Tuberculosis (TB) remains a global health concern, and effective testing and diagnosis are crucial for controlling its spread. This guide provides a detailed overview of tuberculosis tests and the diagnostic process, aiming to enhance understanding for healthcare professionals and individuals seeking information.
Understanding Targeted TB Testing
Targeted testing is a strategic approach focused on identifying and treating latent TB infection (LTBI) in high-risk individuals. By proactively addressing LTBI, we can prevent the progression to active TB disease and reduce transmission within communities. This strategy is vital in achieving TB elimination goals.
Why “Think TB”?
While TB prevalence is lower in the U.S. compared to past decades, it’s essential for healthcare providers to maintain awareness and “Think TB.” Symptoms of TB disease can be subtle or mimic other conditions, potentially leading to delayed or missed diagnoses. This delay can prolong patient illness and increase the risk of transmission. Therefore, considering TB, especially in patients with risk factors, is paramount for timely diagnosis and intervention.
For general information on testing, refer to Testing for Tuberculosis.
Determining the Right Approach to TB Testing
Targeted Testing Recommendations
The Centers for Disease Control and Prevention (CDC) and the U.S. Preventive Services Task Force (USPSTF) advocate for targeted TB testing for individuals at increased risk of TB infection. Routine TB infection screening is a critical component of healthcare for these populations. Identifying risk factors is the cornerstone of deciding who should be tested.
Conversely, routine testing for low-risk individuals is generally discouraged. In low-risk populations, the likelihood of false-positive results increases, potentially leading to unnecessary evaluations and treatments, and misallocation of healthcare resources.
While certain situations, such as employment or school enrollment, might necessitate TB testing irrespective of risk, the CDC emphasizes risk-based targeted testing as the most effective strategy.
The frequency of TB testing varies depending on individual risk factors, ranging from a single test for low-risk individuals to annual testing for those with ongoing exposure risks.
Crucially, TB testing should always be coupled with a clear plan for follow-up care, ensuring proper evaluation and treatment for individuals diagnosed with either latent TB infection or active TB disease. For specific guidance, consult your state or local TB program.
Identifying TB Risk Factors
TB risk factors are broadly categorized into two groups:
- Increased risk of exposure to TB bacteria
- Increased risk of developing TB disease once infected
Individuals at Higher Risk of TB Exposure
- Close contacts of individuals with known or suspected infectious TB disease.
- People born in or frequent travelers to countries with high TB prevalence (refer to the WHO’s global TB report for a list of high-burden countries).
- Residents or former residents of congregate settings with higher TB risk, such as homeless shelters, correctional facilities, and nursing homes.
- Employees of high-risk congregate facilities.
- Healthcare workers who care for TB patients.
- Locally identified populations with increased latent TB infection or TB disease incidence, potentially including underserved communities, low-income groups, or individuals with substance use disorders.
- Infants, children, and adolescents exposed to adults at increased TB risk.
Individuals at Higher Risk of Developing TB Disease Post-Infection
- People living with HIV.
- Children under 5 years old.
- Individuals recently infected with TB bacteria (within the past two years).
- People with a history of untreated or inadequately treated TB disease.
- Individuals receiving immunosuppressive therapies, such as TNF-alpha antagonists, systemic corticosteroids (≥15 mg prednisone/day), or post-transplant immunosuppressants.
- People with underlying conditions like silicosis, chronic renal failure, leukemia, or head, neck, or lung cancer.
- People with diabetes mellitus.
- Individuals who have undergone gastrectomy or jejunoileal bypass.
- People with low body weight (
Alt text: Close-up of a healthcare provider injecting tuberculin PPD solution for a TB skin test on a patient’s forearm.
Recommended Tuberculosis Tests
Two primary tests are available to detect TB infection:
- TB blood tests (Interferon Gamma Release Assays – IGRAs): Examples include QuantiFERON®-TB Gold Plus (QFT-Plus) and T-SPOT®.TB test (T-Spot).
- TB skin test (Mantoux tuberculin skin test – TST): Also known as the PPD test.
It’s important to note that TB blood tests or skin tests are generally not recommended for individuals with documented prior positive TB test results or previous TB disease treatment. Repeat testing in such cases is unlikely to provide additional clinical value.
TB Blood Tests (IGRAs)
TB blood tests analyze the immune response in whole blood when exposed to TB antigens. In individuals with TB infection, white blood cells typically react to these antigens by releasing interferon-gamma (IFN-γ), which the test measures.
Currently, two FDA-approved IGRAs are available in the U.S.:
- QuantiFERON®-TB Gold Plus (QFT-Plus)
- T-SPOT®.TB test (T-Spot)
A key advantage of TB blood tests is that they require only one patient visit to draw blood. They are also the preferred method for individuals aged 5 and older who have received the Bacille Calmette-Guérin (BCG) vaccine, as BCG vaccination can sometimes cause false-positive skin test results.
For in-depth information, see Clinical Testing Guidance for Tuberculosis: Interferon Gamma Release Assay.
TB Skin Test (Mantoux Tuberculin Skin Test – TST)
The TB skin test, or Mantoux test, involves injecting a standardized amount of tuberculin PPD into the forearm skin. This intradermal injection, known as the Mantoux method, uses purified protein derivative (PPD) of tuberculin solution, the only FDA-approved solution for this test.
