What are the next steps for a patient with a positive Quantiferon Gold (Interferon-Gamma Release Assay) test?

Management of a Positive QuantiFERON-TB Gold Test

A positive QuantiFERON-TB Gold (QFT-G) test requires immediate evaluation to rule out active tuberculosis disease, followed by treatment for latent tuberculosis infection (LTBI) if active disease is excluded. 1

Initial Evaluation After Positive QFT-G

1. Rule out active TB disease:

   • Perform a chest radiograph to look for abnormalities consistent with TB 1
   • Conduct thorough symptom screening (fever, night sweats, weight loss, cough)
   • If any symptoms or radiographic abnormalities are present:
     • Collect 3 sputum specimens for acid-fast bacilli smear
     • Order mycobacterial culture
     • Request nucleic acid amplification testing

2. Medical history assessment:

   • Recent TB exposure or contact with infectious TB cases
   • Country of origin (higher risk if from TB-endemic region)
   • Prior TB treatment history
   • HIV status (recommend HIV testing if unknown)
   • Presence of immunosuppressive conditions

Treatment of Latent TB Infection

Once active TB disease is excluded, initiate LTBI treatment promptly:

First-line regimen:

• Isoniazid for 9 months 2
  • Adults: 300 mg daily
  • Children: 10-15 mg/kg daily (maximum 300 mg)

Alternative regimens:

• Rifampin for 4 months

  • Adults: 600 mg daily
  • Children: 10-20 mg/kg daily (maximum 600 mg)

• Isoniazid plus rifapentine weekly for 3 months (directly observed therapy) 3

  • Rifapentine dosing based on weight:
    • 10-14 kg: 300 mg
    • 14.1-25 kg: 450 mg
    • 25.1-32 kg: 600 mg
    • 32.1-50 kg: 750 mg

    • 50 kg: 900 mg

  • Isoniazid:
    • Adults: 15 mg/kg (maximum 900 mg) weekly
    • Children 2-11 years: 25 mg/kg (maximum 900 mg) weekly

Monitoring During LTBI Treatment

• Monthly clinical assessment for:

  • Medication adherence
  • Signs of hepatotoxicity (nausea, vomiting, abdominal pain, jaundice)
  • Peripheral neuropathy (with isoniazid)
  • Other adverse effects

• Laboratory monitoring:

  • Baseline liver function tests (LFTs)
  • Regular LFT monitoring for patients:
    • Over 35 years of age
    • With history of liver disease
    • With regular alcohol consumption
    • Taking other hepatotoxic medications

Special Considerations

• Immunocompromised patients:

  • Higher priority for LTBI treatment due to increased risk of progression to active TB 2
  • If on immunosuppressive therapy (e.g., adalimumab), consider initiating LTBI treatment at least 1 month before starting or immediately if already on immunosuppressive therapy

• Pregnancy:

  • Defer treatment until after delivery unless high risk of progression to active TB
  • If treatment necessary during pregnancy, isoniazid with pyridoxine is preferred

• Children:

  • Higher priority for LTBI treatment due to increased risk of progression to active TB
  • Dosing adjustments based on weight

Important Caveats

1. A positive QFT-G does not distinguish between active TB and LTBI; clinical evaluation is essential 1

2. QFT-G typically remains positive even after successful LTBI treatment, so it should not be used to monitor treatment response 4

3. The risk of progression from LTBI to active TB is highest within the first 2 years after infection, particularly in:

   • Young children (<5 years)
   • HIV-infected individuals
   • Persons receiving immunosuppressive therapy
   • Those with silicosis, diabetes, chronic renal failure, or malnutrition

4. Unlike the tuberculin skin test (TST), QFT-G has higher specificity and is not affected by prior BCG vaccination 1, 5

5. Indeterminate QFT-G results may occur in immunocompromised patients and require clinical judgment regarding repeat testing or alternative approaches 1

By following this systematic approach, you can effectively manage patients with positive QFT-G results, preventing progression to active TB disease and its associated morbidity and mortality.