II. Epidemiology

  1. Concurrent HIV Infection confers a 10% conversion to Active Tuberculosis per year (highest rate)
  2. Overall rate of progression from Latent Tuberculosis to Active Tuberculosis: 5-15%
    1. Latent Tuberculosis progression is responsible for >80% of Active Tuberculosis cases in the United States
    2. Half of latent to Active Tuberculosis progressions occur within the first 2 years following infection
      1. Progression within 2 years in otherwise healthy patient (e.g. non-HIV): 5%
      2. Progression after 2 years in otherwise healthy patient (e.g. non-HIV): 5%

III. Precautions

  1. Latent Tuberculosis is a lab diagnosis based on positive Screening Tests (IGRA, PPD)
    1. Latent Tuberculosis patients are asymptomatic
  2. Active Tuberculosis patients are symptomatic (cough, Hemoptysis, Night Sweats, weight loss)
    1. Active Tuberculosis patients are treated with multi-drug regimens to prevent resistance
    2. Do not treat Latent Tuberculosis patients with single agent until Active Tb is excluded by history
  3. Latent Tb management requires provider vigilence
    1. Educate and monitor compliance (important to complete course)
    2. Be alert for hepatotoxicity (Isoniazid, rifamycins) and limit Alcohol and other Hepatotoxins
    3. Observe for Thrombocytopenia with rifamycins
    4. See specific agents for additional recommendations (e.g. Vitamin B6 and Isoniazid, Rifamycin Drug Interactions)

IV. Indications: Strongest Indications for Latent Tuberculosis Treatment

V. Contraindications: Latent Tuberculosis Treatment

  1. Age over 35 years (risk of hepatitis) is no longer an absolute contraindication
  2. Prophylaxis indications regardless of age
    1. Recent PPD conversion
    2. Chest XRay shows healed Tuberculosis (see Tuberculosis Related Chest XRay Changes)
    3. Immunocompromised patient (e.g. HIV)

VI. Protocols: First-Line Short Courses

  1. Background
    1. Short courses for 3-4 months are preferred for Latent Tuberculosis management over traditional 6-9 month courses
      1. Similar efficacy as with Isoniazid 6-9 month monotherapy course
      2. Higher compliance and completion rates compared with longer courses
      3. Less hepatotoxicity compared with longer courses
  2. Isoniazid and Rifapentine for 3 months (3HP)
    1. Indications
      1. Preferred regimen for adults and children >2 years
      2. Also preferred in HIV positive patients (unless Rifampin Drug Interactions prohibit)
      3. Rifapentine has multiple Drug Interactions but less than with Rifampin
      4. Requires observed therapy (patient must come to clinic weekly for administered dose)
    2. Combination of both Isoniazid (INH) and Rifapentine both weekly for 12 weeks
      1. Each dose must be physician observed (due to risk of drug resistant Tuberculosis if stopped early)
    3. Protocol (Age >=2 years)
      1. Isoniazid (INH) 15 mg/kg (25 mg/kg if age 2-11 years) up to 900 mg weekly for 12 weeks AND
      2. Rifapentine (Priftin) weekly for 12 weeks
        1. Weight 10 to 14 kg: Rifapentine 300 mg weekly
        2. Weight 14.1 to 25 kg: Rifapentine 450 mg weekly
        3. Weight 2.5.1 32 kg: Rifapentine 600 mg weekly
        4. Weight 32.1 to 49.9 kg: Rifapentine 750 mg weekly
        5. Weight >50 kg (and adults): Rifapentine 900 mg weekly
    4. Efficacy: 90% effective
      1. As effective and safe as other Latent Tb regimens with significantly higher completion rates
        1. Njie (2018) Am J Prev Med 55(2):244-252 +PMID: 29910114 [PubMed]
    5. References
      1. Sterling (2011) N Engl J Med 365:2155-2166 [PubMed]
  3. Rifampin for 4 months (4R)
    1. Indications
      1. Short course self-administered monotherapy
      2. Cost may be prohibitive - very expensive (10-20 times the cost of Isoniazid)
    2. Contraindications
      1. Do not use as monotherapy in HIV Infection
      2. Review Drug Interactions before use (multiple rifampin Drug Interactions, but less with Rifabutin)
    3. Allows for shorter course and lower hepatotoxicity risk
    4. Rifampin Routine Dosing (intermittent dosing not recommended when used alone)
      1. Adults 10 mg/kg up to 600 mg orally daily for 4 months
      2. Child 10-20 mg/kg/day (max 600 mg/day) for 4 months
    5. Efficacy: 60% effective
      1. Not inferior to Isoniazid for 9 months, and better completion rates with less adverse effects
        1. Menzies (2018) N Engl J Med 379(5):440-53 +PMID: 30067931 [PubMed]
  4. Isoniazid and Rifampin for 3 months (3HR)
    1. Indications
      1. Adults and children of all ages including HIV positive patients
    2. Contraindications
      1. Rifampin Drug Interactions
    3. Protocol: Taken daily for 3 months
      1. Isoniazid (INH) 5 mg/kg in adults (10-20 mg/kg in children) up to 300 mg daily AND
      2. Rifampin 10 mg/kg in adults (15-20 mg/kg in children) up to 600 mg daily

