Tuberculosis Flashcards

1
Q

what is BCG

A

bacille calmette-Guerin

isolated from mycoplasma bovis

vaccine

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2
Q

what are diseases of importance that mycobacteria cause

A

tuberculosis - mycobacterium tuberculosis, mycobacterium bovis and leprosy (mycobacterium leprae)

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3
Q

what do mycobacteria cause

A

granulomatous lesions (tubercules) in tissues of a wide range of domestic and wild animals and humans

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4
Q

where does the mycobacteria survive and replicate in the host

A

macrophages of the host

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5
Q

is mycobacteria an anerobic or aerobe

A

aerobic

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6
Q

does mycobacteria form spores

A

non spore forming

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7
Q

is mycobacteria motile

A

non motile

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8
Q

is mycobacteria gram negative or positive

A

positive

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9
Q

what is the shape of mycobacteria

A

rods

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10
Q

how is mycobacteria stained

A

acid fast

bind phenol dyes (carbon fuchsin) and resist acid alcohol decolorization (ziehl neelsen stain)

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11
Q

is mycobacteria easy to grow

A

yes relatively simple

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12
Q

is mycobacteria rapid or slow growing

A

rapid (<7d) or slow growing (weeks or months)

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13
Q

what is unique about mycobacteria cell walls

A

lipid rich

acid fastness related to presence of peptidoglycan but particularly glycoplipids

lipids in cell wall related to pathogenicity (survival in phagolysome of macrophages, resists drying, extreme pH and other stresses)

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14
Q

what do the lipids in the cell wall of mycobacteria relate to

A

lipids in cell wall related to pathogenicity (survival in phagolysome of macrophages, resists drying, extreme pH and other stresses)

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15
Q

what are mycobacterium spp of clinical importance

A
  • Mycobacterium tuberculosis*
  • Mycobacterium bovis*
  • Mycobacterium avium subspecies paratuberculosis*
  • Mycobacterium avium complex* (including subspecies avium)
  • Mycobacterium leprae*
  • Mycobacterium lepraemurium, M. ulcerans, M. kansasii, M. fortuitum and M. chelonae*
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16
Q

what does Mycobacterium tuberculosis cause

A

TB in humans

Cats, dogs, chickens, pigs, parrots, canaries, guinea pigs, mice (cattle — rare)

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17
Q

what does Mycobacterium bovis cause

A

Bovine tuberculosis

TB in humans (badgers, deer) other ruminants, pigs and more rarely horses, dogs, cats, sheep

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18
Q

what does Mycobacterium avium subspecies paratuberculosis cause

A

Johne’s disease in cattle, sheep, goats, and deer (rarely other animals)

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19
Q

what does Mycobacterium avium complex (including subspecies avium) cause

A

TB in birds, poultry very susceptible

Pigs susceptible but not cattle

Sporadic cases in horses, dogs and cats

Opportunist in humans (AIDS — M. avium)

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20
Q

what does Mycobacterium leprae cause

A

Leprosy

Human, mice, armadillos

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21
Q

what does Mycobacterium lepraemurium, M. ulcerans, M. kansasii, M. fortuitum and M. chelonae cause

A

Skin ulceration and lymph node involvement in many different species

Chronic RTI

22
Q

what is shown here

A

mycobacteria in acid fast (ziehl neelsen) stain

23
Q

what do the mycolic acids do in the cell wall of mycobacteria

A

Resist phagocyte digestion

24
Q

what do the sulfatides in the mycobacteria cell wall do

A

Sulfatides

Prevent phagocyte activation and phagosome-lysosome fusion

25
Q

what do trehalose di-mycolate (Cord factor) do in the cell wlal of mycobacteria

A

Trehalose di-mycolate (cord factor)

Inhibits phagocyte chemotaxis, activation, phagosome-lysosome fusion and digestion

26
Q

what do the lipoarabinomannan (LAM) do in the cell wall of mycobacteria

A

Lipoarabinomannan (LAM)

Prevents phagocyte activation and digestion within the phagocyte

27
Q

what do the mycosides of the cell wall of mycobacteria do

A

Mycosides

Prevent intracellular killing and digestion

28
Q

what do the cell wall antigens of mycobacteria do

A

Cell wall antigens in general induce delayed type hypersensitivity (DTH)

29
Q

what determines the outcome of infection with mycobacteria (TB) in humans

A

the ability to mount an effective activated macrophage response

30
Q

what are the outcomes of a TB infection (4)

A
  1. Infects, killed by immune response, no disease
  2. Infects, lies dormant for many years, no disease (infection contained) (most common)
  3. Infects, lies dormant for many years, re-activates and causes acute disease
  4. Infects, causes rapid acute disease, may disseminate (children, immunocompromised, HIV)
31
Q

what is the immune response to mycobacterial infections

A

Antibody response irrelevant to protection

  • Th1 (CMI) required to limit the disease and provide protection

Immune status of host important

  • Active response results in lymphocyte infiltration, central necrosis in the lesion, tubercule many limited by a fibrin capsule

Response kay kill the bacteria but often is only able to restrict the disease

Reactivation occurs with stress/immunosuppression

IFN gamma from CD4 lymphocytes activates macrophages to all intracellular mycobacterial infected cells

