An IGRA (QuantiFERON-TB Gold Plus, QFT-Plus) test returns an indeterminate result in a healthcare worker undergoing pre-employment TB screening. QFT-Plus uses two antigen tubes (TB1 with ESAT-6/CFP-10 CD4 stimulation, TB2 with CD8 as well). Which of the following scenarios most commonly causes an indeterminate QFT-Plus result?
- A High background (nil tube) interferon-gamma due to recent BCG vaccination
- B Cross-reactivity with environmental NTM causing false elevation of TB antigen tubes
- C Recent active tuberculosis disease with anergy
- D Low mitogen (positive control) response due to lymphopenia or immunosuppression ✓
Explanation
QFT-Plus is deemed indeterminate when the mitogen (positive control) tube IFN-gamma response is <0.5 IU/mL, indicating poor lymphocyte responsiveness. This is most commonly caused by lymphopenia, generalised immunosuppression (corticosteroids, biologics, HIV with low CD4), or pre-analytical errors (delayed processing >16 hours, wrong incubation temperature). BCG vaccination causes false positives in the TST but not in IGRA because ESAT-6 and CFP-10 are not present in BCG. Active TB can occasionally cause indeterminate results due to anergy, but this is less common than immunosuppression.
Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.