Introduction We have previously reported prospective data of TB risk in close contacts of tuberculosis with single step interferon gamma release assay (IGRAs) screening 8–12 weeks after index notification and shown a lower positive predictive value of the test in contacts with a higher risk of prior exposure and remote latent tuberculosis infection (LTBI).
We hypothesised that a dynamic change in IGRA response using a two step approach may better identify recent LTBI.
Method Two-step IGRA screening with QuantiFERON TB Gold-In Tube (QFT) was implemented in adult (>16 years) contacts of smear positive pulmonary TB at Leicester. QFT testing was performed as soon as possible after index notification (T1) and if negative repeated after 8–12 weeks (T2). Quantitative QFT values were recorded in all contacts and in those having two tests, the change calculated. Data was mapped to the contacts’ risk of remote infection (low, moderate, high) and estimated duration of exposure to the index case based on the reported date of symptoms onset.
Results 397 contacts of 46 smear positive TB cases were identified. 116 children were excluded. 49 adults did not attend for testing (17.4%). 100 contacts (43%) were QFT positive at T1. In regression analysis duration of index symptoms was independently associated with this outcome (p = 0.001). ROC curve analysis in subgroups stratified by risk of remote LTBI demonstrated the strongest association to be in the lowest risk group (AUC = 0.93, p < 0.0001), with no significant association in the high risk group (AUC = 0.57, p = 0.404). 132 contacts were QFT neg at T1 and 109 returned for repeat testing. For the persistently QFT neg group the change in QFT was ± 1 log10 fold between visits. 9 (8.2%) contacts seroconverted. Two subgroups were identified based on the magnitude of change. In 4 contacts the change was within 1 log fold. In the remainder the change was ≥ 2 log fold and all in this subgroup seroconverted with 150 days of symptoms onset in the index.
Conclusions Serial IGRA with ≥ 2 log10 fold change may indicate recent infection. This may be detectable in contacts of index cases with an early diagnosis.