QuantiFERON-TB Gold Plus Assay Specificity in Children and Adolescents With Suspected Tuberculosis—A Multicenter Cross-sectional Study in Spain

Soler-Garcia, Aleix; Gamell, Anna; Santiago, Begoña; Monsonís, Manuel; Cobo-Vázquez, Elvira; Bustillo-Alonso, Matilde; Tagarro, Alfredo; Pérez-Gorricho, Beatriz; Espiau, María; Piqueras, Ana Isabel; Korta-Murúa, Javier; Rodríguez-Molino, Paula; Lobato, Zulema; Pérez-Porcuna, Tomàs; Tebruegge, Marc; Noguera-Julián, Antoni

doi:10.1097/inf.0000000000003173

Cited by 6 publications

(23 citation statements)

References 17 publications

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“…We recently reported that QFT-Plus is no more sensitive or specific than previous QFT assays in children and adolescents with TBD 20 22. In this study, we aimed to determine the performance of QFT-Plus in a large cohort of paediatric patients at risk of TB in a low-burden country by including children undergoing LTBI screening as part of contact tracing (CTR), migrant screening and screening prior to initiation of immunosuppressive medication.…”

Section: Introductionmentioning

confidence: 99%

Performance of QuantiFERON-TBGold Plus assays in children and adolescents at risk of tuberculosis: a cross-sectional multicentre study

Soler-Garcia

Gamell

Pérez-Porcuna

et al. 2021

Thorax

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IntroductionThe QuantiFERON-TB Gold Plus (QFT-Plus) assay, which features two antigen-stimulated tubes (TB1 and TB2) instead of a single tube used in previous-generation interferon-gamma release assays (IGRAs), was launched in 2016. Despite this, data regarding the assay’s performance in the paediatric setting remain scarce. This study aimed to determine the performance of QFT-Plus in a large cohort of children and adolescents at risk of tuberculosis (TB) in a low-burden setting.MethodsCross-sectional, multicentre study at healthcare institutions participating in the Spanish Paediatric TB Research Network, including patients <18 years who had a QFT-Plus performed between September 2016 and June 2020.ResultsOf 1726 patients (52.8% male, median age: 8.4 years), 260 (15.1%) underwent testing during contact tracing, 288 (16.7%) on clinical/radiological suspicion of tuberculosis disease (TBD), 649 (37.6%) during new-entrant migrant screening and 529 (30.6%) prior to initiation of immunosuppressive treatment. Overall, the sensitivity of QFT-Plus for TBD (n=189) and for latent tuberculosis infection (LTBI, n=195) was 83.6% and 68.2%, respectively. The agreement between QFT-Plus TB1 and TB2 antigen tubes was excellent (98.9%, κ=0.961). Only five (2.5%) patients with TBD had discordance between TB1 and TB2 results (TB1+/TB2−, n=2; TB1−/TB2+, n=3). Indeterminate assay results (n=54, 3.1%) were associated with young age, lymphopenia and elevated C reactive protein concentrations.ConclusionsOur non-comparative study indicates that QFT-Plus does not have greater sensitivity than previous-generation IGRAs in children in both TBD and LTBI. In TBD, the addition of the second antigen tube, TB2, does not enhance the assay’s performance substantially.

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Section: Introductionmentioning

confidence: 99%

Performance of QuantiFERON-TBGold Plus assays in children and adolescents at risk of tuberculosis: a cross-sectional multicentre study

Soler-Garcia

Gamell

Pérez-Porcuna

et al. 2021

Thorax

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“…A recent meta-analysis on QFT-Plus in adults, which included 578 TB cases reported by six studies, estimated the assay sensitivity in adults with TB disease to be between 90% and 98% 16. To our knowledge, only six studies evaluating the performance of QFT-Plus in children with TB disease have been published so far,14–16 25–27 with the first four including fewer than 60 paediatric TB cases combined. The currently largest paediatric study, which was conducted in Spain and included 158 paediatric patients with TB disease (46.8% microbiologically-confirmed), reported a substantially lower sensitivity estimate (82.9% (95% CI 77.0% to 88.8%)) than most adult studies 14.…”

Section: Discussionmentioning

confidence: 99%

“…Those data are consistent with our sensitivity estimate of 83.8% (95% CI 80.2% to 87.8%) in a far larger paediatric study population recruited from 16 European countries. Another study from the same group, which also included children with suspected TB who ultimately had alternative diagnoses, found that QFT-Plus assays had a specificity, sensitivity, positive predictive value and negative predictive value of 91.5%, 87.3%, 86.4% and 91.2%, respectively 26…”

Section: Discussionmentioning

confidence: 99%

Performance of QuantiFERON-TB Gold Plus assays in paediatric tuberculosis: a multicentre PTBNET study

