Quantiferon Test Does Not Detect MAC Infection
The Quantiferon test is not recommended for the diagnosis of Mycobacterium avium complex (MAC) disease as it is specifically designed to detect Mycobacterium tuberculosis infection. 1
How Quantiferon Tests Work
Quantiferon tests are interferon-gamma release assays (IGRAs) that detect the release of interferon-gamma from sensitized T-cells when exposed to specific mycobacterial antigens:
- Original QuantiFERON-TB (QFT): Uses tuberculin PPD from M. tuberculosis and avian sensitin from M. avium as antigens 1
- QuantiFERON-TB Gold (QFT-G): Uses more specific antigens (ESAT-6 and CFP-10) that are present in M. tuberculosis but absent from BCG vaccine strains and most nontuberculous mycobacteria 1
Why Quantiferon Cannot Reliably Detect MAC
Specific Contraindication: The CDC explicitly states that QFT is "not recommended for diagnosis of M. avium complex disease" 1
Antigen Specificity: QFT-G uses ESAT-6 and CFP-10 antigens that are specific to M. tuberculosis and absent from most nontuberculous mycobacteria including MAC 1
Low Positive Rate in MAC Patients: Research shows only 11.3% of patients with confirmed MAC disease showed a positive response with QFT-G, and these positive results were attributed to previous tuberculosis infection rather than MAC 2
Cross-Reactivity Considerations
While the original QFT test included avian sensitin as a control antigen to help differentiate between M. tuberculosis and nontuberculous mycobacterial infections, this was used to improve specificity for TB detection, not to diagnose MAC 1.
Clinical Implications
If MAC infection is suspected:
- Direct microbiological methods (culture) remain the gold standard for diagnosis
- Molecular methods specific for MAC identification should be used
- Quantiferon tests should not be relied upon for MAC diagnosis
Common Pitfalls to Avoid
Misinterpreting positive results: A positive Quantiferon in a patient with MAC disease likely indicates concurrent latent TB infection rather than detecting the MAC infection itself 2
False reassurance: A negative Quantiferon does not rule out MAC infection
Confusion between test generations: The original QFT (no longer commercially available) used avian sensitin, but this was to improve TB detection specificity, not to diagnose MAC 1
For patients with suspected MAC infection, appropriate diagnostic approaches include sputum culture, bronchoscopy with bronchoalveolar lavage for culture, or tissue biopsy with culture and molecular testing specific for MAC.