Interferon-gamma Release Assay Results Research Articles

Comparison of the standardized incidence ratio of tuberculosis among workers at medical and educational institutions: a nationwide LTBI observational cohort study

BackgroundThe objective of this study was to determine the incidence of tuberculosis (TB) among workers at medical institutions based on interferon-gamma release assay (IGRA) and compare it with that of workers at educational institutions and the general population. MethodsFrom March 2017 to December 2020, we used a cohort of workers from medical and educational institutions in Korea, who underwent IGRA as part of a national screening program for latent tuberculosis infection (LTBI). After connecting to the National Health Insurance Service (NHIS) database to detect for any actual cases of active TB, we estimated standardized incidence ratio (SIR) and the expected number of cases to compare the incidence of TB with that of the general population. ResultsSignificant disparities in TB incidence were revealed among workers in medical and educational institutions, based on IGRA results, age, and occupation. Individuals positive for IGRA in medical institutions displayed substantially higher SIR for TB, 7.19 (6.15–8.41), compared to counterparts in educational institutions, 3.69 (3.02–4.51). Comparing by age group, we see that the SIRs are higher in younger age groups compared to older ones, with 37.30 (28.11–49.50) and 11.89 (7.28–19.41) for IGRA-positive medical and education workers under 30 years of age, respectively. In the results by occupation within the medical institutions, nurses had the highest SIR at 14.17 (11.14–18.04). ConclusionsHealthcare workers in medical institutions are more likely to develop actual TB after a positive result of LTBI screening in Korea. Intensive management and surveillance programs should be reinforced.

Role of interferon-gamma release assay for screening and monitoring of latent tuberculosis infection in kidney transplant recipients

BackgroundThe reactivation of tuberculosis (TB) among kidney transplant (KT) recipients in an endemic area is of general concern. However, the epidemiology of latent TB infection (LTBI) status and its dynamic change responses have not been explored.MethodsBetween September 2020 and August 2021, a prospective study was conducted to investigate the status of LTBI in KT recipients who received a 9-month isoniazid universal prophylaxis. This status was measured using the interferon-gamma release assay (IGRA) with T-SPOT.TB before transplant, as well as at one month and nine months post-transplant.ResultsNinety-one KT recipients had a mean (SD) age of 45 (11) years, and 41% were female. Sixty-eight (75%) patients received a deceased donor allograft, and eighty-six (91%) patients received induction immunosuppressive therapy. The IGRA results were positive, borderline, negative, and indeterminate in 14 (15.4%), 6 (6.6%), 64 (70.3%), and 7 (7.8%) patients, respectively. Among 84 evaluable patients, 20 (23.8%) KT recipients were defined as having LTBI. Older age was significantly associated with LTBI (OR 1.06 [95% CI 1.01–1.12], p = 0.03). Among the 77 KT recipients who completed monitoring, 55 had negative IGRA results. Three (5.4%) KT recipients had conversion post-transplant. One of them developed pulmonary TB at 1 week after the transplant. Among the 13 patients with positive results, 8 (61.5%) remained positive, 1 (7.7%) had an indeterminate result at 1-month post-transplant and subsequently tested positive at 9 months post-transplant, and 4 (30.8%) experienced reversion to negative results throughout the study.ConclusionsIn a high TB-endemic area, one-quarter of KT recipients were reported to have LTBI, and the dynamic change of IGRA response in KT recipients is plausible post-transplant.

Agreement between Mycobacterium tuberculosis antigen-based skin test and interferon-gamma release assay in elderly individuals aged ≥65 years in China

