Performance of Current Diagnostic Tools in Detecting Latent Tuberculosis Among Healthcare Workers: A Systematic Review.

Testing for latent tuberculosis infection is essential for diagnosing Mycobacterium tuberculosis infections in asymptomatic individuals. Preventing the transition of latent to active tuberculosis is imperative, especially in high-risk populations such as healthcare workers. Interferon-gamma release assays (IGRAs) and the Mantoux/tuberculin skin test (TST) are two examples of diagnostic instruments utilized for detection. Systematic evaluations of the characteristics of widely available tests are very helpful for diagnosticians because these tests might not be easily accessible in situations with limited resources. This systematic review aims to evaluate and compare the diagnostic accuracy of tests for latent tuberculosis infection in healthcare workers. The review, conducted from 2013 to 2024, aimed to identify studies on "Latent Tuberculosis," "Healthcare workers," "Diagnostic modalities," "TST," "Interferon-gamma release assays," and "IGRA." The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines and developed a data extraction toolkit. Three authors independently reviewed the literature, ensuring uniformity. Discrepancies were resolved through discussions and mediation until a consensus was reached. Statistical significance was defined as a p-value of 0.05 or lower. The review provides valuable insights into the diagnostic accuracy of these tests, particularly in high-risk populations. The TST had a sensitivity of 76.5% (confidence interval (CI) = 61.5-91.5%) and specificity of 77.2% (CI = 65-85%). Its positive predictive value (PPV) was 54.8% (CI = 45-65%), and the negative predictive value (NPV) was 88.5% (CI = 85-92%), with an odds ratio of 63.6 and an area under the curve (AUC) of 0.72. QuantiFERON-TB Gold In-Tube (QFT-GIT) showed a sensitivity of 68.35% (CI = 67.15-70.55%) and a specificity of 82.32% (CI = 72.32-97.47%). Its PPV was 56% (CI = 54-92%), and NPV was 92.7% (CI = 89-96%), with an odds ratio of 357.9 and an AUC of 0.767. QuantiFERON-TB Gold Plus (QFT-Plus) had a sensitivity of 85% (CI = 78.9-91.1%) and a specificity of 73.52% (CI = 35.71-93.75%). Its PPV was 59.2% (CI = 39.3-78.2%), and NPV was 95% (CI = 91.2-98%), with an odds ratio of 125.39 and an AUC of 0.89. T-SPOT.TB showed a sensitivity of 92% (CI = 87-97%) and a specificity of 95.7% (CI = 94-98%). Its PPV was 86.8% (CI = 85-95.8%), and NPV was 95.8% (CI = 92.5-96.7%), with an odds ratio of 1.03 and an AUC of 0.7. CLIA-IGRA had a sensitivity of 100% (CI = 99.9-100%) and a specificity of 95.57% (CI = 95.57-100%). Its PPV was 96.8% (CI = 96.8-100%), and NPV was 99.8% (CI = 99.8-100%), with an odds ratio of 1509 and an AUC of 0.97. HBHA-induced IGRA showed a sensitivity of 86.4% (CI = 71.1-97.3%) and a specificity of 82.5% (CI = 66.4-92.6%). Its PPV was 86.8% (CI = 66.7-95.3%), and NPV was 86.4% (CI = 57.8-95.7%), with an odds ratio of 6.18 and an AUC of 0.886. There are specific benefits and drawbacks of each diagnostic test for latent tuberculosis infection. With its exceptional sensitivity and specificity, the CLIA-IGRA test is a top choice for a precise diagnosis of tuberculosis. Practical factors such as availability and cost, however, might prevent its widespread usage. Both the QuantiFERON and TST are still useful tools, especially when used in certain populations or situations when their performance characteristics meet clinical requirements.

Management implications of latent TB among under-five children at risk: Insights from a community study in Mumbai, India.

