Published online March 2, 2009
PEDIATRICS Vol. 123 No. 3 March 2009, pp. e419-e424 (doi:10.1542/peds.2008-1722)
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ARTICLE

Performance of Commercial Blood Tests for the Diagnosis of Latent Tuberculosis Infection in Children and Adolescents

Barbara Maria Bergamini, MDa, Monica Losi, PhDb, Francesca Vaienti, MDa, Roberto D'Amico, PhDc, Barbara Meccugni, BScd, Marisa Meacci, BScd, Donatella De Giovanni, MDa, Fabio Rumpianesi, MDd, Leonardo M. Fabbri, MDb, Fiorella Balli, MDa and Luca Richeldi, MD, PhDb

Departments of a Pediatrics
b Respiratory Diseases
c Statistics, University of Modena and Reggio Emilia, Modena, Italy
d Microbiology and Virology Laboratory, Policlinico Hospital of Modena, Modena, Italy

BACKGROUND. The accurate diagnosis of latent tuberculosis infection reduces the risk of progression to severe disseminated disease. However, in young children, a major limitation of the standard tuberculin skin test is that false-negative results cannot be detected. The new interferon-{gamma} release assays QuantiFERON-TB Gold (Cellestis Carnegie Victoria, Australia), QuantiFERON-TB In-Tube (Cellestis), and T-SPOT.TB (Oxford Immunotec, Abingdon, United Kingdom) show promise of greater accuracy, but they may also be affected by impaired cellular immunity, resulting in indeterminate results (ie, insufficient response in positive-control wells).

OBJECTIVE. To evaluate the impact of age on the performance of interferon-{gamma} release assays when used in a routine hospital setting among children tested for suspected active or latent TB infection.

METHODS. We retrospectively studied 496 children 0 to 19 years of age who had been tested with the tuberculin skin test and at least 1 interferon-{gamma} release assay: 181 with QuantiFERON-TB Gold and 315 with QuantiFERON-TB In-Tube. In 154 of the children, paired interferon-{gamma} release assay testing was available: 87 with QuantiFERON-TB Gold/T-SPOT.TB and 67 with QuantiFERON-TB In-Tube/T-SPOT.TB.

RESULTS. Compared with T-SPOT.TB, the rates of indeterminate results were significantly higher for both QuantiFERON-TB Gold and QuantiFERON-TB In-Tube. QuantiFERON-TB Gold and QuantiFERON-TB In-Tube also gave indeterminate results more frequently in children <4 years of age than in those ≥4 years of age. Indeterminate results were associated with younger age for both QuantiFERON-TB Gold and QuantiFERON-TB In-Tube but not for T-SPOT.TB. Considering age as a binary variable (<4 and ≥4 years of age), a significantly higher concentration of phytohaemagglutinin-produced interferon-{gamma} was observed in older children with both QuantiFERON-TB Gold and QuantiFERON-TB In-Tube.

CONCLUSIONS. Different blood tests for the diagnosis of latent tuberculosis infection in children seem to perform differently, because both QuantiFERON-TB tests were more likely than T-SPOT.TB to give indeterminate results in children <4 years of age.

Key Words: tuberculosis infection • diagnosis • children • interferon-{gamma}

Abbreviations: IGRA—interferon-{gamma} release assay • IFN-{gamma}—interferon-{gamma} • ELISA—enzyme-linked immunosorbent assay • ELISPOT—enzyme-linked immunospot • QFT-G—QuantiFERON-TB Gold • QFT-IT—QuantiFERON-TB Gold In-Tube • TST—tuberculin skin test • LTBI—latent tuberculosis infection • TB—tuberculosis • ESAT-6—early secretory antigen target 6 • CFP10—culture filtrate protein 10 • SFU—spot-forming unit • OR—odds ratio • CI—confidence interval

Accepted Dec 4, 2008.


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