QuantiFERON-TB reversion in children and adolescents with tuberculosis.

We analyzed 136 children with tuberculosis disease or infection and a positive QuantiFERON-TB (QFT) assay, followed-up for a median of 21 months (0.4-11years). QFT reversed in 16.9% of cases, with significant decreases in TB1 (-1.72 vs. -0.03 IU/ml, p=0.001) and TB2 (-1.65 vs. -0.43 IU/ml, p=0.005) levels compared to non-reverters. We found a higher QFT reversion rate among children under 5 years (25.0% vs 11.9%, p=0.042), and those with TST induration <15mm (29% vs 13.3%, p=0.055). Our data reveal that, although QFT test remained positive in the majority of children, reversion occurred in 16% of cases in a progressive and stable pattern. Younger age and reduced TST induration were associated with QFT reversion.

QuantiFERON-CMV assay by chemiluminescence immunoassay: Is it more suitable for real-live monitoring of transplant patients?

BACKGROUND: The QuantiFERONCMV (QF-CMV) assay is an interferon-gamma release assay (IGRA) used to monitor CMV-specific cell-mediated immunity (CMV-CMI) by ELISA in transplant patients. However, a chemiluminescent immunoassay (CLIA) has been developed to quantify IFNG in the QuantiFERON-Tuberculosis (TB) to detect latent TB infection. OBJECTIVES: The aim of this work is to compare the results of QF-CMV by ELISA with those obtained by CLIA in an automated Liaison XL analyzer using the QuantiFERON-TB Gold Plus reagents. STUDY DESIGN: The QF-CMV assay had been performed by ELISA in kidney and lung transplant patients between July 2019-April 2023 at the IMIBIC/Reina Sofía Hospital (Cordoba, Spain). The remaining QF-CMV supernatants had been preserved at -80 ºC from then. Now, the IFNG levels in the same samples were determined by CLIA. RESULTS: One hundred and three QF-CMV supernatants from kidney (n = 50) and lung (n = 53) transplant patients were selected. An agreement of 87.4 % (kappa coefficient 0.788) between CLIA and ELISA was observed. Thirteen (12.6 %) discrepant results were detected. Some Indeterminate results by ELISA converted to Non-reactive by CLIA (0.53-0.92 IU/mL for Mitogen-Nil values). Likewise, borderline Non-reactive results by ELISA were above the 0.2 IU/mL cut-off by CLIA and then were Reactive (0.21-0.31 for CMV-Nil values). CONCLUSION: CLIA shows substantial concordance with ELISA and acceptable discrepancies. The possible higher sensitivity of CLIA returns a higher number of Reactive results, which entails potential clinical consequences. Therefore, a new threshold to confer protection against CMV infection after transplantation needs to be defined.

No seroconversion in a retrospective study analyzing QuantiFERON TB-gold testing in pediatric psoriasis and hidradenitis suppurativa patients taking biologic therapy at an academic center in New York City.

Guidelines are inconsistent regarding annual QuantiFERON® TB Gold (QFT) tests in children taking biologics for dermatological conditions, and there is limited research on seroconversion, especially in regions with high tuberculosis (TB) prevalence. A retrospective review of pediatric patients taking biologic treatment for psoriasis or hidradenitis suppurativa (HS) who had one baseline and at least one follow-up QFT test was conducted to assess for seroconversion during treatment. Thirty-two patients were included, with no instances of seroconversion. These findings suggest that routine annual TB rescreening for pediatric patients taking biologic therapy for dermatologic conditions may not be necessary without additional TB exposure risks or symptomatology.

Interferon-gamma release assay conversion after Mycobacterium tuberculosis exposure specifically associates with greater risk of progression to tuberculosis: A prospective cohort study in Leicester, UK.

