Persistently Retained Interferon-Gamma Responsiveness in Individuals with a History of Pulmonary Tuberculosis

Abstract

The interferon gamma (IFN-γ) release assays (IGRAs) are the best method of detecting Mycobacterium tuberculosis infection. However, reports on IGRAs results obtained during and right after the treatment of tuberculosis (TB) have presented differing results. Some studies have shown declining responses, whereas other reports described persistent, fluctuating, or increasing responses. We postulated that the IGRA-positivity will decrease or revert long time after treatment of TB, and thus, evaluated the response of IGRA in subjects with a history of pulmonary TB. Seventy subjects (M:F = 51:19; age = 53.2 ± 11.8 years) underwent tuberculin skin tests (TSTs) and IGRA. The interval of time elapsed after the completion of anti-TB treatment was < 10 years for 16 subjects, 10-20 years for 13 subjects, 20-30 years for 16 subjects, and ≥ 30 years for 25 subjects. The TST was positive in 49 subjects (74%) and negative in 17 subjects (26%). The IGRA was positive in 52 subjects (74%) and negative in 18 subjects (26%). The IFN-γ level and the size of induration showed good correlation (r = 0.525, P < 0.001). However, the correlation between time elapsed after the completion of anti-TB treatment and the size of induration or that between time and the IFN-γ level was not significant. The TST and IGRA were positive in 72.7% and 68.0% of subjects ≥ 30 years after the treatment of pulmonary TB. In conclusion, majority of subjects with a history of pulmonary TB are IGRA-positive, even a few decades after the completion of anti-TB treatment.

Factors associated with prevalent Mycobacterium tuberculosis infection and disease among adolescents and adults exposed to rifampin-resistant tuberculosis in the household

“…Like others, we found that a previous history of TB treatment was associated with Mtb infection [7] and with TB disease [6,14,[16][17][18][19][20][21]. A positive IGRA test could [22] and even decades after completing treatment of active TB disease [23]. We observed the highest prevalence of Mtb infection in HHCs 25-49 years of age, with a pattern similar to early TST surveys [24,25] and a 2002 report from The Gambia [11] of increasing prevalence with age and declines in older adults.…”

A Perspective on the Success and Failure of BCG

“…Mtb -specific CD4 + T-cell responses are elevated during active TB, and a proportion of these cells can persist as memory cells after successful treatment ( 35 , 36 ). It has been estimated that ~70% of people cured of pulmonary TB exhibit positive tuberculin reaction and IGRA up to 30 years after treatment ( 37 ). With Mtb reinfection, these hosts are more likely to mount hyperactive CD4 + T-cell responses, leading to active TB.…”

Overlooked, dismissed, and downplayed: reversion ofMycobacterium tuberculosisimmunoreactivity

“…Similarly, biological or assay variability are commonly suggested as reasons for IGRA reversion [ 49 , 75 , 76 ]. Some emphasise that the “majority” with immunoreactivity “remain” positive [ 77 , 78 ]; cite studies from high-incidence settings and/or in strong reactors and report that reversion occurs infrequently [ 79 , 80 ]; or draw attention to the “stability” of negative responses, rather than the more dynamic positive responses [ 47 ]. Lastly, reversion that is observed to occur soon after presumed infection has been labelled “transient conversion” [ 81 , 82 ], giving the impression it is a phenomenon that exclusively occurs soon after exposure.…”