ObjectivesTo determine the agreement of Mycobacterium tuberculosis (TB) antigen-based skin test (TBST) with interferon-gamma release assay (IGRA) in elderly individuals aged ≥65 years beyond instruction for use in China. MethodsBased on the baseline survey of randomized controlled trial with the objective of exploring suitable regimens for TB preventive treatment, M. tuberculosis infection was tested using TBST and IGRA in parallel in rural residents aged 50–70 years using a cross-sectional study design. ResultsA total of 21 219 participants with both TBST and IGRA results were included in this analysis. The concordance between TBST and IGRA was 89.4% (95% CI, 89.0–89.8%) with a kappa coefficient of 0.61 (95% CI, 0.60–0.62). In those aged ≥65 years, the concordance was 86.5% (95% CI, 85.6–87.4%) with a kappa coefficient of 0.55 (95% CI, 0.52–0.58). 21.2% (35/165) of the participants with indeterminate IGRA results were TBST positive, and nine of them were aged ≥65 years. Discussion: The consistent agreement between TBST and IGRA in individuals aged ≥65 years suggests that TBST has the potential to be used in the elderly with age beyond instruction for use in China. The respective diagnostic performance of each test will be analysed when the longitudinal data on incident TB is obtained in the future.

Predictors of interferon-gamma release assay results and their association with COVID-19 infection outcomes.

An 'indeterminate' interferon-gamma release assay (IGRA) result used in the diagnosis of latent TB infection (LTBI) is most commonly due to an inadequate control (or 'mitogen') response, which may reflect underlying T-cell dysfunction. We performed a single-centre, retrospective study on COVID-19 patients admitted to a tertiary referral hospital who had IGRA testing conducted over a 5-month period. The primary outcomes included predictors of indeterminate IGRA results and associations with COVID-19 outcomes. A total of 181 patients were included for analysis. Approximately one-third of patients hospitalised with COVID-19 with IGRA testing performed (60/181) had an indeterminate result. The likelihood of an indeterminate IGRA was increased in patients with a history of solid organ transplant and a higher severity of COVID-19 at the time of testing. An indeterminate IGRA was associated with a higher risk of severe COVID-19 and a higher risk of admission to the ICU during admission to the hospital. No difference in mortality between the two subgroups was found. Our study demonstrated that COVID-19 patients on immunosuppression had a high likelihood of an indeterminate IGRA result, which was associated with markers of disease severity and immunosuppression. In this cohort, an indeterminate result was associated with worse COVID-19 outcomes.

Conversion or reversion of interferon gamma release assays for Mycobacterium tuberculosis infection: a systematic review and meta-analysis.

Interferon-gamma release assays (IGRA) are widely used for diagnosis of latent tuberculosis infection. However, with repeat testing, IGRA transformation (conversion or reversion) may be detected and is challenging to interpret. We reviewed the frequency of and risk factors for IGRA transformation. We screened public databases for studies of human participants that reported the frequency of IGRA transformation. We extracted study and subject characteristics, details of IGRA testing and results. We calculated the pooled frequency of IGRA transformation (and transient transformation) and examined associated risk factors. The pooled frequency of IGRA conversion or reversion from 244 studies was estimated at 7.3% (95% CI 6.1-8.5%) or 22.8% (20.1-25.7%), respectively. Transient conversion or reversion were estimated at 46.0% (35.7-56.4%) or 19.6% (9.2-31.7%) of conversion or reversion events respectively. Indeterminate results seldom reverted to positive (1.2% [0.1-3.5%]). IGRA results in the borderline positive or negative range were associated with increased risk of conversion or reversion (pooled OR: conversion, 4.15 [3.00-5.30]; reversion, 4.06 [3.07-5.06]). BCG vaccination was associated with decreased risk of conversion (0.70, 0.56-0.84), cigarette smoking with decreased risk of reversion (0.44, 0.06-0.82), and female sex with decreased risk of either conversion or reversion (conversion, 0.66 [0.58-0.75]; reversion, 0.46 [0.31-0.61]). IGRA conversion is less common than reversion, and frequently transient. Research is needed to determine whether individuals with reversion would benefit from tuberculosis preventive treatment. Re-testing of people with indeterminate results is probably not indicated, since indeterminate results seldom revert to positive.

Retrospective analysis of the clinical utility of multi-cytokine profiles in smear-negative pulmonary tuberculosis.

