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 9 months of daily isoniazid, with alternative options including 4 months of daily rifampin, 3 months of daily isoniazid plus rifampin, or the 12-dose once-weekly isoniazid and rifapentine regimen. 1, 2

Risk Assessment and Testing

Before initiating preventive therapy, proper assessment is essential:

1. Testing for latent TB infection:

   • Tuberculin skin test (TST) with ≥5mm induration considered positive for:
     • HIV-infected persons
     • Recent contacts of TB cases
     • Persons with fibrotic changes on chest radiograph
     • Immunosuppressed patients 1, 2
   • TST with ≥10mm induration considered positive for other high-risk groups
   • Interferon-gamma release assays (IGRAs) may also be used

2. Rule out active TB disease:

   • Chest radiography and clinical evaluation mandatory before starting preventive therapy 1
   • Symptom screening (cough, fever, weight loss, night sweats)

Standard Preventive Treatment Regimens

Primary Recommended Regimens:

1. Isoniazid (INH) regimen:

   • 9 months of daily isoniazid (highest level of evidence) 1, 2
   • Add pyridoxine (vitamin B6) to prevent peripheral neuropathy 1
   • Can be given twice weekly under directly observed therapy (DOT)

2. Alternative regimens:

   • 4 months of daily rifampin alone 1, 3
   • 3 months of daily isoniazid plus rifampin 1, 3
   • 12 weekly doses of isoniazid plus rifapentine (3HP regimen) for adults and children ≥2 years 4, 3, 5

Special Populations

HIV-infected individuals:

• Preventive therapy should be initiated regardless of TST results if they are close contacts of active TB cases 1
• Minimum 12 months of therapy recommended 2
• Careful consideration of drug interactions with antiretroviral therapy when using rifampin or rifabutin-containing regimens 1

Children:

• Children <5 years who are close contacts should receive preventive therapy even with negative TST initially (window prophylaxis) 1, 2
• Repeat TST after 12 weeks; continue therapy if positive 2
• Children have higher risk of progression to active TB, especially within first year of exposure 6, 7

Immunosuppressed patients:

• Patients on TNF-α antagonists, transplant recipients, and those on immunosuppressive therapy should be prioritized for preventive treatment 1, 2
• Careful monitoring for adverse effects is essential

Drug-Resistant TB Exposure

For contacts of drug-resistant TB cases:

• INH-resistant TB: 4 months of daily rifampin 1
• MDR-TB (resistant to both INH and rifampin): Consultation with TB expert required 1
• Individual risk assessment needed for contacts of MDR-TB patients 1
• Close monitoring for 2 years after exposure regardless of treatment decision 1

Implementation Considerations

Prioritization for DOT:

1. Children <5 years
2. HIV-infected or immunocompromised individuals
3. Contacts with TST conversion
4. Persons with social or behavioral factors affecting adherence 1

Monitoring:

• Monthly clinical evaluation for adherence and adverse effects 1
• Liver function monitoring, especially for older adults and those with risk factors
• Education about TB, treatment, and potential adverse effects

Clinical Pearls and Pitfalls

• The risk of TB disease is highest in the first year after exposure, with approximately 2.15% cumulative incidence 7
• US/Canadian-born contacts may have higher rates of TB development than foreign-born contacts when left untreated 8
• Treatment completion is critical - TB developed in 9.8% of contacts who did not initiate treatment versus only 0.2% of those who completed treatment 8
• Never start preventive therapy before ruling out active TB disease, as monotherapy could lead to drug resistance
• Consider the drug susceptibility pattern of the source case when selecting a preventive regimen 1

By implementing appropriate preventive treatment regimens based on risk assessment, we can significantly reduce the progression to active TB disease among high-risk groups and close contacts, thereby reducing TB-related morbidity and mortality.