Key points
- All persons with signs or symptoms of TB disease, or a positive result from a TB blood test or skin test should be medically evaluated for TB disease.
- Latent TB infection is diagnosed if the person has a positive result from a TB blood test or skin test and a medical evaluation does not indicate TB disease.
- TB disease is diagnosed by medical history, physical examination, chest x-ray, and other laboratory tests, including culture.
Considerations
All persons with signs or symptoms of TB disease or a positive result from a TB blood test (interferon-gamma release assay [IGRA]) or tuberculin skin test (TST [TB skin test]) should be medically evaluated for TB disease.
Latent TB infection
Testing for TB infection should be a routine and integral part of health care for patients with increased risk for TB. Diagnosing and treating people with latent TB infection prevents the development of TB disease. Preventing TB disease can stop the spread of TB to others. However, before initiating treatment for latent TB infection, TB disease must be excluded.
TB disease
TB disease was the leading cause of death for many groups and regions in the United States at the beginning of the 20th century, bur is not as common in the United States now. Some health care providers have never met someone who has TB disease and might not consider the possibility of TB disease when evaluating patients who have symptoms. As a result, the diagnosis of TB disease may be delayed or even overlooked, and the patient may remain ill and possibly infectious for a prolonged period.
Most people with TB disease have one or more symptoms that lead them to seek medical care, but occasionally, TB disease is discovered during a medical examination for an unrelated condition. Usually, when patients have symptoms, the symptoms have developed gradually, and have been present for weeks or even months.
Diagnosis
A complete medical evaluation for TB disease has five components:
- Medical history
- Physical examination
- TB blood tests or TB skin test
- Chest radiograph
- Bacteriologic examination (sputum smear microscopy, nucleic acid amplification testing, culture, and drug susceptibility testing)
When conducting a medical history, the health care provider should ask about the following:
- If any symptoms of TB disease are present, and if so, for how long,
- If there is a known exposure to a person with TB disease,
- Whether or not the person has been diagnosed with and/or treated for latent TB infection or TB disease in the past,
- If the person has risk factors for exposure to TB bacteria, and
- If the person has underlying medical conditions, especially HIV, other immunocompromising conditions, or diabetes that can increase the risk for progression from latent TB infection to TB disease.
A physical examination cannot be used to confirm or rule out TB disease. However, it is an essential part of any evaluation and can:
- Provide valuable information about the patient's overall condition,
- Inform the method of diagnosis, and
- Reveal factors that may affect treatment if the patient is diagnosed with TB disease.
Some signs of extrapulmonary TB disease (for example, redness and swelling over the infected lymph nodes of scrofula) may be observed during a physical examination.
There are two tests that are used to determine if a person has been infected with TB bacteria:
- TB blood test (Interferon Gamma Release Assay [IGRA])
- TB skin test (Mantoux tuberculin skin test [TST])
Selecting a test
Health care providers may consider the reasons and context for testing, test availability, and the overall cost effectiveness of testing when selecting a suitable test for TB infection.
- Health care providers are encouraged to use TB blood tests to detect TB infection. TB blood tests are preferred for:
- People who have received the BCG vaccine and
- People who might be less likely to return for TB skin test reading and interpretation.
- People who have received the BCG vaccine and
- TB skin tests are an acceptable alternative in situations where a TB blood test is not available, is too costly, or is too burdensome.
- Current CDC guidelines recommend the TB skin test as the method of testing for children younger than 5 years of age.
Interpreting test results
A positive TB blood test result or TB skin test result usually means TB infection. More tests, such as a chest radiograph, are needed to rule out TB disease.
Some people with TB disease may have a negative TB blood test or TB skin test result. If a patient has signs or symptoms of TB disease, health care providers should not wait for TB blood test or TB skin test results before starting other diagnostic tests.
Chest radiographs (x-rays) help differentiate between latent TB infection and pulmonary TB disease in people with positive results from a TB blood test or TB skin test.
A posterior-anterior chest radiograph is used to detect chest abnormalities. Lesions may appear anywhere in the lungs and may differ in size, shape, density, and cavities. These abnormalities may suggest TB disease but cannot be used to definitively diagnose TB disease.
Normal findings on chest radiography generally can be used to rule out pulmonary TB in a person who has had a positive reaction to a TB blood test or TB skin test and no symptoms of disease. Rare exceptions have been noted in HIV-infected patients whose immune status has not been restored by anti-viral treatment.
Examinations of clinical specimens (e.g., sputum, urine, or cerebrospinal fluid) are of critical diagnostic importance. The specimens should be examined and cultured in a laboratory that specializes in testing for M. tuberculosis. Contact your state TB program for information about public health laboratory services for your area.
Treatment generally should not be delayed while waiting for bacteriologic results if TB disease is the presumptive diagnosis. Treatment can be started as soon as specimens have been collected or even while specimens are being collected if a patient is very ill. Consultation with a TB expert is recommended for deciding when to start treatment in relation to specimen collection.
Optimal bacteriologic examination has five parts:
- Specimen collection, transport, and processing
- Acid-fast bacilli (AFB) smear classification
- Direct detection of M. tuberculosis in clinical specimens using nucleic acid amplification (NAA) and, as applicable, molecular detection of resistance
- Specimen culture and identification of M. tuberculosis
- Drug susceptibility testing using growth-based and molecular methods
Specimen collection, transport, and processing
Patients presumed to have pulmonary TB disease may cough up sputum (phlegm) into a sterile container for processing and examination.
