Abstract
ABSTRACTWe investigated whether the difference of antigen tube 2 (TB2) minus antigen tube 1 (TB1) (TB2−TB1) of the QuantiFERON-TB gold plus test, which has been postulated as a surrogate for the CD8+ T-cell response, could be useful in identifying recent tuberculosis (TB) exposure. We looked at the interferon gamma (IFN-γ) responses and differences in TB2 and TB1 tubes for 686 adults with QFT-plus positive test results. These results were compared among groups with high (368 TB contacts), low (229 patients with immune-mediated inflammatory diseases [IMID]), and indeterminate (89 asylum seekers or people from abroad [ASPFA]) risks of recent TB exposure. A TB2−TB1 value >0.6 IU·ml−1 was deemed to indicate a true difference between tubes. In the whole cohort, 13.6%, 10.9%, and 11.2% of cases had a TB2>TB1 result in the contact, IMID, and ASPFA groups, respectively (P = 0.591). The adjusted odds ratios (aORs) for an association between a TB2−TB1 result of >0.6 IU·ml−1 and risk of recent exposure versus contacts were 0.71 (95% confidence interval [CI], 0.31 to 1.61) for the IMID group and 0.86 (95% CI, 0.49 to 1.52) for the ASPFA group. In TB contact subgroups, 11.4%, 15.4%, and 17.7% with close, frequent, and sporadic contact had a TB2>TB1 result (P = 0.362). The aORs versus the close subgroup were 1.29 (95% CI, 0.63 to 2.62) for the frequent subgroup and 1.55 (95% CI, 0.67 to 3.60) for the sporadic subgroup. A TB2−TB1 difference of >0.6 IU·ml−1 was not associated with increased risk of recent TB exposure, which puts into question the clinical potential as a proxy marker for recently acquired TB infection.IMPORTANCE Contact tuberculosis tracing is essential to identify recently infected people, who therefore merit preventive treatment. However, there are no diagnostic tests that can determine whether the infection is a result of a recent exposure or not. It has been suggested that by using the QuantiFERON-TB gold plus, an interferon gamma (IFN-γ) release assay, a difference in IFN-γ production between the two antigen tubes (TB2 minus TB1) of >0.6 IU·ml−1 could serve as a proxy marker for recent infection. In this large multinational study, infected individuals could not be classified according to the risk of recent exposure based on differences in IFN-γ in TB1 and TB2 tubes that were higher than 0.6 IU·ml−1. QuantiFERON-TB gold plus is not able to distinguish between recent and remotely acquired tuberculosis infection, and it should not be used for that purpose in contact tuberculosis tracing.
Highlights
Contact tracing is central to tuberculosis (TB) control and prevention by helping to identify and treat people who have been recently infected [1]
In this study, we could not validate previous findings suggesting that a TB22TB1 value .0.6 IUÁml21 served as a proxy marker for recent infection
In one study [11], 14 of 105 (13.3%) infected contacts had a TB22TB1 value .0.6 IUÁml21, and the quantitative tube 2 (TB2) interferon gamma (IFN-g) response was higher in contacts living in the same room as index cases than in other contacts
Summary
Contact tracing is central to tuberculosis (TB) control and prevention by helping to identify and treat people who have been recently infected [1]. Room as index cases [11], data highly suggestive of newly acquired infection These studies included small numbers of individuals with TB22TB1 values .0.6 IUÁml, and they did not compare contacts with groups without risk of recent exposure. We investigated whether the QFT-plus could be used to identify individuals recently exposed to TB and thereby act as a surrogate marker for newly acquired infection. This was done by identifying TB2, TB1, and TB22TB1 IFN-g levels in individuals with different risks of recent TB exposure. We anticipated a gradient in the proportions of individuals with TB22TB1 IFN-g values .0.6 IUÁml across the groups (with the highest rates in contacts and lower rates in individuals without risk of recent TB exposure)
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