Buonsenso

Noguera-Julián

Moroni

et al. 2022

Thorax

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RationaleIn 2016, a new interferon-gamma release assay (IGRA) was introduced, QuantiFERON-TB Gold Plus (QFT-Plus), claimed to have improved sensitivity in active tuberculosis (TB).ObjectivesThis study aimed to determine the performance of QFT-Plus, compared with previous generation IGRAs and the tuberculin skin test (TST), in children with TB in Europe.MethodsMulticentre, ambispective cohort study within the Paediatric Tuberculosis Network European Trials Group (ptbnet), a dedicated paediatric TB research network comprising >300 members, capturing TB cases <18 years-of-age diagnosed between January 2009 and December 2019.Measurements and main results1001 TB cases from 16 countries were included (mean age (IQR) 5.6 (2.4–12.1) years). QFT-Plus was performed in 358, QFT Gold in-Tube (QFT-GIT) in 600, T-SPOT.TBin 58 and TST in 636 cases. The overall test sensitivities were: QFT-Plus 83.8% (95% CI 80.2% to 87.8%), QFT-GIT 85.5% (95% CI 82.7% to 88.3%), T-SPOT.TB77.6% (95% CI 66.9% to 88.3%) and TST (cut-off ≥10 mm) 83.3% (95% CI 83.3% to 86.2%). There was a trend for tests to have lower sensitivity in patients with miliary and/or central nervous system (CNS) TB (73.1%, 70.9%, 63.6% and 43.5%, respectively), and in immunocompromised patients (75.0%, 59.6%, 45.5% and 59.1%, respectively).ConclusionsThe results indicate that the latest generation IGRA assay, QFT-Plus, does not perform better than previous generation IGRAs or the TST in children with TB disease. Overall, tests performed worse in CNS and miliary TB, and in immunocompromised children. None of the tests evaluated had sufficiently high sensitivity to be used as a rule-out test in children with suspected TB.

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“…The most widely used immunological tests, such as the tuberculin skin test (TST) and the first-generation Interferongamma release assays (IGRAs, such as the QuantiFERON-TB Gold in Tube (QFT-GIT) and the T-SPOT.TB), although useful and effective in detecting specific immune responses, cannot distinguish within the complex and wide spectrum of TB infection and such these assay do not have prognostic value [8][9][10][11][12]. For these reasons, a new-generation IGRA, the QuantiFERON-TB Gold Plus (QFT-Plus) has been developed, adding to the predecessors an additional antigen tube (TB2), containing shorter peptides of ESAT-6 and CFP-10 which can stimulate both CD4 + and CD8 + T cells, and keeping the same TB1 tube of the QFT-GIT that only stimulates CD4 + cells.…”

Section: Introductionmentioning

confidence: 99%

“…According to early adult studies, the possibility to discriminate CD4 + and CD8 + responses can add sensitivity and specificity in adults and help discriminate active TB from LTBI [10]. However, early pediatric reports demonstrated that in children also the QFT-Plus is not able to discriminate the more complex spectrum of TB disease [8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Commercially available CD4 + and CD8 + IFN-γ release assays combined with an HBHA-induced IGRA improve the characterization of the tuberculosis spectrum and monitoring of treatment in children

et al. 2023

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Commercially available Interferon-γ release assays (IGRAs), including the last-generation QuantiFERON TB-Plus (QFT-Plus), are effective in aiding the diagnosis of tuberculosis (TB) infection but cannot distinguish latent TB subjects from active TB patients. The aim of this study was to prospectively evaluate the performance of an HBHA-based IGRA, combined with commercially available IGRAs, to assess their usefulness as a prognostic biomarkers and aid in the monitoring of TB treatment in children. Following clinical, microbiological, and radiological assessment, children younger than 18 years of age classified as either LTBI or active TB were tested at baseline and during treatment by the QuantiFERON TB-Plus (QFT) assay and an aliquot of whole-blood was stimulated with HBHA. Among the 655 children evaluated, 559 (85.3%) were classified as “Non TB”, 44 patients (6.7%) with active TB, and 52 (7.9%) with LTBI. The median HBHA-IGRA IFN-gamma responses were able to discriminate active TB from LTBI (0.13 IU/ml vs 1.995, (p < 0,0001), those with asymptomatic TB from those with symptomatic TB (1.01 IU/ml vs 0.115 IU/ml, p 0.017), or more severe TB (p 0.022), and significantly raised during successful TB treatment (p < 0.0001). Conversely, CD4 + and CD8 + responses were similar in all groups of patients, although active TB patients had higher CD4 + responses and LTBI higher CD8 + responses. Conclusion: HBHA-based IGRA, combined with CD4 + and CD8 + responses assessed by commercially available IGRAs, is a useful support in the characterization of the TB spectrum in children and monitoring of TB-therapy. What is Known:• Current immune diagnostics are not able to discriminate active and latent Ttuberculosis, including the recently approved QFT-PLUS..• New immunological assays with prognostic value are highly needed. What is New:• HBHA-based IGRA, combined with CD4+ and CD8+ responses assessed by commercially available IGRAs, is a useful support for the differentiation of active and latent TB in children..• HBHA-based IGRA, combined with CD4+ and CD8+ responses assessed by commercially available IGRAs, is a useful support in the monitoring of TBtherapy in children..

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QuantiFERON-TB Gold Plus Assay Specificity in Children and Adolescents With Suspected Tuberculosis—A Multicenter Cross-sectional Study in Spain

Cited by 6 publications

References 17 publications

Performance of QuantiFERON-TBGold Plus assays in children and adolescents at risk of tuberculosis: a cross-sectional multicentre study

Performance of QuantiFERON-TBGold Plus assays in children and adolescents at risk of tuberculosis: a cross-sectional multicentre study

Performance of QuantiFERON-TB Gold Plus assays in paediatric tuberculosis: a multicentre PTBNET study

Commercially available CD4 + and CD8 + IFN-γ release assays combined with an HBHA-induced IGRA improve the characterization of the tuberculosis spectrum and monitoring of treatment in children

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