Interferon-gamma Release Assay Test Research Articles

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.

Evaluation of interferon gamma release assay to measure t-cell response in COVID-19 patients from intensive care units and inpatient departments.

Interferon gamma release assay (IGRA) is an in vitro blood test to measure interferon gamma (IFN-γ) released from antigen-specific Tcells after stimulation with pathogen-specific peptides. In this study, it was aimed to investigate the T-cell response using IGRA and to compare various laboratory values in Coronavirus Disease (COVID-19) patients hospitalized either in hospital inpatient departments or in intensive care units. Atotal of 100 patients (50+50) who were identified as positive for COVID-19 through the molecular method in Selcuk University Faculty of Medicine Infectious Diseases Service and Reanimation Intensive Care Unit were included in the study. IFN-γ levels in blood samples collected from patients were determined using the QuantiFERON Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) (QIAGEN, Germany) kit. The patients' gender, age, c-reactive protein (CRP), aspartate aminotransferase (AST), alanine transaminase (ALT), interleukin (IL)-6, lymphocyte count, procalcitonin, and D-dimer results were obtained from the hospital automation system. Thirty-eight of the IGRA test results were negative, 44 were positive and 18 were inconclusive. The age of patients with negative IGRA test results was significantly higher (p<0.001) compared to patients with positive results. There were no significant differences between patients' IGRA test results and gender, prognosis, IL-6, lymphocyte counts, CRP, AST, and ALT values.Age, death rates, D-dimer, CRP, procalcitonin, AST and ALT values of patients hospitalized in the intensive care unit were significantly higher (p<0.001) compared to the those hospitalized in the inpatient department, while conversely, the lymphocyte values were lower (p<0.001). The relatively higher IGRA negative results in the elderly, negative and intermediate results in intensive-care patients, and low lymphocyte levels in intensive-care patients indicate that the cellular immune response is diminished and/or absent. The death rates, D-dimer, CRP, procalcitonin, AST and ALT values of the patients hospitalized in the intensive care unit were higher compared to those from the in-patient department, indicating the severity of inflammation and signaling the development of organ failure. In the light of these findings, we suggest that IGRA tests may serve as aguide in immunomodulatory therapy (Tab. 2, Fig. 2, Ref.27). Text in PDF www.elis.sk Keywords: COVID-19, interferon gamma release assay test, Tcell response.

Evaluation of Interferon-Gamma Release Assay Testing and Tuberculin Skin Test for Early Diagnosis of Tuberculosis in Children and Adolescents

Evaluation of Interferon-Gamma Release Assay Testing and Tuberculin Skin Test for Early Diagnosis of Tuberculosis in Children and Adolescents

Prevalence of Latent Tuberculosis Infection Among Rheumatology Patients and Management Practices in the United Arab Emirates: A Single-Center Retrospective Cohort Study.

Introduction Prior to immunosuppression, rheumatology patients are routinely screened for latent tuberculosis (TB) infection using interferon-gamma release assays (IGRAs). Variability in the management of latent and indeterminate IGRA results across institutionslimited long-term outcome data. A retrospective study was conducted at Tawam Hospital, United Arab Emirates, to investigate the incidence and management protocols associated with positive and indeterminate IGRAresults, as well as TBinfection, among patients with rheumatic conditions. Methods A single-center retrospective observational study was performed at Tawam Hospital, Abu Dhabi, UAE. Ethical approval for this study was obtained from the Tawam Human Research Ethics Committee. Laboratory records and the hospital's electronic medical system were used to obtain information about IGRA results over a 12-year period (April 2010-April 2022). The hospital's electronic medical system was used to obtain patient information and subsequent management approaches of positive and indeterminate IGRAs.Moreover, long-term follow-up data were collected to determine the risk of TB reactivation in the cohort. Results We found a total of 1,012 positive and 223 indeterminate IGRA test results within the 12-year period. Within the rheumatology department, 123 positive and 39 indeterminate IGRA results were identified. In the indeterminate IGRA group, the majority were women (n = 24, 61.5%) and UAE nationals (n = 22, 56.4%), and their mean age was 38.6 years. Systemic lupus erythematosus was the most prevalent rheumatologic condition (n = 21, 53.8%). Thirteen (33.3%) were on disease-modifying anti-rheumatic drugs (DMARDs) and 26 (66.7%) were on corticosteroids during IGRA testing. A total of eight patients (20.5%) received anti-TB medications. In the positive IGRA group, the mean age was 55.7 years and the female-to-male ratio was 3:1. The most common rheumatologic condition was rheumatoid arthritis (n = 69, 56%). Sixty-five (52.8%) patients were on conventional DMARDs, 43 (34.9%) were on corticosteroids during IGRA testing, and 74 (60%) 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-tumor necrosis factor alpha inhibitor treatment in combination with methotrexate. No cases of active TB infection were observed in the indeterminate IGRA group. Conclusion Long-term data on the risk of TB activation in positive and indeterminate IGRA results for rheumatological conditions are low. It is recommended to reassess the choice of using anti-TNF-α, with a positive IGRA result if no other feasible alternatives can be offered. Our findings stress the importance of age, underlying diseases, and immunosuppressive treatments in interpreting IGRA results and guiding patient management. A large multicenter study is needed to understand the differences and outcomes of such patients in TB endemic and nonendemic geographical areas.

