Diseases associated with Clostridium species

Clostridia are all potent producers of exotoxins, upon which their pathogenicity depends. The
toxins of the different organisms vary in their effects and in the manner in which they gain entry
to the circulation; they may be:
• Ingested preformed in the feed, as in botulism
• Absorbed from the gut after abnormal proliferation of the causative organism in the
alimentary tract, as in enterotoxemia
• Elaborated in a more proper infection of the tissues, such as blackleg.
Other clostridial infections develop as local infections with elaboration of toxins in minor lesions,
as in tetanus, black disease, braxy and bacillary hemoglobinuria.

Pathogenic clostridia are commonly present in soils rich in humus and may multiply in soil in
warm weather following heavy rain. They are also found in the intestinal contents of normal
animals and cause disease only in special circumstances. The diseases caused by clostridia can be
effectively prevented in almost all instances by vaccination with killed culture vaccines.

Bacillary Hemoglobinuria

Etiology
Clostridium haemolyticum (C. novyi type D) is a soil-borne anaerobe. In infected areas the organism
is often found in the livers of healthy cattle. Under anaerobic conditions the organism grows and
produces a necrotoxic and hemolytic toxin that is responsible for the clinical disease. Damage to the
liver has been suggested as precipitating causes.

Epidemiology
Occurrence
Bacillary hemoglobinuria has been reported principally from the western part of the USA, Canada,
Mexico, Venezuela, Chile, Turkey, Australia, New Zealand, the UK, and Ireland.

Risk factors
Animal risk factors
Cattle are the usual species involved although occasional cases occur in sheep and rare cases in pigs.
As is the case in many clostridial diseases, animals in good condition are more susceptible.

Environmental risk factors

Bacillary hemoglobinuria is a disease of the summer and autumn months. A primary association
occurs with pastures that also are associated with the occurrence of liver fluke.

The disease is spread from infected to noninfected areas by flooding, natural drainage, contaminated
hay from infected areas, or carrier animals. Contamination of pasture may occur from feces or from
decomposing cadavers.

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Pathogenesis
It is probable that under natural conditions in endemic areas invasion occurs from the alimentary
tract after ingestion of contaminated material. Migrating flukes are the primary factor leading to
liver necrosis and the establishment of anaerobic conditions in the liver that will lead to the
multiplication of the causative organism. Under the anaerobic conditions, the necrotoxic and
hemolytic beta toxin is released systemically to result in toxemia, generalized vascular damage
and intravascular hemolysis.

Clinical Findings
Animals brought into contact with the infection in endemic areas seldom develop disease until 7-10
days later. The illness is of short duration and cattle at pasture may be found dead without signs
having been observed. More often there is a sudden onset, with complete cessation of rumination,
feeding, lactation, and defecation. Abdominal pain is evidenced by disinclination to move and an
arched back posture. Grunting may be evident on walking. Respiration is shallow and labored and
the pulse is weak and rapid. Fever (39.5-41°C) is evident in the early stages but the temperature
subsides to subnormal before death. Edema of the brisket is a common finding. The feces are dark
brown; there may be diarrhea with much mucus and some blood. The urine is dark red. Jaundice is
present but is never very obvious. The duration of the illness varies from 12 hours in dairy cows in
advanced pregnancy to 4 days in dry stock. Pregnant cows often abort. Severe dyspnea is evident
just before death. The disease in sheep presents with similar signs.

Clinical Pathology
The red color of the urine is due to the presence of hemoglobin: there are no free red cells. In the
later stages there is anemia, the erythrocyte count being depressed. Leukocyte counts vary
considerably. Differential counts vary similarly, with a tendency to neutrophilia in severe cases.
Blood cultures during the acute stages of the disease may be positive.

Necropsy Findings
Rigor mortis develops quickly. The perineum is soiled with bloodstained urine and feces.
Subcutaneous, gelatinous edema, which tends to become crepitant in a few hours, and extensive
petechial or diffuse hemorrhages in subcutaneous tissue are characteristic. There is a variable degree
of jaundice. Excessive amounts of fluid, varying from clear to bloodstained and turbid, are present
in the pleura, pericardial and peritoneal cavities. Generalized subserous hemorrhages are also
present. Similar hemorrhages appear under the endocardium. Hemorrhagic abomasitis and enteritis
are accompanied by the presence of bloodstained ingesta or free blood. The characteristic lesion of
bacillary hemoglobinuria is an ischemic infarct in the liver. One or more may be present in any part
of the organ and vary from 5-20 cm in diameter. The infarct is pale, surrounded by a zone of
hyperemia, and has the general appearance of local necrosis. Red urine is present in the kidneys and
bladder and petechiation is evident throughout the kidney.

Diagnosis
C. haemolyticum can be isolated from the liver infarct and many other organs from a fresh carcass,
but postmortem invaders quickly obscure its presence. A positive fluorescent antibody test on
impression smears taken from the hyperemic zone around the liver infarct and stained with FITC-
labeled rabbit antisheep C. novyi antiserum will confirm the presence of C. novyi-type organisms
but cannot differentiate type B from type D. A PCR test to identify toxin –producing genotypes of
Clostridium spp. may assist in the identification of isolates.
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Samples for confirmation of diagnosis
• Bacteriology - tissue from edge of liver infarct, placed in an airtight container; four air-dried
impression smears from lesion border (anaerobic CULT, FAT)
• Histology - fixed liver lesion, kidney

Differential Diagnosis
The diagnosis of bacillary hemoglobinuria is largely a question of differentiation from other
diseases in which hemoglobinuria, myoglobinuria, and hematuria are cardinal signs. In an animal
found dead differentiation from other clostridial diseases and anthrax may be required.

• Acute leptospirosis
• Postparturient hemoglobinuria
• Hemolytic anemia caused by cruciferous plants
• Babesiosis and anaplasmosis
• Enzootic hematuria
• Chronic copper poisoning (sheep)

Treatment
Specific treatment includes the immediate use of penicillin or tetracyclines at high doses and
antitoxic serum if available. Prompt treatment is essential: provided that the serum is administered
in the early stages of the disease, hemoglobinuria may disappear within 12 hours.

Supportive treatment – including blood transfusion, parenteral fluid, and electrolyte solutions - is of
considerable importance. Care is required during treatment and examination, as undue excitement or
exercise may cause sudden death. Hemopoiesis should be facilitated by the provision of mineral
supplements containing iron, copper, and cobalt.

Control
A formalin-killed whole culture adsorbed on aluminum hydroxide gives good protection for a year
in cattle. Vaccination is carried out 4-6 weeks before the expected occurrence of the disease. Annual
revaccination of all animals over 6 months of age is necessary in enzootic areas. The carcasses of
animals dying of the disease should be disposed of by burning or deep burial.

Blackleg
Etiology
True blackleg, the clostridial myositis of skeletal muscles, is associated with Clostridium chauvoei.

Epidemiology
Occurrence
When the disease occurs it is usual for a number of animals to be affected within the space of a few
days. The disease is enzootic in particular areas, especially when they are subject to flooding; such an
area may vary in size from a group of farms to an individual field.

The case fatality rate in blackleg approaches 100%.

