Tuberculosis (TB) remains a global health concern, and timely diagnosis is crucial for effective treatment and prevention of its spread. This guide provides a detailed overview of TB diagnosis, focusing on targeted testing, risk factors, available diagnostic tests, and interpretation of results.
Targeted Testing for Tuberculosis
Targeted TB testing is a strategic approach aimed at identifying and treating latent TB infection (LTBI) in individuals at higher risk of developing TB disease. By focusing on at-risk populations, this strategy helps prevent the progression from LTBI to active TB disease, contributing significantly to public health efforts to eliminate TB. Treating LTBI is a key step in preventing TB disease and reducing TB transmission within communities.
Why “Think TB” is Essential
While TB prevalence is lower in the United States compared to past decades, it’s vital for healthcare providers to maintain a high index of suspicion. TB symptoms can sometimes be subtle or mimic other conditions, leading to delayed or missed diagnoses. Therefore, it’s crucial for healthcare professionals to “Think TB,” especially when evaluating patients presenting with relevant symptoms or risk factors. Early consideration of TB in differential diagnoses ensures prompt testing and treatment, improving patient outcomes and reducing the potential for further transmission.
Determining the Right Diagnostic Approach
Targeted Testing Recommendations
The Centers for Disease Control and Prevention (CDC) and the U.S. Preventive Services Task Force (USPSTF) strongly recommend targeted testing for individuals at increased risk of TB infection. Routine TB infection testing is an integral part of healthcare for these higher-risk patients.
Conversely, routine testing is not recommended for individuals at low risk of TB infection. Testing low-risk populations increases the likelihood of false-positive results, which can lead to unnecessary further evaluations and treatments. Furthermore, it can divert valuable healthcare resources away from effective TB prevention efforts in high-risk groups. While certain situations like employment or school enrollment might mandate TB testing regardless of risk, the CDC generally advises against risk-independent testing approaches.
The frequency of TB testing is determined by an individual’s specific risk factors. This can range from a single, one-time test for individuals at low risk of future TB exposure to annual testing for those with ongoing exposure risks. It’s crucial that TB testing is always conducted with a clear plan for follow-up care, ensuring appropriate evaluation and treatment for all individuals diagnosed with either latent TB infection or active TB disease. Consult your local or state TB program for detailed guidance and resources.
Identifying TB Risk Factors
Individuals at risk for TB fall into two primary categories:
- Those at increased risk of exposure to TB bacteria.
- Those at increased risk of developing TB disease once infected.
Groups at Higher Risk of TB Exposure:
- Close Contacts: Individuals who have been in close contact with persons known or suspected to have active, infectious TB disease.
- Travel to TB-Prevalent Countries: People born in or who frequently travel to countries with a high burden of TB.
- Congregate Living Settings: Individuals currently or formerly residing in large group settings where TB transmission is more likely, such as homeless shelters, correctional facilities, and nursing homes.
- High-Risk Workplace Environments: Employees in high-risk congregate settings.
- Healthcare Workers: Healthcare professionals who provide care to patients with TB disease.
- Locally Defined High-Incidence Populations: Populations identified locally as having a higher incidence of latent TB infection or TB disease, potentially including medically underserved communities, low-income populations, or individuals with substance use disorders.
- Infants, Children, and Adolescents: Young individuals exposed to adults who are at increased risk for latent TB infection or TB disease.
Groups at Higher Risk of TB Disease Progression (Once Infected):
- HIV Infection: People living with HIV are at significantly higher risk.
- Young Children: Children under 5 years of age.
- Recent TB Infection: Individuals newly infected with TB bacteria within the past two years.
- Prior Untreated TB: People with a history of inadequately treated or untreated TB disease.
- Immunosuppressive Therapy: Patients receiving immunosuppressant medications, such as TNF-alpha antagonists, systemic corticosteroids (equivalent to or greater than 15 mg of prednisone daily), or post-organ transplant immunosuppressive drugs.
- Specific Medical Conditions: Individuals with silicosis, chronic renal failure, leukemia, or cancers of the head, neck, or lung.
- Diabetes Mellitus: People with diabetes.
- Post-Gastric Bypass/Jejunoileal Bypass: Individuals who have undergone gastrectomy or jejunoileal bypass surgery.
- Low Body Weight: People with significantly low body weight.
- Substance Use: Individuals who use substances, particularly injection drugs.
- Locally Defined High-Incidence Populations: Similar to exposure risk, this includes medically underserved and low-income populations identified locally.
Recommended TB Tests: Blood Tests and Skin Tests
Two primary tests are used to determine TB infection:
- TB Blood Tests (Interferon Gamma Release Assays – IGRAs): These tests analyze the immune response to TB bacteria in a blood sample.
- TB Skin Test (Mantoux Tuberculin Skin Test – TST): This test involves injecting a small amount of tuberculin under the skin and observing the reaction.
It’s important to note that TB blood tests or skin tests are generally not necessary for individuals with documented prior positive TB test results or previous TB disease treatment. In most cases, a repeat test will likely yield a positive result and not provide additional clinical value.
TB Blood Tests (IGRAs)
TB blood tests, or IGRAs, detect TB infection by measuring the immune response in whole blood when exposed to TB antigens. White blood cells from TB-infected individuals typically react to these antigens by releasing interferon-gamma (IFN-γ), which the test measures.
