What to do next if the Quantiferon (Interferon-Gamma Release Assay) test is positive for latent tuberculosis (TB) infection?

Management of a Positive QuantiFERON Test

If your QuantiFERON test is positive, immediately obtain a chest radiograph to exclude active tuberculosis disease, then assess risk factors to determine if latent TB treatment is warranted. 1

Immediate Next Steps

1. Rule Out Active Tuberculosis Disease (Critical First Step)

• Obtain a chest radiograph to look for evidence of active TB or old healed lesions 1
• Screen for TB symptoms including cough, fever, night sweats, weight loss, and hemoptysis 1
• Perform sputum examination if any respiratory symptoms are present or if chest X-ray shows abnormalities 1
• Never initiate single-drug latent TB treatment until active TB is definitively excluded 1

2. Perform Targeted Clinical Assessment

• Take a detailed TB exposure history focusing on recent contact with active TB cases, travel to or origin from TB-endemic countries, and duration of exposure 1, 2
• Assess for high-risk medical conditions including HIV infection, immunosuppressive therapy (especially TNF-α antagonists), diabetes mellitus, silicosis, end-stage renal disease, and malignancy 1, 3
• Offer HIV testing because HIV infection dramatically increases both the risk of active TB and the urgency of treating latent TB infection 1

3. Do NOT Repeat Testing

• Do not perform a tuberculin skin test (TST) after a positive QuantiFERON result as both tests should prompt the same evaluation and management 1
• The exception is in low-risk populations where CDC guidelines recommend confirming a positive QuantiFERON with TST before starting treatment 4

Treatment Decision Algorithm

High-Priority Groups (Treat Latent TB)

Initiate treatment if the patient has any of the following high-risk factors: 1

• HIV/AIDS infection (≥5 mm TST equivalent) 1, 3
• Close contacts of persons with newly diagnosed infectious TB 3
• Recent converters (within 2 years) 3
• Chest radiograph showing fibrotic lesions consistent with old healed TB 1, 3
• Silicosis 1
• Immunosuppressive therapy, including TNF-α antagonists 5, 1
• Prolonged corticosteroid therapy 3
• Diabetes mellitus 1
• End-stage renal disease 3
• Hematologic malignancies 3
• Recent immigrants from high TB burden countries 1

Moderate-Priority Groups (Consider Treatment)

Consider treatment for: 1

• Healthcare workers 1
• Prisoners 1
• Homeless persons 1
• Injection drug users 1

Low-Risk Populations

• For persons under age 35 with no risk factors and ≥15 mm TST equivalent, treatment may be considered 3
• For persons over age 35 without additional risk factors, weigh the risk of hepatitis from treatment against the risk of TB progression 3

Recommended Treatment Regimens

Choose one of the following evidence-based regimens: 1

1. Isoniazid 5 mg/kg (maximum 300 mg) daily for 9 months (preferred) 1
2. Isoniazid 5 mg/kg (maximum 300 mg) daily for 6 months (alternative) 1
3. Rifampin 10 mg/kg (maximum 600 mg) daily for 4 months 1
4. Isoniazid plus rifampin daily for 3-4 months 1
5. Rifapentine plus isoniazid once weekly for 12 weeks (requires directly observed therapy) 1

Special Populations

• HIV-infected patients: Require minimum 12 months of therapy 3
• Patients with fibrotic pulmonary lesions or silicosis: Require 12 months of isoniazid or 4 months of isoniazid and rifampin 3
• Pregnant women: Should be treated with isoniazid; chest radiograph with abdominal shielding should be performed even in first trimester 1

Monitoring During Treatment

• Monthly clinical assessment for all patients, with education about hepatitis symptoms 1
• Baseline and periodic liver function tests for patients with risk factors including pregnancy, HIV infection, and heavy alcohol use 1

Critical Pitfalls to Avoid

• Do not use QuantiFERON to monitor treatment response or confirm cure as the test remains positive after treatment in 85-88% of patients 6, 2
• Do not use QuantiFERON to diagnose active TB disease because active TB suppresses interferon-gamma responses, leading to false-negative results 4
• Do not delay treatment in high-risk patients while waiting for confirmatory testing 4
• In patients starting anti-TNF therapy, yearly QuantiFERON testing should be done if high-risk exposure continues, though caution is needed as the test can remain positive after latent TB treatment 5