TUBERCULOSIS: Overview of Tests

Screening tests
Testing for M. tuberculosis may begin with a TB screening test. This is not used as a general screen but is targeted at those who are at a high risk for contracting the disease and at those who work or live with high-risk people. The TB screening test may also be done as part of a physical examination prior to starting school or a new job.
The TB skin test is performed on the patient's skin by injecting a purified protein derivative (PPD) solution just under the skin. This provokes a hypersensitivity skin reaction (a red raised bump) in those who may have been infected by M. tuberculosis. The reaction is evaluated by a health care worker at 48 or 72 hours. Positive results may indicate a latent TB infection and should be followed by other tests, such as chest X-rays, to look for signs of active disease. False-positive results may be seen in people who have had a BCG (Bacille Calmette-Guérin) vaccination while false-negative results may be seen in those with weakened immune systems. This method of screening also requires a second visit for the results to be evaluated.

The interferon gamma release assays (IGRAs) are relatively new blood tests that can be used as an alternative or follow up to the TB skin test to help diagnose a latent TB infection. It is not affected by previous IGRA, TB skin tests, or by BCG vaccination. It does not require the patient to return in 48 to 72 hours for evaluation, and there is no local skin reaction. However, these tests have special handling and transport time restrictions. There are limited data on its use with children and those with suppressed immune systems. A positive IGRA must be followed up in a similar fashion to a positive TB skin test in order to determine if an active infection is present.

Active Tuberculosis
AFB Smear and Culture
To diagnose TB of the respiratory tract, 3 to 5 sputum specimens are collected first thing in the morning on different days when they are most likely to contain the most mycobacteria. If extrapulmonary TB is suspected, samples are collected based upon where in the body the infection is likely to be. Multiple samples of gastric (stomach) washings/aspirates or urine may be collected and submitted to the laboratory. Sometimes cerebrospinal fluid (CSF), biopsied tissue, or other body fluids are also collected.
A presumptive diagnosis of TB can be made by examining a smear of the patient's specimen under the microscope after it has been treated with a special stain to detect acid fast bacteria (AFB). Positive AFB smears are likely to indicate a TB infection since M. tuberculosis is the most common acid-fast bacillus in the lungs, but the smears cannot distinguish between the different species of "acid-fast" bacilli. A culture is required for a definitive diagnosis.
AFB cultures are performed on respiratory samples or other body fluid samples. Specialized nutrient media and prolonged incubation provide a supportive environment for the slow-growing mycobacteria. The results of cultures are definitive, but they take time - days to several weeks for positive samples. Cultures are held for six to eight weeks before being reported as negative. Once M. tuberculosis has been identified and treatment has begun, AFB smears and cultures are used to monitor the effectiveness of treatment.
TB molecular tests (nucleic acid amplification test, NAAT) detect the genetic material of M. tuberculosis. They are useful because they can generally provide results in about 24 hours as opposed to the several weeks required for culture. The 2009 guidelines from the Center for Disease Control and Prevention (CDC) recommend that a TB NAAT be performed on at least one sample from someone with signs and symptoms of TB. The results are evaluated in conjunction with results of an AFB smear. Like AFB smears, both positive and negative results must be confirmed with AFB cultures. However, if both AFB smear and molecular test are positive, the doctor will begin treatment of the affected person before results of the culture are available.

Susceptibility testing is done to determine if the strain causing the infection has developed resistance to the drugs used most often to treat the infection. Testing can be performed on media containing the antibiotic used to treat TB, which can take several weeks for the result, or testing can be done in a broth culture and results can be available in 7 days. There are molecular tests available that can also be used to detect specific genes in the DNA of the bacteria that confer resistance to certain drugs. However, these tests are currently only available in areas outside of the United States.

A liquid culture method called Microscopic-Observation Drug-Susceptibility (MODS) assay has been developed. This method takes only about 7 days to diagnose TB and detects bacterial resistance to antibiotics. It can recognize the presence of mycobacteria much more quickly than traditional culture and can help health care providers diagnose and treat the disease at an earlier stage. It has the potential to help control the spread of infectious TB in resource-limited countries. The benefits and limitations of this test are being evaluated.

A rapid, automated molecular test that detects the genetic material of TB has been developed to help diagnose infections. Within two hours, the test can detect the presence of TB and determine if it is resistant to one of the most commonly prescribed drugs used to treat the infection, rifampin. In 2010, the World Health Organization endorsed use of the test, but it is not currently sold in the US as it has not yet been approved by the US Food and Drug Administration (FDA).

Non-Laboratory Tests
X-rays are often used as a follow-up to positive TB skin tests to look for signs of mycobacteria growth and to help determine whether someone has active tuberculosis or a latent TB infection. Infection with TB can cause a number of characteristic findings on x-rays, including cavities (holes) and calcification in organs such as the lungs and kidneys. More information on radiological tests can be found at RadiologyInfo.
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