. Pulmonary TB screening and close-contact investigation were conducted using acid-fast staining, sputum culture, GeneXpert testing, tuberculin skin testing (TST), interferon-gamma release assay (IGRA), and chest computed tomography (CT). GraphPad Prism 9.5.1 was utilized for data analysis. Collected epidemic data were comprehensively analyzed by rate comparison. The TB cluster outbreak epidemic was identified with an index case confirmed positive. The initial screening was conducted on potential close contacts of the index case, and the TST's positive rate (diameter ≥ 5 mm) and strong positive rate (diameter ≥ 15 mm) among these close contacts were 65.60% (21/32) and 34.40% (11/32), respectively. Moreover, the latent TB infection (LTBI) rate (diameter ≥ 10 mm) was 43.75% (14/32), and the IGRA's positive rate was 9.30% (3/32). Chest CT scans did not reveal any abnormalities. Surprisingly, 5 of the close contacts developed active TB in the second screening, accompanied by changes from negative to positive TST and/or IGRA results, after 3 months of follow-up. Accordingly, we expanded the screening scope to include another 28 general contacts. We found that the positive rate (78.00%, 25/32), strong positive rate (50.00%, 16/32), and LTBI rate (62.50%, 20/32) of the 32 close contacts were significantly higher than those of the additional general contacts (28.00%, 8/28; 14.3%, 4/28; 25.00%, 7/28), as indicated by p < 0.05. In the event of an epidemic TB outbreak, it is essential to rapidly identify the source of infection and initiate timely screening of close contacts. The initial screening should be focused on individuals without LTBI, who are at higher risk of developing TB. In purified protein derivative-negative individuals living in groups, additional vaccination or revaccination with Bacille Calmette-Guérin may help prevent cluster outbreaks of TB.

The Interferon-Gamma Release Assay versus the Tuberculin Skin Test in the Diagnosis of Mycobacterium tuberculosis Infection in BCG-Vaccinated Children and Adolescents Exposed or Not Exposed to Contagious TB.

Children have an increased risk of developing active tuberculosis (TB) after exposure to Mycobacterium tuberculosis (M.tb), and they are more likely to develop the most severe forms of TB. Rapid diagnosis and treatment of latent M.tb infection (LTBI) is essential to lessen the devastating consequences of TB in children. The aim of the study was to evaluate TST (tuberculin skin test) and IGRA (interferon-gamma release assay) utility in identifying LTBI in a cohort of Bacille Calmette-Guérin (BCG)-vaccinated Polish children and adolescents exposed or not exposed to contagious TB. In addition, we asked whether quantitative assessment of IGRA results could be valuable in predicting active TB disease. Of the 235 recruited volunteers, 89 (38%) were TST-positive (TST+), 74 (32%) were IGRA-positive (IGRA+), and 62 (26%) were both TST+ and IGRA+. The frequency of TST positivity was significantly higher in the group with (59%) than without TB contact (18%). The percentage of TST+ subjects increased with age from 36% in the youngest children (<2 years) to 47% in the oldest group (>10 years). All positive IGRA results were found solely in the group of children with TB contact. There was a significant increase in the rate of positive IGRA results with age, from 9% in the youngest to 48% in the oldest group. The 10 mm TST cutoff showed good sensitivity and specificity in both TB exposed and nonexposed children and was associated with excellent negative predictive value, especially among nonexposed volunteers. Mean IFN-γ concentrations in IGRA cultures were significantly higher in the group of LTBI compared to the children with active TB disease, both TST+ and TST-. Both TST and IGRA can be used as screening tests for BCG-vaccinated children and adolescents exposed to contagious TB.

Identification of Active Pulmonary Tuberculosis Among Patients With Positive Interferon-Gamma Release Assay Results: Value of a Deep Learning-based Computer-aided Detection System in Different Scenarios of Implementation.

