Positive Interferon-gamma Release Assay Test Research Articles

Latent Tuberculosis in Healthcare Professionals: A Cross-Sectional Study

Tuberculosis (TB) is a dangerous disease caused by the bacterium Mycobacterium tuberculosis. Its transmission occurs through aerosols, making healthcare workers particularly vulnerable to it. At the San Cecilio Clinical University Hospital in Granada (HUCSC), preventive measures such as the use of personal protective equipment (PPE) and IGRA (interferon-gamma release assay) tests were implemented to detect latent tuberculosis infection. At HUCSC, between 2022 and 2024, 4.75% (92/1936) of workers were found to have positive IGRA test results, with no significant differences observed between professional categories. However, variability in positive IGRA rates was noted across different medical departments, with pulmonology and sample handling being the most affected. Additionally, a relationship was found between age and the likelihood of obtaining a positive IGRA test result. These findings underscore the importance of targeted preventive measures and a multifaceted approach to controlling and preventing tuberculosis in workplace environments.

P604 Exploring the role of chest X-ray in latent tuberculosis screening in Inflammatory Bowel Disease

Abstract Background Patients being treated with biologics or JAK inhibitors have an increased reactivation risk of latent tuberculosis infection (LTBI), and this is associated with a more severe infective course. Current ECCO guidance recommends the screening for LTBI by a combination of patient clinical data and epidemiological factors, chest X-ray (CXR), and tuberculin skin test or interferon-gamma release assay (IGRA) prior to starting immunosuppressive treatment. The evidence supporting CXR is categorized at evidence level 5, and information on its use in screening for LTBI originates from two decades ago. Apart from radiation exposure, a single posterior-anterior view has limited diagnostic capabilities. This study aims to determine the relation between CXR findings and IGRA test results in patients undergoing LTBI screening before commencing immunosuppressive therapy for Inflammatory bowel disease (IBD) patients in a low-risk population. Methods This is a retrospective analysis whereby IBD patients (≥16 years) on biologics or JAK inhibitors were identified from our local database. The clinical data, epidemiological, CXR and IGRA result were then analysed from the electronic case records. The IGRA test used was the QuantiFERON-TB Gold. Results A total of 356 patients were included in the study, with 58.7% (n=209) being male. Among these patients, the majority had Crohn's disease (66.6%, n=236), 30.1% (n=109) had ulcerative colitis, and the remaining 2.8% were classified as having IBD-unclassified. Most patients (97.1%) had been exposed to anti-TNF alpha medications and 13.2% were exposed to multiple biologicals. The mean age of IBD diagnosis was 30.3 years (SD+/-15.7). None of the patients had any clinical suggestion nor any evidence for exposure to TB. None of the CXRs performed revealed any radiological signs of prior TB infection. 93.8% (n=334) of the IGRA results were negative and 4.2% (n=15) were categorized as indeterminate. Among those with indeterminate results, 66.7% (n=10) were undergoing corticosteroid treatment for active disease. The remaining 2.0% (n=7) had a positive IGRA test and were treated for LTBI.None of these patients had TB reactivation when then treated with biologicals. Conclusion This research highlights that performing routinely a CXR in individuals with a negative IGRA offers little to no benefit, and subjects patients to unnecessary radiation. It also demonstrates the importance of conducting the IGRA test early, before initiating any immunosuppressive treatment. Furthermore, in patients with a negative IGRA, if chest imaging is required for screening purposes, opting for an ultra-low dose CT might be more prudent than a CXR, as it visualises the lungs better and the radiation exposure is not substantially different.

