Interferon-gamma Release Assay Research Articles

Cost-effectiveness of diagnostic technologies for mycobacterium tuberculosis infection in India and Brazil.

The economic value of new skin-based tests and blood-based interferon-γ release assays (IGRAs) for tuberculosis (TB) infection is not yet well-established. This study evaluates the cost and cost-effectiveness in two high-burden countries by comparing:(a) new skin-based tests(Diaskintest and Cy-Tb) with the purified protein derivative (PPD)-tuberculin test (TST);(b) IGRAs (Standard E TB-Feron ELISA (TBF))with approved IGRAs (QuantiFERON-TB Gold Plus (QFT-GP)and TSPOT.TB); and (c) the best performing skin-based test with the best performing IGRA) based on cost effectiveness. In this paper, we developed a decision tree model for India and Brazil from a health system perspective. To quantify the effect of parameter variability and uncertainty, we performed both univariate and probabilistic sensitivity analysis. The study findings reveal that among skin-based tests, the Diaskintest is more cost-effective compared to TST-PPD at 22.6 USD and 41.0 USD per correctly diagnosed case of TB infection for Brazil and India, respectively. For blood-based assays, TSPOT.TB outperforms QFT-GP and TBF due to its lower cost and higher effectiveness. When compared with Diaskintest, TSPOT.TB has an incremental cost of approximately 8 USD and 6 USD for India and Brazil respectively but is more effective. The incremental cost-effectiveness ratio (ICER) was 74 USD and 55 USD for India and Brazil, respectively. In summary, while Diaskintest is potentially cost-saving when compared to TSPOT.TB in these two high-burden TB countries but the TSPOT.TB demonstrates higher effectiveness.

The performance of a new rapid interferon gamma release assay based on fluorescence immunochromatography for Mycobacterium tuberculosis infection testing in village doctors in China.

The performance of a new rapid interferon gamma release assay based on fluorescence immunochromatography for Mycobacterium tuberculosis infection testing in village doctors in China.

English

Objective: To measure Tuberculin Skin Test (TST) at 48 and 72 hours and, if there are differences, to determine the concordance and whether it is of clinical significance (change in the TST score). Material and method: Prospective study of those admitted to prison between March and June 2023, screened by means of TST read at 48 and 72 hours by trained personnel, assessed according to criteria in force in Spain. When the measurement varied, concordance was checked using the kappa index and its clinical significance. To determine variables associated with clinical significance, bivariate and mutivariate analysis was performed using logistic regression. Results: 488 cases were studied. TST was positive in 20.1, 23.4 and 23.8% at 48 hours, 72 hours or any of them, respectively.There was more TST positive in foreigners or BCG vaccinated. The reading varied in 35.2% (mean deviation 5.5 +/–4.4 mm) and was higher at 72 hours (86% of different cases). Inter-reading concordance was excellent overall (κ = 0.892) and in BCG vaccinated (κ = 0.805), but moderate in immunocompromised (κ = 0.421). Discordance was clinically significant in 3.7% and was not associated with any variable. Discussion: TST concordance at 48-72 hours is excellent, but in some patients (3.7% in this work) the score is incorrect, more so in readings at 48 hours. The proportion is low, but can be reduced if the reading is taken at 72 hours and Interferon Gamma Release Assay tests are used in some cases (immunocompromised, etc.).

Burden and challenges in managing TB infection among people with occupational exposure to silica in India.

Occupational exposure to silica increases the risk of TB infection (TBI) and disease. This study aimed to determine the prevalence of TBI and explore challenges in TBI management in such individuals in two districts of India during 2023. This was an explanatory mixed-methods study with a quantitative cohort design and qualitative descriptive in-depth interviews. Among 1,555 individuals with occupational exposure to silica, 593 (38%, 95% CI 36-41) underwent interferon-gamma release assay (IGRA) for TBI, of whom 255 (43%, 95% CI 39-47) were found IGRA-positive. Males with occupational silica exposure for ≥20 years had a significantly higher risk of TBI. Of these 160 individuals eligible for TB preventive therapy (TPT), 153 (96%, 95% CI 92-98) were initiated on TPT and 124 (81%, 95% CI 74-88) completed TPT. The low uptake of IGRA was attributed to the stigma associated with TB and reluctance to undergo any medical evaluation. Compared to the general population, individuals with occupational exposure to silica have an almost two times higher prevalence of TBI. Further research is required to identify the threshold of silica exposure to be considered for screening for TBI. Efforts to increase awareness and decrease stigma can improve the uptake of testing for TBI and TB disease.

