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Comparison of Two Interferon-Gamma Release Assays for Pediatric Tuberculosis Infection
James T Gaensbauer1,2, Randall R Reves3, Dolly Katz4
1Mayo Clinic Center for Tuberculosis, Mayo Clinic, Rochester, MN, United States.
Insights
In pediatric tuberculosis infection testing, QuantiFERON-TB Gold In-Tube (QFT-GIT) showed more positive results than T-SPOT.TB (T-SPOT), with differences unrelated to borderline test values.
Area of Science:
- Pediatric infectious diseases
- Immunology
- Diagnostic test performance
Background:
- Interferon-gamma release assays (IGRAs) are crucial for identifying tuberculosis infection (TBI) to prevent pediatric tuberculosis (TB).
- Limited comparative data exist for the two main IGRAs in US pediatric populations.
- This study addresses the need for comparative performance data of T-SPOT.TB and QuantiFERON-TB Gold In-Tube in children.
Purpose of the Study:
- To compare the performance of T-SPOT.TB and QuantiFERON-TB Gold In-Tube (QFT-GIT) in a large US pediatric cohort.
- To investigate if quantitative results near test cutoffs explain discordance between the two IGRAs.
- To provide data for informed clinical and public health decisions regarding pediatric TBI screening.
Main Methods:
- A US multicenter study identified 3793 children (aged 0-15 years) tested with both T-SPOT.TB and QFT-GIT.
- Results were compared using McNemar's Chi-square tests, stratified by age and testing reason.
- Quantitative results of discordant cases were analyzed to assess proximity to test cutoffs.
Main Results:
- QFT-GIT yielded a higher positivity rate (10.1%) compared to T-SPOT.TB (7.4%) (P < .001).
- This difference was consistent across most age groups and testing indications.
- Discordance was not explained by results near the standard cutoffs for either test.
Conclusions:
- QFT-GIT demonstrated a higher proportion of positive tuberculosis infection test results than T-SPOT.TB in this pediatric cohort.
- The observed discordance between the two IGRAs was not attributable to quantitative results falling close to the diagnostic thresholds.
- Findings highlight differences in IGRA performance in children and suggest further investigation into discordance factors.
Introduction:
Identifying tuberculosis infection (TBI) using interferon-gamma release assays (IGRAs) is a primary component of clinical and public health efforts to prevent pediatric tuberculosis (TB). Pediatric data comparing the 2 IGRAs in the United States are very limited. We compared the performance of the 2 IGRAs among a large pediatric cohort tested for TBI and assessed whether discordance might be due to quantitative results close to test cutoff values.
Methods:
Children aged 0-15 years with both T-SPOT.TB (T-SPOT) and QuantiFERON-TB Gold In-Tube (QFT-GIT) tests were identified from a US multicenter study enrolling people at elevated risk of TBI or progression to TB disease. Results were compared using McNemar's Chi-square tests with stratification by age category and testing reason. Percent agreement and kappa statistics were also calculated. We characterized quantitative test results among children with discordant QFT-GIT-positive/T-SPOT-negative results.
Results:
Among 3793 children, a higher number had positive QFT-GIT than T-SPOT (10.1% vs 7.4%, P < .001). This difference was noted for all age categories except <2 years, and for children with close-contact and non-close contact test indications. Among discordant QFT-GIT-positive/T-SPOT-negative children, lowering the positive threshold for T-SPOT to include borderline spot counts (5-7) did not eliminate the discordance, nor were QFT-GIT antigen-minus-nil results concentrated in the range just above the standard cutoff of 0.35 IU/mL.
Conclusions:
In a large pediatric cohort tested for TBI, QFT-GIT had a higher proportion of positive results than T-SPOT, and discordance was not related to quantitative results close to the established diagnostic cutoffs.
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