Search Results (74)

Background: Disease-modifying drugs (DMDs) for multiple sclerosis (MS) slightly increase the risk of tuberculosis (TB) disease. The QuantiFERON-TB-Plus (QFT-Plus) test is approved for TB infection (TBI) screening. Currently, there are no data available regarding the characterization of QFT-Plus response in patients with MS. Objectives: This study aimed to compare the magnitude of QFT-Plus responses between patients with MS and TBI (MS-TBI) and TBI subjects without MS (NON-MS-TBI). Additionally, discordant responses to TB1/TB2 stimulation were documented. Results were evaluated considering demographic and clinical data, particularly the impact of DMDs and the type of TB exposure. Methods: Patients with MS (N = 810) were screened for TBI (2018–2023). Thirty (3.7%) had an MS-TBI diagnosis, and 20 were recruited for the study. As a control group, we enrolled 106 NON-MS-TBI. Results: MS-TBI showed significantly lower IFN-γ production in response to TB1 (p = 0.01) and TB2 stimulation (p = 0.02) compared to NON-MS-TBI. The 30% of TB2 results of MS-TBI fell into the QFT-Plus grey zone (0.2–0.7 IU/mL). Only 7% of NON-MS-TBI showed this profile (p = 0.002). Conclusions: MS-TBI had a lower QFT-Plus response and more borderline results compared to NON-MS-TBI. Future studies should clarify the significance of the borderline results in this vulnerable population to improve QFT-Plus accuracy regarding sensitivity, specificity, and TB prediction. Full article

Background/Objectives: Patients with immune-mediated inflammatory diseases (IMIDs) treated with disease-modifying antirheumatic drugs (DMARDs) are at increased risk of latent tuberculosis infection (LTBI) reactivation, influenced by DMARD type. This study aimed to determine LTBI prevalence using interferon-gamma release assays (IGRAs) and identify associated risk factors in IMID patients in a middle-high TB burden setting in Mexico. Methods: A cross-sectional study was conducted from July 2024 to April 2025 at an IMID clinic. Patients aged ≥18 years, either receiving DMARDs or prior to initiating treatment, were included. LTBI was diagnosed using the QuantiFERON-TB Gold Plus assay. Bivariate analysis was performed using the chi-square test, and multivariate analysis was conducted. Results: LTBI prevalence was 34.2% (95% CI 29.1–39.7%) according to QFT-Plus and 35.6% (95% CI 29.7–42.0%) according to TSTs (n = 230). Prior TB exposure was the strongest risk factor (aOR 4.20, 95% CI 1.74–10.12, p = 0.001), while rheumatoid arthritis was associated with a lower LTBI likelihood (aOR 0.31, 95% CI 0.16–0.59, p < 0.001). Conclusions: A high prevalence of LTBI was observed in patients with IMIDs treated with DMARDs. Prior tuberculosis exposure was strongly associated with LTBI. These findings highlight the importance of LTBI screening in this population to prevent reactivation. Full article

Latent tuberculosis infection (LTBI) is prevalent in patients with type 2 diabetes. We aimed to examine the relationship between serum levels of aryl hydrocarbon receptor (AhR) and LTBI in patients with type 2 diabetes. In this cross-sectional study, patients with type 2 diabetes were screened for LTBI using the QuantiFERON-TB (QFT) test. Of 543 patients screened for LTBI, 133 (24.5%) were QFT-positive. The QFT-positive patients had higher AhR levels than the QFT-negative patients (44.6 [interquartile range: 25.4–58.6] pg/mL vs. 37.8 [interquartile range: 17.4–55.0] pg/mL; p = 0.004). According to the receiver operating characteristic curve, the area under the curve was 0.584 (95% confidence interval: 0.528–0.639; p = 0.004) and the optimal cutoff value for serum AhR levels was of 37.7 pg/mL for differentiating a QFT-positive result. By a multivariable logistic regression analysis, the patients with high AhR levels had a greater risk of being QFT positive than those with low AhR levels (odds ratio = 1.902, 95% confidence interval: 1.254–2.886; p = 0.003). In conclusion, in patients with type 2 diabetes, a high serum AhR level was associated with LTBI. Full article