Reactive arthritis in connective tissue diseases; one should be vigilant for joint tuberculosis.

The incidence of tuberculosis (TB) is increasing worldwide. Bone and joint TB are the most common types of extra-pulmonary TB, but can easily be misdiagnosed, since articular TB commonly mimics other joint diseases, including reactive and degenerative arthritis, and articular manifestations associated with systemic autoimmune diseases. Furthermore, patients with systemic auto-immune diseases are often more prone to mycobacterial infection. The diagnosis of joint TB can be made using a combination of the following methods: clinical evaluation, imaging, tuberculin skin test, interferon-gamma release assays, nucleic acid amplification tests, and Gene X-pert MTB/rifampicin assay.

A case of squamous cell carcinoma of the lung misdiagnosed as tuberculosis. Is HPV infected by oral sex the causative agent?

BackgroundThe integration of high-risk human papilloma virus (HPV) DNA into the human genome has been implicated in cervical carcinogenesis and head and neck squamous cell cancer. However, its role in lung squamous cell carcinoma is not well understood. In addition, tuberculosis (TB) and lung cancer(LC) share similar clinical symptoms and imaging features, increasing the risk of misdiagnosis.Case PresentationThe patient presented with a 16-month history of hemoptysis, chest pain, and occasional fatigue, without fever, chills, or history of mechanical damage or autoimmune diseases. Examination revealed normal vital signs and laboratory parameters, except for a positive interferon-gamma release assay indicating tuberculosis infection. Bronchoscopic examinations identified congestion and edema of the tracheal wall, along with a tiny lesion in the right wall of the trachea. She had been misdiagnosed with tuberculosis. However, the diagnosis of squamous cell carcinoma was eventually confirmed by endoscopic biopsy. The patient’s macrogenomic second-generation sequencing (mNGS) of the bronchoscopic biopsy specimen was positive for HPV-16.The patient’s sex partner tested positive for HPV-16 in penile scrapings, indicating HPV transmission through oral sex.ConclusionsThis case highlights the potential for HPV infection acquired through oral sex to lead to lung squamous cell carcinoma. It emphasizes the importance of considering HPV-associated malignancies in patients with respiratory symptoms who engage in oral sexual behaviors.

Integrated Imaging Probe and Bispecific Antibody Development Enables In Vivo Targeting of Glypican-3–Expressing Hepatocellular Carcinoma

Abstract Glypican-3 (GPC3) is a proteoglycan with high sensitivity and specificity for hepatocellular carcinoma (HCC). We describe the integrated development and validation of a GPC3-targeting optical imaging probe and T cell–redirecting antibody (TRAB) as a theranostic strategy for the detection and treatment of HCC. A novel TRAB targeting GPC3 on HCC tumor cells and the CD3 T-cell receptor as well as a distinct GPC3-specific optical imaging probe were developed from a short peptide. The efficacy of GPC3/CD3 TRAB was evaluated in vitro using IFNγ release and calcein-AM assays. Patient-derived xenografts were used to assess the in vivo efficacy of GPC3/CD3 TRAB and the GPC3 imaging probe for the detection of GPC3+ HCC. GPC3/CD3 TRAB caused a dose-dependent escalation in IFNγ release from inactive peripheral blood T cells (P = 0.001) and higher tumor-cell lysis (P = 0.01) compared with controls in vitro. Intratumorally injected GPC3/CD3 TRAB resulted in significant prolongation of tumor doubling time in the GPC3+ tumors, with an associated reduction of tumor fluorescent signal from the HiLyte 488–conjugated GPC3-specific peptide on optical imaging. These data demonstrate that HCC cell targeting using a GPC3/CD3 TRAB derived from a small peptide enabled effective T-cell activation and induction of a cytotoxic response toward GPC3+ HCC tumor cells both in vitro and in vivo. GPC3-specific optical imaging enabled the detection of the GPC3+ HCC cells and noninvasive monitoring of tumor response to adoptive immunotherapy. The integrated development of a targeted therapeutic and molecular imaging probe provides a promising paradigm for the development of cancer theranostics.

