What is the recommended diagnostic and treatment approach for an asymptomatic individual exposed to Tuberculosis (TB)?

Diagnosis and Management of Asymptomatic TB-Exposed Individuals

For an asymptomatic individual exposed to tuberculosis, immediately perform tuberculin skin testing (TST) or interferon-gamma release assay (IGRA), followed by chest radiography if the test is positive (≥5 mm induration for contacts), and initiate treatment for latent TB infection after excluding active disease. 1, 2

Initial Diagnostic Approach

Testing Strategy Based on Exposure Priority

High-priority contacts (children <5 years, immunocompromised individuals, HIV-infected persons) require:

• Immediate TST or IGRA testing at initial evaluation 1
• Chest radiography regardless of test results 1, 2
• Second TST 8-10 weeks post-exposure if initial test is negative and exposure occurred <8 weeks prior 1

Medium-priority contacts (immunocompetent adults with significant exposure):

• TST at baseline and repeat testing 8-10 weeks after last exposure 1
• Chest radiography if TST shows ≥5 mm induration 1, 2

Low-priority contacts (limited exposure):

• Single TST at end of window period (8-10 weeks post-exposure) 1
• This approach avoids misinterpreting the booster phenomenon as recent infection 1

Interpreting Positive Tests

A positive TST is defined as:

• ≥5 mm induration for all TB contacts, HIV-infected persons, and immunosuppressed individuals 1, 2, 3
• This threshold applies universally to exposed individuals regardless of other risk factors 1

IGRAs (QuantiFERON-TB Gold, T-SPOT.TB) may be preferred over TST in BCG-vaccinated populations due to higher specificity and no cross-reactivity with BCG vaccine 2, 4, 5

Excluding Active TB Disease

Before treating latent infection, active TB must be ruled out:

• Obtain chest radiography immediately for all positive test results 1, 2, 3
• Assess for TB symptoms: chronic cough (>3 weeks), hemoptysis, fever, night sweats, weight loss 6, 3
• Collect sputum for mycobacteriologic testing only if chest radiograph is abnormal or symptoms are present 1, 6
• Three sputum samples on different days maximize diagnostic sensitivity 6

Critical pitfall: Healthy contacts with normal chest radiographs do not require sputum collection 1

Treatment of Latent TB Infection

Preferred Regimens (in order of recommendation)

First-line option: 3 months of weekly rifapentine plus isoniazid (3HP)

• Highest adherence rates 3
• Reduces TB incidence by 36% in HIV-negative contacts 3

Alternative regimens:

• 4 months of daily rifampin alone (4R): Best adherence and acceptable efficacy 3
• 3 months of daily rifampin plus isoniazid (3RH): Reduces TB incidence by 48% in HIV-positive patients 1, 3
• 6 months of daily isoniazid: Highly effective but longer duration 1, 7

Special Populations Requiring Immediate Treatment

Children <5 years with exposure:

• Initiate treatment immediately after excluding active disease, even if initial TST is negative (<5 mm) 1
• This "window prophylaxis" continues until repeat TST at 8-10 weeks post-exposure 1
• If second test remains negative, discontinue treatment; if positive, complete full course 1

HIV-infected contacts:

• Treat with full course of latent TB therapy regardless of initial TST result once active disease is excluded 1, 3
• Even severely immunocompromised patients with negative TST should receive treatment after exposure 1

Immunocompromised contacts (organ transplant, immunosuppressive therapy):

• Treat for latent infection even with negative initial testing if exposure is documented 2, 3

Monitoring During Treatment

Essential Adjunctive Therapy

• Administer pyridoxine (vitamin B6) with all isoniazid-containing regimens to prevent peripheral neuropathy 2, 3, 7
• Especially critical for HIV-infected persons, pregnant women, diabetics, and alcoholics 2, 7

Hepatotoxicity Surveillance

• Monitor liver function tests every 2-4 weeks during treatment 2
• Educate patients about hepatotoxicity symptoms: nausea, vomiting, jaundice 2
• Grade 3-4 liver toxicity is most common with 9-month isoniazid regimens 3

Directly Observed Therapy Considerations

DOT is recommended for all patients receiving latent TB treatment, particularly:

• High-risk contacts with poor adherence history 7
• HIV-infected persons (highest priority for DOT) 1, 7
• Children and adolescents 7

Twice-weekly or thrice-weekly regimens must be administered by directly observed therapy 7

Critical Pitfalls to Avoid

• Do not confuse TST conversion with the booster phenomenon: Standard conversion definition (≥10 mm increase over 2 years) is irrelevant when using the 5 mm threshold for contacts 1
• Do not delay treatment in high-risk contacts: Children <5 years and HIV-infected persons require immediate treatment after exposure, even with negative initial testing 1
• Do not perform routine sputum testing: Only indicated if chest radiograph is abnormal or symptoms are present 1
• Do not use single-drug therapy for active disease: If active TB cannot be excluded, initiate multi-drug therapy for active disease, not latent infection treatment 8, 7