To evaluate the accuracy of a deep learning-based computer-aided detection (CAD) system in identifying active pulmonary tuberculosis on chest radiographs (CRs) of patients with positive interferon-gamma release assay (IGRA) results in different scenarios of clinical implementation. We collected the CRs of consecutive patients with positive IGRA results. Findings of active pulmonary tuberculosis on CRs were independently evaluated by the CAD and a thoracic radiologist, followed by interpretation using the CAD. Sensitivity and specificity were evaluated in different scenarios: (a) radiologists' interpretation, (b) radiologists' CAD-assisted interpretation, and (c) CAD-based prescreening (radiologists' interpretation for positive CAD results only). We conducted a reader test to compare the accuracy of the CAD with those of 5 radiologists. Among 1780 patients (men, 53.8%; median age, 56y), 44 (2.5%) were diagnosed with active pulmonary tuberculosis. The CAD-assisted interpretation exhibited a higher sensitivity (81.8% vs. 72.7%; P =0.046) but lower specificity than the radiologists' interpretation (84.1% vs. 85.7%; P <0.001). The CAD-based prescreening exhibited a higher specificity than the radiologists' interpretation (88.8% vs. 85.7%; P <0.001) at the same sensitivity, with a workload reduction of 85.2% (1780 to 263). In the reader test, the CAD exhibited a higher sensitivity than radiologists (72.7% vs. 59.5%; P =0.005) at the same specificity (88.0%), and CAD-assisted interpretation significantly improved the sensitivity of radiologists' interpretation (72.3%; P <0.001). For identifying active pulmonary tuberculosis among patients with positive IGRA results, deep learning-based CAD can enhance the sensitivity of interpretation. CAD-based prescreening may reduce the radiologists' workload at an improved specificity.

Prevalence of latent tuberculosis infection among participants of the national LTBI screening program in South Korea - A problem of low coverage rate with current LTBI strategy.

The Government of South Korea launched a national preemptive latent tuberculosis infection (LTBI) screening program in 2016, including more than 1. 6 million population in congregate settings. The objective of this study was to analyze LTBI prevalence and its risk factors in each setting. Additionally, the proportion of LTBI pool covered by the current national LTBI strategy was investigated. Database for results of interferon gamma release assay (IGRA), X-ray, and baseline demographic information was linked with National Health Information Database, national tuberculosis (TB) surveillance database, and national contact investigation database. Participants were categorized into three groups: Group A, workers of postpartum care centers, social welfare facilities and educational institutions; Group B, first year students in high school and out-of-school youths; and Group C, inmates of correctional facilities. Relative risks of LTBI by sex, age, place of living, income level, and comorbidities were calculated. A total of 444,394 participants in Group A, 272,224 participants in Group B, and 11,511 participants in Group C who participated in the national LTBI screening program between 2017 and 2018 were included, with LTBI prevalence of 20.7, 2.0, and 33.2%, respectively. Age was the single most important risk factor in Group A and Group C. Low-income level was another risk factor commonly identified in all groups. Among participants with positive IGRA results, 2.7, 4.4, and 3.3% in Groups A, B and C, respectively, had past TB exposure history since 2013. Current LTBI guideline targeting high or moderate TB risk disease covered 6.5, 0.6, and 1.1% of participants with positive IGRA results in Groups A, B and C, respectively. Only a small proportion of participants with positive IGRA results could be covered by the current LTBI strategy. Expansion of LTBI strategy by identifying further high-TB risk group in the general population is required.

501. Interferon-gamma Release Assays for Diagnosis of Latent TB Infection in Chronic Kidney Disease and Dialysis Patients

