Interferon-Gamma Release Assays Differentiate between Mycobacterium avium Complex and Tuberculous Lymphadenitis in Children

Martínez-Planas, Aina; Baquero‐Artigao, Fernando; Santiago, Begoña; Fortuny, Clàudia; Méndez-Echevarría, Ana; Rabes, T. del Rosal; Bustillo-Alonso, Matilde; Gale, Inés; Guerrero, Carmelo; Blázquez‐Gamero, Daniel; Canet, Anna; Lillo, Miguel; Calavia, Olga; Cuadros, Esmeralda Núñez; Falcón-Neyra, Lola; Soriano‐Arandes, Antoni; Ingen, Jakko van; Tebruegge, Marc; Noguera-Julián, Antoni; Vallmanya, Teresa; Minguell, Laura; Martin‐Nalda, Andrea; Soler‐Palacín, Pere; Espiau, María; Lobato, Zulema; García, Lourdes; Velázquez, Miguel Ángel Rado; Herranz, M. Angel Sauras; Arroyo, Mireia; Gutiérrez, Carmelo; Gavilán, César; Piqueras, Ana Isabel; Martinón‐Torres, Federico; Villanueva, Isabel; Rueda, Santiago; Ramos, Marta Illán; Morales, Ana; Roa, Miguel; Pérez-Gorricho, Beatriz; Pinto, Enrique Villalobos; Sanz-Santaeufemia, Francisco José; Álvarez, Javier; Álvarez, Cristina; Guarch, Borja; Montero, M. Ángeles; Cilleruelo, María José; Otheo, Enrique; Calvo, Cristina; Murua, José Javier Korta; Mellado, María José; Rojo, Pablo; Moreno-Pérez, David; Neth, Olaf; Santos, Mar; Hernández, Tomasa Centella; Hidalgo, M. Lafuente; Cepillo, Antonio

doi:10.1016/j.jpeds.2021.05.008

Cited by 10 publications

(5 citation statements)

References 36 publications

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“…We recently reported on the performance of QFT-Plus assay in children and adolescents (<18 years-of-age) at risk of TB infection who underwent a QFT-Plus between September 2016 and June 2020 in Spain, a low-endemic country. 6 This cross-sectional study was performed within the Spanish Pediatric TB Research Network, 7,8 for which approval was obtained from the Hospital Carlos III Ethics Committee (Madrid, ref. P13/12).…”

Section: Methodsmentioning

confidence: 99%

The Value of the Second QuantiFERON-TB Gold-Plus Antigen Tube at Diagnosis and at Treatment Completion in Spanish Children With Tuberculosis

Soler-Garcia,

Gamell,

Monsonís

et al. 2023

Pediatric Infectious Disease Journal

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We studied 295 children (tuberculosis disease, n = 159; latent tuberculosis infection, n = 136) with positive QuantiFERON-TB Gold-Plus assay results. No significant differences between first and second antigen tube interferon-gamma responses were detected, irrespective of patient and disease characteristics at diagnosis. Of patients with a repeat assay after treatment completion (n = 65), only 16.9% converted to negative results.

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Section: Methodsmentioning

confidence: 99%

The Value of the Second QuantiFERON-TB Gold-Plus Antigen Tube at Diagnosis and at Treatment Completion in Spanish Children With Tuberculosis

Soler-Garcia,

Gamell,

Monsonís

et al. 2023

Pediatric Infectious Disease Journal

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“…Recently, the use of TB-IGRAs alone has been reported as suitable to distinguish lymphadenitis caused by MAC from tuberculous lymphadenitis in children. 11 When comparing 2 groups with either NTM- or TB-confirmed lymphadenitis, a specificity of 96.9% for the diagnosis of TB and positive and negative predictive values of 95.7% and 93.9% were obtained, respectively. This study presents a promising perspective for the use of TB-IGRAs in this scenario; however, this strategy should be evaluated further to test its validity in a prospective study.…”

Section: Discussionmentioning

confidence: 90%

“…10 Previous studies indicate that a negative TB-IGRA independently of the TST result could discard M.tb infections. 10,11 A recent revision of 4 cohorts of contact TB children under 2 years of age evidenced that none of 575 untreated children with negative IGRA test results progressed to TB disease. 12 However, a negative TB-IGRA should be interpreted cautiously, given the low sensitivity reported in some studies, especially in young children.…”

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confidence: 99%

Development and Evaluation of an NTM-IGRA to Guide Pediatric Lymphadenitis Diagnosis

