Positive Interferon-gamma Release Assay Research Articles

Differentiating between active and latent tuberculosis with chest computed tomography

PurposeThe purpose of this study was to evaluate the capabilities of chest computed tomography (CT) in distinguishing between active and latent tuberculosis in patients positive for interferon-gamma release assay (IGRA) testing, and to compare the performance of CT with that of quantitative IGRA testing in a low incidence setting. Materials and methodsPatients with latent or active tuberculosis define by an IGRA positive test were retrospectively recruited. Sensitivity, specificity and accuracy were determined for CT variables and quantitative IGRA results. Final diagnosis of active tuberculosis was based on clinical data and microbiological culture. Univariable and multivariable analyses were performed using logistic regression model to identify CT variables associated with the diagnosis of active tuberculosis. ResultsA total of 92 patients with positive IGRA results who underwent CT examination were included. There were 54 men and 38 women with a mean age of 53.5±18 (SD) years (range: 40–68 years). Of them, 22 patients (24%) had positive Mycobacterium tuberculosis culture and 70 (76%) had latent tuberculosis. Among CT variables, consolidation had the greatest sensitivity (77%; 95%CI: 60–95%) and “tree-in-bud” the greatest specificity (97%; 95% CI: 93–100%) for the diagnosis of active tuberculosis. At univariable analysis “tree-in-bud”, splenic calcification and non-calcified lung nodules were the significant variables independently associated with active tuberculosis. At multivariable analysis, the adjusted odds ratio of “tree-in-bud” was 42.91 (95% CI: 5.62–327.42). Using an optimal threshold of 51 spots, quantitative IGRA yielded 64% sensitivity (95% CI: 44–84%) and 61% specificity (95% CI: 50–73%) for the diagnosis of active tuberculosis. ConclusionsIn a low incidence setting, chest CT, especially when “tree-in-bud” pattern is present, is superior to quantitative IGRA testing to identify patients with active tuberculosis among those with positive IGRA testing.

Frequency of Positive Conversion of Interferon-Gamma Release Assay Results Among Patients With Inflammatory Bowel Disease Treated With Non-tumor Necrosis Factor Inhibitors.

Considering the risk of reactivation of latent tuberculosis infection (LTBI), not only before starting tumor necrosis factor inhibitors but also before non-TNF inhibitor therapy, LTBI screening is routinely recommended for patients with inflammatory bowel disease (IBD). However, data on the positive conversion of LTBI test results during non-TNF inhibitor therapy are scarce. Among IBD patients treated with vedolizumab and/or ustekinumab, a total of 91 patients who had negative baseline interferon-gamma release assay (IGRA) results, assessed by QuantiFERON®-TB Gold In-tube or QuantiFERON®-TB Gold Plus, were enrolled. Serial LTBI test results after starting non-TNF inhibitor therapy were collected, and patients' clinical characteristics were analyzed. Positive IGRA conversion was observed in six of 91 patients (6.6%). The cumulative IGRA conversion–free survival rates after starting therapy were 97.7% after 1 year and 86.7% after 2 years. Ulcerative colitis was more common among converters compared with non-converters (66.7 vs. 23.5%, P = 0.040). Among six converters, four had been treated with vedolizumab, one with ustekinumab, and the other with vedolizumab followed by ustekinumab. All six patients had been previously exposed to TNF inhibitors before non-TNF inhibitor therapy: five to infliximab and one to both infliximab and adalimumab. After positive IGRA conversion, none of the six converters developed active tuberculosis while maintaining non-TNF inhibitor therapy (median 6.8 months, range 0.4–32.1 months). Positive IGRA conversion among IBD patients treated with vedolizumab and/or ustekinumab appears to occur somewhat frequently, but its clinical implications remain to be elucidated.

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.

