Tuberculosis diagnostic tools
Tuberculosis, caused by the bacterium Mycobacterium tuberculosis, kills over 2 million people each year. It is estimated that approximately one-third of the world population is infected with M. tuberculosis, though the majority will never develop active disease. Almost 1 in 20 cases of tuberculosis worldwide is resistant to multiple drugs (known as multidrug-resistant TB or MDR-TB).
Tuberculosis can be a difficult disease to diagnose, mainly due to the difficulty in culturing this slow-growing organism in the laboratory. It takes 4–12 weeks for a laboratory culture to be clearly positive. While microscopy and culture are still the major backbone for laboratory diagnosis of tuberculosis, rapid diagnosis still relies on a medical evaluation including a medical history, a chest X-ray and a physical examination, and may also include a tuberculin skin test or serological tests. These methods are used in rich countries but are probably not available in much of the developing world where the majority of tuberculosis carriers live.
New TB tests are being developed that offer the hope of offering cheaper, faster and more accurate TB testing. The majority of new molecular tests use polymerase chain reaction (PCR)-based detection of nucleic acids, including both DNA and RNA, which are specific to M. tuberculosis, or mutations in mycobacterial genes which are associated with resistance to anti-tuberculosis drugs such as isoniazid and rifampicin. Other new diagnostic tests use PCR or antibody assays to detect the release of interferon-gamma in response to mycobacterial infection. Recently, microarray techniques have been employed extensively for the detection of drug resistance-related mutations.
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While genetic assays are useful for rapid detection of drug resistance compared to the time taken by culture-based methods, not all drug-resistant isolates have mutations in the “hot spots” of genes commonly associated with drug resistance. Another drawback of some tests is their inability to detect minor populations of drug-resistant organisms in cultures from clinical samples. In defining drug resistance, the presence of 1–10% of drug-resistant organisms in culture can make it functionally drug resistant. However, routine nucleic acid hybridization assays require about 15–20% of a drug-resistant strain in a culture to qualify as a mutant isolate.
Interferon-gamma tests have been quite successful in detecting latent TB infection in areas with concurrent vaccination programs, since these tests do not get “confused” by the presence of an immunogen. Currently, two types of test for the detection of interferon-gamma production by T lymphocytes are available, ELISA and ELISPOT. These tests seem to reflect the degree of exposure to M. tuberculosis in household contacts of TB patients and occupational contact in TB hospitals. The major obstacles in implementing interferon-gamma tests include their high costs, requirement of highly trained personnel and fresh blood samples, all formidable obstacles in most areas with high TB prevalance.
Mycobacterium tuberculosis has no significant animal or environmental reservoirs and shows limited genetic diversity. In spite of this, TB continues to be a widespread and devastating disease. The need for new faster-acting diagnostic tests and better drugs is clear.
Tuberculosis: diagnostics. Tuberculosis (Edinb). 2007 87 Suppl 1: S14-7 doi:10.1016/j.tube.2007.05.001
Related:
- Tuberculosis – is the white plague winning?
- How can we overcome the barriers to treating drug-resistant TB?
- The Influence of Host and Bacterial Genotype on the Development of Tuberculosis
Tags: Antibiotics, Bacteria, Biology, Health, Medicine, Microbiology, Podcast, Science, Tuberculosis
Thank you for an interesting article. For the past three years, I have been researching and writing a narrative nonfiction book about life at a tuberculosis sanatorium in Minnesota where I lived on the san’s dairy farm as a child. When I tell people that it is estimated that one-third to one-half of the world’s population is infected with M. tuberculosis, they find it unbelievable. That’s when I show them articles like yours.
Pat Nelson