BACKGROUND: Latent tuberculosis infection (LTBI) management is crucial to WHO's End TB Strategy. Indian guidelines recommend treating under-five children with household TB contacts after ruling out active TB, regardless of TBI testing. However, the precise LTBI burden among children in high TB burden settings like India is unknown. A community-based study in Mumbai's urban slums screened and managed under-five children at LTBI risk to understand its epidemiology and inform TB control interventions. METHODS: Total 369 eligible under-five children were enrolled for the study. LTBI screening was done using Tuberculin skin test and Interferon gamma release assay. Active TB was ruled out before initiation of TB preventive therapy among LTBI positives. Statistical tests like chi-square, logistic regression analysis and Hosmer-Lemeshow test were used. RESULTS: Overall, LTBI prevalence among under-five children was 12.4% by IGRA and 21.4% by TST. Undernourished children had significantly lower LTBI positivity by IGRA (p = 0.027), while those with household contacts, longer contact duration and drug-resistant tuberculosis (DR-TB) exhibited proportionally greater IGRA positivity (p = <0.001). CONCLUSION: The study found a lower LTBI prevalence among under-five children compared to adults, with key risk factors being HHC, DR-TB contact, and prolonged exposure. These findings suggest the need to revise or revisit the TPT framework for this age group in India, particularly by implementing a test-and-treat approach.

A regression predictive model for QuantiFERON-TB Gold Plus® indeterminate results in immunosuppressed patients.

Background: Screening for latent tuberculosis infection using Interferon-Gamma Release Assays is a routine procedure prior to the initiation of anti-tumor necrosis factor (TNF) biotherapy or immunosuppressive therapy. However, indeterminate results are relatively frequent and are an obstacle to treatment initiation. Aim: The aim of this cross-sectional study was to estimate the frequency of indeterminate QuantiFERON-TB Gold Plus® test results in Tunisian patients, and to analyze the potential clinico-biological risk factors associated with these indeterminate results. Methods: Whole blood samples from 712 patients being monitored for autoimmune diseases and candidates for anti-TNF biotherapy or switch of immunosuppressive therapy were used to screen for latent tuberculosis infection using the QuantiFERON-TB Gold Plus® test. Based on literature background, the following variables were tested for the association with indeterminate results: gender, age, diabetes, immunosuppressive drugs, lymphocyte count, Neutrophil-to-lymphocyte ratio, serum albumin, and estimated glomerular filtration rate. Results: The QuantiFERON-TB Gold Plus® test was negative in 572 (80.3%) patients, positive in 106 (14.9%), and indeterminate in 34 (4.8%) cases. Positive results were significantly associated with a family history of confirmed and treated tuberculosis, OR (95% CI) = 52 (20.2-134.3). The use of immunosuppressive drugs and duration of treatment were significantly associated with the occurrence of indeterminate results: OR (95% CI) = 24.5 (5.8-103) and OR (95% CI) = 1.004 (1.002-1.007), respectively. Biologically, lymphopenia, hypoalbuminemia, and decreased estimated glomerular filtration rate were significant risk factors for indeterminate results: p = 5 E-6, p = 4.3 E-4, and p = 0.002, respectively. Thus, a multiple logistic regression model based on these three biological parameters enabled us to develop a predictive score for indeterminate results with a sensitivity of 91.2% and a specificity of 99.9%, AUC = 0.9964 (0.9917-1), p = 2.8 E-52. Conclusion: Immunosuppressive therapy, lymphopenia, hypoalbuminemia, and kidney failure appeared to be risk factors for indeterminate QuantiFERON-TB Gold Plus® results.

Diagnostic accuracy of QuantiFERON-TB Gold Plus with Chemiluminescence Immunoassay: a systematic review and meta-analysis.

INTRODUCTION: Tuberculosis (TB) remains a global health challenge, underscoring the need for accurate diagnosis, particularly for Latent TB Infection. This meta-analysis assesses the diagnostic performance of QuantiFERON-TB Gold Plus (QFT) using Enzyme-Linked Immunosorbent Assay (ELISA) with Chemiluminescence Immunoassay (CLIA). AREAS COVERED: We systematically reviewed studies comparing QFT-CLIA with QFT-ELISA for TB detection. The literature search was carried out on PubMed, Scopus, and Web of Science, covering publications up to September 15, 2023. We included studies that assessed sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR), Diagnostic Odds Ratio (DOR), and concordance. EXPERT OPINION: QFT-CLIA demonstrated high sensitivity of 0.97 (95% CI: 0.95-0.99) and specificity of 0.99 (95% CI: 0.92-1.0), with PLR of 72.19 (95% CI: 11.25-463.17), NLR of 0.03 (95% CI: 0.02-0.05), and DOR of 2494.55 (95% CI: 301.67-20627.87). The overall agreement between QFT-CLIA and QFT-ELISA was strong (0.92, 95% CI: 0.88-0.97), although the agreement for indeterminate results was slightly lower (0.83, 95% CI: 0.70-0.96). The high diagnostic accuracy and broader quantitative range of QFT-CLIA compared to ELISA may lead to more positive results and better classification of borderline cases. However, further research is needed to validate its diagnostic capabilities.

