17 Oct, 16 | by EBM
By Dr. Geoffrey Modest
Given the recent article of the USPSTF LTBI (latent TB infection) recommendations (http://blogs.bmj.com/ebm/2016/10/11/primary-care-corner-with-geoffrey-modest-md-uspstf-ltbi-screening-recommendations/ ) I decided to bring up another study which questions the role of IGRAs (interferon-γ release assays) –see King TC. Am J Respir Care 2015; 192(3): 367. I initially decided that the prior articles and blogs were pretty concerning about the stability of IGRAs, but this study does add another wrinkle: it was an industry-sponsored study, still had pretty striking conclusions that 1 in 5 people with positive IGRAs would revert to negative, yet then concluded that T-SPOT.TB (one of the IGRAs) is “an accurate and reliable way to screen healthcare workers”.
- 20,095 pairs of T-SPOT.TBresults from 16,412 health care workers (HCWs) at 19 geographically diverse US hospitals (urban, suburban, rural), looking at serial T-SPOT.TB testing, from 2010 to 2014, where the second test result was at least 150 days after the first one.
- 77% female, median age 41 and no other demographics included
- Their analysis excluded those with borderline tests from either the initial or subsequent test, approx 2.3% of the results
- Conversion was defined as a negative result turning positive; reversion was the opposite
- The mean conversion rate was 0.8%, but 2.3% in hospitals that checked only high risk HCWs, and 0.6% in hospitals that checked all HCWs
- The mean reversion rate was 17.6%, but 13.9% in hospitals that checked only high risk HCWs, and 20.7% in those that checked all HCWs
- The baseline test positivity rate was 2.3%, but varied from 0-27.4%; and was 8.4% in hospitals that checked only high risk
- There was a strong correlation between observed conversion rates by T-SPOT and reported TB incidence of the state where the hospital was located
- 23% of those with borderline results were positive on retesting
- Of course, one of the primary issues with LTBI screening is that there is no gold standard.
- This article does cite 5 studies which challenge the IGRA’s stability and reliability.
- The researchers think their test was better (again, remember that this is an industry-sponsored study), and had lower reversion rates than other studies because: they had higher and more rigorous cutpoints than prior T-SPOT tests (though, without a gold standard, hard really to know the effect of this on the sensitivity of the test), they have lower likelihood of sample processing errors than QuantiFERON IGRAs, but they do note that all IGRAs, which measure an immune response to TB, are subject to “biological variability”. It is also unknown in this study whether the patients had been treated or not, which other studies have suggested might be part of the reason for reversions (though the authors did not comment on this).
- One really interesting note is that this industry-sponsored study was able to state on the one hand that though >20% of the HCWs who had a positive IGRA actually reverted to negative about 1 year later, on the other hand they concluded that the IGRA is an accurate/reliable test. It seem to me as a casual observer that the possibility of 20% false positives, which they acknowledge as a possibility, is a tad high. And any positive can lead to unnecessary but potentially toxic drugs, potential stigma, etc. So, as mentioned in prior blogs, I am sticking with the PPD, except in unusual circumstances (e.g., the patient really cannot get the PPD read in 48-72 hours).