To evaluate cytokine profiles and interferon-gamma release assay (IGRA) for their diagnostic capabilities in the differentiation of tuberculosis (TB) from non-TB conditions, as well as smear-negative pulmonary tuberculosis (SNPT) from smear-positive pulmonary tuberculosis (SPPT). A total of 125 participants were included, 77 of whom had TB and 48 who didn't, and demographic, clinical, and laboratory data were collected, including cytokine levels and IGRA results. The TB patients were further divided into 2 subgroups: SNPT (n=42) and SPPT (n=35). Compared to non-TB, the TB group had lower BMI, higher WBC, neutrophils, monocytes, ESR and CRP (p<0.05). TB patients showed higher IL-2, IL-6, IFN-γ, IL-8 (p<0.001) and higher IGRA positivity (88.3% versus [vs.] 29.2%, p<0.001). Between SNPT and SPPT, moderate effect sizes were observed for IFN-α, IL-2, IL-10, IL-8 (Cohen's d 0.59-0.76), with lower IGRA positivity in SNPT (81.0% vs. 97.1%, p=0.015). ROC analysis indicated IFN-α, IL-2, IL-10, IL-8 had moderate accuracy for SNPT diagnosis (AUCs 0.668-0.734), and combining these improved accuracy (AUC 0.759, 80% sensitivity, 64.2% specificity). A multi-biomarker approach combining these cytokines demonstrates enhanced diagnostic accuracy for tuberculosis.

Effect of Smoking on Longitudinal Interferon-ϒ Release Assay Results among Close Contacts of People with Pulmonary Tuberculosis.

Diagnosis of M. tuberculosis (Mtb) infection in close contacts is critical for TB control. Smoking is a risk factor for Mtb infection and TB disease but its effect on longitudinal interferon-gamma release assay (IGRA) results remains unknown. We conducted a multi-site prospective study in Brazil between 2015-2019, among close contacts of adults with culture-confirmed pulmonary TB. IGRA was performed at baseline, month 6 if negative at baseline, and month 24-30 after enrollment. IGRA results were categorized as IGRA-positive (maintained from baseline to last visit), IGRA-conversion (from negative to positive at any time), IGRA-reversion (from positive to negative at any time), and IGRA-negative (maintained from baseline to last visit). Associations between IGRA results and smoking status at baseline (current/former vs never) in contacts were evaluated using propensity score-adjusted logistic regression models. Estimated propensity score was used as a covariate in models, which regressed the outcome (IGRA-positive, IGRA-conversion, IGRA-reversion) on smoking status. Of 430 close contacts, 89 (21%) were IGRA-positive, 30 (7%) were converters, 30 (7%) were reverters and 22 were indeterminate. Smoking frequency was 26 (29%) among IGRA-positive contacts, 7 (23%) in converters, and 3 (10%) in reverters. Smoking in contacts was associated with lower odds of IGRA-reversion (adjusted odds ratio = 0.16; 95% confidence interval = [0.03-0.70]). We did not detect associations between smoking and IGRA-positive or IGRA-conversion. Our findings highlight the importance of smoking on longitudinal IGRA results. This has implications for clinical care and clinical trials in which IGRA status is monitored or used as an outcome.

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.

IGRA-based INH regimen for prevention of active tuberculosis after kidney transplantation: A single-centre retrospective study

ObjectivesTo evaluate the effectiveness and safety of Interferon-gamma release Assay (IGRA)-based isoniazid (INH) prophylaxis strategy to prevent tuberculosis (TB) infection in kidney transplantation (KT) with a risk of TB occurrence. MethodsAdult KT recipients (KTRs) between June 2014 and July 2021 were retrospectively enrolled. The development of active TB after KT was evaluated. ResultsOf 925 KTRs, 111 (12.0%) developed active TB. Among the 501 KTRs at a risk of TB occurrence, 70 (14.0%) patients developed active TB, while 41 (9.7%) of 424 patients without risk factors developed active TB (P = 0.05). Two hundred thirty-nine KTRs received IGRA test with 62 (25.9%) were positive. None of IGRA positive patients (0/40) receiving INH prophylaxis developed active TB, whereas 8 out of 22 patients who had positive IGRA results without INH prophylaxis developed active TB (0 vs. 36.4%, P < 0.01). Of note, for those in risk group but with negative IGRA result, no active TB was found even without INH prophylaxis. Although alanine aminotransferase and aspartate aminotransferase in INH prevention group were higher than those before treatment, they did not exceed three-fold of limit of reference range. ConclusionsIGRA-based INH treatment is an effective and safe protocol to prevent the development of active TB in KTRs.