A trained healthcare professional must assess the skin reaction 48-72 hours after injection. This involves measuring any induration (swelling) at the injection site to determine a positive or negative result.
TB skin tests remain a viable alternative when TB blood tests are unavailable, cost-prohibitive, or impractical.
Current CDC guidelines recommend the TB skin test as the primary testing method for children under 5. However, it’s worth noting that some experts and the American Academy of Pediatrics (AAP) may recommend or utilize TB blood tests even in this younger age group. Healthcare providers should consult AAP guidance for detailed recommendations on TB testing in children.
Further details are available in Clinical Testing Guidance for Tuberculosis: Tuberculin Skin Test.
Alt text: Healthcare worker carefully measuring the induration of a patient’s TB skin test reaction with a ruler during a follow-up appointment.
Interpreting Tuberculosis Test Results
Understanding TB Blood Test Results
Interpretation of TB blood test results varies based on the specific test used.
- QFT-Plus: Results are based on the quantity of IFN-γ released in response to TB antigens and control substances after blood incubation.
- T-Spot: Results compare the number of IFN-γ producing cells (spots) generated after blood incubation with test substances.
Laboratories should provide both qualitative (positive, negative, indeterminate, etc.) and quantitative results.
- Qualitative Results:
- QFT-Plus: Reported as positive, negative, or indeterminate.
- T-Spot: Reported as positive, borderline, negative, or invalid.
- Quantitative Results: Numerical values reflecting responses to TB antigens and controls (nil and mitogen). While specific interpretive guidelines for quantitative IGRA results are lacking, they can be useful in conjunction with risk factors to clarify qualitative results in individual cases.
Interpreting TB Skin Test Results
TB skin test interpretation depends on measuring induration (firm swelling) in millimeters (mm), considering the individual’s risk of TB infection, and the risk of progression to active disease if infected. Detailed interpretation guidelines are available at Clinical Testing Guidance for Tuberculosis: Tuberculin Skin Test.
Only trained healthcare professionals should interpret TB skin test results. Consult your state and local public health authorities for regulations regarding who is authorized to administer and interpret TB skin tests in your jurisdiction.
Positive TB Test Result: What It Means
A positive TB blood test or skin test typically indicates TB infection (latent or active). Further investigations, such as a chest X-ray, are necessary to rule out active TB disease.
It’s crucial to remember that a negative TB blood test or skin test result does not always exclude active TB disease. These tests should not be the sole basis for excluding or confirming active TB. If a patient presents with TB disease symptoms, prompt initiation of other diagnostic tests is essential, regardless of TB test results.
Diagnosing Tuberculosis
Medical evaluation for TB disease is warranted for individuals exhibiting TB disease signs or symptoms, or those with a positive result from either a TB blood test (IGRA) or a tuberculin skin test (TST).
Latent TB infection (LTBI) is diagnosed when an individual has a positive TB test result, but a medical evaluation rules out active TB disease.
A comprehensive medical evaluation for active TB disease includes five key components:
- Medical History: Assessing risk factors, past TB exposure, and symptoms.
- Physical Examination: Evaluating general health and looking for signs of TB disease.
- TB Infection Test: Utilizing either a TB blood test or TB skin test.
- Chest Radiograph: Imaging to detect lung abnormalities suggestive of TB disease.
- Bacteriologic Examination: Analyzing sputum samples through smear microscopy, nucleic acid amplification testing (NAAT), culture, and drug susceptibility testing.
Culture remains the gold standard for microbiologic confirmation of active TB disease.
For more detailed information, consult Clinical and Laboratory Diagnosis for Tuberculosis.
Next Steps After Diagnosis
Effective treatment regimens are available for both latent TB infection and active TB disease. Treatment decisions are guided by:
- Drug susceptibility testing results (for active TB) or presumed source case susceptibility (for LTBI).
- Co-existing medical conditions (e.g., HIV, diabetes).
- Potential drug-drug interactions.
Consultation with a TB expert is recommended for patients requiring alternative regimens due to suspected drug resistance, drug allergies, or drug-drug interactions.
Further information on treatment options is available at Treatment for Latent TB Infection and TB Disease.
Reporting TB Cases
Latent TB Infection Reporting
Reporting requirements for latent TB infection vary by jurisdiction. Consult your state TB program for local reporting guidelines.
TB Disease Reporting
TB disease is a nationally notifiable condition, and reporting is mandatory in all states. Healthcare providers must adhere to state and local regulations regarding TB disease reporting.
All cases of clinically active or suspected TB disease should be promptly reported to the local or state health department.
A TB disease case definition, as outlined by the Tuberculosis Case Definition for Public Health Surveillance, is used for public health surveillance purposes.
The CDC publishes an annual surveillance report summarizing TB cases in the United States, available at TB Data and Statistics.
Resources for Further Information
- Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children
- Core Curriculum on Tuberculosis: What the Clinician Should Know – A comprehensive manual for clinicians managing TB.
- Mantoux Tuberculin Skin Test Toolkit – Resources for healthcare providers on administering and interpreting TB skin tests.