Background/Objectives: Healthcare workers (HCWs) are globally recognized as a high-risk group for tuberculosis (TB) infection. However, limited data exist on the prevalence of latent TB infection (LTBI) and associated occupational risk factors in the Mexican context. Identifying the burden of LTBI is essential for effective prevention. This study aimed to estimate the prevalence of LTBI among HCWs in a tertiary care hospital in Mexico and to explore associated risk factors. Methods: An analytical cross-sectional study was conducted among 300 HCWs (including physicians, nurses, and stretcher-bearers) at a tertiary-level hospital in Mexico. Sociodemographic and occupational data were collected through a structured questionnaire. LTBI screening was performed using the tuberculin skin test (TST), with positive results confirmed via the QuantiFERON-TB Gold assay. Associations between relevant variables and LTBI were assessed using logistic regression models, adjusted for potential confounders. Results: The prevalence of LTBI was 16.7%. After adjusting for confounders, male HCWs had significantly higher odds of LTBI compared to females (adjusted odds ratio [aOR] = 2.02; 95% confidence interval [CI]: 1.06–3.80). Although elevated odds of LTBI were also observed among physicians, stretcher-bearers, and those with direct contact with TB patients, these associations were not statistically significant. Conclusion: LTBI represents a relevant occupational health issue among HCWs, with nearly one in six workers affected. Early detection and prevention of TB in healthcare settings are critical to protecting individual workers and public health. These findings highlight the need to strengthen occupational TB surveillance and prevention strategies in similar healthcare environments. Full article

Healthcare workers (HCWs) face an increased risk of tuberculosis (TB) due to occupational exposure. This study aimed to estimate the point prevalence of TB infection (TBI) from the initial test performed, while the reversion and conversion were done by subsequent testing at one year among HCWs in Puducherry, India. A prospective cohort study was conducted among a sample of proportionately chosen HCWs based on their occupational strata of a tertiary hospital in 2022. TBI was assessed using IGRA (4th generation QuantiFeron—TB gold plus kits) after TB symptom screening. The IGRA test was repeated at the end of one year. Reversion was defined as a positive IGRA test at the baseline and had values < 0.2 IU/L in TB1 or TB2 tubes during follow-up. Conversion was defined as a negative IGRA result at the baseline and had values of >0.7 IU/L in TB1 or TB2 tubes during follow-up. Of the 400 HCWs included, the mean (SD) age was 37 (7) years. Median (IQR) work experience was 15.7 (10–21) years. TBI was seen in 150 HCWs (37.7%, 95% CI: 33.0–42.7), and one had active TB. A total of 128/150 HCWs with TBI at baseline were followed up, and 15 had TBI reversion (11.7 per 100 person-years; 95% CI: 6.7–18.5). Thirteen HCWs (5.6 per 100 person-years; 95% CI: 3.3–9.8) had TBI conversion. Full article

Background/Objectives: Classic Hodgkin lymphoma (cHL) is a predominantly curable B-cell malignancy. However, primary refractory and relapsed (R/R) cHL remain therapeutic challenges, especially in regions with high tuberculosis (TB) prevalence, where clinical and radiologic features overlap and can obscure the correct diagnosis. This article, presenting a case of R/R cHL mimicking disseminated TB, reviews the evolving paradigm in R/R cHL management. Methods: A 30-year-old Middle Eastern male with advanced nodular sclerosis cHL initially achieved a complete remission (CR) with escalated BEACOPP chemotherapy. Shortly afterward, he developed respiratory symptoms and diffuse miliary pulmonary nodules, highly suggestive of disseminated TB. Despite extensive negative TB workup, including QuantiFERON-TB Gold testing, sputum acid-fast bacilli (AFB) staining, and PCR, his imaging raised concern for recurrent cHL. Due to the small size and diffuse distribution of nodules, biopsy was unfeasible, prompting empiric salvage therapy with DEHAP-Carbo, brentuximab vedotin (BV), and nivolumab. Results: The rapid and robust metabolic response on PET/CT supported lymphoma relapse rather than TB. Following four cycles of this combined regimen, he proceeded to autologous stem cell transplantation and achieved a second CR. Conclusions: This case highlights the diagnostic difficulties in differentiating cHL relapse from TB in endemic regions, emphasizes the critical role of PET/CT in guiding therapy when histopathological confirmation is impractical, and illustrates the impact of novel immunotherapies in improving outcomes. By underscoring the importance of early diagnostic suspicion and multimodal assessment, this article also reviews the evolving paradigm in R/R cHL management, where personalized approaches and targeted agents increasingly complement or replace traditional chemotherapy regimens. Full article