Abstract Background Patients with chronic kidney disease (CKD), especially end-stage kidney disease (ESKD), are at risk of developing tuberculosis (TB). Due to their relatively immunosuppresses condition, reactivation from latent TB infection (LTBI) is the core pathogenesis in these populations. However, the prevalence of LTBI among Thai CKD patients, assessed by a high sensitivity and specificity test such as interferon-gamma release assay (IGRA), has never been thoroughly explored. We aimed to investigate the prevalence and predictors for LTBI among Thai CKD patients, including ESKD individuals receiving renal replacement therapy (RRT) either by hemodialysis (HD) or peritoneal dialysis (PD). Methods All CKD patients who underwent an investigation for LTBI status at Ramathibodi hospital were prospectively recruited from September 2020 to November 2021 and retrospectively reviewed from December 2020 to November 2021. Those with positive or borderline IGRA results using T SPOT®.TB without clinical or radiological findings compatible with active TB was diagnosed with LTBI. The LTBI prevalence was determined by CKD staging and type of dialysis. Predictors for LTBI were assessed by logistic regression analysis. Results A total of 199 CKD patients were enrolled; 102 prospectively and 97 retrospectively. There were 173 evaluable patients included with a mean (SD) age of 53 (16) years, and 44% were male. Of those, 95 (55%) had ESKD and maintained on RRT. Overall, 39 (22.5%) CKD patients had LTBI with the prevalence of 25%, 12.5%, 25%, 25% and 24.2% in those with CKD stage 1, 2, 3a, 3b and ESKD, respectively (p=0.89). Among ESKD patients, those who were maintained on HD had a higher proportion of LTBI than those on PD (28.9% vs. 5.3%, p=0.03). In multivariate analysis, drinking alcohol was significantly associated with LTBI (OR 8.51; [95%CI 1.24-58.38]; p=0.029), and HD therapy was marginally associated with LTBI (OR 8.14; [95%CI 0.95-69.91]; p=0.056) among ESKD patients. Conclusion In TB endemic settings, one-fifth of patients with CKD and a quarter of ESKD patients could carry LTBI status. Alcohol consumption and HD therapy could better identify high-risk ESKD patients and potentially screen for LBTI. Disclosures All Authors: No reported disclosures.

The cascade of care for latent tuberculosis infection in congregate settings: A national cohort analysis, Korea, 2017-2018.

BackgroundIn 2017, Korea implemented a nationwide project to screen and treat latent tuberculosis infection (LTBI) in high-risk for transmission public congregate settings. We aimed to assess programme success using a cascade of care framework.Materials and methodsWe undertook a cohort study of people from three congregate settings screened between March 2017 and December 2018: (1) first-grade high school students, (2) employees of educational institutions, (3) employees of social welfare facilities. We report percentages of participants with LTBI completing each step in the cascade of care model. Poisson regression models were used to determine factors associated with not visiting clinics, not initiating treatment, and not completing treatment.ResultsAmong the 96,439 participants who had a positive interferon-gamma release assay result, the percentage visiting clinics for further assessment, to initiate treatment, and who then completed treatment were 50.7, 34.7, and 28.9%, respectively. Compared to those aged 20–34 years, individuals aged < 20 years and aged ≥ 65 years were less likely to visit clinics, though more likely to complete treatment once initiated. Using public health centres rather than private hospitals was associated with people “not initiating treatment” (adjusted risk ratio [aRR], 3.72; 95% confidence interval [CI], 3.95–3.86). Nine-month isoniazid monotherapy therapy was associated with “not completing treatment,” compared to 3-month isoniazid and rifampin therapy (aRR, 1.28; 95% CI, 1.16–1.41).ConclusionAmong participants with LTBI from three congregate settings, less than one third completed treatment. Age, treatment centre, and initial regimen were important determinants of losses to care through the cascade.

Serial interferon-gamma release assay in lung cancer patients receiving immune checkpoint inhibitors: a prospective cohort study.

Recent advancements in cancer immunotherapy using immune checkpoint inhibitors (ICIs) have received considerable attention. Although advantageous, ICI therapies cause unique immune-related adverse events (irAEs) in some patients. Moreover, infectious diseases, such as tuberculosis, have been recognized as emerging concerns during immunotherapy. We aimed to evaluate the interferon-gamma release assay (IGRA) conversion rate and active tuberculosis incidence during immunotherapy to elucidate the incidence of tuberculosis reactivation after ICI therapy induction.We prospectively assessed IGRA results in lung cancer patients who received ICI monotherapy before ICI treatment and at 6 and 12months after ICI treatment. We also assessed computed tomography findings to determine the presence of active tuberculosis when positive IGRA results were obtained. The ICIs used were nivolumab, pembrolizumab, atezolizumab, and durvalumab.In all, 178 patients were prospectively recruited between March 2017 and March 2020. Of these, 123 completed serial IGRAs, of whom 18, 101, and 4, respectively, had positive, negative, and indeterminate IGRAs at baseline. Three and four patients, respectively, showed IGRA reversion and conversion during immunotherapy. One patient with a sustained, stable positive IGRA and one with IGRA conversion developed active pulmonary tuberculosis during immunotherapy.We found that 3.3% and 1.6% of the patients developed IGRA conversion and active tuberculosis, respectively. Of the four patients who developed IGRA conversion, one developed active pulmonary tuberculosis during immunotherapy. Another patient with sustained, stable positive IGRA developed active tuberculosis. Physicians should be alert to tuberculosis development during ICI therapy, and IGRA testing is a useful tool to assess the risk of developing active tuberculosis.

