Tuberculosis Test - QuantiFERON (QFT)

QuantiFERON (QFT) is an interferon-γ release assay (IGRA) that aids in the evaluation of tuberculosis (TB) infections (latent or active)¹ and is recommended by the CDC as an alternative to the tuberculin skin test (TST) in certain situations. This modern alternative offers improved performance and quicker results.

• QFT has been shown to be more accurate than the TST in identifying people who may have latent TB infection.²
• QFT has been shown to be more reliable than the TST in identifying those who may progress to active TB.³ QFT is >99% specific,^1,4 nearly eliminating false-positive readings; and false positive rates for TST have been published as low as 3% in non–BCG-vaccinated populations⁵ and as high as 65% when using a 10-mm induration as the cutoff in BCG vaccinated
• A meta-analysis calculated a pooled sensitivity for TST at 70%,⁴ (23 of 25 studies in developed countries) and a pooled sensitivity for QFT at 84% (13 studies in developed countries).⁴

Improving Upon Technology Limitations

False-positive TST results may burden the system

• QFT’s increased accuracy may yield better outcomes for patients, allowing for more confidence in correctly identifying TB infection, with significant cost savings through fewer false positive results. Studies show that switching to QFT provides significant program cost advantages.⁹

• One study reported up to 32% reduction in cost compared to the TST. When deciding whether to perform a follow-up chest X-ray, the study suggests that using QFT instead of TST may reduce the need. If a positive QFT result is the discrete referral decision driver vs. a positive TST (using the data in the study), a QFT positive result might have reduced the chest x-ray referral by 37.5% in the group with no BCG vaccination, who also had a prior TST inoculation history. A QFT positive result might also have reduced the referrals within all study participants by 60% (includes sum of no BCG/no TST history; BCG; and TST/no BCG history participants).⁹
• QFT contains TB mycobacterial proteins (ESAT-6, CFP-10, and TB 7.7),¹which are not found in the BCG vaccine or PPD (tuberculin purified protein derivative) TST injection.^8,10 Because of this highly specific composition, QFT overcomes many of the shortcomings of the TST, and it is not affected by previous BCG vaccinations or exposure to non-tuberculosis Mycobacteria, both with the added benefit of providing a laboratory-based, objective result.

TB Testing for Biologics and Other Immunosuppressive Therapy

Common autoimmune disorders such as inflammatory bowel disease, Crohn’s disease, rheumatoid arthritis, or plaque psoriasis are commonly treated with biologics in order to slow the progression of the disease.¹² Because biologics work on the patient’s immune system¹³, the package insert for many biologics instructs the prescriber to perform a tuberculosis (TB) test before the patient starts on the biologic. Common biologics include infliximab¹², adalimumab¹⁴, and certolizumab¹⁵ (Humira^®14, Enbrel^®16, Otezla^®17, and Xeljanz^®18) which can cause a latent tuberculosis infection (LTBI) to activate.

Approximately 11 million individuals in the US are currently infected with LTBI, thus it is critical for patients to be screened for TB infection prior to initiation of immunosuppressive treatment, including biologic agents for autoimmune diseases.¹⁹

QuantiFERON®-TB Gold is a recommended screening test for those patients being placed on biologic treatment and other immunosuppressive therapy.

​QuantiFERON®-TB Gold Limitations

Spontaneous interferon-γ production (independent of TB stimulation) or lack of a response to mitogen (due to anergy or immune suppression) may render the results indeterminate. A negative result should not be used alone to exclude M tuberculosis infection in persons with symptoms or signs suggestive of TB disease. Those who have a negative result but who are likely to have latent TB infection (LTBI) and who are at greater risk for severe illness or poor outcome if TB disease occurs, might need treatment or closer monitoring for disease.¹ In healthy persons who have a low likelihood both of M tuberculosis infection and of progression to active tuberculosis if infected, a single positive IGRA or TST result should not be taken as reliable evidence of M tuberculosis infection. Because of the low probability of infection, a false-positive result is more likely. In such situations, the likelihood of M tuberculosis infection and of disease progression should be reassessed, and the initial test results should be confirmed. Repeat testing (using a newly collected specimen), with either the initial test or a different test, may be considered on a case-by-case basis. For such persons, an alternative is to assume, without additional testing, that the initial result is a false positive.⁸