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Source of infection
Blackleg is a soil-borne infection but the portal by which the organism enters the body is still in
dispute. It is presumed that the portal of entry is through the alimentary mucosa after ingestion of
contaminated feed or associated with erupting teeth. The bacteria may be found in the spleen, liver,
and alimentary tract of normal animals, and contamination of the soil and pasture may occur from
infected feces or decomposition of carcasses of animals dying of the disease. True blackleg develops
when spores that are lodged in normal tissues are caused to proliferate by mechanisms such as
trauma or anoxia.

Transmission
In cattle the disease usually occurs without a history of trauma but in sheep is almost always
associated with a wound infection. Infection of skin wounds at shearing and docking and of the navel
at birth may cause the development of local lesions. Infections of the vulva and vagina of the ewe at
lambing may cause serious outbreaks and the disease has occurred in groups of young ewes and rams
up to a year old, usually as a result of infection of skin wounds caused by fighting. Occasional
outbreaks have occurred in sheep after vaccination against enterotoxemia. Presumably the
formalinized vaccine causes sufficient tissue damage to permit latent spores of the organism to
proliferate.

Risk factors
Environment risk factors
Typical blackleg of cattle has a seasonal incidence, with most cases occurring in the warm months of
the year. In some areas there is an increased prevalence in years of high rainfall. Outbreaks of
blackleg in cattle have occurred following excavation of soil, which suggests that disturbance of the
soil may expose and activate latent spores.

Animal risk factors

In cattle the disease is largely confined to young stock between the ages of 6 months and 2 years,
although disease occurs occasionally in younger animals and cattle up to 3 years. In the field, risk
factors include rapidly growing cattle and a high plane of nutrition. Elevation of the nutritional status
of sheep by increased protein feeding increases their susceptibility to blackleg. In sheep there is no
restriction to age group.

Pathogenesis
In true blackleg the stimulus that results in growth of the latent bacterial spores is unknown. There is
usually no history of trauma. Toxin formed by the organism produces a severe necrotizing myositis
locally in skeletal muscles, and a systemic toxemia that is usually fatal. In cattle and sheep atypical
outbreaks of sudden death occur in which the lethal lesion is a clostridial cardiac myositis.

Clinical Findings
Cattle
If the animal is observed before death there is severe lameness, usually with pronounced swelling of
the upper part of the affected leg. On closer examination the animal will be found to be very
depressed and have complete anorexia and ruminal stasis, and a high temperature (41°C) and pulse
rate (100-120/min). Pyrexia is not present in all cases. In the early stages the swelling is hot and
painful to the touch but soon becomes cold and painless, and edema and emphysema can be felt. The
skin is discolored and soon becomes dry and cracked.
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Although the lesions are usually confined to the upper part of one limb, occasional cases are seen
where the lesions are present in other locations such as the base of the tongue, the heart muscle, the
diaphragm and psoas muscles, the brisket, and the udder. Lesions are sometimes present in more than
one of these locations in one animal. The condition develops rapidly and the animal dies quietly 12-
36 hours after the appearance of signs. Many animals die without signs having been observed.

Sheep
When blackleg lesions occur in the limb musculature in sheep, there is a stiff gait and the sheep is
disinclined to move because of severe lameness in one limb or, more commonly, in several limbs.
The lameness may be severe enough to prevent walking in some animals but be only moderate in
others. Subcutaneous edema is not common and gaseous crepitation cannot be felt before death.
Discoloration of the skin may be evident but skin necrosis and gangrene do not occur.

In those cases where infection occurs through wounds of the skin, vulva, or vagina there is an
extensive local lesion. Lesions of the head may be accompanied by severe local swelling due to
edema and there may be bleeding from the nose. In all instances there is high fever, anorexia, and
depression, and death occurs very quickly. Sheep and cattle with cardiac myositis associated with C.
chauvoei are usually found dead.

Clinical Pathology
It may be possible to obtain material suitable for cultural examination by needle puncture or swabs
from wounds. There are no constant changes in hematological parameters or serum biochemistry.

Necropsy Findings
Cattle found dead of blackleg are often in a characteristic position; lying on the side with the affected
hindlimb stuck out stiffly. Bloating and putrefaction occur quickly and bloodstained froth exudes
from the nostrils and anus. Clotting of the blood occurs rapidly. Incision of the affected muscle mass
reveals dark red to black, swollen tissue with a rancid odor and thin, sanguineous fluid containing
bubbles of gas. Freshly cut surfaces are often dry and may have a metallic sheen. The heart and all
skeletal muscles, including those of the tongue, diaphragm, and lumbar region, must be checked, as
the lesion may be small and escape cursory examination. The thoracic cavity and the pericardial sac
may contain excess bloodstained fluid with variable amounts of fibrin. This serositis is often
overlooked, or is misinterpreted as a component of pleuropneumonia. The lungs are usually
congested and may be atelectatic as a result of abdominal tympany.

In sheep the muscle lesions are more localized and deeper and the subcutaneous edema is not so
marked, except around the head. Gas is present in the affected muscles but not in such large amounts
as in cattle. When the disease has resulted from infection of skin wounds, the lesions are more
obvious superficially, with subcutaneous edema and swelling and involvement of the underlying
musculature. When invasion of the genital tract occurs, typical lesions are found in the perineal
tissues and in the walls of the vagina and occasionally the uterus.
In the special case of pregnant ewes, typical lesions may involve the entire fetus and cause abdominal
distension in the ewe.

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Diagnosis
In typical cases of blackleg in cattle a definite diagnosis can be made on the clinical signs and the
necropsy findings. Definitive identification of C. chauvoei is by fluorescent antibody staining.
Isolation of the organism from specimens collected from the lesion may also be attempted.

Differential Diagnosis
• Malignant edema
• Anthrax
• Lightning strike
• Bacillary hemoglobinuria
• Other causes of sudden unexpected death

Treatment
Treatment of affected animals with penicillin and surgical debridement of the lesion, including
fasciotomy, is indicated if the animal is not moribund. Recovery rates are low because of the
extensive nature of the lesions. Large doses (40 000 IU/kg BW) should be administered,
commencing with crystalline penicillin intravenously and followed by longer-acting preparations.
Blackleg antiserum is unlikely to be of much value in treatment unless very large doses are given.

Control
Cattle
On farms where the disease is enzootic, annual vaccination of all cattle between 3 and 6 months with
two vaccinations given 4w ks apart followed by an annual booster vaccination is recommended. This
should be done just prior to the anticipated danger period. Maternal immunity persists for at least 3
months and will interfere with active immunity in calves vaccinated before this age.

In an outbreak all unaffected cattle should be vaccinated immediately and injected with penicillin at a
dose of 10 000 IU/kg BW intramuscularly or a combination of penicillin and benzathine penicillin.
Movement of the cattle from the affected pasture is advisable.
Sheep
With sheep in areas where the disease is enzootic, the maiden ewes should be vaccinated twice, the
last vaccination given about 1 month before lambing and a subsequent yearly booster given at the
same time before lambing. This will prevent infection of the ewes at lambing and will also protect
lambs against umbilical infection at birth and infection of the tail wound at docking, provided the tail
is docked at a young age. If an outbreak commences in a flock of ewes at lambing time, prophylactic
injections of penicillin and antiserum to ewes requiring assistance are recommended.

A single vaccination of wethers can also be carried out 2-3 weeks before shearing if infection is
anticipated. Because of the common occurrences of the disease in young sheep, vaccination before
they go on to pasture and are exposed to infection of skin wounds from fighting is recommended in
danger areas.
It is important that carcasses of animals dying of blackleg are destroyed by burning or deep burial to
limit soil contamination.