Background/Objectives: HIV and Mycobacterium tuberculosis (M.tb) co-infection presents a major global health burden. The immune response to M.tb is largely orchestrated by cluster of differentiation 4-positive (CD4⁺) T cells, with CD8⁺ T cells playing an auxiliary role. This study aims to investigate the immunometabolic response of CD4⁺ and CD8⁺ T cells to M.tb antigens, analysed using metabolomics, to elucidate metabolic shifts that may influence immune function in an HIV+ environment. Methods: Whole blood samples from newly diagnosed, treatment-naïve HIV+ individuals were stimulated with M.tb antigens early secreted antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10) using the QuantiFERON^® (QFT) Gold Plus assay. Following incubation, plasma samples were analysed through untargeted nuclear magnetic resonance (1^H-NMR) spectroscopy. Metabolomic data were processed using MetaboAnalyst, with differential metabolites identified through multivariate statistical analyses. Results: Metabolic profiling of PBMCs revealed distinct differences in response to M.tb antigens between CD4⁺ and CD4⁺/CD8⁺ T-cell activation. CD4⁺ T cells exhibited enhanced glycolysis, with elevated levels of metabolites that are linked largely to the Warburg effect. Additionally, vitamin D levels were found to correlate with certain metabolites, suggesting a role in modulating immune responses. Conclusions: These findings suggest a complex interplay between immune cell metabolism and activation in HIV+ individuals. The study demonstrates that HIV and M.tb co-infection significantly influences the broader metabolic profile of peripheral blood mononuclear cells (PBMCs), highlighting the altered metabolic pathways that are critical in immune responses and disease progression. These findings contribute to the understanding of immunometabolism in co-infection and emphasise the need for further research into targeted metabolic interventions. Full article

The cutoff value of the commercial interferon (IFN)-γ release assay (QuantiFERON-CMV) proposed by the manufacturer is assumed to be predictive. We aimed to determine the optimal cutoff value for protection against clinically significant cytomegalovirus (CMV) infection within 30 days. We analyzed two different cohorts: adult CMV seropositive kidney transplant (KT) recipients with antithymocyte globulin (ATG) induction from the TIMOVAL study and seropositive lung transplant (LT) patients from the CYTOCOR study. The optimal cutoff value was established using Youden’s index. We estimated the predictive capacity of the cutoff value through the AUROC and assessed the diagnostic accuracy of the assay at the different cutoff values. We finally evaluated clinical variables that could improve the predictive ability of the assay on a predictive score. Four hundred-four samples from 130 transplant recipients were analyzed. The optimal cutoff value was ≥2.2 IU/mL for both populations, with a positive predictive value of 99% and 99.5% (95% CI, 98–100%) for KT and LT recipients, respectively. The AUROC of the predictive score was 0.85 (95% CI, 0.73–0.97). Using the proposed cutoff value and the Quanti-CMV score may allow the individualization of preventive strategies and serve as an objective tool to support clinical decision-making. Full article

Latent tuberculosis infection (LTBI) remains a significant global health concern, particularly in regions with high tuberculosis (TB) prevalence, such as South Africa. This pilot study aimed to evaluate the prevalence of LTBI and assess patient knowledge about the condition in a primary healthcare clinic in rural Eastern Cape, South Africa. A cross-sectional design was used, and convenience sampling recruited outpatients aged 18 years and older with no prior history of TB. Blood samples were analyzed using the QuantiFERON-TB Gold assay to determine LTBI status, and a survey assessed patient knowledge of LTBI. Strong positive correlations were observed between what patients understand by the term LTBI and how LTBI differs from TB (0.70), what patients understand by the term LTBI and the risk factors for developing LTBI (0.70), how LTBI differs from TB and the risk factors for developing LTBI (0.78), and how LTBI differs from TB and the recommended treatments for LTBI (0.79), indicating overlap in understanding. In contrast, there were negative correlations between if patients had ever heard of latent LTBI before and their understanding of the term LTBI (−0.25), the risk factors for developing LTBI (−0.22), LTBI progressing to active TB (−0.27), and the recommended treatments for LTBI (−0.27). This divergence points to different dimensions of patient knowledge and awareness. Age, gender, occupation, comorbidities, and HIV status showed varying LTBI positivity trends. Among younger patients aged 20–29, 15.4% tested positive, while the 30–39 group showed a nearly equal split between positive (48.1%) and negative cases. A higher positivity rate was seen in females (39.1%) compared to males (31.6%). Unemployed individuals had higher positivity rates, suggesting socioeconomic factors’ influence. Comorbidities, especially hypertension, diabetes, and asthma, correlated with higher LTBI positivity among females, but this was less evident in males. HIV-positive patients had a higher LTBI-negative rate compared to HIV-negative patients. A logistic regression model (accuracy 70%) identified demographic and health factors predicting LTBI outcomes, with comorbidities, particularly hypertension and diabetes, significantly increasing the likelihood of LTBI positivity. These findings suggest that demographic and health factors, including age, gender, occupation, comorbidities, and HIV status, may predict LTBI positivity. Full article

