Interferon-gamma Release Assay Research Articles

WCN25-808 Concordance between Cy-TB and Interferon gamma release assay (IGRA) for diagnosing latent Tuberculosis infection in chronic kidney disease patients attending Nephrology OPD in an Indian tertiary care centre

WCN25-808 Concordance between Cy-TB and Interferon gamma release assay (IGRA) for diagnosing latent Tuberculosis infection in chronic kidney disease patients attending Nephrology OPD in an Indian tertiary care centre

Tuberculosis infection prevalence and treatment completion among refugees in the United States.

Identifying and treating tuberculosis infection (TBI) among refugees at elevated risk for developing TB disease is crucial for TB prevention and elimination in the United States (U.S.). However, current evidence is limited by small sample sizes, inclusion of refugees from only a single country, and/or reliance solely on the tuberculin skin test (TST). Refugees in a large cohort study from 10 U.S. sites underwent evaluation for TBI using three available tests: the TST and two interferon-gamma release assays (IGRAs). This study calculated TBI prevalence and assessed tuberculosis preventive treatment (TPT) completion among refugees, defining TBI prevalence as positive results on at least two tests. Among 8960 refugees enrolled July 2012 through May 2017, TBI prevalence was 23.2% (95% confidence interval [CI]: 22.4%-24.1%). Completion of TPT was 81.2% (95% CI: 79.6%-82.7%). Shorter treatment regimens of 3 months were associated with higher treatment completion compared to regimens of 6 months or longer. The high TBI prevalence among refugees is a concern, but their high TPT acceptance and completion rates offer an opportunity. IGRA-based tests are preferred in this population; however, limited resources underscore the need for more precise screening approaches to better identify high-risk individuals who truly require TPT.

CD14++CD16- classical monocyte subset secreting IL-1ß and IL-10 is associated with 'Tuberculosis Resisters' phenotype.

Mycobacterium tuberculosis (M.tb) infection can lead to various outcomes, including active tuberculosis or latent tuberculosis infection (LTBI). Household contacts of TB cases have a high risk of acquiring LTBI. However, some contacts exposed to M.tb remain negative for tuberculin skin test (TST) and interferon-gamma release assay (IGRA) tests and are called 'TB resisters'. Characterization of immune responses in 'TB resisters' may help to understand correlates of protection against M.tb. Based on the TST and IGRA tests, household contacts were divided into 'LTBI' and 'TB Resisters'. Peripheral blood mononuclear cells (PBMCs) of the study participants were isolated and processed to characterize the monocyte subsets based on CD14 and CD16 expression in flow cytometry. Monocyte intracellular cytokine expression (IL-10, IL-6, TNF-α and IL-1ß) was assessed after Lipopolysaccharide (LPS) stimulation. LTBI and active TB patients showed a higher frequency of intermediate and non-classical monocyte subsets depicting the infectious stage. Higher frequency of classical monocyte subsets was associated with 'TB resisters'. Marked expression of IL-1ß and a higher monocyte to lymphocytes (M/L) ratio was seen in PTB, LTBI and TB resister groups compared to healthy controls indicating active disease or exposure to M.tb. Classical Monocytes (CM) were further found to be associated with higher expression of IL-1ß and IL-10 in the 'TB resister group', which might help in the clearance of infection at an early stage. LTBI and PTB showed significantly higher TNF-α producing monocytes than healthy controls and 'TB Resisters'. IL6-producing monocytes were significantly higher in LTBI compared to other study groups. These findings could further be explored with follow-up in cohort of 'TB resisters'. Also, the role of IL-1ß and IL10 secreting classical monocytes in early clearance of infection could be explored with in vitro mechanistic studies.

