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

Recommended Preventive Treatment Regimens for Latent Tuberculosis Infection 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 6-9 months of isoniazid, 3-4 months of rifampin alone, 3-4 months of isoniazid plus rifampin, or 3 months of weekly rifapentine plus isoniazid. 1

Identifying Candidates for Preventive Treatment

Preventive treatment should be offered to the following groups after active TB has been excluded:

1. Close contacts of infectious TB patients:

   • All contacts with positive tuberculin skin test (TST) ≥5 mm or positive IGRA 1
   • Special attention to contacts who are:
     • Children under 5 years (highest priority to those under 3 years) 1
     • HIV-infected individuals 1
     • Persons on immunosuppressive therapy 1

2. High-risk individuals with LTBI:

   • HIV-infected persons 1
   • Patients initiating anti-TNF treatment 1
   • Patients receiving dialysis 1
   • Patients preparing for organ/hematological transplantation 1
   • Persons with silicosis 1
   • Persons with fibrotic changes on chest radiograph 2
   • Persons with diabetes mellitus 2

Recommended Treatment Regimens

Standard Drug-Susceptible TB Exposure:

1. First-line options:

   • 6-9 months of isoniazid daily 1
   • 3-4 months of rifampin alone 1, 2
   • 3-4 months of isoniazid plus rifampin 1
   • 3 months of weekly rifapentine plus isoniazid 1, 3

2. Special considerations:

   • HIV-infected contacts should receive at least 9-12 months of isoniazid 1, 2
   • Persons with fibrotic lesions should receive 12 months of isoniazid or 4 months of isoniazid plus rifampin 2
   • Directly observed therapy (DOT) is recommended for intermittent dosing regimens 1

Drug-Resistant TB Exposure:

1. INH-resistant TB exposure:

   • 4 months of daily rifampin 1

2. MDR-TB exposure:

   • Requires individualized regimens based on the drug susceptibility pattern of the source case 1
   • Consultation with TB experts is strongly recommended 1
   • Close clinical monitoring is essential even if preventive treatment is not given 1

Window Period Prophylaxis

For high-risk contacts with initial negative TST/IGRA:

• Treatment should be initiated and continued until a second test is performed 8-12 weeks after last exposure 1
• This applies particularly to:
  • Children under 5 years 1
  • HIV-infected individuals 1
  • Other immunocompromised persons 1

Monitoring and Adherence

1. Baseline evaluation:

   • Clinical assessment to exclude active TB
   • Liver function tests for those with risk factors for hepatotoxicity
   • HIV testing for those with unknown status

2. Follow-up monitoring:

   • Monthly clinical assessment for symptoms of hepatotoxicity
   • Education about adverse effects
   • Strategies to enhance adherence (DOT when feasible)

Common Pitfalls and Caveats

1. Failure to rule out active TB before starting preventive therapy can lead to inadequate treatment and development of drug resistance.

2. Drug interactions with rifampin/rifapentine, particularly with antiretroviral medications and other commonly used drugs, require careful consideration 1.

3. Hepatotoxicity risk increases with age, alcohol use, and pre-existing liver disease. Isoniazid should be used with caution in these populations.

4. Poor adherence to longer regimens is common. The newer shorter regimens may improve completion rates 3.

5. MDR-TB contacts require special consideration. Standard preventive regimens may be ineffective, and the risk-benefit ratio of alternative regimens is not well established 4.

6. Pregnancy considerations: Isoniazid with pyridoxine is generally considered safe but should be started after the first trimester when possible.

The evidence strongly supports that completing preventive therapy significantly reduces the risk of developing active TB disease among contacts, with one study showing reduction from 9.8% TB development in untreated contacts to just 0.2% in those who completed treatment 5. This substantial benefit in reducing morbidity and mortality makes preventive therapy a critical component of TB control and elimination efforts.