Thyroid Tuberculosis Causing Fever of Unknown Origin in a Patient With Multinodular Goiter

Introduction: Tuberculosis (TB) involving the thyroid gland is rare and typically results in hypothyroidism. Here we report a case of thyroid TB that presented with hyperthyroidism. Clinical Case: A 54-year-old woman with a history of hyperthyroidism due to toxic multinodular goiter presented to the emergency department with fever of unknown origin associated with sore throat, non-productive cough, night sweats, diarrhea, and right anterior neck pain that worsened with coughing. Her fevers were intermittent, ranging from 38 to 39 degrees Celsius, and would subside with acetaminophen. She reported that her symptoms had started after getting a thyroid [Tc-99m] pertechnetate scan and 24 hour [I-131] sodium iodide uptake study a month prior. The scan at the time revealed hyperfunctioning thyroid nodules in the lower lobes bilaterally. The 24-hour uptake was 20.2% which is within the normal range of 7 to 30%. TSH on presentation was 0.01 mIU/L (Normal range 0.3-5.50 mIU/L), free T4 was 2.05 ng/dL (Normal range 0.76 -1.7 ng/dL), and free T3 was 5 pg/mL (Normal range 1.9-3.9 pg/mL). Exam revealed a multinodular goiter, which was firm with mild tenderness, and no cervical lymphadenopathy. Infectious workup was unremarkable other than a positive interferon-gamma release assay. As for TB risk factors, the patient immigrated to the United States from Albania about 13 years prior. The patient denied any known TB exposure, neither had she been treated for TB. Radiograph and computed tomography (CT) of the thorax were unremarkable other than re-demonstration of the multinodular goiter. Fluorodeoxyglucose-18 positron emission tomography (FDG-PET), which was performed to identify any focus of active TB, had revealed intense, infiltrative, heterogeneous FDG uptake of the nodular thyroid gland with reactive level 3 and 4 cervical lymph nodes. Also, the scan revealed hyper-metabolic hilar, pre-tracheal, and sub-carinal lymph nodes which could represent latent TB. Further workup for any other foci of active TB including broncho-alveolar lavage, sputum cultures, lumbar puncture, and bone marrow biopsy were unremarkable. Thyroid ultrasound revealed 2 right sided and 3 left sided thyroid nodules, mostly solid and hypoechoic. Fine needle aspiration of nodules revealed benign follicular nodules bilaterally, however the left aspirate contained loose aggregates of histiocytes consistent with non-necrotizing granulomas. Acid-fast bacilli stain of the aspirate was negative. The patient was started on therapy for active TB with isoniazid, rifampin, pyrazinamide, and ethambutol. Six weeks after treatment her fevers had resolved. Conclusion: Thyroid TB should be considered when the severity of symptoms cannot be explained by the degree of hyperthyroidism alone in patients with increased risk of TB. Additionally, TB in the thyroid can be challenging to identify in a patient with known underlying thyroid disease.

Surveillance of Employees of Swiss Federal Asylum Centres for Latent Tuberculosis Infection

Background: Asylum seekers in Switzerland have to register in federal asylum centres (FACs) before formal permission to enter the country. Some of them may have active tuberculosis (TB), exposing fellow refugees and employees. Objectives: The aim of this study was to assess the risk of TB infection among employees of Swiss FACs. Methods: Between 2010 and 2018, a free interferon-gamma release assay (IGRA) was offered to all employees of 8 FACs, at employment and at yearly intervals. We defined latent TB infection as IGRA conversion from negative to positive. IGRA-positive employees were referred to a medical centre for further clinical follow-up. Results: 1,427 tests were performed among 737 employees (54.6% male). 403 (55%) persons were tested only once; 330 (44.5%) were tested several times; for 4 (0.5%) persons, the number of IGRA tests is unknown. Twenty employees (2.7%) had a positive IGRA at baseline, 2 (0.6%) converted from negative to positive during follow-up, resulting in an incidence of 22/10,000 person-years. We observed no case of active TB among employees. Conclusions: The prevalence of latent TB among employees to Swiss FACs and the risk of acquiring TB infection through work-related exposure are low. Yearly IGRA controls in the absence of documented TB exposure seem unnecessary.

