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Bacteriology and Mycology > Neurotoxigenic Clostridium > Flashcards

Neurotoxigenic Clostridium Flashcards

1
Q

What are the Gram Positive Spore Forming Anaerobes?

A
  • Clostridium
  • Clostridioides
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2
Q

What are the Gram Positive Nonspore-Forming Anaerobes?

A
  • Actinomyces
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3
Q

What are the characteristics of Clostridium?

A
  • Gram +
  • Spore Forming
  • Rod shaped
    • Except C. spiroforme
  • Motile
    • Except C. perfringens
  • Ferment CHO and Proteins
  • Fermentation products have a putrid odor
    • Butyric acid and Amines
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4
Q

What is the Habitat of Clostridium?

A

Ubiquitous in soil and alimentary tract of animals

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5
Q

How many species of Clostridium are there?

A
  • >150 species
  • ~20 cause diseases
  • 14 produce exotoxins (Alpha, Beta, Gamma, Delta, etc)
  • Size: 20 - 600 KDa
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6
Q

What is the mode of infection for Clostridium?

A
  • Ingestion with feed/water
  • Wound contamination
  • Non Contagious
  • Require Oxygen-free environments for growth
    • Ischemia due to tissue injury
    • Mixed infection with facultative organisms
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7
Q

What is Costridioides difficile?

A
  • Major human pathogen
    • also animal pathogen
  • Causes:
    • Humans = Pseudomembranous colitis
    • Animals = Enterocolitis
  • “C. diff infection” (CDI) or “C. diff associated diarrhea” (CDAD)
  • Based on 16 rRNA sequence analysis it is not a Clostridium
    • Named Clostridioides to retaine C. diff name
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8
Q

What are the Neurotoxifenic Clostridia?

A
  • C. tetani
  • C. Botulinum
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9
Q

What is Clostridium tetani?

A
  • Causative agent of tetanus
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10
Q

What is the mode of infection of Clostridium tetani?

A
  • Wound contamination:
    • Horses - nail wounds
    • Sheep/goats - Castration & docking
    • Calves - Umbilicus
    • Cattle - Castration, dehorning, nose ringing of bulls, after calving
  • Clinical signs after 1 - 3 weeks
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11
Q

What are the virulence factors of Clostridium tetani?

A
  • Tetanolysin​
  • Tetanospasmin
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12
Q

What is Tetanolysin?

A
  • hemolytic toxin
  • causes tissue necrosis
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13
Q

What is Tetanospasmin?

A
  • A potent neurotoxin
    • 0.00000002 mg is LD50 for a mouse
  • An AB toxin
  • One antigenic type worldwide
  • A protease plasmid-encoded protein (MW 150,000)
  • NEED TO WATCH LECTURE/REVIEW NOTES for rest of slide
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14
Q

What is the mechanism of action of Tetanospasmin?

A
  1. Binds to ganglioside receptors on nerve cells
  2. Moves by retrograde axonal transport to the cenral nervous system
  3. Blocks release of neurotranitters (GABA and glycine)
  • Results in spastic paralysis
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15
Q

What is the pathogenesis of Clostridium tetani?

A
  1. Enters wounds as spores or vegetative cells
  2. Spores germinate and organisms grow
  3. Produce toxin within 4-8 hours
  4. Toxin moves retrogradely along axon fibers to the spinal cord “Ascending tetanus”
    • Regional muscles show signs first “localized tetanus”
    • More common in dogs
  5. Toxin enters lymphatics and blood (toxemia)
  6. Affects motor nerve centers of face and neck, then limbs “Descending tetanus”
    • “Generalized tetanus
    • More common in horses, pigs, and humans
  7. Death due to respiratory failure
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16
Q

What is Idiopathic Tetanus?

A
  • No known cause
  • No visiblewounds
  • Ingestion of preformedtoxin or toxin is produced in the gut
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17
Q

What animals are susceptible to Clostridium tetani?