Tubercolosi vertebrale atipica: un caso clinico e revisione della letteratura

Background - Rates of Extrapulmonary Tuberculosis (TB) are higher in paediatric patients, especially in those from endemic areas. Bone TB is mostly located in the spine and in children may cause rapid bone destruction with severe deformity and neurological deficits. Case report - The paper reports the case of a 14-year-old male patient from Pakistan presenting with neurological symptoms and neuroradiological features suspicious for malignant tumour. After surgical removal of the mass, PCR test showed spinal TB. Tuberculin skin test (TST) and Interferon-Gamma Release Assays (IGRA) resulted negative. Discussion - False negative IGRA and TST test results can occur due to several factors, including immunodeficiency disorders. Some cases of spinal TB do not have typical radiological features, causing diagnostic delays or mistakes. Non-typical spinal TB features include: (1) involvement of the posterior elements of the spinal column; (2) skip lesions; (3) non-osseous TB involving spinal cord, cauda equina, and/or meninges. Conclusion - The differential diagnosis between spinal TB and malignancy might be challenging. Consequently, considering TB in children with neurological symptoms and/or vertebral neoformation, especially in patients coming from endemic areas, is recommended. TB diagnosis should not be excluded in case of non-typical radiological features, negative TST and IGRA or history of anti-TB vaccination. This approach should facilitate a timely diagnosis for appropriate treatment, avoiding neurological sequalae and delayed deformities.

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

2511. Screening for Hepatitis B Virus (HBV) and Tuberculosis (TB) Infection among Non-U.S.-Born Adults from High HBV and TB Burden Countries

Abstract Background Hepatitis B virus (HBV) infection and tuberculosis (TB) infection both disproportionately affect non-U.S.–born persons from countries with hepatitis B surface antigen (HBsAg) seroprevalence ≥2% or TB incidence rates ≥20/100,000 population. Early identification and treatment of chronic HBV and TB infection are critical to reduce morbidity and mortality, but little is known about HBV and TB screening among non-U.S.–born persons in the United States. Methods In a cross-sectional study using electronic health record data, we assessed HBV and TB infection screening practices among Kaiser Permanente Northern California eligible members aged ≥18 years born in countries with intermediate to high burdens of both HBV and TB infection. HBV screening was defined as testing for HBV surface antigen and HBV core antibody. TB infection screening was defined as testing with interferon gamma release assay or tuberculin skin test. We calculated the proportion of individuals from intermediate and high HBV-TB burden countries who had HBV or TB infection screening and the proportion of patients positive for HBV or TB infection. Results Of 498,339 non-U.S.–born adults, 275,708 (55.3%) were born in intermediate or high HBV-TB burden countries. Most patients were aged ≥50 years (65.3%) and 23.5% had diabetes. Among persons born in intermediate or high HBV-TB burden countries, 67.1% were screened for HBV infection, 29.4% were screened for TB infection, and only 23.7% were screened for both HBV and TB infection. Among all persons born in intermediate or high HBV-TB burden countries (both screened and unscreened), 3.7% had HBV infection and 10.1% had TB infection. Among 231,431 persons born in intermediate or high HBV-TB burden countries without current or prior HBV infection, 72.9% had received at least one HBV vaccine dose. Conclusion Among non-U.S.–born adults from intermediate or high HBV-TB burden countries, we found low screening proportions, intermediate prevalence of chronic HBV infection and high prevalence of TB infection. Given the large population of persons from intermediate or high HBV-TB burden countries in Kaiser Permanente Northern California, screening for both infections at the same time could improve early diagnosis and treatment for both conditions. Disclosures Jacek Skarbinski, MD, Genentech: Grant/Research Support|Gilead Sciences: Grant/Research Support Robert J. Wong, MD, MS, Gilead Sciences: Grant/Research Support

