Overview
- Organisms present in the soil, alimentary tract and faeces
- Endospores may be present in liver and may be reactivated to cause disease
- Neurotoxic clostridia, Clostridium tetani and Clostridium botulinum affect neuromuscular function but cause no tissue damage
- Histotoxic clostridia cause localised lesions in tissues and may cause toxaemia
- C. perfringens cause inflammatory lesions in the gastrointestinal tract and enterotoxaemias in sheep
Characteristics
- Large Gram-positive rods
- Obligate anaerobes
- Fermentative, catalase negative, oxidase negative
- Straight or slightly curved
- Motile by flagellae
- Require enriched media for growth
- Produce endospores which vary in shape and location and cause bulging of mother cell
Pathogenesis and pathogenicity
- Produce extracellular digestive enzymes and toxic substance known as exotoxins
- Exotoxins cause necrosis, haemolysis and death
- Collagenase, hyaluronidase and DNase enymes facilitate spread through tissues
Neurotoxic clostridia
Clostridium tetani
- Causes tetanus
- Acute, potentially fatal intoxication affecting many species
- Horses and man particularly susceptible; carnivores fairly resistant
- Found in horse faeces
- Characteristics:
- Terminal, spherical endospores give mother cells a drumstick appearance
- Enodospores resistant to boiling and chemicals but susceptible to autoclaving
- Swarming growth and haemolytic on blood agar
- Many serotypes but all produce same neurotoxin, tetanospasmin, therefore antibodies neutralise all
- Pathogenesis:
- Endospores introduced via damaged tissues e.g. penetrating wounds
- Damaged tissue creates an anaerobic environment, allowing germination of spores
- Tetanospasmin made by bacteria replicating in damaged tissue
- Absorbed toxin affects neuromuscular junction distant from site of toxin production
- Neurotoxin binds irreversibly to ganglioside receptors on motor neurons and is transported to nerve cell body
- Toxins transported across synapse to terminals of inhibitory neurons where they block transmission of signals
- Spastic paralysis by constant tensing of muscles results
- Toxin can be blood-borne and bind to motor terminals throughout the body as well as in the CNS
- Clinical signs:
- Incubation period 5-10 days
- Stiffness, localised spasms, altered heart and respiratory rates, dysphagia, altered facial expression, lock-jaw from mastigatory muscle spasm
- Tonic muscle contraction easily stimulated
- Treatment:
- Antitoxin IV or into subarachnoid space on 3 consecutive days
- Toxoid subcutaneously to promote active immune response
- Penicillin to kill vegetative cells
- Debridement and flushing of wound with hydrogen peroxide
- Fluids, sedatives, muscle relaxants
- Control:
- Toxoid vaccine for farm animals
- Debridement of wounds in horses
Clostridium botulinum
- Ubiquitous organism
- Oval, subterminal endospores; spores survive boiling for hours
- Causes botulism, a potentially fatal intoxication
- Germination of endospores, growth of bacterial cells and toxin production in anaerobic conditions e.g. decaying carcasses and vegetation
- Disease in animals consuming rotting carcasses and in herbivores through contamination of feed
- Pathogenesis:
- Intoxication on ingestion and absorbtion of toxin from GIT into the blood
- Occasionally germination of spores in wounds or GIT
- Neurotoxin carried to peripheral nervous system
- Toxin binds gangliosides irreversibly at the neuromuscular junction
- Blocks release of acetylcholine
- Clinical signs:
- Dilated pupils, dry mucus membranes, decreased salivation, tongue flacidity, dysphagia in farm animals
- Incoordination and knuckling followed by flacid paralysis and recumbency
- Paralysis of respiratory muscles leads to death
- Flacid paralysis of legs and wings in birds
- Diagnosis:
- Mouse inoculation with infected serum
- Toxin detection by PCR, ELISA
- Toxin neutralisation tests in mice
- Treatment: polyvalent antiserum neutralises unbound toxin
- Toxoid vaccine used in endemic regions
- Implicated in equine grass sickness
Histotoxic infections
- Exotoxins cause local tissue necrosis and systemic effects which can be fatal - toxaemia
- C. chauvei and C. septicum present in muscle as latent spores which can germinate to cause infection
- C. novyi type B and C. haemolyticum have latent spores in the liver
- When inoculated into wounds, cause malignant oedema and gas gangrene
- Endospores persist in the soil
- Most ingested spores excreted in faeces, but some become dormant in tissues
- Tissue injury leads to reduced oxygen tensions allowing germination and replication of bacteria
- Exotoxins cause local necrosis
- Activated spores in the liver and muscles cause endogenous infections including blackleg, infectious necrotic hepatitis and bacillary haemoglobinuria
- Inoculation of wounds causes exogenous infections including malignant oedema and gas gangrene
Clostridium chauvei
- Black leg:
- Acute disease of cattle and sheep
- Endogenous infection in young cattle with latent spores in muscles, activated by trauma
- Exogenous infection via wounds in sheep of any age
- Gangrenous cellulitis and myositis caused by exotoxins leads to rapid death
- Skeletal muscle damage with lameness, swelling and crepitus due to gas accumilation
- Dyspnoea due to lesions in tongue and throat muscles
- Myocardial and diaphragmatic lesions can cause sudden death
- Fluorescent antibody test for diagnosis
- Causes gas gangrene, along with Clostridium septicum
Clostridium septicum
- Causes malignant oedema:
- Infection via wounds
- Cellutis with minimal gangrene and gas formation
- Tissue swelling die to oedema; coldness and discoloration of overlying skin
- Toxaemia with depression; death may be rapis if extensive lesions
- Causes braxy:
- Abomasitis of sheep
- Disease occurs during winter
- Rapidly fatal; anorexia, depression, fever
- Causes gas gangrene and myositis
Clostridium novyi
- Infectious necrotic hepatitis/black disease:
- Acute disease of sheep, occasionally cattle
- Hepatic necrosis caused by exotoxins of C. novyi type B in liver damaged by Fasciola hepatica
- Rapid death
- Dark discoloration of skin caused by subcutaneous venous congestion
- Fluorescent antibody test diagnostic
- Causes gas gangrene and myositis.