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 Tetanus

Etiology
An exotoxin, tetanospasmin, is produced by Clostridium tetani growing under anaerobic conditions.
The organism forms spores that can persist in soil for many years. The spores are resistant to many
standard disinfection procedures, including steam heat at 100°C for 20 minutes but can be destroyed
by heating at 115°C for 20 minutes.

Epidemiology
Occurrence
Tetanus occurs in all parts of the world and is most common in closely settled areas under intensive
cultivation. It occurs in all farm animals, mainly as individual, sporadic cases, although outbreaks are
occasionally observed in young cattle, young pigs, and lambs following wounding management
procedures.
Case fatality rate
In young ruminants the case fatality rate is over 80%, but the recovery rate is high in adult cattle. In
horses it varies widely between areas. In some areas almost all animals die acutely, in others the
mortality rate is consistently about 50%.
Source of infection
C. tetani organisms are commonly present in the feces of animals, especially horses, and in the soil
contaminated by these feces. Surveys in different areas of the world show it is present in 30-42% of
soil samples. The survival period of the organism in soil varies very widely from soil to soil.
Transmission
The portal of entry is usually through deep puncture wounds but the spores may lie dormant in the
tissues for some time and produce clinical illness only when tissue conditions favor their
proliferation. For this reason the portal of entry is often difficult to determine. Puncture wounds of the
hooves are common sites of entry in horses. Introduction to the genital tract at the time of parturition
is the usual portal of entry in cattle. A high incidence of tetanus may occur in young pigs following
castration and in lambs following castration, shearing, docking, vaccinations, or injections of
pharmaceuticals especially anthelmintics. Docking by the use of elastic band ligatures is reputed to be
especially hazardous. Neonatal tetanus occurs when there is infection in the umbilical cord
associated with insanitary conditions at parturition.
Animal risk factors
The neurotoxin of C. tetani is exceedingly potent but there is considerable variation in susceptibility
between animal species, horses being the most susceptible and cattle the least. The variation in
prevalence of the disease in the different species is partly due to this variation in susceptibility but is
also because exposure and wounding management practices are more likely to occur in some species
than in others.
Importance
Tetanus is important because of its high case fatality and the very long convalescence in the
survivors.

Pathogenesis
The tetanus bacilli remain localized at their site of introduction and do not invade surrounding tissues.
They proliferate and produce tetanolysin and tetanospasmin only if certain environmental conditions
are attained, particularly a lowering of the local tissue oxygen tension. Tetanolysin promotes local
tissue necrosis.
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Tetanospasmin diffuses to the systemic circulation, is bound to motor end-plates and travels up
peripheral nerve trunks via retrograde intra -axonal transport. The exact mechanisms by which the
toxin exerts its effects on nervous tissue are not known but it blocks the spontaneous and nerve-
impulse-evoked release of neurotransmitter, resulting in the disinhibition of gamma motor neurons.
No structural lesions are produced but there is central potentiation of normal sensory stimuli so that a
state of constant muscular spasticity is produced and normally innocuous stimuli cause exaggerated
responses. Death occurs by asphyxiation due to fixation of the muscles of respiration.

Clinical Findings
The incubation period varies between 3 days and 4 weeks, with occasional cases occurring as long as
several months after the infection is introduced. In sheep and lambs cases appear 3-10 days after
shearing or docking.

Clinical findings are similar in all animal species. Initially, there is an increase in muscle stiffness,
accompanied by muscle tremor. There is trismus with restriction of jaw movements, prolapse of the
third eyelid, stiffness of the hind limbs causing an unsteady, straddling gait, and the tail is held out
stiffly, especially when backing or turning. Retraction of the eye and prolapse of the third eyelid - a
rapid movement of the third eyelid across the cornea followed by a slow retraction - is one of the
earliest and consistent signs (with the exception of sheep) and can be exaggerated by sharp lifting of
the muzzle or tapping the face below the eye. Additional signs include an anxious and alert
expression contributed to by an erect carriage of the ears, retraction of the eyelids and dilation of the
nostrils, and hyperesthesia with exaggerated responses to normal stimuli.

The animal may continue to eat and drink in the early stages but mastication is soon prevented by
tetany of the masseter muscles, and saliva may drool from the mouth. If food or water are taken,
attempts at swallowing are followed by regurgitation from the nose. Constipation is usual and the
urine is retained, partly as a result of inability to assume the normal position for urination. The rectal
temperature and pulse rate are within the normal range in the early stages but may rise later when
muscular tone and activity are further increased. In cattle, particularly young animals, bloat is an early
sign but is not usually severe and is accompanied by strong frequent rumen contractions.

As the disease progresses, muscular tetany increases and the animal adopts a 'sawhorse' posture.
Uneven muscular contractions may cause the development of a curve in the spine and deviation of the
tail to one side. There is great difficulty in walking and the animal is inclined to fall, especially when
startled. Falling occurs with the limbs still in a state of tetany and the animal can cause itself severe
injury. Once down it is almost impossible to get a large animal to its feet again. Tetanic convulsions
begin in which the tetany is still further exaggerated. Opisthotonos is marked, the hind limbs are stuck
out stiffly behind and the forelegs forward. Sweating may be profuse and the temperature rises, often
to 42°C. The convulsions are at first only stimulated by sound or touch but soon occur spontaneously.
In fatal cases there is often a transient period of improvement for several hours before a final, severe
tetanic spasm during which respiration is arrested.

The course of the disease and the prognosis vary both between and within species. The duration of a
fatal illness in horses and cattle is usually 5-10 days but sheep usually die on about the third or fourth
day. A long incubation period is usually associated with a mild syndrome, a long course and a
favorable prognosis. Mild cases that recover usually do so slowly, the stiffness disappearing gradually
over a period of weeks or even months. The prognosis is poor when signs rapidly progress.
8
Animals vaccinated in the past year have a better prognosis, as do horses that have received parenteral
penicillin and tetanus antitoxin and in which the wound was aggressively cleaned when fresh.

Clinical Pathology
There are no specific abnormalities in blood or cerebrospinal fluid and no antemortem test of value in
confirming the diagnosis. Blood levels of tetanus toxin are usually too low to be detected.

Necropsy Findings
There are no gross or histological findings by which a diagnosis can be confirmed, although a search
should be made for the site of infection. Culture of the organism is difficult but should be attempted.
If minimal autolysis has occurred by the time of necropsy, the identification of large Gram-positive
rods with terminal spores ('tennis-racket morphology') in smears prepared from the wound site or
spleen is supportive of a diagnosis of tetanus.

Samples for confirmation of diagnosis

Bacteriology - air-dried impression smears from spleen, wound site (cyto- Gram stain), culture swab
from wound site in anaerobic transport media; spleen in sterile, leakproof container (anaerobic CULT,
bioassay) .

Treatment
The main principles in the treatment of tetanus are to:
• Eliminate the causative bacteria
• Neutralize residual toxin
• Control muscle spasms until the toxin is eliminated or destroyed
• Maintain hydration and nutrition
• Provide supportive treatment.
There are no structural changes in the nervous system, and the management of cases of tetanus
depends largely on keeping the animal alive through the critical stages.

Elimination of the organism is usually attempted by the parenteral administration of penicillin in

large doses, preferably by intravenous administration. If the infection site is found, the wound should
be aggressively cleaned and debrided but only after antitoxin has been administered, because
debridement, irrigation with hydrogen peroxide, and the local application of penicillin may facilitate
the absorption of the toxin.

