Lecture 17 and 18: Clostridium 2 and 3 Flashcards
What is the causative agent of botulism
Clostridium botulinum
Where is C. Botulinum found
Endospores distributed in soils and aquatic environments
What type of hemolysis does C. Botulinum have
B-hemolysis
What are the 7 types of toxins for C. Botulinum
A, B, C, D, E, F, G
T or F: the antitoxin for C. Botulinum must match the toxin type to be effective
True
What disease does C. Botulinum cause
Flaccid paralysis
What type of C. Botulinum is in most animal species
C1
What is the most common C. Botulinum toxin in cattle
Type D
How do cattle get type D C. Botulinum
Pica (starvation or phosphorus deficiency) leads to eating carcasses or bones that contain BoNT
85% of cases in horses with C. Botulinum are caused by what toxin type
B
What is shaker foal syndrome
Less than 4 week old foals are found dead or with progressive symmetric motor paralysis- stilted gait, muscular tremors, or unable to stand for >4-5 minutes to due ingestion of Type B C. Botulinum spores
Describe the action of Botulinum neurotoxin and how it results in flaccid paralysis
- Binds receptor and is endocytosed at NMJ
- Enters cytosine of host cell and cleaves SNARE proteins required for membrane fusion of synaptic vesicle and cell membrane
- Blocks release of ACh
- Muscles can’t contract—> flaccid paralysis
What are the main clinical manifestations of C. Botulinum
- Tongue, jaw, and tail flaccidity
- In coordination and knuckling at fetlocks
- Flaccid paralysis
- Paralysis of respiratory muscles ultimately leads to death
Based on these photos what are you worried about
c. Botulinum
How can you dx C. Botulinum
- Culture
- Detect BoNT or C. Botulinum in food
- Inoculate in mice- wasp waist
T or F: C. Botulinum toxin from dead animal proves that being cause of death
No not significant can inoculate after death
How can you dx C. Botulinum
- PCR- toxin genes
- ELISA
How do you tx C. Botulinum
- Evacuation of stomach and purging for recent ingestion
- Polyvalent antiserum- binds unbound toxin, is serotype specific
Is there a vaccine available for C. Botulinum
Yes, for foals and horses: Botvac- type B toxoid
What 3 diseases can Clostridium Chauvoei cause
- Blackleg
- Clostridial myositis
- Black quarter
What type of hemolysis is observed with C. Chauvoei
Beta
Where is C. Chauvoei that causes blackleg found
Naturally in intestinal tract of animals
Once C. Chauvoei that causes blackleg is in intestinal tract of animals where does it go
Organism crosses epithelial layer of GI tract and enters tissues (liver, skeletal muscle, cardiac muscle)
Phagocytized by macrophages and endospores remain dormant
Blackleg causes by C. Chauvoei is considered a ___ disease
Endogenous
What is the virulence factor for C. Chauvoei causing blackleg and what does it do
CctA: Clostridium Chauvoei toxin A: pore forming toxin that perforates cell membrane
Who is most commonly infected with C. Chauvoei that causes blackleg
Young well fed cattle 6 months to 2 years
What does C. Chauvoei cause in sheep
Gas gangrene
How does C. Chauvoei get into sheep
Wound infections following injury from shearing, docking, castration, crutching
T or F: C. Chauvoei that causes gas gangrene in sheep is nearly 100% fatal
True
What is the pathogenesis of blackleg caused by C. Chauvoei
- Germination of spores in anoxic tissues
- CctA generates lesions (dark, dry, emphysematous, hemorrhagic)
- Metabolism- gas
What is the likely cause and disease
C. Chauvoei, causing blackleg disease
What are the clinical manifestations of C. Chauvoei causing blackleg disease
- Gangrenous cellulitis and crepitant myositis- large muscles in back, limbs and neck
- Acute development of lameness, edema, crepitation
How can you dx blackleg caused by C. Chauvoei
- Muscles are dark red to black, dry, spongy, sweet odor, infiltrated with small bubbles, neutrophils
- Smear infected tissues gram + rods
- Fluorescent antibodies
What is treatment for blackleg in outbreak setting
- Vaccinate susceptible animals and tx prophylactically with penicillin up to 14 days (multivalent vax)
- Move cattle from affected grazing grounds
How can you control blackleg
Vaccinate with multivalent bacterin vaccine
What is the cause of infectious necrotic hepatitis aka black disease
C. Novyi
Where is C. Novyi found
Soil, often present in intestine and liver of herbivores
Black disease often coincides with presence of ___
Liver fluke: F. Hepatica
What are the virulence factors associated with C. Novyi type B and what do they do