Background: Lung transplantation is a life-saving option for patients with end-stage respiratory diseases, but risk of infections remains critical for ensuring long-term organ function. This study aimed to assess immune recovery in lung transplant recipients by measuring IFN-γ levels using the QuantiFERON Monitor Test (QFM). Results were correlated with episodes of infection and organ rejection to explore the assay’s predictive potential. Methods: A retrospective study was conducted on 15 lung transplant recipients at the Lung Transplant Centre of Turin (Città della Salute e della Scienza di Torino, Italy) between December 2019 and January 2023. Patients were divided into a High Infection (HI) group (with >3 infections) and Low Infection (LI) group (with ≤3 infections). QFM assays were performed after 18 months post-transplant. Results: HI patients had lower QFM levels compared to LI (68.84 ± 21.98 vs. 380.54 ± 104.64 UI/mL, p = 0.033). A QFM value <89.5 UI/mL was associated with increased infection risk (p < 0.05). Patients with lower QFM levels also exhibited higher rates of MRSA bacteremia during hospitalization (50% HI vs. 0% LI, p = 0.04). No differences were observed in acute or chronic rejection rates, but LI patients showed more frequent alveolar neutrophilia at the fourth month post-transplant (0% HI vs. 55.5% LI, p = 0.04). Conclusion: lower QFM values were associated with higher infection risk, highlighting the assay’s potential for immune monitoring. In this study, a QFM value of 89.5 UI/mL showed good predictive accuracy for infections beyond 18 months. Further studies are needed to refine QFM’s role in post-transplant care. Full article

Human T-cell leukemia virus type 1 (HTLV-1) is associated with an increased risk of tuberculosis (TB). This study aimed to evaluate the performance of the QuantiFERON-TB Gold (QFT) test for the diagnosis of Mycobacterium tuberculosis (MTB) infection in HTLV-1-infected individuals. HTLV-1-infected participants were divided into four groups: HTLV-1-infected individuals with a history of tuberculosis (HTLV/TB), individuals with positive HTLV and tuberculin skin tests (HTLV/TST+) or negative TST (HTLV/TST−), and HTLV-1-negative individuals with positive TST results (HN/TST+). We compared the diagnostic performance of the QFT assay with that of the TST as a reference and evaluated test sensitivity, specificity, accuracy, likelihood ratio, and diagnostic odds ratio. The results showed a higher frequency of positive TST results and induration diameter ≥10 mm in HTLV-1-infected individuals than in the controls. The QFT test was more frequently positive in the HTLV/TB group than in the other groups, while a combined analysis of HTLV/TB and HTLV/TST+ indicated a QFT sensitivity of 57.5%. No significant differences were found in the other diagnostic performance measures, as QFT test results were in agreement with TST results, particularly in TST-negative individuals. Given the low sensitivity of QFT for LTBI in individuals infected with HTLV-1, the TST may be preferable in regions where both infections are endemic. Full article

Background: Cellular and humoral immunity are key to the immune response against SARS-CoV-2, but the comparability and correlation across different assays remain underexplored. This study compares three T-cell and three antibody assays in two vaccine groups. Methods: This prospective longitudinal cohort study involved 46 naïve healthcare workers: a total of 11 in the homologous mRNA-1273 group (three doses) and 35 in the heterologous ChAd group (two ChAd doses followed by a BNT booster). Blood samples were collected at five time points. Cellular immunity was assessed using ELISPOT and two commercial interferon-gamma release assays: (IGRA)-QuantiFERON SARS-CoV-2 (QF) and Covi-FERON ELISA (CoVF). Humoral immunity was evaluated using total and IgG antibody assays and a surrogate virus neutralization test. Results: The mRNA-1273 group exhibited stronger and more consistent responses than the ChAd group. The correlations between ELISPOT and IGRA varied from weak to moderate (ρ = 0.300–0.410), while QF-IGRA and CoVF-IGRA showed stronger correlations (ρ = 0.700–0.737). The ELISPOT assay showed substantial agreement with QF [Ag2]-IGRA (k = 0.697–0.774) and CoVF [O-sp]-IGRA (k = 0.641–0.718), and an 80.4% agreement rate (k = 0.608) was found between the QF [Ag2]- and CoVF [O-sp]-IGRA tests. Three antibody assays demonstrated very strong correlations with each other and substantial to near-perfect agreement with ELISPOT (k = 0.866–0.949), QF [Ag2]-IGRA (k = 0.807–0.831), and CoVF [O-sp]-IGRA (k = 0.753–0.777). Conclusions: SARS-CoV-2-specific cellular and antibody responses vary by platform and vaccine type, highlighting the importance of measuring both T-cell and B-cell responses using multiple assays to comprehensively assess immune status. Full article

