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

Author:

Bergamini Barbara Maria1,Losi Monica2,Vaienti Francesca1,D'Amico Roberto3,Meccugni Barbara4,Meacci Marisa4,De Giovanni Donatella1,Rumpianesi Fabio4,Fabbri Leonardo M.2,Balli Fiorella1,Richeldi Luca2

Affiliation:

1. Departments of Pediatrics

2. Respiratory Diseases

3. Statistics, University of Modena and Reggio Emilia, Modena, Italy

4. Microbiology and Virology Laboratory, Policlinico Hospital of Modena, Modena, Italy

Abstract

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-γ 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-γ 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-γ release assay: 181 with QuantiFERON-TB Gold and 315 with QuantiFERON-TB In-Tube. In 154 of the children, paired interferon-γ 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-γ 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.

Publisher

American Academy of Pediatrics (AAP)

Subject

Pediatrics, Perinatology, and Child Health

Reference22 articles.

1. Khan EA, Starke JR. Diagnosis of tuberculosis in children: increased need for better methods. Emerg Infect Dis. 1995;1(4):115–123

2. Lewinsohn DA, Gennaro ML, Scholvinck L, Lewinsohn DM. Tuberculosis immunology in children: diagnostic and therapeutic challenges and opportunities. Int J Tuberc Lung Dis. 2004;8(5):658–674

3. Newton SM, Brent AJ, Anderson S, Whittaker E, Kampmann B. Paediatric tuberculosis. Lancet Infect Dis. 2008;8(8):498–510

4. Miyawaki T, Seki H, Taga K, Sato H, Taniguchi N. Dissociated production of interleukin-2 and immune γ interferon by phytohaemagglutinin stimulated lymphocytes in healthy infants. Clin Exp Immunol. 1985;59(2):505–511

5. Huebner RE, Schein MF, Bass JB Jr. The tuberculin skin test. Clin Infect Dis. 1993;17(6):968–975

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