Key points
- CDC recommends testing people who are at increased risk for TB infection.
- People with symptoms of TB disease or positive TB blood test or TB skin results should be evaluated for TB disease.
- TB testing activities should be accompanied by a plan for medical evaluation and treatment.
Considerations
Targeted testing
Targeted testing for tuberculosis (TB) is a strategy to diagnose and treat latent TB infection among persons who are at risk for developing TB disease. Treating latent TB infection supports U.S. TB elimination goals through preventing TB disease, stopping the spread of TB to others.
Think TB
TB is not as common in the United States as it was many years ago and health care providers may not always 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.
It is important for health care providers to "Think TB," especially for patients with risk factors.
Determining an approach
Targeted testing
CDC and the U.S. Preventive Services Task Force (USPSTF) recommend testing people who are at increased risk for TB infection. Testing for TB infection is a routine and integral part of health care for patients with increased risk for TB.
People who are at low risk generally should not be tested because the predictive value of a positive result is lower. Testing people at low risk increases the number of false positive test results and can divert resources away from preventing TB among those most likely to develop it. False positive results cause people to undergo unnecessary evaluation and treatment.
TB testing activities should generally be targeted towards groups or people at risk. Certain individuals may be required to have testing for employment or school attendance independent of risk. CDC discourages a testing approach that is independent of a risk assessment.
Frequency of testing depends on a person's risk factors. This could range from one-time only testing among persons at low risk for future TB exposure to annual testing among those at continued risk of exposure.
TB testing activities should be done only when there is a plan for follow-up care to evaluate and treat all individuals diagnosed with latent TB infection or TB disease. Contact your state or local TB program for more information.
Risk factors for TB
People at risk for TB fall into two broad categories:
- People who are at high risk of exposure to or infection with TB bacteria
- People who are at high risk of TB disease developing once infected with TB bacteria
People at high risk of exposure to or infection with TB bacteria
- Contacts of people known or presumed to have infectious TB disease
- People who were born in or who frequently travel to countries where TB disease is common
- People who currently live or used to live in large group settings where TB is more common, such as homeless shelters, correctional facilities, or nursing homes
- Employees of high-risk congregate settings
- Health care workers who serve patients with TB disease
- Populations defined locally as having an increased incidence of latent TB infection or TB disease, possibly including medically underserved populations, low-income populations, or persons with alcohol use or substance use disorders
- Infants, children, and adolescents exposed to adults who are at increased risk for latent TB infection or TB disease
People who are at high risk of developing TB disease once infected with TB bacteria
- People with HIV
- Children younger than 5 years of age
- People recently infected with TB bacteria (within the last 2 years)
- People with a history of untreated or inadequately treated TB disease
- People who are receiving immunosuppressive therapy such as tumor necrosis factor-alpha (TNF) antagonists, systemic corticosteroids equivalent to/greater than 15 mg of prednisone per day, or immunosuppressive drug therapy following organ transplantation
- People with silicosis; chronic renal failure; leukemia; or cancer of the head, neck, or lung
- People with diabetes mellitus
- People who have had a gastrectomy or jejunoileal bypass
- People with low body weight (<90% of ideal body weight)
- People who use substances (such as injection drug use)
- Populations defined locally as having an increased incidence of TB disease, including medically underserved and low-income populations
Recommended tests
There are two tests that are used to determine if a person has been infected with TB bacteria: TB blood tests (Interferon Gamma Release Assay [IGRA]) and the TB skin test (Mantoux tuberculin skin test).
TB blood tests or skin tests should not be performed on people who have written documentation of a previous positive TB test results (TB blood test or TB skin test) or treatment for TB disease. Most people who have a positive TB test result will continue to have a positive test result. Additional TB blood tests or skin tests will probably not contribute to medical care, regardless of the result.
TB blood tests (sometimes called IGRAs) measure the immune response in whole blood after it has been mixed with controls and with synthetic peptides that are designed to simulate TB antigens. The white blood cells in most people who have TB infection are sensitive to the test antigens and release interferon-gamma (IFN-γ). The tests measure the amount of the IFN-γ response.
The U.S. Food and Drug Administration (FDA) has approved these two TB blood tests that are commercially available in the United States:
- QuantiFERON®-TB Gold Plus (QFT-Plus)
- T-SPOT®.TB test (T-Spot)
Only one visit is required to draw blood for the test. TB blood tests are the preferred method of TB testing for people 5 years of age and older who have received the bacille Calmette-Guérin (BCG) vaccine.
