When is treatment for latent tuberculosis (TB) recommended in asymptomatic individuals?

Treatment of Latent Tuberculosis Infection (LTBI) in Asymptomatic Individuals

Treatment for latent tuberculosis infection is strongly recommended for high-risk asymptomatic individuals, including people living with HIV, close contacts of pulmonary TB cases, patients on immunosuppressive therapy, and those with certain medical conditions that increase risk of TB reactivation. 1

Who Should Be Tested and Treated for LTBI

Testing and treatment should be targeted to individuals at high risk for developing active TB disease. The WHO guidelines specifically recommend systematic testing and treatment for:

Strong Recommendations:

• People living with HIV
• Adult and child contacts of pulmonary TB cases
• Patients initiating anti-TNF treatment
• Patients receiving dialysis
• Patients preparing for organ or hematological transplantation
• Patients with silicosis
• Patients with fibrotic lesions on chest radiograph consistent with old TB 1

Conditional Recommendations (based on epidemiology and resources):

• Prisoners
• Healthcare workers
• Immigrants from high TB burden countries
• Homeless persons
• Illicit drug users 1

Medical Conditions That Increase Risk:

• Diabetes mellitus
• Chronic renal failure
• Leukemias and lymphomas
• Carcinoma of the head, neck, or lung
• Significant weight loss (>10% of ideal body weight)
• History of gastrectomy or jejunoileal bypass 1, 2

Diagnostic Testing for LTBI

Two main tests are used to diagnose LTBI:

1. Tuberculin Skin Test (TST): Interpretation depends on risk factors:

   • ≥5 mm induration: HIV-positive individuals, recent contacts of TB cases, persons with immunosuppression, abnormal chest radiographs consistent with prior TB
   • ≥10 mm induration: Recent immigrants from high-prevalence countries, injection drug users, residents/employees of high-risk settings, laboratory personnel, persons with clinical risk conditions, children <4 years
   • ≥15 mm induration: Persons with no known risk factors 1

2. Interferon-Gamma Release Assays (IGRAs): May have advantages over TST including higher specificity, better correlation with TB exposure, and less cross-reactivity with BCG vaccination 1, 3

Important: Chest radiography should be performed before LTBI treatment to rule out active TB disease 1

Treatment Regimens for LTBI

Once LTBI is diagnosed and active TB is ruled out, treatment should be initiated with one of the following regimens:

1. Isoniazid for 9 months (preferred regimen)

   • Daily or twice weekly (if directly observed)
   • Most effective based on randomized trials 1

2. Isoniazid for 6 months

   • Alternative that still provides substantial protection
   • May be more cost-effective in certain settings 1

3. Rifampin plus isoniazid for 3-4 months 1

4. Rifampin alone for 3-4 months 1

5. Rifapentine plus isoniazid for 12 weeks 1

Monitoring During Treatment

• Baseline liver function tests (ALT, AST, bilirubin) are indicated for:

  • Patients with HIV infection
  • Pregnant women and those in immediate postpartum period
  • Persons with history of chronic liver disease
  • Regular alcohol users
  • Persons at risk for chronic liver disease 1

• Routine laboratory monitoring during treatment is indicated for:

  • Persons with abnormal baseline liver function tests
  • Persons at risk for hepatic disease
  • Evaluation of possible adverse effects 1

Special Considerations

1. HIV-infected individuals: Should receive at least 12 months of therapy when using isoniazid 2

2. Patients with fibrotic pulmonary lesions: Should receive 12 months of isoniazid or 4 months of isoniazid plus rifampin 2

3. Children: Isoniazid for 9 months is the only recommended regimen 1

4. Pregnant women: Rifampin is not recommended 1

5. Elderly patients (>35 years): The risk of hepatitis must be weighed against the risk of tuberculosis, but treatment is still recommended for those with additional risk factors 2

Pitfalls and Caveats

1. Poor adherence: Treatment completion rates can be low due to the long duration of therapy in asymptomatic individuals. Consider shorter regimens or directly observed therapy for patients at risk of non-adherence 1

2. Hepatotoxicity: Monitor for signs of liver injury, especially in older adults, those with underlying liver disease, or regular alcohol users 1

3. Drug interactions: Rifampin-based regimens have significant drug interactions that must be considered before initiation

4. Immunocompromised patients: TST may have reduced sensitivity; consider using IGRA or dual testing strategy 4, 5

5. Never add a single drug to a failing regimen for active TB as this can lead to drug resistance 1