- May be involved in cutaneous lesions
- Causes big head in rams - oedema of subcutaneous tissues of the head, neck and cranial thorax; necrotising lethal alpha toxin
Clostridium perfringens type A
- [[General Pathology - Necrosis#Gas Gangrene|Gas gangrene
- Extensive bacterial invasion of damaged muscle
- Gas production causing subcutaneous crepitus
- Similar manifestations as malignant oedema
Clostridium haemolyticum
- Causes bacillary haemoglobinuria in cattle, occasionally sheep
- Endogenous infection - endospores dormant in liver
- Fluke migration allows germination
- Beta toxin causes intravascular haemolysis and hepatic necrosis
- Haemoglobinuria due to destruction of red blood cells
Clostridium sordelli
- Causes gas gangrene, myositis and abomasitis (lambs)
Treatment of histotoxic infections
- Early penicillin
- Vaccination with bacterin or toxoid at 3 months and booster after 3 weeks, then annually
Diagnosis
- Anaerobic transport medium
- Culture on blood agar enriched with yeast extract, vitamin K and haemin
- Anaerobic culture with hydrogen supplement and 5-10% carbon dioxide for 48 hours
- Colonies of C. perfringens are 5mm diameter, circular, flat and grey
- C. perfringens colonies are surrounded by a zone of double haemolysis
- Positive cAMP test with Sreptococci agalactiae
- Biochemical tests
- Toxins identified in body fluids by toxin neutralisation or protection tests in lab animals
- Nagler reaction to detect alpha toxin - plate neutralisation test
- Fluorescent antibody tests for histotoxic clostridia
- ELISA, PCR for toxin detection
Enteropathogenic and enterotoxaemic clostridia
- General:
- Clostridium perfringens types B, C and D
- Found in soil, feaces and intestinal tract
- Survive in soil as spores
- Husbandry, changes in diet and environment predispose to proliferation in the intestine
- Pathogenesis and pathogenicity:
- Clostridial replication and overgrowth in the interstinal tract of sheep
- Production of potent exotoxins which cause local and systemic effects of enterotoxaemia
- Type of toxins produced determine clinical syndrome
- Haemolysins, collagenases and hyaluronidases also produced
- C. perfringens type A:
- Necrotising enterocolitis in pigs and necrotic enteritis in chickens
- Canine haemorrhagic gastroenteritis
- Typhlocolotis in horses
- C. perfringens type B:
- Lamb dysentery
- Up to 30% morbidity and high mortality
- Affects lambs in first week of life
- Abdominal distension, pain, bloody faeces, sudden death
- Bacterial overgrowth in the intestine of the lamb due to immature bacterial flora
- Lack of proteases in the immature gut prevents cleavage of the beta toxin, allowing it to cause disease
- Haemorrhagic enteritis and ulceration in the small intestine
- Fluid in the peritoneal cavity and pericardial sac due to increased capillary permeability
- C. perfringens type C:
- Acute enterotoxaemia in adult sheep, 'struck'
- Sudden death or terminal convulsions in sheep at pasture
- Beta toxin plays major role in pathogenesis of the disease
- Post mortem: jejunal ulceration; hyperaemia in small intestine; fluid accumulation in peritoneal cavity; congestion of peritoneal vessels; petechial haemorrhages
- Haemorrhagic enteritis in piglets
- Peracute enterotoxaemia often of entire litter with mortality rates 80%
- Infection from sow's faeces
- Death within 24 hours in young piglets
- Chronic disease in older piglets
- Dullness, anorexia, bloody faeces, perianal hyperaemia
- Post mortem: necrosis of terminal small intestinal mucosa, caecum and colon and blood-stained contents; serosanguinous fluid in pleural and peritoneal cavities
- Necrotic enteritis in chickens:
- Broilers under 12 weeks
- Acute enterotoxaemia, sudden onset and high mortality
- Necrosis of small intestine
- Predisposing factors include diet changes, coccidial infection and intestinal hypomotility
- C. perfringens type D:
- Pulpy kidney disease in well-fed 3-10 week-old lambs
- Follows overeating high grain diet or luchious pasture
- Starch from partially digested food enterering the intestine from the rumen allows rapid clostridial proliferation
- Epsilon toxin activated by proteolytic enzymes causes toxaemia
- Lambs found dead or with opisthotonos, convulsions, coma in acute phases
- Blindness and head pressing in subacute disease; bloat in later stages
- Hyperglycaemia, glycosuria
- Post mortem: hyperaemia in intestine; fluid in pericardial sac; kidney autolysis with pulpy cortical softening (acute death)
- Subacute death causes symmetrical encephalomalacia and haemorrhage in basal ganglia and midbrain
- C. perfringens type E:
- Enteritis in rabbits, haemorrhagic enteritis in calves