Elsevier

The Lancet

Volume 356, Issue 9235, 23 September 2000, Pages 1099-1104
The Lancet

Review
Specific immune-based diagnosis of tuberculosis

https://doi.org/10.1016/S0140-6736(00)02742-2Get rights and content

Summary

Current diagnostic tests for tuberculosis based on tuberculin have poor specificity, and both BCG vaccination and exposure to non-tuberculosis mycobacteria produce a response similar to that induced by infection with Mycobacterium tuberculosis. The identification of regions of the M tuberculosis genome that are not present in BCG and non-tuberculous mycobacteria provides a unique opportunity to develop new highly specific diagnostic reagents. We describe the current status of attempts to exploit this information and summarise recent research that has used defined antigens for an accurate and rapid test for tuberculosis infection based on the detection of T cells sensitised to M tuberculosis either by blood tests in vitro or skin tests in vivo.

Section snippets

Tuberculosis and diagnosis

Fast and accurate diagnosis of tuberculosis is a very important element of global health measures to control the disease. The gold standard in diagnosis remains clinical examination, combined with direct microscopic examination of sputum and culture of bacteria. Culture of M tuberculosis can take up to 8 weeks, and in 10–20% of cases the bacillus is not successfully cultured.5, 6 Diagnosis in these patients should be based on clinical findings and radiographic examination. This process

Current use of tuberculin

The TST measures the induction of cutaneous induration as a result of delayed-type-hypersensitivity reactions after intradermal injection of PPD. PPD is prepared by precipitation of proteins from heat-killed cultures of M tuberculosis, resulting in a mixture of complex antigens that is poorly defined and contains many individual proteins in varying stages of denaturation. The TST, when combined with direct smear examination, allows an immediate diagnosis of TB infection; however, interpretation

Specific antigens of M tuberculosis

The need for antigens specific to M tuberculosis for diagnosis of tuberculosis as well as for epidemiological analyses has been recognised for many years.32, 33 Initial attempts to extract antigens specific to the tuberculosis complex by adsorption with crossreacting antibodies were able to increase specificity somewhat.17 However, this approach did not produce truly specific antigens because of the difficulty in completely removing the large number of potentially cross-reactive antigens and

New initiatives in tuberculosis diagnosis

Sputum microscopy is the only immediate test for diagnosis of tuberculosis. However, the sensitivity of microscopy varies from 22% to 65%64 and in western countries generally only around 40–50% of cases have smear-positive samples.6, 65 Culture on BACTEC or Lowenstein-Jensen media takes 4–8 weeks and increases this proportion to around 80%.5, 6 Nonetheless, this addition still leaves a substantial percentage of cases dependent on clinical findings for diagnosis (a notoriously difficult problem

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