Histotoxic & Enteropathogenic Clostridia Flashcards
How do histotoxic Clostridia cause infection?
present as latent spores in muscle and liver where, once activated by anaerobic conditions, can secrete exotoxins that induce local tissue necrosis and lethal systemic effects
- each species produces different toxins
Where are histotoxic Clostridia endospores widely distributed?
in the environment and can persist for long period in the soil where it can be ingested and moved from the GI tract to liver and muscle
How is egg yolk agar used as a differential/enriched media for growing Clostridium species?
differentiates species based on lecithinase activity
- lecithovitellin is a normal lipoprotein in egg yolk and can be split by lecithinase into phosphorylocholine and insoluble diglyceride, which results in the formation of precipitate in the medium (white opaque zone)
What is most affected by C. chauvoei in black leg?
thick-muscled areas become necrotic, emphysematous, and edematous
What is the pathogenesis of endogenous and exogenous infections caused by histotoxic infections?
ENDOGENOUS: spores in intestinal lumen —> tissue (phagocytes) —> tissue injury (reduced oxygen) —> spore germination —> vegetative bacteria produce exotoxins —> necrosis and toxemia
EXOGENOUS: infected wounds
What 4 Clostridium species cause malignant edema? How is it commonly caused?
- C. perfringens type A
- C. noyvi
- C. chauvoei
- C. sordellii
puncture wound that becomes infectious (exogenous)
How does malignant edema present?
dark hemorrhagic muscle, edema in subcutaneous tissue, fibrin production
What causes Braxy? What is it?
C. septicum
infectious disease which causes sudden death in sheep, commonly occurs in winter, when sheep eat frosted root crops or frosted grass, which damages the mucosa of the abomasum, allowing it to enter, causing abomasitis and a fatal bacteremia
What causes black disease? What is it typically associated with? How does it present?
C. noyvi
spores awakened by parasitic infection caused by Fasciola hepatica
gas bubbles on liver causing a spongy appearance
What is the most distinguishing feature of sudden death in sows?
Black disease caused by C. noyvi
What causes bacillary hemoglobinuria? What are 2 common signs?
C. hemolyticum
- dark purple/red “port wine” colored urine and dark-colored feces
- yellow color or pale gum and eye sclera (jaundice) with pinpoint red blood spots (petechia)
- caused by hemoglobin breakdown
What determines resistance to histotoxic Clostridium resistance?
circulating antibodies to toxins and cellular components
In what 2 ways can a laboratory diagnosis of histotoxic Clostridium infection be reached?
- immunofluorescence of infected tissue smears show sporulated Gram-positive rods
- detection in tissue or identification in culture using PCR (flagellin and other genes)
What are 2 requirements to histotoxic Clostridium isolation?
- strict anaerobic conditions
- culture medium rich in cysteine and water-soluble vitamins
Treatment for histotoxic Clostridium infections is often distressing. What treatment is done?
IV penicillin
How are histotoxic Clostridium infections controlled in cattle, ewes, and lambs? What is recommended when cases are first observed?
CATTLE are vaccinated at 3-6 months (should precede exposure)
pregnant EWES are vaccinated 3 weeks prior to parturition
LAMBS are vaccinated by their first year
change of pasture
What Clostridium species is enteropathogenic? Where are they typically found?
C. perfringens type A, B, C, D, E
GI tract
What are 3 factors that predispose sheep to the development of C. perfringens?
- low proteolytic activity in the neonatal intestine (unable to break down toxins)
- incomplete establishment of normal intestinal flora in neonates
- dietary influences in older animals - abrupt change to or gorging on a rich diet; intestinal hypomotility
What is the common toxin produced by all enteropathogenic Clostridia?
α-toxin
- used for diagnostics in hemolytic activity (hot-cold lysis)
What is Type A enterotoxemia responsible for? What makes it able to do this?
tissue destruction caused by active toxins and connective tissue toxins
What are 6 diseases caused by Type A enterotoxemia?
- gastritis and hemolytic diseases of ruminants (yellow lamb disease)
- hemorrhagic enteritis in cattle, horses, and infant alpacas
- necrotic enteritis in poultry
- canine hemorrhagic gastroenteritis
- food posioning in humans
- antibiotic-associated diarrhea
What 3 toxins are most important in Type A enterotoxemia?
- α-toxin
- perfringlolysin O
- enterotoxins
Hemorrhagic abomastitis:
C. perfringens Type A
Chicken necrotic enteritis is associated with what co-infection?
coccidia
(fibrin plaques = necrosis)
What disease is Type B enterotoxemia responsible for? Why are the affected animals susceptible?
lamb dysentery in newborn lambs
- absence of microbial competition in the neonatal intestine
- low proteolytic activity in the neonatal intestine (so that colostrum can be absorbed and maternal antibodies can be transfered)
What toxin is responsible for producing hemorrhagic enteritis characteristic to Type B enterotoxemia? What is it susceptible to?
