Neurotoxigenic Clostridium Flashcards
What are the Gram Positive Spore Forming Anaerobes?
- Clostridium
- Clostridioides
What are the Gram Positive Nonspore-Forming Anaerobes?
- Actinomyces
What are the characteristics of Clostridium?
- 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
What is the Habitat of Clostridium?
Ubiquitous in soil and alimentary tract of animals
How many species of Clostridium are there?
- >150 species
- ~20 cause diseases
- 14 produce exotoxins (Alpha, Beta, Gamma, Delta, etc)
- Size: 20 - 600 KDa
What is the mode of infection for Clostridium?
- Ingestion with feed/water
- Wound contamination
- Non Contagious
- Require Oxygen-free environments for growth
- Ischemia due to tissue injury
- Mixed infection with facultative organisms
What is Costridioides difficile?
- 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
What are the Neurotoxifenic Clostridia?
- C. tetani
- C. Botulinum
What is Clostridium tetani?
- Causative agent of tetanus
What is the mode of infection of Clostridium tetani?
- 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
What are the virulence factors of Clostridium tetani?
- Tetanolysin
- Tetanospasmin
What is Tetanolysin?
- hemolytic toxin
- causes tissue necrosis
What is Tetanospasmin?
- 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
What is the mechanism of action of Tetanospasmin?
- 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
What is the pathogenesis of Clostridium tetani?
- 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
What is Idiopathic Tetanus?
- No known cause
- No visiblewounds
- Ingestion of preformedtoxin or toxin is produced in the gut
What animals are susceptible to Clostridium tetani?
- 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
What is the incubation period of Clostridium tetani?
1 - 3 weeks
What are the types of Tetanus?
- Localized infection
- More common in dogs & cats
- Generalized infection
- More common in horses, pigs and humans
What are the clinical signs of Tetanus?
- 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
What are the clinical signs of Generalized Tetanus?
- Regurgitation of food & water
- pharyngeal and laryngeal spasms
- Drooling
- Exaggerated response to external stimuli
- Opisthotonous
- Risus sardonicus
- Convulsions
What is Opisthotonous?
What is Risus Sardonicus?
How do you diagnose Tetanus?
- 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
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
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
What are the caracteristics of Clostridium botulinum?
- Gram - rods, subterminal spores
- Cause of Botulism
What is botulism?
- a disease characterized by flaccid paralysis of skeletal muscles
- Caused by botulinum toxin
- Produced by:
- C. botulinum
- C. butyricum
- C. barati
- Produced by:
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
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
What is Botulinum?
- A-B toxin
- Protein, MW 150,000
- Bacteriophage encoded (in some types)
- Principal site of action is at the myoneural junction
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
What is the pathogenesis of Botulism Toxin?
- Toxin enters blood
- Binds to ganglioside receptors at neuromuscular junctions
- Internalized in the nerve cell
- Blocks acetyl choline release
- Produces a flaccid paralysis
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
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
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
What are the clinical signs of Botulism in Birds?
- Wings, legs, neck become paralyzed
- Cannot retract nictitating membrane
How do horses get botulism?
- Forage poisoning (spoiled food)
- Wound botulism
- Shaker foal syndrome
- affects 2-8 weeks old
- Tremors
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
What is Visceral Botulism?
- Reported in cattle
- Growth of C. botulinum in the intestinal tract and production of toxin
What are the clinical signs of Visceral Botulism?
- Nonspecific
- Indigestion
- Chronic laminitis
- Edema of the ventral abdomen
How is botulism diagnosed?
- Clinical Signs: Progressive flaccid paralysis
- Isolation and PCR confirmation
- Toxin demonstration in mouse
- ELISA to identify the toxin types
Is there Treatment for Botulism?
- Only in subacute cases
- Multivalen anti-toxins
- Ruminal or Stomach lavage
- Fluid and Nutritional Support
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
How do humans get botulism?
- 3 forms:
- Fodd borne botulism* (90% of cases)
- Infant botulism
- Wound infection
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
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
How is Dysautonomia diagnosed?
- Pupillary function test
- administration of dilute pilocarpine solution
What are the applications of botulism toxin?
- “Botox”
- Therapeutic:
- Migraines
- Muscle spasms
- Cosmetic
- Remove facial wrinkles