Villar-Hernández,

Latorre,

Noguera-Julian

et al. 2023

Pediatric Infectious Disease Journal

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Background: Diagnosis of nontuberculous mycobacteria (NTM) infections remains a challenge. In this study, we describe the evaluation of an immunological NTM-interferon (IFN)-γ release assay (IGRA) that we developed using glycopeptidolipids (GPLs) as NTM-specific antigens. Methods: We tested the NTM-IGRA in 99 samples from pediatric patients. Seventy-five were patients with lymphadenitis: 25 were NTM confirmed, 45 were of unknown etiology but compatible with mycobacterial infection and 5 had lymphadenitis caused by an etiologic agent other than NTM. The remaining 24 samples were from control individuals without lymphadenitis (latently infected with M. tuberculosis, uninfected controls and active tuberculosis patients). Peripheral blood mononuclear cells were stimulated overnight with GPLs. Detection of IFN-γ producing cells was evaluated by enzyme-linked immunospot assay. Results: NTM culture-confirmed lymphadenitis patient samples had a significantly higher response to GPLs than the patients with lymphadenitis of unknown etiology but compatible with mycobacterial infection (P < 0.001) and lymphadenitis not caused by NTM (P < 0.01). We analyzed the response against GPLs in samples from unknown etiology lymphadenitis but compatible with mycobacterial infection cases according to the tuberculin skin test (TST) response, and although not statistically significant, those with a TST ≥5 mm had a higher response to GPLs when compared with the TST <5 mm group. Conclusions: Stimulation with GPLs yielded promising results in detecting NTM infection in pediatric patients with lymphadenitis. Our results indicate that the test could be useful to guide the diagnosis of pediatric lymphadenitis. This new NTM-IGRA could improve the clinical handling of NTM-infected patients and avoid unnecessary misdiagnosis and treatments.

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“…Bacillus Calmette-Guérin (BCG) vaccination is not part of the routine childhood immunization program in Spain, except for the Basque Country, where a single dose was given at birth until 2013. The Spanish Societies of Pediatric Rheumatology, Pediatric Gastroenterology and Pediatric Infectious Diseases, and the Spanish Pediatric TB Research Network [19,20] provided support by encouraging their members to participate in this project. Ultimately, a total of 17 pediatric tertiary referral centers participated in the study.…”

Section: Setting and Participating Centersmentioning

confidence: 99%

Dual latent tuberculosis screening with tuberculin skin tests and QuantiFERON-TB assays before TNF-α inhibitor initiation in children in Spain

et al. 2022

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Tumor-necrosis-factor-α inhibitors (anti-TNF-α) are associated with an increased risk of tuberculosis (TB) disease, primarily due to reactivation of latent TB infection (LTBI). We assessed the performance of parallel LTBI screening with tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube assays (QFT-GIT) before anti-TNF-α treatment in children with immune-mediated inflammatory disorders in a low TB-burden setting. We conducted a multicenter cohort study involving 17 pediatric tertiary centers in Spain. LTBI was defined as the presence of a positive TST and/or QFT-GIT result without clinical or radiological signs of TB disease. A total of 270 patients (median age:11.0 years) were included, mainly with rheumatological (55.9%) or inflammatory bowel disease (34.8%). Twelve patients (4.4%) were diagnosed with TB infection at screening (LTBI, n = 11; TB disease, n = 1). Concordance between TST and QFT-GIT results was moderate (TST+/QFT-GIT+, n = 4; TST−/QFT-GIT+, n = 3; TST+/QFT-GIT-, n = 5; kappa coefficient: 0.48, 95% CI: 0.36–0.60). Indeterminate QFT-GIT results occurred in 10 patients (3.7%) and were associated with young age and elevated C-reactive protein concentrations. Eleven of 12 patients with TB infection uneventfully completed standard LTBI or TB treatment. During a median follow-up period of 6.4 years, only 2 patients developed TB disease (incidence density: 130 (95% CI: 20–440) per 100,000 person-years), both probable de novo infections.Conclusion: A substantial number of patients were diagnosed with LTBI during screening. The dual strategy identified more cases than either of the tests alone, and test agreement was only moderate. Our data show that in children in a low TB prevalence setting, a dual screening strategy with TST and IGRA before anti-TNF-α treatment is effective. What is Known:• The optimal screening strategy for latent tuberculosis in children with immune-mediated inflammatory disorders remains uncertain.• Children receiving anti-TNF-α drugs are at increased risk of developing severe tuberculosis disease. What is New:• A dual screening strategy, using TST and an IGRA assay, identified more children with latent tuberculosis than either of the tests alone.• Identification and treatment of latent tuberculosis before initiation of anti-TNF-α therapy averted incident tuberculosis cases.

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Interferon-Gamma Release Assays Differentiate between Mycobacterium avium Complex and Tuberculous Lymphadenitis in Children

Cited by 10 publications

References 36 publications

The Value of the Second QuantiFERON-TB Gold-Plus Antigen Tube at Diagnosis and at Treatment Completion in Spanish Children With Tuberculosis

The Value of the Second QuantiFERON-TB Gold-Plus Antigen Tube at Diagnosis and at Treatment Completion in Spanish Children With Tuberculosis

Development and Evaluation of an NTM-IGRA to Guide Pediatric Lymphadenitis Diagnosis

Dual latent tuberculosis screening with tuberculin skin tests and QuantiFERON-TB assays before TNF-α inhibitor initiation in children in Spain

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