LECTURE 12 and 13: CLOSTRIDIUM
READING: QUINN (2011) CHAPTER 24
LEARNING OBJECTIVES:
· Describe the pathogenesis and clinical signs of the major neurotoxic (tetanus and botulism),
histotoxic (Blackleg, black disease, malignant oedema) and enterotoxic (enterotoxaemia, C. difficile)
clostridial diseases
· Recognise the growing importance of Clostridium difficile as a potential animal and zoonotic
pathogen
· List the major clostridial diseases of animals and their aetiological agent
· Outline the control of clostridial diseases of animals using vaccination and other strategies
REVISION QUESTIONS:
1) Compare and contrast the pathogenesis and clinical signs of tetanus and botulism.
Tetanus (Clostridium tetani) Botulism (Clostridium botulinum)
Acquired from traumatised tissue Acquired from ingestion (decaying vegetation,
canned food), occasionally in wounds
Both Heavy chain: Receptor binding and internalisation of toxin
(Low pH in endosome -> penetrate endosome membrane -> pores (internalization))
- Bind to ganglioside (motor neuron - Difference = toxins remain at the
terminal) -> transport to CB & CNS neuromuscular junction.
dendritic processes by vesicles - retrograde
intra-axon flow (travel up axons -> ventral
horn)
Both light chain: Toxic moiety -> hydrolysis of synaptobrevin containing neurotransmitter
- Block inhibitory neurotransmitter release - irreversible interference of neurotransmitter
-> spastic paralysis (acetylcholine in here) release -> flaccid
paralysis
Different site of action: neuromuscular junction of
cholinergic nerves & peripheral autonomic
synapses
Sx: Spastic paralysis (localised spasms) Sx: Flaccid paralysis
- Stiff legged gait ‘saw-horse’, - Dilated pupils, decreased salivation (dry
- masticatory muscle spasm ‘lock-jaw’ mucous membranes, dysphagia)
- Latent tetanus: extended incubation, - Paralysis of respiratory muscle ->
wound may have healed abdominal breath or even death
,2) All clostridial diseases in animals can be prevented by vaccination and/or treatment with
antiserum. Discuss the accuracy of this statement using examples.
Not all the clostridial disease in animals can be prevented by vaccination.
- Effective: Many clostridial diseases eg Cl tetani, Cl botulinum, (Cl septicum, Cl perfringens (type C
and D), Cl novyi (Type B), Cl chauvoei)
- Not preventable: Cl. perfringens type A, (Cl difficile, Cl spiroforme and Cl piliforme)
For antiserum, blood-borne Cl. tetani can bind to motor terminals throughout the body before CNS
transfer, which can be prevented by antitoxins. However, this treatment is limited to the early course
of the disease as the bound toxins cannot be neutralised.
3) Enterotoxaemia is an enteric disease that may affect all species of domestic animals. What
Clostridium species is involved and what is its normal habitat? Discuss the syndromes produced
by this organism in chickens, pigs and sheep and its pathogenesis.
Clostridium perfringens
Normal habitats = soil, faeces and intestinal tract of animals (Types B,C,D survive as spores in soil for
months; Type A constitutes part of normal intestinal flora and is widely distributed in soil)
Sheep: Pulpy kidney diseases (overeating disease)
- Type D Clostridium perfringens
- Mostly secrete Epsilon (ε) toxin, which is an inert prototoxin and activated by trypsin which
then produces heat stable toxin that cause necrosis of intestine
- Sheep are resistant to the toxin but huge amount of toxins - by diet change, cause problem
- Affect intestinal permeability
- Damage kidney and brain blood vessel
- Clinical signs: sudden onset of convulsions and coma (CNS signs eg blindness, head pressing)
Also: Lamb dysentery (Caused by type B, secreting both beta and epsilon toxin with predominant
activity by one or another depending on intestinal conditions), Struck (caused by type C, beta toxins -
terminal convulsions/sudden death)
Pigs: Hemorrhagic enteritis
- Type C
- Binding of beta toxin to vascular endothelial cells -> vascular necrosis
- Intestinal mucosa necrosis present at postmortem examination
- Piglets preacute enterotoxaemia (death within 24h onset), Older pigs chronic
(anorexia, blood-stained faeces)
- A less severe necrotizing enterocolitis (unweaned piglets/feeder pigs) is caused by type A
strain
Chickens: Necrotic enteritis
- Type A, and less frequently type C
- NetB important virulence factor for necrotic enteritis while alpha toxin is of less important as
it can induce protective immune response
#ppt: beta = necrosis of intestine; epsilon = neurotoxic, necrotising brain and kidney
,4) Discuss the epidemiology, treatment and prevention of botulism and tetanus in horses.
