Trajectories of Interferon-Gamma Release Assay Results Over 2 Years in Independent Cohorts From China, South Africa, Tanzania, and the United States.

Abstract

There is an ongoing debate about whether clearance of Mycobacterium tuberculosis infection occurs and at what magnitude. Recent studies quantifying "uncertainty zones" of interferon-gamma release assays (IGRAs) provide a more stringent estimate of reversion. When accounting for uncertainty zones through stringent cutoffs, what are the trajectories of IGRAs results over 2 years of testing? Five cohorts from South Africa, China, Tanzania, and the United States tested with an IGRA 3 or more times were followed up for stringent conversion and reversion. The annual risk of IGRA reversion was assessed following an IGRA conversion and among those with baseline positivity. A total of 26,596 IGRA measurements were taken over 13,593 years of follow-up (N_participants = 7,683). Stringent reversion at year 2 following stringent conversion at year 1 varied between cohorts, occurring in 48% (43/90) for Wantai, 37% (22/59) for QuantiFERON, and 17% (2/12) for T-SPOT.TB, respectively. In the US cohorts, stringent reversion at year 1 following stringent conversion at 6 months was 58% (15 of 26) for QuantiFERON and 18% (12 of 60) for T-SPOT.TB. Stringent reversion at 1 year following baseline positivity occurred in 12% (47 of 404) for Wantai, 21% (10 of 48) for QuantiFERON, and 44% for T-SPOT.TB (45 of 102). In one cohort from China (N = 399; age range, 59 years [interquartile range, 48-67 years]), IGRA reversion was more common in younger participants (adjusted OR [aOR], 0.95; 95% CI, 0.93-0.97) and those without recent close TB exposure (aOR, 0.35 [95% CI, 0.11-1.03] in South Africa; aOR, 0.10 [95% CI, 0.01-0.61] in China). These results suggest high annual rates of IGRA reversion, even with the use of uncertainty zones; reversion rates decreased over time from exposure and at older ages.