Advanced tests to diagnose latent tuberculosis

Quantiferon Gold and TSPOT.TB can reliably diagnose latent tuberculosis

Tuberculosis is the single largest infectious killer of mankind. It has been aptly named as 'Captain of all men of death'. Not all persons exposed to tubercle bacillus develop active tuberculosis. In many of them the infection is contained by the immune system. Such a state is called as latent tuberculosis. Though they still harbour the tuberculous infection, their effective immune system prevents the multiplication of the bacillus and its spread. But if the immune system is compromised on a later date, the latent tuberculosis becomes active tuberculosis. This situation commonly occurs in HIV positive individuals and those on chronic steroid therapy. It has been estimated that 5 to 10% of patients with latent tuberculosis would eventually develop active tuberculosis in their lifetime. 

The test available till recently to diagnose latent tuberculosis was Mantoux test or Tuberculin Skin Testing (TST). This test is based on the immunologic principle of delayed hypersensitivity. In this test purified protein derivative of Mycobacterium tuberculosis is instilled intradermally on the forearm and size of the swelling that occurs at the site is measured after 2 to 3 days. Although it has been in use for the past 100 years, the test has low sensitivity and specificity with an accuracy around 66%. Prior BCG vaccination and immunosuppression as in HIV  infection can lead to false and unreliable results in TST. Furthermore it has operational disadvantages as the patients need to return after 2 to 3 days for reading the induration (swelling). The only major advantage of TST is its low cost and the familiarity of heathcare personnel with this test.

The newer tests are based on Interferon Gamma Release Assays (IGRA). The two commerically available IGRA tests are the Quantiferon Gold and TSPOT.TB. In these tests blood samples are collected and the peripheral mononuclear cells are exposed to TB antigens. The quantity of interferon gamma produced is measured and  results are expressed as positive, negative and indeterminate. These tests are more sensitive and specific and the accracy comes to around 96%. They are not affected by prior BCG vaccination and are better than TST in HIV positive individuals. Studies conducted at several countries have strongly affirmed the usefullness of this test in TB control program. The only major limitation seems to be the cost, which has limited its widespread use.

Monday, September 16, 2013