Screening Practices and Risk Factors for Co-Infection with Latent Tuberculosis and Hepatitis B Virus in an Integrated Healthcare System — California, 2008-2019

BackgroundHepatitis B virus (HBV) and latent tuberculosis infection are associated with a significant global burden, but both are underdiagnosed and undertreated. We described the screening patterns and risk factors for co-infection with latent tuberculosis and HBV within a large healthcare system. MethodsUsing data from Kaiser Permanente Southern California during 2008-2019, we described HBV infections, defined as a positive HBV surface antigen, e-antigen, or DNA test, and latent tuberculosis, defined as a positive Mantoux tuberculin skin test or interferon-gamma release assay test. We estimated adjusted odds ratios (aOR) for co-infection among screened adults with either infection. ResultsAmong 1997 HBV patients screened for latent tuberculosis, 23.1% were co-infected, and among 35,820 patients with latent tuberculosis screened for HBV, 1.3% were co-infected. Among HBV patients, co-infection risk was highest among Asians compared with White race/ethnicity (29.4% vs 5.7%, aOR 4.78; 95% confidence interval [CI], 2.75-8.31), and persons born in a high-incidence country compared with low-incidence countries (31.0% vs 6.6%; aOR 4.19; 95% CI, 2.61-6.73). For patients with latent tuberculosis, risk of co-infection was higher among Asian (aOR 9.99; 95% CI, 5.79-17.20), or Black race/ethnicity (aOR 3.33; 95% CI, 1.78-6.23) compared with White race/ethnicity. Persons born in high-incidence countries had elevated risk of co-infection compared with persons born in low-incidence countries (aOR 2.23; 95% CI, 1.42-3.50). However, Asians or persons born in high-incidence countries were screened at similar rates to other ethnicities or persons born in low-incidence countries. ConclusionsLatent tuberculosis risk is elevated among HBV patients, and vice versa. Risk of co-infection was highest among persons born in high-incidence countries and Asians. These findings support recent guidelines to increase HBV and tuberculosis screening, particularly among persons with either infection.

Latent tuberculosis infection in Korean patients with multiple sclerosis and neuromyelitis optica spectrum disorder

BackgroundLatent tuberculosis infection (LTBI) is defined as an immune response to Mycobacterium tuberculosis infection that does not manifest clinically as active tuberculosis (TB). Since some immunotherapies can alter cellular immunity, LTBI screening has been recommended for patients with multiple sclerosis (pwMS) before initiation of long-term immunotherapies. In this study, we investigated the frequency of LTBI in Korean pwMS and patients with neuromyelitis optica spectrum disorder (pwNMOSD) and reported the long-term observation of untreated LTBI under various immunotherapies. MethodsWe enrolled pwMS or pwNMOSD who visited the Neurology department of the National Cancer Center between 2017 and 2021. LTBI was determined based on positive results of interferon-gamma release assay (IGRA) using QuantiFERON Gold Plus test and no evidence of active TB. Annual chest X-ray and careful monitoring for TB symptoms were performed until April 2023 or the time of follow-up loss. ResultsAmong 531 patients who underwent the IGRA test, 25 pwMS (10.5%) and 42 pwNMOSD (14.3%) were diagnosed with LTBI. Of the 67 patients with LTBI, 59 patients (24 pwMS and 35 pwNMOSD) declined to receive preventive anti-TB drugs. None of the 59 with untreated LTBI demonstrated TB reactivation during 74.8 person-years in pwMS and 166.1 person-years in pwNMOSD. In addition, eight patients who completed the treatment for LTBI experienced no TB reactivation for a median of 5.5 years. ConclusionThe LTBI prevalence in Korean pw MS and pwNMOSD was 10.5% and 14.3%, respectively, which was much higher than that in pwMS from Western countries. Notably, none of the 59 patients with untreated LTBI showed TB reactivation over 240 person-years even under long-term immunotherapies, indicating the need for additional research to stratify the risk of LTBI-reactivation.

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.

A costing framework to compare tuberculosis infection tests

ObjectiveTo develop a framework to estimate the practical costs incurred from, and programmatic impact related to, tuberculosis (TB) infection testing—tuberculin skin tests (TST) versus interferon gamma release assay (IGRA)—in a...