OBJECTIVES: We investigated whether quantifying the serial QuantiFERON-TB Gold (QFT) response improves tuberculosis (TB) risk stratification in pulmonary TB (PTB) contacts. METHODS: A total of 297 untreated adult household PTB contacts, QFT tested at baseline and 3 months after index notification, were prospectively observed (median 1460 days). Normal variance of serial QFT responses was established in 46 extrapulmonary TB contacts. This informed categorisation of the response in QFT-positive PTB contacts as converters, persistently QFT-positive with significant increase (PPincrease), and without significant increase (PPno-increase). RESULTS: In total, eight co-prevalent TB (disease ≤3 months after index notification) and 12 incident TB (>3 months after index notification) cases were diagnosed. Genetic linkage to the index strain was confirmed in all culture-positive progressors. The cumulative 2-year incident TB risk in QFT-positive contacts was 8.4% (95% confidence interval, 3.0-13.6%); stratifying by serial QFT response, significantly higher risk was observed in QFT converters (28%), compared with PPno-increase (4.8%) and PPincrease (3.7%). Converters were characterised by exposure to index cases with a shorter interval from symptom onset to diagnosis (median reduction 50.0 days, P = 0.013). CONCLUSIONS: QFT conversion, rather than quantitative changes of a persistently positive serial QFT response, is associated with greater TB risk and exposure to rapidly progressive TB.

Cost-Effectiveness Analysis Comparing QuantiFERON-TB Gold Plus Test and Tuberculin Skin Test for the Diagnosis of Latent Tuberculosis Infection in Immunocompetent Subjects in Colombia.

OBJECTIVES: To determine the cost-effectiveness of the QuantiFERON-TB Gold Plus (QFT-Plus) test versus the tuberculin skin test in diagnosing latent tuberculosis infection in immunocompetent subjects in the context of the Colombian healthcare system. METHODS: A hypothetical cohort of 2000 immunocompetent adults vaccinated with Bacillus Calmette-Guérin at birth who are asymptomatic for tuberculosis disease was simulated and included in a decision tree over a horizon of <1 year. The direct healthcare costs related to tests, antituberculosis treatment, and medical care were considered, and diagnostic performance was used as a measure of effectiveness. The incremental cost-effectiveness ratio (ICER) was estimated, and univariate deterministic and probabilistic sensitivity analyses were carried out using 5000 simulations. The currency was the US dollar for the year 2022, with a cost-effectiveness threshold of $6666 USD (1 gross domestic product per capita for 2022). RESULTS: QFT-Plus was cost-effective with an ICER of $5687 USD for each correctly diagnosed case relative to a threshold of $6666 USD. In the deterministic analysis, QFT-Plus was cost-effective in half of the proposed scenarios. The variable that most affected the ICER was the prevalence of latent tuberculosis and test sensitivities. In the probabilistic analysis, QFT-Plus was cost-effective in 54.74% of the simulated scenarios, and tuberculin skin test was dominant in 13.84%. CONCLUSIONS: The study provides evidence of the cost-effectiveness of QFT-Plus compared with the tuberculin skin test in diagnosing latent tuberculosis infection in immunocompetent adults in the Colombian context.

Tuberculin test using Indian indigenous purified-protein derivative (PPD) shows only moderate agreement with international standard PPD.

Background: In India, the prevalence of Latent TB infection (LTBI) is estimated to be around 40%. Various formulations of PPD(Purified protein derivative) are available, for diagnosis of LTBI, which may give variable responses. The commercially available PPD in India is by Arkray Healthcare (TST-Arkray). It is unclear if this product may have a similar sensitivity compared to other internationally accepted tuberculins (TST-Tubersol). Objectives: To assess the performance of the two TSTs compared to Quantiferon-Gold Plus (QFT-Plus). Methodology: A blood sample was collected for the QFT-Plus test. Both the TSTs were placed in the right and the left volar aspect of the forearms and 48 hrs later, the subjects came back to the study site for reading. Results: Among the 512 participants who were recruited, 326 subjects were healthcare professionals and 186 subjects were household contacts of patients with tuberculosis. They were tested with both TST-Tubersol and TST-Arkray, 139(27 %) participants tested positive for TST-Tubersol (≥10 mm), whereas 203 participants (40.1 %)tested positive for TST-Arkray. There was moderate agreement between the two tests with k = 0.58. Also, there was only poor agreement between both the TSTs with QFT Plus(kappa = 0.19 for Tubersol and 0.17 for Arkray). With QFT-Plus as gold standard, the sensitivity, specificity, PPV and NPV of TST-Tubersol, ast an induration cut-off of 10 mm was 46.8 %,76.3 %,31.8 % and 85.8 %. respectively and TST- Arkray; 60.6 %, 64 %, 28.5 % and 87.2 % respectively. Conclusion: The Indian TST (Arkray Diagnostics) has shown moderate agreement with the internationally accepted Tubersol. Additionally, there was poor agreement between the TSTs and QFT plus test.