The QuantiFERON CMV (QCMV) test evaluates specific adaptive immune system activity against CMV by measuring IFN-γ released by activated CD8+ T lymphocytes. We aimed to evaluate the QCMV test as a predictive tool for CMV manifestations and acute or chronic lung allograft rejection (AR and CLAD) in lung transplant (LTx) patients. A total of 73 patients were divided into four groups based on donor and recipient (D/R) serology for CMV and QCMV assay: group A low-risk for CMV infection and disease (D−/R−); group B and C at intermediate-risk (R+), group B with non-reactive QCMV and group C with reactive QCMV; group D at high-risk (D+/R−). Group D patients experienced higher viral replication; no differences were observed among R+ patients of groups B and C. D+/R− patients had a higher number of AR events and group C presented a lower incidence of AR. Prevalence of CLAD at 24 months was higher in group B with a higher risk of CLAD development (OR 6.33). The QCMV test allows us to identify R+ non-reactive QCMV population as the most exposed to onset of CLAD. This population had a higher, although non-significant, susceptibility to AR compared to the R+ population with reactive QCMV. Full article

Actinomycosis, an uncommon granulomatous infection caused by the Actinomyces species, rarely targets as primary involvement the limb and is often linked to traumatic incidents. In this report, we present the case of a 44-year-old female who developed multiple small nodules on her left foot over approximately 12 months. Some nodules exhibited firmness and a violet hue, while others discharged a yellowish fluid. The patient had no significant comorbidities. Despite thorough blood paraclinical assessments, including complete blood count, serological HIV testing, and QuantiFERON-TB Gold testing, no abnormalities were detected. Bacteriological examinations and cultures of the discharge yielded negative results. Dermatoscopic examination revealed ovoid yellowish structures, with confocal microscopy highlighting granulomas. A subsequent skin biopsy confirmed characteristic changes indicative of actinomycosis. Although systemic antibiotic therapy with penicillin derivatives was initially considered, the patient’s documented allergic history to this medication class, verified through allergological testing, prompted the initiation of doxycycline treatment. Notably, significant improvement was observed at the 3-month follow-up. This case underscores the importance of reporting rare instances of actinomycosis due to its diagnostic complexity and management challenges. Full article

Background: The coexistence of HIV infection and latent tuberculosis infection (LTBI) presents a significant public health concern due to the increased risk of tuberculosis (TB) reactivation and progression to active disease. The multicenter observational cohort study, TUBHIVIT, conducted in Italy from 2017 to 2023, aimed to assess the prevalence of LTBI among people living with HIV (PLHIV) and their outcomes following LTBI screening and therapy initiation. Methods: We performed a prospective study in five referral centers for HIV care in Italy. PLHIV who consented Tto participate underwent QuantiFERON-TB Gold Plus and clinical, microbiological, and radiological assessments to exclude subclinical tuberculosis, as opportune. PLHIV diagnosed with LTBI who started chemoprophylaxis were followed until the end of therapy. Results: A total of 1105 PLHIV were screened for LTBI using the QuantiFERON-TB Gold Plus test, revealing a prevalence of 3.4% of positive results (38/1105). Non-Italy-born individuals exhibited a significantly higher likelihood of testing positive. Thirty-one were diagnosed with LTBI, 1 showed active subclinical TB, and 6 were lost to follow-up before discriminating between latent and active TB. Among the PLHIV diagnosed with LTBI, 83.9% (26/31) started chemoprophylaxis. Most individuals received 6–9 months of isoniazid-based therapy. Of the 26 PLHIV commencing chemoprophylaxis, 18 (69.2%) completed the therapy, while 3 discontinued it and 5 were still on treatment at the time of the analysis. Adverse events were observed in two cases, while in one case the patient refused to continue the treatment. Full article