Right to Occupational Safety: Prevalence of Latent Tuberculosis Infection in Healthcare Workers. A 1-Year Retrospective Survey Carried out at Hospital of Lecce (Italy).

Prevention of latent tuberculosis infection (LTBI) in healthcare workers (HCWs) to ensure the "Right to Occupational Safety" is a special challenge globally, as HCWs have a higher risk of acquiring the infection in hospital settings because of frequent close exposure to patients suffering from tuberculosis (TB). Aretrospective study was performed with the aim of assessing the prevalence of LTBI related to demographical and occupational risk factors among HCWs employed in a large hospital in Italy. The study involved 1461 HCWs screened for LTBI by Mantoux tuberculin skin test (TST) and then confirmed with Interferon Gamma Release Assay (IGRA) test in case of positivity. Immunosuppressed and BGC-vaccinated workers were tested directly with IGRA. LTBI was diagnosed in 4.1% of the HCWs and the prevalence resulted lower than other studies conducted in low TB incidence countries. The variables significantly linked with higher frequency of the infection were: age ≥40 years (OR = 3.14; 95% CI: 1.13-8.74; p < 0.05), length of service ≥15 years (OR = 4.11; 95% CI: 1.48-11.43; p < 0.05) and not being trained on TB prevention (OR = 3.46; 95% CI: 1.85-6.46; p < 0.05). Not trained HCWs presented a higher risk of LTBI also after adjustment for age and length of service, compared to trained HCWs. screening of HCWs for LTBI should be always considered in routinely occupational surveillance in order to early diagnose the infection and prevent its progression. Safety policies in hospital settings centered on workers' training on TB prevention is crucial to minimize LTBI occurrence in HCWs.

P24 TB or not TB? A case of severe multi-organ erosive rheumatoid arthritis in a Ukrainian refugee

P24 TB or not TB? A case of severe multi-organ erosive rheumatoid arthritis in a Ukrainian refugee

Tubercular Serpiginous-Like Choroiditis in Patients with Negative TB-Immunoreactivity Tests

ABSTRACT Background Serpiginous-like choroiditis (SLC) denotes ocular tuberculosis (TB), in the presence of positive tuberculin skin test (TST) or interferon gamma release assay (IGRA). Methods Retrospective review of SLC patients from a TB-endemic country, with negative TST and IGRA tests, but responsive to anti-TB therapy. Results Fifteen patients (13 bilateral) with active SLC were included. Eleven (73.3%) patients had received corticosteroids ± immunosuppressive therapy prior to presentation. Chest radiographic abnormalities were found in four (26.7%) patients. We treated all patients with a combination of anti-TB therapy (ATT) and corticosteroids. Paradoxical worsening was noted in nine (60%) patients, complete resolution of lesions in 12 (80%), persistent inflammation (post-ATT) in one, while two were yet to complete ATT. None had recurrence after complete resolution of lesions (median follow-up of 71 weeks [range 15–676 weeks]). Conclusions TB-SLC may present with negative TST and IGRA tests but may still have clinical appearance, and treatment response, like test-positive disease.

Screening for Latent Tuberculosis Infection using Interferon-Gamma Release Assay Test among Healthcare Workers

Healthcare workers (HCWs) represent a significant demographic for screening latent tuberculosis infection (LTBI) due to their potential exposure to infectious patients. Tests based on immunology detection, such as the tuberculin skin test (TST) and the interferon-gamma release assay (IGRA), have been pivotal in diagnosing LTBI. The objective of this study was to evaluate the efficacy of the IGRA test in detecting LTBI compared to the TST among HCWs in an infectious disease hospital. In a cross-sectional study conducted in August 2019 at the Sulianti Saroso Infectious Disease Hospital, we examined 84 HCWs selected through consecutive sampling. Participants were assessed using questionnaires, and the IGRA and TST tests were performed. The findings revealed that 42 (50%) HCWs tested positive for LTBI based on the IGRA test. Most were female, aged 36-45 years, had direct exposure to TB patients, and had been in the healthcare profession for over a decade. The concordance between the TST and IGRA test, as indicated by a κ value, was 0.234. Furthermore, a significant correlation was observed between the incidence of LTBI and the duration of the healthcare profession (p=0.016). In conclusion, our research suggests that both TST and IGRA tests can effectively detect LTBI. The IGRA test had a higher positivity rate among HCWs with over ten years of service.