High Prevalence of Tuberculosis Infection and Disease in Child Household Contacts of Adults With Rifampin-resistant Tuberculosis.

Household contact (HHC) investigation is an important strategy to identify individuals with tuberculosis (TB) exposure, infection and disease, including those who may benefit from tuberculosis preventive therapy (TPT). Data in children exposed to rifampin-resistant TB are limited. In preparation for and to inform the feasibility of an interventional trial, HHC of adults with pulmonary rifampin-resistant TB from high TB-burden countries were evaluated in a cross-sectional study. Using interferon-gamma release assay and study-specific and 2015 international consensus definitions of intrathoracic TB in children, we evaluated the prevalence and predictors of TB infection and disease in child (<15 years) HHCs. Of 303 child HHCs, median age (range) 7 years (0-14), 57% [95% confidence interval (CI): 50%-64%] had a positive interferon-gamma release assay result (TB infected). TB infection was associated with the index case smoking (P = 0.034), being the parent or sleeping in the same room (P = 0.002) and the child HHC being age ≥5 years and having attended school (P = 0.013). Four had study-defined confirmed TB and 9 had probable TB, a prevalence of 4.3% (95% CI: 2.6%-7.1%). Using the international consensus definitions, 4 had confirmed TB and 49 had unconfirmed TB, a prevalence of 17.2% (95% CI: 12.9%-22.4%). Twenty (7%) children had received TPT. The prevalence of TB infection and disease was high in child HHC exposed to rifampin-resistant TB. Few children had routinely received TPT. High-quality evidence is needed to inform strong recommendations for and access to TPT in children exposed to TB resistant to rifampin.

High glycosylated hemoglobin level as a risk factor of latent tuberculosis infection in patients with uncomplicated type 2 diabetes mellitus

Background Diabetes mellitus (DM) is known to increase the risk of infection including tuberculosis (TB). Some studies also showed that 2-15% of latent TB infection (LTBI) will progress to active TB. This study aimed to obtain the prevalence of LTBI and to determine the risk factors of LTBI in patients with type 2 diabetes mellitus (T2DM). Methods This was a cross-sectional study on 242 adult T2DM patients. For LTBI screening we performed the interferon gamma release assay (IGRA) (Quantiferon TB Gold Plus test) and for confirmation of active TB (pulmonary TB) we performed GeneXpert MTB/Rif sputum examination and chest X-ray. Glycosylated hemoglobin (HbA1c) levels, smoking history and BCG scar were collected. Multivariate logistic regression was used to analyze the data. Results Positive IGRA results were found in 99 of 242 uncomplicated T2DM patients while LTBI was found in 82 patients (33.8%). There were significant differences between T2DM patients with latent TB and T2DM patients without infection in HbA1c and specific IFN-ã levels (TB1 minus nil and TB2 minus nil), i.e. 8.5% and 7.6%, 2.5 IU/mL and 0.06 IU/mL, and 2.6 IU/mL and 0.08 IU/mL, respectively. Multivariate analysis showed that the risk factors for LTBI in T2DM patients were smoking history, HbA1c &gt;7%, and no BCG scar. Conclusions Because LTBI is prevalent in T2DM, it is important to screen for it in T2DM patients due to the risk of developing severe active TB. Absence of a BCG scar and high HbA1c levels are strong predictors of LTBI in T2DM patients.

