VEIN : Sheep Health & Production : Chapter 14. Sudden death

Under particular dietary conditions, Clostridium perfringens type D proliferates in the small intestine and produces toxins, the principal one being the necrotizing, highly lethal, epsilon toxin. Absorption of this toxin leads rapidly to diarrhoea, convulsions and death. Death may occur so quickly that the diarrhoea is never exhibited.

The conditions which lead to the proliferation of the organism in the intestine are complex. A common factor in many outbreaks is that the sheep are offered a diet to which they are not accustomed. Before ruminal flora adapt to the changed diet partially digested food may spill into the intestine and, if that food includes starch, Cl perfringens may proliferate using the starch as a substrate. The fact that starch is a preferred substrate for this organism leads to the association between the disease, lush feed conditions and individual animals with high growth rates. The disease also occurs under pasture conditions which are anything but lush, for reasons which are not always clear.

The epsilon toxin produces a profuse diarrhoea, stimulation and then depression of the CNS. Damage to the vascular endothelial cells in a variety of organs leads to some characteristic necropsy findings.

Clinical signs of animals acutely affected include clonic convulsions, frothing and sudden death. If they survive more than a few hours there will be a pasty diarrhoea, staggering, opisthotonus and convulsions or, more commonly, struggling. Older sheep may survive for longer (24 hours) and some may even recover.

Necropsy findings

The disease is most frequently diagnosed by necropsy. Putrefaction occurs quickly. In animals examined soon after death, necropsy findings provide reliable diagnostic evidence of the disease.

There is an excess of straw-coloured pericardial fluid, lung oedema with froth and haemorrhages in the endocardium, epicardium and parietal peritoneum. The intestinal contents are creamy, particularly if death was rapid. ’Pulpy kidney’ is not a particularly useful sign because the ’pulpiness’ is in fact a more rapid than usual autolysis.

Glycosuria virtually always occurs and is a consequence of hepatic glycogenolysis and extreme hyperglycaemia. The finding of glycosuria is a useful contribution to diagnosis but not completely pathognomic; glucose is fermented in urine within hours of death. (Note that glycosuria is not a sign of enterotoxaemia in cattle.)

Brain histopathology is particularly useful; often there are symmetrical areas of haemorrhage, oedema and softening, particularly in the basal ganglia but also in other areas.

Control by husbandry procedures

Outbreaks of enterotoxaemia are often controllable by changes to the management of the affected mobs which alter the dietary predispostion to the disease. Exercise, a change of pasture or diet, particularly to one with more roughage, will often stop deaths dramatically. In lambs, tailing and marking and the check in growth rate which accompanies the procedures will usually stop an outbreak. In the case of prime lambs over eights of age, weaning will serve the same purpose.

The results of attempts to control enterotoxaemia in this way are not always successful, or the procedures necessarily practicable. Antiserum is commercially available and is effective in preventing the disease, but only for a few weeks. Antiserum is of no use in treatment of clinical cases of enterotoxaemia.

Control with immunization

A commercial vaccine containing epsilon toxoid of Cl perfringens type D is available from several manufacturers. In describing the use of the vaccine, there are some conventions which are normally observed for describing the first and subsequent administrations of the product.

Dose of vaccination	Name used to describe
1	Primary
2	Secondary
3	First booster
4	Second booster

The protection afforded by one vaccination is short-lived. Complete protection will, therefore, only come from carefully timed, repeat doses of vaccine. The timing varies with the quality of protection desired.

Absolute protection

Protection of lambs to 14 weeks of age

Vaccination of ewes such that they receive a secondary vaccination or booster in the last two weeks of pregnancy will provide passive protection of all lambs to 8 weeks of age, but less than 100% of all lambs will still be protected by maternal antitoxin at 14 weeks of age. Estimates of the proportion of lambs protected vary from 30% to 40%[1][2][3][4] depending on the timing of the ewes’ vaccination history and where one considers the protective level of serum antitoxin to lie between 0.1 and 0.25 [5][6].

