What are the diagnostic methods for latent tuberculosis (TB) infection?

From the Guidelines

Latent tuberculosis infection (LTBI) is best diagnosed using interferon-gamma release assays (IGRAs) over tuberculin skin test (TST), as IGRAs perform better in diagnosis and are less affected by treatment with glucocorticoids, DMARDs, or immunosuppressants, as suggested by the most recent evidence 1. When diagnosing LTBI, it is essential to consider the individual's risk factors and medical history. The diagnosis primarily involves two types of tests: the tuberculin skin test (TST) and interferon-gamma release assays (IGRAs).

• The TST involves injecting a small amount of purified protein derivative (PPD) under the skin, with results read 48-72 hours later by measuring the size of induration.
• A positive result varies based on risk factors, with ≥5mm considered positive in high-risk individuals, ≥10mm in moderate-risk groups, and ≥15mm in low-risk persons.
• IGRAs, such as QuantiFERON-TB Gold and T-SPOT.TB, are blood tests that measure immune response to TB antigens and are preferred for BCG-vaccinated individuals as they don't cross-react with the vaccine. These tests only indicate infection with TB bacteria, not active disease, so chest X-rays and symptom evaluations are necessary to rule out active TB before confirming a latent TB diagnosis, as recommended by recent guidelines 1. It's also important to note that neither test can distinguish between latent and active TB, nor can they predict progression to active disease, which occurs in approximately 5-10% of infected individuals over their lifetime. In cases of high suspicion for latent TB and/or in high-endemic countries, performing both TST and IGRA can be considered, as the concordance between different IGRAs is good, and one is not recommended over the other 1. Given the most recent evidence, IGRA is the preferred method for screening for latent tuberculosis, and it should be used in conjunction with chest X-ray and symptom evaluation to confirm the diagnosis 1.

From the Research

Diagnosis of Latent TB

To diagnose latent tuberculosis (TB) infection, two main tests are used:

• Tuberculin skin test (TST)
• Interferon-gamma release assays (IGRAs)

These tests detect the presence of TB infection by measuring the immune response to TB antigens.

Types of Tests

There are two types of IGRAs:

• QuantiFERON-TB Gold In-Tube test (QFT-GIT)
• T-SPOT.TB

These tests are used to detect the release of interferon-gamma in response to TB antigens.

Comparison of Tests

Studies have compared the accuracy of TST and IGRAs in diagnosing latent TB infection:

• A study published in 2014 found that IGRAs, especially T-SPOT.TB, were more sensitive and specific than TST in detecting TB infection 2.
• A systematic review and meta-analysis published in 2020 found that IGRAs had a better predictive ability than TST in identifying individuals who would progress to active TB disease 3.
• Another study published in 2017 found that IGRAs were not significantly different from TST in identifying latent TB infection in immunocompromised individuals, but the results were inconsistent and should be interpreted with caution due to uncertainty and risk of bias 4.

Test Results

The results of these tests can be used to identify individuals with latent TB infection:

• A positive TST or IGRA result indicates that an individual has been infected with TB at some point in their lives.
• A negative result does not necessarily rule out TB infection, as some individuals may not produce a positive response to the test.

Treatment

Individuals with latent TB infection may be eligible for treatment to prevent the development of active TB disease:

• A study published in 2018 found that treatment with isoniazid for 6 months or isoniazid and rifampicin for 3 months was effective in preventing the development of active TB disease in individuals with latent TB infection 5.
• The choice of treatment regimen depends on various factors, including the individual's medical history and the presence of any underlying health conditions.

Limitations

While TST and IGRAs are useful tools for diagnosing latent TB infection, they have some limitations:

• False-negative results can occur, especially in individuals with weakened immune systems.
• False-positive results can also occur, especially in individuals who have received the BCG vaccine.
• The tests may not be able to distinguish between latent and active TB infection.

Overall, the diagnosis of latent TB infection requires a combination of medical history, physical examination, and laboratory tests, including TST and IGRAs 6.