Latent tuberculosis infection in psoriasis patients

Aims: Psoriasis is a chronic, inflammatory, and life-long skin disease. Patients may need to change the treatment regimen by time due to the course of the disease. According to the guidelines, patients should be screened for latent tuberculosis infection (LTBI) before starting treatment with biological agents. We aimed to evaluate the associations between positive interferon-gamma release assay (IGRA) tests, the chest CT findings and inflammatory blood markers of the psoriasis patients who have undergone screening for LTBI before starting systemic treatment with biological agents or conventional options. Methods: The electronic medical records, Chest CT reports and blood tests of 123 consecutive patients with a diagnosis of psoriasis who were candidates for systemic treatment (methotrexate, cyclosporin and biological agents) and screened for LTBI were examined. Results: The mean age of the patients was 49.24 and 64 (52%) of them were males. 37(30%) had a family history of tuberculosis 103(83%) of them had BCG vaccination scars. 59% had radiological features on their Chest CT scans. 28% of the patients had positive Quantiferon test results. When compared to the Quantiferon negative group, there was no difference between the two groups according to demographic characteristics, comorbidities, family history of tuberculosis, BCG vaccination status, smoking habits, occupation, and qualification details (p>0.05). The values of WBC, neutrophils, lymphocyte, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, systemic inflammation index and erythrocyte sedimentation rates were found statistically higher in the patients with positive Quantiferon test (p<0.05). Conclusion: The patients with psoriasis requiring systemic treatment and having positive IGRA test results have increased levels of inflammation. Psoriasis and LTBI might have a synergistic action in the inflammatory response which necessitates further studies to find out the associations between these two entities.

1882. Contact Investigation of Congenital Tuberculosis in a Neonatal Intensive Care Unit in South Korea

Abstract Background Congenital tuberculosis (TB) is uncommon and difficult to detect in neonates due to its nonspecific symptoms. We conducted a contact investigation of infants and healthcare workers (HCWs) exposed to a neonate with congenital TB in a neonatal ICU (NICU) in Korea. Methods A premature infant born was admitted to NICU on September 16, 2022. On October 24, the infant's mother was diagnosed with miliary TB, and infant’s sputum AFB stain showed 4 positive results. All NICU infants and HCWs during the same period were screened for active pulmonary TB using chest radiography (CXR) immediately. Exposed infants were evaluated with a TST and CXR three months after exposure. Interferon-Gamma Release Assay (IGRA) testing was performed on those with a positive TST or abnormal CXR finding. Prophylactic rifampin was provided to the exposed infants for 3 months, as index had isoniazid-resistant M. tuberculosis infection. Exposed HCWs underwent IGRA testing immediately after exposure (1st IGRA) and at 8 to 10 weeks post-exposure (2nd IGRA), and CXR was performed 6 months after exposure. Results Five out of 82 exposed infants had positive TST (≥ 10 mm) results, while all 31 infants who underwent IGRA testing had negative results. All five with positive TST had received BCG vaccination a median 105 days before. Of the 119 exposed HCWs, three had a conversion; two had negative results (on annual IGRA testing performed according to the national TB prevention Act) before exposure and positive at 1st IGRA test, and one had negative 1st IGRA test then positive 2nd IGRA test. None had active TB during 6-month follow-up. Conclusion We found that 6% of exposed infants had positive TST results and 0% had positive IGRA, while 2.5% of exposed HCWs had conversion. Considering the possibility of false positive TST results due to prior BCG vaccination, the chance of transmission to the infants would be 0%; otherwise, it would be 6.1%. Disclosures All Authors: No reported disclosures

S3127 Peritoneal Tuberculosis in an Immunocompetent Patient With Findings of Chronic Liver Disease and Peritoneal Carcinomatosis

