Latent tuberculosis and tuberculin skin testing

What it is

The diagnosis of latent TB infection involves demonstration of immune memory to mycobacterial proteins. Two tests are available for that: the tuberculin skin test and interferon-gamma release assays.

How it is diagnosed

The Mantoux skin test consists of an intradermal injection of one-tenth of a milliliter of PPD tuberculin and represents delayed type hypersensitivity. The size of induration is measured 48-72 hours later; erythema, that is redness, should not be measured. A positive result is a delayed hypersensitivity reaction evident 48-72 hours after the intradermal injection of purified protein derivative, giving a raised indurated lesion above 6 mm in diameter in nonvaccinated adults, or above 15 mm in BCG-vaccinated adults.

False negative, anergic, skin tests occur with immunosuppression due to HIV infection with CD4+ below 200/mm3, in sarcoidosis, with drugs such as chemotherapy, anti-TNF therapy and steroids, and through cross-reactivity with non-tuberculous mycobacteria and BCG vaccination. The skin test is also written down as having low sensitivity and specificity, useful only in primary or deep-seated infection.

These limitations may be overcome by interferon-gamma release assays. They detect T-cell secretion of interferon-gamma following exposure to M tuberculosis-specific antigens, ESAT-6 and CFP-10. A sample of either purified T cells or whole blood is incubated in the presence of antigens specific to Mycobacterium tuberculosis, and the release of interferon-gamma by the cells is measured by ELISA. They are highly specific compared with the skin test and have a similar or better sensitivity; their disadvantage is that they do not differentiate between active and latent infection.

A positive screening test, along with a review of systems, a physical examination and a chest radiograph that do not show evidence of active infection, confirms the diagnosis of latent TB. A second set of numbers for the same test goes by risk group rather than by BCG shot: >= 5 mm is positive in the immunocompromised, that is HIV and post-transplant, and in an asymptomatic person with contact of a patient with un-treated active TB; >= 10 in healthworkers; and >= 15 in the normal population. These sit beside the numbers above and the two sets do not agree, so read both. Why the blood test exists at all is written beside it: a tuberculin test can give a positive result regardless of presence of TB infection for an individual who has previously had a BCG shot, and for that reason interferon gamma release assay, a blood test, is used for screening. Mantoux test, PPD and TST are three names for the one test.

The screen is also ordered ahead of a drug rather than after an exposure. In JIA, remission is maintained on methotrexate, with liver and renal function followed, and on biologic agents, the anti-TNF drugs - and beside those biologic agents is written: do a chest x ray to rule out latent TB. So the chest film here is not for a contact or a symptom; it is the step before starting the drug that would let a latent infection go.