Diagnostic value of interferon-γ release assay in patients with COPD complicated with pulmonary tuberculosis

BackgroundThe common diagnostic methods for tuberculosis have been showing reduced sensitivity among chronic obstructive pulmonary disease patients. This study was conducted to evaluate and analyse the diagnostic value of an interferon-γ release assay in COPD patients complicated with pulmonary tuberculosis.MethodsA nested case-control study was conducted on 123 COPD patients hospitalized at the Fifth Hospital of Shijiazhuang, Hebei Province, from January 2019 to June 2021. Thirty-one patients with active pulmonary tuberculosis complicated with COPD composed the observation group (Group A), 31 patients with nonactive pulmonary tuberculosis complicated with COPD composed the COPD control group (Group B), and 31 patients with active pulmonary tuberculosis not complicated with COPD composed the non-COPD control group (Group C). An interferon-γ release assay, a purified protein derivative of tuberculin (PPD) test, an anti-tuberculosis antibody test, a test of Mycobacterium tuberculosis by sputum smear microscopy and a test of Mycobacterium tuberculosis by PCR method were used to test patients in each group. The positive detection rates generated from the five test methods were compared and analysed.ResultsIn COPD patients complicated with active pulmonary tuberculosis, the differences in the percentage of patients with positive interferon-γ release between the PPD test, anti-tuberculosis antibody test, Mycobacterium tuberculosis by sputum smear microscopy and PCR test results were statistically significant.ConclusionIn patients with COPD complicated with active pulmonary tuberculosis, the percentage of patients who were positive according to the interferon-γ release assay was higher than that according to the sputum smear microscopy, PCR detection of Mycobacterium tuberculosis in sputum specimen, and detection of anti-tuberculosis antibodies. COPD-related complications did not affect the T-SPOT; the greater the T-SPOT value was, the greater the likelihood of active TB. For patients who are T-SPOT positive but clinically considered to have inactive tuberculosis, regular follow-ups should be performed to observe changes in the patient’s condition.

P0584 Rituximab versus infliximab for the treatment of PR3-ANCA Positive Moderately to Severely Active Ulcerative Colotis: A retrospective Multicentre Real-World Study

Abstract Background Patients with ulcerative colitis (UC) who are positive for anti-neutrophil cytoplasmic antibodies(ANCA) tend to have a poor response to infliximab(IFX)1-3. We aimed to evaluate the comparative efficacy and safety of rituximab (RTX) versus IFX in moderately to severely active UC patients who are Proteinase 3-ANCA(PR3-ANCA) positive. Methods This retrospective multicentre real-world study encompassed three medical centres in Hubei, China. Patients with moderate to severely active UC who are positive for PR3-ANCA were categorized into the RTX group(100mg or 200mg by intravenous injection every 2 weeks for a total dose between 400mg and 900mg, n=12) and IFX group(5 mg/kg of intravenous at weeks 0, 2, and 6, followed by maintenance doses every 8 weeks, n=26) based on the biological therapy. The Mayo Clinic Score (MCS) was utilised to evaluate the efficacy endpoints at week 22, encompassing clinical remission(primary endpoint), clinical response, endoscopic response, endoscopic improvement, and endoscopic remission. Safety endpoints focused on opportunistic infections and drug-related adverse reactions. Inverse probability of treatment weighting(IPTW) and multifactorial logistic regression analysis(MLRS) were employed to mitigate the effects of potential confounding factors. Results The rates of clinical remission(83.33% vs. 23.08% and 93.20% vs. 25.40%), clinical response(100.00% vs. 65.38% and 100.00% vs. 64.60%), endoscopic response(100.00% vs. 34.62% and 100.00% vs. 36.06), endoscopic improvement(50.00% vs. 11.54% and 75.07% vs. 11.29%), and endoscopic remission(100.00% vs. 34.62% and 100.00% vs. 36.06%) were significantly higher in patients treated with RTX compared with those treated with IFX, both prior to and following IPTW(all P<0.05). In MLRS, RTX was associated with higher odds of achieving clinical remission at week 22 versus IFX before and after IPTW[OR(95%CI): 143.854(1.060-19521.653) and 190.499(4.147-1.000*105), all P<0.05]. In terms of safety endpoints, elevated interferon-gamma release assays(IGRAs) were noted in none of the RTX patients, and 2 IFX patients (7.69%). No patients exhibited elevated EBV-DNA, HBV-DNA, CMV-DNA, or experienced severe infections. Conclusion RTX demonstrated superior efficacy versus IFX in moderately to severely active UC patients with positive PR3-ANCA, with a comparable safety profile.

Tuberculosis screening in hidradenitis suppurativa patients on tumor necrosis factor inhibitors: a retrospective chart review.