A
  • Horse - 1 (most susceptible)
  • Guinea Pig - 2
  • Human - 3
  • Mouse - 12
  • Rabbit - 24
  • Dog - 600
  • Cat - 7,200
  • Chicken - 360,000 (least susceptible)
  • Cattle > Buffaloes > Sheep > Goats > Pigs
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18
Q

What is the incubation period of Clostridium tetani?

A

1 - 3 weeks

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19
Q

What are the types of Tetanus?

A
  • Localized infection
    • More common in dogs & cats
  • Generalized infection
    • More common in horses, pigs and humans
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20
Q

What are the clinical signs of Tetanus?

A
  • Stiff gait, difficulty in walking
  • Prolapse of the third eyelid
  • Trismus (lockjaw); drooling of saliva
  • Stiffness of head, neck, ears, extremitis, and tail
  • Dehydration because of inability to drink
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21
Q

What are the clinical signs of Generalized Tetanus?

A
  • Regurgitation of food & water
    • pharyngeal and laryngeal spasms
  • Drooling
  • Exaggerated response to external stimuli
  • Opisthotonous
  • Risus sardonicus
  • Convulsions
22
Q

What is Opisthotonous?

A
23
Q

What is Risus Sardonicus?

A
24
Q

How do you diagnose Tetanus?

A
  • Based on clinical signs
  • History: Obvious sites of infection
  • Smears from the site of infection
  • PCR assay can be used to confirm with isolate or with wund materil
  • Toxin demonstration
25
Q

How is Tetanus Treated?

A
  • Wound debridement and topical antibiotic administration (Penicillin)
  • Tetanus antitoxin (to neutralize unbound toxin)
  • Sedation and muscle relaxation therapy
    • i.e.: acetylpromazine, xylazine
  • Keep animal in a dark quite place
26
Q

How do you prevent Tetanus?

A
  • Toxoid vaccine is effective
  • Immunity lasts for about a year
  • Horses vaccinated prior to surgery
  • Passive immunization at the time of castration, docking, and shearing on tetanus prone farms with tetanus antitoxin
  • Skin and instrument disinfection
27
Q

What are the caracteristics of Clostridium botulinum?

A
  • Gram - rods, subterminal spores
  • Cause of Botulism
28
Q

What is botulism?

A
  • a disease characterized by flaccid paralysis of skeletal muscles
  • Caused by botulinum toxin
    • Produced by:
      • C. botulinum
      • C. butyricum
      • C. barati
29
Q

What is the mode of infection for C. botulinum?

A
  • Ingestion of preformed toxin
  • Intoxication, not an infection
  • Production of toxin in the gut can also happen; toxico-infection
30
Q

What are the Virulence factors of C. botulinum?

A
  • Potent neruotoxin: Botulinum
    • ​Secreted as a complex of toxin and nontoxin units, called progenitor toxin
    • Nontoxic components include hemagglutinin (HA) and nontxic nonhemagglutinin (NTHA)
      • protects against digestive enzymes
    • May require activation by proteolytic enzymes
31
Q

What is Botulinum?

A
  • A-B toxin
  • Protein, MW 150,000
  • Bacteriophage encoded (in some types)
  • Principal site of action is at the myoneural junction
32
Q

What are the toxigenic types of Botulinum?

A
  • 7 groups:
    • A - G : differ in potency and antigenicity
    • A, B, E, and rarely F: Human Botulism
    • C, D: Animals
    • Mosaic toxin types: C/D and D/C
    • Type G: only reported in Argentina
      • now different species, C. argentinense
33
Q

What is the pathogenesis of Botulism Toxin?

A
  1. Toxin enters blood
  2. Binds to ganglioside receptors at neuromuscular junctions
  3. Internalized in the nerve cell
  4. Blocks acetyl choline release
  5. Produces a flaccid paralysis
34
Q

How are Tetanus and Botulism Toxins Similar?