Incidence of Tuberculosis Among Immigrants in Korea Who Participated in a Latent Tuberculosis Infection Screening Program.

With a rapid decrease in tuberculosis (TB) incidence, the significance of latent tuberculosis infection (LTBI) has been underscored in South Korea. Although South Korea does not have a high proportion of immigrants compared to other countries, there is a growing argument that it should actively embrace immigrants as a solution to address issues of low birth rates and population aging. This study aimed to assess TB incidence among immigrants who participated a pilot LTBI screening program in South Korea. Records of immigrants participated in a pilot LTBI screening program in South Korea between 2018 and 2019 were linked with Korean National TB Surveillance System to determine TB development. Participants underwent interferon-gamma release assay (IGRA) and chest X-rays. Standardized incidence ratios (SIRs) stratified by age, country of origin's TB burden was calculated with a reference group of general South Korean population. Of a total of 9,517 participants, 14 TB cases were identified. Participants with positive IGRA results who did not initiate LTBI treatment showed TB incidence of 312.5 per 100,000 person-years, whereas those with negative results showed TB incidence of 34.4 per 100,000 person-years, resulting in an incidence rate ratio of 9.08 (95% confidence interval [CI], 2.50-32.99). SIR of TB among total participants including those with negative IGRA results was 2.60 (95% CI, 1.54-4.38; P < 0.001), whereas SIR among those with positive IGRA results was 5.86 (95% CI, 3.15-10.89; P < 0.001). In the calculation of SIR among participants with positive IGRA results, those aged under 35 from high TB-burden countries or intermediate TB-burden countries showed a high SIR (18.08; 95% CI, 2.55-128.37; P = 0.004), and 11.30 (95% CI, 2.82-45.16; P < 0.001), respectively). Contrary to previous reports that suggest the majority of elderly population with a positive IGRA result were due to remote infection and had a lower TB risk compared to younger ages, SIR among those aged 65 or over from intermediate TB-burden countries was 6.15 (95% CI, 0.87-43.69; P = 0.069), which was comparable to that in younger participants aged between 35 and 49 (SIR, 4.87; 95% CI, 1.22-19.49; P = 0.025) or those aged between 50 and 64 (SIR, 4.62; 95% CI, 1.73-12.31; P = 0.002). Young immigrants with positive IGRA results from countries with high or intermediate TB burden showed a relatively high TB risk compared to a general South Korea population. In addition, unexpected high TB risk was observed among elderly immigrants with positive IGRA results. In establishing future policies for LTBI in immigrants in South Korea, screenings should primarily focus on younger age group (who aged under 35). Additionally, further research is needed on the high TB risk observed in elderly immigrants.

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.

Prevalence of indeterminate tuberculosis interferon-gamma release assays in COVID-19 patients: Systematic review and meta-analysis.

The reliability of interferon-gamma-release-assays (IGRAs) for tuberculosis (TB) testing in coronavirus disease 2019(COVID-19) patients is unknown. This study aimed to systematically review the prevalence of indeterminate TB-IGRA following SARS-CoV-2 infection or vaccination and to review associated factors. This systematic literature review was guided according to the PRISMA guidelines by searching PubMed, Scopus, Web of Science, Clinicalkey, and Cochrane Library. Studies reporting results of TB-IGRA tests (QuantiFERON [QFT]-TB, T-SPOT.TB) in COVID-19 patients or vaccines were included. The random effects model was used to assess the prevalence of indeterminate IGRA results. Heterogeneity was evaluated using the Τ 2 and 95% predictive interval. Of the 273 citations screened, 12 articles were included in the final analysis including a total of 2107 patients. The overall pooled effect size proportion of indeterminate QFT-TB results, estimated in eightstudies using the QFT-TB Plus assay, was 0.26 (95%CI: 0.205-0.324, Τ 2 = 0.158). The mean true effect size was 0.26 (95% predictive interval: [0.110-0.500]). A subgroup analysis was not undertaken due to the small number of studies. Indeterminate QFT-TB rates were associated with COVID-19 severity, steroid treatment, inflammation-related parameters, neutrophilia, and lymphopenia. Indeterminate QFT-TB results in COVID-19 patients occur in almost one-quarter of tests performed. Further studies are needed to assess associated factors.

