Newer diagnostic modalities for tuberculosis.

Abstract

The gold standard for diagnosis of tuberculosis is demonstration of mycobacteria from various body fluids. This is often not possible in children due to pauci-bacillary nature of illness. Significant improvement in understanding of molecular biology of Mycobacterium tuberculosis has led to development of newer diagnostic techniques of tuberculosis. Polymerase chain reaction (PCR) is an emerging diagnostic tool for diagnosis of TB in children. However, its role in day-to-day clinical practice needs to be defined. A negative PCR never eliminates possibility of tuberculosis, and a positive result is not always confirmatory. The PCR may be useful in evaluating children with significant pulmonary disease when diagnosis is not readily established by other means, and in evaluating immunocompromised children (HIV infection) with pulmonary disease. In the absence of good diagnostic methods for tuberculosis, a lot of interest has been generated in serodiagnosis. ELISA has been used to detect antibodies to various purified or complex antigens of M. tuberculosis in children. Despite a large number of studies published over the past several years, serology has found little place in the routine diagnosis of tuberculosis in children, even though it is rapid and does not require specimen from the site of disease. Sensitivity and specificity depend on the antigen used, gold standard for the diagnosis of tuberculosis and the type of tubercular infection. Though most of these tests have high specificity, their sensitivity is poor. In addition, these tests may be influenced by factors such as age, prior BCG vaccination and exposure to environmental mycobacteria. The serological tests, theoretically, may not be able to differentiate between infection and disease. At present, serodiagnosis does not appear to have any role in diagnosis of childhood pulmonary tuberculosis. A new test (QuantiFERON-TB or QFT) that measures the release of interferon-gamma in whole blood in response to stimulation by purified protein derivative is comparable with the tuberculin skin testing to detect latent tubercular infection, and is less affected by BCG vaccination. It can also discriminate responses due to nontuberculous mycobacteria, and avoids variability and subjectivity associated with placing and reading the tuberculin skin test. Polymerase chain reaction based test for identification of katG and rpoB mutation which are associated with isoniazid and rifampicin resistance may help in early identification of drug resistance in mycobacterium.