For absolute protection, vaccination of lambs should, therefore, commence before they are eight weeks of age if the ewes received a secondary or booster vaccination in late pregnancy, earlier if the ewes did not. Vaccination of lambs can be done within a few days of birth and is effective. Colostral antibodies do not appear to prevent the development of the lamb’s immune response to active immunisation but very high levels of passively acquired antitoxin may reduce the response.

Thus, if lamb marking is performed eight weeks after the start of lambing when most lambs are 5 to 7 weeks of age, secondary or booster vaccination of the ewes two weeks before lambing starts and vaccination of the lambs at marking will virtually guarantee their continuous protection to 14 weeks of age. All lambs will remain protected for 6 to 8 weeks after their primary vaccination; 80% will remain protected after a further 8 to 10 weeks[7].

Protection of lambs beyond 14 weeks of age

To maintain continuous, complete protection, a secondary vaccination should be given within six to eight weeks of the primary dose. It is effective in raising titres to a high level if given two weeks or more after the primary vaccination, but not if given after only one week[8]. The period between primary and secondary doses can be extended to 15 weeks[2] or, probably, longer, based on experiences with other immunogenic agents. As the period between the two initial doses lengthens, however, an increasing proportion of the flock becomes susceptible to the disease. The usual manufacturer’s recommendation that at least four weeks intervene between primary and secondary doses appears to be based on avoiding any possible interference with maternally derived antitoxin by the time of the secondary vaccination.

The duration of immunity following secondary vaccination is probably 15 weeks for 90% of the flock, but only 50% are still protected at 24 weeks. Some reports suggest shorter periods of protection. In Figure 14.1, note the wide range in immune responses and the increase with time in the number of susceptible animals. The minimum protective level here is considered to be 0.15 units/ml of serum (from Jansen, 1967a).

Protection to 1 year of age

Vaccination of ewes in late pregnancy and lambs at 8 and 14 weeks of age will ensure virtually complete protection of all lambs to seven months of age. Each booster vaccination given to animals under 1 year of age will afford a further four months protection to 100% of the flock and five to six months protection to 80% of the flock.

Protection beyond 1 year of age

Booster vaccinations given at least 1 year after the primary vaccination lead to prolonged immunity of 1 year’s duration at least. Further boosters given to animals in their third year of life will produce an immunity of at least 3 years’ duration[7].

Minimum effective protection

An alternative aim to complete protection is the protection of sheep only at those times of the year and at those ages which present the greatest risk of disease. Most deaths from enterotoxaemia occur in animals between 2 weeks and 18 months of age. It is more common during seasonal conditions which favour rapid growth and in British breed and British breed-Merino cross sheep, rather than straight-bred Merinos[9].

On any property, therefore, it may be possible to devise a vaccination program which requires less intense treatment than that affording absolute protection. For example, if enterotoxaemia causes the deaths of lambs before weaning, booster vaccination of ewes in late pregnancy and vaccination of lambs at marking only may completely resolve the problem. If deaths at hogget age occur, one vaccination early in life (coinciding with marking or weaning) and a secondary vaccination before the risk period some months later may be appropriate.

Unless deaths from enterotoxaemia are occurring before ten weeks of age there appears to be no justification for vaccination of ewes annually and in late pregnancy. Many of the recommendations to do so stem from experiences with British breed sheep and their crosses in this and other countries under more intense systems of management than are common in Australia[10].

Economically optimal protection

Vaccination of sheep is practiced primarily to increase the financial success of sheep raising. Vaccination has a cost, in terms of the purchase and storage of vaccine, the labour required to administer it and the losses in production associated with any untoward effects of vaccination. Vaccination programs which afford complete protection to all sheep which are considered at risk, but for which the risk of enterotoxaemia is low, may not be economically justified.