Expression of Vitamin D Receptor (VDR) gene and VDR polymorphism rs11574113 in pulmonary tuberculosis patients and their household contacts

The vitamin D receptor mediates the effect of vitamin D, which has received substantial attention in its involvement in reducing the risk of tuberculosis (TB). This study sought to see if VDR gene expression and VDR SNP rs11574113 was linked to a person's likelihood of developing tuberculosis. New Pulmonary Tuberculosis (PTB) VDR gene expression and Household Contact (HC) samples VDR gene expressions were examined by the quantitative real-time PCR (qPCR) method, while VDR SNP rs11574113 was identified by PCR followed by sequencing. Latent TB infection in household contacts was screened using an Interferon-Gamma Release Assay (IGRA). Eighty-three PTB, 77 HCs (45 positive-IGRA and 28 negative-IGRA) were involved in this study. Among the 45 positive-IGRA HC, 28 (62.2%) were spouses of index cases. IGRA results showed that 28 out of 37 (75.7%) samples of all spouses recruited have positive IGRA results. VDR gene expression of PTB was 0.2 and 0.25 downregulated compared to negative-IGRA and positive-IGRA HC, respectively (p = 0.014 and p = 0.011). VDR gene expression of positive-IGRA was also 0.788 downregulated compared to negative-IGRA HC but did not reach statistical significance (p = 0.945). The high expression of the VDR gene may be influenced by variant of VDR SNP rs11574113. G/G genotype and G/C genotype were associated with higher VDR gene expression compared to C/C genotype (ORa = 9.754 95% CI 1.482–64.195, p = 0.018 and ORa = 9.723 95% CI 1.416–66.751, p = 0.021, respectively). However, rs11574113 was not found to be associated with TB incidence and IGRA positivity. Approximately 20% of the people with PTB had higher levels of VDR gene expression than those who were not (ORa = 0.736 95% CI 0.542–0.998, p = 0.049). VDR gene expression may be associated with the susceptibility of tuberculosis. This study also shows an immense rate of TB infection among spouses of PTB patients based on IGRA.

Determinants of losses in the latent tuberculosis infection cascade of care in Brazil

IntroductionFactors associated with losses in the latent tuberculosis infection (LTBI) cascade of care in contacts of patients with tuberculosis (TB) were investigated in a multicentre prospective cohort from highly endemic...

Pulmonary tuberculosis and management of contact patients in a Department of Nephrology and Kidney Transplantation

ObjectivesTo describe the investigation, follow-up, management, and outcomes in a cohort of chronic kidney disease (CKD) and kidney transplant recipients (KTR) exposed to a case of pulmonary tuberculosis (TB). MethodsContacts were investigated following a concentric circles approach and followed-up according to their level of priority. In those with evidence of latent TB infection, treatment decision was based on the level of exposure, individual vulnerability, as well as the results of an interferon-gamma release assay. ResultsA total of 130 patients with CKD and 180 KTR were identified as contacts and followed-up over a 2-year period. Few vulnerable high-priority contacts received anti-TB treatment, including the two (100%) highly exposed patients in circle 1, 11/78 (14.1%) CKD patients and 4/142 (2.8%) KTR in circle 2, and 10/52 (19.2%) CKD patients and 2/36 (5.6%) KTR in circle 3; all had a positive interferon-gamma release assay result. No incident cases of TB disease occurred. ConclusionsThese findings suggest that latent TB treatment, as recommended in European guidelines, might be reasonably avoided in vulnerable high-priority contacts of circle 2, with a negative interferon-gamma release assay and in countries with low prevalence of TB.

Association between Malnutrition Inflammation Score and Latent Tuberculosis among Chronic Hemodialysis Patients

Objective: To investigate the association of malnutrition with latent tuberculosis (TB) among chronic kidney disease (CKD) patients on hemodialysis (HD). Methods: This was a cross-sectional study conducted at the Hemodiaylisis Unit of Dr. Hasan Sadikin General Hospital, Bandung, Indonesia. Subjects were patients aged &gt;18 years who had undergone HD twice a week for at least three months. Patients suspected of active tuberculosis (TB), malignancy, or immunocompromised were excluded. Latent TB was diagnosed using the interferon-gamma release assays (IGRA). Malnutrition was defined by a malnutrition inflammation score (MIS) of less than 5. All data including age, sex, CKD etiologies, and laboratory findings were obtained and recorded in a case report form. Results: A total of 120 subjects were involved in this study. Subjects with positive, negative, and indeterminate IGRA results were 39.2%, 56.7%, and 4.2%, respectively. There was no significant differences in subjects characteristics between positive and negative IGRA subjects. The MIS&gt;5 was shown to have no statistically significant association with positive IGRA subjects (OR=3.47, 95%CI 0.93–12.93). Conclusion: Malnutrition based on an MIS score of less than 5 is not statically associated, but clinically associated, with latent TB. Further causal inference study to investigate these associations is needed.