Hidradenitis suppurativa (HS) patients treated with tumor necrosis factor (TNF) inhibitors are at an increased risk for tuberculosis (TB) reactivation, necessitating baseline latent TB infection (LTBI) screening. However, evidence regarding the value of periodic LTBI screening in this population is limited. In this single-center retrospective chart review, we investigated the LTBI rate in HS patients treated with adalimumab or infliximab. The cohort included 92 patients with an average treatment duration of 37.4 months and a median Interferon-Gamma Release Assay (IGRA) number of 3. The cumulative observation time was 286 person-years. Our investigation found no positive LTBI results in HS patients on TNF inhibitors, challenging clinicians to reconsider the utility of serial screening for such patients who are otherwise at low risk for TB. Further research is essential for the development of evidence-based guidelines to optimize patient care and healthcare resource allocation.

High risk of drug-resistant tuberculosis in IGRA-negative contacts: should preventive treatment be considered?

Deciding whether to provide preventive treatment to contacts of individuals with multidrug-resistant (MDR) tuberculosis is complex. We present the diagnostic pathways, clinical course and outcome of tuberculosis treatment in eight siblings from a single family. Tuberculosis disease was diagnosed by Mycobacterium tuberculosis culture and molecular detection of M. tuberculosis-specific DNA from bronchopulmonary specimens using GeneXpert® MTB/RIF. M. tuberculosis infection was diagnosed by an interferon-gamma release assay (IGRA; QuantiFERON®-TB Gold Plus). Whole exome sequencing for genetic predisposition to mycobacterial infection was performed in one patient. Six of eight siblings aged 16-20 years from a migrant family of Somali origin were diagnosed with pulmonary MDR tuberculosis over a 12-month period. The remaining male siblings, aged 11 and 14 years, were asymptomatic during contact investigation. Chest radiographs, computed tomography (CT) scans, sputum cultures and nucleic acid amplification tests were negative, and the IGRA did not detect M. tuberculosis infection. A repeat CT scan eight months later was unremarkable, and repeated sputum cultures remained negative. In the absence of sufficient evidence of M. tuberculosis infection, no preventive treatment was offered. At month seven of consistent clinical observation, both children were diagnosed with pulmonary tuberculosis; the older with advanced disease and subsequent post-tuberculosis lung disease. Whole exome sequencing revealed no Mendelian variant associated with susceptibility to mycobacterial infection. When significant risk of tuberculosis transmission exists, close contacts of MDR tuberculosis patients should be offered preventive treatment with levofloxacin despite a negative IGRA test result.

Comparison of Two Interferon-Gamma Release Assays for Pediatric Tuberculosis Infection.

Identifying tuberculosis infection (TBI) using interferon-gamma release assays (IGRAs) is a primary component of clinical and public health efforts to prevent pediatric tuberculosis (TB). Pediatric data comparing the 2 IGRAs in the United States are very limited. We compared the performance of the 2 IGRAs among a large pediatric cohort tested for TBI and assessed whether discordance might be due to quantitative results close to test cutoff values. Children aged 0-15 years with both T-SPOT.TB (T-SPOT) and QuantiFERON-TB Gold In-Tube (QFT-GIT) tests were identified from a US multicenter study enrolling people at elevated risk of TBI or progression to TB disease. Results were compared using McNemar's Chi-square tests with stratification by age category and testing reason. Percent agreement and kappa statistics were also calculated. We characterized quantitative test results among children with discordant QFT-GIT-positive/T-SPOT-negative results. Among 3793 children, a higher number had positive QFT-GIT than T-SPOT (10.1% vs 7.4%, P < .001). This difference was noted for all age categories except <2 years, and for children with close-contact and non-close contact test indications. Among discordant QFT-GIT-positive/T-SPOT-negative children, lowering the positive threshold for T-SPOT to include borderline spot counts (5-7) did not eliminate the discordance, nor were QFT-GIT antigen-minus-nil results concentrated in the range just above the standard cutoff of 0.35 IU/mL. In a large pediatric cohort tested for TBI, QFT-GIT had a higher proportion of positive results than T-SPOT, and discordance was not related to quantitative results close to the established diagnostic cutoffs.

