What are the screening tests for tuberculosis (TB)?

Screening Tests for Tuberculosis

The primary screening tests for tuberculosis infection are the interferon-gamma release assay (IGRA) and the tuberculin skin test (TST), with IGRA generally preferred in most clinical scenarios, particularly in BCG-vaccinated populations and those on immunosuppressive therapy. 1, 2

Core Screening Tests

Interferon-Gamma Release Assays (IGRAs)

• Two commercial IGRAs are approved: QuantiFERON-TB Gold In-Tube and T-SPOT.TB, both requiring only a blood sample with results available within 8-30 hours 1
• IGRA is preferred over TST in individuals with prior BCG vaccination, those already on immunosuppressive therapy (including corticosteroids), and situations where return for TST reading is unlikely 1, 2
• IGRA demonstrates superior specificity compared to TST, particularly in BCG-vaccinated populations, with lower false-positive rates 1, 3
• IGRA has better predictive value for progression to active TB, with a pooled risk ratio of 9.35 for disease progression in untreated IGRA-positive individuals versus 4.24 for TST-positive individuals 4
• IGRA-positive individuals benefit more from preventive treatment (RR 3.09 for untreated vs treated) compared to TST-positive individuals (RR 1.11) 4

Tuberculin Skin Test (TST)

• TST requires intradermal placement of tuberculin purified protein derivative with interpretation of induration at 48-72 hours 1
• TST has significant limitations including cross-reactivity with BCG vaccination and most non-tuberculous mycobacteria, leading to false-positive results 3, 5
• TST demonstrates high rates of anergy in immunosuppressed patients, with 83% of patients on steroids or immunomodulators showing anergic responses versus 43% not on these therapies 1
• TST and IGRA show poor agreement in many populations, particularly in dialysis patients (only 19.6% of IGRA-positive patients were TST-positive) 6

Screening Algorithm by Clinical Scenario

Standard Approach

• Begin with individual TB risk assessment including history of TB exposure, country of origin, living/working conditions, immunosuppressive conditions, and HIV status 2
• Perform symptom evaluation for cough, fever, night sweats, weight loss, and hemoptysis 2
• Test with either IGRA or TST in individuals without documented prior latent TB infection (LTBI) or TB disease 1, 2
• For asymptomatic low-risk individuals with positive initial test, perform a second confirmatory test (either IGRA or TST); consider infected only if both tests are positive 1, 2
• Obtain chest radiography after positive IGRA or TST to distinguish latent TB from active disease 1, 2

Testing Strategy Options

Guidelines describe four main approaches, though IGRA preference is increasingly emphasized 1:

1. Two-step TST-first approach: TST followed by IGRA when TST is negative (to increase sensitivity in immunocompromised) or when TST is positive (to increase specificity in BCG-vaccinated individuals) 1

2. Either test alone: IGRA or TST, but not both 1

3. Dual testing: IGRA and TST together to increase sensitivity, with pooled disease progression rate of 6.1% in dual-positive individuals 1, 4

4. IGRA only: Replacing TST entirely, which is the preferred modern approach 1

High-Risk Populations Requiring Screening

• Healthcare personnel should receive baseline screening with risk assessment, symptom evaluation, and testing (IGRA or TST) prior to starting work 1, 2
• Patients initiating anti-TNF biologics or immunosuppressive therapy must be screened using clinical risk stratification, chest x-ray, and IGRA (preferred over TST due to lower false-positives with corticosteroids/BCG) 1, 2
• Foreign-born persons from high TB burden countries (Africa, Asia, Eastern Europe, Latin America, Russia) require screening 2
• Close contacts of active pulmonary TB cases including household members and frequent visitors 2
• Persons living with HIV require TB screening 2
• Patients with hematologic malignancies, head and neck squamous cell carcinoma, and lung cancer warrant screening based on substantially increased TB incidence 1
• Patients preparing for organ or hematological transplantation 2
• Patients with chronic kidney disease or on dialysis (though IGRA detects more cases than TST: 36% vs 17%) 2, 6
• Residents of congregate settings (correctional facilities, homeless shelters, long-term care facilities) 2
• Patients with diabetes, malignancies, hepatitis C, rheumatoid arthritis, or vitamin D deficiency 2

Post-Exposure Screening Protocol

• Perform symptom evaluation immediately when exposure is recognized 1, 2
• Test with IGRA or TST at the time exposure is identified in individuals without documented prior LTBI or TB disease 1, 2
• If initial test is negative, repeat testing 8-10 weeks after last exposure using the same test type as the initial test 1, 2
• Persons with documented prior LTBI or TB disease do not need repeat testing after exposure, but should have clinical evaluation if TB disease is suspected 1, 2

Critical Pitfalls and Caveats

• Do not repeat IGRA or TST in persons who previously tested positive; instead, monitor for clinical signs and symptoms of active TB 2
• IGRA has significant limitations in serial testing due to spontaneous variability and lack of validated definitions for conversion and reversion, making interpretation of category changes difficult 3
• Both tests perform poorly at predicting individual risk for progression to active TB, though IGRA performs better than TST 3, 4
• Testing should only be performed in persons without documented prior LTBI or TB disease to avoid unnecessary repeat testing 1, 2
• Indeterminate IGRA results occur in 2.7% of tests and warrant clinical judgment, as one case of TB reactivation occurred in a patient with an indeterminate test on immunosuppressive therapy 1
• After positive screening, active TB must be excluded through clinical history, physical examination, chest radiograph, and respiratory sampling (3 sputum specimens for AFB smear, culture, and nucleic acid amplification) before initiating LTBI treatment 1

Treatment Following Positive Screening

• Treatment is encouraged for all persons with untreated LTBI unless medically contraindicated 1, 2
• Preferred regimens include: isoniazid plus rifapentine once weekly for 3 months, isoniazid plus rifampin daily for 3-4 months, rifampin alone daily for 4 months, and isoniazid alone for 9 months 2
• For patients starting biologics including rituximab, initiate or resume biologic therapy after at least 1 month of LTBI treatment 2
• Dual-positive individuals (both IGRA and TST positive) who are untreated versus treated show the highest benefit from preventive treatment (RR 7.84) 4