False-Positive QuantiFERON Gold Tests

Abstract

INTRODUCTION: Quantiferon Gold (QFT-G) uses Mycobacterium Tuberculosis (MTB) specific proteins early secretory antigenic target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) to stimulate host lymphocytes in whole blood (1). If previously exposed to MTB the sensitized lymphocytes will secrete interferon-gamma (IFN-gamma) that is then detected by enzyme linked immunosorbent assay. The major test advantage over tuberculin skin test (TST) is that BCG vaccinations and environmental mycobacteria may react with TST but are negative with QFT-G. The US Food and Drug Administration has approved QFT-G as a diagnostic aid in the detection of both MTB disease and infection without disease (latent MTB). False positive QFT-G testing has not been reported yet. CASE PRESENTATION: Setting: TB clinic of a city hospital. Case Report: We report four cases referred to our TB clinic with positive quantiferon tests from employee health. All four had negative TST in the preceding months, were asymptomatic, and denied any close contact with any active TB patient. In addition, all four subjects had repeat TST testing immediately after the quantiferon test and all four TST were zero mm. Three of the subjects were US born with no travel history outside the country and the fourth subject was living in US for greater than 5 years. Two of four subjects were known to be HIV negative. The mitogen positive control was elevated at greater than 9 IU above background in all QFT-G tests. This suggests that occult immunosuppressive diseases were not present. DISCUSSIONS: It is estimated that there is about a 4.2% prevalence of latent MTB in the U.S. population versus an 18.7% prevalence of latent MTB in foreign born subjects in the U.S. (2). There is an estimated sensitivity and specificity of the QFT-G of 90% and 98%, respectively. This calculates out to positive predictive values of 67 and 91% for the QFT-G in the U.S. born and foreign born living in the U.S., respectively. Theoretically, based on this calculation the false positive rate could be as high as 33% in the U.S. born population. CONCLUSION: The U.S. born population with a low prevalence of latent MTB are more likely to have false positive QFT-G tests, albeit it can occur up to 9% of the time in foreign born subjects in the U.S. Therefore, the use of QFT-G alone for the detection of latent MTB in healthy populations could be problematic.