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 >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>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.

Infection Control Impact on Patient with Tuberculosis Chroretinitis in KSA Hospital Based Analysis

Tuberculosis (TB) is an infectious disease responsible for significant morbidity and mortality worldwide. WHO estimates that one third of the world’s population is currently infected, with 9 million new cases occurring annually, leading to 3 million deaths per year, the disease affects the ocular anterior segment, the posterior segment, and adnexa. , The intraocular manifestations of TB include “mutton fat” keratic precipitates, posterior synechiae, vitreous snowballs, snow banking, retinal vasculitis, choroiditis, serpiginous-like choroiditis, and panuveitis] A definitive diagnosis of intraocular TB requires culture data, and direct demonstration of Mycobacterium tuberculosis in smears and via polymerase chain reaction (PCR) of intraocular fluid, The purpose of this study is to describe the ocular manifestations, diagnosis and treatment of tuberculosis and to emphasize the fact that ocular tuberculosis may occur in the absence of systemic clinical activity and may mimic several clinical entities The current study is an observational consecutive case series of patients diagnosed with intraocular tuberculosis managed at a hospital. Study the prevalence of ocular TB in cross section eye care center Magrabi hospital Jeddah, KSA, from June 1, 2013 to December 31, 2015. diagnosis of ocular TB is often presumed in the presence of suggestive ocular findings in combination with any of the following: Systemic findings consistent with TB infection, Positive interferon gamma release assay, Positive tuberculin skin test in asymptomatic individuals, Acid-fast bacilli (AFB) on direct smear or culture of MTB from ocular samples, Polymerase chain reaction (PCR), Fluorescein angiography (FA), RESULTS: 86 of 2542 patients for examination of retina in retina clinic were diagnosed as suspected tuberculosis chroretinitis, 20 percent of them had conformed diagnosed as TB. out Of 86, 24 (27.9%) had at least one episode of oculacomplaints, 7 patients were conformed with PCR. CONCLUSION: The diagnosis of presumed ocular tuberculosis remains a clinical challenge, although interferon-γ release assays they currently lack the specificity to distinguish between latent tuberculosis infection and active tuberculosis. molecular diagnostic PCR may be valuable in our ability to establish an earlier etiologic diagnosis and institute appropriate antimycobacterial therapy and ensure from implementation of infection control measurements.

Agreement between the results of tuberculin skin test and Interferon-Gamma Release Assays in renal transplant candidates.

Introduction:Identification of latent tuberculosis (TB) infection is important in kidney transplant candidates. Due to the absence of a gold standard, both tuberculin skin test (TST) and interferon-gamma release assays (IGRA) are used to screen patients. The aim of this study was to evaluate the agreement of these two tests in patients undergoing renal transplantation.Materials and Methods:Two hundred kidney transplant candidates at a referral center in 2014–2017 were included in this study. TST and Quantiferon-Gold (QFT-G) tests were performed for all patients before transplantation. In case of a positive result in any of the tests, patients were administered a 9-month prophylaxis treatment using isoniazid. Cohen's kappa coefficient (k) test was used to determine the agreement between the two tests.Results:The mean age of patients was 40.72 ± 18.33. Nine (4.5%) patients had positive TST and 16 (8%) had positive IGRA. Concordance of the two tests was evaluated as medium (κ = 0.44 and P < 0.001). No association was found between the underlying causes of renal failure and skin test positive or IGRA. The tests showed a poor agreement among diabetics, candidates of re-transplantation, and those who were on dialysis for longer than a year (κ < 0.20).Conclusion:TST or IGRA can be used to screen TB in kidney transplant candidates with a moderate agreement. However, we suggest using both TST and QFT-G in diabetics, re-transplant candidates, and those on dialysis for >1 year.

Chest Radiographs and CT Findings during Healthcare Workers' Tuberculosis Screening Using Interferon-Gamma Release Assay: Retrospective Observational Study.

