Latent tuberculosis infection (LTBI)

Background

• LTBI is defined as infection with Mycobacterium tuberculosis in the absence of clinical disease and is detected by the presence of an immune response to M. tuberculosis antigens.
• About one-quarter of the world's population has LTBI.
• 8 high-burden countries account for 2/3 of active TB cases in the world: India, China, Indonesia, Philippines, Pakistan, Nigeria, Bangladesh, and South Africa
• Populations at an increased risk for acquiring M. tuberculosis infection include:
  • close contacts of persons with known active pulmonary TB
  • infants, children, and adolescents exposed to adults at a higher risk for LTBI or active TB
  • persons born in areas or who visit areas with a high prevalence of TB
  • healthcare workers
  • residents or workers in congregate settings such as prisons or homeless shelters
  • the medically underserved, low-income populations, and persons who abuse alcohol or illicit drugs
• When untreated, in the absence of HIV infection, 5%-10% of patients with LTBI develop active TB over the course of their lifetimes.

Evaluation

• Testing for LTBI should be performed in at-risk populations.
• Options for testing include the tuberculin skin test (TST) and interferon-gamma release assays (IGRAs).
• TST assesses for a delayed hypersensitivity response to intradermally injected M. tuberculosis purified protein derivative and requires reading 48-72 hours after the injection.
• TST results are measured in millimeters of induration and interpretation varies with presence of comorbidities, radiographic findings, age, and epidemiologic risk factors (see chart).
• IGRAs measure blood levels of interferon or interferon-producing T cells induced by M. tuberculosis antigens.
• Use of IGRAs for testing is preferred in patients with a history of Bacille Calmette-Guérin (BCG) vaccination or when patients are unlikely to return to obtain TST results.
• For patients with a positive TST or IGRA, exclude active tuberculosis by a review of symptoms and a chest x-ray.

Management

• Preferred regimens for management of LTBI differ between professional organizations.
  • The CDC has issued guidance regarding use of rifampin and rifapentine for treatment of active and latent TB infection after some manufacturers detect nitrosamine impurities in their products.
  • WHO 2018 recommendations:
    • Isoniazid monotherapy for 6 months is the recommended therapy for adults and children.
    • Alternative regimens include:
      • rifampicin (rifampin) monotherapy for 3-4 months may be offered as alternative in countries with low TB incidence.
      • isoniazid plus rifapentine weekly for 3 months may be considered as alternative in countries with high TB incidence.
      • isoniazid plus rifampicin (rifampin) daily for 3 months is alternative for children and adolescents aged < 15 years in countries with high TB incidence.
  • NTCA/CDC 2020 recommendations
    • Preferred regimens include:
      • isoniazid plus rifapentine once weekly for 3 months recommended for adults and children aged ≥ 2 years, including persons with HIV if drug interactions allow.
      • rifampin (rifampicin) monotherapy daily for 4 months recommended for adults and children without HIV.
      • consider isoniazid plus rifampin (rifampicin) daily for 3 months in adults and children without HIV and persons with HIV if drug interactions allow.
    • Isoniazid monotherapy for 6 or 9 months are alternative regimens in adults and children who are unable to take a preferred regimen due to drug intolerability or drug-drug interactions.
• Dosing for all recommended regimens:
  • Isoniazid monotherapy
    • Adults 5 mg/kg/day.
    • Children 10 mg/kg/day (WHO) or 10-20 mg/kg/day (NTCA/CDC) (maximum 300 mg/day) orally once daily.
    • Vitamin B6 (pyridoxine) should be given with isoniazid to patients at risk for neuropathy and those who are pregnant or breast feeding (typical prophylaxis dose is 25-50 mg/day orally)
  • Isoniazid plus rifapentine orally once weekly
    • For adults and children > 12 years of age:
      • Isoniazid 15 mg/kg (maximum 900 mg)
      • Rifapentine according to weight-based dosing
        • 300 mg for patients 10-14 kg
        • 450 mg for patients 14.1-25 kg
        • 600 mg for patients 25.1-32 kg
        • 750 mg for patients 32.1-49.9 kg
        • 900 mg for patients ≥ 50 kg
    • For children 2-11 years of age:
      • Isoniazid 25 mg/kg (maximum 900 mg)
      • Rifapentine weight-based dosing same as above
  • Rifampin (rifampicin) monotherapy in adults 10 mg/kg/day and children 15 mg/kg/day (WHO) or 15-20 mg/kg/day (NTCA/CDC) (maximum 600 mg/day).
  • Isoniazid plus rifampin
    • Isoniazid in adults 5 mg/kg/day and children 10 mg/kg/day (WHO) or 10-20 mg/kg/day (NTCA/CDC) (maximum 300 mg/day)
    • Rifampin in adults 10 mg/kg/day and children 15 mg/kg/day (WHO) or 15-20 mg/kg/day (NTCA/CDC) (maximum 600 mg/day)
• Treatment for patients with known exposure to multidrug-resistant TB (MDR-TB) should be determined by the resistance pattern identified in the source case and managed by a specialist.
• Most regimens are associated with hepatotoxicity; liver function testing is not recommended routinely but should be monitored in patients with chronic liver disease, HIV infection, those who use alcohol regularly, and during pregnancy and postpartum.