A
  • Both:
    • Are neurotoxins
    • Are extracellular toxins
    • Are Proteins made of heavy and light chains
    • MW = 150,000
    • Share considerable AA sequence similarity
35
Q

How are Tetanus and Botulism Toxins Different?

A
  • Tetanus:
    • encoded by Plasmid
    • One antigenic type
    • Produced in the body (infection)
    • Acts primarily on CNS
    • Inhibits Gamma amino butyric acid and glycine release
    • Spastic paralysis
  • Botulinum:
    • Encoded by Chromosome (C&D) or Bacteriophage (A - G)
    • 8 antigenic types
    • Generally produced outside the body (intoxication)
    • Acts primarily on PNS
    • Inhibits Acetyl choline
    • Flaccid paralysis
36
Q

How are birds infected with Botulism?

A
  • Limberneck in chickens
    • Fly larvae pick up the toxin
    • Eaten by birds
  • Western Duck Sickness
    • Flooding leads to death of invertebrates
    • C. botulinum grows
    • Ducks in inertebrates
37
Q

What are the clinical signs of Botulism in Birds?

A
  • Wings, legs, neck become paralyzed
  • Cannot retract nictitating membrane
38
Q

How do horses get botulism?

A
  • Forage poisoning (spoiled food)
  • Wound botulism
  • Shaker foal syndrome
    • affects 2-8 weeks old
    • Tremors
39
Q

How do cattle get Botulism?

A
  • Lamziekte / Loin Disease
    • ​Chew on bones and flesh in phosphorous deficient areas “Pica”
    • Ingest toxin present in the dried flesh
    • Silage
40
Q

What is Visceral Botulism?

A
  • Reported in cattle
  • Growth of C. botulinum in the intestinal tract and production of toxin
41
Q

What are the clinical signs of Visceral Botulism?

A
  • Nonspecific
  • Indigestion
  • Chronic laminitis
  • Edema of the ventral abdomen
42
Q
A
43
Q

How is botulism diagnosed?

A
  • Clinical Signs: Progressive flaccid paralysis
  • Isolation and PCR confirmation
  • Toxin demonstration in mouse
  • ELISA to identify the toxin types
44
Q

Is there Treatment for Botulism?

A
  • Only in subacute cases
  • Multivalen anti-toxins
  • Ruminal or Stomach lavage
  • Fluid and Nutritional Support
45
Q

How is Botulism prevented?

A
  • Toxin is heat labile, cooking destroys the toxin.
  • Good Husbandry practices:
    • proper disposal of carcasses
    • Avoid using spoiled feeds
    • Phosphorus supplemetation
  • Vaccination:
    • Type specific or bivalent or trivalent
46
Q

How do humans get botulism?

A
  • 3 forms:
    • Fodd borne botulism* (90% of cases)
    • Infant botulism
    • Wound infection
47
Q

What is Dysautonomia?

A
  • A syndrome characterized by degenerative neuropathy affecting the autonomic nerve system
  • Seen mostly in dogs and rarely in cats
  • Reportded in horses in EuropeObserved mostly in outdoor dogs, usually younger than 2y
  • Reported only in MO and KS
  • Exact cause unknown, Clostridial botulinum toxin is suspected, but no evidence
48
Q

What are the clinical signs of Dysautonomia?

A
  • Acute onset of vomiting
  • inppetance
  • Absence of lactimation and pupillary light response
  • Protrusion of the nictitating membran
  • loss of anla sphincter function
  • peracute cases may die without prior clinical signs
  • Tongue paralysis (drooling, problems with deglutition and prehension of food), progressive muscle weakness and recumbency
49
Q

How is Dysautonomia diagnosed?

A
  • Pupillary function test
    • administration of dilute pilocarpine solution
50
Q

What are the applications of botulism toxin?

A
  • “Botox”
  • Therapeutic:
    • Migraines
    • Muscle spasms
  • Cosmetic
    • Remove facial wrinkles

Bacteriology and Mycology (35 decks)

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