QuantiFERON™ TB Gold Plus Test

Tuberculosis kills more people worldwide than any other single infectious agent. But most people carrying the bacteria that causes it have no idea. An estimated one quarter of the world's population harbors a latent TB infection, meaning the bacteria are alive inside the body but held in check by the immune system. These people feel fine, have normal chest X-rays, and would never suspect they are infected. The QuantiFERON TB Gold Plus test is designed to find them.

The test works by drawing a tube of your blood and exposing your white blood cells to proteins found only on TB bacteria. If your immune system has encountered TB before, a specific type of white blood cell (called T cells) will recognize those proteins and release a signaling molecule called interferon-gamma (IFN-gamma). The amount of IFN-gamma your cells produce is what the lab measures. A strong response means your immune system has been primed by TB exposure. A weak or absent response suggests it has not.

What This Test Can and Cannot Tell You

A positive result means your immune system has been sensitized to Mycobacterium tuberculosis. It does not tell you whether you have latent infection (bacteria present but dormant) or active disease (bacteria multiplying and potentially contagious). That distinction requires additional evaluation, typically a chest X-ray and a clinical assessment of symptoms like prolonged cough, night sweats, and unexplained weight loss. This is the single most misunderstood aspect of the test.

The test uses two antigen tubes, called TB1 and TB2. TB1 stimulates a type of immune cell called CD4+ T-helper cells. TB2 targets both CD4+ cells and CD8+ cytotoxic T cells (immune cells specialized in killing infected cells directly). This dual-tube design is what distinguishes the Gold Plus version from its predecessor. Research suggests that stronger CD8+ responses (reflected by a TB2 reading that exceeds TB1 by more than 0.6 IU/mL) may lean toward active disease or very recent infection, though this distinction is not yet validated for clinical decision-making.

Advantages Over the Tuberculin Skin Test

The traditional tuberculin skin test (TST) has been used for over a century, but it carries a major limitation: it cross-reacts with the BCG vaccine, which is given to children in most countries outside the United States. If you received BCG as a child, your TST may come back positive even though you were never infected with TB. The QuantiFERON test avoids this problem entirely because it uses proteins (ESAT-6 and CFP-10) that are found on TB bacteria but are absent from the BCG vaccine strain and from most harmless environmental mycobacteria.

In large studies comparing the two, QuantiFERON showed higher specificity (about 98% versus roughly 60% in BCG-vaccinated populations) with comparable or slightly better sensitivity (approximately 89% versus 60-81% for TST). The blood test also requires just one visit for a blood draw, whereas the skin test requires two visits: one to place the test and another 48 to 72 hours later to read the result. Patients who do not return for that second visit never get their answer.

Who Should Get Tested

The U.S. Preventive Services Task Force and the CDC recommend this test for people at elevated risk of TB exposure or at elevated risk of progressing from latent infection to active disease. You should know your status if any of the following apply to you.

• Born in or lived in a high-prevalence country: this includes much of Africa, Asia, Eastern Europe, Latin America, and the Pacific Islands, as well as countries like Mexico, the Philippines, Vietnam, India, China, Haiti, and Guatemala.
• Lived or worked in congregate settings: homeless shelters, correctional facilities, or long-term care facilities where TB transmission risk is higher.
• Close contact with someone diagnosed with active TB: household members, coworkers, or others with prolonged shared air exposure.
• Immunosuppressed: HIV infection, organ transplant medications, TNF-alpha inhibitor therapy (used for conditions like rheumatoid arthritis or Crohn's disease), or long-term corticosteroid use (at least 15 mg per day for a month or more).

Healthcare workers in contact with TB patients should also be tested. If you have no epidemiologic risk factors and no immunosuppression, routine screening is not recommended because the positive predictive value drops sharply when the chance of actual infection is very low.

Understanding Your Results

The lab reports your result as positive, negative, or indeterminate, based on how much IFN-gamma your T cells produced after exposure to TB antigens. The FDA-approved cutoff is 0.35 IU/mL. Results at or above that level are considered positive. But the number itself carries additional information.

These tiers are drawn from large registry studies in Sweden and Spain. Your lab will report using the FDA binary cutoff (positive or negative at 0.35 IU/mL), but the quantitative value printed on the report gives you more context. Results well above 1.0 IU/mL are far more likely to reflect true infection than results hovering around 0.4 IU/mL.