An observational study on prevalence of latent tuberculosis infection and outcome of 3HP treatment in patients under hemodialysis in Taiwan

Identification and treatment for latent tuberculosis infection (LTBI) are of great epidemiological importance of controlling tuberculosis (TB) worldwide. Identification in high-risk population on dialysis and treatment with 12-week weekly rifapentine plus isoniazid (3HP) help improve prevention outcomes effectively. We conducted a single-center, nonrandomized follow-up study on end-stage renal disease patients on hemodialysis. The interferon-gamma release assay (IGRA) was used for the diagnosis of LTBI. Participants were treated with 3HP, and treatment responses were recorded and analyzed. A total of 123 of the 641 patients showed positive IGRA results. The male sex, age >60 years, low serum albumin level (<4.0g/dL), and hypercalcemia (serum calcium level>10.2mg/dL) were associated with IGRA positivity. Seventy-five patients were treated with 3HP, with a completion rate of 66.67%. The male sex, albumin level >4.0g/dL, and absence of adverse drug reaction were associated with increased completion rates. Adverse drug reactions included dizziness, fatigue, nausea and vomiting, fever, and hypertension. Risk factors for LTBI in dialysis patients were identified to prioritize LTBI screening and initiate early treatment. The completion rate in dialysis patients were approximately 2 of 3 patients with mild adverse drug reaction, leading to discontinuation of the treatment.

Tuberculosis in Internationally Displaced Children Resettling in Harris County, Texas, USA, 2010-20151.

US guidelines have recommended testing children emigrating from high tuberculosis-incidence countries with interferon-gamma release assays (IGRAs) or tuberculin skin tests (TSTs). We describe the Harris County (Texas) Public Health Refugee Health Screening Program's testing results during 2010-2015 for children <18 years of age: 5,990 were evaluated, and 5,870 (98%) were tested. Overall, 364 (6.2%) children had >1 positive test: 143/1,842 (7.8%) were tested with TST alone, 129/3,730 (3.5%) with IGRA alone, and 92/298 (30.9%) with both TST and IGRA. Region of origin and younger age were associated with positive TST or IGRA results. All children were more likely to have positive results for TST than for IGRA (OR 2.92, 95% CI 2.37-3.59). Discordant test results were common (20%) and most often were TST+/IGRA- (95.0%), likely because of bacillus Calmette-Guérin vaccination. Finding fewer false positives supports the 2018 change in US immigration guidelines that recommends using IGRAs for recently immigrated children.

Impact of comorbidities on the performance of interferon-gamma release assay in an elderly Greek population without overt immunodeficiency

Background The prevalence of latent tuberculosis infection (LTBI) increases with age. Interferon-gamma release assay (IGRA) is a T-cell based assay widely used for the detection of LTBI.Objectives To identify the prevalence of LTBI among an elderly Greek population using IGRA and to evaluate comorbidities associated with LTBI.Methods Individuals aged at least 65 years who were non-immunocompromised and had no history of active tuberculosis infection (TBI) underwent IGRA to identify LTBI. Participant characteristics were compared between the LTBI and non-LTBI groups. Interferon-gamma (INFγ) levels were analysed in each group.Results A total of 130 (38.7%) participants with LTBI and 206 (61.3%) participants without LTBI were included. Multivariate logistic regression analysis identified the following features that were independently associated with a positive IGRA result: female sex (odds ratio [OR]: 0.45; 95% confidence interval [CI]: 0.28-0.72; P=0.001), chronic heart failure (OR: 0.41; 95% CI: 0.22-0.77; P=0.005), history of major surgery (OR: 0.55; 95% CI: 0.33-0.92; P=0.022) and Charlson Comorbidity Index >3 (OR: 3.06; 95% CI: 1.46-6.40; P=0.003). Production of stimulated INFγ was significantly lower in the non-LTBI group.Conclusions Female sex, history of chronic heart failure and history of any surgical intervention were independently associated with a negative IGRA result, and CCI >3 was associated with a positive IGRA result. These results indicate careful interpretation of IGRA is required among elderly individuals with these characteristics.

