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

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 assa...

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Published in:European journal of pediatrics 2023-01, Vol.182 (1), p.307-317
Main Authors: Calzada-Hernández, Joan, Anton, Jordi, Martín de Carpi, Javier, López-Montesinos, Berta, Calvo, Inmaculada, Donat, Ester, Núñez, Esmeralda, Blasco Alonso, Javier, Mellado, María José, Baquero-Artigao, Fernando, Leis, Rosaura, Vegas-Álvarez, Ana María, Medrano San Ildefonso, Marta, Pinedo-Gago, María del Carmen, Eizaguirre, Francisco Javier, Tagarro, Alfredo, Camacho-Lovillo, Marisol, Pérez-Gorricho, Beatriz, Gavilán-Martín, César, Guillén, Sara, Sevilla-Pérez, Belén, Peña-Quintana, Luis, Mesa-Del-Castillo, Pablo, Fortuny, Clàudia, Tebruegge, Marc, Noguera-Julian, Antoni
Format: Article
Language:English
Subjects:
C-reactive protein
Child
Children
Cohort Studies
Humans
Immunosuppressive agents
Infections
Inflammatory bowel diseases
Inflammatory diseases
Interferon-gamma Release Tests - methods
Latent Tuberculosis - diagnosis
Latent Tuberculosis - drug therapy
Latent Tuberculosis - epidemiology
Medicine
Medicine & Public Health
Patients
Pediatrics
Skin tests
Spain - epidemiology
Tuberculin
Tuberculin - therapeutic use
Tuberculin Test - methods
Tuberculosis
Tumor Necrosis Factor Inhibitors - therapeutic use
Tumor Necrosis Factor-alpha - therapeutic use
Tumor necrosis factor-α
Tumors
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Summary: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.
ISSN:1432-1076
0340-6199
1432-1076
DOI:10.1007/s00431-022-04640-3