Tetanus antitoxin is administered but is of little value once signs have appeared. For optimal results
horses should receive 300 000 IU 12-hourly for three injections. Local injection of some of the
antitoxin around the wound is advised.

Relaxation of the muscle tetany can be attempted with various drugs. Chlorpromazine (0.4-0.8 mg/kg
body weight (BW) intravenously, 1.0 mg/kg BW intramuscularly, three or four times daily) and
acetylpromazine (0.05 mg/kg BW twice daily) administered until severe signs subside, are widely
used 3,5 A combination of diazepam (0.01-0.4 mg/kg) and xylazine (0.5-1.0 mg/kg, intravenously or
intramuscularly) may be effective in horses refractory to phenothiazine tranquilizers.

9
Hydration can be maintained by intravenous or stomach-tube feeding during the critical stages when
the animal cannot eat or drink. The use of an indwelling tube should be considered because of the
disturbance caused each time the stomach tube is passed. Feed and water containers should be
elevated and the feed should be soft and moist.

Additional supportive treatment includes slinging of horses during the recovery period when
hyperesthesia is diminishing. Affected animals should be kept as quiet as possible and provided with
dark, well-bedded quarters with nonslip flooring and plenty of room to avoid injury if convulsions
occur. Administration of enemas and catheterization may relieve the animal's discomfort. This level
of nursing, plus penicillin, ataractic drug and antitoxin for an average of 14 days, can deliver
something like a 50% recovery by an average of 27 days, but the cost is high.

Horses that fall frequently sustain bone fractures and may need to be destroyed.

Control
Many cases of tetanus could be avoided by proper skin and instrument disinfection at castrating,
docking, and shearing time. These operations should be carried out in clean surroundings; in the case
of lambs docked in the field, temporary pens are to be preferred to permanent yards for catching and
penning.

Passive immunity
Short-term prophylaxis can be achieved by the injection of 1500 IU of tetanus antitoxin. The
immunity is transient, persisting for only 10-14 days.
Tetanus antitoxin
Tetanus antitoxin should be given to any horse with a penetrating wound or deep laceration, and the
wound should also be cleaned aggressively. Tetanus toxoid can be administered at the same time as
tetanus antitoxin, provided they are injected at different sites and using different syringes. Animals
that suffer injury are usually given an injection of antitoxin and one of toxoid to insure complete
protection.

Tetanus antitoxin is often routinely given to mares following foaling and to newborn foals. In some
areas the risk for tetanus in young foals is high and repeated doses of antitoxin at weekly intervals
may be required for protection.

On farms where the incidence of tetanus in lambs is high, antitoxin is usually given at the time of
docking or castration; 200 IU has been shown to be effective. The risk for tetanus in calves is lower
than in lambs and tetanus antitoxin is not commonly given at the time of castration.

Active immunity
Available vaccines are formalin-inactivated adjuvanated toxoids; they induce long lasting immunity.
Primary vaccination requires two doses 3-6 weeks apart. Protective titers are obtained within 14 days
of the second injection and last for at least a year and up to 5 years.

Traditionally foals have received primary vaccination at 3-4 months of age, however there is evidence
that maternal antibodies acquired by foals born to mares vaccinated shortly before parturition
significantly inhibit the antibody response of the foal to primary vaccination until it is 6 months of
age and that primary vaccination should be delayed until that age.
10
Although immunity lasts longer than 1 year, it is common to revaccinate horses yearly with a single
booster injection. Pregnant mares should receive a booster injection 4-6 weeks before foaling to
provide adequate colostral immunity to the foal.

Ewes are immunized with a similar schedule except that the primary doses are usually given at a
managementally convenient time when the flock is yarded. A prelambing booster vaccination is given
yearly. Commonly, commercial vaccines for sheep also contain antigens for other clostridial diseases
for which sheep are at high risk.

Vaccination of cattle is usually not considered unless an outbreak of the disease has occurred in the
immediate past and further cases may be anticipated.

Botulism
Etiology
The causative organism Clostridium botulinum, a spore-forming anaerobe, produces neurotoxins
during vegetative growth. Spores can survive in the environment for over 30 years. Under favorable
conditions of warmth and moisture the spores germinate and vegetative cells multiply rapidly
laborating a stable and highly lethal toxin which, when ingested, or absorbed from tissues, causes the
disease. The toxin is also capable of surviving for long periods, particularly in bones or if protected
from leaching. Seven antigenically distinct toxin types (A-G), some with subtypes, have been
identified. Farm animal disease is produced primarily by types B, C and D.

The organism is present in the alimentary tract of animals that have recently ingested contaminated
material and may be introduced into new areas in this way, or by birds and blowflies.

Epidemiology
Occurrence
Botulism has no geographical limitations, isolated cases and sporadic outbreaks occurring in most
countries. The source of exposure to toxin and the risk for disease differ between regions because of
differences in food storage, feeding, and management practices. Outbreaks can be associated with
conserved feeds or animals on pasture. The disease usually occurs in a number of animals at one time
and has a high case fatality rate.
Source of infection
Most incidents of botulism are associated with the ingestion of preformed toxin (forage botulism).
Toxin in feeds may result from the primary growth of C. botulinum in the feed or from the
contamination of the feed with toxincontaining carrion (carrion-associated botulism). Less common
sources are growth with toxin production in wounds (wound botulism) or growth and toxin
production in the alimentary tract (toxicoinfectious botulism).

Forage botulism occurs when pH, moisture, and anaerobic conditions in the feedstuff allow the
vegetative growth of C. botulinum and the production of toxin. This can occur in a number of spoiled
stored forages. Cereal silages carry a risk in the USA. Silage and hay may spoil to a stage suitable for
the growth of C. botulinum. This is most likely if the forage is very succulent or is wet by rain when it
is made.

11
Proliferation of the organism can occur in decaying vegetable material. The disease has also occurred
in horses fed on spoiled vegetables and potatoes contaminated by C. botulinum, and on alfalfa
haylage packed in airtight aluminum foil envelopes. Grass clippings allowed to accumulate and decay
in a pile have poisoned horses, as has round bale hay that spoiled after rain. Decaying grass at the
base of old tussocks and in trampled stubble are known to be suitable sites for growth of C.
botulinum. Cases have occurred with brewer's grains, and highmoisture grain has the potential for
toxicity.

Carrion-associated botulism
This is almost always the cause of botulism in animals on pasture, and carrion is also a common cause
of botulism in animals on conserved feeds. Carrion includes domestic and wild animals and birds. In
endemic botulism areas, the carcass of dead animals is invaded by C. botulinum and high
concentrations of toxin are produced such that very small amounts of flesh or bone have lethal
concentrations. Most outbreaks of carrion associated botulism are associated with type C and D
strains, these strains producing much higher concentrations of toxin in carrion than type A and B
strains. Toxin can persist in carrion for at least 1 year. Where the carcasses of rodents, cats, and birds
contaminate hay or Silage, toxin can leach out and contaminate surrounding hay or other feeds to
cause multiple cases of botulism. In one instance a single mouse carcass is believed to have
contaminated 200 000 tons of alfalfa cubes.

