False Positives Plague IGRA Testing for TB Exposure

Interferon-γ release assays (IGRAs) have some advantages over standard tuberculin skin testing (TST): They are simple blood tests, in contrast to cumbersome two-stage or four-stage TST protocols. A temporary nationwide shortage of the tuberculin skin test reagent recently drove many institutions to use IGRAs for routine screening. However, as more IGRAs are used, more problems have emerged with interpreting them (NEJM JW Gen Med Aug 7 2012

Researchers at one tertiary care medical center in California, where TST was replaced by IGRA for annual employee screening in 2008, have analyzed their experience with the test. Among almost 10,000 healthcare workers who were tested two or more times during the first 2 years of the program, 1223 people (13%) initially tested positive; 828 of these initial positives (68%) remained positive on repeat testing. Among the 8227 employees with initial negative IGRA tests, 4% subsequently tested positive, for a startlingly high conversion rate (roughly 10 times that seen in previous years when TST was used). Almost 75% of these converters had IGRA values in the very low–positive range. Almost 90% of the new “converters” were retested a mean 3 months later: 64% reverted to negative.

The researchers found that raising the cutoff value for a positive IGRA from 0.35 to 5.3 IU/mL eliminated most of these presumably false positives and yielded conversion rates consistent with those of previous years — but raising the cutoff this high also lowered the number of persistent and, presumably, true-positive test results by more than 50%.