Trajectories of interferon-gamma release assay results over two years in independent cohorts from China, South Africa, Tanzania, and the United States.
Chen C., Xue H., Horsburgh CR., Amour M., Hatherill M., Tameris M., von Reyn CF., Rees C., Shen Y., McShane H., García-Basteiro AL., Liu D., Wang Y., Nathavitharana RR., Graviss EA., Shao Y., Liu Q., Lu W., Zhu L., Martinez L.
BACKGROUND: 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 (IGRA) provide a more stringent estimate of reversion, potentially indicating clearance. RESEARCH QUESTION: When accounting for 'uncertainty zones' through stringent cutoffs, what are the trajectories of interferon-gamma release assays in cases of Mycobacterium tuberculosis infection? STUDY DESIGN AND METHODS: We followed five cohorts from South Africa, China, Tanzania, and the United States tested with an IGRA test three or more times for stringent conversion and reversion. The annual risk of IGRA reversion was assessed after an IGRA conversion and among those with baseline positivity. RESULTS: 26,596 IGRA measurements were taken over 13,593 years of follow-up (Nparticipants=7,683). Stringent reversion at year 2 after 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 U.S. cohorts, stringent reversion at year 1 after stringent conversion at 6 months was 58% (15/26) for QuantiFERON and 18% (12/60) for T-SPOT.TB. Stringent reversion at 1 year after baseline positivity occurred in 12% (47/404) for WANTAI, 21% (10/48) for QuantiFERON and 44% for T-SPOT.TB (45/102). In one cohort from (N=399; age range, 59 years [IQR, 48-67]), IGRA reversion was more common in younger participants (Adjusted Odds Ratio [aOR], 0.95; 95% CI, 0.93-0.97) and those without recent close tuberculosis exposure (aOR, 0.35; 95%CI, 0.11-1.03 in South Africa; 0.10; 95%CI, 0.01-0.61 in China). INTERPRETATION: These results suggest high annual rates of IGRA reversion, even with the use of 'uncertainty zones'; reversion rates decreased with time from exposure and at older ages.