Mycobacteria (TB and Leprosy) Flashcards

1
Q

Describe the 4 species of mycobacteria and their diseases

A
  1. M. tuberculosis - tuberculosis in humans
    • Often called “TB” for tubercle bacilli
      • Bacilli = shape
      • Tubercle = lesions they cause in the lungs
  2. M. bovis - tuberculosis in cows
    • We can get infected by consuming unpasteurised milk from infected cow
    • Important for vaccine for tuberculosis (BCG)
  3. M. avium - tuberculosis-like illness in humans, particularly AIDS patients (functioning T cells = usually not a problem)
  4. M. leprae - leprosy in humans
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2
Q

What does it mean for TB to be latent or active?

How many people have latent?

A
  • Infection is latent (immune response present but asymptomatic) or active (infection symptoms)
  • 2 billion people have latent TB –> 10% with latent develop active
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3
Q

Describe Mycobacterium tuberculosis

Is it Gram negative or positive?

A
  • Intracellular pathogen, lives in macrophages
  • Slow generation time, level 3
  • It is impermeable to stains and dyes due to the mycolic acid layer (hydrophobic layer)
    • Tree of life = Gram positive
    • Acid fast
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4
Q

Describe the cell envelope of mycobacteria

What properties does it incur?

A
  • Has mycolic acid (wax layer) link to the cell wall by the arabinoglycan structure
  • Incurs 4 properties:
    1. Resistance to ABx; cannot penetrate envelope
    2. Resistance to acids and bases in phag
    3. Resistance to osmotic lysis (influx fluid) from complement deposition
    4. Resistant to oxidative stress - key for phag survival
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5
Q

Describe the acid fast stain test

A
  1. Stain sample on slide with carbol-fuchsin dye
    • Melts max layer
  2. Wash with EtOH, HCl
    • Dye can now penetrate
  3. Counter stain with methylene blue
    • Acid fast = red
    • Non-acid fast = blue
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6
Q

Describe stage 1 of tuberculosis

A
  • Inhalation of organisms into lungs (via droplet nuclei - 1 droplet contains 3 bacteria); does this to be immediately take up by lung macrophages
    • 1 bacteria = TB!
    • Droplets stay airborne
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7
Q

Describe stage 2 of tuberculosis

A
  • 7-21 days after exposure, TB inhibits fusion of lysosome to phagosome, survives and mulitples within (key virulence factor)
  • TB lyses macrophages, escape and infect more
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8
Q

Describe stage 3 of tuberculosis

A
  • Infected macrophages become surrounded by lymphocytes and form granulomas (tubercles)
    • T cells activate macrophages by secreting IFN-gamma, but it is hard to activate ones in the centre
  • Latent infection - TB can’t escape but can’t be killed
  • Chronic inflammation = cheesy nodules in lungs
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9
Q

Describe stage 4 of tuberculosis

A
  • Granuloma grows
  • At some point, tubercle erodes into airways –> transmission
  • Deterioration of host immunity (breakdown in T) –> active tuberculosis
    • Ex., HIV/AIDS, age, undernourishment, etc.
  • Caseous center liquefies = cavities in lung
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10
Q

Describe the 2 types of tuberculosis

A
  1. Pulmonary (most cases)
    • Progressive, irreversible lung destruction
    • Bacteremia
  2. Extra pulmonary/miliary (immunocompromised individuals)
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11
Q

Describe the general symptoms of TB

A
  • >2 weeks cough with thick/bloody mucus
  • Flu like symptoms
  • Chest pain, shortness of breath, weight loss (consumption). pallor/pale skin (the white death)
  • Extra pulmonary symptoms vary depending on where TB has spread systemically
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12
Q

How is TB diagnosed?

A
  • PPD: purified protein derivate taken from M. tuberculosis is injected
    • Positive = red/swollen at 48 h indicating latent/active, BCG, previously treated but still have T response
    • Negative = not infected, immunocompromised, not infected long enough
  • Chest x-ray looks for shadowing = lesions, granulomas
  • Staining of sputum (coughed mucous) for acid fast test, culturing
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13
Q

How is TB treated?

A

Active TB kills 2/3 people untreated

  • 6 months of antibiotics = short treatments
    • Slow growth = longer treatments
  • Cocktail to prevent complete resistance
    • Rifampin: inhibits RNA polymerase
    • Isoniazid: inhibits mycolic acid synthesis
      • others
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14
Q

Define the terms MDR, XDR, and TDR-TB

A
  • MDR-TB = multi-drug resistant: TB does not respond to first-line drugs (rifampin and isoniazid)
  • XDR-TB = extensively drug resistant: TB resistant to first and second line drugs used to treat MDR-TB
  • TDR-TB = total drug resistant: nothing can be done for treatment
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15
Q

What is the BCG (TB vaccine?)

A
  • “bacille Calmette-Guerin”; living vaccine prepared from attenuated M. bovis
  • It is controversial due to variable efficacy (how well it works - probably varies due to different strains) for pulmonary TB
  • Effective against miliary TB
  • Vaccine leaves scar and gives false positive for TB test
  • Recommended for individuals with high risk to exposure
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16
Q

What is leprosy (Hansen’s disease) caused by?

What are the symptoms?

Who is affected by it?

A
  • Mycrobacterium leprae
  • Incudbation of 5 years but less infectious than TB
  • Symptoms: damage to skin, nerves, limbs, eyes
  • Developing countries; 2 mil permanently disabled (low estimate due to stigma)
    • Stigma = rejected by family, friends; murdered
17
Q

Describe the tuberculoid form of leprosy (1 of 2 forms)

A
  • Occurs if cell-mediated immunity is good; macrophages kill bacteria
  • Lesions appear from nerve damage (anesthetic areas)
    • Bacteria not recovered from lesion
  • TB positive
  • Self limiting (immune system success)
18
Q

Describe the lepromatous form of leprosy (2 of 2 forms)

A
  • Occurs when cell-mediated immunity is absent; inactive macrophages
  • M. leprae survives, multiples in macrophages and Schwann cells = nerve damage, prone to serious injury (macrophages cause the damage)
  • Lion-like appearence
  • Lesions become secondarily infected = bone breakdown, disfigurements, mutilation
19
Q

Is it true that most incidents of M. leprae are cleared without incident?

A

Yes; most people clear, some get tuberculoid, others progress to lepromatous

20
Q

Describe the pathogen M. leprae

A
  • “Gram positive” (tree), acid fast, rod shaped, mycolic acid wax envelope
  • Can be grown in foot pads of mice or armadillo, not in vitro
21
Q

How is leprosy treated?

A
  • Leprosy is treatable with antibiotics
  • Multiple drugs must be used just like TB
    • Dapsone, rifampin, clofazime
    • 1 dose of this MDT (multidrug therapy) = not infectious anymore
22
Q

What is spectinamide?

A

A novel antibiotic with the potential to treat drug resistant tuberculosis infections