Neurotoxigenic Clostridium Flashcards
(50 cards)
1
Q
What are the Gram Positive Spore Forming Anaerobes?
A
- Clostridium
- Clostridioides
2
Q
What are the Gram Positive Nonspore-Forming Anaerobes?
A
- Actinomyces
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
4
Q
What is the Habitat of Clostridium?
A
Ubiquitous in soil and alimentary tract of animals
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
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
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
8
Q
What are the Neurotoxifenic Clostridia?
A
- C. tetani
- C. Botulinum
9
Q
What is Clostridium tetani?
A
- Causative agent of tetanus
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
11
Q
What are the virulence factors of Clostridium tetani?
A
- Tetanolysin
- Tetanospasmin
12
Q
What is Tetanolysin?
A
- hemolytic toxin
- causes tissue necrosis
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
14
Q
What is the mechanism of action of Tetanospasmin?
A
- Binds to ganglioside receptors on nerve cells
- Moves by retrograde axonal transport to the cenral nervous system
- Blocks release of neurotranitters (GABA and glycine)
- Results in spastic paralysis
15
Q
What is the pathogenesis of Clostridium tetani?
A
- Enters wounds as spores or vegetative cells
- Spores germinate and organisms grow
- Produce toxin within 4-8 hours
- Toxin moves retrogradely along axon fibers to the spinal cord “Ascending tetanus”
- Regional muscles show signs first “localized tetanus”
- More common in dogs
- Toxin enters lymphatics and blood (toxemia)
- Affects motor nerve centers of face and neck, then limbs “Descending tetanus”
- “Generalized tetanus
- More common in horses, pigs, and humans
- Death due to respiratory failure
16
Q
What is Idiopathic Tetanus?
A
- No known cause
- No visiblewounds
- Ingestion of preformedtoxin or toxin is produced in the gut
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
18
Q
What is the incubation period of Clostridium tetani?
A
1 - 3 weeks
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
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
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
How is Tetanus Treated?
* 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
How do you prevent Tetanus?
* 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
What are the caracteristics of *Clostridium botulinum?*
* Gram - rods, subterminal spores
* Cause of Botulism
28
What is botulism?
* a disease characterized by flaccid paralysis of skeletal muscles
* Caused by botulinum toxin
* Produced by:
* *C. botulinum*
* *C. butyricum*
* *C. barati*
29
What is the mode of infection for *C. botulinum?*
* Ingestion of preformed toxin
* Intoxication, not an infection
* Production of toxin in the gut can also happen; toxico-infection
30
What are the Virulence factors of *C. botulinum?*
* 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
What is Botulinum?
* A-B toxin
* Protein, MW 150,000
* Bacteriophage encoded (in some types)
* Principal site of action is at the myoneural junction
32
What are the toxigenic types of Botulinum?
* 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
What is the pathogenesis of Botulism Toxin?
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
How are Tetanus and Botulism Toxins Similar?
* Both:
* Are neurotoxins
* Are extracellular toxins
* Are Proteins made of heavy and light chains
* MW = 150,000
* Share considerable AA sequence similarity
35
How are Tetanus and Botulism Toxins Different?
* 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
How are birds infected with Botulism?
* **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
What are the clinical signs of Botulism in Birds?
* Wings, legs, neck become paralyzed
* Cannot retract nictitating membrane
38
How do horses get botulism?
* Forage poisoning (spoiled food)
* Wound botulism
* Shaker foal syndrome
* affects 2-8 weeks old
* Tremors
39
How do cattle get Botulism?
* **Lamziekte / Loin Disease**
* ****Chew on bones and flesh in phosphorous deficient areas "Pica"
* Ingest toxin present in the dried flesh
* Silage
40
What is Visceral Botulism?
* Reported in cattle
* Growth of *C. botulinum* in the intestinal tract and production of toxin
41
What are the clinical signs of Visceral Botulism?
* Nonspecific
* Indigestion
* Chronic laminitis
* Edema of the ventral abdomen
42
43
How is botulism diagnosed?
* Clinical Signs: Progressive flaccid paralysis
* Isolation and PCR confirmation
* Toxin demonstration in mouse
* ELISA to identify the toxin types
44
Is there Treatment for Botulism?
* Only in subacute cases
* Multivalen anti-toxins
* Ruminal or Stomach lavage
* Fluid and Nutritional Support
45
How is Botulism prevented?
* 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
How do humans get botulism?
* 3 forms:
* **Fodd borne botulism\* (90% of cases)**
* Infant botulism
* Wound infection
47
What is Dysautonomia?
* 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
What are the clinical signs of Dysautonomia?
* 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
How is Dysautonomia diagnosed?
* Pupillary function test
* administration of dilute pilocarpine solution
50
What are the applications of botulism toxin?
* "Botox"
* Therapeutic:
* Migraines
* Muscle spasms
* Cosmetic
* Remove facial wrinkles
