3.6 Serological methods for diagnosis of tuberculosis


A serological test for tuberculosis has been pursued throughout the twentieth century. Particular interest has been focused on patients with extrapulmonary forms of tuberculosis, since they generally do not have readily accessible diagnostic targets such as chest radiography or sputum. However, unlike many infectious diseases for which serodiagnosis has proven a highly valuable tool, tuberculosis has largely defied efforts at developing a methodology that is sensitive, specific, and practical for clinical use.

The major problem with the specificity issue lies with distinguishing between the infected versus the diseased state; also problematic is the serological reaction to prior BCG vaccination. This is particularly relevant in the developing nations where a simple test like serological examination would be of greatest utility: in such countries, approximately 40% of the population have latent tuberculosis infection, and substantial numbers have been vaccinated with M. bovis BCG. Analysis of the many and varied studies of the serodiagnosis of tuberculosis indicates that there is a diversity of antigens potentially involved, that there is a wide array of immune responses associated with different forms of tuberculosis disease (cavitary pulmonary, noncavitary pulimonary, and extrapulmonary). Last time scientific research is directed to following c seroantigens and techniques:

— Antigen of 38 Kilodaltons
— Antigen 5
— Antigen A60 Antigen of 88 Kilodaltons
— Multiantigen Analysis

The application of modern methods of biochemical reserch enables to increase sensitivity and specificity of research of individual proteins, at which direct participation occur practically all physiological and pathophysiological of the host reaction. On character of functions and number of individual properties these proteins can conditionally be divided on several groups:

  • proteins connected with immune reaction (IgG, IgA, IgM, СЗ, С4 – complement components);
  • proteins, reactants of a sharp phase of an inflammation: C-reactive prtein, alpha1 – glycoprotein, alpha1 – antitrypsin;
  • Transport proteins: albumin, haptoglobin, alpha2 – macroglobulin, ceruloplasmin;
  • Proteins acting in the host, mainly, in process of nutrition: transferin, ferritin, pre-albumin.

Although very attractive from a clinical perspective (a simple blood test to diagnose tuberculosis), serological testing with currently available technology offers neither sufficient sensitivity nor sufficient specificity to allow it to function as a primary, first-line screening test for the detection of active cases of tuberculosis.

Thus, now serological methods do little to enhance the diagnostic yield above the current, very economical standard diagnostic tool, microscopy and conventional MBT detection. But rapid progress of virtuoso molecular biology will bring new effective and cheap, serological tests. If one or more of the above tests were employed and interpreted in a manner that maximized their sensitivity, “clearly negative” results might effectively “rule out” tuberculosis in given patients. This could prove to be of considerable clinical and public health utility.

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