Latent Tuberculosis Infection and Associated Risk Factors among People Living with HIV and HIV-Uninfected Individuals in Lithuania.

People living with HIV (PLHIV) with latent tuberculosis infection (LTBI) are at increased risk of tuberculosis (TB) reactivation compared to the HIV-negative population. Lithuania belongs to the 18 high-priority TB countries in the European region. The aim of this study was to compare the prevalence of LTBI and LTBI-related risk factors between PLHIV and HIV-uninfected populations. A cross-sectional study was conducted in three Lithuanian Infectious Diseases centres from August 2018 to May 2022 using the interferon gamma release assay (IGRA) and tuberculin skin test (TST) in Vilnius, and IGRA only in Siauliai and Klaipeda. Cohen's kappa was used to assess IGRA and TST agreement. A structured questionnaire was completed by the study participants. LTBI-related risk factors were identified using a multivariable logistic regression model. In total, 391 PLHIV and 443 HIV-uninfected individuals enrolled, with a median age of 41 (IQR 36-48) and 43 (IQR 36-50), consisting of 69.8% and 65.5% male, respectively. The prevalence of LTBI defined by positive IGRA and/or TST among PLHIV was higher compared to that in the HIV-uninfected population (20.5% vs. 15.3%; OR 1.42; 95% CI 1.02-2.03; p = 0.04). The concordance between IGRA and TST was fair: kappa = 0.23 (95% CI 0.09-0.34). In multivariable analyses, association with injecting drug use (IDU) (ORa 2.25, 95% CI 1.27-3.99, p = 0.01) and imprisonment (ORa 1.99, 95% CI 1.13-3.52, p = 0.02) in all participants, IDU (ORa 2.37, 95% CI 1.09-5.15; p = 0.029) in PLHIV and a history of contact with an active TB patient (ORa 3.33, 95% CI 1.53-7.24; p = 0.002) in HIV-uninfected individuals were significant associations evidenced by LTBI. The prevalence of LTBI among PLHIV in Lithuania is higher compared to that in the HIV-uninfected population and the European average. The association with IDU in PLHIV emphasizes the need for integrated HIV, TB and substance abuse treatment to provide patient-centred care.

Use of Interferon-Gamma Release Assays in Children

While interferon-gamma release assays (IGRAs) are widely used for detecting tuberculosis (TB) infection, tuberculin skin tests (TSTs) remain preferred for children under the age of 2 years. The preference for TST stems from concern over IGRA sensitivity in young children. However, TSTs are susceptible to false-positive results following Bacille Calmette-Guérin (BCG) vaccination, which is common in infancy, and exposure to nontuberculous mycobacteria. We reviewed available data for IGRA performance in children under age 2 years. Across four cohorts of high-risk children under age 2 (mostly case contacts or those born in tuberculosis endemic regions), 0 of 575 untreated children with negative IGRA test results progressed to tuberculosis disease-including 0 of 70 who were TST positive but IGRA negative. While neither TSTs nor IGRAs are perfectly sensitive for the diagnosis of tuberculosis infection, IGRAs are an acceptable alternative to TST in children <2 years of age.

Screening for Latent Tuberculosis Infection in Solid Organ Transplant Recipients to Predict Active Disease: A Systematic Review and Meta-Analysis of Diagnostic Studies.

This is a systematic review and meta-analysis of diagnostic test accuracy studies to assess the predictive value of both tuberculin skin test (TST) and interferon-gamma release assays (IGRA) for active tuberculosis (TB) among solid organ transplantation (SOT) recipients. Medline, Embase, and the CENTRAL databases were searched from 1946 until June 30, 2022. Two independent assessors extracted data from studies. Sensitivity analyses were performed to investigate the effect of studies with high or low risk of bias. Methodological quality of each publication was assessed using QUADAS-2. A total of 43 studies (36 403 patients) with patients who were screened for latent TB infection (LTBI) and who underwent SOT were included: 18 were comparative and 25 noncomparative (19 TST, 6 QuantiFERON-TB Gold In-Tube [QFT-GIT]). For IGRA tests taken together, positive predictive value (PPV) and negative predictive value (NPV) were 1.2% and 99.6%, respectively. For TST, PPV was 2.13% and NPV was 95.5%. Overall, PPV is higher when TB burden is higher, regardless of test type, although still low in absolute terms. Incidence of active TB was similar between studies using LTBI prophylaxis (mean incidence 1.22%; 95% confidence interval [CI], .2179-2.221) and those not using prophylaxis (mean incidence 1.045%; 95% CI, 0.2731-1.817; P = .7717). Strengths of this study include the large number of studies available from multiple different countries; limitations include absence of gold standard for diagnosis of latent TB and low incidence of active TB. We found both TST and IGRA had a low PPV and high NPV for the development of active TB posttransplant. Further studies are needed to better understand how to prevent active TB in the SOT population.