CD1 restricted T cells recognize glycolipids

Exposure to environmental mycobacteria provides some cross-protection which may limit the disease caused by virulent species (also complicates skin testing)

32
Q

what are the outcomes of bovine tuberculosis infection

A
33
Q

how is bovine TB spread

A

Is promoted by high densities of animals and immune suppression

34
Q

what usually occurs after exposure in bovine TB

A

Leads to tubercules in the lungs and associated lymph nodes (bronchial and retropharyngeal)

35
Q

how does bovine TB spread throughout body

A

Spread to intestine (via sputum) and serosal surfaces

Pleural lesions

  • Pearls disease

Further disease spread (usually hematogenous) to liver, spleen, kidney, brain etc

36
Q

how is bovine TB treated

A

Antibiotic treatments are long term and very expensive

  • Tuberculin testing and culling of exposed animals
37
Q

what lesions are seen in PM of bovine TB

A

multifocal to coalescing caseous granulomas

38
Q

describe the epidemiology of bovine TB

A

Cattle transmit infection to cattle via infected respiratory droplets –> Resp route

Badgers transmit M. bovis between themselves by respiratory route and biting

Mums transmit to cubs

Cattle may get M. bovis from badgers via grazing on pasture contaminated with badger urine, feces and bronchial pus or badgers urinate and defecate in cattle feeders

Aerosol transmission via coughing may be possible or via dried badger saliva in cattle houses

This may apply to battle to badger transmission

39
Q

how is TB controlled by badger culling

A

Badger culling has significant impacts on the incidence of bTB in cattle

Culling of badger in define areas prevents infection on farms

Culling badgers in areas with no barriers makes survivors wander and spread infection further

Need vaccine for cows and wildlife

BCG works well in badgers both IM and orally

BCG in neonatal calves, adults?

40
Q

how well does the TB vaccine work in cattle

A

Will protect cattle against TB

The degree of protection varied considerably between studies

Neonatal or young calves can be protected at least as well as older calves

Systemic as well as mucosal (oral or endobronchial) delivery of BCG leads to protection

Its (or another better vaccine) use in cattle and other domestic animals will require the development of a diagnostic test that can be used alongside vaccination to differentiate vaccinated and infected cattle (DIVA test)

41
Q

what are the options of control of bovine TB

A

Culling — Ireland (with vaccination of badgers using BCG)

Culling — England (achieve certain percentage in high TB areas to decrease disease?

Vaccination of badgers — Wales

Badger vaccination across UK? — needles, baits?

Cattle vaccination

42
Q

how is mycobacterial infection diagnosed

A

Immunological detection

Microscopy

Culture

43
Q

how is mycobacteria diagnosed using immunological detection

A

Tuberculin testing using PPD (purified protein derivative) from the relevant bacterial species

PPD contains a mixture of proteins, carbohydrates, lipids and DNA

Gamma interferon assay

44
Q

how is mycobacteria diagnosed using lab

A

Microscopy

  • Ziehl Nielsen staining, rhodamine/auramine fluorescent stain) of appropriate specimens from site of infection

Culture

  • Lymph node, tissue lesions, sputum, aspirates, milk
  • Decontamination of specimens with sodium hydroxide
  • Lowenstein Jensen medium (slants) incubated for up to 8 weeks
  • ID by growth rate, colonial appearance, biochemical techniques, now increasingly molecular techniques (DNA probes, specific species primers for PCR)
45
Q

what is the intradermal test for bovine TB

A

The tuberculin test is carried out at 1, 2, 3, or 4 year intervals depending on the freq of TB in the area

Animal ID and two sites prepared on the side of neck

Inject PPD

Re-measure fold after 72 hours

If reaction to M. bovis PPD is 5mm greater than to M. avium then defined a reactor

If 1-4mm then retested within 40-60 days

Measure lymphocyte infiltration into site

If previous exposure increased TB specific lymphocytes in lesion hence increase in size

Rest of herd analyzed using ‘severe interpretation’ which is 3mm

46
Q

what infection does mycobacterium avium cause

A

non human primates, cattle and pigs infection is confined to the lymph node

causes disseminated disease in HIV/AIDs patients

47
Q

describe the pathogenesis of paratuberculosis (Johne’s disease)

A
48
Q

what is the gross pathology of John’es disease

A

thickened corrugated infection of ileum

49
Q

what does Mycobacterium leprae cause

A

Leprosy in humans and primates, cutaneous lesions and nerve damage

Irradiated mice foot pads, nine banded armadillos

Tuberculoid leprosy:

  • Little disfigurement
  • Few organisms in well-contained granulomatous lesions in tissue

Lepromatous leprosy:

  • Disfigurement, nodular swellings full of bacteria
  • Anesthesia
  • Shortening of toes and fingers in response to repeated unfelt trauma; spontaneous
50
Q

what does Mycobacterium lepraemurium: cause

A

Skin lesions (especially on head and tail) of cats and rodents

51
Q

what does Mycobacterium ulcerans: cause

A

Skin, nodules (skin granulomas) which can ulcerate

mainly humans

52
Q

what does Mycobacterium marinum cause

A

Fatal infections common in poikilotherms

Fish tank/swimming pool granuloma from humans