How to Interpret QuantiFERON Test Results

A QuantiFERON result tells you whether your immune cells react to proteins found almost only in TB bacteria, which is a sign you have been infected at some point.1QIAGEN. What is QuantiFERON? | QuantiFERON testing It cannot tell an old infection from a new one, or a sleeping infection from active illness, so a positive is a starting point rather than a diagnosis.2QuantiFERON.com. QuantiFERON-TB Gold Frequently Asked Questions Health Professionals How far your number sits above the cutoff matters as much as the word “positive,” because results just over the line often flip back on retesting.

What the Tubes and Numbers on Your Report Mean

Your blood is mixed with TB proteins, and the test measures interferon-gamma, a chemical signal your immune cells release if they have met TB before.3QIAGEN. How to test with QuantiFERON TB | QFT-Plus The report gives this signal in IU/mL.

Your blood is split among four tubes, and each has a job:

A result is positive when TB1 or TB2 minus Nil is 0.35 IU/mL or more and at least 25% above Nil.8PubMed Central. Factors associated with indeterminate QuantiFERON-TB Gold Plus Test Results during the COVID-19 pandemic The newer version, QuantiFERON-TB Gold Plus, has the TB2 tube; older reports list one TB tube.9PubMed Central. QuantiFERON-TB Gold Plus CD8+ T cell responses in contacts with tuberculosis disease and recent tuberculosis infection

To read a sample report, find the Nil value first and subtract it from each TB tube. Then see whether one or both TB tubes passed the cutoff. Check that the mitogen value is high, which shows your cells worked. Last, look at the final interpretation line the lab prints.

Everyone’s blood releases a little interferon-gamma even with no TB proteins present, and that background varies from person to person. Subtracting Nil leaves only the response to TB proteins. The 25%-above-Nil requirement is a second safeguard that stops a high-background sample from being called positive on a small bump.

How Much the Size of a Positive Number Matters

People with values above 0.7 had a positive skin test 91% of the time, versus 53% for values of 0.2 to 0.34.10PubMed Central. Optimization and Interpretation of Serial QuantiFERON Testing to Measure Acquisition of Mycobacterium tuberculosis Infection And 87% of people with active TB had values above 0.7.11PubMed Central. Optimization and Interpretation of Serial QuantiFERON Testing to Measure Acquisition of Mycobacterium tuberculosis Infection

Results near the cutoff often change on retest. About half of results between 0.2 and 0.99 were below 0.2 when retested within weeks.12PubMed Central. A borderline range for Quantiferon Gold In-Tube results Of initial positives from 0.35 to 0.99, about 55% fell back under the cutoff on retest.13PubMed Central. A borderline range for Quantiferon Gold In-Tube results Some low results are genuine, though: in people exposed to someone with TB, two-thirds with borderline results showed other signs of infection.14PubMed. Borderline QuantiFERON results and the distinction between specific responses and test variability A borderline result means more if you know you were exposed.

Low numbers wobble because any blood test has some natural variation, so a 0.38 and a 0.30 may reflect essentially the same immune state. How the sample was drawn, handled, and run can also nudge a borderline value across the line.

Your own background changes how a number reads. A person who grew up where TB is common, or lived with someone who had it, starts with a higher chance of real infection, so the same value more often reflects true infection. In a low-risk person with no exposure, a weak positive is more likely to be a wobble. That is why your doctor will ask about birthplace, travel, work, and contacts.

If your value is just over 0.35, ask for your exact number, not just the word positive. Ask whether a repeat test is reasonable, and mention any known TB exposure or travel.

Why a Positive Result Does Not Mean You Have TB Disease

A positive TB blood test usually means TB infection, and more tests are needed to rule out TB disease.15Centers for Disease Control and Prevention. Clinical Testing and Diagnosis for Tuberculosis Most infected people have a sleeping (latent) infection, where bacteria sit dormant, cause no symptoms, and cannot spread. The test itself cannot tell this sleeping infection from active disease.16Massachusetts Department of Public Health. Medical Evaluation for Persons with Positive Test Results Indicating TB Infection Because a sleeping infection can become active later, treatment is often offered.

Several signs would point toward active TB: a cough lasting more than three weeks, unexplained weight loss and fevers, and night sweats. Without them, active disease is less likely but still possible, so it is still checked.

TB spreads when someone with active disease in the lungs or throat coughs bacteria into the air; sleeping bacteria are held in check, so none are coughed out. A person with a positive test and no active disease does not need to avoid family, coworkers, or classmates while awaiting follow-up unless symptoms appear. Workplaces and schools often ask for clearance after a chest X-ray, and that clearance is about ruling out active disease, not about the blood test itself.