Underestimated latent tuberculosis infection burden among school contacts in China: a cross-sectional study

BackgroundPrevious research has indicated a low tuberculin skin tests (TST) strong positive rate in school tuberculosis (TB) screening implemented by community-level medical and health care institutions in China. The research objective was to evaluate the latent tuberculosis infection (LTBI) detection gap in school contact investigation in China.MethodsIn this cross-sectional study, school contacts were investigated by Chongqing Municipal Institute of Tuberculosis between January 2022 and April 2024 in Chongqing, China. TST, creation tuberculin skin test (C-TST), or Interferon-gamma release assays (IGRA) were conducted for immunological diagnostic methods. The LTBI detection gap among school contacts was assessed by comparing with the data implemented by community-level medical and health care institutions from 2021 to 2022.ResultsIn 6063 participants, 4233 were tested using TST, 1799 were tested using C-TST, and 31 were tested using IGRA. Seven students were confirmed to have active TB. The LTBI prevalence rate using TST and C-TST was 15.2% (95%CI, 14.1-16.3%) and 3.6% (95%CI, 2.7-4.4%) respectively. A LTBI detection gap of 10.3% was identified when comparing with TST results implemented by community-level medical and health care institutions (χ2 = 636, P < 0.001).ConclusionsTB school contact investigation plays an important role in controlling TB epidemic. However, there may be a LTBI detection gap, likely due to poor quality control of TST implemented by community-level medical and health care institutions.

Micronutrient status and risk of Mycobacterium tuberculosis infection in Indonesian tuberculosis case contacts.

Certain micronutrient levels have been associated with the risk of developing TB disease. We explored the possible association of selected at-risk micronutrient levels with the development of Mycobacterium tuberculosis (M.tb) infection. This cohort study in Bandung, Indonesia, followed Interferon Gamma Release Assay (IGRA) negative TB case contacts with a repeat IGRA test at 3 mo. At baseline, blood was analysed for haemoglobin, 25-hydroxyvitamin D, retinol-binding protein, C-reactive protein, alpha-1-acid glycoprotein, serum transferrin receptor (sTfR), ferritin, zinc and selenium. Total body iron was calculated using ferritin and sTfR status. Associations between case contact micronutrient concentration and IGRA conversion were estimated using Poisson regression. Of 430 contacts, 115 (27%) underwent IGRA conversion. Ferritin concentration (adjusted for inflammation) was positively associated with risk of IGRA conversion (incidence rate ratio [IRR] for ferritin=1.17; 95% CI 1.01 to 1.35; p=0.03), but other select micronutrients were not. This association held for ferritin in the final multivariable model (IRR=1.27; 95% CI 1.09 to 1.47; p=0.002). The risk of developing M.tb infection, as defined by IGRA conversion, is associated with increasing ferritin. Interventions in TB case contacts to temporarily reduce iron levels, including considering withholding any iron supplementation, may be worthy of evaluation.

Immune responses of cattle vaccinated by various routes with Mycobacterium bovis Bacillus Calmette-Guérin (BCG)

BackgroundMycobacterium bovis BCG is the human tuberculosis vaccine and is the oldest vaccine still in use today with over 4 billion people vaccinated since 1921. The BCG vaccine has also been investigated experimentally in cattle and wildlife by various routes including oral and parenteral. Thus far, oral vaccination studies of cattle have involved liquid BCG or liquid BCG incorporated into a lipid matrix. Lyophilization is an established technique used for stabilizing bioproducts such as vaccines.MethodsIn the current study, cattle were vaccinated in two phases. In each phase, cattle were divided into three groups. Group 1 received BCG injected SQ, Group 2 received liquid BCG delivered to the posterior oral cavity, Group 3 orally consumed lyophilized BCG contained within a gelatin capsule placed within a small amount of a commercial alfalfa product.ResultsNo vaccinated cattle were positive by an interferon gamma release assay. All but 4 animals were negative by tuberculin skin testing prior to vaccination: the 4 non-negative animals being categorized as suspects. Sixteen weeks post-vaccination all but 1 animal was negative, it being categorized as a suspect. An in vitro antigen stimulation assay and flow cytometry were used to detect antigen-specific CD4, CD8 and γδ T cell responses following vaccination. Oral vaccination of animals with lyophilized BCG did not result in any increases in the frequency of CD4, CD8 or γδ T cell proliferative or IFN-γ responses at any of the time points analyzed in either phase 1 or 2. In contrast, vaccination with BCG SQ and liquid BCG delivered to the posterior pharynx, resulted in an increase in the frequency of proliferating and IFN-γ-producing CD4 T cells with peak responses at 9–12 weeks post-vaccination. Similar to oral lyophilized BCG vaccinated animals, we did not observe any significant increases in the frequency of CD8 and γδ T cell proliferative and IFN-γ responses following SQ or oral liquid vaccinated animals.ConclusionsThese data would suggest that vaccination with oral lyophilized BCG does not induce a measurable, antigen-specific cell mediated responses in the periphery, when compared to BCG administered SQ or liquid BCG administered via the oral route. However, vaccination with either SQ or liquid BCG delivered to the posterior pharynx does induce measurable CD4 T cell responses in the periphery.

