Clostridium species

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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

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
• • Colitis X
  • Peritonitis in cattle
  • Dysphagia in horses
  • Myositis
• C. perfringens type E:
  • Enteritis in rabbits, haemorrhagic enteritis in calves