- TcnA- Clostridium Novyi toxin A (alpha toxin)- lethal necrotizing, activates GTP binding proteins leading to edema
- B-toxin- potent phospholipase
What is the pathogenesis of black disease
- C. Novyi type B (in sheep and cattle)
- Endospores ingested and migrate to Kupffer cells in liver where they remain dormant
- Liver cell injury (flukes)—> tissue becomes anoxic so endospores germinate and produce toxins
- Sudden death ~2 days
Darkening of SQ tissues and blackening of carcass after death is a hallmark of what disease, caused by what
Black disease, caused by C. Novyi type B
How can you dx. black disease
- Liver lesions- grayish yellow gross lesions, fluke tracts
- Large gram + rods
- Fluorescent antibodies
Cow liver, what likely caused these lesions
C. Novyi causing black disease, also flukes
Black disease in pigs is due to infection with what intestinal roundworm
Ascaris
What is the most distinguishing sign of black disease in pigs
Spongy liver
Liver from pig, what is disease and cause
black disease caused by C. Novyi and infection with Ascaris
What is tx for C. Novyi type B
No treatment available, typically animals found dead to rapid deterioration
How can you control C. Novyi type B
- Vaccination with multivalent bacterin-toxoid (longterm immunity)
- Control flukes
What is the causative agent of bacillary hemoglobinuria (red water disease)
C. Haemolyticum
What species is commonly affected by C. Haemolyticum and where
Ruminants in Rocky Mountains, pacific coast, Gulf of Mexico
How do ruminants get C. Haemolyticum
Grazing in pastures infested with liver flukes encysted on vegetation which decrease O2 leading to sporulation of C. Haemolyticum endospores
What is the virulence factor on C. Haemolyticum and what does it do
B-toxin- hemolytic necrotizing phospholipase C
What is the pathogenesis of C. Haemolyticum
- Ingestion of endospores which are absorbed by intestine
- Spores transported to liver and remain dormant with high O2
- Grazing leads to ingestion of cysts for liver fluke
- Young liver flukes ex cyst in duodenum, burrow in intestinal wall and migrate to liver
- Burrow and feed on parenchyma of liver
- Create anaerobic tissue causing germination of C. Haemolyticum and toxic produced
- Leading to hepatocyte necrosis and endovascular thrombosis
What is the clinical manifestation for Bacillary hemoglobinuira caused by C. Haemolyticum
- Acute- sudden death in 10-12hrs
- Subacute (3-4) days- fever jaundice, anorexia, abdominal pain, rapid deep breathing, decreased milk production, blood in feces and urine
Cow bladder with red “water” in urine, what is likely cause and disease
C. Haemolyticum causing bacillary hemoglobinuria
How can you dx C. Haemoglobinuria/ bacillary hemoglobinuira
- Hx
- Necropsy- lesions/ infarcts on liver
- Decreased blood cell and hemoglobin concentration
What is tx for Bacillary hemoglobinuira
- Antitoxin
- Blood transfusion and fluid therapy
T or F: antibiotics are an effective tx for bacillary hemoglobinuira
False- likely ineffective
How do you control C. Haemolyticum/ bacillary hemoglobinuira
Vaccination- seasonal 1 dose prior to dry season
What is the primary cause of malignant edema- gas gangrene leading to necrotizing Clostridial infection of soft tissue
C. Septicum
C. Septicum has high incidence in what species
Horses and cattle
Where is C. Septicum found
Soils, animal and human small intestine
How do animals get infected with C. Septicum
Endospores or vegetative cells contaminate wounds
What are the virulence factors associated with C. Septicum and what does it do
- ATX- alpha toxin- pore forming lethal toxin—> leads to cell oncosis/ swelling or ischemic death
How does the C. Septicum toxin spread
Hematogenous spread
What are the risk factors for C. Septicum
Poor hygiene practices
What are the general signs of C. Septicum
Develop 6-49ers after injury or endospore activation leading to anorexia, intoxication, high fever, local lesions, reluctance to move
What local lesions are associated with C. Septicum
- Large amounts of exudate infiltrate SQ or intramuscular CT, muscles are dark brown, black or red
- Progressed state- extensive sloughing of skin
What lesion occurs in post patruient cows caused by C. Septicum
1-3 days after calving get necrotizing vulvovaginitis and metritis associated with lacerations at parturition, marked edema, severe toxemia, and death
What is likely cause. You also noted skin sloughing off locally.
