Mycobacteria Flashcards

1
Q

What are five properties shared by all mycobacteria?

A
  1. Aerobic
  2. Non-spore forming
  3. Bacilli
  4. Grow slowly in culture (1-8 weeks)
  5. Cell walls contain long chain fatty acids
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2
Q

What are the 6 layers of the mycobacterial “cell wall”

A
  1. outer lipid
  2. Lipoarabinomannan
  3. Mycolic acid
  4. Polysaccharides
  5. Peptidoglycan
    6 Lipid bilayer
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3
Q

What are the 2 subdivisions used to group mycobateria?

A

Tuberculosis complex or non-tuberculosis (atypical) mycobacteria

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4
Q

What is the morphology of Mycobacterium tuberculosis?

A
  • thin/straight/curved rods
  • obligate aerobes
  • non spore-forming
  • single, pairs, or in masses
  • high lipid content in cell wall (60% mycolic acid)
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5
Q

What kinds of staining can/can’t be used on M. tuberculosis?

A
  • Not stained by gram staining

- Stains with Ziehl-Neelsen or Kinyoun Staining

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6
Q

What does acid fast bacilli mean? how does the staining work?

A

Once stained with red dye, resist de -colorizationwith 3% HCl in alcohol

appear red against a blue background

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7
Q

What is the generation time for M. tuberculosis?

A

18-20 hours so very long

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8
Q

What kind of lesions are formed by M. tuberculosis when there are large numbers of organisms?

A

Cavitary lesions

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9
Q

How do drug resistant strains of M. tuberculosis arise? Why?

A

spontaneous chromosomal mutations at a predictable low frequency

M. tuberculosis does not interact/exchange genetic material with other bacteria

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10
Q

What two factors contribute to the selection pressure on drug resistant strains of M. tuberculosis?

A

misuse of antituberculosis drugs, such as monotherapy or the addition of single drugs to failing regimens

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11
Q

In Canada, which groups of the population have the highest instances of TB?

A

Aboriginal and foreign born populations

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12
Q

Which province/territory has the highest rates of TB?

A

Nunavut

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13
Q

What is the source of infection typically for M. tuberculosis?

A

other infected humans

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14
Q

What is the ghon focus?

A

the granuloma formed at the primary infection site

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15
Q

What is milary TB? when does it occur?

A

Occurs when infective foci in the lungs seed or rupture into one of the branches of the pulmonary venous return to the heart
- widespread hematogenous dissemination of bacteria to most organs of the body.

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16
Q

What organs tend to be affected by millary TB?

A

liver, bone marrow, spleen, adrenals, meninges, kidneys, fallopian tubes and epidydymis

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17
Q

What kind of endo/exotoxins does M. tuberculosis produce?

A

none!

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18
Q

What is a physical adaptation that virulent strains of M. tuberculosis demonstrate?

A

Cording - parallel bundles of organisms intertwined

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19
Q

What 3 things are responsible for the virulence of M. tuberculosis?

A
  1. survival and multiplication in macrophages
  2. Delayed hypersensitivity reaction to tuberculo proteins
  3. Cell wall lipids that produce granulomatous lesions
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20
Q

What is Pott’s Disease?

A

Extra-pulmonary TB infection of the bones, joints, and neurons

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21
Q

For the tuberculin skin test, where do you need to inject the tuberculin protein? When do you read it?

A

into the dermis of the skin

read after 48-72 hours

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22
Q

What is the tuberculin skin test for?

A

used to determine previous exposure to Tuberculo-protein

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23
Q

What are the criteria for a positive vs. negative tuberculin skin test?

A

positive: induration of =/> 10 mm OR 5 mm in certain circumstances
- ex: HIV patients, people who have been exposed to infectious TB in the past 2 years, patients displaying fibronodular disease on x-ray

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24
Q

What does a positive tuberculin test tell you?

