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 either 9 months of daily isoniazid, 3 months of weekly isoniazid plus rifapentine, or 4 months of daily rifampin, with the selection based on drug susceptibility of the source case. 1

Identification of High-Risk Groups

High-risk individuals who should be tested for latent TB infection (LTBI) include:

• Close contacts of persons with infectious TB
• HIV-infected individuals
• Patients initiating anti-TNF treatment
• Patients receiving dialysis
• Patients preparing for organ or hematological transplantation
• Persons with silicosis
• Persons taking immunosuppressive therapy for organ transplantation
• Persons taking TNF-α antagonists
• Persons taking ≥15 mg/day of prednisone chronically 1

Testing for LTBI

Before initiating preventive treatment:

• Administer tuberculin skin test (TST) using 5-TU purified protein derivative (PPD) by the Mantoux method
• A positive result is ≥5 mm induration for HIV-infected persons and close contacts of TB patients
• Interferon-gamma release assays (IGRAs) are an acceptable alternative
• Active TB must be ruled out through clinical evaluation and chest radiography 1

Preventive Treatment Regimens

Standard Drug-Susceptible TB Exposure

For contacts of drug-susceptible TB, the following regimens are recommended:

1. Isoniazid-based regimens:

   • 9 months of daily isoniazid (AI recommendation) 1, 2
   • 9 months of twice-weekly isoniazid (BII recommendation) - requires directly observed therapy (DOT) 1

2. Rifamycin-based regimens:

   • 3 months of weekly isoniazid plus rifapentine (for adults and children ≥2 years) 3, 4
   • 4 months of daily rifampin alone (BIII recommendation) 1, 4
   • 3-4 months of daily isoniazid plus rifampin 1

Drug-Resistant TB Exposure

For contacts of drug-resistant TB patients:

• INH-resistant TB: 4 months of daily rifampin 1
• MDR-TB: Consultation with a TB expert is required as regimens are not fully tested for efficacy and are often poorly tolerated 1, 5
• Contacts should be monitored for 2 years after exposure 1

Prioritization for Treatment

Priority for preventive treatment should be given to:

1. Children under 5 years of age
2. HIV-infected individuals and other immunocompromised persons
3. Contacts with TST conversion from negative to positive
4. Persons at high risk of non-adherence due to social or behavioral factors 1

Monitoring During Treatment

• All contacts on preventive therapy should be evaluated in person at least monthly
• Monitor for adherence and adverse effects
• Directly observed therapy (DOT) is recommended for intermittent dosing regimens and when feasible for other regimens
• For self-supervised treatment, check adherence monthly through home visits, pill counts, or clinic appointments 1

Special Considerations

HIV Co-infection

• HIV-infected contacts should receive preventive treatment regardless of TST results after active TB is excluded
• Treatment should be for at least 12 months in HIV-infected persons 1, 2
• Antiretroviral therapy should be considered alongside TB preventive treatment 1

Children

• Children under 5 years are at particularly high risk and should be prioritized for preventive therapy
• TST-negative children who are close contacts should receive window prophylaxis until a repeat TST can be done 12 weeks after contact 2, 6

Potential Drug Interactions

When using rifampin or rifapentine:

• Consider potential interactions with protease inhibitors and non-nucleoside reverse transcriptase inhibitors
• Rifampin should not be administered with protease inhibitors
• Careful evaluation of all medications is required before selecting a regimen 1

Treatment Effectiveness

Preventive treatment significantly reduces TB risk in contacts:

• Untreated TST-positive contacts: 9.8% develop TB (1951 cases/100,000 person-years)
• Partially treated contacts: 1.8% develop TB (290 cases/100,000 person-years)
• Contacts completing treatment: 0.2% develop TB (31 cases/100,000 person-years) 7

By following these recommendations and ensuring high rates of treatment completion, the risk of TB disease among high-risk groups and close contacts can be substantially reduced, contributing to overall TB control efforts.