Direct carrion ingestion can occur where cattle subsist on a phosphorus deficient diet and manifest
osteophagia, with subsequent ingestion of carrion. The disease is likely to occur in outbreak form. In
sheep, pica is more usually associated with a dietary deficiency of protein or net energy. Occasional
outbreaks occur that are due to drinking of water contaminated by carcasses of dead animals.
Wetlands where outbreaks of avian botulism have occurred are likely to have repeated occurrences
because of soil contamination.

Wound botulism
Wound botulism is rare but is recorded in horses following castration, with omphalophlebitis,
umbilical hernias treated with clamps, with an infected wound and in association with an injection
abscess

Toxicoinfectious botulism
This results when toxin is produced by C. botulinum present in the intestine. The disease is also called
the 'shaker foal syndrome'. It is a disease of young foals up to 8 months of age with the highest
prevalence in foals 3-8 weeks of age.

Risk factors
Animal risk factors
Botulism is most common in birds, particularly the domestic chicken and wild waterfowl. Cattle,
sheep, and horses are susceptible but pigs, dogs, and cats appear to be resistant. The horse appears to
be particularly susceptible to type B toxin. Cattle and sheep are usually affected by types C and D.
Environment risk factors
Botulism in range animals has a seasonal distribution. Outbreaks are most likely to occur during
drought periods when feed is sparse, phosphorus intake is low and carrion is plentiful. Silage-
associated botulism is also seasonal with the feeding of silage.

12
Importance
Severe outbreaks with high case fatality rates can occur when contaminated feed is fed to large
numbers of animals. Under extensive grazing conditions massive outbreaks of carrion-associated
botulism also occur unless the animals are vaccinated.

Zoonotic implications
Botulinum toxin is identified as a possible agent for bioterrorism.
The meat and milk from cattle that have botulism should not be used for human consumption.

Pathogenesis
The toxins of C. botulinum are neurotoxins and produce functional paralysis without the development
of histological lesions. Botulinum toxins are absorbed from the intestinal tract or the wound and
carried via the bloodstream to peripheral cholinergic nerve terminals including neuromuscular
junctions, postganglionic parasympathetic nerve endings, and peripheral ganglia. The heavy chain of
the toxin is responsible for binding to the receptors and translocation into the cell and the light chain
of the toxin for resultant blockade of the release of acetylcholine at the neuromuscular junction.
Flaccid paralysis develops and the animal dies of respiratory paralysis.

Clinical Findings
Cattle and horses
Signs usually appear 3-17 days after the animals gain access to the toxic material, but occasionally as
soon as 1 day, the incubation period being shorter as the amount of toxin available is increased.
Peracute cases die without prior signs of illness, although a few fail to take water or food for a day
beforehand. The disease is not accompanied by fever and the characteristic clinical picture is one of
progressive symmetric muscular paralysis affecting particularly the limb muscles and the muscles of
the jaw, tongue, and throat. Muscle weakness and paralysis commence in the hindquarters and
progress to the forequarters, head, and neck. The onset is marked by very obvious muscle tremor and
fasciculation, often sufficient to make the whole limb tremble. Colic may be an initial sign in horses.

In most cases the disease is subacute. Restlessness, incoordination, stumbling, knuckling, and ataxia
are followed by inability to rise or to lift the head. Mydriasis and ptosis occur early in the clinical
course. Skin sensation is retained. Affected animals lie in sternal recumbency with the head on the
ground or turned into the f1ank.

Tongue tone is reduced, as is the strength of tongue retraction. In some cases the tongue becomes
paralyzed and hangs from the mouth, the animal is unable to chew or swallow and it drools saliva. In
others there is no impairment of swallowing or mastication and the animal continues to eat until the
end. This variation in signs is often a characteristic of an outbreak, all the cases having tongue
paralysis or all of them not having it. Ruminal movements are depressed. Defecation and urination are
usually unaffected, although cattle may be constipated. Paralysis of the chest muscles results in a
terminal abdominal-type respiration. Sensation and consciousness are retained until the end, which
usually occurs quietly, and with the animal in lateral recumbency, 1-4 days after the commencement
of illness.
Occasional field cases and some experimental cases in cattle show mild signs and recover after an
illness of 3-4 weeks. These chronic cases show rest-lessness and respiratory distress followed by
knuckling, stumbling, and disinclination to rise.

13
Anorexia and adipsia are important early signs but are often not observed in pastured animals. In
some there is a pronounced roaring sound with each respiration. The roaring persists for up to 3
months. During the major part of the illness the animals spend most of their time in sternal
recumbency. In some animals there is difficulty in prehending hay but concentrate and ensilage may
be taken. This disability may persist for 3 weeks.

Sheep
Sheep do not show the typical flaccid paralysis of other species until the final stages of the disease.
There is stiffness while walking, and incoordination and some excitability in the early stages. The
head may be held on one side or bobbed up and down while walking (limber neck). Lateral switching
of the tail, salivation, and serous nasal discharge are also common. In the terminal stages there is
abdominal respiration, limb paralysis, and rapid death.

Clinical Pathology
There are no changes in hematological values or serum biochemistry that are specific to botulism.

Laboratory diagnosis of botulism in the live or dead animal is difficult because of the lack of sensitive
confirmatory laboratory tests. Laboratory confirmations is attempted by:
• Detection of preformed toxin in serum, intestinal tract contents, or feed
• Demonstration of spores of C. botulinum in the feed or gastrointestinal contents
• Detection of antibody in recovering or clinically normal at-risk animals.

Necropsy Findings
There are no specific changes detectable at necropsy, although the presence of suspicious feedstuffs in
the forestomachs or stomach may be suggestive. There may be nonspecific subendocardial and
subepicardial hemorrhages and congestion of the intestines. Microscopic changes in the brain are also
nonspecific, consisting mainly of perivascular hemorrhages in the corpus striatum, cerebellum, and
cerebrum. Nonetheless, unless classic flaccid paralysis was observed clinically, the brain should be
examined histologically to eliminate other causes of neurological disease. The presence of C.
botulinum in the alimentary tract is a further test. The presence of toxin in the gut contents is
confirmatory if found but is often misleading, because the toxin may have already been absorbed. The
presence of the toxin in the liver at postmortem examination is taken as evidence that the disease has
occurred. In addition to traditional bioassays such as the mouse protection test, newer methods for
toxin detection include ELISA techniques, and a recently described immuno-polymerase chain
reaction (PCR) assay.
Samples for confirmation of diagnosis
• Bacteriology – suspected contaminated feed material, liver, rumen contents, plus serum
from clinically affected herdmates
• Histology - formalin-fixed brain.
Differential Diagnosis
A presumptive diagnosis is made on the clinical signs and history, occurrence in unvaccinated
animals and the ruling out of other diseases with a similar clinical presentation. The symmetric motor
paralysis of botulism with muscle paralysis that progresses to recumbency in 1 -4 days is a major
differential for botulism from other causes of neurological dysfunction in large animals.

14
Ruminants
Clinically and at necropsy the disease resembles parturient paresis in cattle and hypocalcemia in
sheep but the conditions under which the diseases occur are quite different.
• Tick paralysis
• Paralytic rabies
• Poisoning by Phalaris aquatica
• Organophosphate/carbamate poisoning
• Louping ill in sheep
Horses
• Equine protozoal myelitis
• Equine encephalomyelitis
• Hepatic encephalopathy
• Paralytic rabies
• Ionophore toxicity

Treatment
Recent studies report a survival rate in foals of 96% which was achieved by the early administration
of antitoxin (before complete recumbency) coupled with a high quality of intensive care fluid
therapy, enteral or parenteral feeding, nasal insufflation with oxygen and mechanical ventilation
if required.