Effects of different vaccination regimes on the immunodiagnosis of tuberculosis in goats and evaluation of defined antigens

Tuberculosis (TB) in goats is a chronic infectious disease caused by Mycobacterium tuberculosis complex (MTBC) organisms that pose a great health and economic challenge for the caprine industry in some European and developing countries. It is also a zoonotic disease posing a risk for public health. The control programs of the disease are based on a test-and-slaughter strategy, and vaccination is not feasible with available vaccines due to its interferences with the current TB immunodiagnosis. There is still a need for the development of an effective TB vaccine and, concurrently, diagnostic methods that allow differentiation between infected and vaccinated animals (DIVA approach). In this study, we investigated the interferences caused by the tuberculin (PPD)-based TB diagnostic tests in goats immunized by different mucosal and parenteral vaccination strategies: three single-dose strategies based on intranasal administration of BCG and two heat-inactivated M. bovis (HIMB) vaccines, and two prime-boost strategies based on parenteral BCG or HIMB priming and intranasal HIMB boosting. In addition, the defined antigens ESAT-6, CPF10, and EspC were evaluated as alternative diagnostic reagents to PPDs. At week 14 after prime vaccination of the animals, skin tests, IFN-γ release assay, and antibody detection assays were performed. The two prime-boosted and the single-dose intranasal BCG groups displayed greater cell-mediated immune responses to PPDs than the two single-dose intranasal HIMB vaccines. However, the use of reagents based on the defined antigens eliminated or reduced the vaccine-induced diagnostic interferences in all groups. Based on these results, the use of defined antigens in the current immunodiagnostic tests appears to be suitable in a future goat TB vaccination scenario.

Impact of Combined Antiretroviral Treatment (cART) on Latent Cytomegalovirus Infection.

Cytomegalovirus infections and reactivations are more frequent in people living with HIV (PLWH) and have been associated with increased risk of HIV progression and immunosenescence. We explored the impact of combination antiretroviral therapy (cART) on latent CMV infection in 225 young adults parenterally infected with HIV during childhood. Anti-CMV IgG antibodies were present in 93.7% of participants, with lower levels correlating with longer cART exposure and better immunologic parameters. Patients with immunological treatment success (CD4 > 350 cells/mL) had significantly lower CMV IgG titers compared to those with suboptimal immune response to cART. In total, 78% of the tested patients had robust CMV-specific T-cell responses, measured by an IFN-γ release assay. A good immune response to treatment was significantly associated with CMV-specific cellular immunity: IFN-γ level was positively correlated with CD4 and CD8-T cell counts. No differences were observed between patients with suppressed/non-suppressed HIV viremia in terms of CMV humoral and cellular immune response. CMV DNA was detected in only 17% of participants, with lower levels among those with cART-induced immune recovery. The successful antiretroviral treatment with subsequent immunologic reconstitution may lead to restoration of CMV-specific immune responses and effective control of latent infection, limiting episodes of CMV reactivation in HIV-positive individuals.

