Jonathan W Uzorka1, Ailko W J Bossink2, Willeke P J Franken3, Steven F T Thijsen4, Eliane M S Leyten5, Alida C van Haeften6, Gert Doornenbal6, Peter Boonstra6, Tom H M Ottenhoff1, Sandra M Arend7. 1. Department of Infectious Diseases, Leiden University Medical Center, Room C5P-40, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands. 2. Department of Pulmonology, Hospital Diakonessenhuis, Jagersingel 1, 3707 JA, Zeist, Utrecht/Zeist, The Netherlands. 3. Department of Clinical Chemistry, Certe Location Medical Center Leeuwarden, Borniastraat 34, 8934 AD, Leeuwarden, The Netherlands. 4. Department of Medical Microbiology, Hospital Diakonessenhuis, Bosboomstraat 1, 3582 KE, Utrecht, The Netherlands. 5. Department of Internal Medicine, Haaglanden Medical Center, Lijnbaan 32, 2512 VA, Den Haag, The Netherlands. 6. Department of Infectious Diseases, Municipal Health Service of Utrecht (GGD), Stadsplateau 1, 3521 AZ, Utrecht, The Netherlands. 7. Department of Infectious Diseases, Leiden University Medical Center, Room C5P-40, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands. Electronic address: s.m.arend@lumc.nl.
Abstract
BACKGROUND: QuantiFERON (QFT) results near the cut-off are subject to debate. We aimed to investigate which borderline QFT results were due to Mycobacterium tuberculosis (Mtb)-specific responses or to test variability. METHODS: In a contact investigation, tuberculin skin test (TST), QFT and T-SPOT.TB (T-SPOT) were performed in 785 BCG-unvaccinated contacts. Contacts with a low-negative (<0.15), borderline (0.15-0.35), low-positive (0.35-0.70) or high-positive QFT (≥0.70 IU/mL) were compared with respect to exposure, TST and T-SPOT results. Development of active tuberculosis was assessed. RESULTS: Borderline QFT results occurred in threefold excess over test variability (p = 0.0027). In contacts with low-negative, borderline or positive QFT results, a positive TST occurred in 24.9%, 62.1% and 91.4% (p < 0.0001) and a positive T-SPOT result in 6.3%, 41.3% and 86.4%, respectively (p < 0.0001). Two-third (20/29) of contacts with a borderline and 14/16 (88%) with a low-positive QFT had a positive TST and/or T-SPOT, indicating probable Mtb-infection. During 12 years of follow-up, seven patients were diagnosed with active tuberculosis, two of whom after a low-positive QFT. CONCLUSIONS: In this study, most borderline and low-positive QFT results were Mtb-specific, showing the biological significance of a borderline QFT. The clinical relevance, however, will be most distinct in patients who are or will be immunocompromised.
BACKGROUND: QuantiFERON (QFT) results near the cut-off are subject to debate. We aimed to investigate which borderline QFT results were due to Mycobacterium tuberculosis (Mtb)-specific responses or to test variability. METHODS: In a contact investigation, tuberculin skin test (TST), QFT and T-SPOT.TB (T-SPOT) were performed in 785 BCG-unvaccinated contacts. Contacts with a low-negative (<0.15), borderline (0.15-0.35), low-positive (0.35-0.70) or high-positive QFT (≥0.70 IU/mL) were compared with respect to exposure, TST and T-SPOT results. Development of active tuberculosis was assessed. RESULTS: Borderline QFT results occurred in threefold excess over test variability (p = 0.0027). In contacts with low-negative, borderline or positive QFT results, a positive TST occurred in 24.9%, 62.1% and 91.4% (p < 0.0001) and a positive T-SPOT result in 6.3%, 41.3% and 86.4%, respectively (p < 0.0001). Two-third (20/29) of contacts with a borderline and 14/16 (88%) with a low-positive QFT had a positive TST and/or T-SPOT, indicating probable Mtb-infection. During 12 years of follow-up, seven patients were diagnosed with active tuberculosis, two of whom after a low-positive QFT. CONCLUSIONS: In this study, most borderline and low-positive QFT results were Mtb-specific, showing the biological significance of a borderline QFT. The clinical relevance, however, will be most distinct in patients who are or will be immunocompromised.
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