VII. Protocols: Latent Tuberculosis Long Course Treatment

  1. See Isoniazid for specific precautions and Vitamin B6 supplementation guidelines
  2. Typical long course: 9 months (unless otherwise noted - see below)
  3. Course of 9 months is now also recommended in cases previously treated for 12 months
    1. Human Immunodeficiency Virus (HIV)
    2. Immunosuppression
    3. Chest XRay showing healed Tuberculosis (e.g. apical fibronodular changes)
  4. Protocol
    1. Duration
      1. Standard therapy: 9 months (90% effective)
      2. Shorter course: 6 months (60-80% effective, but better compliance)
    2. Isoniazid Routine Dosing
      1. Adults 5 mg/kg up to 300 mg orally daily
      2. Child 10-20 mg/kg/day (max 300 mg/day)
    3. Isoniazid Alternative Dosing
      1. Adult: 15 mg/kg up to 900 mg twice weekly supervised
      2. Child: 20-40 mg/kg twice weekly (maximum 900 mg) supervised

VIII. Protocols: Resistant Exposures

  1. Isoniazid Resistant Tuberculosis Exposure
    1. Rifampin 600 mg qd
    2. Ethambutol for 6-12 months
  2. Multi-drug resistant Tb Exposure:
    1. Pyrazinamide 25-30 mg/kg/day and
    2. Ethambutol 15-25mg/kg/day and
    3. Fluoroquinolones
      1. Ofloxacin 400mg bid or
      2. Ciprofloxacin 750 mg bid

IX. Protocols: Discontinued - Rifampin and Pyrazinamide

  1. No longer recommended for Latent Tuberculosis Treatment due to hepatotoxicity
  2. Details listed for historical purposes only
    1. Rifampin 600 mg qd for 2 months
    2. Pyrazinamide 25mg/kg qd for 2 months
  3. Higher risk of hepatotoxicity than with 6 months INH
    1. Observe serial Liver Function Tests closely
    2. Jasmer (2002) Ann Intern Med 137:640-7 [PubMed]

X. Monitoring

  1. See Isoniazid for toxicity related to Neuropathy and Hepatotoxicity
  2. See Rifampin regarding Drug Interactions

XI. Resources

  1. Treatment Regimens for Latent Tuberculosis or LTBI (CDC)
    1. https://www.cdc.gov/tb/topic/treatment/ltbi.htm

XII. References

  1. Orman, Moran and Swaminathan in Herbert (2016) EM:Rap 16(11): 2-3
  2. Hartman-Adams (2014) Am Fam Physician 89(11): 889-96 [PubMed]

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Related Studies

Ontology: Latent Tuberculosis (C1609538)

Definition (MSH) The dormant form of TUBERCULOSIS where the person shows no obvious symptoms and no sign of the causative agent (Mycobacterium tuberculosis) in the SPUTUM despite being positive for tuberculosis infection skin test.
Concepts Disease or Syndrome (T047)
MSH D055985
English Latent tuberculosis, latent tuberculosis, latent tuberculosis (diagnosis), latent TB, Infection, Latent Tuberculosis, Latent Tuberculosis Infections, Tuberculoses, Latent, Latent Tuberculosis Infection, Tuberculosis Infection, Latent, Latent Tuberculosis, Infections, Latent Tuberculosis, Latent Tuberculoses, Tuberculosis Infections, Latent, Tuberculosis, Latent, Latent Tuberculosis [Disease/Finding]
Dutch latente tuberculose
Portuguese Tuberculose latente, Tuberculose Latente, Infecção Tuberculosa Latente
Spanish Tuberculosis latente, Infección Tuberculosa Latente, Tuberculosis Latente
Japanese センプクケッカク, 潜伏結核, 潜在性結核感染, 結核症-潜伏, 結核-潜伏, 潜伏結核症
Czech Latentní tuberkulóza, latentní tuberkulóza
French Infection tuberculeuse latente, Tuberculose latente
German Latente Tuberkulose-Infektion, Latente Tuberkuloseinfektion, Latente Tuberkulose
Italian Infezione tubercolare latente, Tubercolosi latente
Russian ЛАТЕНТНАЯ ТУБЕРКУЛЕЗНАЯ ИНФЕКЦИЯ, ЛАТЕНТНЫЙ ТУБЕРКУЛЕЗ, SKRYTAIA FORMA TUBERKULEZA, LATENTNYI TUBERKULEZ, СКРЫТАЯ ФОРМА ТУБЕРКУЛЕЗА, TUBERKULEZ LATENTNYI, ТУБЕРКУЛЕЗ ЛАТЕНТНЫЙ, LATENTNAIA TUBERKULEZNAIA INFEKTSIIA
Swedish Latent tuberkulos
Polish Gruźlica utajona
Hungarian latens tuberculosis
Norwegian Latent tuberkulose