What is the recommended preventive treatment regimen for high-risk groups and close contacts of individuals with active tuberculosis (TB)?

Recommended Preventive Treatment Regimens for TB in High-Risk Groups and Close Contacts

For high-risk groups and close contacts of individuals with active tuberculosis, the recommended preventive treatment regimen is isoniazid daily for 9 months, or alternatively, a 3-month regimen of weekly isoniazid and rifapentine (3HP) for those aged 2 years and older. 1, 2

Identifying Candidates for Preventive Treatment

High-Risk Groups Requiring TB Preventive Treatment:

• Persons with HIV infection (≥5mm TST induration) 3
• Close contacts of persons with newly diagnosed infectious TB (≥5mm TST) 1, 3
• Persons with fibrotic lesions on chest radiographs (≥5mm TST) 3
• Persons initiating anti-TNF treatment 1
• Patients receiving dialysis 1
• Patients preparing for organ or hematological transplantation 1
• Persons with silicosis 1, 3
• Persons with diabetes mellitus 3
• Persons on prolonged corticosteroid therapy 3

Recommended Treatment Regimens

First-Line Regimens:

1. Isoniazid (INH) daily for 9 months 1

   • Standard dose: Adults - 5mg/kg up to 300mg daily
   • Add pyridoxine (vitamin B6) to prevent peripheral neuropathy
   • Directly observed therapy (DOT) recommended when feasible

2. Isoniazid and Rifapentine (3HP) 1, 2

   • Once weekly for 12 weeks (12 doses total)
   • Rifapentine dosing based on weight:
     • 10-14 kg: 300 mg
     • 14.1-25 kg: 450 mg
     • 25.1-32 kg: 600 mg
     • 32.1-50 kg: 750 mg

     • 50 kg: 900 mg

   • Isoniazid dosing:
     • Adults and children ≥12 years: 15 mg/kg (max 900 mg)
     • Children 2-11 years: 25 mg/kg (max 900 mg)
   • Must be taken with food to increase bioavailability
   • Not recommended for children under 2 years

3. Rifampin daily for 4 months 1

   • Alternative when isoniazid cannot be used
   • Particularly useful for contacts of isoniazid-resistant, rifampin-susceptible TB

4. Isoniazid and Rifampin daily for 3-4 months 1

   • Alternative shorter regimen with good efficacy

Special Considerations

Drug-Resistant TB Exposure:

• For contacts of drug-resistant TB patients, treatment must be tailored based on the resistance pattern of the source case 1
• For MDR-TB contacts:
  • Individual risk assessment is essential 1
  • Consultation with TB expert required 1
  • Careful clinical monitoring for 2 years after exposure 1
  • Standard preventive regimens may not be effective

HIV Co-infection:

• HIV-infected contacts should receive preventive therapy regardless of TST results 1
• Minimum of 12 months of therapy recommended for HIV-infected persons 3
• Careful consideration of drug interactions with antiretroviral therapy is essential 1
• Rifapentine-containing regimens require caution due to potential drug interactions with antiretrovirals 1

Prioritizing DOT for Specific Groups:

1. Contacts aged <5 years 1
2. HIV-infected or immunocompromised contacts 1
3. Contacts with TST conversion from negative to positive 1
4. Contacts with social or behavioral factors affecting adherence 1

Monitoring During Treatment

• Monthly clinical evaluation for all contacts on treatment 1
• Monitor for symptoms of hepatotoxicity (nausea, vomiting, abdominal pain, jaundice)
• Baseline liver function tests for patients with risk factors for hepatotoxicity
• Regular liver function monitoring for patients on rifapentine 2
• Use incentives and enablers to improve adherence 1

Common Pitfalls and Caveats

1. Failure to rule out active TB before starting preventive therapy

   • Always exclude active TB disease through clinical evaluation, chest radiography, and when indicated, sputum examination 1, 4

2. Overlooking drug interactions

   • Rifamycins (rifampin, rifapentine) interact with many medications including antiretrovirals, oral contraceptives, and anticoagulants 1

3. Poor adherence leading to treatment failure

   • Treatment completion rates often fall below the target of 85% 1
   • Consider shorter regimens for better adherence when appropriate

4. Inadequate monitoring for adverse effects

   • Hepatotoxicity is a significant concern, especially with isoniazid
   • Risk increases with age, alcohol use, and pre-existing liver disease

5. Inappropriate regimen selection for drug-resistant TB contacts

   • Standard regimens may be ineffective for MDR-TB contacts
   • Drug susceptibility results of the source case are crucial for regimen selection 1

The evidence strongly supports that completing preventive treatment significantly reduces the risk of developing active TB disease, with completion of treatment reducing TB incidence by up to 90% compared to no treatment 5, 6.