TB - Tuberculosis

Original article by Tom Leach and Lily Stanley | Last updated on 3/5/2015
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Organism

Mycobacterium tuberculosis
 

Transmission

Via droplet spread - only the pulmonary form is infectious
Usually needs sustained close contact with an infectious case.
 

Epidemiology

  • Roughly one third of the world's population has been infected with M. tuberculosis (2 billion people)
  • Nearly nine million new cases of TB, and 1.4 million deaths from TB per year (majority in developing countries)
  • Leading cause of death due to a curable infectious disease
  • Significant number cases occur in those co-infected with HIV.
  • Approximately 9000 cases reported each year in the United Kingdom (mostly in large cities, especially in London), causing 350 deaths each year
  • Around 10% of cases are drug resistant
  • Incidence is increasing in developing countries, due to increased drug resistance, HIV and an ageing population

 

Risk factors

  • HIV (13% cases also have HIV)
  • Overcrowding/close contact with active case (1/3 chance of contracting from household member)
  • Ethnic minority groups
  • Malnutrition
  • IV drug use
  • Chronic lung disease
  • Immunosuppression

Pathogenesis

  • Mycobacteria reach the pulmonary alveoli
  • These are engulfed by alveolar macrophages and replicated within them.
  • These carry the bacteria to hilar lymph nodes to try and control the infection.

Primary site of infection (in the lungs) = "Ghon focus" (generally in upper lobe)

  • Lymphocytes surround the infected macrophages along with fibrolasts and this causes granuloma formation
  • This prevents dissemination of bacteria (prevents extra-pulmonary TB)
  • Inside these lesions, the bacteria may develop abnormal cell death in the centre (caseous necrosis) and can eliminate the bacteria
  • In some instances infection can be cleared, or can become dormantlatent infection
  • It can then later become reactivated (secondary TB), precipitated by acquired impaired immune function.

Alternatively, if there is a failure of the above mechanism...
The bacteria may gain entry to the bloodstream can spread throughout the body and set up many foci of infection (tubercles) (e.g. miliary TB).This is extra-pulmonary TB

  • Those with less effective immune systems progress to primary progressive tuberculosis
  • For less immunocompetent people, granulomas are formed but then the necrotic tissue undergoes liquefaction and the fibrous wall breaks down. Necrotic material then
    • Drains into bronchi and is coughed up and can infect others
    • Drains into nearby blood vessels and seeds to other areas leading to extrapulmonary TB

 

Clinical features

  • 90% of cases exhibit pulmonary features only
  • 10% exhibit extrapulmonary features

Complications

Multi-drug resistant TB (MDR-TB)- can develop of TB is not properly treated.

Diagnosis

Active TB

  • CXR
  • Samples e.g. sputumpus, or a tissue biopsy:
    • 3 separate sputum samples in pulmonary TB (including one early morning sample)
    • Can do broncoscopy and lavage or gastric washings
    • Ziehl-Neelsen (ZN) stain - rapid direct microscopy for acid-fast bacilli
    • Löwenstein-Jensen culture (takes 4-8 weeks due to slow bacterial growth and sensitivities take a 3-4 weeks more)

*treatment should be started before culture results are back, and continued even if cultures are negative*
 

Latent tuberculosis

Mantoux tuberculin skin test-used to screen people at high risk for TB

Treatment

Antibiotics

For more infor see 'extra info' section below

 

Prevention

  • Vaccination (BCG)
  • Public health measures: treatment/prophylaxis of contacts etc
  • Notifiable disease in UK
 

Extra Info

Drugs used in TB

Rifamycins
Inhibits DNA transcription
Rifamycin, rifabutin
Cidal
Nausea, anorexia, pseudomembranous colitis, hepatotoxicity, orange colouration of excreted bodily fluids, toxicity syndromes, drug interactions
Also used in mycobacterial infections – these most commonly occur in those with HIV. Resistance prevents more widespread use
Widespread – develops rapidly
Y
?
?
?
Isoniazid
Inhibits synthesis of cell wall
Isoniazid
Cidal / static
Nausea, vomiting, constipation, peripheral neuropathy, hepatitis, SLE-like-symptoms
Bactericidal on dividing organisms, static on resting. Only effective against myobacteria
Occurs rapidly if used alone
N
N
N
?
Pyrazinamide
Lowers intracellular pH, disrupting synthesis of fatty acids
pyrazinamide
Cidal
Hepatotoxicity, nausea, vomiting, arthralgia, sideroblastic anaemia
Only effective against myobacteria
Occurs rapidly if used alone
N
N
N
?
Ethambutol
Interferes with cell wall synthesis
Ethambutol
Static
Optic neuritis – resulting in red/green colourblindness. neuritis
Only effective against myobacteria
Uncommon
N
N
N
 
 

Myobacteria

This is its own genus of bacteria (like G+ or G-). The group include TB and leprosy. They are acid fast. They are also aerobic.
 
Acid fast
This basically means the organisms are difficult to stain using normal staining techniques. The name refers to the fact they can’t be stained by normal acid (ethanol) staining techniques. These bacteria are often particularly difficult to culture and identify; e.g. TB takes around 6-8 weeks