There are several parameters to consider when estimating the risk of death from enterotoxaemia. Firstly, seasonal conditions influence the likelihood of an outbreak and the frequency of suitable conditions may vary from farm to farm. Secondly, management factors, including the choice of maternal and sire breeds influence the probability of an enterotoxaemia outbreak. Thirdly, when an outbreak does occur, it usually only affects one age group within the flock and the mortality rate is commonly 5% to 10%⁽⁹⁾. The variable morbidity may be due to differences in individual animals’ genetic susceptibility, growth rate or immune status. Immunity may stem from natural exposure, one or more immunisation treatments earlier in life, a combination of both or, in the case of lambs, persistence of colostral protection. 20% of unvaccinated animals in Western Australian flocks have protective levels of antitoxin[11].

Similarly, following vaccination, fewer than 100% of animals are protected and the duration of protection varies between animals. The cost-benefit of vaccination against enterotoxaemia must be calculated on the basis of the improvement in protection afforded by vaccination, the risk of losses and the cost of vaccination. For example, in a prime lamb flock, reliance on colostral protection following booster vaccination of ewes in late pregnancy may leave some lambs susceptible to enterotoxaemia between 15 weeks of age and sale. The improvement in protection provided by a vaccination of lambs at 8 weeks of age may not be justified after considering the cost of vaccination, the risk of any enterotoxaemia in lambs of that age, the small proportion of the flock which loses its maternal protection and the damage done to skins and carcases by the injection[3][4].

A computer program has been developed to aid decision making for disease prevention in livestock and can be used to explore the economic rationale of clostridial vaccination. The program is called VAX-N-OMICS and is supported by an ’Agnote’ from the NSW Department of Agriculture and Fisheries[12]. The results from a run with this program for one particular scenario are reported in Figure 14.2.

Producers often make the decision to risk some losses from enterotoxaemia for the sake of timing the administration of vaccine to coincide with other husbandry procedures, such as lamb marking. Considering the cost of labour for mustering and the often marginal cost-benefit of vaccination, such a policy is usually rational, as demonstrated in the ’break-even’ table in Figure 14.2.

As will be discussed below, epsilon toxoid is now virtually always sold in combination with other vaccines, particularly tetanus toxoid and CLA vaccine. The extra protection afforded by these components of the vaccine must also be considered when evaluating the cost-benefit of enterotoxaemia vaccination.

Enterotoxaemia caused by Cl perfringens types A,B,C and E

Type A has been recorded as causing a highly fatal haemolytic disease in sheep. Type A produces more alpha toxin than other types; this toxin is haemolytic. It also is associated with wound infections, causing gas gangrene. Type B causes an enterotoxaemia of lambs under 3 weeks of age - Lamb dysentery. The disease is uncommon in Aust. Toxins involved are (alpha,) beta and epsilon.

Type C causes Struck in UK - an enterotoxaemia with haemorrhagic enteritis and peritonitis affecting adult sheep, usually when feed is abundant. Type B produces alpha and beta toxins. Type E is reported as causing enterotoxaemia in lambs. It produces the iota toxin.

Figure 14.1 the decline in epsilon antitoxin titre in sheep receiving secondary and first booster doses of enterotoxaemia vaccine.

Infectious necrotic hepatitis (Black disease)

A fatal, peracute intoxication caused by Cl novyi type B which proliferates in the liver following tissue damage which produces an anaerobic environment. This anaerobic environment is most often produced by migrating immature F hepatica.

Spores of Cl novyi are continuously ingested by grazing animals where black disease occurs and some spores cross the intestinal wall and populate reticuloendothelial cells - including those in the liver. Immature flukes leave tunnels about 5 mm in diameter which are surrounded by necrotic zones. Any latent spores in these necrotic zones become vegetative, produce toxins which extend the necrotic areas and further multiply.

The disease occurs mainly in adult sheep and less frequently in young sheep and goats. Morbidity rates are usually low (5% to 10%) but the disease is always fatal. It occurs in most areas where liver fluke occurs and is most likely to be seen when sheep are ingesting metacercariae - summer and autumn.

