Tuberculosis

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Basics

Description

  • Active tuberculosis (TB)
    • Primary infection or reactivation of latent infection
    • Without preventive therapy, affects 10% of infected individuals
    • Risk increases with immunosuppression: highest risk first 2 years after infection. Reactivation risk increases with comorbid disease (e.g., HIV, diabetes).
    • Well-described forms: pulmonary (85% of cases), miliary (disseminated), meningeal, abdominal, lymphadenitis (scrofula)
  • Usually acquired by inhalation of airborne bacilli from an individual with active TB. Bacilli multiply in alveoli and spread via macrophages, lymphatics, and blood. Three possible outcomes:
    • Eradication: Tissue hypersensitivity halts infection within 10 weeks.
    • Primary TB
    • Latent TB (See “Tuberculosis, Latent (LTBI).”)

Pediatric Considerations

  • Children more commonly have severe disease, higher risk, and faster rate of progression to disease.
  • Most children with pulmonary TB are asymptomatic.
  • Pediatric TB treatment should be directly observed (directly observed therapy [DOT]) using four drugs.

Epidemiology

Incidence
  • Worldwide (2017): 10.4 million (133 cases per 100,000) population; highest incidence in Asia and Africa. Higher burden countries have approximately 150 cases/100,000 population
  • United States (2018): 9,093 (2.8/100,000); incidence in foreign-born 14 times that of U.S.-born persons. Incidence in the U.S. declined by 1.3% from 2017–2018. California, Florida, Texas, and New York account for half of all new TB cases in the US.

Prevalence
  • Worldwide (2016): Indirect estimates are uncertain due to variance in reporting systems. World Health Organization estimates 10 million new cases of TB in 2017.
  • Mortality
    • Worldwide (2017): 1.6 million deaths due to TB. Second leading infectious cause of death worldwide

Etiology and Pathophysiology

  • Mycobacterium tuberculosis, Mycobacterium bovis, or Mycobacterium africanum are causative organisms.
  • Spread by aerosol droplets (5–10 micron diameter) and reach alveolar space. Alveolar macrophages ingest and migrate.
  • Cell-mediated response by activated T lymphocytes and macrophages forms a granuloma (“tubercle”) that limits bacillary replication. If bacterial replication continues, the tubercle grows with spread to regional lymph nodes. An expanding tubercle within the lung parenchyma combined with regional lymph node enlargement is called a Ranke complex.
  • As the infection is contained, destruction of the macrophages produces early “solid necrosis.” In 2 to 3 weeks, “caseous necrosis” develops and LTBI ensues. In the immunocompetent, granuloma undergoes “fibrosis” and calcification. In the immunocompromised, primary progressive TB develops. Cavitary lesions may form. Necrotic lesions may rupture into bronchioles with resulting aerosolization of tuberculous bacilli.

Risk Factors

  • For infection: homeless, correctional facilities, close contact with infected person, ethnic minorities born in endemic areas of the world living in areas with high incidence of active TB, health care workers; medically underserved, low income, substance abuse
  • For development of disease once infected: chronic renal failure; lymphoma; silicosis; diabetes mellitus; cancer of head, neck, or lung; children <5 years of age; malnutrition; systemic corticosteroids; HIV; immunosuppressive drugs; IV drug abuse, alcohol abuse, cigarette smokers; <2 years since infection with M. tuberculosis; history of gastrectomy or jejunal bypass; <90% of ideal body weight

General Prevention

  • Screen for and treat LTBI. Report active TB to health department; test and treat all close contacts.
  • Bacillus Calmette-Guérin (BCG) vaccine: relatively ineffective in adults. In children, live attenuated M. bovis prevents 50% of pulmonary disease and 80% of meningitis and miliary disease. More commonly used in endemic countries. In the United States BCG is generally not recommended and very rarely used for high-risk children with negative PPD and ongoing exposure from parents or close contacts.

