From the Guidelines
Tuberculosis (TB) testing is recommended for individuals at risk of TB infection, including those with symptoms, close contacts of TB patients, healthcare workers, and people from high-prevalence regions, using either the tuberculin skin test (TST) or interferon-gamma release assays (IGRAs) like QuantiFERON-TB Gold or T-SPOT.TB, as recommended by the most recent guidelines from the National Tuberculosis Controllers Association and CDC in 2020 1.
Testing Methods
The two main testing methods are:
- TST: a small amount of purified protein derivative is injected under the skin, and the site is examined 48-72 hours later; a raised, hardened area of 10mm or larger generally indicates a positive result (5mm for high-risk individuals)
- IGRAs: require a blood sample and measure immune response to TB proteins, with results available within 24 hours
Testing Frequency and Follow-up
Testing frequency depends on risk factors, with annual testing recommended for healthcare workers and those with ongoing exposure. Positive results require follow-up with:
- Chest X-rays to distinguish between latent TB infection and active TB disease
- Possibly sputum tests to confirm active TB disease
Treatment
Treatment varies accordingly, with:
- Latent TB typically treated with isoniazid for 6-9 months or rifampin for 4 months, as recommended by the WHO guidelines for low TB burden countries in 2015 1
- Active TB requiring a multi-drug regimen for 6-12 months
Key Considerations
- The QuantiFERON-TB test is an approved alternative to TST for diagnosing latent TB infection, as recommended by the CDC in 2003 1
- Testing should be primarily targeted at diagnosing infected patients who will benefit from treatment
- The most recent guidelines from the National Tuberculosis Controllers Association and CDC in 2020 should be followed for the treatment of latent TB infection, which includes three preferred rifamycin-based regimens and two alternative monotherapy regimens with daily isoniazid 1
From the FDA Drug Label
Isoniazid is recommended as preventive therapy for the following groups, regardless of age. (Note: the criterion for a positive reaction to a skin test (in millimeters of induration) for each group is given in parenthesis): 1 Persons with human immunodeficiency virus (HIV) infection (≥ 5 mm) and persons with risk factors for HIV infection whose HIV infection status is unknown but who are suspected of having HIV infection. 2. Close contacts of persons with newly diagnosed infectious tuberculosis (≥ 5 mm) 3 Recent converters, as indicated by a tuberculin skin test (≥ 10 mm increase within a 2-year period for those < 35 years old; ≥ 15 mm increase for those ≥ 35 years of age). 4 Persons with abnormal chest radiographs that show fibrotic lesions likely to represent old healed tuberculosis (≥ 5 mm). 5 Intravenous drug users known to be HIV-seronegative (> 10 mm). 6 Persons with the following medical conditions that have been reported to increase the risk of tuberculosis (≥ 10 mm): The guidelines for Tuberculosis (TB) testing are as follows:
- Positive reaction criteria:
- ≥ 5 mm for persons with HIV infection, close contacts of persons with newly diagnosed infectious tuberculosis, and persons with abnormal chest radiographs
- ≥ 10 mm for recent converters, intravenous drug users, and persons with certain medical conditions
- Candidate groups for preventive therapy:
- Persons with HIV infection
- Close contacts of persons with newly diagnosed infectious tuberculosis
- Recent converters
- Persons with abnormal chest radiographs
- Intravenous drug users
- Persons with certain medical conditions
- Foreign-born persons from high-prevalence countries
- Medically underserved low-income populations
- Residents of facilities for long-term care
- Children who are less than 4 years old with > 10 mm induration from a PPD Mantoux tuberculin skin test
- Persons under the age of 35 with a tuberculin skin test reaction of 10 mm or more who are members of high-incidence groups
- Persons under the age of 35 with a tuberculin skin test reaction of 15 mm or more and no risk factors 2
From the Research
Guidelines for Tuberculosis (TB) Testing
The guidelines for TB testing are as follows:
- Individuals with symptoms of TB disease warrant testing 3
- The U.S. Preventive Services Task Force recommends testing individuals at increased risk of latent TB infection (LTBI) with an interferon-gamma release assay or tuberculin skin testing 3
- Contacts of infectious TB patients should be monitored, especially those at highest risk of developing TB 4
- Standard prophylaxis for pulmonary TB consists of isoniazid monotherapy for 6 to 12 months 4
Testing Methods
The following testing methods are used for TB:
- Tuberculin skin test (TST) 5, 6, 7
- Interferon-gamma release assays (IGRA) 5, 6, 7
- IGRA seem to be more accurate than TST in bacillus Calmette-Guerin vaccinated subjects and patients with autoimmune diseases 5
- T-SPOT.TB was significantly more sensitive than TST in detecting TB infection 7
Interpretation of Test Results
The interpretation of test results is as follows:
- A positive test result should be followed by chest radiography and, in patients with suspected pulmonary TB disease, sputum collected for diagnosis 3
- The agreement between IGRA and TST test results can be low, potentially helping to identify more cases of LTBI if the two tests are used in parallel 6
- Patients with HIV infection, diabetes, oncologic diseases, and inflammatory diseases may present different outcomes between IGRA and TST 6
Treatment and Reporting
The following guidelines are recommended for treatment and reporting:
- Preferred treatment regimens for LTBI include isoniazid in combination with rifapentine or rifampin, or rifampin alone for a duration of three and four months, respectively 3
- Treatment of drug-susceptible TB disease includes an eight-week intensive phase with four drugs, followed by a continuation phase lasting 18 weeks or more 3
- Both suspected and confirmed cases of LTBI and TB disease must be reported to local or state health departments 3