The TB skin test is also called the Mantoux tuberculin skin test (TST) or PPD. With a TB skin test, a health care provider injects a small, premeasured amount of sterile tuberculin PPD solution into the skin on the palm side of the forearm. This is sometimes called the Mantoux TST method. PPD stands for purified protein derivative of tuberculin solution, which comes in a single standard concentration. It is the only kind of TB skin test solution that is FDA-approved for this test method.
After 48–72 hours, the skin test reaction must be examined by a trained health care worker. The health care worker measures any swelling where the tuberculin was injected to determine if the reaction to the test is positive or negative.
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, while noting that some experts use TB blood tests in younger children. Health care providers may choose to consult the American Academy of Pediatrics (AAP) guidance1 on the use of TB blood tests in children.
Interpreting test results
Interpreting TB blood test results
Interpretation of TB blood test results depends on the test being used.
- QFT-Plus results are based on the amount of IFN-γ that is released in response to the antigens and to the control substances after the blood has been incubated these substances.
- T-Spot results are based on comparing the number of IFN-γ producing cells (spots) produced after the blood has been incubated with these substances.
Laboratories should provide both the qualitative and quantitative results.
- For qualitative results
- QFT-Plus results are reported as positive, negative, or indeterminate.
- T-Spot results are reported as positive, borderline, negative, or invalid.
- QFT-Plus results are reported as positive, negative, or indeterminate.
- Quantitative results are reported as numerical values that include responses to the TB antigen and two controls, nil and mitogen.
- Specific guidance is not available for interpreting quantitative IGRA results.
- These results may be helpful for understanding qualitative results in individual cases, in combination with risk factors.
- Specific guidance is not available for interpreting quantitative IGRA results.
Interpreting TB skin test results
Interpretation of TB skin test reactions depends on the measurement of induration (firm swelling) in millimeters (mm) across the arm, the person’s risk of acquiring TB infection, and the risk of progression to disease if infected. For more details on interpreting TB skin test results, please visit Clinical Testing Guidance for Tuberculosis: Tuberculin Skin Test.
TB skin results should only be read by a trained health care professional. Consult with your state and local public health authorities to determine who is authorized to place and read TB skin tests in your state.
What a positive result means
A positive result from a TB blood test or TB skin test 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 result from a TB blood test or TB skin test. Results from these tests cannot be used as the only information for excluding or confirming TB disease. If a patient has symptoms of TB disease, health care providers should not wait for the result from a TB blood test or TB skin test before starting other diagnostic tests.
Diagnosis
All persons with signs or symptoms of TB disease, a positive result from a TB blood test (interferon-gamma release assay [IGRA]), or a positive result from a tuberculin skin test (TST) should be medically evaluated for TB disease.
A diagnosis of latent TB infection is made if a person has a positive TB blood test or TB skin test result, and a medical evaluation does not indicate TB disease.
A complete medical evaluation for TB disease has five components:
- Medical history
- Physical examination
- Test for TB infection (TB blood test or TB skin test)
- Chest radiograph
- Bacteriologic examination (sputum smear microscopy, nucleic acid amplification testing, culture, and drug susceptibility testing)
Culture is the gold standard microbiologic test for the diagnosis of TB disease.
Next steps
Several treatment regimens for patients with latent TB infection or TB disease are available. Health care providers can choose the appropriate 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.
For patients who need an alternative regimen because drug resistance is suspected or because of drug allergies or drug-drug interactions, consultation with a TB expert is recommended.
Reporting cases
Latent TB infection
Latent TB infection is reportable in some states and localities. 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.
A 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.
CDC publishes an annual surveillance report that summarizes incident cases of TB in the United States.
Resources
Core Curriculum on Tuberculosis: What the Clinician Should Know
- 2024. "Tuberculosis", Red Book: 2024–2027 Report of the Committee on Infectious Diseases, Committee on Infectious Diseases, American Academy of Pediatrics, David W. Kimberlin, MD, FAAP, Ritu Banerjee, MD, PhD, FAAP, Elizabeth D. Barnett, MD, FAAP, Ruth Lynfield, MD, FAAP, Mark H. Sawyer, MD, FAAP. Available from: https://publications.aap.org/redbook/book/755/chapter/14083107/Tuberculosis