What is the recommended preventive treatment for latent tuberculosis infection (LTBI) in high-risk groups and close contacts?

Recommended Preventive Treatment for Latent Tuberculosis Infection in High-Risk Groups and Close Contacts

The recommended preventive treatment regimens for latent tuberculosis infection (LTBI) in high-risk groups and close contacts include: 6 or 9 months of isoniazid, 12 weeks of rifapentine plus isoniazid, 3-4 months of isoniazid plus rifampicin, or 3-4 months of rifampicin alone. 1

Identification of High-Risk Groups

The WHO guidelines strongly recommend systematic testing and treatment of LTBI in the following high-risk populations:

• People living with HIV
• Adult and child contacts of pulmonary TB cases
• Patients initiating anti-tumor necrosis factor treatment
• Patients receiving dialysis
• Patients preparing for organ or hematological transplantation
• Patients with silicosis 1

Conditional recommendations for systematic testing and treatment exist for:

• Prisoners
• Healthcare workers
• Immigrants from high TB burden countries
• Homeless persons
• Illicit drug users 1

Diagnostic Evaluation Before Treatment

Before initiating LTBI treatment, a proper diagnostic evaluation should be conducted:

1. Either commercial interferon-gamma release assays (IGRAs) or Mantoux tuberculin skin testing (TST) can be used to test for LTBI 1
2. Chest radiography must be performed before LTBI treatment to rule out active TB disease 1
3. For TST, the following cutoff values apply based on risk groups:
   • ≥5 mm: HIV-infected persons, recent contacts of TB patients, persons with fibrotic changes on chest radiograph, and immunocompromised patients 2
   • ≥10 mm: Intravenous drug users (HIV-negative), persons with medical conditions increasing TB risk (diabetes, prolonged corticosteroid therapy, etc.), and high-incidence groups 2
   • ≥15 mm: Persons <35 years with no other risk factors 2

Treatment Regimens

Standard Regimens

1. Isoniazid (INH) regimens:

   • 6 months of daily isoniazid
   • 9 months of daily isoniazid (preferred for highest efficacy) 1, 2
   • 9 months of twice-weekly isoniazid (administered as directly observed therapy) 1

2. Shorter regimens:

   • 12 weeks of once-weekly rifapentine plus isoniazid
   • 3-4 months of daily isoniazid plus rifampicin
   • 3-4 months of daily rifampicin alone 1

Special Populations

1. HIV-infected persons:

   • Should receive a minimum of 12 months of isoniazid therapy 2
   • Higher priority for directly observed therapy (DOT) 1

2. Persons with fibrotic pulmonary lesions or silicosis:

   • 12 months of isoniazid OR
   • 4 months of isoniazid and rifampin, concomitantly 2

3. Close contacts of drug-resistant TB:

   • For contacts of INH-resistant TB: 4 months of daily rifampin
   • For contacts of MDR-TB: Consultation with TB expert recommended as regimens are not fully tested for efficacy and often poorly tolerated 1

Window Period Prophylaxis

For high-risk contacts with initial negative TST/IGRA results, preventive treatment should be initiated during the "window period" (8-12 weeks after last exposure) for:

1. Contacts younger than 5 years (highest priority for those under 3 years)
2. Contacts with HIV infection or who are otherwise immunocompromised 1

If the second test remains negative after the window period:

• For immunocompetent contacts: treatment may be discontinued
• For immunocompromised contacts: complete the full course of therapy 1

Treatment Completion Considerations

Treatment completion rates vary significantly across populations:

• General population: 39-96%
• Close contacts: 48-82%
• HIV-infected individuals: 55-95%
• Immigrants: 7-86% 3

Shorter regimens generally show higher completion rates compared to longer regimens 3. To improve completion rates:

• Consider directly observed therapy (DOT) for high-risk contacts
• Prioritize DOT for children <5 years, HIV-infected persons, and those with risk factors for progression 1
• Monitor for adverse effects, particularly hepatotoxicity in those with liver disease or excessive alcohol consumption 1

Pitfalls and Caveats

1. Risk of hepatotoxicity: Monitor liver function in patients with risk factors (history of liver injury, excessive alcohol consumption, active hepatitis) 1

2. Drug interactions: Be aware of potential interactions, particularly with rifampin-containing regimens

3. Follow-up after exposure to drug-resistant TB: Standard LTBI regimens may be ineffective; consult TB experts 1

4. Balancing risks and benefits: For persons >35 years without additional risk factors, carefully weigh the risk of hepatitis against the risk of TB 2

5. Treatment adherence: Low initiation and completion rates significantly impact effectiveness of preventive treatment 3

By implementing these evidence-based recommendations for LTBI treatment in high-risk groups and close contacts, the risk of progression to active TB disease can be substantially reduced, contributing to TB elimination efforts.