Introduction: Peritoneal tuberculosis (PT) accounts for 1-2% of all tuberculosis cases. Diagnosis of PT can be challenging due to non-specific symptoms, insidious onset, and variable imaging findings. We present a case of PT presenting with ascites and imaging studies suggestive of chronic liver disease (CLD), and peritoneal carcinomatosis. Case Description/Methods: A 48-year-old man presented to our clinic with complaints of increased abdominal girth, weight loss, and night sweats for the past 3 months. Physical exam revealed soft and distended abdomen with shifting dullness. Laboratory tests showed a mild anemia of Hb at 13.0 g/dL (13.1-17.2) and ESR at 34 mm/h (0-15). Abdominal ultrasound (US) revealed the presence of free abdominal fluid, and diffuse heterogenous granular liver parenchyma supporting the diagnosis of CLD. His liver tests were within normal ranges. Ascitic fluid analysis revealed serum ascites albumin gradient (SAAG) of 0.2 g/dL, WBCs of 1.70 × 103 cells/dL (91.8% lymphocytes). Ascitic fluid cytology was negative for malignant cells. Ascitic fluid acid-fast bacilli (AFB) test and mycobacterial culture were negative. Adenosine deaminase (ADA) level in ascitic fluid was 108.5 U/L (0-40). Interferon-gamma release assay (IGRA) test was positive. Contrast-enhanced computed tomography (CT) scan revealed normal liver parenchyma, diffuse thickening and nodularity of the peritoneum, and thickening of omentum with omental cake appearance. CT scan was suggestive of peritoneal carcinomatosis. EGD and colonoscopy were unremarkable. With consistent clinical history, SAAG < 1.1, ascitic fluid with lymphocytic predominance, high ADA levels, and positive IGRA, a diagnosis of PT was made. Anti-tuberculosis treatment was initiated, and the patient’s clinical symptoms have improved. CT scan at the end of treatment showed the resolution of ascites and peritoneal findings (Figure 1). Discussion: Ascites is the most common presenting symptom of PT. High suspicion of PT is important in the setting of ascites of unknown origin. Despite the US findings were suggestive of CLD in this patient, CT scan revealed normal liver findings. Differing PT from peritoneal carcinomatosis might be challenging due to overlapping findings on imaging. Ascitic fluid analysis of SAAG < 1.1, high ADA levels, positive IGRA test should lead towards the diagnosis of PT. AFB and mycobacterial culture of the ascitic fluid may often have low diagnostic yield in PT. Early diagnosis and treatment are important to prevent complications.Figure 1.: A1, A2, Before treatment; axial contrast-enhanced computed tomography scan showing moderate ascites, and diffuse thickening and nodularity of peritoneum. Imaging is suggestive of peritoneal carcinomatosis. B1, B2, After treatment; resolution of ascites and peritoneal findings.

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...

Latent Tuberculosis Infection - Diagnosis and Treatment.

INTRODUCTION:Latent tuberculosis infection (LTBI) is defined as a state of persistent immune response to stimulation by Mycobacterium tuberculosis antigens without evidence of clinically manifested active tuberculosis (TB). Diagnosis and treatment for LTBI are important for TB, especially in high-risk populations. Tuberculin skin test (TST) and interferon-gamma release assays (IGRAs) are used to diagnose LTBI.AIM:The study aims to present the first results with IGRA test compared with TST in the screening of LTBI and the treatment results in the cases with LTBI in Macedonia.MATERIAL AND METHODS:In this study 73 cases diagnosed and treated with LTBI in 2016 were included. For diagnosis of LTBI, we used TST RT -23 5T.U. and commercial IGRA test such as QuantiFERON-TB Gold In-Tube (QFT-IT).RESULTS:Out of 73 cases with LTBI, 61.64% were men, and 38.36% were women. Among all age groups, the most frequent were cases between 5 and 14 years old (54.79%). Among the evaluated risk groups for LTBI, the most frequent were children household contacts with pulmonary TB cases (61-83.65%), followed by people living with HIV (9-12.33%) and only 3 cases with other medical reasons. Positive TST had 34 cases (46.57%) and positive IGRA test 25 cases (34.25%). Regarding the treatment regimes, we use two regimes: 50 cases (68.44%) received 6 months daily regime with Isoniazid, and 23 cases (31.51%) received 3 months daily regime with Isoniazid and Rifampicin. Treatment outcomes showed that the most patients completed treatment regimes: 55 (75.34%) and only 10 (13.09%) interrupted the treatment.CONCLUSION:Despite the progress made in the last few years, several challenges remain to be addressed for better management of LTBI which will contribute to strength TB control in the country.