Latent tuberculosis prevalence in healthcare workers in Laos: a cross-sectional study

BackgroundIndividuals with latent tuberculosis infection (LTBI) have a high risk of active infection, morbidity and mortality. Healthcare workers are a group who have increased risk of infection and onward transmission to their patients and other susceptible individuals; however, LTBI is often undiagnosed, and individuals are asymptomatic. Interferon gamma release assays (IGRA) can detect evidence of TB infection in otherwise asymptomatic individuals and are a good indication of LTBI. Laos, a resource limited country in southeast Asia, has limited data on TB prevalence in the general population or in healthcare workers. This study aimed to estimate the prevalence of LTBI in Lao healthcare workers in Vientiane Capital.MethodsHealthcare workers from high-risk departments from 3 central hospitals in Laos were included (n = 196) and venous blood was tested by IGRA. A questionnaire was administered to determine their knowledge, attitude and practice towards TB and LTBI.Results10.2% of the participants were positive by IGRA, none of whom were previously aware of their TB status. The questionnaire revealed that knowledge and awareness of TB and LTBI were low.DiscussionA significant proportion of healthcare workers in this study had evidence of LTBI infection. These individuals were unaware of their TB status and we suggest that testing and treatment, as well as prevention strategies, should be routinely administered in Lao hospitals.

Comparative Performance of Ante-Mortem Diagnostic Assays for the Identification of Mycobacterium bovis-Infected Domestic Dogs (Canis lupus familiaris).

The domestic dog (Canis lupus familiaris) is a competent host for Mycobacterium (M.) bovis infection but no ante mortem diagnostic tests have been fully validated for this species. The aim of this study was to compare the performance of ante mortem diagnostic tests across samples collected from dogs considered to be at a high or low risk of sub-clinical M. bovis infection. We previously tested a total of 164 dogs at a high risk of infection and here test 42 dogs at a low risk of infection and 77 presumed uninfected dogs with a combination of cell-based and/or serological diagnostic assays previously described for use in non-canid species. The interferon-gamma release assay (IGRA) using peripheral blood mononuclear cells (PBMCs) identified the highest number of test-positive animals (85, 52%), with a suggested specificity of 97.3%, whilst a whole-blood IGRA was found to be unreliable. The production of antigen-specific tumour necrosis factor-alpha (TNF-α) by PBMC in response to a cocktail of ESAT-6 and CFP-10 peptides correlated very strongly with the overall IGRA results, suggesting future diagnostic potential. All three serological assays employed in this study (Idexx M. bovis Ab ELISA, [Idexx Laboratories, Westbrook, ME, USA], DPP VetTB lateral flow assay [Chembio, Medford, NY, USA], and comparative PPD ELISA [in-house]) identified seropositive dogs but, overall, the test-positive rate for the serological assays was only one third that of the cellular-based assays. Circulating serum cytokine concentrations of interferon gamma and TNF-α were not statistically different between the high- and low-risk groups of dogs. While many dogs in the high-risk group had serum biochemical abnormalities, these did not correlate with the findings from the diagnostic TB tests. This study demonstrates, for the first time, the utility of two cellular and three serological assays for detecting sub-clinical M. bovis infections of dogs. Whilst the data suggest a high test specificity for all assays evaluated, further work is needed to validate the sensitivity and specificity of individual or combinations of tests using sufficient numbers of dogs of a known infection status.

Advances in serological and molecular methods for the diagnosis of latent tuberculosis

Introduction: tuberculosis (TB) is an infectious pathology of bacterial origin that is transmitted mainly by air. This disease is caused by Mycobacterium tuberculosis (MTB) and its main area of involvement is the lungs. Clinically, tuberculosis can manifest itself from a non-communicable and asymptomatic latent infection (LTBI) to a highly transmissible active disease. An essential aspect to obtain adequate control of the disease is the detection and diagnosis of both infectious and active cases, in order to interrupt the chain of TB transmission.Objectives: to evaluate the usefulness, efficacy and clinical accuracy of the serological and molecular methods currently used to detect latent tuberculosis.Methods: a bibliographic review was carried out using the PRISMA method. Clinical studies and systematic reviews were included, highlighting those with relevant information on the diagnostic advances used in laboratories for the detection of TB.Results: currently, the interferon gamma release assay (IGRA) and the tuberculin skin test (TST) are used to establish the diagnosis of TB. However, molecular tests such as GeneXpert MTB/RIF, LAMP, PCR have revolutionized the diagnosis of active tuberculosis by offering significant advances in terms of speed, accuracy and accessibility.Conclusions: tests for the diagnosis of tuberculosis include different traditional techniques such as microscopy and culture, as well as innovative molecular and immunodiagnostic tests. However, each of these strategies has its strengths and limitations, so this topic remains a necessary area of research to achieve the eradication of the disease

Assessment and management for latent tuberculosis before advanced therapies for immune-mediated inflammatory diseases: A comprehensive review.

