What to do with a recent immigrant with an initial positive Quantiferon Gold (Interferon-Gamma Release Assay) test and a subsequent negative test, with a normal chest X-ray?

Management of Discordant QuantiFERON Results in a Recent Immigrant

In a recent immigrant with an initial positive QuantiFERON Gold test followed by a negative repeat test and normal chest X-ray, the most prudent approach is to treat this as latent tuberculosis infection (LTBI) given the high-risk population status, despite the discordant results. 1

Risk Assessment and Clinical Context

Recent immigrants from high TB-prevalence countries (>30 cases/100,000) are considered high-risk for LTBI and warrant aggressive screening and treatment. 1

• The initial positive test should carry significant weight in this population, as the probability of true infection is substantially elevated based on country of origin alone 1
• A subsequent negative test does not reliably exclude M. tuberculosis infection, particularly in high-risk individuals 1
• CDC guidelines explicitly state that "multiple negative results from any combination of these tests cannot exclude M. tuberculosis infection" 1

Interpretation of Discordant Results

When initial and repeat IGRA results are discordant, clinical judgment should favor the positive result in high-risk populations. 1

• The 2010 CDC guidelines indicate that repeating an IGRA may be useful when initial results are "indeterminate, borderline, or invalid," but your case describes a clear positive followed by a clear negative 1
• In persons at increased risk for LTBI (which includes recent immigrants), requiring both tests to be positive would inappropriately reduce sensitivity for detecting true infection 1
• The probability of LTBI is greatest when both tests are positive, but a single positive test in a high-risk individual still warrants serious consideration for treatment 1

Active TB Exclusion

Before initiating LTBI treatment, active TB disease must be excluded through clinical evaluation. 1, 2

• The normal chest X-ray is reassuring and represents the minimum required evaluation 1, 2
• Obtain a detailed history for TB symptoms: fever, night sweats, weight loss, chronic cough, hemoptysis 1
• Perform a thorough physical examination looking for signs of extrapulmonary TB 1
• HIV testing is strongly recommended, as HIV infection increases both the risk of progression and urgency of treating LTBI 1, 2
• If any symptoms or signs suggest active TB, obtain sputum samples for acid-fast bacilli smear and culture before starting LTBI treatment 1

Treatment Recommendation

After excluding active TB disease, initiate treatment for LTBI based on the initial positive test result. 1, 2

• The need for LTBI treatment when QuantiFERON is positive should be based on clinical judgment and perceived risk, even if a subsequent test is negative 1
• For persons at increased risk for LTBI (recent immigrants), treatment is recommended when QuantiFERON is positive, regardless of confirmatory testing 1
• Standard LTBI treatment regimens should be offered per current CDC guidelines 2

Important Caveats

Do not perform a tuberculin skin test (TST) to "confirm" or clarify these results. 1, 2

• CDC guidelines explicitly state "no reason exists to follow a positive QFT-G result with a TST" 1, 2
• Adding TST after IGRA testing provides no additional useful information and may cause confusion 1, 2

Understand that QuantiFERON results can fluctuate, particularly around the test's cut-off threshold. 1

• Variability in test results can occur due to biological variation, pre-analytical factors, or borderline IFN-γ responses 1
• This variability does not negate the significance of the initial positive result in a high-risk individual 1

Consider epidemiologic factors that increase confidence in true infection. 3, 4

• Duration of time in high TB-prevalence country before immigration 3
• Known TB exposure or contact history 3
• Previous TB disease or treatment 3