Interferon gamma release assay for identification of latent Mycobacterium tuberculosis infection in HIV hospital staff – The association between occupational and non-occupational exposure

BackgroundTuberculosis remains an important healthcare problem in Poland. At the same time tuberculosis is the most common AIDS defining condition diagnosed in HIV-positive persons in Poland. Therefore, we have investigated the prevalence of latent TB infection among healthcare staff of HIV hospital. Material and methodsThe interferon gamma release assay (IGRA) was offered to all hospital staff. Participants filled in a self-report questionnaire on demographics, work position, time of employment, occupational and non-occupational contact with TB. In statistical analysis nonparametric tests were used for group comparison. A multivariable logistic regression model was developed including all variables with p<0.1 in univariable models. ResultsOverall 86 (20.9%) of 411 HCW participated in the study. Those with positive IGRA test (12.8%) were older, more likely to undergo TB treatment in the past or having a history of home TB contact. There was no statistical difference between the groups in duration of employment, occupational exposure or its frequency. Factors remaining statistically associated with positive IGRA test was age (OR 1.11, [95% CI: 1.00–1.22]) and home TB contact (OR 36.9, [95% CI: 1.97–688.8]), whereas duration of employment (OR 0.98, [95% CI: 0.89–1.09]) and active TB in the past (OR 0.99, [95% CI: 0.04–25.3]) revealed to be non-significant. ConclusionThe prevalence of latent TB infection among healthcare staff was slightly higher than the one reported in other high income countries. However the risk of acquiring tuberculosis among healthcare workers of HIV hospital was mainly linked to non-occupational exposures. IGRA screening may serve as an important tool in limiting tuberculosis transmission.

Positive interferon‐gamma release assay (IGRA) test in a case of non‐tuberculous mycobacterium associated uveitis

AbstractPurpose It is not always known that Interferon‐gamma release assay (IGRA) tests can also react with some non‐tuberculous atypical strains of mycobacteria (NTM). The aim of this work was to review the cross‐reactivity of IGRA tests and its consequences in a case of with a positive IGRA test associated with of a non‐tuberculous mycobacterium (M. kansasii).Methods Report of a 66 year old male uveitis patient with cystoid macular oedema and occult bilateral indocyanine green angiography‐detected choroiditis resistant to inflammation suppressive therapy. A QuantiFERON®‐TB Gold test was positive indicating exposure to the Mycobacterium tuberculosis complex. Before starting antibiotic treatment cultures from bronchial aspirates was performed yielding the agent Mycobacterium kansasii. A review of cross‐reactivity of IGRA tests with non‐tuberculous atypical mycobacteria was performed.Results Drug‐sensitivity of Mycobacterium kansasii was found to be equal to Mycobacterium tuberculosis although a longer duration of therapy is recommended. The patient was treated with anti‐tuberculous drugs for 18 months. Uveitis responded to treatment within three months. A review showed that there are at least 7 NTM strains that cross‐react with IGRA tests some of which do not respond to classical anti‐tuberculous therapy.Conclusion A positive IGRA test is a support for diagnosing tuberculous uveitis. However, these tests cross‐react with NTM atypical strains, some of which do not respond to classical anti‐tubercultuberculous therapy with deleterious consequences if an adequate therapy is not given.

Uveitis with occult choroiditis due to Mycobacterium kansasii: limitations of interferon-gamma release assay (IGRA) tests (case report and mini-review on ocular non-tuberculous mycobacteria and IGRA cross-reactivity)