Control
In range animals, correction of dietary deficiencies by supplementation with phosphorus or protein
should be implemented if conditions permit. Hygienic disposal of carcasses is advisable to prevent
further pasture contamination. Vaccination with type-specific or combined toxoid is practiced in
enzootic areas.

Infectious Necrotic Hepatitis (Black Disease)

Etiology
Clostridium novyi, type B, is the cause of the disease; it is resident in soil and may be present in the
liver of normal animals. The intervention of a necrotic process in the liver, which causes the organism
to proliferate and produce lethal amounts of toxin, is commonly stated to be the precipitating cause.

Although field outbreaks of the disease are usually precipitated by invasion of the liver by immature
liver fluke it is possible that other causes of local hepatic injury, e.g. invasion by cysts of Cysticercus
tenuicollis, and trauma from liver biopsy may precipitate the disease.
Epidemiology
Occurrence
The disease is worldwide in distribution but is of particular importance in Australia and New Zealand
and to a lesser extent in the UK, the US, and Europe. The disease is always fatal in both sheep and
cattle. It is rare in horses.

Risk factors
Animal risk factors
Well-nourished adult sheep in the 2-4-year age group are particularly susceptible, lambs and yearlings
rarely being affected.
15
Environmental risk factors
The epidemiological association between liver fluke and C. novyi has been supported by the
observation that both are more prevalent in the soil in areas where black disease occurs than in other
areas, and the survival of both the bacteria and the fluke is favored by the same type of soil
environment.

A seasonal occurrence is marked because of fluctuation in the liver fluke and host snail population.
Exposure to fluke infestation, as occurs when sheep graze on marshy ground during dry seasons and
drought, is commonly associated with outbreaks of black disease.

Heavy irrigation of pastures creates favorable conditions for the development of flukes and may
predispose disease. Outbreaks in cattle commonly occur on irrigated farms.

Source of infection
Fecal contamination of the pasture by carrier animals is the most important source of infection,
although the cadavers of sheep dead of the disease may cause heavy contamination. Many normal
animals in flocks in which the disease occurs carry C. novyi in their livers, not all strains being
pathogenic. The spread of infection from farm to farm occurs via these sheep and probably also by
infected wild animals and birds and by the carriage of contaminated soil during flooding.

Pathogenesis
Spores of C. novyi are ingested and carried to the liver in the lymphatic system; the organism can be
isolated from the livers of normal animals. Under local anaerobic conditions, such as occur in the
liver when migrating flukes cause severe tissue destruction, the organisms already present in the liver
proliferate, liberating alpha toxin, which is necrotoxic and causes local liver necrosis and more diffuse
damage to the vascular system. The nervous signs observed may be due to this general vascular
disturbance or to a specific neurotoxin.

Clinical Findings
Sheep
Affected sheep commonly die during the night and are found dead without having exhibited any
previous signs of illness. When observation is possible, clinically affected sheep are seen to segregate
from the rest of the flock, lag behind and fall down if driven. There is fever (40-42°C) which subsides
to a premortal (subnormal) level, and some hyperesthesia; respiration is rapid and shallow; the sheep
remains in sternal recumbency and often dies within a few minutes while still in this position. The
course from first illness to death is never more than a few hours and death usually occurs quietly,
without evidence of struggling.
Cattle
Clinical findings are the same in cattle as in sheep but the course is longer, the illness lasting for 1-2
days. Outstanding clinical findings in cattle include a sudden severe depression, reluctance to move,
coldness of the skin, absence of rumen sounds, a low or normal temperature, and weakness and
muffling of the heart sounds. There is abdorninal pain, especially on deep palpation of the liver, and
the feces are semifluid. Periorbital edema may also develop.

Clinical Pathology
Antemortem laboratory examinations are not usually possible because of the peracute nature of the
disease,
16
Necropsy Findings
Bloodstained froth may exude from the nostrils. The carcass undergoes rapid putrefaction. There is
pronounced engorgement of the subcutaneous vessels and a variable degree of subcutaneous edema.
The dark appearance of the inside of the skin, particularly noticeable on drying, has given rise to the
name black disease. Gelatinous exudate may be present in moderate quantities in the fascial planes of
the abdominal musculature. Bloodstained serous fluid is always present in abnormally large amounts
in the pericardial, pleural, and peritoneal cavities. Subendocardial and subepicardial hemorrhages are
frequent.

The liver is swollen, gray-brown and exhibits characteristic areas of necrosis. These are yellow areas
1-2 cm in diameter and are surrounded by a zone of bright red hyperemia. There is usually evidence
of recent invasion by liver fluke, with channels of damaged liver tissue evident on the cut surface of
the liver.

Diagnosis
A diagnosis of black disease requires the culture of C. novyi from the typical liver lesion and the
demonstration of preformed toxin in the peritoneal fluid and/or the liver lesion from a fresh carcass.

Fluorescent antibody techniques are almost as accurate and much less timeconsuming than traditional
anaerobic culture methods. An ELISA for beta toxin in intestinal contents has been described and
PCR techniques for better identification of toxin-producing strains of clostridia are available.

Samples for confirmation of Diagnosis

• Bacteriology - liver in air-tight container; four impression smears from periphery of lesion
(anaerobic CULT, FAT)
• Histology - fixed liver
Differential Diagnosis
• Acute fascioliasis in sheep can cause heavy mortality due to massive liver destruction at the
same time and under the same conditions as does black disease
• Other clostridial disease - blackleg, malignant edema
• Anthrax

Treatment
No effective treatment is available. In cattle and horses the longer course of the disease suggests the
possibility of controlling the clostridial infection by the parenteral use of penicillin or broad-spectrum
antibiotics but reported cases have high case fatality.

Control
Vaccination with an alum-precipitated toxoid is highly effective and can be carried out during the
course of an outbreak.

17
Control of the disease should also be attempted by control of the liver fluke. Pasture contamination
from cadavers should be minimized by burning the carcasses.

Malignant Edema
Clostridial Myonecrosis (Gas Gangrene)

Etiology
Clostridium septicum, C. chauvoei, C. perfringens, C. sordellii, and C. novyi have all been isolated
from lesions typical of malignant edema of animals. In some cases there can be mixed infections.
The occurrence of malignant edema due to C. chauvoei has been discussed in the section on
blackleg.

Epidemiology
All ages and species of animals are affected. The clostridia that cause malignant edema are common
inhabitants of the animal environment and intestinal tract and, although some of the causative
species have a restricted distribution, the disease is general in most parts of the world. The disease
occurs sporadically, affecting individual animals.

Source of infection
The infection is usually soil-borne. A dirty environment that permits contamination of wounds with
soil is the common predisposing cause.

Transmission
In most cases a wound is the portal of entry. Deep puncture wounds accompanied by severe trauma
provide the most favorable conditions for growth of anaerobes, and malignant edema occurs most
frequently under such conditions. Infection may occur through surgical or accidental wounds
following vaccination, intramuscular injection of drugs, venipuncture, or through the umbilical cord
in the newborn. It is assumed that infection is introduced through the wound but cases of malignant
edema can occur following intramuscular injection of drugs despite careful attention to aseptic
technique. Dormant spores of C. perfringens and other Clostridial species can be found in the
normal muscle of horses and it is possible in some cases that these may be activated by anaerobic
conditions produced by the injected material.