Clinical signs are rarely observed. The course of the illness is only a few hours and sheep are usually found dead with no signs of struggling. At necropsy, rapid putrefaction is obvious and variably other signs :

PARAMETERS THAT CAN BE CHANGED BY THE USER

Description	Current value
Vaccine cost	12 c/dose
Labour cost for vaccination	6 c/dose
Percentage of lambs given booster vaccination	100%
Vaccine efficacy	70%
Minimum average lamb value	$10
Vaccine efficacy	70%
Maximum average lamb value	$30
Minimum % clostridial losses	0.0%
Maximum % clostridial losses (max=25%)	10.0%

Enter new value or press <ENTER> to leave value unchanged:
Press <ESC> to return to the menu.
BREAK-EVEN POINT (% deaths prevented)

The table below sets out the break-even point for a vaccination program for a range of lamb values and vaccination costs.

Average lamb value is the average value of lambs in the flock and the vaccination cost is the total cost of vaccination (vaccine plus labour) using a range of costs around your selected figures.

The break-even point is the average percentage of lambs that must be saved to cover the total cost of the program.

VACCINATION AVERAGE LAMB VALUE

Cost	$10	$15	$20	$15	$30
$0.14	4.0%	2.7%	2.0%	1.6%	1.4%
$0.16	4.6%	3.1%	2.3%	1.9%	1.6%
$0.18	5.2%	3.5%	2.6%	2.1%	1.8%
$0.20	5.8%	3.9%	2.9%	2.3%	2.0%
$0.22	6.3%	4.2%	3.2%	2.6%	2.1%

For: Vaccine= 12 c/dose Labour= 6 c/dose Efficacy= 70 % 100 % of lambs receiving booster vaccination.
Press <P> to print hard copy or any other key to continue .......

EXPECTED RETURNS ($/head)

The table below sets out the expected returns (average profit or loss ($ per lamb) after costs are deducted) from a vaccination program for a range of lamb values and disease incidences.

Average lamb value is the average value of all lambs in the flock, and the % deaths prevented is the expected long term average percentage of clostridial deaths per year in an unvaccinated flock.

% Deaths preventes	Average lamb value
	$10	$15	$20	$15	$30
0.00	-0.36	-0.36	-0.36	-0.36	-0.36
2.00	-0.22	-0.15	-0.08	-0.01	-0.06
4.00	-0.08	0.06	0.20	0.34	0.48
6.00	0.06	0.27	0.48	0.69	0.90
8.00	0.20	0.48	0.76	1.04	1.32
10.00	0.34	0.69	1.04	1.39	1.74

For: Vaccine= 12 c/dose Labour= 6 c/dose Efficacy= 70 %
100 % of lambs receiving booster vaccination.

Figure 14.2 : Results from a run with ’VAX-N-OMIC’. The parameters entered are an attempt to estimate the cost-benefit of giving a primary and secondary vaccination with 5-in-1 vaccine to lambs. The expected protection rate averaged over the ensuing 12 months is 70%. If lambs are worth $20, and the death rate is reduced by 2% by vaccination, the return from vaccination is -$0.08 per lamb. The cost of vaccination (including labour) would need to fall to $0.14 per injection to break-even (from Sergeant, 1992).

Malignant oedema

This name embraces severe wound infections of the subcutaneous tissues and intoxications caused by a variety of clostridial organisms - including Cl septicum most commonly, Cl novyi type A, Cl chauvoei, Cl perfringens type A and Cl sordellii. (Cl novyi type A was previously Cl oedematiens.)

’Swelled head’ is the special case of malignant oedema which occurs in rams and is usually caused by Cl novyi type A (type B toxoid is protective). Blackleg is caused by Cl chauvoei but is an infection of muscles.

The disease follows introduction of the organism and the production of at least a small area of anaerobic necrosis. Wounds caused by shearing, marking, mulesing, fighting, vaccination or ’crow pick’ can lead to clostridial infection. Lambed ewes, particularly if there has been dystocia, can develop malignant oedema of the perineal area.