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

BACKGROUND: Latent 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. METHODS: We 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. RESULTS: Among 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. CONCLUSION: The 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.

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

Background and Aims: 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. Methods: 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. Results: 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 eight studies 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. Conclusion: Indeterminate QFT-TB results in COVID-19 patients occur in almost one-quarter of tests performed. Further studies are needed to assess associated factors.

Latent Tuberculosis Infection and COVID-19: Analysis of a Cohort of Patients from Careggi University Hospital (Florence, Italy).

Data regarding the relationship between coronavirus disease (COVID-19) and active or latent tuberculosis (TB) are discordant. We conducted a retrospective study examining the impact of latent tuberculosis infection (LTBI) on the clinical progression of COVID-19 patients. We selected 213 patients admitted with COVID-19 in a tertiary-level Italian hospital (February-December 2020), who underwent a QuantiFERON-TB test (QFT) and/or chest radiological exam. The population was divided into three groups: (i) QFT negative and without radiological TB sequelae (Neg); (ii) QFT positive and without radiological TB sequelae (Pos); (iii) radiological TB sequelae regardless of QFT result (Seq). In-hospital mortality and oro-tracheal intubation (OTI) showed significantly higher results in the Seq group (Seq 50% vs. Pos 13.3% vs. Neg 9.3%, p < 0.001; Seq 16.7% vs. Pos 6.7% vs. Neg 4.9%, p = 0.045). Considering the Pos and Seq groups' patients as the population with defined LTBI, in-hospital mortality (20/51, 39.2%) and OTI risk (7/51, 13.7%) were statistically higher with respect to patients without LTBI (in-hospital mortality: 15/162, 9.3%, p < 0.001; OTI risk: 8/162, 4.9%, p = 0.023), respectively. Multivariate analysis showed that radiological sequelae and the Charlson Comorbidity Index (CCI) were significantly associated with higher mortality rate; despite the higher CCI of Seq population, we cannot exclude the correlation between COVID-19 in-hospital mortality and the presence of radiological TB sequelae.

Outcomes and Challenges in the Programmatic Implementation of Tuberculosis Preventive Therapy among Household Contacts of Pulmonary TB Patients: A Mixed-Methods Study from a Rural District of Karnataka, India.

The National TB Elimination Programme (NTEP) of India is implementing tuberculosis preventive treatment (TPT) for all household contacts (HHCs) of pulmonary tuberculosis patients (index patients) aged <5 years and those HHCs aged >5 years with TB infection (TBI). We conducted an explanatory mixed-methods study among index patients registered in the Kolar district, Karnataka during April-December 2022, to assess the TPT cascade and explore the early implementation challenges for TPT provision. Of the 301 index patients, contact tracing home visits were made in 247 (82.1%) instances; a major challenge was index patients' resistance to home visits fearing stigma, especially among those receiving care from the private sector. Of the 838 HHCs, 765 (91.3%) were screened for TB; the challenges included a lack of clarity on HHC definition and the non-availability of HHCs during house visits. Only 400 (57.8%) of the 692 eligible HHCs underwent an IGRA test for TBI; the challenges included a shortage of IGRA testing logistics and the perceived low risk among HHCs. As HHCs were unaware of their IGRA results, a number of HHCs actually eligible for TPT could not be determined. Among the 83 HHCs advised of the TPT, 81 (98%) initiated treatment, of whom 63 (77%) completed treatment. Though TPT initiation and completion rates are appreciable, the NTEP needs to urgently address the challenges in contact identification and IGRA testing.

QuantiFERON-CMV and monitor predict cytomegalovirus, mortality, and graft-versus-host disease in transplant recipients.