Comparative Evaluation of Diagnostic Performance: Standard E TB Feron ELISA vs QuantiFERON-TB Gold Plus for Latent Tuberculosis Infection Detection in Diverse Risk Groups in Bangladesh.

Background: Around one-quarter of the global population has latent tuberculosis infection (LTBI). If left untreated, LTBI has 5-10% lifetime risk of developing into TB. Interferon-gamma release Assays (IGRAs) are more sensitive than the tuberculin skin test for LTBI detection. However, the high cost and complexity of IGRAs are barriers to adoption in resource-constrained settings. This study evaluated the diagnostic performance of a more affordable IGRA, Standard E TB-Feron (TBE), among different risk groups in Bangladesh. Methods: 532 participants of all age groups were enrolled from the TB Screening and Treatment Centers and Dhaka Hospital of icddr,b between June and September 2023. The participants were categorized into four risk groups: healthy people, healthcare workers/ attendants of TB patients, patients with microbiologically confirmed TB, and people with a history of TB. The diagnostic performance of TBE was compared to QuantiFERON-TB Gold Plus (QFT-Plus) for all groups. GeneXpert, culture, and microscopy were used to confirm TB microbiologically. Results: TBE had an overall agreement of 85.9% (95% CI, 82.5% to 88.7%), positive percent agreement of 86.1% (95% CI, 80.6% to 90.5%), and negative percent agreement of 85.7% (95% CI, 81.3% -89.4%) with QFT-Plus. Among 81 culture-positive patients, TBE and QFT-Plus were positive for 60 (74.1%) and 62 (76.5%) respectively. Among healthy people, TBE and QFT results were positive for 49 (24.5%) and 59 (29.5%) respectively. Among health workers and contacts, TBE and QFT-Plus were positive for 79 (39.5%) and 73 (35.5%) respectively. Conclusion: We found a substantial agreement (Cohen's kappa of 0.71) between TBE and QFT-Plus in detecting LTBI across different groups, suggesting its potential as a cost-effective diagnostic tool. Implementation of TBE in routine clinical practice could increase accessibility to LTBI diagnosis, facilitating the timely initiation of preventative therapy, and leading to a reduction of active TB incidence.

A case of pleural Mycobacterium tuberculosis infection with reversion of Quantiferon Gold Plus results from positive to negative.

Introduction. Mycobacterium tuberculosis (MTB) infections continue to have a high mortality and morbidity burden globally. Interferon-gamma release assays such as Quantiferon Gold Plus (QFG-Plus) aid in diagnosis of latent TB but diagnosis of pleural TB remains challenging. We present a case of active pleural MTB infection with reversion from positive to negative of IGRA result as well as negative Xpert MTB/RIF Ultra PCR result from tissues obtained from pleural biopsy. Case summary. A 52-year-old otherwise healthy male presented in August 2022 with a 2 week history of pleuritic chest pain associated with modest elevation in inflammatory markers. The patient had had a positive QFG-Plus result in 2018, however QFG-Plus during this admission was negative. Computed-tomography pulmonary angiogram and needle thoracocentesis showed an exudative left pleural effusion with predominant lymphocytes. The patient's symptoms failed to resolve with empiric antimicrobial therapy for community-acquired pneumonia. Broncho-alveolar lavage as well as biopsies of pleural tissues via video-assisted thoracoscopic surgery from the left lower lobe yielded negative results on routine microbiological culture as well as Xpert Ultra PCR. Growth of acid-fast bacilli was noted from mycobacterial cultures of pleural tissues which was identified as MTB. Conclusion. Despite significant technological advances, microbiological diagnosis of MTB infections remains challenging. We document QFG-Plus reversion during development from latent to active pleural TB. Decline in the ability of CD4+ and CD8+ T cells to produce interferon gamma in response to TB antigens (ESAT-6 and CFP-10) was likely associated with loss of host control of latent MTB. This case serves as a reminder that despite exhaustive testing with state-of-art diagnostic platforms, MTB infections can still elude discovery.