Animal and management risk factors

In horses intramuscular injection of drugs is the common precipitating factor. Certain drugs may
have a greater propensity to initiate muscle necrosis and disease. Perivascular leaking of drugs is
also a precipitating cause in horses. In all species there is risk with the intramuscular injection of
drugs such as anthelmintics and nutritional supplements, some of which can cause significant tissue
damage at the site, particularly if proper asepsis is not practiced.

Outbreaks can occur in sheep after management practices such as shearing, and docking, or
following lambing. Outbreaks have also been observed in cattle following parturition, sometimes
associated with lacerations of the vulva. Castration wounds in pigs and cattle may also become
infected. Unless treatment is instituted in the early stages the death rate is extremely high.

18
The disease 'swelled head', a form of malignant edema, occurs in young rams 6 months to 2 years
old when they are run in bands and fight among themselves.

Importance
Outbreaks of malignant edema are probably less common as a result of education of farmers and the
availability of vaccines. In the wrong circumstances with improper hygiene severe disease can still
occur.

Pathogenesis
Potent necrotoxins are produced in the local lesion and cause death when absorbed into the
bloodstream. Locally the exotoxins cause extensive edema and necrosis followed by gangrene.

Clinical Findings
Clinical signs appear within 6-48 hours of infection. There is always a local lesion at the site of
infection consisting of a soft, doughy swelling with marked local erythema accompanied by severe
pain on palpation. At a later stage the swelling becomes tense and the skin dark and taut.
Emphysema may or may not be present, depending on the type of infection, and may be so marked
as to cause extensive frothy exudation from the wound. With C. novyi infections there is no
emphysema. A high fever (41-42°C) is always present; affected animals are depressed, weak and
show muscle tremor and usually stiffness or lameness. The mucosae are dry and congested and have
very poor capillary refill. The illness is of short duration and affected animals die within 24-48
hours of the first appearance of signs. New cases continue to appear for 3-4 days after shearing or
other precipitating cause.

When infection occurs at parturition, swelling of the vulva accompanied by the discharge of a
reddish-brown fluid occurs within 2-3 days. The swelling extends to involve the pelvic tissues and
perineal region. The local lesions are accompanied by a profound toxemia and death occurs within
1-2 days.

In 'swelled head' of rams the edema is restricted initially to the head. It occurs first under the eyes
and spreads to the subcutaneous tissues of the head and down the neck.

Clinical Pathology
Examination of a Gram-stained smear of aspirated fluid from edematous swellings or swabs from
wounds will give an early diagnosis, allowing therapy early in the course of the disease. A PCR has
been developed to allow the rapid identification and differentiation of the clostridia associated with
malignant edema in livestock. Hematological examination in horses may show evidence of an
immunemediated hemolytic anemia.
Necropsy Findings
Tissue changes occur rapidly after death, particularly in warm weather, and this must be kept in
mind when evaluating postmortem findings. There is usually gangrene of the skin with edema of the
subcutaneous and intermuscular connective tissue around the site of infection. There may be some
involvement of underlying muscle but this is not marked. The edema fluid varies from thin serum to
a gelatinous deposit. It is usually bloodstained and contains bubbles of gas except in C. novyi
infections when the deposit is gelatinous, clear and contains no gas. A foul, putrid odor is often
present in infections with C. perfringens and C. sordellii.

19
Subserous hemorrhages and accumulations of serosanguineous fluid in body cavities are usual. In
'swelled head' of rams the edema of the head and neck may extend into the pleural cavity and also
involve the lungs.

The histological picture of malignant edema consists of abundant edema fluid, emphysema, and
neutrophils within the connective tissues. Muscle is not spared but the damage is focused along
fascial planes.

Differential Diagnosis
The association of profound toxemia and local inflammation and emphysema at the site of a wound
is characteristic.
• Blackleg. The disease is differentiated from blackleg by the absence of typical muscle
involvement and the presence of wounds.
• Anthrax in pigs and horses
• Photosensitivity in white-faced sheep with swelled head

Treatment
Affected animals should be treated as emergency cases because of the acute nature of the disease.
Specific treatment requires the administration of penicillin (high doses of crystalline penicillin
intravenously, repeated at 4-6-hour intervals) or a broad-spectrum antibiotic. Antitoxin aids in
controlling the toxemia but is expensive and must be given very early in the course of the disease. A
nonsteroidal anti-inflammatory drug (NSAID) and supportive therapy are recommended. Injection
of penicillin directly into and around the periphery of the lesions may be of value in some cases.
Local treatment consists of surgical incision to provide drainage, and irrigation with hydrogen
peroxide.

Control
Hygiene at lambing, shearing, castration and docking is essential to the control of the infection in
sheep. Vaccination with a specific or multivalent clostridial bacterin toxoid will prevent the
occurrence of the disease in enzootic areas. Penicillin can be given prophylactically to animals at
risk for the disease.

Enterotoxemia Complex

Etiology
Because of similar etiology, epizootiology, pathogenesis, diagnosis, treatment and control, the
following infections are summarized as enterotoxemia:
• Clostridium perfringens type A infections, (synonyms: sudden death, hemorrrhagic
enteritis, necrotic enteritis);
• Clostridium perfringens type B enterotoxemia, (synonyms: lamb dysentery, scours, lamb
diarrhea);

20
 • Clostridium perfringens type C enterotoxemia, (synonyms: in sheep: struck, hemorrhagic
enterotoxemia, necrotic enteritis, Braxy-like disease; hemorrhagic enteritis or
enterotoxemia in calves; hemorrhagic necrotizing enteritis, necrohemorrhagic
enterocolitis in foals; and hemorrhagic or necrotizing infectious enteritis, enterotoxemia,
bloody scours in piglets);
• Clostridium perfringens type D enterotoxemia, (synonyms: pulpy kidney disease,
enterotoxemia, overeating disease).

The enterotoxemia complex is caused singularly or in combination by the different types of C.

perfringens.

Epidemiology
Occurrence
Enterotoxemia caused by C. perfringens occurs worldwide in all domestic animals.
Risk factors
Enterotoxemia is triggered by change in the diet of the animal. Most commonly, the change that
triggers disease is an increase in the amount of grain, protein supplement, milk or milk replacer (for
lambs and kids), and/or grass that the animal is ingesting. Collectively, these feeds are rich in starch,
sugar, and/or protein. The local specificity of enterotoxemia depends on the locally restricted
occurrence of the organism in the soil and sometimes in the feed.

Pathogenesis
C. perfringens or C. sordellii which can already be present in the intestine multiply massively
because of the sudden increase in nutrients and produce their characteristic pattern of toxins. The
production of toxins in the cells takes place during the vegetative stage. The free toxin is activated
through proteolysis and enhanced in its effect, i.e. enterotoxin is bound to the membrane of the
epithelium of the intestine within one minute whereby ions play an important part. The C.
perfringens enterotoxin changes its beta-structure into a mainly alpha helix-structure and reacts with
the membrane of the intestine in such a way that the transportation of amino acids is inhibited. This
leads to the formation of pores in the membrane of the intestine thus making it permeable.

