A Three-Way Comparison of Tuberculin Skin Testing, QuantiFERON-TB Gold and T-SPOT.TB in Children

Abstract

BackgroundThere are limited data comparing the performance of the two commercially available interferon gamma (IFN-γ) release assays (IGRAs) for the diagnosis of tuberculosis (TB) in children. We compared QuantiFERON-TB gold In Tube (QFT-IT), T-SPOT.TB and the tuberculin skin test (TST) in children at risk for latent TB infection or TB disease.Methods and FindingsThe results of both IGRAs were compared with diagnosis assigned by TST-based criteria and assessed in relation to TB contact history. Results from the TST and at least one assay were available for 96 of 100 children. Agreement between QFT-IT and T-SPOT.TB was high (93% agreement, κ = 0.83). QFT-IT and T-SPOT.TB tests were positive in 8 (89%) and 9 (100%) children with suspected active TB disease. There was moderate agreement between TST and either QFT-IT (75%, κ = 0.50) or T-SPOT.TB (75%, κ = 0.51). Among 38 children with TST-defined latent TB infection, QFT-IT gold and T-SPOT.TB assays were positive in 47% and 39% respectively. Three TST-negative children were positive by at least one IGRA. Children with a TB contact were more likely than children without a TB contact to have a positive IGRA (QFT-IT LR 3.9; T-SPOT.TB LR 3.9) and a positive TST (LR 1.4). Multivariate linear regression analysis showed that the magnitude of both TST induration and IGRA IFN-γ responses was significantly influenced by TB contact history, but only the TST was influenced by age.ConclusionsAlthough a high level of agreement between the IGRAs was observed, they are commonly discordant with the TST. The correct interpretation of a negative assay in a child with a positive skin test in clinical practice remains challenging and highlights the need for longitudinal studies to determine the negative predictive value of IGRAs.

Diagnosis of tuberculosis infection using interferon-γ-based assays

“…4,7 Discordant results between these tests and TST are frequently found. 7,[45][46][47][48] In a study conducted in Barcelona (Spain), 7 among BCG-unvaccinated children, 60% and 57% of those with positive TST had negative QF-IT and T-SPOT.TB respectively. Latorre et al 49 reported that 48% of children with TST positive and negative T-SPOT.TB had sensitized T cells against Mycobacterium avium sensitins.…”

Diagnostic Value of T SPOT TB in Infant to 5-Year Old Children with Primary Forms of Tuberculosis

“…6, it can be seen that the children, who were in contact with tuberculous adults, have pronounced reactions to both the TST and the T SPOT TB, which once again shows that the close contact with a tuberculous patient affects the immunological reactivity of the body and results in more frequently in a disease [8][9][10]12].…”

Pulmonary Tuberculosis in Children

“…Less than 15% of children with TB have a positive sputum smear and mycobacterial culture detects the bacilli in 30%-40% (1, 2, 6). In the absence of bacteriological confirmation, the diagnosis of childhood TB in countries where TB is endemic is based on close contact with an infectious patient, a positive tuberculin skin test, presence of suggestive clinical signs and syptoms, and or abnormalities on a chest-X ray (17)(18)(19)(20). Chest radiograph findings may be normal for a significant proportion of children with confirmed pulmonary TB.…”

“…The tuberculin skin test (TST) is a widely used as a diagnostic test for evaluation of patients who have symptoms of tuberculosis or in those infections with M tuberculosis is suspected. The sensitivity and the specificity of the TST is about 90% .Efforts are making to develop tests based on detection of antigens, such as lipoarabinomannan in urine or serum samples, and detection of interferon-γ production by sensitized mononuclear cells on stimulation by specific M. tuberculosis antigens ESAT-6 and CFP-10 is an alternative to TST (12)(13)(14)(15)(16)(17)(18). This test (interferon-γ release assays) has not been detected to have a major advantages over the TST in terms of sensitivity or specificity and is more expensive; although, it does not require a second patient visit, and they reduce the chances of human error in interpretation.…”

“…This test (interferon-γ release assays) has not been detected to have a major advantages over the TST in terms of sensitivity or specificity and is more expensive; although, it does not require a second patient visit, and they reduce the chances of human error in interpretation. New tests such as antigen detection could mainly play a role in detection of TB in HIV-infected or malnourished children, however, they require to further evaluation (12,18,19).…”