Tetanus Botulism (type A, B, C in horses)
Epidemiology Endospores from soil and faeces Ingestion of toxin from contaminated hay
introduced into traumatised tissue, Wound contamination (eg umbilicus
which include hoof pricks, cutaneous infection)
wounds and deep penetrating wounds.
Tx - Wound care (eg debridement, H2O2 - Antiserum (cost and availability are
flush -> aerobic conditions that limited), only in early course of disease
inhibit replication) (unbound toxins)
- Neutralise unbound toxins - IV therapeutic agents to enhance
(IV/subarachnoid antitoxins 3 consec transmitter release in neuromuscular
days) junctions
- Toxoid administration SC
- High dose penicillin IM/IV in the
lesion
- Supportive treatment (eg sedative,
relaxant, housing in quiet dark env)
Px Routine vaccination of tetanus toxoid, Routine vaccination of toxoid
booster @1yr and every 5yrs Suspect foodstuffs should not be fed
Provision of balanced diet (if possible) to
prevent pica during drought
5) Compare the epidemiology of botulism outbreaks in cattle and wild birds during intense,
summer droughts/high temperatures.
Cattle:
- Starvation or phosphorus deficiency -> pica -> induce affected animals to chew bones or
carcasses containing botulinum toxins
- Pasture containing rodent carcasses
- Ensiled poultry litter -> bedding/pasture containing poultry carcasses
- Poor quality hay bale
Birds:
- Acquire toxin from dead invertebrates & decaying vegetation
- Consumption of maggots containing toxins
- Summer-massive kills (wetland, pH, salinity, temperature)?
, 6) In the form of a table, outline the aetiological agent/s and disease/s caused by the major
histotoxic, hepatotoxic, enterotoxic and neurotoxic clostridia.
Agent Disease
Histotoxic Clostridia: Cl. chauvoei Blackleg
Cl. septicum Malignant oedema, Braxy
Cl. perfringens (A) Gas gangrene
Hepatotoxic Clostridia: Cl. novyi Black disease
Enterotoxic Clostridia: Cl. perfringens (A-E) Enterotoxaemia
Cl. difficile Pseudomembranous colitis
Cl. piliforme Tyzzer’s disease
Cl. spiroforme Enterotoxaemia in rabbits
Neurotoxic Clostridia: Cl. tetani Tetanus (Muscular spasms)
Cl. botulinum Botulism (Flaccid paralysis)
7) Clostridium difficile is a major cause of nosocomial infections in humans. Discuss its recent
emergence in animals and potential zoonotic aspects (article on web).
Disease in animals & humans are associated with antimicrobial drug therapy (except foals - emerge
without it)
- Treatment suppresses the intestinal normal flora, with persistence of clostridial spores = risk
The incidence & severity (death) of CD1 are increasing, associating with a new hypervirulent strain.
- 16 times more toxin A & 23 times more toxin B in-vitro versus common strains
- Also have genes for binary toxins and high-grade fluoroquinolone resistance.
CD1 broad manifestations in humans eg asymptomatic carrier state, colitis (pseudomembrane) and
fulminant colitis (w/ megacolon/perforation)
Change in CD epidemiology is also associated with aging of the population and increased exposure of
CD outside of hospital.
8) Outline the pathogenesis of Clostridium spiroforme enterotoxaemia in rabbits.
Binary toxin with cytolytic activity produced by C. spiroforme.
- (C perfringens type E i toxin is structurally similar, so can be an antitoxin to neutralise)
Implicated in enterotoxaemia-like condition and is fatal rapidly (within 48h).