Cytomegalovirus (CMV) is the most prevalent infection in recipients of hematopoietic stem cell transplant (HSCT). QuantiFERON-CMV (QF-CMV) and QuantiFERON-Monitor (QFM) assays were used to test whether immune-competent adult allogeneic HSCT recipients with CMV-specific T cells can control CMV infection or reactivation. Our data demonstrated a significant correlation between CMV infection measured by CMV-antigenemia test and QF-CMV results, graft versus host disease (GvHD), and mortality rates. The QF-CMV test revealed that CMV-specific T cells with higher interferon-γ (IFN-γ) release were correlated with lower CMV infection rates. There was a significant negative association between QF-CMV results, GvHD, and mortality rates. Data showed that a one-unit rise in IFN-γ was linked with a 12.7% reduction in GvHD and a 20.7% reduction in the mortality odds ratio. In addition, a negative correlation was found between QF-M results and CMV infection, with the QFM test predicting protection against CMV infection by 1.9%. This is one of the few studies establishing the QF-CMV test's predictive value for GvHD and mortality, its use to monitor HSCT patients for pre-emptive therapy, and the use of the QFM test to predict CMV infection and mortality in HSCT patients. Thus, these assays could be utilized to optimize preventive and pre-emptive therapy procedures to reduce transplant recipient adverse effects and posttransplant therapy costs.

Latent tuberculosis in children and youth with type 1 diabetes mellitus in Dar es Salaam, Tanzania: a cross section survey.

BACKGROUND: Data for latent tuberculosis in patients with type 1 Diabetes in Africa is limited. We assessed the prevalence of latent tuberculosis in youth and children with type 1 Diabetes in Dar es Salaam -Tanzania. METHODS: Our cross-sectional study recruited children and youth with T1DM by stage of puberty, glycaemic control, and age at diagnosis from January to December 2021 in Dar es Salaam. Participants were screened for the presence of latent Tuberculosis using the QuantiFERON test. A positive test was considered to have latent TB. RESULTS: Of the 281 participants, the mean age was 19 (± 6) years, 51.2% were female, and 80.8% had either a primary or secondary level of education at baseline. The prevalence of latent TB was 14.9% and was slightly higher in females (52.4%) than in males. This difference, however, was insignificant (p > 0.05). On the other hand, the proportion of latent TB was significantly higher in uncontrolled HbA1c levels (76.2%) than in those with controlled HbA1c (23.8%) [p = 0.046]. Duration of diabetes and age at diagnosis did not affect the occurrence of latent Tuberculosis [p > 0.05]. Meanwhile, in the regression model, participants with latent TB were more likely to have uncontrolled HbA1c. [p = 0.045] CONCLUSIONS: Despite the methodological limitations, this survey highlights the high prevalence of latent TB among children and youth with diabetes; shouting for better control. These results clearly show the need to screen for Tuberculosis in children and youth with diabetes and start them on prevention as per protocol, especially in tuberculosis-endemic areas like Tanzania.

Xpert MTB/RIF assay for the differential diagnosis between sarcoidosis and tuberculosis intrathoracic lymphadenopathy.