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.

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.

Latent tuberculosis infection in myasthenia gravis patients on immunosuppressive therapy: high incidence yet moderate reactivation rate

Background Immunosuppressive therapies (ISTs) are mainstays for management of myasthenia gravis (MG). Meanwhile, latent tuberculosis infection (LTBI) is common in the setting of high-burden countries. However, the prevalence of LTBI among MG patients and whether receiving ISTs for MG would aggravate LTBI reactivation remain unknown. Methods We retrospectively analyzed the frequency of LTBI via interferon-gamma release assay (IGRA) positivity among hospitalized MG patients from both rural and urban areas in a tertiary hospital, and those receiving ISTs were followed up to investigate the reactivation risk of LTBI. Results A total of 300 MG patients with determinate IGRA results were enrolled, where the frequency of LTBI was 35.0%. Male (OR = 1.910, 95% CI: 1.181–3.089, p = .008) and elderly (OR = 1.044, 95% CI: 1.027–1.061, p < .001) patients were prone to LTBI. Of those with LTBI, 78 individuals on ISTs were successfully followed up for a median duration of 18.3 (8.5–24.0) months, of which 25 (32.1%) received anti-tuberculosis (TB) treatments. The rate of various degrees of adverse events was 82.1% over the course of the follow-up, but was not different between individuals with and without therapies against TB (χ 2 < 0.001, p > .999). Only 1 patient eventually reported lymph node and intestinal TB, with the incidence rate of LTBI reactivation preliminarily estimated to be 0.81 per 100 person years. Conclusion The frequency of LTBI is high in our MG cohort, especially among those with advanced age and males. However, receiving immunosuppressives seems not to increase the risk of LTBI reactivation. LTBI screening is strongly recommended for all MG patients ready to receive ISTs, while preventive anti-TB chemotherapy should be prescribed after weighing potential benefits against the risk of side effects in those with LTBI. In-depth investigation is still entailed to further verify these findings due to the limitation of the retrospective single-center design of our study.

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.

Cellular immune response to SARS-CoV-2 in patients with primary antibody deficiencies.

Primary antibody deficiencies (PAD) are inborn defects of the immune system that result in increased susceptibility to infections. Despite the reduced response to vaccination, PAD patients still benefit from it by reducing the risk of severe infections and complications. SARS-CoV-2 vaccines are recommended in PAD patients, but their immune effects are poorly studied. Here, we analyze virus-specific T-cell responses in PAD patients after booster vaccination against SARS-CoV-2. The study included 57 adult PAD patients on long-term immunoglobulin replacement therapy (IgRT) diagnosed with X-linked agammaglobulinemia (XLA; n = 4), common variable immunodeficiency (CVID; n = 33), isotype defects or IgG subclass deficiency (n = 6), and unclassified IgG deficiency (n = 14). Of those, 49 patients (86%) received vaccination against SARS-CoV-2 using mRNA vaccine (Pfizer-BioNTech). T-cell responses were assessed at a median of 21 (13 - 30) weeks after the booster dose (mainly the third dose) using commercially available interferon-gamma release assay (IGRA) with recombinant SARS-CoV-2 spike S1 protein. Vaccinated PAD patients showed an increased (3.8-fold, p = 0.004) release of IFN-γ upon S1 stimulation. In this group, we also documented higher serum levels of anti-SARS-CoV-2 IgG (4.1-fold, p = 0.01), although they were not associated with IGRA results. Further subgroup analysis revealed very similar IGRA responses in CVID and unclassified IgG deficiencies that were 2.4-fold increased compared to XLA and 5.4-fold increased compared to patients with isotype defects or IgG subclass deficiencies (e.g., vs. CVID: p = 0.016). As expected, CVID and XLA patients showed decreased serum titers of anti-SARS-CoV-2 antibodies compared to other studied groups (e.g., CVID vs. unclassified IgG deficiency: 4.4-fold, p = 0.006). The results did not depend directly on IgRT mode or dose, number of vaccine doses and time from the last booster dose, and clinical manifestations of PAD. Interestingly, anti-SARS-CoV-2 titers were positively correlated with serum immunoglobulin levels before IgRT (e.g., for IgA: r = 0.45, p<0.001; for IgG: r = 0.34, p = 0.009) and the percentage of peripheral blood NK cells (r = 0.48, p<0.001). Our results documented satisfactory in vitro cellular immune response in PAD patients after booster SARS-CoV-2 vaccination. Therefore, even patients with agammaglobulinemia should benefit from vaccination due to the apparent induction of cell-mediated immunity, which, together with IgRT, grants comprehensive protection against the pathogen.

