Discordant QuantiFERON-TB Gold test results among US healthcare workers with increased risk of latent tuberculosis infection: a problem or solution?
OBJECTIVE
In late 2006, our hospital implemented use of the QuantiFERON-TB Gold (QFT-G) assay, a whole-blood interferon-gamma release assay, for detection of tuberculosis infection. All newly hired healthcare workers (HCWs) with positive Mantoux tuberculin skin test (TST) results were routinely tested with the QFT-G assay, to take advantage of its higher specificity. We then undertook a quality assurance review to evaluate the QFT-G test results in HCWs with multiple risk factors for latent tuberculosis infection (LTBI).


METHODS
The clinical records for TST-positive HCWs tested with the QFT-G assay were reviewed. HCWs with 2 or more risk factors commonly associated with LTBI were classified as "increased risk" (IR). IR HCWs who had negative QFT-G test results underwent repeat QFT-G testing and were offered testing with a different interferon-gamma release assay (T-SPOT.TB) and with extended T cell stimulation assays.


RESULTS
Of 143 TST-positive HCWs tested with the QFT-G assay, 26 (18%) had positive results, 115 (81%) had negative results, and 2 (1%) had indeterminate results. Of 82 IR HCWs, 23 (28%) had positive QFT-G test results, and 57 (70%) had negative results. Of the 57 IR HCWs with negative results, 43 underwent repeat QFT-G testing: 41 had negative results again, and 2 had positive results. These 43 HCWs were also offered additional testing with the T-SPOT.TB diagnostic, and 36 consented: 31/36 tested negative, and 5/36 tested positive. Extended assays using the antigens ESAT-6 and CFP-10 confirmed the positive results detected by the overnight assays and yielded positive results for an additional 7/36 (19%) of individuals; strikingly, all 36 HCWs had strongly positive test results with assays using purified protein derivative.


CONCLUSIONS
The extreme discordance between the results of our clinical diagnostic algorithm and the results of QFT-G testing raises concern about the sensitivity of the QFT-G assay for detection of LTBI in our HCWs. Results of extended stimulation assays suggest that many of our IR HCWs have indeed been sensitized to Mycobacterium tuberculosis. It is possible that the QFT-G assay identifies those at higher reactivation risk rather than all previously infected, but, in the absence of long-term follow-up data, we should interpret negative QFT-G results with some caution.
Pollock
Nira R
NR
Department of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA.
Campos-Neto
Antonio
A
Kashino
Suely
S
Napolitano
Danielle
D
Behar
Samuel M
SM
Shin
Daniel
D
Sloutsky
Alex
A
Joshi
Swati
S
Guillet
Jasmine
J
Wong
Michael
M
Nardell
Edward
E
D000328:Adult; D000465:Algorithms; D005260:Female; D006282:Health Personnel; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis; D011785:Quality Assurance, Health Care; D011933:Reagent Kits, Diagnostic; D012307:Risk Factors; D012680:Sensitivity and Specificity; D014374:Tuberculin Test / Q000379:methods*; D014376:Tuberculosis / Q000175:diagnosis* / Q000382:microbiology; D014481:United States
D011933:Reagent Kits, Diagnostic; D007371:Interferon-gamma