- Patients should have at least three consecutive sputum specimens examined, each collected in 8 to 24-hour intervals (at least one collected early in the morning).
- Specimens should be collected in an airborne infection isolation (AII) room, a sputum collection booth, or another isolated, well-ventilated area.
Other sputum specimen collection methods include inducing sputum, bronchoscopy, and gastric washing. Health care providers should use precautions to control the spread of TB bacteria during sputum collection procedures.
In patients who have presumed extrapulmonary TB disease, the way specimens are obtained depends on the part of the body affected.
AFB smear classification
Specimens are smeared onto a glass slide and stained so that they can be examined for acid-fast bacilli (AFB) under a microscope. M. tuberculosis complex organisms are one kind of AFB. Smear examination is a quick procedure, and results should be available within 24 hours of specimen collection.
When AFB are seen in a smear, they are counted and classified as 4+, 3+, 2+ or 1+, according to the number of AFB seen. The greater the number, the more infectious the patient.
Negative smears do not exclude TB disease. The AFB in a smear may be organisms other than M. tuberculosis.
Direct detetion of M. tuberculosis in clinical specimens using nucleic acid amplication (NAA) and, as applicable, molecular detection of resistance
Nucleic acid amplification (NAA) tests are used to amplify DNA and RNA segments to rapidly detect M. tuberculosis DNA in specimens in just hours, compared to a week or more for detection of TB bacteria in culture. CDC recommends that NAA testing be performed on at least one respiratory specimen from each patient with symptoms of pulmonary TB disease for whom:
- A diagnosis of TB disease is being considered but has not yet been established, and
- The test result would alter case management or TB control activities (such as contact investigations)
The Xpert MTB/RIF assay is an NAA test that simultaneously detects and identifies M. tuberculosis complex detects genetic mutations that can predict resistance to rifampin (RIF), one of the most effective drugs used to treat TB. A sputum sample is mixed with a sterilizing reagent provided with the assay, and a cartridge containing the mixture is placed in the GeneXpert machine.
NAA test and Xpert MTB/RIF assay results can help guide health care provider's decisions for patient therapy and isolation; however, they do not replace the need for AFB smear, culture, growth-based drug susceptibility testing, and genotyping. Health care providers and laboratories should ensure patient specimens are available for all recommended mycobacterial testing.
Specimen culture and identification
Culturing the specimen means growing the mycobacteria on solid or in liquid media. All specimens should be cultured, regardless of whether the smear is positive or negative. Culture is the gold standard for laboratory confirmation of TB disease.
- A positive culture for M. tuberculosis confirms the diagnosis of TB disease.
- A negative culture does not necessarily rule out TB disease. Some patients with negative cultures are diagnosed with TB disease based on their clinical presentation.
Specimen culture is important for TB genotyping, a laboratory-based approach used to analyze the genetic material (e.g., DNA) of M. tuberculosis. TB genotyping results, when combined with epidemiologic data, help identify persons with TB disease involved in the same chain of recent transmission.
Drug susceptibility testing
Drug susceptibility tests should be done when a patient is first found to have a positive culture for M. tuberculosis. These tests will determine which drugs will be effective in a combination regimen for treating TB disease.
Molecular Detection of Drug Resistance (MDDR) assays allow rapid detection of drug resistance through the detection of genetic mutations associated with resistance. Respiratory specimens from patients with risk factors for drug-resistant TB disease, AFB smear positive results or NAA test positive results should be sent for molecular drug resistance testing immediately.
CDC's MDDR service is available nationally and free of charge through state public health laboratories.
Growth-based drug susceptibility testing can be done using a liquid medium or a solid medium method. Liquid medium methods are faster than solid media methods for determining susceptibility to first-line TB medications.
The results of both growth-based and molecular drug susceptibility test should inform health care providers' choices of the appropriate drugs for treating each patient.
Next steps
HIV testing
Inform TB patients (e.g., through a patient brochure, practice literature/form, or discussion) that an HIV test will be included in the standard tests and that they may decline the test (opt-out screening). A patient’s decision to decline testing should be noted in their medical record. Know your state's HIV testing laws.
Treatment
Several treatment regimens for patients with latent TB infection or TB disease are available. Health care providers can choose a regimen based on:
- Drug-susceptibility results (for patients with TB disease) or drug-susceptibility results of the presumed source patient, if known (for patients with latent TB infection),
- Coexisting medical conditions (e.g., HIV, diabetes), and
- Potential for drug-drug interactions.
TB disease treatment regimens for patients with special considerations (including pregnant people, breastfeeding people, infants and children, people with HIV, and drug-resistant TB disease) require special management and should be administered in consultation with a TB expert. In some circumstances, the organ site of TB disease is also a factor in the treatment regimen and duration of treatment.
Reporting cases
Latent TB infection
Some states and localities have developed legal reporting requirements for latent TB infection as a tool to prevent TB disease. For information on reporting requirements in your jurisdiction, consult your state TB program.
TB disease
TB is a nationally notifiable disease, and reporting is mandated in all states. Health care providers should comply with state and local laws and regulations requiring the reporting of TB disease.
All persons with clinically active or presumed TB disease should be reported promptly to the local or state health department.
For public health, case of TB disease is defined as an episode of TB disease in a person meeting the laboratory or clinical criteria for TB as defined by the Tuberculosis Case Definition for Public Health Surveillance.
The medical criteria for diagnosing TB disease might be different from the surveillance criteria in some instances. Contact your state TB program for more information.
CDC publishes an annual surveillance report that summarizes incident cases of TB in the United States.