QuantiFERON CMV Test and CMV Serostatus in Lung Transplant: Stratification Risk for Infection, Chronic and Acute Allograft Rejection.

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.

Risk factors for tuberculosis among close IGRA-negative contacts of persons with infectious tuberculosis in Singapore.

OBJECTIVES: Contacts of patients with infectious tuberculosis (TB) testing positive on interferon-gamma release assay (IGRA) are followed up to exclude active disease. However, identifying factors that predispose IGRA-negative contacts to TB could improve screening and follow-up strategies in a medium TB burden country such as Singapore. METHODS: We conducted a retrospective study of IGRA-negative contacts aged ≥2 years identified during contact investigation between January 2014 and December 2022. We examined the risk factors associated with developing active TB among contacts previously testing IGRA-negative, using univariate and multivariable logistic regression and odds ratios with 95% confidence intervals. RESULTS: Of 60,377 IGRA-negative contacts, 150 developed TB disease, and half were notified within 23 months of index patient diagnosis. IGRA-negative contacts of a smear-positive index patient were more likely to develop TB. Independent risk factors for TB were age >50 years, Malay ethnicity, having diabetes or end-stage renal failure, a "family" relationship with the index patient, or exposure in a dormitory or nursing home. CONCLUSIONS: Identifying risk factors could help optimise follow-up strategies and preventive treatment in IGRA-negative individuals. The incidence rate of TB in this group was 150 per 100,000 population, substantially higher than in the community, with a median 92 weeks to develop disease. Findings suggest that follow-up should be extended to 24 months for contacts with these risk factors.

QuantiFERON monitor predicts early cytomegalovirus infection and viral burden in allogeneic hematopoietic stem cell transplantation.

INTRODUCTION: Cytomegalovirus (CMV) infection is a major cause of transplantation-related morbidity and mortality. This study assessed the utility of the QuantiFERON monitor (QFM; Qiagen) for the prediction of early CMV infection and viral burden. METHODS: QuantiFERON-CMV (QF-CMV; Qiagen) and QFM were measured at the post-allogeneic hematopoietic stem cell transplantation (HSCT) week 4. CMV DNA was measured at every visit until post-HSCT week 24. The QFM cutoff specific to CMV infection was established. RESULT: At the post-HSCT week 4, the QFM cutoff predicting CMV infection was 86.95 IU/mL. While QF-CMV results at the post-HSCT week 4 were associated with high-level CMV infection (CMV DNA ≥ 5,000 IU/mL) but not with CMV infection (CMV DNA ≥ 500 IU/mL), QFM was associated with both CMV infection and high-level CMV infection. Both indeterminate QF-CMV and nonreactive QFM were associated with increased peak CMV DNA. CONCLUSION: Low QFM is a risk factor for CMV infection and increased CMV viral loads. QFM at post-HSCT week 4 can be utilized as an assay to predict the risk and burden of early CMV infection in HSCT recipients, in conjunction with other risk factors.

Evaluation of concordance of new QuantiFERON-TB Gold Plus platforms for Mycobacterium tuberculosis infection diagnosis in a prospective cohort of household contacts.

