Should tuberculosis (TB) prevention therapy be taken by all contacts of a TB case?

Should Tuberculosis Prevention Therapy Be Taken by All Contacts of a TB Case?

Not all contacts of a TB case require preventive therapy—treatment decisions should be based on a risk-stratified approach that prioritizes contacts with confirmed M. tuberculosis infection (positive TST/IGRA) and those at highest risk for disease progression, particularly in low TB burden settings. 1, 2

Risk-Stratified Approach to Contact Management

High-Priority Contacts Who Should Receive Preventive Therapy

The following contacts should receive preventive therapy after active TB is excluded:

• HIV-infected contacts should receive preventive therapy regardless of TST results or age after active TB is ruled out 1, 2
• Close contacts with positive TST (≥5 mm induration) or positive IGRA should receive treatment regardless of age 1, 3
• Children under 5 years of age who are close contacts should be considered high-risk and receive preventive therapy, even with initial negative testing, due to rapid progression risk 1, 4
• Immunocompromised individuals including those on TNF-α antagonists, organ transplant recipients, or chronic corticosteroid therapy (>15 mg/day prednisone equivalent) should receive treatment 1, 4
• Contacts with fibrotic chest radiograph changes consistent with prior TB should receive 12 months of preventive therapy 4

Window-Period Prophylaxis for Vulnerable Contacts

Children under 5 years and HIV-infected persons should receive immediate preventive therapy even with negative initial testing, then be retested 8-12 weeks after last exposure 1, 2. This "window-period prophylaxis" prevents rapidly emerging disease in vulnerable populations while awaiting immune response development 1.

Setting-Specific Considerations

High TB Burden Settings

In high-burden settings, a broader approach treating all contacts regardless of TST/IGRA status may be justified, as the number-needed-to-treat ranges from 29-43 contacts to prevent one case of TB disease 5. The effectiveness of preventive treatment is greater in high-burden settings (aHR 0.31) compared to low-burden settings (aHR 0.58) 5.

Low TB Burden Settings

In low-burden settings, a risk-targeted strategy prioritizing contacts with positive TST/IGRA is more appropriate, as the number-needed-to-treat among all contacts ranges from 213-455, compared to only 9-34 among those with confirmed infection 5. This approach balances effectiveness against exposing large numbers to potentially toxic therapy 6.

Recommended Treatment Regimens

Standard preventive therapy options include 1, 4:

• 9 months of daily isoniazid (300 mg for adults, 10 mg/kg for children) - most widely used regimen 3, 4, 7
• 6 months of daily isoniazid - acceptable alternative with slightly lower efficacy 1
• 3-4 months of isoniazid plus rifampicin - equivalent efficacy to longer isoniazid regimens 1, 6
• 4 months of rifampicin alone - option for isoniazid-intolerant patients 3, 4
• 3 months of weekly rifapentine plus isoniazid (3HP) - for persons >2 years, though not yet widely available 1, 7

Special Populations Requiring Modified Approaches

MDR-TB Contacts

For contacts of MDR-TB cases, strict clinical observation and monitoring for 24 months is preferred over preventive treatment 1. The evidence for MDR-TB preventive therapy is sparse (only one small prospective study in children showed benefit: OR 0.2,95% CI 0.04-0.94) 1. Recent meta-analysis suggests tailored regimens based on drug-resistance profiles may reduce progression risk (RR 0.34,95% CI 0.16-0.72), but completion rates and adverse effects remain concerning 8.

If preventive therapy is considered for MDR-TB contacts, it requires 1:

• Comprehensive individual risk assessment balancing benefits versus harms
• Drug susceptibility testing of the index case
• Consultation with TB experts
• Close monitoring for adverse effects and active disease development

Contacts with Prior Positive TST

Contacts with documented prior positive TST generally do not require repeat testing or treatment unless 1:

• They are HIV-infected (should receive treatment regardless of prior history) 1
• They have new high-risk medical conditions
• They had inadequate or no prior treatment for latent infection 1

Monitoring Requirements

All contacts receiving preventive therapy require 1:

• Monthly clinical monitoring visits to healthcare providers
• Education about symptoms requiring immediate treatment cessation (anorexia, nausea, vomiting, abdominal discomfort, dark urine, jaundice) 1
• Baseline liver function tests for persons >35 years with monthly monitoring 3
• Pyridoxine supplementation when receiving isoniazid to prevent peripheral neuropathy 1

Critical Pitfalls to Avoid

Common errors in contact management include:

• Failing to exclude active TB before initiating preventive therapy - always perform chest radiography and clinical evaluation first 1, 3
• Not retesting TST-negative contacts at 8-12 weeks - immune response may not be detectable initially 1
• Treating all contacts uniformly without risk stratification - wastes resources and exposes low-risk individuals to unnecessary drug toxicity 6, 5
• Neglecting HIV testing in appropriate populations - HIV-infected contacts require treatment regardless of TST results 1
• Using rifampin-containing regimens in patients on protease inhibitors or NNRTIs without appropriate dose adjustments or substitution with rifabutin 1