A Propensity Score-Matched Study on the Changes of TB Status and TB-IGRA Values in Patients with Psoriasis with Latent TB Receiving Secukinumab.

The utilization of biologics in patients with psoriasis with latent tuberculosis infection (LTBI) has garnered significant attention. Although the tuberculosis (TB) safety profile of second-generation biologics, including secukinumab, has been partially confirmed in both clinical trials and real-world studies, the necessity for prophylactic therapy in patients with LTBI prior to administering this class of biologics remains a topic of controversy. This study enrolled 62 patients with psoriasis with LTBI who underwent secukinumab with routine TB reexamination. Patients were divided into two groups based on whether they received antituberculosis therapy (ATB; n = 48) or not (NTB; n = 16). We performed a propensity score-matched (PSM) analysis between ATB and NTB subgroups and retrospectively reviewed their interferon-gamma release assays (IGRA) and radiographic results. No active TB case was reported on the basis of medical records and chest radiographs in either two group. Before PSM, the mean reexamining IGRA value was significantly elevated in patients who received prophylactic therapy (P = 0.00), but no significant increase was observed in patients who were not. After PSM, there was no significant IGRA value enhancement whether or not patients received prophylactic treatment. Our data provide additional information on the safety profile of secukinumab in patients with psoriasis with LTBI. Furthermore, our presentation of the reexamined IGRA results revealed no significant elevation in the ATB or NTB group. As such, we believe further exploration is necessary to determine whether anti-TB medication is required prior to administering secukinumab.

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.

Tuberculosis in 0-5-year-old children following TB contact investigations: a retrospective study in a low burden setting.

We assessed the risk of tuberculosis (TB), the management and the outcomes of 0-5-year-old children after TB contact investigations in a low-burden setting. All 0-5-year-old children who attended the TB clinic of Robert Debre Hospital, Paris, France, for a TB contact investigation between June 2016 and December 2019 were included in this retrospective study. The risk factors for TB were assessed using univariate and multivariate analyses. A total of 261 children were included. Forty-six (18%) had TB, including 37 latent tuberculosis infections (LTBIs) and 9 active TB diseases. The prevalence of TB was 21% among high-risk contacts, i.e., household or close contacts and regular or casual contacts. There was no TB among intermediate- or low-risk contacts (0/42). Living under the same roof with (OR: 19.8; 95% CI: 2.6-153), the BCG vaccine (OR: 3.2; 95% CI: 1.2-8.3), contact duration >40 h (OR: 7.6; 95% CI: 2.3-25.3) and sleeping in the room of the index case (OR: 3.9; 95% CI: 1.3-11.7) were independently associated with TB. The BCG vaccine was no longer associated when the analysis was restricted to interferon gamma release assay results. Among children without initial LTBI, antibiotic prophylaxis was not prescribed for 2-5-year-old children or for 32/36 (89%) of 0-2-year-old children who had intermediate- or low-risk contact. Overall, none of these children experienced TB. In our low prevalence setting, the risk of TB in 0-5-year-old children following a household or close contact was high. Further studies are needed to better assess prophylaxis recommendations in intermediate or low risk contact.