Interferon-gamma (IFN-γ) release assays play a pivotal role in tuberculosis infection (TBI) diagnosis, with QuantiFERON-TB Gold Plus-an enzyme-linked immunosorbent assay (ELISA)-among the most widely utilized. Newer QuantiFERON-TB platforms with shorter turnaround times were recently released. We aimed to evaluate these platforms' agreement in the diagnosis of TBI. Blood samples from a prospective cohort of tuberculosis household contacts were collected at baseline and after 12 weeks of follow-up, and tested with LIAISON, an automated chemiluminescence immunoassay (CLIA) system, QIAreach, a lateral flow (QFT-LF) semi-automated immunoassay, and the ELISA QuantiFERON-TB Gold Plus platform. Test concordances were analyzed. ELISA vs CLIA overall agreement was 83.3% for all tested samples (120/144) [Cohen's kappa coefficient (κ): 0.66 (95% CI: 0.54-0.77)]. Samples positive with CLIA provided consistently higher IFN-γ levels than with ELISA (P < 0.001). Twenty-four (16.7%) discordant pairs were obtained, all CLIA-positive/ELISA-negative: 15 (62.5%) had CLIA IFN-γ levels within borderline values (0.35-0.99 IU/mL) and 9 (37.5%) >0.99 IU/mL. QFT-LF showed only 76.4% (68/89) overall agreement with ELISA [κ: 0.53 (95% CI: 0.37-0.68)] with 21 (23.6%) discordant results obtained, all QFT-LF-positive/ELISA-negative. Overall concordance between ELISA and CLIA platforms was substantial, and only moderate between ELISA and QFT-LF. The CLIA platform yielded higher IFN-γ levels than ELISA, leading to an almost 17% higher positivity rate. The techniques do not seem interchangeable, and validation against other gold standards, such as microbiologically-confirmed tuberculosis disease, is required to determine whether these cases represent true new infections or whether CLIA necessitates a higher cutoff. IMPORTANCE: Tuberculosis is an airborne infectious disease caused by Mycobacterium tuberculosis that affects over 10 million people annually, with over 2 billion people carrying an asymptomatic tuberculosis infection (TBI) worldwide. Currently, TBI diagnosis includes tuberculin skin test and the blood-based interferon-gamma (IFN-γ) release assays, with Qiagen QuantiFERON-TB Gold Plus (QFT) being among those most widely utilized. We evaluated Qiagen's newer QFT platforms commercially available in a prospective cohort of tuberculosis contacts. A substantial agreement was obtained between the current QFT-enzyme-linked immunosorbent assay (ELISA) and the new QFT-chemiluminescence immunoassay (CLIA) platform, although QFT-CLIA provided higher concentrations of IFN-γ, leading to a 16.6% higher positivity rate. We highlight that both platforms may not be directly interchangeable and that further validation is required.

Prevalence, Risk Factors, and Result Features in the Detection of Latent Tuberculosis Infection in Thai Healthcare Workers Using QuantiFERON-TB Gold Plus.

Introduction Latent tuberculosis infection (LTBI) is an enormous reservoir for tuberculosis (TB), and healthcare workers (HCWs) are at high risk for TB infection. QuantiFERON-TB Gold Plus (QFT-Plus) is an alternative to the tuberculin skin test for LTBI detection, but data on its application and LTBI detected by QFT-Plus in high TB burden countries are limited. This study aimed to determine the prevalence of LTBI and its risk factors, and to investigate the QFT-Plus results in Thai HCWs. Methods A cross-sectional analytical study was conducted among HCWs at a secondary care hospital in Health Region 5, Thailand. Eligible HCWs were enrolled and underwent QFT-Plus testing. Interferon-gamma (IFN-γ) values in tubes were analysed. The prevalence and associated risk factors for LTBI were assessed based on laboratory and sociodemographic data. Logistic regression analyses were applied to calculate odds ratios (OR, aOR) reported with 95% confidence intervals (CI). Results Of the 269 participants enrolled, their median age was 42 years and 93.31% (n = 251/269) were female. The majority (n = 178/269, 66.17%) were nurses or nurse assistants and 42.75% (n = 115/269) worked in the inpatient medical wards. Overall, the QFT-Plus results showed 110 (40.89%) positive with good agreement (93.68%; κ 0.87) and high correlation (Spearman's ρ 0.91) of IFN-γ concentrations in the two antigen tubes. A true difference in IFN-γ values for predicting a recent infection was found about 7.81% (n = 21/269). By univariate and multivariate analyses, the participants' age > 40 years (OR = 3.21, 95% CI: 1.84-5.64%; aOR = 2.05, 95% CI: 1.07-3.96%), and employment duration > 10 years (OR = 3.19, 95% CI: 1.66-6.37%; aOR = 2.34, 95% CI: 1.05-5.21%) were significantly associated with the increased risk of LTBI (p-value < 0.05). Conclusions The prevalence of LTBI among these HCWs was high, and the increased risk factors for LTBI according to QFT-Plus positivity were age over 40 years and working time in the hospital for more than 10 years. It is important to screen HCWs in this setting for LTBI, particularly those with long employment durations and older ages. The high prevalence of LTBI suggests that LTBI management, such as regular screening and treatment, should be considered together with strengthening preventive measures, especially in high-risk groups.

The Importance of Clinically Correlating Tuberculosis With Indeterminate QuantiFERON Gold Test.

