What is the diagnosis and treatment of Latent Tuberculosis (TB)?

From the Guidelines

Latent tuberculosis infection (LTBI) should be treated with short-course (3-4 months) rifamycin-based treatment regimens, which are preferred over longer-course (6-9 months) isoniazid monotherapy, to prevent progression to active tuberculosis disease. The recommended treatment options include rifampin 600mg daily for 4 months, or the combination of isoniazid 900mg plus rifapentine 900mg once weekly for 12 weeks (3HP regimen) 1. For those who cannot tolerate these options, isoniazid 900mg plus rifampin 600mg twice weekly for 3 months is an alternative. Treatment should be initiated after ruling out active TB through chest X-ray and symptom screening.

Some key points to consider when treating LTBI include:

• Liver function tests should be monitored monthly during treatment, especially for those with risk factors for hepatotoxicity 1.
• Patients should avoid alcohol during treatment and report symptoms like persistent fever, fatigue, abdominal pain, or jaundice immediately.
• Vitamin B6 (pyridoxine) 25-50mg daily is recommended with isoniazid to prevent peripheral neuropathy.
• Treatment completion is crucial as partial treatment may not effectively prevent disease progression.
• LTBI treatment reduces the risk of developing active TB by 60-90%, which is particularly important for immunocompromised individuals, recent contacts of TB cases, and those with radiographic evidence of prior TB 1.
• The bacteria in LTBI remain dormant but viable in the body, with approximately 5-10% lifetime risk of progression to active disease if left untreated.

The 3HP regimen has been shown to be safe and effective in adults and children aged 2-17 years, and can be administered by directly observed therapy (DOT) or self-administered therapy (SAT) 1. It is essential to follow the recommended treatment guidelines to ensure effective prevention of active TB disease and minimize the risk of hepatotoxicity and other adverse events.

From the FDA Drug Label

Although there have not been the same kinds of carefully conducted controlled trials of treatment of Extra pulmonary tuberculosis as for pulmonary disease, increasing clinical experience indicates that a 6 to 9 month short-course regimen is effective For Preventative Therapy of Tuberculosis Before isoniazid preventive therapy is initiated, bacteriologically positive or radiographically progressive tuberculosis must be excluded. In the treatment of tuberculosis, resistant organisms may multiply and the emergence of resistant organisms during the treatment may necessitate a change in the regimen

The diagnosis of Latent Tuberculosis (TB) is typically made by excluding bacteriologically positive or radiographically progressive tuberculosis. The treatment of Latent TB usually involves isoniazid preventive therapy for a sufficient period, typically 6 to 9 months, to prevent the development of active TB. Key considerations in the treatment of Latent TB include:

• Patient compliance: Directly Observed Therapy (DOT) is recommended to ensure patient compliance with drug therapy 2.
• Drug resistance: The emergence of resistant organisms during treatment may necessitate a change in the regimen 2.
• Pregnancy: The treatment regimen should be adjusted for pregnant patients, with isoniazid and rifampin as the initial treatment regimen 2.
• Drug interactions: Concomitant administration of pyridoxine (B6) is recommended in malnourished patients and those predisposed to neuropathy 2.

From the Research

Diagnosis of Latent Tuberculosis (TB)

• The diagnosis of latent tuberculosis infection (LTBI) is typically made using the tuberculin skin test (TST) or interferon-γ release assay (IGRA) 3
• These methods have limitations, and novel biomarkers such as transcriptome-derived host genes in peripheral blood cells are being explored to distinguish LTBI from active tuberculosis (ATB) 3
• Surveillance in high-risk groups, including patients with HIV infection, those using biological agents, organ transplant recipients, and those in close contact with ATB patients, is crucial for early detection and treatment of LTBI 3

Treatment of Latent Tuberculosis (TB)

• The currently recommended preferred regimen for LTBI treatment is 9 months of daily self-administered isoniazid (INH), which has an efficacy of more than 90% if completed properly 4
• However, INH is associated with serious adverse events, including hepatotoxicity, and close follow-up of patients is necessary to monitor for potential side effects 4
• Alternative regimens, such as 2 months of rifampin and pyrazinamide, 3-4 months of INH and rifampin, and 4 months of rifampin, have been studied and shown to have similar efficacy to 9 months of INH 4, 5
• Rifamycin-based regimens, such as once-weekly isoniazid and rifapentine for 3 months, have been successful in preventing progression to TB disease and have higher treatment completion rates compared to INH monotherapy 5, 6, 7
• Ultrashort treatment strategies, such as daily isoniazid plus rifapentine for 1 month, are being evaluated for LTBI treatment 7
• Treatment of LTBI in people likely infected with multidrug-resistant TB is limited, but fluoroquinolones appear to be effective in preventing TB disease 6