Clinical signs develop with 12 to 48 hours of wounding and include local swelling, crepitus, heat and redness, the signs varying on the infecting organism. Cl novyi produces oedema rather than gaseous swelling leading to severe oedema of the face, throat and neck.

At necropsy, the oedema fluid may be thin or gelatinous. Gas is present, except with Cl novyi infections, when the fluid is gelatinous, clear and odourless. Cl perfringens and Cl sordellii infections produce a putrid odour.

The longer course of this disease allows the possibility of treatment - and penicillin can be used. Success is only likely in very early cases or when used prophylactically (for example, after assisting ewes at lambing).

Other clostridial diseases

Blackleg

Bacilliary haemoglobinuria

Has been reported overseas in sheep, but mainly cattle. Caused by Cl novyi type D more commonly called Cl haemolyticum.

Braxy (Bradsot)

Caused by Cl septicum, which infects the abomasal wall and produces a fatal toxaemia. Occurs when sheep are grazing heavily frosted pastures. Has occurred in Tasmania.

Clostridial vaccines

In relation to the previous discussion of important clostridial diseases of sheep, the following vaccines are available :

Pulpy kidney     ATPT[13] Cl perfringens type D
Black disease and Swelled head    ATPT Cl novyi type B
Malignant oedema (some forms)     ATPT Cl septicum
               FICl chauvoei

and for less important diseases of sheep:
Blackleg ATPT Cl chauvoei
ATPT Cl septicum
FI Cl chauvoei

Commonly used combinations include :
3-in-1 vaccine PK, Tet, CLA
6-in-1 vaccine PK, Tet, Mal Oed, Black dis, B Leg, CLA

(CLA vaccine is available with most commercial clostridial combinations and adds little to the cost.)

Where any of malignant oedema, swelled head or black disease are a risk, vaccination with 6-in-1 vaccine should be considered - for example, rams are at risk of swelled head and are valuable, it is rational to ensure they are well protected by vaccination. Where those diseases do not occur with a significant incidence, vaccination with only 3-in-1 should be considered.

Anthrax

Most cases of anthrax in sheep are peracute with sheep dying within 1 to 2 hours of first showing signs. Characteristically, there are discharges of tarry blood from all orifices.

The disease is caused by Bacillus anthracis. It is apparent in smears of blood from animals dead from anthrax as gram positive rods which stain well with methylene blue - a distinguishing feature from clostridia. Spores form when the organisms are exposed to oxygen and the spores can survive in soil for many years. Animals are infected when spores enter the body by ingestion or through wounds. Soil, water or infected feeds (meatmeal, bonemeal) or bones from anthrax carcases provide sources of infection. In outbreaks, spread occurs from animals dead of the disease. The carrier state does not occur.

Within Australia, the disease occurs frequently only in NSW and Victoria and in NSW occurs most frequently between October and April. Within NSW, the higher rainfall country of the tablelands and slopes are practically free of the disease.

The disease is readily transmissible to humans, causing respiratory, alimentary or cutaneous forms of anthrax. Fortunately, the cutaneous form is most common and responds to treatment with antibiotic therapy.

Diagnosis

When investigating sudden deaths of sheep or cattle, particularly in anthrax endemic areas, much care should be taken to avoid opening the carcase of animals dead from anthrax. Effective protective clothing should be worn for any necropsy which has a possibility of sudden death.

Characteristic signs of death from anthrax include tarry blood discharges from any orifices, striking absence of rigor mortis and rapid gaseous decomposition. In such cases, a blood sample should be collected from a superficial vein. A smear is made, air dried, fixed and stained with aqueous polychrome methylene blue.

If a necropsy is undertaken, there are a number of changes characteristic of anthrax. The blood does not clot, there are ecchymotic haemorrhages in many organs, blood tinged serous fluid in body cavities, severe enteritis and enlargement of the spleen with liquefaction of its contents.