PurposeTo investigate the incidence of tuberculosis (TB) in healthcare workers (HCWs) with positive interferon-gamma release assay (IGRA) results based on chest X-ray (CXR) and CT findings and determine the role of imaging in the diagnosis of TB.Materials and MethodsAmong 1976 hospital personnel screened for TB using IGRA, IGRA-positive subjects were retrospectively investigated. Clustered nodular and/or linear streaky opacities in the upper lung zone were considered positive on CXR. The CT findings were classified as active, indeterminate, inactive, or normal. The active or indeterminate class was considered CT-positive.ResultsIGRA was positive in 255 subjects (12.9%). CXR and CT were performed in 249 (99.2%) and 113 subjects (45.0%), respectively. CXR- and CT-positive findings were found in 7 of 249 (2.8%) and 9 of 113 (8.0%) patients, respectively. Among the nine CT-positive subjects, active and indeterminate TB findings were found in 6 (5.3%) and 3 (2.7%) patients, respectively. Microbiological tests, including acid-fast bacilli staining, culture, and polymerase chain reaction for TB, were negative in all nine CT-positive subjects. Empirical anti-TB medications were administered to 9 CT-positive subjects, and 3 of these nine subjects were CXR-negative for pulmonary TB.ConclusionCT helped diagnose asymptomatic TB in IGRA-positive HCWs.

1666. Yield of Tuberculosis Contact Tracing among Veterans after Outpatient Exposure

BackgroundTuberculosis contact tracing (TBCT) is essential to detecting transmission. High priority contacts for TBCT include children less than 5 and those with prolonged, close contact with a tuberculosis (TB) case. Other populations considered high priority include those with certain comorbidities. While data are limited, there is evidence for transmission in outpatient settings with short duration/casual contact. We describe the yield of TBCT among a high priority cohort after exposure in to active TB in VA clinics.MethodsBetween 2016-2019, VA Northern California performed 4 episodes of TBCT in the outpatient setting. In TBCT 1, the index case was an AFB smear positive healthcare worker (HCW) with 30-minute patient appointments. In TBCT 2-4, the index cases were patients, 2 of whom were AFB smear positive. TBCT included patients seen by the HCW (TBCT 1) and those with appointments one hour before or after the index patient in the same clinic (TBCT 2-4). Contacts were offered interferon-gamma release-assay (IGRA). Staff contacts were tested by purified protein derivative (PPD). Comorbidities, prevalent and new cases with positive TB testing were calculated and compared between different groups.ResultsFifty-one percent of veteran contacts had comorbidities placing them in a high priority group for TBCT. Among the 593 patients who had an IGRA during TBCT, 40 (6.7%) tested positive. Twenty-six (4.4%) had no known history of prior positive TB test of whom 6 reported a previous TB exposure history. Veterans exposed to the HCW did not have a higher prevalence of IGRA positivity or a new positive IGRA compared to TBCT 2-4 (5.5% vs 8.0%, p-value 0.22 and 3.4% vs. 5.3%, p-value 0.26). Among the 130 staff tested in TBCT 1-4, one (0.7%) converted during TBCT 1.ConclusionAfter extensive TBCT, the prevalence of latent TB among short duration/casual contacts of TB was 6.7%, similar to the baseline prevalence of latent TB of 6% in California. In this high priority population for TBCT, no difference was seen when there was face-to-face contact versus a shared waiting room with the index case. Staff conversion rate was extremely low. While decisions to perform TBCT in outpatient settings need to be individualized, the yield of TBCT in this population of veterans was low.Disclosures All Authors: No reported disclosures

The relationship between social risk factors and latent tuberculosis infection among individuals residing in England: a cross-sectional study

ObjectiveTo investigate the relationship between social risk factors and latent tuberculosis infection (LTBI) among individuals who are eligible for LTBI screening in the United Kingdom (UK).MethodsThis cross-sectional study used data...