Clinical analysis of 20 cases of perinatal tuberculosis

BackgroundTo analyze the clinical manifestations, diagnostic and therapeutic processes of perinatal tuberculosis in children, providing reference for clinicians in the diagnosis and treatment of this disease.MethodsA retrospective analysis was conducted on the epidemiological history, clinical manifestations, laboratory and imaging findings, and treatment follow-up of 20 cases of perinatal tuberculosis diagnosed in the Second Department of Infectious Disease, Kunming Children’s Hospital, from February 2014 to September 2021.ResultsOf the 20 cases, 13 were male (65.0%) and 7 were female (35.0%). The average age at onset was 35.35 ± 23.03days, with an average time from onset to diagnosis of 24.75 ± 15.55days. Tuberculin skin test (TST) was positive in 1 out of 4 cases (25.0%). Gamma interferon release assays (IGRAs) were positive in 9 out of 17 cases (52.9%).acid-fast staining was positive in 7 out of 16 cases (43.7%), and Mycobacterium tuberculosis nucleic acid polymerase-chain-reaction(PCR) was positive in 14 out of 20 cases (70.0%). Chest CT showed miliary changes in 4 out of 19 cases (21.0%), multiple nodular and patchy opacities in 6 out of 19 cases (31.6%), and pulmonary consolidation and atelectasis in 10 out of 19 cases (52.6%). After anti-tuberculosis treatment, 16 out of 20 cases (80.0%) improved, and no recurrence of tuberculosis was observed during follow-up periods ranging from 9 months to 3 years. The growth and development of these children were similar to those of healthy children.ConclusionThe clinical manifestations and chest imaging features of perinatal tuberculosis are nonspecific. In suspected cases, it is crucial to investigate the mother’s condition thoroughly and complete etiological examinations to achieve early diagnosis and timely treatment, which can improve prognosis.

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

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

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

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. 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. 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). 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.

Field Trial with Vaccine Candidates Against Bovine Tuberculosis Among Likely Infected Cattle in a Natural Transmission Setting.

Background/Objectives: Vaccines may improve the control and eradication of bovine tuberculosis. However, the evaluation of experimental candidates requires the assessment of the protection, excretion, transmission and biosafety. A natural transmission trial among likely infected animals was conducted. Methods: Seventy-four male heifers were randomly distributed (five groups) and vaccinated subcutaneously with attenuated strains (M. bovis Δmce2 or M. bovis Δmce2-phoP), a recombinant M. bovis BCG Pasteur (BCGr) or M. bovis BCG Pasteur. Then, they cohoused with a naturally infected bTB cohort under field conditions exposed to the infection. Results: A 23% of transmission of wild-type strains was confirmed (non-vaccinated group). Strikingly, first vaccination did not induce immune response (caudal fold test and IFN-gamma release assay). However, after 74 days of exposure to bTB, animals were re-vaccinated. Although their sensitization increased throughout the trial, the vaccines did not confer significant protection, when compared to the non-vaccinated group, as demonstrated by pathology progression of lesions and confirmatory tools. Besides, the likelihood of acquiring the infection was similar in all groups compared to the non-vaccinated group (p > 0.076). Respiratory and digestive excretion of viable vaccine candidates was undetectable. To note, the group vaccinated with M. bovis Δmce2-phoP exhibited the highest proportion of animals without macroscopic lesions, compared to the one vaccinated with BCG, although this was not statistically supported. Conclusions: This highlights that further evaluation of these vaccines would not guarantee better protection. The limitations detected during the trial are discussed regarding the transmission rate of M. bovis wild-type, the imperfect test for studying sensitization, the need for a DIVA diagnosis and management conditions of the trials performed under routine husbandry conditions. Re-vaccination of likely infected bovines did not highlight a conclusive result, even suggesting a detrimental effect on those vaccinated with M. bovis BCG.