Prevalence of LTBI in patients with autoimmune diseases and accuracy of IGRA in predicting TB relapse.

The current study evaluated latent tuberculosis infection (LTBI) positivity in a cohort of Indian subjects and the accuracy of IFN-gamma release assay (IGRA) in predicting tuberculosis (TB) reactivation. This cross-sectional, retrospective chart-based study considered patients diagnosed with autoimmune rheumatic diseases (AIRDs), especially those who received treatment with biologics or targeted synthetic (ts)DMARDs. The patients had undergone LTBI screening and IGRA test. The study excluded patients with inadequate information and those who had undergone test exclusively for diagnostic purpose. Statistical analyses were carried out for descriptive, demographic and clinical variables. Accuracy and error rate in predicting the absence of TB reactivation were calculated for IGRA test. The study selected 943 patients who had undergone IGRA pre-screening prior to the initiation of biologics or tsDMARDs with a mean age of 42.93 ± 14.01 years and male-to-female ratio of 1:2.08. RA was the most common primary diagnosis (43.16%). The proportion of subjects who received single, double and triple or more DMARDs or immune suppressants were 54.35%, 33.33% and 7.69%, respectively. Among the selected subjects, 125 patients were LTBI positive and 816 were negative. All patients, except one who tested positive at baseline, received antitubercular prophylaxis. Accuracy of IGRA in predicting the absence of TB reactivation was 99.6%, with an error rate of 0.46. LTBI screening is beneficial in AIRDs patients prior to the prescription of biologics or tsDMARDs. IGRA is ideal for identifying patients with increased likelihood of developing TB upon receiving biologics or tsDMARDs with reasonable accuracy.

Evaluation of the IP-10 mRNA release assay for diagnosis of TB in HIV-infected individuals.

HIV-infected individuals are susceptible to Mycobacterium tuberculosis (M.tb) infection and are at high risk of developing active tuberculosis (TB). Interferon-gamma release assays (IGRAs) are auxiliary tools in the diagnosis of TB. However, the performance of IGRAs in HIV-infected individuals is suboptimal, which limits clinical application. Interferon-inducible protein 10 (IP-10) is an alternative biomarker for identifying M.tb infection due to its high expression after stimulation with M.tb antigens. However, whether IP-10 mRNA constitutes a target for the diagnosis of TB in HIV-infected individuals is unknown. Thus, we prospectively enrolled HIV-infected patients with suspected active TB from five hospitals between May 2021 and May 2022, and performed the IGRA test (QFT-GIT) alongside the IP-10 mRNA release assay on peripheral blood. Of the 216 participants, 152 TB patients and 48 non-TB patients with a conclusive diagnosis were included in the final analysis. The number of indeterminate results of IP-10 mRNA release assay (13/200, 6.5%) was significantly lower than that of the QFT-GIT test (42/200, 21.0%) (P = 0.000026). IP-10 mRNA release assay had a sensitivity of 65.3% (95%CI 55.9% - 73.8%) and a specificity of 74.2% (95%CI 55.4% - 88.1%), respectively; while the QFT-GIT test had a sensitivity of 43.2% (95%CI 34.1% - 52.7%) and a specificity of 87.1% (95%CI 70.2% - 96.4%), respectively. The sensitivity of the IP-10 mRNA release assay was significantly higher than that of QFT-GIT test (P = 0.00062), while no significant difference was detected between the specificities of these two tests (P = 0.198). The IP-10 mRNA release assay showed a lower dependence on CD4+ T cells than that of QFT-GIT test. This was evidenced by the fact that the QFT-GIT test had a higher number of indeterminate results and a lower sensitivity when the CD4+ T cells counts were decreased (P < 0.05), while no significant difference in the number of indeterminate results and sensitivity were observed for the IP-10 mRNA release assay among HIV-infected individuals with varied CD4+T cells counts (P > 0.05). Therefore, our study suggested that M.tb specific IP-10 mRNA is a better biomarker for diagnosis of TB in HIV-infected individuals.