Identifying predictors of interferon-γ release assay results in pediatric latent tuberculosis: a protective role of bacillus Calmette-Guerin?: a pTB-NET collaborative study.
BACKGROUND
Interferon-γ (IFN-γ) release assays are widely used to diagnose latent infection with Mycobacterium tuberculosis in adults, but their performance in children remains incompletely evaluated to date.


OBJECTIVE
To investigate factors influencing results of IFN-γ release assays in children using a large European data set.


METHODS
The Pediatric Tuberculosis Network European Trials group pooled and analyzed data from five sites across Europe comprising 1,128 children who were all investigated for latent tuberculosis infection by tuberculin skin test and at least one IFN-γ release assay. Multivariate analyses examined age, bacillus Calmette-Guérin (BCG) vaccination status, and sex as predictor variables of results. Subgroup analyses included children who were household contacts.


RESULTS
A total of 1,093 children had a QuantiFERON-TB Gold In-Tube assay and 382 had a T-SPOT.TB IFN-γ release assay. Age was positively correlated with a positive blood result (QuantiFERON-TB Gold In-Tube: odds ratio [OR], 1.08 per year increasing age [P < 0.0001]; T-SPOT.TB: OR, 1.14 per year increasing age [P < 0.001]). A positive QuantiFERON-TB Gold In-Tube result was shown by 5.5% of children with a tuberculin skin test result less than 5 mm, by 14.8% if less than 10 mm, and by 20.2% if less than 15 mm. Prior BCG vaccination was associated with a negative IFN-γ release assay result (QuantiFERON-TB Gold In-Tube: OR, 0.41 [P < 0.001]; T-SPOT.TB: OR, 0.41 [P < 0.001]). Young age was a predictor of indeterminate IFN-γ release assay results, but indeterminate rates were low (3.6% in children < 5 yr, 1% in children > 5 yr).


CONCLUSIONS
Our data show that BCG vaccination may be effective in protecting children against Mycobacterium tuberculosis infection. To restrict use of IFN-γ release assays to children with positive skin tests risks underestimating latent infection.
B.M.B.Ch., Ed.M., Department of Paediatric Allergy and Infectious Diseases, Imperial College London, Norfolk Place, London W2 1NY, UK.  r.basu-roy@imperial.ac.uk.
Robindra
R
Basu Roy
Giovanni
G
Sotgiu
Neus
N
Altet-Gómez
Maria
M
Tsolia
Ezia
E
Ruga
Svetlana
S
Velizarova
Beate
B
Kampmann
D001500:BCG Vaccine / Q000097:blood / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005060:Europe; D005260:Female; D006801:Humans; D007223:Infant; D059425:Interferon-gamma Release Tests / Q000379:methods*; D055985:Latent Tuberculosis / Q000097:blood* / Q000517:prevention & control*; D008297:Male; D016017:Odds Ratio; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D014374:Tuberculin Test / Q000379:methods / Q000706:statistics & numerical data
D001500:BCG Vaccine