The annual risk of tuberculosis infection in newly hired researchers and healthcare workers using interferon-gamma release assay in Japan

The tuberculosis (TB) notification rate in Japan is gradually decreasing but has not yet achieved “pre-elimination,” defined by the World Health Organization. To effectively tackle, control, and eliminate TB, estimating and monitoring the annual risk of TB infection (ARI) using tuberculin skin testing (TST) to understand the dynamics of TB epidemiology are significantly important. However, studies estimating ARIs using TST are few considering that Bacillus Calmette-Guérin vaccination coverage is high in Japan. This was a single-center, cross-sectional study conducted between January 2011 and December 2018 in Tokyo area where interferon-gamma release assays (IGRAs) were performed in newly hired researchers of Keio University School of Medicine and healthcare workers of Keio University Hospital to determine TB infection. We estimated the prevalence of TB infection and ARI based on their IGRA results. Among the 3908 subjects, 83 (2.124%) had positive IGRA results. Multiple logistic regression analysis revealed that age was a significant risk factor for positive IGRA result (adjusted odds ratio, 1.046). The ARIs were 0.049%–0.156% between 1986 and 2004, midyears of TB infection, but have not significantly decreased over approximately two decades. To decrease the risk of TB infection, advanced strategies to control and eliminate TB in Tokyo area are significantly required.

Investigating the prevalence of latent Tuberculosis infection in a UK remand prison.

Tuberculosis (TB) remains a major global public health issue and in low-incidence countries guidance identifies the need to screen for and treat latent tuberculosis infection (LTBI) with the prison environment recommended as a setting to perform LTBI screening. This study describes the findings of a LTBI screening programme which took place on entry to a remand prison in the UK. Testing for LTBI was undertaken alongside screening for blood borne viruses in 567 men. During the screening process, information was collected on demographic variables and also specific risk factors based on World Health Organization recommendations. LTBI analysis was performed using Interferon-Gamma Release Assay (IGRA) technique. In total, 40 men returned an IGRA positive result (7.1%). However, irrespective of IGRA/LTBI status there was a substantial burden of risk factors present including previous prison stay, history of substance misuse and no BCG vaccination. Non-White ethnicity, a history of substance misuse and age over 34 years were the most significant factors in identifying individuals who would require treatment for LTBI (Positive IGRA result). The study further demonstrates that the prevalence of LTBI remains increased within the prison environment and is a setting that still requires effective LTBI management.

Screening for latent tuberculosis infection prior to biologic therapy in patients with chronic immune-mediated inflammatory diseases (IMID): Interferon-gamma release assay (IGRA) versus tuberculin skin test (TST)

BackgroundThe screening for latent tuberculosis infection (LTBI) is mandatory before initiating biologics in patients with chronic immune-mediated inflammatory disease (IMID). The recommendations are based on the tuberculin skin test (TST) and interferon-gamma release assay (IGRA). Aim of the workTo evaluate the agreement between the two tests in the diagnosis of LTBI and to identify risk factors associated with positive TST and IGRA results. Patients and methodsMedical records of 105 IMID patients going to receive a biologic agents were extracted in a cross sectional study (2015–2017). No biologics was undertaken before LTBI screening. All patients underwent IGRA and chest radiography. TST was performed in 94 cases. ResultsThe mean age of the patients was 47.7 ± 14.4 years and disease duration of 11.2 ± 7.6 years. Agreement between the 2 tests results was low (κ coefficient = 0.08). The sensitivity of TST and IGRA was equally low but the specificity of IGRA was higher. Replacing TST results by positive IGRA showed that number of patients who would take anti-tuberculous chemoprophylaxis will be significantly reduced by 46.5% (from 40.9% to 21.9%; p = 0.0002). TST results were significantly less positive for patients receiving immunosuppressives than for those receiving no treatment (35.1% vs 42.5%, p = 0.031). IGRA results were associated with absence of Bacilli Calemtte-Guérin vaccination. Age was the only risk factor for LTBI associated with both IGRA and TST positivity (p = 0.031, p = 0.011 respectively). ConclusionsTST and IGRA have a low agreement. Both tests should be included in the strategy to diagnose LTBI prior to biologic therapy in IMID patients.