Diet related predisposing factors
- Low-fibre diets
- Oral antibiotic administration
- Adversely affect intestinal flora (predominantly gram + in rabbits)
READING: QUINN (2011) CHAPTER 24
LEARNING OBJECTIVES:
· Describe the pathogenesis and clinical signs of the major neurotoxic (tetanus and botulism),
histotoxic (Blackleg, black disease, malignant oedema) and enterotoxic (enterotoxaemia, C. difficile)
clostridial diseases
· Recognise the growing importance of Clostridium difficile as a potential animal and zoonotic
pathogen
· List the major clostridial diseases of animals and their aetiological agent
· Outline the control of clostridial diseases of animals using vaccination and other strategies
REVISION QUESTIONS:
1) Compare and contrast the pathogenesis and clinical signs of tetanus and botulism.
Tetanus (Clostridium tetani) Botulism (Clostridium botulinum)
Acquired from traumatised tissue Acquired from ingestion (decaying vegetation,
canned food), occasionally in wounds
Both Heavy chain: Receptor binding and internalisation of toxin
(Low pH in endosome -> penetrate endosome membrane -> pores (internalization))
- Bind to ganglioside (motor neuron - Difference = toxins remain at the
terminal) -> transport to CB & CNS neuromuscular junction.
dendritic processes by vesicles - retrograde
intra-axon flow (travel up axons -> ventral
horn)
Both light chain: Toxic moiety -> hydrolysis of synaptobrevin containing neurotransmitter
- Block inhibitory neurotransmitter release - irreversible interference of neurotransmitter
-> spastic paralysis (acetylcholine in here) release -> flaccid
paralysis
Different site of action: neuromuscular junction of
cholinergic nerves & peripheral autonomic
synapses
Sx: Spastic paralysis (localised spasms) Sx: Flaccid paralysis
- Stiff legged gait ‘saw-horse’, - Dilated pupils, decreased salivation (dry
- masticatory muscle spasm ‘lock-jaw’ mucous membranes, dysphagia)
- Latent tetanus: extended incubation, - Paralysis of respiratory muscle ->
wound may have healed abdominal breath or even death
,2) All clostridial diseases in animals can be prevented by vaccination and/or treatment with
antiserum. Discuss the accuracy of this statement using examples.
Not all the clostridial disease in animals can be prevented by vaccination.
- Effective: Many clostridial diseases eg Cl tetani, Cl botulinum, (Cl septicum, Cl perfringens (type C
and D), Cl novyi (Type B), Cl chauvoei)
- Not preventable: Cl. perfringens type A, (Cl difficile, Cl spiroforme and Cl piliforme)
For antiserum, blood-borne Cl. tetani can bind to motor terminals throughout the body before CNS
transfer, which can be prevented by antitoxins. However, this treatment is limited to the early course
of the disease as the bound toxins cannot be neutralised.
3) Enterotoxaemia is an enteric disease that may affect all species of domestic animals. What
Clostridium species is involved and what is its normal habitat? Discuss the syndromes produced
by this organism in chickens, pigs and sheep and its pathogenesis.
Clostridium perfringens
Normal habitats = soil, faeces and intestinal tract of animals (Types B,C,D survive as spores in soil for
months; Type A constitutes part of normal intestinal flora and is widely distributed in soil)
Sheep: Pulpy kidney diseases (overeating disease)
- Type D Clostridium perfringens
- Mostly secrete Epsilon (ε) toxin, which is an inert prototoxin and activated by trypsin which
then produces heat stable toxin that cause necrosis of intestine
- Sheep are resistant to the toxin but huge amount of toxins - by diet change, cause problem
- Affect intestinal permeability
- Damage kidney and brain blood vessel
- Clinical signs: sudden onset of convulsions and coma (CNS signs eg blindness, head pressing)
Also: Lamb dysentery (Caused by type B, secreting both beta and epsilon toxin with predominant
activity by one or another depending on intestinal conditions), Struck (caused by type C, beta toxins -
terminal convulsions/sudden death)
Pigs: Hemorrhagic enteritis
- Type C
- Binding of beta toxin to vascular endothelial cells -> vascular necrosis
- Intestinal mucosa necrosis present at postmortem examination
- Piglets preacute enterotoxaemia (death within 24h onset), Older pigs chronic
(anorexia, blood-stained faeces)
- A less severe necrotizing enterocolitis (unweaned piglets/feeder pigs) is caused by type A
strain
Chickens: Necrotic enteritis
- Type A, and less frequently type C
- NetB important virulence factor for necrotic enteritis while alpha toxin is of less important as
it can induce protective immune response
#ppt: beta = necrosis of intestine; epsilon = neurotoxic, necrotising brain and kidney
,4) Discuss the epidemiology, treatment and prevention of botulism and tetanus in horses.
