What is the recommended management for latent tuberculosis (TB)?

Management of Latent Tuberculosis Infection

The preferred treatment regimens for latent tuberculosis infection (LTBI) are 3 months of once-weekly isoniazid plus rifapentine, 4 months of daily rifampin, or 3 months of daily isoniazid plus rifampin, as these shorter regimens have similar efficacy with better completion rates and fewer hepatotoxic events compared to traditional isoniazid regimens. 1

Diagnosis and Screening

Before initiating LTBI treatment, active TB must be ruled out:

• Screen for TB symptoms (cough, fever, night sweats, weight loss)
• Perform chest radiography to exclude active disease
• Individuals with TB symptoms or radiological abnormalities should be further investigated for active TB 1

Testing for LTBI

Either of these tests can be used to diagnose LTBI:

• Interferon-gamma release assays (IGRAs)
• Tuberculin skin test (TST)

In high-income and upper middle-income countries with TB incidence <100 per 100,000, either test is appropriate. In low-income and other middle-income countries, TST is preferred over IGRA. 1

Treatment Regimens

Preferred Regimens (ranked by priority) 1

1. 3 months of once-weekly isoniazid plus rifapentine (strong recommendation, moderate quality evidence)

   • Better completion rates
   • Lower hepatotoxicity compared to 9-month isoniazid
   • Excellent tolerability and efficacy

2. 4 months of daily rifampin (strong recommendation, moderate quality evidence)

   • Significantly less hepatotoxicity than isoniazid regimens
   • Higher completion rates than 9-month isoniazid 2
   • Particularly useful for those who cannot tolerate isoniazid

3. 3 months of daily isoniazid plus rifampin (conditional recommendation, very low/low quality evidence)

   • Similar efficacy to longer isoniazid regimens
   • Shorter duration improves adherence

Alternative Regimens

1. 6 months of daily isoniazid (strong recommendation for HIV-negative; conditional for HIV-positive)

2. 9 months of daily isoniazid (conditional recommendation, moderate quality evidence)

   • Traditional regimen with efficacy >90% if completed properly
   • Associated with poor adherence and higher hepatotoxicity 3

Priority Populations for LTBI Testing and Treatment

Strong Recommendation 1

• 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/hematological transplantation
• Patients with silicosis

Conditional Recommendation 1

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

Monitoring and Adverse Effects

Hepatotoxicity Risk

• Rifampin-based regimens have significantly lower hepatotoxicity than isoniazid-based regimens 1
• The 3-month weekly rifapentine plus isoniazid regimen showed 84% fewer hepatotoxic events compared to 9-month isoniazid 1
• 3-4 month rifampin regimen demonstrated 97% fewer hepatotoxic events compared to 6-month isoniazid 1

Clinical Monitoring

• Regular monthly clinical monitoring is recommended for all patients on LTBI treatment
• Educate patients about potential adverse effects and when to seek medical attention
• No routine baseline laboratory testing is required for all patients, but consider for:
  • Patients with suspected liver disorders
  • HIV-infected persons
  • Pregnant women
  • Persons with history of chronic liver disease or regular alcohol use 4

Special Considerations

Drug Interactions

• Rifamycin-based regimens have many drug interactions, including:
  • Warfarin
  • Oral contraceptives
  • Azole antifungals
  • HIV antiretroviral therapy 1
• For patients on antiretrovirals, consult drug interaction resources before selecting a regimen

MDR-TB Contacts

• Limited evidence exists for preventive therapy in contacts of MDR-TB cases
• Management should be guided by comprehensive clinical risk assessment
• Close monitoring for development of active TB for at least 2 years is preferred over preventive treatment 1

Treatment Completion

Treatment completion rates are significantly higher with shorter rifamycin-based regimens compared to the traditional 9-month isoniazid regimen, making them more effective in real-world settings despite similar efficacy in controlled trials 2, 3.

By selecting the most appropriate regimen based on patient factors and drug interactions, providers can maximize the likelihood of treatment completion while minimizing adverse effects, ultimately preventing more cases of active tuberculosis.