The numerous metabolites which are produced by the clostridia in the intestine have a wide range of
pathogenic effects on the organism as soon as the toxins are reabsorbed by the mucosa. Epsilon
toxin in particular, which is produced by C. perfringens in the intestine, damages the mucosa of the
intestine and thus allows proteins of higher molecular weight to pass through. Furthermore, the
toxins lead to the destruction of the endothelium of the vessels, produce edemas in all organs with
capillary hemorrhage which appears in the brain stem as characteristic, focal, symmetric
encephalomalacy (FSE) which is the cause of the often peracute course of the disease.

Mistakes in feed management and/or other anthropogenous influences which may trigger
enterotoxemia are
• Pasture rotation in such a way that the animals are suddenly brought onto a pasture with
fresh young grass especially at the beginning of the vegetation time, e.g. the onset of the
rainy season;
• A sudden change of pasture when animals are brought from poor pastures to reserved
pastures with fresh fodder rich in nutrients, for instance at the end of the dry season;

21
 • An irregular supply of supplementary feed, especially molasses during the dry season or in a
feed-lot;
• A disproportionately high percentage of dry matter and a low proportion of crude fiber in
the diet as it occurs in intensive feeding using industrial byproducts;
• Mistakes in the use of milk replacers or excessive supplementary feeding in young animals
as well as mistakes in management which allow calves to take a disproportionately high
amount of milk from the mother.

The disease is always triggered by a disproportionately excessive feed intake which is rich in
nutrients.
The outbreak of the disease may also be favored through unhygienic keeping conditions of the
animals as well as stress and probably also supplement feed which is contaminated with clostridia.

Those strong and well-fed animals in the feed-lot which had a high position in the hierarchy of the
group are most often exposed to the disease.

Clinical Features
The course of enterotoxemia is mostly peracute. The animals die suddenly on the pasture without
having shown previous signs of a disease. Diarrhea and signs of abdominal pain are only
occasionally observed. Signs of nervous disorder, like excitation, ataxia, blindness, tooth grinding
and convulsion may appear; they are typical indications for lesions in the CNS. The animals may
walk in circles. The temperature may rise or be reduced to sub febrile, the mucosae being grey-
violet in color. A typical sign is the opisthotonus which is present in the animals when they are in
agony. The prognosis if unfavorable, and the animals die with violent abdominal pain and tonic-
clonic convulsions.

Shortly before death, the clostridia penetrate the intestinal wall and are distributed throughout the
organism where they multiply before the onset of rigor mortis. This leads to the histolysis with its
characteristic rancid smell because of the metabolically produced fatty acids. The pulpy kidney in
sheep is the result of this development.

Necropsy findings
Necropsy findings vary according to the course of disease. The rumen is usually overfilled with
feed, and the mucosa of the gastrointestinal tract is reddened, showing mucosal petechiation. In
peracute cases in which a necropsy has been performed soon after death, it is often difficult to
recognize pathological lesions.
With careful inspection, circumscribed small grey-yellow foci of necrosis can be found in ruminants
on the surface of the kidney; the renal cortex is clear to midbrown in color and is of a friable
consistency.

During the acute course, catarrhalic enteritis with ulceration of the mucosae is found in all animal
species. The pericardial cavity contains an excessive amount of serous fluid especially in young
lambs in which clots may form on exposure to air. In older animals, ecchymoses appear in the
myocardium and petechiae or hemorrhages in the muscles of the belly and in the intestine. There is
usually severe edema and congestion of the lungs.

22
The most common lesion in subacute cases in lambs is the presence of necrotic foci and ulcers up to
10 mm in diameter in the mucosa of the small and large intestine. These lesions are surrounded by a
zone of hyperemia and a hemorrhage; some coalesce to form large lesions. Ulcers are usually visible
through the intestinal serosa. In severely affected and more chronic cases the ulcers may perforate,
resulting in peritonitis and copious peritoneal effusion that contains fibrin which causes adherence
of adjacent intestinal loops. The intestinal contents vary from being normal to containing almost
pure blood. In calves, the macroscpopic lesions are located in the small intestine, particularly in the
ileum, ranging from severe generalized enteritis to extensive necrosis of the mucous membrane.
Small, yellow diphtheric patches occur in the necrotic areas and the intestinal contents are blood-
stained. Other lesions include congestion of the mucous membrane of the cecum and colon, swelling
and severe hemorrhaging of the mesenteric lymph nodes, as well as congestion of the liver, spleen
and kidneys.

The fast onset of putrefaction is characteristic for any intoxication caused by C. perfringens. A few
hours after death, anaerobic decay of the internal organs is already present. It is typical that the
kidney which decays inside its capsule turning into a pulpy-greasy mass smells sharply of butter
acid (rancid).

Diagnosis
Clostridial enterotoxemia has to be suspected whenever there is a connection between a change in
feeding and sudden death. Nervous symptoms and opisthotonus shortly before death give a hint to
the cause of disease. If the onset of the disease can be stopped by changing the feed, an important
lead regarding the cause has been found.

The laboratory diagnosis has to be accomplished by demonstrating the toxins in the intestinal
contents of dead animals. For this purpose the intestinal contents have to be collected immediately
postmortem, should be conserved and transported deep-frozen and have to be tested for
pathogenicity in mice. The laboratory animals die in convulsions and with symptoms of the
characteristic opisthotonus. By neutralization with type-specific antitoxins, the relevant type of C.
perfringens can be determined.

The microscopic demonstration of clostridia in the intestinal wall is irrelevant. The isolation of C.
perfringens and C. sordellii from the internal organs can be important if the same type has been
isolated from a number of animals affected by the same disease outbreak so perhaps it can be
prevented with the same vaccine.

Differential diagnosis
Because of the mostly peracute course of the disease and the unclear symptoms as well as necropsy
findings, the disease has also been taken for plant poisoning, other intoxications or grass tetany.
Molasses intoxication is often suspected.

Treatment
If enterotoxemia is recognized on time, it can be treated. High doses of tetracycline
(oxytetracycline 10mg/kg b.w.) are efficient. It is best to apply them i.v. If the type of C. perfringens
which causes the respective disease outbreak is known in valuable animals an efficient treatment can

23
be accomplished by applying type-specific hyperimmune serum. Spectacular successes of treatment
have been obtained with homologous hyperimmune sera.

Control
Appropriate management of animals can control enterotoxemia. Preventing sudden changes of
pasture, the provision of feed containing structurally crude fiber and the gradual adaption of the
animals to new feed which is rich in nutrients, and/or changing the rotating pasture system to open
pasturing are efficient means of disease control. Furthermore, care should be taken that feed or
supplement feed in intensive production systems or the feed which is used for young animals is free
of contaminants. The equipment for mixing and transportation as well as application of the feed has
to be kept clean.

If the types of pathogens which are relevant at the respective site are known, enterotoxemia can be
prevented with a homologous toxoid vaccine. A booster vaccination shortly before the onset of the
rainy season will be an efficient prophylactic measure. Enterotoxemia in lambs can be prevented by
booster vaccination of the ewes. The simultaneous application of partially purified hyperimmune
serum and oil adjuvant toxoid vaccine protected lambs against C. perfringens type D enterotoxemia.
Site- and type-specific toxoids prevent enterotoxemia much better than polyvalent vaccines. As
well, young animals which are fattened in a feed-lot can be protected in this way.

An outbreak of enterotoxemia in a herd can be controlled by applying oxytetracycline (LA) to all

animals (10 mg/kg b.w.).

An efficient measure for preventing the disease in a feed-lot is the application of feed antibiotics
(chlortetracycline) provided they are withdrawn at least 4 weeks prior to slaughter.

24