Chest x-ray
Acid-fast stain and culture
Tuberculin skin test (TST) or interferon-gamma release assay (IGRA)
When available, nucleic acid amplification test (NAAT)
Pulmonary tuberculosis is often suspected based on one of the following:
Chest x-rays taken while evaluating respiratory symptoms (cough lasting > 3 weeks, hemoptysis, chest pain, dyspnea), an unexplained illness, fever of unknown origin (FUO), or a positive tuberculin skin test (TST)
IGRA done as a screening test or during contact investigation
Suspicion for TB is higher in patients who have fever, cough lasting > 2 to 3 weeks, night sweats, weight loss, and/or lymphadenopathy and in patients with possible TB exposure (eg, via infectious family members, friends, or other contacts; institutional exposure; or travel to TB-endemic areas).
Initial tests are chest x-ray and sputum examination and culture. If the diagnosis of active TB is still unclear after chest imaging and sputum examination, TST or IGRA may be done, but these are tests for infection not active disease. NAATs (eg, polymerase chain reaction [PCR]–based) are rapid and can be diagnostic.
Like most clinical tests, positive TB test results are statistically more likely to be false positives when the prior probability of TB infection is low (see also Understanding Medical Tests and Test Results).
Once TB is diagnosed, patients should be tested for HIV infection, and those with risk factors for hepatitis B or hepatitis C should be tested for those viruses. Baseline tests (eg, complete blood count, basic blood chemistry including hepatic and renal function) should be done.
Acid-fast staining, microscopic analysis, and mycobacterial culture of fluid and tissue samples, and, when available, nucleic acid amplification testing (NAAT)
Chest x-ray
Tuberculin skin test (TST) or interferon-gamma release assay (IGRA)
Testing is similar to that for pulmonary TB (see Diagnosis of TB), including chest x-ray, TST or IGRA, and microscopic analysis (with appropriate staining) and mycobacterial cultures of affected body fluids (cerebrospinal fluid, urine, or pleural, pericardial, or joint fluid) and tissue for mycobacteria. Blood culture results are positive in about 50% of patients with disseminated TB; such patients are often immunocompromised, often by HIV infection. However, cultures and smears of body fluids and tissues are often negative because few organisms are present; in such cases, NAATs may be helpful.
NAATs can be done on fresh fluid or biopsy samples and on fixed tissue (eg, if TB was not suspected during a surgical procedure and cultures were not done). NAATs typically are not approved for extrapulmonary TB diagnosis but are commonly used in hopes of an early diagnosis for medical care and public health reasons, pending culture. Although a positive NAAT result almost always supports a TB diagnosis, a negative result does not rule out TB in most cases because the negative predictive value is generally unknown and may depend on specimen processing and other factors that are not standardized.
Typically, lymphocytosis is present in body fluids. A very suggestive finding in the cerebrospinal fluid is a glucose level < 50% of that in serum and an elevated protein level.
If all tests are negative and miliary TB is still a concern, biopsies of the bone marrow and the liver are done. If TB is highly suspected based on other features (eg, granuloma seen on biopsy, positive TST or IGRA result plus unexplained lymphocytosis in pleural fluid or cerebrospinal fluid), treatment should usually proceed despite inability to demonstrate TB organisms.
Chest x-ray and other imaging can also provide helpful diagnostic information. Chest x-ray may show signs of primary or active TB; in miliary TB, it shows thousands of 2- to 3-mm interstitial nodules evenly distributed through both lungs.