C. Septicum
How do you dx C. Septicum
- Fluorescent antibodies
- PCR
- Gram stain- gram + rods
What is a helpful way to dx C. Septicum in horses
Clostridial diseases cause IMHA so do blood smear, notice echinocytosis: toxin altered RBC membranes
Blood smear from horse, you also note dark brown/black muscles and sloughing of skin. What is likely cause and how does histo support that
C. Septicum
Histo: echinocytosis: toxin altered RBC membranes
What is tx for C. Septicum
High dose penicillin, tetracycline or broad spectrum antibiotics
How do you control C. Septicum
Multivalent vaccine
What is causative against of Big head or swollen head
C. Novyi type A- TcnA toxin
What is common cause of Big head or swollen head
Young rams butting heads, breaks in skin, endospores enter, bruising provides good conditions for endospore germination
What is tx for big head or swollen head
Broad spectrum antibiotic or penicillin
How do you control big head or swollen head
Multivalent vaccine
What is likely cause and disease
C. Novyi type A causing big head/ swollen head
What clostridial causes gas gangrene
C. Perfringens type A
Where is C. Perfringens type A found
Soil, marine sediment, GI tract
How do animals get infected with C. Perfringens type A
Infection following trauma
What is key virulence factor for C. Perfringens type A
CPA-alpha toxin-phospholipase, hemolytic, necrotizing
What are clinical signs of C. Perfringens Type A
Rapid progression, extensive invasion of damaged skeletal muscle, gas production- SQ crepitation
How do you dx C. Perfringens type A
- Fluorescent antibodies of bacteria
- Anaerobic isolation and culture- double zone of hemolysis on blood agar (target shape)
What is likely cause
C. Perfringens type A
What is tx for C. Perfringens type A
Usually ineffective but Penicillin or other broad spectrum antibiotic
How do you control C. Perfringens type A
Vaccination for cattle: toxoid A
NOT PART OF MULTIVALENT VACCINE
What clostridium is associated with ruminants and horses and causes fatal myositis and hepatic disease
Paeniclostridium sordellii
What is toxin for P. Sordellii and what does it do
TcsL- toxin clostridium sordellii- modifies Ras and Rac GTPases altering cell cytoskeleton leading to apoptosis
Myonecrosis caused by __organism is fatal
P. Sordellii
What are the clinical manifestations in horses with P. Sordellii
- Acute rhabdomyolysis- breakdown muscle tissue leading to release of myoglobin in blood
- Hepatic disease
- Fatal disease in perinatal foals
What does P. Sordellii cause in sheep
Fatal uterine infections post labor
What is tx for P. Sordellii
There is no tx
How do you control P. Sordellii
Multivalent vaccine
What does the alpha toxin associated with C. Perfringens do and what is it also known as
Aka CPA or PLC
Hydrolyzes phosphatidylcholine and sphingomyelin and leads to production and release of IL-8, neutrophil chemoattractant
What does beta toxin of C. Perfringens do and what is it also known as
Aka CPB
Pore forming toxin targeting array of host cells
What does epsilon toxin of C. Perfringens do and what is it also known as
Aka ETX
Pore forming toxin that binds lipid rafts in host cell membranes leading to ion exchange and apoptosis
What does the iota toxin for C. Perfringens do and what is it also known as is
Aka ITX
Ia enters cell via Ib pore and disrupts host cell actin leading to cell death
What does enterotoxin for C. Perfringens do and what is it also known as
Aka CPE
Causes pore formation in apical side of epithelial cells- loss of ion homeostasis and apoptosis
What does NetB toxin of C. Perfringens do and what is it also known as
Aka necrotic enteritis toxin B
Recognizes cholesterol free regions in cell membranes, forms pores that allow entry of ions
What is the most widespread toxotype for C. Perfringens in environment
Type A-CPA toxin
What C. Perfringens toxin is a common inhabitant of mammalian microbiota
Type A- CPA toxin
CPA toxin is known to be a critical toxin in what 2 diseases
- Gas gangrene
- Gangrenous mastitis
Abomasum from cow, what C. Perfringens toxin likely caused this
type A- CPA toxin
What toxins are included in type B C. Perfringens
CPA, CPB, ETX toxins
What clostridium type causes lamb dysentery
Type B- CPA, CPB and ETX toxins