Can a Negative Result Be Wrong

With a weakened immune system, from HIV or anti-rejection drugs, the test more often gives false negatives.17European AIDS Treatment Group. Standard tests alone not sufficient to predict TB in immunocompromised individuals Low white blood cell counts roughly double or triple the chance of a false negative in people with TB.18PubMed Central. Factors associated with false negative interferon-γ release assay results in patients with tuberculosis: A systematic review with meta-analysis Pregnancy lowers the immune signal, so a negative during pregnancy cannot reliably rule out infection.19PubMed Central. Effects of Pregnancy and Isoniazid Preventive Therapy on Mycobacterium tuberculosis Interferon Gamma Response Assays in Women With HIV Even so, in HIV-negative pregnant women, the standard 0.35 cutoff still appears adequate.20PubMed Central. Longitudinal Mycobacterium tuberculosis-Specific Interferon Gamma Responses in Ethiopian HIV-Negative Women during Pregnancy and Postpartum

High-dose steroids and some cancer treatments also reduce this response, so a negative in these groups means less than in a healthy person. Severe illness, malnutrition, and very advanced TB itself can also blunt the response, so someone truly sick with TB can still test negative.

Handling matters too. If blood sits 6 to 12 hours before incubation, about 1 in 5 true positives turned negative.21PubMed Central. Preanalytical delay reduces sensitivity of QuantiFERON-TB gold in-tube assay for detection of latent tuberculosis infection Where possible, have blood drawn where the lab processes it promptly.

Timing is another factor. After a new exposure, the immune system needs several weeks to build the response the test detects, so a test done right after contact can be negative even if infection took hold. Doctors often repeat testing about eight to ten weeks after the last exposure if the first test was earlier.

A negative should not end the question if you have TB symptoms, since it does not rule out disease. If you are immunosuppressed, your doctor may add a skin test or X-ray. Tell your doctor about any recent close contact with someone who has TB.

What an Indeterminate Result Means

An indeterminate result means the test gave no usable answer. It comes from a mitogen value below 0.5 or a Nil value above 8.0 IU/mL.22PubMed Central. Factors associated with indeterminate QuantiFERON-TB Gold Plus Test Results during the COVID-19 pandemic Low mitogen can come from low white cell counts, mishandled samples, or tube-filling problems.23PubMed Central. Factors associated with indeterminate QuantiFERON-TB Gold Plus Test Results during the COVID-19 pandemic Delays before incubation raised indeterminate results to 17% at 12 hours.24PubMed Central. Immediate incubation reduces indeterminate results for QuantiFERON-TB Gold in-tube assay Steroids and immune-suppressing drugs are a known cause.25PubMed Central. Dynamic QuantiFERON Response in Psoriasis Patients Taking Long-Term Biologic Therapy Children get these results less often than adults, about 2% versus 5%.26PubMed Central. QuantiFERON-TB Performs Better in Children, Including Infants, than in Adults with Active Tuberculosis: a Multicenter Study

A very high Nil means the blood was already releasing a lot of signal without any TB proteins, which can come from other infections, inflammation, or autoimmune disease, so a TB tube cannot be read reliably. A low mitogen means your cells did not respond to the check, so the lab cannot tell whether a quiet TB tube means no infection or just cells that did not wake up.

Usually the test is simply repeated. If you take immune drugs, a skin test or X-ray may be used instead. If your first sample failed from handling, a repeat draw processed quickly often works. Tell the person drawing your blood about any steroids or immune medicines. If the repeat also fails, that pattern points toward your own immune state rather than a lab error, and your doctor will usually move to a different type of test.

False Positives in Routine Work Screening

A conversion means switching from negative to positive between tests. Among low-risk US healthcare workers, 4.4% converted over 2 years, and about 65% of those retested reverted.27PubMed Central. Challenges with QuantiFERON-TB Gold Assay for Large-Scale, Routine Screening of U.S. Healthcare Workers Most new positives in this setting looked like false positives.28PubMed Central. Challenges with QuantiFERON-TB Gold Assay for Large-Scale, Routine Screening of U.S. Healthcare Workers Modeling suggests yearly screening without retests could yield 29 false positives per true infection over ten years.29PubMed Central. Serial testing for latent tuberculosis using QuantiFERON-TB Gold In-Tube: A Markov model A confirmatory retest cut that false-positive share from about 25% to 4%.30PubMed Central. Serial testing for latent tuberculosis using QuantiFERON-TB Gold In-Tube: A Markov model When almost nobody in a group is truly infected, even a small false-positive rate produces more wrong positives than real ones, and each yearly test is another chance for a borderline value to cross the line.

