Mycobacterium tuberculosis - Tuberculosis

Indications for Testing

Risk of Latent Infection

Individuals who are at increased risk for TB infection should undergo laboratory testing. Those with elevated risk include people who have spent time with someone who has TB disease, people from a country where TB is common, healthcare workers who care for high-risk patients, and people who work in high-risk settings such as correctional facilities or long-term care facilities.  Many institutions require LTBI testing before employment or enrollment.

Suspected Active Tuberculosis

Individuals with clinical suspicion for TB disease should receive diagnostic testing. Pulmonary TB should be suspected in persons who experience coughing for longer than 3 weeks, hemoptysis, or chest pain. Other symptoms of TB disease include unexplained weight loss, loss of appetite, night sweats, fever, or fatigue. 

Laboratory Testing

Tests for Latent Infection

LTBI tests investigate the presence of MTB bacterium in an individual by measuring immune response. Two main types of tests are used to determine the presence of LTBI: skin and blood tests. Screening tests cannot differentiate between LTBI and TB disease and should not be used in patients with active disease symptoms. Generally, screening tests should not be used for testing persons with a low risk of LTBI or TB disease.  A tuberculin skin test (TST) or an interferon-gamma release assay (IGRA) can be used interchangeably for persons with moderate to high risk of infection, although clinical evaluation may help determine that one test is better suited for a specific situation. 

Mantoux Tuberculin Skin Test

A TST is performed by injecting tuberculin into the lower arm. The reaction should be evaluated at a second appointment 2-3 days after the initial injection. A positive result indicates the presence of MTB. A negative result indicates that TB infection is unlikely.  The TST is the preferred test for children 5 years or younger who are at high risk for infection and disease progression.  A TST is not recommended for persons who have been vaccinated for TB with bacille Calmette-Guérin (BCG) because of an increased risk of false-positive results. Persons who have had a severe reaction to a TST previously should instead undergo IGRA testing in future evaluations.

Interferon-Gamma Release Assay Blood Test

IGRAs measure the immune response to MTB. IGRA testing is preferred in individuals who may have difficulty returning for a follow-up appointment and in those who have received BCG as a vaccine or for cancer therapy.  IGRA testing is relatively fast and does not require a follow-up appointment to determine results. However, IGRAs should not be used for children 5 years or younger.

Tests for Active Tuberculosis

A definitive diagnosis of active TB requires bacteriologic confirmation.  For pulmonary TB, the preferred sample type is freshly expectorated sputum; a volume of 5-10 mL is preferred, but testing can be performed on volumes as low as 3 mL.  If the patient is not spontaneously producing sputum, induced sputum is also acceptable.  The recommended sample type varies for extrapulmonary TB.  For a complete and accurate medical evaluation, samples should be tested with a combination of the tests described below. These tests are generally ordered concurrently.

Acid-Fast Bacilli Smear

For all patients with suspected pulmonary TB, the CDC recommends performing an acid-fast-bacilli (AFB) smear on three different sputum specimens.  A positive AFB smear can indicate TB disease, but does not confirm MTB infection. This is because some nontuberculous mycobacteria (NTM) are also acid fast.  AFB smears are rapid first-line tests, and their results correlate with the likelihood of TB transmission, but accurate species identification requires positive culture or NAAT results. 

Nucleic Acid Amplification Tests

The CDC recommends performing a NAAT on the initial respiratory specimen from patients with suspected pulmonary TB.  NAATs are rapid and highly specific, although they are often less sensitive than culture. A NAAT, unlike an AFB smear, can distinguish MTB from NTM. A positive NAAT result with or without a positive AFB smear is considered sufficient evidence for TB diagnosis. 

NAATs and other molecular tests (such as sequencing) can detect various drug-resistance genes. Molecular tests are recommended for rapid identification of drug resistance and susceptibility. Diagnostic test results and patient history should be taken into account when considering which NAAT is most appropriate. 

Culture

Mycobacterial culture is a recommended test for the diagnosis of TB, and a positive culture is considered confirmatory. The CDC recommends that all specimens be cultured, regardless of AFB smear results.  However, because of the relatively long turnaround time for culture (up to 6-8 weeks), a positive culture is not always necessary to begin or continue treatment.  Once growth is detected, species identification can be performed if necessary.

Once MTB growth is confirmed, drug susceptibility testing should be performed. Culture-based drug susceptibility testing is considered the gold standard to identify drug-resistant TB. At a minimum, susceptibility for isoniazid, rifampin, pyrazinamide, and ethambutol should be evaluated. As in diagnosis, culture is the most sensitive and specific test to elucidate drug resistance and susceptibility, but it is limited by its relatively long turnaround time.  Patients who do not respond adequately to treatment or who continue to have positive culture results after 3 months of therapy should have drug resistance and susceptibility testing repeated. 

Tests for Extrapulmonary Tuberculosis

An AFB smear, culture, and NAAT should be used to evaluate extrapulmonary TB, but the selection of sample type and quantity requires clinical evaluation.