BACKGROUND: The aim of this study was to evaluate the role of Xpert MTB/RIF assay in the detection of Mycobacterium tuberculosis for differentiating tuberculosis intrathoracic lymphadenopathy from sarcoidosis intrathoracic lymphadenopathy. METHODS: The patients who were suspected to having sarcoidosis or tuberculosis intrathoracic lymphadenopathy at the Shanghai Pulmonary Hospital between October 1, 2020 and June 30, 2021 were retrospectively evaluated in this study. All patients underwent endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and Xpert analysis. Differences in clinical and radiological features were recorded. The diagnostic performances of EBUS-TBNA Xpert, acid-fast bacilli, culture, and peripheral blood QuantiFERON-TB Gold (QFT) for differentiating sarcoidosis from tuberculosis intrathoracic lymphadenopathy were analyzed. RESULTS: A total of 119 patients were included in this analysis. Of those, 83 patients were finally diagnosed with sarcoidosis (N = 50) and tuberculosis (N = 33) intrathoracic lymphadenopathy. Young individuals were more likely to have tuberculosis versus sarcoidosis intrathoracic lymphadenopathy (P = 0.006). Markers of inflammation, including fever, leukocytes, and serum ferritin levels, were significantly higher in tuberculosis versus sarcoidosis intrathoracic lymphadenopathy (P < 0.01). Bilateral lung involvement and symmetry intrathoracic lymphadenopathy were more common in sarcoidosis intrathoracic lymphadenopathy (P < 0.01). In addition, the longest diameter of intrathoracic lymphadenopathy (in cm) was significantly larger in sarcoidosis intrathoracic lymphadenopathy (P = 0.001). However, the largest diameter of lung lesions was significantly shorter (P = 0.005). The sensitivity and specificity values of Xpert and QFT for differentiating these two diseases were 69.70% and 100%, and 96.43% and 91.84%, respectively. CONCLUSION: Xpert MTB/RIF is recommended for the diagnosis of tuberculosis intrathoracic lymphadenopathy using EBUS-TBNA samples. A negative QFT suggests the exclusion of the diagnosis of tuberculosis intrathoracic lymphadenopathy.

Accuracy of QuantiFERON in active tuberculosis suspects with comorbidities and nontuberculous mycobacterial infection in Northern California.

The QuantiFERON-TB Gold (QFT) is routinely utilized in North American health systems to detect a cellular immune response to Mycobacterium tuberculosis antigens in symptomatic and asymptomatic patients. The sensitivity of QFT in tuberculosis (TB) patients with comorbidities is not well established and the specificity of QFT in patients with nontuberculous mycobacteria (NTM) infections is incompletely understood. Between 2012 and 2023, all patients with culture-positive TB and patients with NTM infection per the expert diagnostic guidelines or biopsy-proven NTM infection who had a concurrent QFT test were included in this study. The sensitivity and specificity of QFT were measured in TB and NTM patients, respectively. In 109 patients with active TB, the overall sensitivity of QFT was 78.0% (85/109; 95% CI: 70.1, 85.7). The sensitivity was 86.0% (49/57; 95% CI: 76.6, 94.8) and 69.2% (36/52; 95% CI: 56.7, 81.8) in immunocompetent and immunocompromised patients, respectively. The overall specificity of QFT in 88 patients with NTM infection was 76.1% (67/88; 95% CI: 67.2, 85.0). After the exclusion of 17 NTM patients with risk factors for latent TB infection, the specificity was 94.4% (67/71; 95% CI: 89.1, 99.7). Two patients had NTM species known to cross-react with QFT. In two NTM patients infected with species (Mycobacterium intracellulare subsp. intracellulare and Mycobacterium intracellulare subsp. chimaera) not known to cross-react, whole genome sequencing did not detect ESAT-6 or CFP-10. In Northern California, the QFT assay demonstrated moderately low to moderately high sensitivity in TB patients and very high specificity in NTM patients, thus ruling out concerns for cross-reactivity with NTM.

Comparison of the Standard E TB-Feron ELISA and QuantiFERON-TB Gold PLUS assays: the advantageous use of whole recombinant protein antigens for latent tuberculosis diagnosis.

The laboratory diagnosis of latent tuberculosis is often performed using interferon-gamma release assays. Here, we compared two enzyme-linked immunosorbent assay-based interferon-gamma release assays, namely, the newly developed Standard E TB-Feron enzyme-linked immunosorbent assay (STFE) and the QuantiFERON-TB Gold PLUS assay (QFT-GP), using samples from 155 participants. The STFE is based on using whole EAST6 and CFP10 recombinant antigens for latent tuberculosis diagnosis. The participants were classified into four groups and screened using both assays per the manufacturers' instructions. Thereafter, two statistical analyses were conducted to compare the obtained results. First, the STFE results were compared with the QTF-GP results (used as the gold standard) to calculate the total concordance, sensitivity, and specificity of STFE. Second, positivity and negativity concordances were calculated to differentiate healthy participants from participants with tuberculosis. The STFE showed 97% and 94% sensitivity and specificity, respectively. Furthermore, its positivity and negativity concordances were 91% and 98%, respectively. These results indicate the coordinated clinical performance of STFE in detecting latent tuberculosis and its improved performance in targeting tuberculosis-infected participants. Based on the comparison of the latent tuberculosis diagnostic abilities of STFE and QFT-GP, we establish the suitability and superior performance of STFE as a diagnostic tool.