The Borderline Problem

Results near the cutoff are the test's biggest weakness. A Spanish study of nearly 10,000 patients found that among those with borderline positive results (0.35 to 0.7 IU/mL), 60.9% reverted to negative on repeat testing, and none of those who reverted went on to develop active TB. A Swedish national registry of over 58,000 patients found a similar pattern: 38.3% of borderline results reverted to negative.

This means that a single borderline positive result, on its own, is not reliable enough to trigger a months-long course of preventive antibiotics. If your result falls in this zone, repeat the test before making treatment decisions. Borderline results occur more frequently in people born in Africa or South America and in older adults, but these patterns reflect epidemiologic exposure risk, not a need for different cutoffs.

Dose-Response: Higher Levels, Higher Risk

For people with confirmed positive results, the actual IFN-gamma level may carry prognostic information. The largest study on this question tracked over 50,000 test results in Norway (using the predecessor QFT-GIT assay, which measures the same analyte with a slightly different antigen tube design). People with IFN-gamma levels above 4.0 IU/mL had roughly ten times the rate of developing active TB compared to those with levels just above the cutoff.

A UK study of about 9,600 TB contacts and recent migrants confirmed this dose-response pattern: TB incidence rose with higher IFN-gamma values. These findings have not yet been replicated specifically with the Gold Plus version. A 2025 European study in immunocompromised individuals found that the quantitative result did not strongly predict progression in most immunocompromised groups, with the exception of people living with HIV who had detectable viral loads and low CD4 counts. The prognostic value of the raw number remains a topic of active research.

When Results Can Be Misleading

The test's coefficient of variation is about 14% overall, but it climbs to 27% for values near the cutoff (0.25 to 0.80 IU/mL). Normal expected variability is plus or minus 0.60 IU/mL from one draw to the next. This means a result of 0.40 IU/mL could easily be 0.00 or 0.80 on a retest, without any change in your actual infection status. Any result near the borderline should be confirmed.

Several factors can push results toward a false negative (making you look uninfected when you are not).

• Corticosteroids: Glucocorticoid therapy caused false-negative results in 25% of children and indeterminate results in 28.6% of adults in clinical studies. In a laboratory model, dexamethasone converted 30% of positive tests to negative by suppressing IFN-gamma production.
• Severe illness: Hospitalization and severe COVID-19 each increased indeterminate results nearly 4-fold. Severe anemia roughly doubled the odds of an indeterminate reading.
• Low lymphocyte counts: A lymphocyte count at or below 1.19 x 10^9/L, a neutrophil count at or above 5.88 x 10^9/L, or a neutrophil-to-lymphocyte ratio at or above 4.33 all predict false-negative results. A systematic review confirmed that low lymphocyte counts nearly tripled the odds of a false negative.
• Advanced age and cancer: Being 65 or older increased false-negative odds by 57%. Having an active malignancy more than doubled them.

TNF-alpha inhibitors (such as infliximab, used for autoimmune diseases) converted up to 30% of positive results to negative in a laboratory model. If you are on immunosuppressive therapy and your test is negative, discuss with your physician whether retesting after immune reconstitution is appropriate. Common medications like statins, metformin, GLP-1 receptor agonists, proton pump inhibitors, and levothyroxine have not been shown to interfere with this test.

Tracking Your Results Over Time

A single reading is a snapshot. For borderline results, repeat testing is not optional; it is the only way to determine whether the initial result reflects true infection or measurement noise. Among people with borderline results who were retested, more than half reverted to negative. Among HIV-positive individuals with initially positive results, 72% reverted on repeat testing, underscoring the instability of low-positive values in immunocompromised people.

If your initial result is clearly positive (above 1.0 IU/mL) and confirmed, serial retesting is generally not needed for the purpose of confirming infection. However, if you are being treated for latent TB, tracking IFN-gamma levels during treatment is of limited value: the largest randomized trial (2,618 participants) found no significant difference in reversion rates between those treated with preventive antibiotics and those who were not (19.0% versus 20.7%). The test was designed as a diagnostic tool, not a treatment-monitoring tool.

For people who test negative but remain in a high-risk setting (healthcare workers, ongoing household contacts), retesting annually or after a known exposure is reasonable. If you are about to start immunosuppressive therapy, get tested before starting the medication, since the drugs can suppress your immune response and produce a falsely reassuring negative.