Kinetics of the QuantiFERON^®-TB Gold In-Tube test during treatment of patients with sputum smear-positive tuberculosis in relation to initial TST result and severity of disease

Abstract

The QuantiFERON-TB Gold In-Tube test (QFN) measures interferon-gamma production in response to Mycobacterium tuberculosis antigens. Our aim was to assess the kinetics of the QFN and initial tuberculin skin test (TST) result in relation to severity of disease in a tuberculosis (TB) endemic area. Smear-positive TB patients (n = 71) were recruited at Gondar University Hospital, Ethiopia. The TST, QFN, CD4+ cell count and clinical symptoms (TB score) were assessed and followed up during treatment. From baseline to 7 months after treatment, there was a significant decrease in QFN reactivity (93.8% to 62.5% in HIV-negative/TB; 70.3% to 33.3% in HIV-positive/TB patients) down to a level comparable to a control group of blood donors (51.2%). The agreement between TST and QFN was poor in TB patients compared to healthy controls. A negative TST correlated to more advanced TB in contrast to a negative QFN test. We conclude that the QFN reactivity is significantly reduced at the end of treatment against active TB to the background level of healthy blood donors, and that the agreement between TST and QFN is poor including correlation to the severity of disease.

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

“…Most studies (23/30) had completion rates greater than 70%. One study included a significant proportion of HIV positive patients (54%) [56], with a further 3 studies including a small proportion (<10%) of HIV positive patients [52,64,73].…”

“…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].…”

“…Immunocompromised: There were four studies that included HIV positive patients [52,56,64,73]. One reported a statistically significant decrease in IFN-γ response [73], whilst two showed no significant change [52,64] and one did not report significance testing or were very small pilot studies [56].…”

“…One reported a statistically significant decrease in IFN-γ response [73], whilst two showed no significant change [52,64] and one did not report significance testing or were very small pilot studies [56]. Thee studies included patients who were likely immunocompromised by either disease or therapy (two studies in rheumatic disease and one in inflammatory bowel disease), undergoing therapy for LTBI [47,65,68].…”

“…was seen in both adults and children, although less commonly in studies which included immunocompromised patients [52,56,64,73]. Reduction in IFN-γ levels with treatment was reported more frequently in studies of active TB [51, 57-59, 61, 67, 69, 71, 73-76] than in LTBI, where generally changes in IFN-γ responses were not statistically significant [47,48,52,54,63,65,68,75].…”