The U.S. Food and Drug Administration (FDA) has approved two commercially available TB blood tests:
- QuantiFERON®-TB Gold Plus (QFT-Plus)
- T-SPOT®.TB test (T-Spot)
A significant advantage of TB blood tests is that they require only one patient visit for blood collection. TB blood tests are also the preferred method for individuals aged 5 years and older who have received the Bacille Calmette-Guérin (BCG) vaccine, as BCG vaccination can sometimes cause false-positive results on TB skin tests.
TB Skin Test (Mantoux Tuberculin Skin Test – TST)
The TB skin test, also known as the Mantoux tuberculin skin test (TST) or PPD test, involves a healthcare provider injecting a standardized amount of tuberculin PPD solution into the forearm skin. The PPD, or purified protein derivative of tuberculin, is the only FDA-approved solution for this type of skin test.
The skin test reaction must be evaluated by a trained healthcare professional 48 to 72 hours after administration. The healthcare worker measures any induration (swelling) at the injection site to determine if the reaction is positive or negative.
TB skin tests are a suitable alternative when TB blood tests are unavailable, cost-prohibitive, or impractical. Current CDC guidelines recommend the TB skin test as the preferred method for children under 5 years of age, although some experts may utilize TB blood tests even in younger children. Consulting guidelines from the American Academy of Pediatrics (AAP) is recommended for pediatric TB testing decisions.
Interpreting TB Test Results
Interpreting TB Blood Test (IGRA) Results
The interpretation of TB blood test results varies depending on the specific test used.
- QFT-Plus: Results are based on the amount of IFN-γ released in response to TB antigens and control substances after blood incubation.
- T-Spot: Results are determined by comparing the number of IFN-γ producing cells (spots) after blood incubation with test substances.
Laboratories should provide both qualitative and quantitative results for TB blood tests.
- Qualitative Results:
- QFT-Plus: Reported as positive, negative, or indeterminate.
- T-Spot: Reported as positive, borderline, negative, or invalid.
- Quantitative Results: Reported as numerical values reflecting responses to TB antigens and nil and mitogen controls. While specific interpretation guidelines for quantitative IGRA results are limited, these values can be helpful in understanding qualitative results in individual cases, especially when considered alongside risk factors.
Interpreting TB Skin Test Results
TB skin test interpretation relies on measuring the induration (firm swelling) in millimeters (mm) at the injection site, along with assessing the individual’s risk of TB infection acquisition and progression to disease if infected. Detailed guidelines for interpreting TB skin test results are available in the CDC’s clinical testing guidance.
TB skin test results must be read by a trained healthcare professional. Consult state and local public health authorities to determine authorized personnel for TB skin test placement and reading in your jurisdiction.
Understanding a Positive TB Test Result
A positive result from either a TB blood test or TB skin test generally indicates TB infection. Further evaluation, typically including a chest X-ray, is necessary to rule out active TB disease. It’s important to recognize that some individuals with active TB disease may have negative results on TB blood tests or skin tests. Therefore, these tests alone cannot definitively exclude or confirm active TB disease. If a patient presents with symptoms suggestive of TB disease, healthcare providers should initiate other diagnostic tests without waiting for TB blood test or skin test results.
Diagnosis of TB Infection and Disease
Individuals exhibiting signs or symptoms of TB disease, or those with positive results from a TB blood test (IGRA) or tuberculin skin test (TST), require medical evaluation for TB disease.
A diagnosis of latent TB infection (LTBI) is made when an individual has a positive TB blood test or skin test result, but a medical evaluation rules out active TB disease.
A comprehensive medical evaluation for TB disease comprises five key components:
- Medical History: Detailed patient history, including risk factors and symptoms.
- Physical Examination: Thorough physical assessment.
- TB Infection Test: Either a TB blood test or TB skin test.
- Chest Radiograph: Imaging to assess for lung abnormalities.
- Bacteriologic Examination: Sputum smear microscopy, nucleic acid amplification testing, culture, and drug susceptibility testing to confirm TB disease and determine drug resistance patterns. Culture remains the gold standard for microbiologic diagnosis of TB disease.
Next Steps After Diagnosis
Numerous effective treatment regimens are available for both latent TB infection and active TB disease. Healthcare providers select the most appropriate regimen based on factors such as:
- Drug susceptibility results (for active TB disease) or presumed source patient’s drug susceptibility (for LTBI, if known).
- Coexisting medical conditions (e.g., HIV, diabetes).
- Potential for drug-drug interactions.
Consultation with a TB expert is recommended when alternative regimens are needed due to suspected drug resistance, drug allergies, or drug-drug interactions.
Reporting TB Cases
Latent TB Infection Reporting
Reporting requirements for latent TB infection vary by state and locality. Consult your state TB program for specific reporting guidelines in your jurisdiction.
TB Disease Reporting
TB disease is a nationally notifiable condition, and reporting is mandatory in all states. Healthcare providers must comply with state and local regulations for reporting TB disease cases. All individuals with clinically active or suspected TB disease should be promptly reported to the local or state health department. A TB disease case is defined as an episode of TB disease in a person meeting the laboratory or clinical criteria outlined in the CDC’s Tuberculosis Case Definition for Public Health Surveillance. The CDC publishes an annual surveillance report summarizing TB cases in the United States.
Resources for Healthcare Professionals
- 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: Link to Guidelines
- Core Curriculum on Tuberculosis: What the Clinician Should Know: Link to Core Curriculum (A comprehensive manual for clinicians managing patients with or at risk for TB.)
- Mantoux Tuberculin Skin Test Toolkit: Link to Toolkit (Resources for healthcare providers on TB skin test administration and interpretation.)