Older lambs that have loss of condition, depression, reluctance to suckle and neurological signs likely have what perfringens type
Type B-CPA, CPB, ETX (ETX causes brain lesions)
What toxins are associated with C. Perfringens type C
CPA, CPB and some CPE
Changes to __lead to overgrowth of C. Perfringens type C
Microbiota
C. Perfringens type C is often detected in feces of __that is transferred to ___ shortly after pig
Sows, piglets
What happens in calves with C. Perfringens type C
Acute diarrhea, abdominal pain, convulsions, opsithotonos (necrotizing enteritis)
What happens in pigs with infected with C. Perfringens type C
Acutely ill within few days of birth: diarrhea, dysentery, reddening of anus (necrotizing enteritis)
High fatality rate
What happens in foals infected with C. Perfringens type C
Acute dysentery, toxemia, and rapid death (necrotizing enteritis)
How do you dx C. Perfringens type C
Necropsy- hemorrhagic enteritis with ulceration of mucosa
Intestines have deep blue-purple appearance
What is tx for C. Perfringens type C
Usually ineffective but type C antitoxin or antibiotic in piglets less than 2hrs of age
How do you control C. Perfringens
- Vaccination of pregnant animals in last 3rd or pregnancy
- Antitoxin to newborn of unvaccinated mother
Intestines of piglet, calve, or foal that had acute diarrhea, dysentery. What is likely cause
C. Perfringens type C
What toxins are associated with Type D C. Perfringens
CPA, ETX, and some CPE
What C. Perfringens type is also called overeating disease, pulpy kidney
Type D
What species is likely infected with C. Perfringens type D and what is cause
Lambs from 3-10 weeks or weaned in feedlots due to high carbohydrate diets, lush green pastures
What is the virulence factor and pathogenesis associated with C. Perfringens type D
- Overgrowth of type D with production of ETX
- ETX is absorbed into blood stream and disseminates
- Edema and necrotic lesions in brains, lungs, and kidneys
Why would colostrum be effective at preventing C. Perfringens type D
Colostrum contains trypsin inhibitors which is what activates protoxin in GI tract
How do you dx C. Perfringens type D
- Fecal smears with G+ rods
- Confirmation of ETX gene via PCR
How do you control for C. Perfringens type D
- Vaccination
- For outbreaks use antitoxin and revaccinate
What toxins are in C. Perfringens type F
CPA and CPE toxins
What species are typically affected by C. Perfringens type F
Cats and dogs
What are some clinical signs of C. Perfringens type F in dogs and cats
Diarrhea, dehydration, fever abdominal pain, with or without hypovolemic shock (hemorrhage)
How do you dx C. Perfringens type F
Large gram + bacilli in feces or ELISA for CPE
How do you tx C. Perfringens type F
IV fluids and metronidazole
What is mechanism of action of metronidazole
Breaks DNA blocks replication and transcription
What toxins are present in C. Perfringens type G
CPA and NetB toxins
What does C. Perfringens type G cause in birds
Necrotic enteritis in poultry
What are some signs of C. Perfringens type C in poultry
Sudden increase in morality, depression, ruffled feathers, diarrhea
What does the necropsy look like of poultry infected with C. Perfringens type G
Dark, swollen, and firm liver, distended gall bladder, watery brown, blood tinged fluid, foul-smelling brown fluid in intestines
Where is C. Difficicle found
Large intestine of healthy and sick animals, resistant spores found wherever animal is housed
C. Difficle associated with diarrhea is linked to changes in ___ caused by ___
Intestinal microbiota caused by antibiotics, feed changes, stress, NSAIDS
C. Difficle disease is worse in animals with expanded LI like __, ___, and ___
Horses, rabbits and swine
How is C. Difficle spread
Massive number in feces of antibiotic treated animals
What toxins are associated with C. Difficle and what do they do
- CDT- C. Difficle transferase
- TcnA and TcdB: glycosylating toxins induce cytoskeletal changes compromising epithelial cell barrier
All 3 toxins disrupt actin cytoskeleton and induce severe inflammatory response
How do you dx C. Difficle
- Fecal PCR for toxin genes
- ELISA for TcdA and TcdB toxins
How do you tx C, Difficle
Metronidazole, fecal transplants
How do you control C. Difficle
Probiotics at time of antibiotics to reduce risk