Tuberculosis (TB) is a highly contagious airborne infection of the lungs. It can present in active form, as well as latent form. The clinical manifestations of tuberculosis can present as either subacute or chronic. Some symptoms include weight loss, night sweats, fevers, and hemoptysis. This case highlights the importance of clinical judgment and follow-up testing when patient presentation does not correlate with initial results. We share a perplexing encounter where a 34-year-old male presented with hemoptysis, fevers of unclear origin, and an indeterminate QuantiFERON Gold result and was empirically started on rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) therapy. RIPE therapy includes the gold standard medications used to treat tuberculosis.

Evaluating the diagnostic accuracy of QIAreach QuantiFERON-TB compared to QuantiFERON-TB Gold Plus for tuberculosis: a systematic review and meta-analysis.

Accurate tuberculosis (TB) diagnosis remains challenging, especially in resource-limited settings. This study aims to assess the diagnostic performance of the QIAreach QuantiFERON-TB (QFT) assay, with a specific focus on comparing its diagnostic performance with the QuantiFERON-TB Gold Plus (QFT-Plus). We systematically reviewed relevant individual studies on PubMed, Scopus, and Web of Science up to January 20, 2024. The focus was on evaluating the diagnostic parameters of the QIAreach QFT assay for TB infection, which included sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and concordance with the QFT-Plus assay. QIAreach QFT demonstrated strong diagnostic performance with a pooled sensitivity of 99% (95% CI 95-100%) and specificity of 94% (95% CI 85-97%). Additionally, it showed a PLR of 15.6 (95% CI 6.5-37.5) and NLR of 0.01 (95% CI 0-0.03). The pooled PPV and NPV were 88% (95% CI 70-98%) and 100% (95% CI 99-100%), respectively. Concordance analysis with QFT-Plus revealed a pooled positive percent agreement of 98% (95% CI 88-100%) and pooled negative percent agreement of 91% (95% CI 81-97%), with a pooled overall percent agreement of 92% (95% CI 83-98). In conclusion, QIAreach QFT has shown promising diagnostic performance, with a strong concordance with QFT-Plus. However, further studies are needed to comprehensively evaluate its diagnostic performance in the context of TB infection.

Quantitative interferon-gamma releasing assay in predicting tuberculosis in South Korean military: a retrospective cohort study.

OBJECTIVE: The interferon-gamma releasing assay (IGRA) has been widely used to diagnose latent tuberculosis infection (TBI). However, there are limited data on the association between performance in the IGRA and risk of tuberculosis disease (TBD), as well as on the appropriate IGRA threshold for initiating TBI treatment. METHODS: The analysis was performed using the IGRA results in the Korean Military Manpower Administration database (January 2017 to December 2021), and TBD cases reported to the Korean Military Medical Command (January 2017 to June 2023). All Korean candidates for 18-month military service underwent the IGRA in the pre-enlistment examination, and enlistees who tested positive (≥0.35 IU/mL) were advised to receive TBI treatment before enlistment. RESULTS: From 2017 to 2021, 1 647 941 individuals were screened, with 29 574 testing positive for IGRA. Excluding nonenlistees namely individuals with TBD before enlistment, 19 387 individuals were IGRA positive and 1 356 324 IGRA negative. Of the positives, 4351 were excluded due to discontinued or ongoing TBI treatment at or after enlistment. During follow-up of 9219 untreated and 5818 treated positive individuals and 1 356 324 negatives, TBD occurred in 22 of the IGRA-positive individuals (97.5/100 000 person-years [95% CI, 61.1-147.7]), predominantly in the untreated group (18 cases, 130.1/100 000 person-years [95% CI, 77.1-205.7]) compared to the treated group (4 cases, 45.9/100 000 person-years [95% CI 12.5 - 117.4]), whereas 57 cases occurred in the IGRA-negative group (2.8/100 000 person-years [95% CI, 2.2-3.6]). Elevating the cutoff of IGRA from 0.35 IU/mL to 1.33 IU/mL increased positive predictive value (0.2% vs. 0.4%, p 0.03), with insignificant loss of sensitivity (24% vs. 20%, p 0.69) and decreased numbers needing treatment from 790.5 to 415.3. DISCUSSION: Elevated IGRA levels before enlistment are associated with risk of TBD during military service. It is worth considering raising the IGRA threshold for treatment of TBI in cohorts of healthy, young military individuals.

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.

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.

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.

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.