Developing a diagnostic method for latent tuberculosis infection using circulating miRNA

BackgroundMycobacterium tuberculosis is known to cause latent tuberculosis infection (LTBI) in 25–50% of the cases, of whom 10–20% develop active tuberculosis (TB). Notably, no marker currently exists for judging the therapeutic effect of TB; it is currently judged by chest X-ray and clinical symptoms. We attempted to establish a marker for distinguishing LTBI from active TB and to identify the probability of recurrence after TB treatment, using information on circulating miRNA expression.MethodsIn total, 32 patients were enrolled in this study: 16 with an onset or recurrence of active TB, and 16 with LTBI showing positive interferon-gamma release assays (IGRA) test and chest X-ray. Total RNA from serum in an exosome-rich fraction was first extracted, followed by miRNA expression analysis using a next-generation sequencer, then, this data were analyzed using miRDeep2.ResultsUsing the expression information of eight miRNAs, LTBI and TB could be diagnosed with an accuracy of 71.8% (odds ratio: 6.16, p value = 3.20e-02).ConclusionsA novel method for efficiently differentiating between LTBI and active TB was established. This method appears to be promising for evaluating the therapeutic effect of TB, as it can be performed in a minimally invasive manner.

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.

DAR-901 vaccine for the prevention of infection with Mycobacterium tuberculosis among BCG-immunized adolescents in Tanzania: A randomized controlled, double-blind phase 2b trial

BackgroundSRL172 prevented disease due to Mycobacterium tuberculosis in a Phase 3 trial. DAR-901 represents a scalable manufacturing process for SRL172. We sought to determine if DAR-901 would prevent infection with M. tuberculosis among BCG-primed adolescents age 13–15 years in Tanzania. MethodsAdolescents with a negative T- SPOT.TBR interferon gamma release assay (IGRA) were randomized 1:1 to three intradermal injections of DAR-901 or saline placebo at 0, 2 and 4 months. Repeat IGRAs were performed at 2 months, and at 1, 2, and 3 years. The primary efficacy outcome was time to new TB infection (IGRA conversion to positive); the secondary outcome was time to persistent TB infection (IGRA conversion with repeat positive IGRA). ResultsAmong 936 participants screened 667 were eligible and randomized to their first dose of vaccine or placebo (safety cohort). At 2 months, 625 participants remained IGRA-negative and were scheduled for the additional two doses (efficacy cohort). DAR-901 was safe and well-tolerated. One DAR-901 recipient developed a vaccine site abscess. Neither the primary nor secondary endpoints differed between the two treatment arms (p = 0.90 and p = 0.20, respectively). DAR-901 IGRA converters had median responses to ESAT-6 of 50.1 spot-forming cells (SFCs) vs. 19.6 SFCs in placebo IGRA converters (p = 0.03). ConclusionsA three-dose series of 1 mg DAR-901 was safe and well-tolerated but did not prevent initial or persistent IGRA conversion. DAR-901 recipients with IGRA conversion demonstrated enhanced immune responses to ESAT-6. Since protection against disease may require different immunologic responses than protection against infection a trial of DAR-901 to prevent TB disease is warranted.Trial Registration. The trial is registered at ClinicalTrials.gov as NCT02712424.

Chest roentgenography is complementary to interferon-gamma release assay in latent tuberculosis infection screening of rheumatic patients

