Interferon-gamma release assay conversion after M. tuberculosis exposure specifically associates with greater risk of progression to tuberculosis: a prospective cohort study in Leicester (UK)

Objectives

We investigated whether quantifying the serial QuantiFERON-TB Gold (QFT) response improves tuberculosis (TB) risk stratification in pulmonary TB (PTB) contacts.

Methods

297 untreated adult household PTB contacts, QFT tested at baseline and 3 months after index notification, were prospectively observed (median 1460 days). Normal variance of serial QFT responses was established in 46 extra-pulmonary TB contacts. This informed categorisation of the response in QFT-positive PTB contacts as: converters; persistently QFT-positive with significant increase (PP_increase); and without significant increase (PP_no-increase).

Results

Eight co-prevalent TB (disease ≤ 3 months after index notification) and 12 incident TB (>3 months after index notification) cases were diagnosed. Genetic linkage to the index strain was confirmed in all culture-positive progressors. Cumulative 2-year incident TB risk in QFT-positive contacts was 8.4% (95% CI, 3.0% - 13.6%); stratifying by serial QFT response, significantly higher risk was observed in QFT-converters (28%), compared with PP_no-increase (4.8%) and PP_increase (3.7%). Converters were characterised by exposure to index cases with a shorter interval from symptom onset to diagnosis (median reduction 50.0 days, p=0.013).

Conclusion

QFT conversion rather than quantitative changes of a persistently positive serial QFT response, associates with greater TB risk and exposure to rapidly progressive TB.