3.2 Latent tuberculosis infection

Diagnosis is based on exclusion of active TB and demonstration of latent tuberculosis infection (LTBI).

For demonstrating LTBI, one of the following tests may be performed. However, these tests are not mandatory prior to initiating LTBI treatment in:

• Children under 5 years household contact of a TB case;
• Children and adults with HIV infection [1] Citation 1. World Health Organization. Latent tuberculosis infection: updated and consolidated guidelines for programmatic management. Geneva: World Health Organization; 2018.
  https://apps.who.int/iris/bitstream/handle/10665/260233/9789241550239-eng.pdf .

3.2.1 Tuberculin skin test

A positive tuberculin skin test (TST) indicates that a mycobacterial infection has occurred.

For interpretation of TST results, see Appendix 9.

TST has several limitations:

• It does not distinguish infection by M. tuberculosis or by environmental mycobacteria.
• It does not distinguish latent and active TB.
• Prior BCG vaccination can result in a false positive TST.
• False negative TST is common, particularly in patients with HIV infection and malnourished children.

After having ruled out active TB, a positive TST is an indication for treatment of LTBI (Chapter 16).

Notes:

• TST is also used to check the absence of TB in neonates on isoniazid monotherapy (Chapter 16).
• Other skin tests are available, but have not yet been evaluated by WHO.

3.2.2 Interferon gamma release assays

The test is performed in vitro on blood to which M. tuberculosis antigens are added. This results in the rapid stimulation of memory T cells and release of interferon-gamma in patients previously exposed to the bacillus.

The following tests measure:

• QuantiFERON-TB Gold In-Tube: the amount of interferon-gamma released.
• T-SPOT.TB test: the number of interferon-gamma producing T cells [2] Citation 2. Pai M., et al. Gamma interferon release assays for detection of Mycobacterium tuberculosis infection. Clin Microbiol Rev, 2014. 27(1): p. 3-20.
  https://doi.org/10.1128/CMR.00034-13 .

The advantage of IGRAs over TST is the absence of cross-reaction with BCG vaccine and most environmental mycobacteria.

IGRAs have some limitations:

• They do not distinguish latent and active TB.
• They are more complex than TST (equipment and trained laboratory technicians) and are not widely available.

A positive test indicates that LTBI is likely; a negative test indicates that it is unlikely.

After having ruled out active TB, a positive IGRA is an indication for treatment of LTBI (Chapter 16).