Limited usefulness of QuantiFERON-TB Gold In-Tube® for monitoring anti-tuberculosis therapy

Abstract

The usefulness of IFN-gamma release assays to monitor the efficacy of anti-tuberculosis (TB) treatment is controversial. Sixty patients affected by culture-confirmed pulmonary TB (M = 36; mean age: 39.2 yr; Italians = 28) were serially tested in a low prevalence setting by means of QuantiFERON-TB GOLD In-Tube (QFT-IT) at baseline and after a successful six-month therapy regimen (T6). A sub-group of 40 cases was also tested at 1 and 3 months. Overall, 88.3% of patients scored a QFT-IT positive result at baseline, with the higher proportion of TB-specific IFN-gamma responses in foreign-born patients (p = 0.04). TB-specific responses were highly variable over time, the within-person variability being correlated with baseline IFN-gamma levels (r = 0.731; p < 0.001). Overall, 61.6% of cases still tested QFT-IT positive at the completion of therapy. Average IFN-gamma levels increased over time, being persistently significantly higher in Italian patients than in foreign-born cases both at baseline (p = 0.03) and at T6 (p = 0.02). Reversion mainly occurred in patients (26.6%) with baseline IFN-gamma levels close to the conventional cut-off value. No indeterminate results were recorded at any study time point. In conclusion, QFT-IT adds no significant information to clinicians for treatment monitoring when applied in routine clinical practice in a low prevalence setting. Kinetics of T cell responses upon TB treatment and reversion (and conversion) thresholds need to be addressed. Diversity of IFN-gamma responses among patients of different geographic origin is an issue to be investigated further.

Temporal interferon-gamma release response to Mycobacterium kansasii infection in an anorexia nervosa patient

“…The decreasing kinetics observed for the IGRA response upon treatment of M. kansasii disease were similar to those reported for TB or latent TB, although this pattern was not observed in all studies (Bocchino et al, 2010;Carrara et al, 2004;Chiappini et al, 2012;Katiyar et al, 2008;Kobashi et al, 2009a;Mori, 2009;Pai et al, 2006). Several hypotheses were raised for these discrepancies, such as reinfection in high burden settings, persistence of effector T-cells and within-subject variability (Chiappini et al, 2012;Ewer et al, 2006;Pai et al, 2006;van Zyl-Smit et al, 2009).…”

Facts and dilemmas in diagnosis of tuberculosis in wildlife

“…However, this relation between treatment and IFN-γ decline was not found in other human studies [122,123].…”

Interferon gamma release assays for monitoring the response to treatment for tuberculosis: A systematic review

“…Twenty studies included only adults [47, 48, 50, 53, 55-59, 61, 62, 64-66, 68-71, 73, 76], three studies were done in children [54,63,75] and seven studies had a mixed population [49,51,52,60,67,72,74] (usually including only a small number of children and/or adolescents).…”

“…There was an overall decrease in magnitude (measured as a median or mean) of IFN-γ responses with treatment in 16 studies [51, 53, 55, 57-59, 61, 62, 67, 69, 71-76], whilst 9 showed no significant change [47-49, 52, 54, 63-65, 68], two studies found an overall increase in the magnitude of IFN-γ response [50,70], and three did not report significance testing or were very small pilot studies [56,60,66]. Active TB: 12 of the 18 studies investigating active TB patients reported a statistically significant decrease in the median or mean IFN-γ response [51, 57-59, 61, 67, 69, 71, 73-76], whilst 4 showed no significant change [49,54,63,64], one study found an overall increase in the magnitude of IFN-γ response [50], and one did not report significance testing [56] (table 1). Studies that included both TSPOT.TB and QFT to measure IFN-γ response reported concordant reductions in both assays [74][75][76].…”