Anthrax must be differentiated from other causes of sudden death of sheep, particularly blackleg amongst the clostridial diseases discussed and from some of the following causes of sudden death.

Other causes of sudden death

A number of other disease conditions which have been reviewed in other sections of the notes can, under certain conditions, cause sudden death. These include :

Bloat
Lightning strike
Exposure/hypothermia
Anaphylaxis and anaphylactoid reactions

There are a number of plant toxicoses and chemical poisonings causing sudden death, including :

Poisoning with nitrate/nitrite, cyanogenetic and cardiac glycosides, fluoroacetates
Poisoning with lead, copper, arsenic
Blue-green algal poisoning
Green cestrum poisoning
Phalaris sudden death

Grazing of Phalaris aquatica can lead to a syndrome of sudden death or to a staggers syndrome. The staggers syndrome is an acute, or more commonly, chronic nervous system disorder, associated with the presence of tryptaminic alkaloids in the phalaris plant. This form of phalaris intoxication is discussed further in the section on diseases of the nervous system. The sudden death form of the disease has also been called the ’cardiac’ form and the ’peracute’ form.

Recent evidence suggests that phalaris sudden death is not caused by tryptamine alkaloids[14], despite earlier evidence that it was[15]. Furthermore, outbreaks of phalaris sudden death seem to be of at least two types. The two most apparent classifications are the ’cardiac’ form and the more recently described ’polioencephalomalacic’ form. Some forms of sudden death appear to be difficult to classify as either of these, and may be associated with cyanide or nitrate intoxication[16].

The cardiac form is a cardio-respiratory disorder precipitated by a disturbance of the flock, particularly mustering, following a short period of grazing phalaris. Outbreaks are clustered in late summer and autumn. Usually fewer than 1% of the flock at risk are affected. Affected sheep collapse; some subsequently recover but most die. In animals examined alive the heart is in ventricular fibrillation and, although the sheep continue to breathe, cyanosis is marked. There are no signs of nervous system derangement clinically or at necropsy.

The polioencephalomalacic form need not be precipitated by disturbance. Sheep die rapidly and any seen alive show blindness, depression, aimless wandering, head pressing, tremors, opisthotonus, recumbency and convulsions or coma. The clinical signs and the necropsy findings are very similar to the polioencephalomalacia of thiamine deficiency. If thiamine is involved in this disease, the active chemical must be a particularly potent thiamine antagonist, because the onset of disease can occur so soon after exposure to the pasture. The peak incidence is autumn and early winter. Disease incidence can be high, up to 14%, but more commonly around 5%[15].

The earlier descriptions of field outbreaks of phalaris sudden death do not distinguish between cardiac and polioencephalomalacic forms so it is difficult to know if predisposing conditions are similar for both. It has been observed that highly fertile soils, particularly those improved with phosphate fertilizers and leguminous plants[17], seem to be more toxic than less fertile ones. Deaths can occur within 2 hours of commencing grazing or as long as several weeks after access[18]. Outbreaks are related to the sudden access of hungry sheep to phalaris pasture, particularly pasture which has been spelled from grazing and is shooting[19].

Prevention of mortalities by grazing management is worthwhile but no strategy can be guaranteed. It would appear unwise to graze hungry sheep on phalaris pastures and the risk seems to be higher if the pasture is freshly shooting and is on a soil likely to be high in nitrogen. Wherever possible, phalaris should be continuously grazed. Intraruminal cobalt pellets, which protect against phalaris staggers, do not protect against phalaris sudden death[20]. Phalaris sudden death occurs on low alkaloid cultivars of P aquatica like Sirolan[21].

Exposure/hypothermia

Losses of sheep following shearing when exposed to low temperatures, rain and high wind chill factors can be very high, particularly in summer and if the sheep have been losing weight prior to shearing. Losses as high as 90% of the recently shorn sheep have been recorded and mortalities can occur in sheep as long as 28 days off-shears[22].

Sheep Health & Production

Chapter 14. Sudden death

Enterotoxaemia (pulpy