Within-subject variability and boosting of T-cell interferon-gamma responses after tuberculin skin testing.

RATIONALE: The optimal strategy for the diagnosis of latent tuberculosis infection is controversial. Adoption of a two-step strategy (tuberculin skin test [TST] followed by an IFN-gamma release assay [IGRA], compared with an IGRA alone), may be limited by TST-mediated boosting of subsequent IGRA responses. Assessment of within-subject IGRA variability will aid in establishing thresholds for conversions and reversions, and interpretation of serial testing results. OBJECTIVES: To determine short-term IGRA variability and the impact of TST on subsequent IGRA results. METHODS: Within-subject variability and TST-mediated boosting of IGRA responses were evaluated in 26 South African participants with varying exposure risk. IGRAs (T-SPOT.TB, QuantiFERON-TB Gold In-Tube [QuantiFERON-TB-GIT], PPD, and heparin-binding hemagglutinin) were repeated four times over 21 days pre-TST, and on Days 3, 7, 28, and 84 post-TST administration. MEASUREMENTS AND MAIN RESULTS: All participants showed within-subject IGRA variability. Changes of +/-3 spots (T-SPOT.TB) or +/-80% from the mean IFN-gamma response (QuantiFERON-TB-GIT) over 3 weeks explained 95% of the variability. Spontaneous conversions/reversions occurred in 7 of 26 subjects (27%) (6 for T-SPOT.TB and 1 for QuantiFERON-TB-GIT [P = 0.049]) during the within-patient variability studies (pre-TST). After the TST eight subjects (33%) boosted above the defined baseline variability. By Day 7 post-TST, but not Day 3, 2 (12.5%) initially IGRA-negative test subjects converted. By contrast, boosting of PPD and heparin-binding hemagglutinin occurred by Day 3 post-TST. CONCLUSIONS: When using a two-step screening strategy it appears safe to perform a QuantiFERON-TB-GIT or T-SPOT.TB IGRA within 3 days of performing the TST. A 3-spot or 80% IFN-gamma response variation, on either side of baseline values, explains 95% of the short-term variability and may be useful for interpreting conversions and reversions, and values close to the cut-point.

Characteristic magnetic resonance imaging low T2 signal intensity of necrotic lung parenchyma in children with pulmonary tuberculosis.

PURPOSE: To show that necrotic areas of the lung demonstrated on computed tomographic scanning in children with primary pulmonary tuberculosis (TB) may be of low signal intensity on T2. MATERIALS AND METHODS: Review of magnetic resonance imaging scans (T1/T2/STIR/postgadolinium T1) in 6 children scanned because of low-density necrotic areas demonstrated on computed tomography scanning prior to bronchoscopic confirmation of pulmonary TB. RESULTS: Abnormalities included airspace consolidation in 6 children (100%); central necrosis in 6 children (100%); nodules in 2 children (33.3%); and lymphadenopathy in 6 children (100%). Low T2 signal in the areas of necrosis was demonstrated in all 6 children (100%) and in an area of at least 2 × 2 cm; 1 child also showed an area of high signal (16.67%). Airspace consolidation demonstrated T2 high signal in all the children (100%). Both children with nodules demonstrated at least 1 nodule with a low signal in addition to the majority of high-signal nodules. Post gadolinium, the consolidation and all high-signal nodules demonstrated enhancement, whereas the areas of lung necrosis and low signal nodules showed no enhancement. CONCLUSION: Lung parenchymal necrosis in primary pulmonary TB in children may be of low signal intensity on T2 and STIR magnetic resonance imaging. This may be distal to lymphobronchial obstruction and is probably due to the caseating necrosis.