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Comparison of Two Interferon- Assays and Tuberculin Skin Test for Tracing Tuberculosis Contacts

¹ Leiden University Medical Center, Infectious Diseases, Leiden, The Netherlands; ² Diakonessenhuis Utrecht, Medical Microbiology and Immunology, Utrecht, The Netherlands; ³ Municipal Health Authority, Tuberculosis Control, Utrecht, The Netherlands; ⁴ KNCV Tuberculosis Foundation, The Hague, The Netherlands; ⁵ Academisch Medisch Centrum, Centre for Infection and Immunity Amsterdam, Amsterdam, The Netherlands; ⁶ Diakonessenhuis Utrecht, Clinical Chemistry, Utrecht, The Netherlands; ⁷ Diakonessenhuis Utrecht, Pulmonology, Utrecht, The Netherlands; and ⁸ Heart Lung Center Utrecht, Pulmonology, Utrecht, The Netherlands

Correspondence and requests for reprints should be addressed to Dr. Ailko Bossink, Ph.D., Department of Pulmonology, Diakonessenhuis Utrecht/Zeist, P.O. Box 80250, 3508 TG Utrecht, The Netherlands. E-mail: aikbossink{at}mac.com

Background: The tuberculin skin test (TST) has low specificity. QuantiFERON-TB Gold (QFT-G) and T-SPOT.TB are based on interferon (IFN)- responses to Mycobacterium tuberculosis–specific antigens. A novel in-tube format of QFT-G (QFT-GIT) offers logistical advantages.

Objective: To compare TST, QFT-GIT, and T-SPOT.TB in bacillus Calmette-Guérin unvaccinated contacts and correlate results with measures of recent exposure.

Methods: When a supermarket employee with smear-positive tuberculosis had infected most close contacts, a contact investigation among more than 20,000 customers was performed. We recruited subjects randomly on the day of TST administration (n = 469) and subjects with TST of more than 0 mm on the day of TST reading (n = 316). QFT-GIT and T-SPOT.TB were performed. Demographic data and measures of exposure were collected. TST results were analyzed at a cutoff of 10 or 15 mm. Blood tests were interpreted following the manufacturers' criteria and by varying cutoff levels.

Results: Among 785 study participants, TST results were associated with age, whereas positive IFN- responses were significantly associated with cumulative shopping time, most markedly for QFT-GIT. Among participants with a TST of 15 mm or greater, sensitivity of QFT-GIT and T-SPOT.TB was 42.2 and 51.3%, respectively. Interassay agreement was 89.6% ( = 0.59). By varying cutoff values, agreement between the IFN- assays was optimal at 93.6% ( = 0.71) using a cutoff of 0.20 IU/ml for QFT-GIT and 13 spots for T-SPOT.TB.

Conclusions: Blood test results were associated with exposure, whereas the TST was not. A possible lack of sensitivity of IFN- assays in detecting individuals with TST of 15 mm or greater, despite negative bacillus Calmette-Guérin vaccination status, warrants further investigation into alternative cutoff values.

Key Words: contact tracing • ELISPOT • interferon- • latent tuberculosis infection • tuberculosis • tuberculin skin test

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Interferon- assays may be used to replace the tuberculin skin test (TST) in the diagnosis of (latent) tuberculosis. However, little is known about the performance of two commercially available interferon- release assays compared with the TST in contact-screening investigations. What This Study Adds to the Field Interferon- assay results are associated with the degree of tuberculosis exposure, whereas TST is not.

 

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