Tuberculosis (TB), caused by Mycobacterium TB, is the most significant infectious cause of mortality across the globe. While TB disease can prey on immunocompetent individuals, it is more likely to occur in immunocompromised individuals. Immune-mediated inflammatory diseases (IMIDs) are a group of diseases (rheumatoid arthritis, inflammatory bowel disease, ankylosing spondylitis, psoriasis, hidradenitis suppurative, autoimmune blistering diseases, and others) where there may be a need for systemic immunosuppression to control the disease manifestations, treat symptoms and improve long term outcomes. Immunosuppression may predispose them to active TB either from recent infection or reactivation of Latent TB (LTB). The major determinants of reactivation include the type of therapy (highest risk with TNF inhibitors and JAK inhibitors) and the underlying TB endemicity. The strategy to avoid TB reactivation includes the detection of LTB using tests that detect immunoreactivity to TB antigens (interferon-gamma release assays or tuberculin skin test) and treating LTB before or with initiation of IMID therapies. Available diagnostic tests have deficiencies in diagnostic sensitivity to detect LTB and even worse capability in predicting reactivation of TB. In addition to immunological tests, more stringent strategy utilizing one or many LTB equivalents may point towards subclinical TB. LTB equivalents include clinical (past history of TB, recent exposure to TB) and radiological criteria (use of chest roentgenogram, computed tomography, or, sometimes positron emission tomography - computed tomography). The present review summarizes the risk factors for TB reactivation in patients initiated on advanced therapies, geographically appropriate strategies for LTB testing, and treatment of LTB.

Evaluation of circadian rhythm of SARS-CoV-2 interferon-gamma release assay (IGRA) in healthy vaccinated individuals: a case-series

Evaluation of circadian rhythm of SARS-CoV-2 interferon-gamma release assay (IGRA) in healthy vaccinated individuals: a case-series

Prevalence and exposure variables of latent infection by mycobacterium tuberculosis in healthcare workers.

To identify in the scientific literature the prevalence, diagnostic methods, and exposure variables of latent infection by Mycobacterium tuberculosis in healthcare workers. An integrative review of the scientific literature based on the following review question: What are the available scientific evidence in the literature that address the prevalence of latent infection by Mycobacterium tuberculosis in healthcare workers and its association with possible risk factors among these workers? Being a physician or nurse, being older, and being male were generally associated with higher prevalences. The study also showed that interferon-gamma release assays were more commonly used as a diagnostic method compared to skin tests. More studies are needed regarding the epidemiology of latent infection by Mycobacterium tuberculosis in the context of healthcare workers, aiming for higher impact actions that contribute to the reduction of tuberculosis worldwide.

Low agreement and frequent invalid controls in two SARS-CoV-2 T-cell assays in people with compromised immune function.

T-cell response plays an important role in SARS-CoV-2 immunogenicity. For people living with HIV (PWH) and solid organ transplant (SOT) recipients there is limited evidence on the reliability of commercially available T-cell tests. We assessed 173 blood samples from 81 participants (62 samples from 35 PWH; 111 samples from 46 SOT recipients [lung and kidney]) with two commercial SARS-CoV-2 Interferon-γ (IFN-γ) release assays (IGRA; SARS-CoV-2 IGRA by Euroimmun, and IGRA SARS-CoV-2 by Roche). The reliability between the tests was judged as low (Cohen's kappa [κ] = 0.20; overall percent agreement [OPA] = 66%). A high proportion of tests were invalid (22% Euroimmun; 8% Roche). When excluding these invalid tests, the agreement was higher (κ = 0.43; OPA = 90%). The low reliability between the two T-cell tests indicates that results should be interpreted with caution in SOT recipients and PWH and that SARS-CoV-2 T-cell tests need to be optimized and further validated for use in vulnerable patient populations.