After a surprise positive at work, ask your occupational health office about a repeat test, and report any exposure at work. Do not start treatment before a medical evaluation. A repeat that comes back negative, especially with a lower number, makes a true new infection less likely, though the full picture includes your exposure history. Programs differ in how they handle a conversion followed by a negative repeat, so ask what your office’s policy is.

A switch to positive carries more weight when it comes with a known exposure, such as caring for a patient later found to have active TB. A large jump in the number, well above the cutoff, is also more convincing than a slight crossing of 0.35.

Keep copies of past negatives and values. They let a doctor see whether your number rose steadily or just wobbled near the line. If you change jobs or clinics, bring them along, since a new employer may otherwise treat your positive as a first.

BCG Vaccine and Other Germs

The TB proteins in the test are missing from the BCG vaccine strain, so BCG should not make it positive.31PubMed Central. Non-Tuberculous Mycobacteria and the Performance of Interferon Gamma Release Assays in Denmark Among BCG-vaccinated healthcare workers, 85% had positive skin tests but only 10% had positive QuantiFERON.32PubMed. Comparison of the interferon- gamma release assay and the tuberculin skin test for contact investigation of tuberculosis in BCG-vaccinated health care workers If you had BCG and a positive skin test, the blood test is the better guide.33PubMed. Predictors for a positive QuantiFERON-TB-Gold test in BCG-vaccinated adults with a positive tuberculin skin test

Tell your doctor about BCG, since it helps them choose a test and read an earlier skin test. BCG given long ago does not explain a positive blood test, so a positive in a vaccinated person is still followed up.

Most environmental mycobacteria lack these proteins, but a few, such as M. kansasii and M. marinum, carry them.34PubMed Central. Non-Tuberculous Mycobacteria and the Performance of Interferon Gamma Release Assays in Denmark The test still correctly read about 98% of uninfected people as negative even when they had common lung mycobacterial infections.35PubMed Central. Specificity of QuantiFERON-TB Plus, a New-Generation Interferon Gamma Release Assay One case of a false positive was reported from M. gordonae.36PubMed. False-positive QuantiFERON TB-Gold test due to Mycobacterium gordonae

These cases are uncommon, but mention known lung mycobacterial disease to your doctor. M. marinum comes from fish tanks and water and causes skin infections, so tell them if you handle either.

What Happens After a Positive Result

Everyone with a positive result should be checked for active TB.37Massachusetts Department of Public Health. Medical Evaluation for Persons with Positive Test Results Indicating TB Infection A doctor examines you for weight loss, fever, swollen glands, and chest findings.38Massachusetts Department of Public Health. Medical Evaluation for Persons with Positive Test Results Indicating TB Infection A chest X-ray helps separate latent infection from lung disease.39Massachusetts Department of Public Health. Medical Evaluation for Persons with Positive Test Results Indicating TB Infection The X-ray looks for patches, cavities, or scarring in the lungs that suggest active or past disease. Sputum tests follow if the X-ray is abnormal or you have breathing symptoms.40Massachusetts Department of Public Health. Medical Evaluation for Persons with Positive Test Results Indicating TB Infection With a normal X-ray and no symptoms, treatment for latent infection is usually offered.

Sputum testing means coughing up phlegm from deep in the lungs, often on several mornings. The lab looks for TB bacteria under the microscope and grows them in culture. Culture results can take weeks, so a doctor may start planning before they are final.

Treatment for latent TB is usually 3 to 9 months of antibiotics, and it lowers the chance of future active TB. Discuss liver tests and side effects with your doctor, and ask about shorter regimens.

Testing While on Biologic Drugs

Among psoriasis patients on biologics, 6.5% converted over about 3 years.41PubMed. QuantiFERON TB-gold conversion rate among psoriasis patients under biologics: a 9-year retrospective study Conversions were most often seen with anti-TNF drugs such as adalimumab.42PubMed. QuantiFERON TB-gold conversion rate among psoriasis patients under biologics: a 9-year retrospective study Anti-TNF drugs block a signal that helps the immune system wall off TB bacteria, so a sleeping infection can wake up.

Test before the first dose. It gives a baseline, so any later switch to positive can be recognized as new, and a test after the drug has started may be falsely negative because the medicine dampens the response. Steroids can cause indeterminate results. A positive usually means treating latent TB before or alongside the drug.