European researchers develop test to pinpoint TB
A group of European researchers have developed a test that can diagnose active tuberculosis (TB) in people even when traditional tests have failed. The findings are published in the American Journal of Respiratory and Critical Care Medicine.
The research team, the Tuberculosis Network European Trialsgroup (TBNET), a scientific consortium founded in 2006 to research new methods of TB diagnosis, used the ELISPOT (enzyme-linked immunospot assay) test to develop the new method. They found that immune cells that are specific to TB bacilli are concentrated in the airways of patients who have active tuberculosis. These cells can be identified quickly using the ELISPOT test. The test can distinguish between latent TB infection, known as �lasting tuberculosis immune responses� (LTBI), and active TB by comparing the frequencies of TB-specific lymphocytes in the blood with those in the lung.
About a third of the world's population is infected with the mycobacterium that causes TB but only about 10% to 20% of those will go on to develop the disease. The others have LTBI which can develop into TB at any time.
Sputum testing has traditionally been used for TB diagnosis: when TB bacilli show up on sputum tests, a positive diagnosis of TB can be established quickly. Unfortunately, in about 50% of these tests the TB bacilli cannot be identified so a more accurate method is needed.
Dr Christoph Lange from the Research Center Borstel Leibniz-Center for Medicine and Biosciences in Germany, who led the TBNET research, said: �In this study we showed that a differentiation between active pulmonary tuberculosis and LTBI is possible by using the ELISPOT test.�
TB spreads quickly because it is disseminated through the air when infected people sneeze, spit or talk. It is the seventh leading cause of death worldwide and its incidence is rising again after a period of decline from the 1960s when the successful use of the Bacille Calmette-Guérin (BCG) vaccine led to a decline in the disease. TB usually attacks the lungs but other parts of the body can be affected too including the spine and the circulatory system.
To test the ELISPOT method, the TBNET researchers recruited 347 patients who were believed to have TB, but were either unable to produce sputum or had had 3 negative sputum tests. The ELISPOT test was performed using bronchoaveolar lavage (BAL, a method in which fluid is squirted into the lung and then withdrawn for analysis).
Of the 347 patients, 71 were diagnosed with active pulmonary TB and the results for patients with active TB were accurate in 91.5% of cases.
'These findings show us that positive results in the BAL ELISPOT were highly indicative of actual cases of active TB,' Dr Lange said. 'A negative BAL ELISPOT result almost excludes active tuberculosis.
'Future research about the immunodiagnosis of tuberculosis will need to identify indicators of treatment success that will allow safe discontinuation of anti-tuberculosis therapy without an increased risk of the reactivation,' he pointed out. 'This will be of great clinical importance to guide the treatment of individuals with LTBI and active tuberculosis, especially in cases of drug-resistant strains of mycobacterium tuberculosis.'
Dr Lange also pointed out that in 2008 a 27-institution consortium was established in Europe for the study of drug resistant tuberculosis (<http://www.tbpannet.eu/>) and was granted EUR 12 million by the EU. The result is the TB PAN-NET (�Pan-European network for the study and clinical management of drug resistant tuberculosis�) project, supported by the �Health� Thematic area of the EU�s Seventh Framework Programme (FP7).
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Document Reference: Jafari, C et al. (2009) Bronchoalveolar lavage enzyme-linked immunospot for a rapid diagnosis of tuberculosis. American Journal of Respiratory and Critical Care Medicine (in press, published online 9 July). DOI: 10.1164/rccm.200904-0557OC
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