The QuantiFERON TB test has been shown to be accurate in HIV-positive individuals with moderately advanced disease, but in the severely immunocompromised the test may be impaired by T-cell anergy.^2,3 Active TB disease may result in a negative test as reduction of in vitro IFN-γ release has been described and may be due to suppressive cytokines associated with TB disease.⁴ Patients with mycobacterial infections, other than tuberculosis, might also be responsive to ESAT-6, CFP-10, and TB7.7, as the genes encoding these proteins are present in M kansasii, M szulgai, and M marinum.⁵

References

1. QuantiFERON-TB Gold (QFTR) ELISA [package insert]. Germantown, MD; QIAGEN Group. 2016.
2. Diel R, Loddenkemper R, Meywald-Walter K, Niermann S, Niehaus A. Predictive value of a whole blood IFN-y assay for the development of active tuberculosis disease after recent infection with mycobacterium tuberculosis. Am J Respir Crit Care Med. 2008;177:1164-1170.
3. Diel R, Loddenkemper R, Niermann S, Meywald-Walter K, Nienhaus A. Negative and positive predictive value of a whole-blood interferon-y release assay for developing active tuberculosis.Am J Respir Crit Care Med. 2011;183:88-95.
4. Deil R, Loddenkemper R, Nienhaus A. Evidence-based comparison of commercial interferon-y release assays for detecting active TB: a metaanalysis. Chest. 2010;137:952-968.
5. Pai M, Zwerling A, Menzies D. Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection: An update. Ann Intern Med. 2008;149(3):177-184.
6. Mori T, Sakatani M, Yamagishi F, et al. Specific detection of tuberculosis infection. Am J Respir Crit Care Med. 2004;170:59-64.
7. Andersen P, Munk ME, Pollock J M, Doherty TM. Specific immune-based diagnosis of tuberculosis. Lancet. 2000;356:1099-1104.
8. Centers for Disease Control and Prevention. Updated Guidelines for Using Interferon Gamma Release Assays to Detect Mycobacterium tuberculosis Infection – United States, 2010. MMWR 2010;59(NoRR-55).
9. Nienhaus A, Schablon A, Le Bacle CL, Siano B, Diel R. Evaluation of the interferon-y release assay in healthcare workers. Int Arch Occup Environ Health. 2007.
10. Beglinger C, Dudler J, Mottet, et al. Screening for tuberculosis infection before initiation of anti-TNF-α therapy. Swiss Med Wkly. 2007;137:621-622.
11. Centers for Disease Control and Prevention: Guidelines for using the QuantiFERONR-TB Gold Test for detecting Mycobacterium tuberculosis Infection, United States. 2005;54(NoRR-15).
12. REMICADE® [package insert]. Horsham, PA: Janssen Biotech, Inc. 2013.
13. Singh JA, Wells GA, Christensen R, et al. Adverse effects of biologics: a network metaanalysis and Cochrane overview. Cochrane Database of Systematic Reviews, Feb 2011.
14. HUMIRA^® [package insert]. North Chicago, IL: Abbott Laboratories. 2012.
15. CIMZIA® [package insert]. Smyrna, GA: UCB, Inc. 2016.
16. ENBREL® [package insert]. Thousand Oaks, CA: Amgen Inc. 2013.
17. Yu DT. General guidelines for use of anti-tumor necrosis factor alpha agents in ankylosing spondylitis and in peripheral and non-radiographic axial spondyloarthritis. 2017. www.uptodate.com.
18. Xeljanz [package insert]. New York, NY: Pfizer Labs. 2012.
19. Department of Health and Human Services/Centers for Disease Control and Prevention. Updated guidelines for using Interferon gamma release assays to detect Mycobacterium tuberculosis infection. Morbidity and Mortality Weekly Report, Jun 25, 2010.