Comparison of CD4+/CD8+ Lymphocytic Subpopulations Pre- and Post-Antituberculosis Treatment in Patients with Diabetes and Tuberculosis.

Is there a CD4+ and CD8+ immunity alteration in patients with pulmonary tuberculosis (TB) and diabetes (DM) that does not recover after antituberculosis treatment? This prospective comparative study evaluated CD4+ and CD8+ lymphocytic subpopulations and antituberculosis antibodies in patients with diabetes and tuberculosis (TB-DM), before and after antituberculosis treatment. CD4+ T cell counts were lower in patients with TB-DM compared to those with only TB or only DM, and these levels remained low even after two months of anti-TB treatment. Regarding the CD8+ T cell analysis, we identified higher blood values in the DM-only group, which may be explained by the high prevalence of latent tuberculosis (LTBI) in patients with DM. IgM antituberculosis antibodies levels were elevated in patients with only TB at baseline, and 2 months post-anti-TB treatment, IgG did not express any relevant alterations. Our results suggest an alteration in CD4+ immunity in patients with TB-DM that did not normalize after antituberculosis treatment.

Tuberculosis screening practices and outcomes in an australian dialysis unit.

BACKGROUND: The World Health Organisation (WHO) recommends all dialysis patients undertake routine screening for latent tuberculosis infection (LTBI) in high income countries such as Australia. However, we employ a targeted screening approach in our Australian dialysis unit in line with local and some international guidelines. We analysed our practices to assess the validity of our approach. METHODS: A retrospective review of new dialysis patients during the period 2012-2018 was undertaken. Patient records were reviewed for basic demographic data, comorbidities, LTBI screening using Quantiferon Gold (QFG), and outcomes, including episodes of active TB, to June 2020. RESULTS: 472 patients were included. WHO high risk country of origin patients accounted for 22% (n = 103). 229 patients (48.5%) were screened using QFG. The single main indication for screening was transplantation waitlisting. 34 patients had a positive QFG result. Active tuberculosis developed in two patients during the observation period. Both occurred in the screened cohort, the cases having previously tested negative via QFG at 11 and 16 months, prior to the development of active tuberculosis. No patients in the unscreened cohort developed active tuberculosis during the observation period. WHO high risk country of origin was associated with positive QFG status, odds ratio 10.4 (95% CI 3.3-31.2). CONCLUSION: The data failed to show a benefit from widening of the screening program within our dialysis unit. However, a much larger sample size will be required to confidently assess the impact of the current approach on patient outcomes. Analysis of current screening practices and outcomes across all Australian dialysis services is warranted to assess the risks and benefits of widening the screening practices to include all dialysis patients as recommended by the WHO.

Predicting stringent QuantiFERON-TB Gold Plus conversions in contacts of tuberculosis patients.

OBJECTIVES: To assess associations between disease severity in index TB patients and QuantiFERON-TB Gold Plus (QFT-Plus) results in contacts, and predictors for QFT-Plus conversion in contacts over 6-12 months. METHODS: TB patients (n = 295) and the contacts (n = 1051) were enrolled during 2018-2021 with QFT-Plus performed at baseline and months 6 and 12. A strong CD8 response was defined as TB2 interferon gamma (IFN-γ) response minus TB1 >0.6 IU/ml and stringent conversion as change from QFT-plus negative to high-positive QFT-Plus (TB1 or TB2 IFN-γ responses >0.7 IU/ml). RESULTS: Contacts with index TB patients with sputum smear >1+ was associated with positive QFT-Plus compared to those without (p < 0.001). Contacts with index TB patients with bilateral lung disease were more likely to have strong CD8 responses than those without (p = 0.038). QFT-Plus stringent conversion occurred in 9.7% of contacts over 6-12 months. A TB1 IFN-γ response ≥0.03 IU/ml combined with a TB2 ≥0.06 IU/ml was predictive of a 19-fold increased risk for QFT-Plus stringent conversion in contacts (odd ratio 19.565 [8.484-45.116], p < 0.001). CONCLUSION: Bacterial burden and bilateral lung disease of index TB patients were associated with positive QFT-Plus and strong CD8 responses in contacts. TB1 and TB2 IFN-γ responses were synergistically predictive of stringent conversion in contacts.