BackgroundA study of latent tuberculosis infection (LTBI) burden by chest roentgenography (CXR) with reference to interferon-gamma release assay (IGRA) is still lacking in rheumatic patients of an intermediate tuberculosis burden area.MethodsWe retrospectively reviewed clinical data of patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA) receiving LTBI screening for biologics from Jan 2013 to April 2014.ResultsA total of 238 rheumatic patients who underwent LTBI screening were included in this study, of whom 46 (19.3%) had positive IGRA tests, 178 (74.8%) had negative results, and 14 (5.9%) had indeterminate results. Radiological findings suggesting healed tuberculosis (CXR-old-TB) were found in 18.1% of all patients, 23.9% in the IGRA -positive patients vs 16.9% in the IGRA-negative patients (OR 1.55 95% CI: 0.71–3.39, p = 0.27). Forty (40/46, 87.0%) IGRA-positive patients received isoniazid prophylaxis and 77.5% of them finished treatment. Six patients developed adverse effects of isoniazid treatment, resulting in an overall number needed to harm (NNH) of 6.7 (40/6). IGRA-non-positive patients with old TB-suggestive CXR comprised 13.4% (32/238) of all our rheumatic patients, and one of them developed pulmonary tuberculosis within one year after screening.ConclusionsLTBI disease burden in rheumatic patients is substantial according to the estimation of CXR and IGRA screening. Correlation between CXR and IGRA is not significant in rheumatic patients, which implies their complementary roles. IGRA-non-positive patients with old TB-suggestive CXR comprise a significant portion in rheumatic patients and merit cautious follow-up by rheumatologists, tuberculosis specialists, and pulmonologists.

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.

Association of vitamin D levels and risk of latent tuberculosis in the hemodialysis population.

Vitamin D is essential in the host defense against tuberculosis (TB). Suboptimal vitamin D status is common in the hemodialysis population. Hemodialysis patients have an increased risk compared to the general population latent tuberculosis infection (LTBI). However, the association between vitamin D deficiency and LTBI in this population remains unclear. We conducted a cross-sectional study between March and May 2017. Interferon-gamma release assay (IGRA) through QuantiFERON-TB Gold In-Tube was used to assess LTBI. Plasma 25-hydroxycholecalciferol (25-OHD) levels were measured by Elecsys Vitamin D Total assay. Suboptimal vitamin D levels included vitamin D insufficiency 20-29ng/mg and vitamin D deficiency <20ng/mL. Predictors for LTBI were analyzed. A total of 287 participants were enrolled. The suboptimal vitamin D level was 31.4% (90/287), which including the vitamin D deficiency was 13.9% (40/287). A total of 49.1% (141/287) people received nutritional vitamin D supplementation. The prevalence of IGRA positivity in this study was 25.1% (72/287). There was no significant difference in vitamin D concentrations or the proportion of vitamin D supplementation among the IGRA-positive and IGRA-negative groups (p=0.789 and 0.496, respectively). In multivariate analysis, age >65 years old (odds ratio (OR), 1.89; 95% CI, 1.08-3.31; p=0.026) and TB history (OR, 3.51; 95% CI, 1.38-8.91; p=0.008) were independent predictors of IGRA positivity. This is the first study to report that vitamin D deficiency was not associated with IGRA positivity in a hemodialysis population. Aging and TB history were both independent predictors for LTBI.

Screening migrants from tuberculosis high-endemic countries for latent tuberculosis in Oman: A cross sectional cohort analysis

To fulfil the World Health Organization (WHO) End TB strategy, screening for tuberculosis (TB) in immigrants is an important component of the strategy to reduce the TB burden in low-incidence countries. Oman has an annual TB incidence rate of 5.7 per 100000 and transmission from migrants with activated latent TB infection (LTBI) to nationals is a concern. The aim of this study was to determine the proportion of migrants to the Sultanate of Oman with LTBI.The study used an interferon-gamma release assay (IGRA) to assess previous exposure to TB, defining LTBI and a positive IGRA with a normal chest X-ray. 1049 subjects were surveyed. Six participants were excluded from the analysis as they had been recently vaccinated and 1 had an indeterminate result, thus 1042 subjects were included.The overall IGRA-positive rate was 22.4% (234/1042), 30.9% and 21.2% of African and Asian migrants, respectively, were IGRA-positive. Fifty-eight of the participants had a strong IGRA reactivity defined as more than 4 IU/ml.The study shows the proportion of migrants from Asia and Africa with LTBI and 24.7% (58/234) of IGRA-positive migrants had an IGRA of >4 IU/ml, defining a subpopulation with a high risk of developing active TB in the first two years of arrival to the country.

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.