A

that they have been exposed to M. tuberculosis at some point in their life

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25
Q

What two factors can generate false positive tuberculin tests?

A
  1. Previous vaccination with BCG

2. Infection with a strongly cross-reacting non-tuberculosis mycobacteria

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26
Q

What 4 factors can generate false negative tuberculin tests?

A
  1. very recent TB infection (will only turn positive after about 4-6 weeks)
  2. Overwhelming (ie. Millary TB) infection
  3. Immunosuppression or anergy
  4. Incorrect administration of test
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27
Q

What is another method (besides the tuberculin test) to diagnose latent TB?

A

Interferon Gamma Release Assays (IGRAS)

28
Q

How do IGRAS work?

A

measure T cell release of interferon gamma following stimulation by antigens specific to Mycobacterium tuberculosis
- measuring the cell mediated immune response

29
Q

What are some benefits of IGRAS > tuberculin test? A downside?

A
  1. IGRAS will crossreact with fewer non TB mycobacteria
  2. Only need 1 visit
  3. Not affected by the BCG vaccine
  4. similar sensitivity between the two

problem: more expensive

30
Q

What kind of testing (4) is done to diagnose active TB? What are the requirements?

A
  1. Microscopic examination of sputum that has been acid fast stained
    - need at least 3 specimens collected 1 hr apart
  2. Do PCR on smear positive specimens
  3. Chest radiograph
  4. Culture
31
Q

What are some symptoms of active TB?

A

Weight loss, night sweats, fever, chills, active productive cough

32
Q

What is the % sensitivity for chest radiographs as a method of diagnosing active TB? What are they useful for?

A

about 70-80 % but only if done with other testing methods

useful for evaluating symptoms and treatment

33
Q

What is the most sensitive and specific method of testing for active TB?

A

Culture

34
Q

Clinical and radiographic findings are ____ in diagnosis

A

non-confirmatory

35
Q

How sensitive is AFB staining of sputum samples/microscopy?

A

about 60%

36
Q

What two treatments need to be performed on Mycobacteria detected in direct smears (if they have been contaminated by normal flora)

A
  1. Decontaminating agent (NaOH)

2. Mucolytic agents also used for sputum specimens to dissolve mucus (N-acetyl L- cysteine)

37
Q

What 5 forms of samples can you obtain to test for pulmonary TB?

A
  1. At least 3 sputum specimens
  2. Bronchial washings after bronchoscopy
  3. Bronchoalveolar lavage (BAL)
  4. Gastric aspirates (especially in children)
  5. Pleural fluid in Pleural Effusion
38
Q

What kind of samples do you need to obtain for extrapulmonary TB? What are 3 examples?

A

Often need to be biopsies

  • Liver and bone marrow biopsy in disseminated TB
  • CSF in meningitis
  • Urinary tract disease: First-void morning urine for 3-6 days
39
Q

What is different between the culture protocol for sputum vs CSF ?

A

Sterile body fluids (e.g. CSF, pleural fluid) and tissue cultured directly while sputum & urine treated prior to culture
- treatment: digestion and decontamination

40
Q

What is the difference between solid and liquid media for the culture of TB?

A

Liquid media: quicker growth and more sensitive but more prone to contaminants
- tend to use one of each media types

41
Q

What 3 methods are used to determine growth of M. tuberculosis in culture?

A
  1. Colonial morphology, pigment, growth rate
  2. Biochemical tests: e.g. M. tuberculosis produce niacin and others do not
  3. Molecular methods
42
Q

What are the 4 first line drugs used to treat TB? Which two are the most active and important? WhY? which one is bacteriostatic

A
  1. Isoniazid
  2. Rifampicin
    - these are the most active/important
    - bactericidal
    - effective intra and extracellularly
  3. Pyrazinamide
    - bactericidal
    - active at acid pH within cells
  4. Ethambutol
    - bacteriostatic
43
Q

How long do you treat someone with the first line treatment of drugs for TB?