Ocular tuberculosis is difficult to diagnose but should be suspected when uveitis fails to respond to inflammation suppressive therapy. Interferon-gamma release assays (IGRAs) represent a substantial help to diagnose suspected ocular tuberculosis especially in non-endemic areas. Indocyanine green angiography (ICGA) is able to detect clinically silent choroiditis that, when associated with a positive IGRA test, should lead the clinician to suspect ocular tuberculosis, warranting specific therapy. The fact that IGRA tests can also react with some atypical strains of mycobacteria is not always known. We report here a case with resistant post-operative inflammation that presented with occult ICGA-detected choroiditis and a positive IGRA test that was most probably due to the non-tuberculous mycobacterium (NTM) Mycobacterium kansasii. A 66 year-old man presented with a resistant cystoid macular oedema (CMO) in his left eye after combined cataract and epiretinal membrane surgery. At entry, his best-corrected visual acuity (BCVA) was 0.5 for far and near OS. Intraocular inflammation measured by laser flare photometry was elevated in the left eye (54.4 ph/ms) and also in the right eye (50.9 ph/ms). Four subTenon's injections of 40 mg of triamcinolone did not produce any substantial improvement. Therefore a complete uveitis work-up was performed. Fluorescein angiography showed CMO OS and ICGA showed numerous hypofluorescent dots and fuzziness of choroidal vessels in both eyes. Among performed laboratory tests, the QuantiFERON®-TB Gold test was positive. After a pulmonological examination disclosing a right upper lobe infiltrate, the patient was started on a triple anti-tuberculous therapy. Bronchial aspirate, obtained during bronchoscopy, was Ziehl-positive and culture grew M. kansasii. Nine months later, BCVA OS increased to 1.0 and flare decreased to 40.2 ph/ms. The CMO OS resolved angiographically and did not recur with a macula still slightly thickened on OCT. Suspected ocular tuberculosis based on clinical findings and a positive IGRA test can, in rare instances, be due to atypical mycobacteria that also produce positive IGRA tests such as M. kansasii, M. szulgai, M. gordonae, M. flavescens and M. marinum. In our case failure to isolate the atypical mycobacterium would not have had negative therapeutic consequences, as M. kansasii is sensitive to the standard anti-tuberculous treatments, which is not the case with other NTMs.

The Role of the Interferon Gamma Release Assay in Assessing Recent Tuberculosis Transmission in a Hospital Incident

In 2007, an extensive contact screening investigation into onward transmission of tuberculosis was instigated at a hospital in Northern Ireland following diagnosis of pulmonary multi-drug resistant TB in a healthcare worker. Interferon gamma release assays (IGRAs) were used to test 333 patients and 98 staff. We investigated for evidence of onward transmission and recent infection based on analysis of clinical, demographic and IGRA data. We also described within-patient variability of IGRA results. Among patients and staff, increasing age of patients was the only factor associated with IGRA positivity. Greatest within-subject variability of IU/mL in serially-tested patients/staff was seen in those with a positive IGRA test and this did not correlate with increased exposure to the index case. IGRA positivity being largely explained by increasing age in patients and previous TB contact in staff lends weight to the conclusion that IGRA positivity reflected previous infection rather than recent transmission.

Comparative Performance of Tuberculin Skin Test, QuantiFERON-TB-Gold In Tube Assay, and T-Spot.TB Test in Contact Investigations for Tuberculosis

Mycobacterium tuberculosis (MTB)-specific interferon-gamma release assays (IGRAs) are an alternative or adjunct to the tuberculin skin test (TST) in identifying recent contacts with latent tuberculosis infection (LTBI), but there are scarce data directly comparing performance of the tests. To evaluate the agreement between both IGRAs and to determine which contacts were most likely to represent LTBI, the QuantiFERON-TB-Gold In Tube assay (QFT) and the T-Spot.TB test (T-Spot) were compared in TST-positive persons recently exposed to pulmonary tuberculosis cases. Prospectively enrolled close contacts (n = 812) of 123 culture-confirmed tuberculosis source cases underwent IGRA testing using standardized collected data. Factors independently influencing the risk of MTB infection and their interactions with each other were evaluated by multivariate analysis. Five variables were found to significantly predict a positive IGRA test result (age, source case acid-fast bacilli positive and/or coughing, cumulative exposure time, foreign origin). There was excellent agreement between the two IGRAs (93.9%, kappa = 0.85), with QFT finding 30.2% of contacts positive and T-Spot finding 28.7%. Assuming positivity to both IGRAs as true infection, sensitivity of the TST at > 10 mm was 72% and at > 15 mm was 39.7%. The use of either IGRA as a replacement for the TST would decrease the number of LTBI suspects to be investigated by approximately 70%. IGRAs are a more accurate indicator of the presence of LTBI than the TST. Both QFT and T-Spot appear to be valuable public health tools, showing excellent agreement with each other.