When is treatment of latent tuberculosis infection (LTBI) recommended?

When to Treat Latent Tuberculosis Infection (LTBI)

Treatment of LTBI should be offered to all individuals at high risk for progression to active TB disease, irrespective of age, after active TB has been definitively excluded. 1

Who Should Receive LTBI Treatment

Highest Priority Groups (TST ≥5 mm positive)

• HIV-infected persons must receive treatment given their 5-10% annual reactivation risk (compared to 5-15% lifetime risk in HIV-negative individuals). 1
• Recent close contacts of persons with infectious pulmonary TB should be treated immediately, regardless of test results, after active TB is excluded. 1, 2
• Patients on immunosuppressive therapy, including those initiating anti-TNF biologics, preparing for organ or hematological transplantation, or receiving high-dose corticosteroids. 3, 1
• Persons with chest radiographs showing fibrotic changes consistent with prior untreated TB. 3

High-Risk Groups (TST ≥10 mm positive)

• Recent immigrants (within 5 years) from high TB prevalence countries. 3
• Injection drug users. 3
• Healthcare workers and residents/employees of high-risk congregate settings with TB exposure. 3, 4
• Patients with specific medical conditions: silicosis, diabetes mellitus, chronic renal failure requiring dialysis, leukemias and lymphomas, head/neck/lung carcinoma, >10% weight loss, gastrectomy, or jejunoileal bypass. 3, 1
• Children <5 years old with positive testing. 1

Lower Risk Groups (TST ≥15 mm positive)

• Persons at low risk for TB, for whom testing is not generally indicated, require ≥15 mm induration to be considered positive. 3

Critical Pre-Treatment Requirements

Active TB disease must be definitively ruled out before initiating any LTBI treatment. This is accomplished through: 1

• History and physical examination assessing for TB symptoms (persistent cough, weight loss, night sweats, hemoptysis, fever, anorexia). 1, 2
• Mandatory chest radiography (posterior-anterior view) to exclude active pulmonary TB. 1, 2
• Sputum samples for acid-fast bacilli smear and culture if symptoms or abnormal chest X-ray are present. 1

Key Principles for Treatment Decisions

Targeted testing should only be conducted among high-risk groups and discouraged in low-risk populations. 3 The decision to treat considers: 5

• Risk of TB infection and development (relative risk ≥4 warrants active consideration). 5
• Impact of potential TB development on the individual. 5
• Possible manifestation of treatment side effects. 5
• Prospects of treatment completion. 5

Special Populations

Pregnant Women

• High-risk pregnant women (HIV-infected or recent infection) should receive LTBI treatment without delaying for the first trimester. 1

Children

• All children <4 years old or those exposed to adults in high-risk categories should be treated with TST ≥10 mm. 3
• Isoniazid for 9 months is the only recommended regimen for children. 1

Patients with Drug-Resistant Source Cases

• Isoniazid-resistant, rifampin-susceptible: rifampin + pyrazinamide for 2 months, or rifampin alone for 4 months. 1
• Multidrug-resistant (isoniazid + rifampin resistant): pyrazinamide + ethambutol or pyrazinamide + quinolone for 6-12 months. 1

Common Pitfalls to Avoid

• Never treat LTBI without first excluding active TB disease through proper evaluation and chest radiography. 1
• Do not withhold treatment based on age alone in high-risk individuals (e.g., healthcare workers with ongoing exposure). 4
• Avoid the rifampin-pyrazinamide regimen routinely due to unacceptable hepatotoxicity rates. 1, 6
• Do not use intermittent dosing without directly observed therapy (DOT)—twice or thrice weekly regimens must always be directly observed. 1