Commonly Associated Conditions

Immunosuppression; HIV coinfection; malignancy

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Basics

Description

  • Active tuberculosis (TB)
    • Primary infection or reactivation of latent infection
    • Without preventive therapy, affects 10% of infected individuals
    • Risk increases with immunosuppression: highest risk first 2 years after infection. Reactivation risk increases with comorbid disease (e.g., HIV, diabetes).
    • Well-described forms: pulmonary (85% of cases), miliary (disseminated), meningeal, abdominal, lymphadenitis (scrofula)
  • Usually acquired by inhalation of airborne bacilli from an individual with active TB. Bacilli multiply in alveoli and spread via macrophages, lymphatics, and blood. Three possible outcomes:
    • Eradication: Tissue hypersensitivity halts infection within 10 weeks.
    • Primary TB
    • Latent TB (See “Tuberculosis, Latent (LTBI).”)

Pediatric Considerations

  • Children more commonly have severe disease, higher risk, and faster rate of progression to disease.
  • Most children with pulmonary TB are asymptomatic.
  • Pediatric TB treatment should be directly observed (directly observed therapy [DOT]) using four drugs.

Epidemiology

Incidence
  • Worldwide (2017): 10.4 million (133 cases per 100,000) population; highest incidence in Asia and Africa. Higher burden countries have approximately 150 cases/100,000 population
  • United States (2018): 9,093 (2.8/100,000); incidence in foreign-born 14 times that of U.S.-born persons. Incidence in the U.S. declined by 1.3% from 2017–2018. California, Florida, Texas, and New York account for half of all new TB cases in the US.

Prevalence
  • Worldwide (2016): Indirect estimates are uncertain due to variance in reporting systems. World Health Organization estimates 10 million new cases of TB in 2017.
  • Mortality
    • Worldwide (2017): 1.6 million deaths due to TB. Second leading infectious cause of death worldwide

Etiology and Pathophysiology

  • Mycobacterium tuberculosis, Mycobacterium bovis, or Mycobacterium africanum are causative organisms.
  • Spread by aerosol droplets (5–10 micron diameter) and reach alveolar space. Alveolar macrophages ingest and migrate.
  • Cell-mediated response by activated T lymphocytes and macrophages forms a granuloma (“tubercle”) that limits bacillary replication. If bacterial replication continues, the tubercle grows with spread to regional lymph nodes. An expanding tubercle within the lung parenchyma combined with regional lymph node enlargement is called a Ranke complex.
  • As the infection is contained, destruction of the macrophages produces early “solid necrosis.” In 2 to 3 weeks, “caseous necrosis” develops and LTBI ensues. In the immunocompetent, granuloma undergoes “fibrosis” and calcification. In the immunocompromised, primary progressive TB develops. Cavitary lesions may form. Necrotic lesions may rupture into bronchioles with resulting aerosolization of tuberculous bacilli.

Risk Factors

  • For infection: homeless, correctional facilities, close contact with infected person, ethnic minorities born in endemic areas of the world living in areas with high incidence of active TB, health care workers; medically underserved, low income, substance abuse
  • For development of disease once infected: chronic renal failure; lymphoma; silicosis; diabetes mellitus; cancer of head, neck, or lung; children <5 years of age; malnutrition; systemic corticosteroids; HIV; immunosuppressive drugs; IV drug abuse, alcohol abuse, cigarette smokers; <2 years since infection with M. tuberculosis; history of gastrectomy or jejunal bypass; <90% of ideal body weight

General Prevention

  • Screen for and treat LTBI. Report active TB to health department; test and treat all close contacts.
  • Bacillus Calmette-Guérin (BCG) vaccine: relatively ineffective in adults. In children, live attenuated M. bovis prevents 50% of pulmonary disease and 80% of meningitis and miliary disease. More commonly used in endemic countries. In the United States BCG is generally not recommended and very rarely used for high-risk children with negative PPD and ongoing exposure from parents or close contacts.

Commonly Associated Conditions

Immunosuppression; HIV coinfection; malignancy

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