Systematic review of the economic impact of novel Mycobacterium tuberculosis specific antigen-based skin tests for detection of TB infection compared with tuberculin skin test and interferon-gamma release assays.

The Purified Protein Derivative tuberculin skin tests (TST) and blood-based Mycobacterium tuberculosis (M.tb) specific interferon-gamma release assays (IGRA) are the currently used tests for identifying individuals with TB infection for preventive treatment. However, challenges around access and implementation have limited their use. Novel M.tb specific skin tests (TBST) such as Diaskintest, ESAT6-CFP10 (C-TST), C-Tb (also known as Cy-Tb), and DPPD may provide accurate and scalable options but evidence synthesis on their economic impact is lacking. We conducted two separate systematic reviews to compare the costs and cost-effectiveness of (1) the novel skin tests TBST (primary), and (2) TST and IGRA tests (secondary), to support WHO guideline development. We searched for articles presenting economic evaluations of the diagnostic tests using a health provider perspective and related to TB infection in humans. We considered papers written in English, Chinese or Russian. In the primary review, eight studies for novel TBST were found. One study in Brazil assessed cost-effectiveness of C-TST and Diaskintest and seven in Russia assessed the Diaskintest, while none evaluated C-Tb or DPPD. The review showed on average, Diaskintest kit costs (in 2021 USD) $1.60 (1.50 - 1.70), while full unit costs were estimated at $5.07. C-TST unit cost was $9.96. The second review found 32 articles on IGRA and/or the TST. These presented an average TST full unit cost of $37.88, and $87.81 for IGRA. Studies' quality for TBST was limited while high-quality studies were found for TST and IGRA tests. In conclusion, there is limited evidence regarding the costs and cost-effectiveness of novel TBST. Conversely, there is substantial evidence for TST and IGRA tests, but most studies were performed in high-income and low-TB burden settings and their cost-effectiveness varied between and within risk groups without clear economic consensus.

Cost-effectiveness of screening with transcriptional signatures for incipient TB among U.S. migrants.

Host-response-based transcriptional signatures (HrTS) have been developed to identify "incipient tuberculosis (TB)". No study has reported the cost-effectiveness of HrTS for post-arrival migrant screening programs in low-incidence countries. To assess the potential health impact and cost-effectiveness of HrTS for post-arrival TB infection screening among new migrants in the United States. We used a discrete-event simulation model to compare four strategies: (1) no screening for TB infection or incipient TB; (2) 'IGRA-only', screen all with interferon gamma release assay (IGRA), provide TB preventive treatment for IGRA-positives; (3) 'IGRA-HrTS', screen all with IGRA followed by HrTS for IGRA-positives, provide incipient TB treatment for individuals testing positive with both tests; and (4) 'HrTS-only', screen all with HrTS, provide incipient TB treatment for HrTS-positives. We assessed outcomes over the lifetime of migrants entering the U.S. in 2019, assuming HrTS met the WHO Target Product Profile (TPP) optimal criteria. We conducted sensitivity analyses to evaluate the robustness of results. The IGRA-only strategy dominated the HrTS-based strategies under both healthcare sector and societal perspectives, with an incremental cost-effectiveness ratio of $78,943 and $89,431 per quality-adjusted life-years (QALY) gained, respectively. This conclusion was robust to varying costs ($15-300) and characteristics of HrTS, and the willingness-to-pay threshold ($30,000-150,000/ QALY gained), but sensitive to the rate of decline in TB progression risk after U.S. entry. Our findings suggest that HrTS meeting the WHO TPP is unlikely to be a cost-effective component of post-arrival screening for migrants entering the U.S.