β-toxin
trypsin
What are 4 common signs of Type B enterotoxemia?
- depression
- anorexia
- abdominal pain
- diarrhea
What is the principal virulence factor in Type C enterotoxemia? What favors its action?
β-toxin
most common in neonatal calves, foals, piglets, and lambs —> protease inhibitors in colostrum
What does Type C enterotoxemia cause in older sheep typically in Europe?
Struck - rapidly fatal toxemia-bacteriemia (β-toxin) with similar signs as being struck by lightning
What animals are most affected by Type D enterotoxemia? What 2 diseases are most common?
older lambs (< 1 yr) and sometimes goats and calves
- overeating diseases
- pulpy kidney disease
What 3 actions cause upsets in the flora making animals more susceptible to Type D enterotoxemia?
- abrupt change to a rich diet
- gorging on an energy-rich diet
- intestinal hypomotility, a consequence of overeating
What toxin is responsible for Type D enterotoxemia? What does it cause? What is it activated by?
ε-toxin
increases intestinal permeability, causes vascular damage, fluid losses, edema, and encephalomalacia
trypsin
(predilection to older animals!)
What is the main finding in pulpy kidney caused by Type D enterotoxemia?
typically acute death with few or no symptoms, but infected animals have been found to have glycosuria and breakdown of kidney tissue
Encephalomalacia:
Type D enterotoxemia
What regulates immunity to enteropathogenic Clostridia?
antibody-mediated and correlates with anti-toxin levels
In what 3 ways can a diagnosis of enteropathogenic Clostridia be made?
- non-motile and produces a polysaccharide capsule in tissue
- spores are rarely demonstrated in exudates
- isolation in blood agar in anaerobic environment
What happens when enteropathogenic Clostridia cultured on blood agar are examined with transmitted lights?
colonies are surrounded by double-zone hemolysis, consisting of an inner clear zone and an outer hazy one
- non-proteolytic and no distinct odor
How can cases of enterotoxemia be diagnosed in the lab?
Giesma, Gram-positive rods
positive CAMP test with S. agalactiae
How does C. perfringens respond to stormy fermentation test?
clotting of milk followed by gaseous disruption
- milk proteins are digested
Why is treatment for enterotoxemia so difficult?
most causes are too acute for successful treatment
- antitoxin of appropriate type can be given to sick animals and those at risk (only lasts 2-3 weeks)
What are the 3 main ways of controlling enterotoxemia?
- active immunization of dams with bacterin-toxoid combos prior to parturition
- preventing overeating
- antibiotic treatment (rarely successful due to acute presentations)
What is the morphology of Clostridium difficile? What does it typically cause in humans?
Gram-positive, motile, encapsulated, spore-forming anaerobic rod
antibiotic-associated diarrhea, pseudomembranous colitis
What toxin is responsible for disease in C. difficile infection? What does it do?
Toxin A (ToxA, TcdA), an enterotoxin
breakdown of cytoskeletal components of the infected cell, causing the disruption of the tight junctions between intestinal epithelial cells (cell death!)
What immune response is C. difficile responsible for?
influx of polymorphonuclear cells, causing the synthesis of prostaglandings and secretion of chloride ions and water (diarrhea)
What are the 4 steps to C. difficile infection?
- “trigger event” - antibiotics, chemotherapy
- normal flora disruption and colonization of C. difficile
- adherence to large intestine and toxin production (pili, fimbriae, epithelial cell death)
- intense inflammatory response - fluid/electrolyte secretion, diarrhea
What antitoxin works in human infections of C. difficile?
oral bovine antitoxin
What selective media are used to culture C. difficile?
cycloserine, cefoxitin, and fructose agar (CCFA)
In what 3 ways is C. difficile controlled/treated? Why are disinfectants not useful?
- diarrhea responds rapidly to metronidazole and vancomycin
- probiotics
- hand-washing and good hygiene practices
not effective against spores
What does C. piliforme cause?
acute fatal diarrheal diseases of laboratory mice with focal liver necrosis (Tyzzer’s disease)
What does C. sordellii cause in ruminants and horses?
fatal myositis and hepatic diseases
What does C. colinum cause?
quail disease, ulcerative enteritis, and necrotizing hepatitis of several fowl species
What does C. spiroforme cause?
juvenile (mucoid) enteritis and antibiotic-induced enteritis in rabbits