Tetanus Botulism (type A, B, C in horses)
Epidemiology Endospores from soil and faeces Ingestion of toxin from contaminated hay
introduced into traumatised tissue, Wound contamination (eg umbilicus
which include hoof pricks, cutaneous infection)
wounds and deep penetrating wounds.
Tx - Wound care (eg debridement, H2O2 - Antiserum (cost and availability are
flush -> aerobic conditions that limited), only in early course of disease
inhibit replication) (unbound toxins)
- Neutralise unbound toxins - IV therapeutic agents to enhance
(IV/subarachnoid antitoxins 3 consec transmitter release in neuromuscular
days) junctions
- Toxoid administration SC
- High dose penicillin IM/IV in the
lesion
- Supportive treatment (eg sedative,
relaxant, housing in quiet dark env)
Px Routine vaccination of tetanus toxoid, Routine vaccination of toxoid
booster @1yr and every 5yrs Suspect foodstuffs should not be fed
Provision of balanced diet (if possible) to
prevent pica during drought
5) Compare the epidemiology of botulism outbreaks in cattle and wild birds during intense,
summer droughts/high temperatures.
Cattle:
- Starvation or phosphorus deficiency -> pica -> induce affected animals to chew bones or
carcasses containing botulinum toxins
- Pasture containing rodent carcasses
- Ensiled poultry litter -> bedding/pasture containing poultry carcasses
- Poor quality hay bale
Birds:
- Acquire toxin from dead invertebrates & decaying vegetation
- Consumption of maggots containing toxins
- Summer-massive kills (wetland, pH, salinity, temperature)?
, 6) In the form of a table, outline the aetiological agent/s and disease/s caused by the major
histotoxic, hepatotoxic, enterotoxic and neurotoxic clostridia.
Agent Disease
Histotoxic Clostridia: Cl. chauvoei Blackleg
Cl. septicum Malignant oedema, Braxy
Cl. perfringens (A) Gas gangrene
Hepatotoxic Clostridia: Cl. novyi Black disease
Enterotoxic Clostridia: Cl. perfringens (A-E) Enterotoxaemia
Cl. difficile Pseudomembranous colitis
Cl. piliforme Tyzzer’s disease
Cl. spiroforme Enterotoxaemia in rabbits
Neurotoxic Clostridia: Cl. tetani Tetanus (Muscular spasms)
Cl. botulinum Botulism (Flaccid paralysis)
7) Clostridium difficile is a major cause of nosocomial infections in humans. Discuss its recent
emergence in animals and potential zoonotic aspects (article on web).
Disease in animals & humans are associated with antimicrobial drug therapy (except foals - emerge
without it)
- Treatment suppresses the intestinal normal flora, with persistence of clostridial spores = risk
The incidence & severity (death) of CD1 are increasing, associating with a new hypervirulent strain.
- 16 times more toxin A & 23 times more toxin B in-vitro versus common strains
- Also have genes for binary toxins and high-grade fluoroquinolone resistance.
CD1 broad manifestations in humans eg asymptomatic carrier state, colitis (pseudomembrane) and
fulminant colitis (w/ megacolon/perforation)
Change in CD epidemiology is also associated with aging of the population and increased exposure of
CD outside of hospital.
8) Outline the pathogenesis of Clostridium spiroforme enterotoxaemia in rabbits.
Binary toxin with cytolytic activity produced by C. spiroforme.
- (C perfringens type E i toxin is structurally similar, so can be an antitoxin to neutralise)
Implicated in enterotoxaemia-like condition and is fatal rapidly (within 48h).
Diet related predisposing factors
- Low-fibre diets
- Oral antibiotic administration
- Adversely affect intestinal flora (predominantly gram + in rabbits)