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

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

Latent Tuberculosis in Healthcare Professionals: A Cross-Sectional Study

Tuberculosis (TB) is a dangerous disease caused by the bacterium Mycobacterium tuberculosis. Its transmission occurs through aerosols, making healthcare workers particularly vulnerable to it. At the San Cecilio Clinical University Hospital in Granada (HUCSC), preventive measures such as the use of personal protective equipment (PPE) and IGRA (interferon-gamma release assay) tests were implemented to detect latent tuberculosis infection. At HUCSC, between 2022 and 2024, 4.75% (92/1936) of workers were found to have positive IGRA test results, with no significant differences observed between professional categories. However, variability in positive IGRA rates was noted across different medical departments, with pulmonology and sample handling being the most affected. Additionally, a relationship was found between age and the likelihood of obtaining a positive IGRA test result. These findings underscore the importance of targeted preventive measures and a multifaceted approach to controlling and preventing tuberculosis in workplace environments.

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

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

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

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

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 infectionin 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.

Contribution of QuantiFERON TB gold in tube to the diagnosis of tuberculous pleurisy: a monocentric prospective study

Introduction The diagnosis of tuberculous (TB) pleurisy remains difficult because of its paucibacillary character. Several authors have studied the usefulness of interferon gamma release assays in the early diagnosis of TB pleurisy, whereas these tests are designed for the detection of latent TB infection. Our objective is to study the performance and clinical relevance of QuantiFERON TB Gold in Tube (QFT-GIT) in the diagnosis of TB pleurisy in Algeria. Patients and methods QFT-GIT was tested in vitro in serum and pleural fluid on a prospective recruitment of 158 immunocompetent patients with pleural effusion. Results Of the 158 cases of pleurisy identified, 84 (53.84%) were TB, diagnosed and proven by conventional methods, and 72 (46.15%) were non-TB, of whom 67 (93%) were confirmed of neoplastic origin, five (7%) secondary to a systemic disease and two of nonspecific inflammatory origin. Our results showed a high pleural sensitivity of QFT-GIT (97.62%) compared to serum sensitivity (80.95%). In contrast, serum specificity (83.78%) was higher than pleural specificity (72.97%). When we used the optimal values from the receiver operation characteristics curve analysis, the area under the curve of interferon-gamma produced by the QFT-GIT test was significantly higher in the pleural fluid than in the blood. Area under the curve of TB antigen interferon-gamma response was 92, 18 [95% confidence interval (CI)=87.56–96.79], nil tube was 95.71% (95% CI=92.43–99), and mitogen tube was 65.34 (95% CI=57.71–72.98). Conclusion QFT-GIT in pleural fluid appears in our study as a useful test for the diagnosis of TB pleurisy, but its diagnostic accuracy needs to be validated in further large-scale research.

Evaluation of Diagnostic Performance of Three Commercial Interferon-Gamma Release Assays for Mycobacterium tuberculosis

Interferon-gamma release assays (IGRAs) have gained attention for the diagnosis of latent tuberculosis infection (LTBI) due to their higher specificity compared to the tuberculin skin test (TST). However, the IGRA’s performance varies across different populations. This study evaluated the diagnostic performance of three IGRAs (TBF-FIA, TBF-ELISA, and QFT-Plus) in Ghana, comparing them among individuals exposed and unexposed to MTB infection. Conducted in TB clinics across three regions, this prospective and cross-sectional study included healthy individuals with no known TB exposure (unexposed group) and patients with confirmed active TB (exposed group). Blood samples were tested using all three assays as per the manufacturers’ guidelines. The TBF-ELISA showed 3.4% higher sensitivity but 4.6% lower specificity compared to QFT-Plus. The TBF-FIA had sensitivity of 78.5–87.3% and specificity of 82.9–90.0%. These findings indicate that while the three IGRAs offer similar diagnostic accuracy, the variations in specificity and limited data on assays like TBF-FIA require further investigation.