Evaluation of the fully automated LIAISON®XL chemiluminescence analyzer for QuantiFERON®-CMV testing in transplant recipients.

BACKGROUND: Monitoring CMV-specific cell-mediated immunity by the QuantiFERON®-CMV (QF-CMV) may be useful in predicting the risk of CMV infection in transplant recipients (TR). OBJECTIVES: As the QuantiFERON-Tuberculosis (QFT®-Plus) became available on the fully automated LIAISON®XL chemiluminescence (CLIA) analyzer, we evaluated the performance of the QF-CMV on the LIAISON®XL analyzer using the QuantiFERON®-TB Gold Plus reagent. STUDY DESIGN: Between 2018 and 2022, 81 samples from TR were collected at the Department of Virology of Limoges Hospital, France. Whole blood was collected into each of the three QF-CMV collection tubes: a CMV-antigen tube (QF-Ag), a mitogen tube (QF-Mg) (positive control), and a nil tube (negative control). The QF-CMV was performed on the LIAISON®XL analyzer, and results were compared with those obtained by conventional microplate ELISA. RESULTS: Intra- and inter-assay coefficients of variation were inferior to 20%. No inter-sample contamination was found (p=0.366). The level of concordance between CLIA and the commonly used ELISA method was 88.9%. Positive and negative percent agreements were 92.3% and 85.7%, respectively, with a very good agreement between assays (κ=0.818). Most discordances were due to indeterminate- or negative-ELISA/positive-CLIA results (most of ELISA results were borderline). Linear regression analyses demonstrated a strong correlation between both assays (QF-Ag Pearson's r=0.978, QF-Mg Pearson's r=0.963). No significant difference was observed in median QF-CMV values between both assays (QF-Ag p=0.776; QF-Mg p=0.853; Mann-Whitney U test). The Bland-Altman plots showed a minor difference in IFN-γ release (QF-Ag -0.069 IU/ml, 95% limits of agreement (LoA): -1.589; 1.451; QF-Mg 0.190 IU/ml, 95% LoA: -2.070; 2.450). CONCLUSION: Automated QF-CMV with CLIA is comparable to QF-CMV performed by ELISA with a presumably higher sensitivity for IFN-γ detection that may result in the conversion of samples close to the ELISA cut-off into positive results. Moreover, the use of a random-access analyzer allows to optimize the follow-up of TR.

Association of Mycobacterium tuberculosis infection test results with risk factors for tuberculosis transmission.

Background: Close contacts infected with Mycobacterium tuberculosis are at high risk of tuberculosis (TB) disease and a priority for preventive treatment. Three tests measure infection: two interferon-gamma release assays (IGRAs) and the tuberculin skin test (TST). The objective of our study was to assess the association of positive test results in contacts with infectiousness of the presumed TB source case. Methods: Contacts in a cohort study at 10 United States sites received both IGRAs (QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB (T-SPOT)) and TST. We defined test conversion as negative for all tests at baseline and positive for at least one on retest. Risk ratios (RR) and 95% confidence intervals (CI) assessed association of positive test results with increased infectiousness of the TB case-defined as acid-fast bacilli (AFB) on sputum microscopy or cavities on chest radiographs- and contact demographics. Results: Adjusted for contacts' age, nativity, sex, and race, IGRAs (QFT-GIT RR = 6.1, 95% CI 1.7-22.2; T-SPOT RR = 9.4, 95% CI 1.1-79.1), but not TST (RR = 1.7, 95% CI 0.8-3.7), were more likely to convert among contacts exposed to persons with cavitary TB disease. Conclusions: Because IGRA conversions in contacts are associated with infectiousness of the TB case, their use may improve efficiency of health department contact investigations by focusing efforts on those likely to benefit from preventive treatment in the United States.