A

Treat with all 4 drugs for 2 months and then drop it down to just Isoniazid and Rifampicin for the remaining 4 months

44
Q

When are patients non-infectious?

A

after about 2 -3 of chemo

45
Q

When are second line drugs added?

A

added to combination if resistance or toxicity contraindicate first line drugs

46
Q

What are some examples of second line drugs?

A
Para-Aminosalicylic acid (PAS)
Streptomycin
Ethionamide
Cycloserine F
Fluoroquinolones
Kanamycin, ect    
.....
47
Q

What 4 factors are responsible for the long treatment time for TB?

A
  1. Long doubling time of tubercle bacilli (12-24 h)
  2. Intra-phagocytic survival and multiplication.
  3. Metabolically inactive bacilli are not killed by drugs
  4. Caseous material interferes with drug action
48
Q

What are mono and poly resistant TB defined as?

A

Mono-resistant: Resistance to a single drug

Poly-resistant: Resistance to more than one drug, but not the combination of isoniazid and rifampicin

49
Q

What is MDR TB? XDR TB?

A

Multidrug-resistant (MDR): Resistance to at least isoniazid and rifampicin

Extensively drug-resistant (XDR): MDR plus resistance to fluoroquinolones and at least 1 of the 3 injectable drugs (amikacin, kanamycin, capreomycin

50
Q

Where are atypical mycobacteria (NTM) usually acquired from?

A

the environment

51
Q

What is the distribution of atypical mycobacteria?

A

worldwide

52
Q

What is the instance of case to case transmission for NTM?

A

no evidence of it occurring

53
Q

What kind of media do NTM grow on? how do they grow compared to TB?

A

grow on the same media just more quickly

54
Q

What are 4 traits of NTM that differentiate them from TB?

A
  1. Colonial morphology
  2. Niacin test – negative
  3. Relatively more resistant to anti-TB drugs
  4. Diseases typically less invasive
55
Q

what is the pathogen responsible for leprosy/Hansen’s disease?

A

Mycobacterium leprae

56
Q

Most new cases of leprosy originate where?

A

India, Brazil and Indonesia

57
Q

What are three characteristics of M. leprae?

A

long incubation period (usually 5, up to 20 years)
won’t grow on artificial culture media
low virulence/pathogenicity

58
Q

Shedding of M. leprae from which part of the body is important in transmission?

A

shedding from the nose

59
Q

What is the range of presentation for M. leprae?

A

discolored patches of skin, growths (nodules) on the skin, painless ulcers, painless swellings, skin numbness

60
Q

The severity of leprosy lesions depends on..?

A

the cell mediated immune response mounted by the person

61
Q

A good CMI response to M. leprae will usually result in?

A

Lesions that have numerous lymphocytes with few organisms in them - “Tuberculoid leprosy”.

62
Q

A poor CMI response to M. leprae will usually result in?

A

Lesions that have numerous bacilli in them - “Lepromatous leprosy”.

63
Q

An intermediate CMI response to M. leprae will usually result in?

A

between tuberculoid and lepromatous - called borderline leprosy

64
Q

What is another name for tuberculoid leprosy? what do the lesions typically look like?

A

aka. Paucibacilary
Few skin lesions
peripheral nerve involvement/thickening (sensory>motor)

65
Q

What is another name for lepromatous leprosy? what do the lesions typically look like?

A

aka. Multibacilary
Multiple lesions, symmetrical
Less nerve involvement

66
Q

How do you test for M. leprae? what kind of specimens do you obtain?

A

Skin biopsy snips from ear lobe
AFB (Fite), PCR…does not grow in artificial culture
- special acid fast stain with a weaker decolourizer and PCR

67
Q

How do you treat M. leprae? what determines the length of treatment? (3 drugs)

A

Duration depends on severity (Paucibacillary X 12m, Multibacillary X 24 m)

Dapson, Rifampin, Clofazimin