How is latent tuberculosis (TB) diagnosed?

From the Guidelines

Latent tuberculosis (TB) is diagnosed through specific tests, primarily the tuberculin skin test (TST) and interferon-gamma release assays (IGRAs) such as QuantiFERON-TB Gold or T-SPOT.TB, as recommended by the World Health Organization guidelines for low TB burden countries 1. The diagnosis of latent TB involves detecting the presence of TB bacteria in the body without active disease symptoms. The main diagnostic methods include:

• The tuberculin skin test (TST), which involves injecting a small amount of purified protein derivative under the skin and examining the site 48-72 hours later for a reaction (induration) 1.
• Interferon-gamma release assays (IGRAs) such as QuantiFERON-TB Gold or T-SPOT.TB, which involve a blood test that measures the immune response to TB proteins and are preferred for people who have received the BCG vaccine since they're not affected by prior vaccination 1. A positive result varies based on risk factors but generally means an induration of 5-15mm or more for the TST. The World Health Organization guidelines for low TB burden countries recommend systematic testing and treatment of LTBI in high-risk individuals, including people living with HIV, adult and child contacts of pulmonary TB cases, and patients with certain medical conditions 1. Once diagnosed, treatment typically involves antibiotics such as isoniazid (INH) for 6-9 months, rifampin for 4 months, or a combination of INH and rifapentine weekly for 3 months, with the choice of regimen depending on factors like potential drug interactions, medical history, and risk of liver disease 1. Regular monitoring during treatment is essential to check for side effects, particularly liver function. Key considerations for diagnosing latent TB include:
• Using either commercial interferon-gamma release assays or Mantoux tuberculin skin testing to test for LTBI 1.
• Performing chest radiography before LTBI treatment to rule out active TB disease 1.
• Recommending treatment regimens for LTBI, including 6 or 9 month isoniazid, 12 week rifapentine plus isoniazid, 3–4 month isoniazid plus rifampicin, or 3–4 month rifampicin alone 1.

From the FDA Drug Label

Isoniazid is recommended as preventive therapy for the following groups, regardless of age. Candidates for preventive therapy who have HIV infection should have a minimum of 12 months of therapy. 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)

Latent TB diagnosis is typically made through a combination of:

• Tuberculin skin test (≥ 5 mm, ≥ 10 mm, or ≥ 15 mm induration, depending on the individual's risk factors)
• Medical history and risk factors, such as:
  • HIV infection
  • Close contact with someone with infectious tuberculosis
  • Recent conversion
  • Abnormal chest radiographs
  • Certain medical conditions (e.g., silicosis, diabetes mellitus) 2

From the Research

Latent TB Diagnosis Methods

• The diagnosis of latent tuberculosis (TB) infection requires a positive test for infection and negative evaluation for active disease 3.
• Current tests for latent TB infection measure an immunologic response and include:
  • Tuberculin skin test (TST)
  • Interferon-gamma release assays (IGRAs), such as T-SPOT.TB and QuantiFERON 3, 4
• IGRAs are preferred in bacille Calmette-Guérin-vaccinated populations, while TST is still used when cost or logistical advantages exist 3.

Test Characteristics

• Both TST and IGRAs have low positive predictive values, meaning they are not perfect for predicting future TB risk 5, 3.
• IGRAs have a better predictive ability than TST for the progression of latent infection to active tuberculosis disease 6.
• The pooled risk ratio for disease progression in untreated individuals who were positive by IFN-γ release assay versus those who were negative was 9·35 (95% CI 6·48-13·49) compared with 4·24 (3·30-5·46) for TST 6.

Limitations and Future Directions

• Neither TST nor IGRA can accurately differentiate between latent TB infection and active TB 5, 7.
• There is a need for tests that can differentiate the TB spectrum and better predict future TB risk 3.
• Research is ongoing to identify immunological markers that can distinguish latent TB infection from active TB and evaluate the effectiveness of treatment 7.