Should I perform an Interferon-Gamma Release Assay (IGRA) test to rule out tuberculosis?

When to Use Interferon-Gamma Release Assay (IGRA) Testing for Tuberculosis

IGRAs are preferred over tuberculin skin tests (TST) for diagnosing latent tuberculosis infection in BCG-vaccinated individuals and populations with low rates of return for TST reading, such as homeless persons and drug users. 1

Indications for IGRA Testing

IGRAs measure interferon-gamma released by T cells when exposed to specific M. tuberculosis antigens. There are two FDA-approved IGRAs:

1. QuantiFERON-TB Gold In-Tube (QFT-GIT)
2. T-SPOT.TB

Situations Where IGRA is Preferred Over TST:

• Persons who have received BCG vaccination (as a vaccine or for cancer therapy) 1, 2
• Groups with historically low rates of returning for TST reading (e.g., homeless persons, drug users) 1
• Healthcare workers and others requiring occupational screening 1

Situations Where TST is Preferred Over IGRA:

• Children under 5 years of age 1

Situations Where Either Test Can Be Used:

• Contact investigations for persons exposed to active TB 1
• Periodic screening for occupational exposure to TB 1
• General screening for latent TB infection 1

Combined Testing Approach (Both IGRA and TST)

In certain situations, using both tests may be beneficial:

1. When initial test is negative and:

   • Risk for infection, progression, and poor outcomes is high (e.g., HIV-infected persons, children <5 years) 1
   • Clinical suspicion for active TB exists 1

2. When initial test is positive and:

   • Additional evidence is needed to encourage treatment compliance (e.g., foreign-born healthcare workers who attribute positive TST to BCG) 1
   • Testing healthy persons with low risk for infection and progression 1

Advantages of IGRAs

• Higher specificity (fewer false positives) in BCG-vaccinated individuals 2
• Results available within 24 hours without requiring a return visit 1
• Not subject to reader bias or interpretation errors 1
• Associated with higher treatment completion rates for latent TB infection compared to TST (55.0% vs 42.2%) 3

Limitations of IGRAs

• Higher cost than TST, though potentially offset by reduced false positives 1
• Requires proper blood collection and handling 1
• Limited data on predictive value for progression to active TB 2
• May have indeterminate results, particularly in immunocompromised patients 2

Important Considerations

• Neither IGRAs nor TST can distinguish between latent TB infection and active TB disease 1
• Diagnosis should never be based solely on IGRA or TST results but should include epidemiologic and medical history as well as other clinical information 1
• In persons with symptoms, signs, or radiographic evidence of active TB, a positive result with either test should be taken as evidence of M. tuberculosis infection 1
• In healthy persons with low likelihood of infection and progression, a single positive result should not be taken as reliable evidence of infection 1

Algorithm for IGRA Testing Decision

1. Assess patient risk factors:

   • BCG vaccination status
   • Risk of not returning for TST reading
   • Age (under 5 years or not)
   • Immunocompromised status
   • Risk for progression to active TB

2. Choose appropriate test:

   • If BCG-vaccinated or low likelihood of return → IGRA preferred
   • If child under 5 years → TST preferred
   • If immunocompromised → Consider both tests to increase sensitivity
   • If routine screening in low-risk individual → Consider avoiding testing altogether

3. Interpret results in clinical context:

   • Positive result requires evaluation for active TB before diagnosing latent TB
   • Negative result does not exclude infection in high-risk individuals
   • Indeterminate results may require repeat testing

Remember that unnecessary testing of low-risk individuals should be avoided as it increases false-positive results and diverts resources from higher priority activities 1.