Pyrrolizidine alkaloids are toxins contained in many plants of which two, heliotrope and Paterson's curse, are common in southern NSW. The toxins cause liver damage and one of the results of this damage is impaired copper metabolism leading to a build up of copper in the liver.
Two disease syndromes are common: an uncomplicated liver failure or copper poisoning when stored copper is suddenly released from the liver.
Effective strategies for the control of pyrrolizidine alkaloidosis include grazing management, breed selection, removal of copper from the liver using molybdenum and sulphate and chemical and biological control of the plants.
Pyrrolizidine alkaloids are found in many plants, most notably in south-eastern Australia in heliotrope (Heliotropum europium) and Paterson's curse (Echium plantagineum) as well as several Senecio species.
Pyrrolizidine alkaloids are mainly hepatotoxic although some damage to the brain, kidney and lung has been reported (McBarron, 1976). The liver damage produces two distinct syndromes: a chronic liver failure and a haemorrhagic crisis related to a copper storage disorder.
The chronic copper poisoning may kill 10-30% of a flock and so can be one of the most severe diseases of sheep in southern NSW.
Various approaches to the control of pyrrolizidine alkaloidosis have been taken with variable success, these include selection of breeds of sheep which are less likely to eat the plants, control of the plants either through herbicides or biological agents and using substances which stimulate the excretion of copper.
There are two plant species most commonly associated with pyrrolizidine alkaloidosis in southern NSW.
Heliotrope (Heliotropum europium) also called caterpillar weed, wandary curse, common heliotrope, European heliotrope or potato weed (Cunningham et al, 1981). Heliotrope is a blue/green summer active annual plant with a prostrate habit and distinctive white flower. It can grow prolifically on disturbed ground when it has little competition, and is a very common weed associated with cereal stubble and summer fallow.
Paterson's curse (Echium plantagineum) also known as salvation Jane, purple bugloss, purple viper's bugloss, plantain leaved viper's bugloss and Riverina bluebell (Cunningham et al, 1981). Paterson's curse is a cool season active broad leafed plant with a distinctive purple (occasionally white or pink) flower which can grow up to 2 metres high and can also grow prolifically when it has little competition.
Several Senecio spp have also been seen associated with pyrrolizidine alkaloidosis particularly S cunninghamii, bushy groundsel and S quadridentatus, cotton fireweed which are thin-stemmed erect perennial plants.
The key change produced by pyrrolizidine alkaloids is a change in hepatocytes called megalocytosis (Jubb & Kennedy 1970). This is enlargement of the cells believed to be caused by interference with the cells ability to divide. This change occurs within a few weeks of ingestion and is irreversible and repeated ingestion produces cumulative changes (ibid).
A significant feature of affected hepatocytes is their affinity to copper, although the author's observations indicate that this is confined to sheep and only following poisoning by heliotrope. When this stored copper is released into the bloodstream, usually as a result of some external stress factor, it produces intravascular haemolysis.
This secondary or chronic copper poisoning, also known as toxaemic jaundice, occurs only in sheep which have ingested significant amounts of heliotrope, usually but not exclusively over a period of several years, or ingest plants with a significant amount of available copper. In the Riverina the main source of copper appears to be subterranean clover (Trifolium subterraneum) which appears to occasionally cause primary copper poisoning. Of interest in recent years the Riverina has experienced wet summers where heliotrope has grown prolifically and dry winters where subterranean clover has not grown well and there have been very few cases of chronic copper poisoning observed by the author.
Neither condition appears to be a result of ingestion of Paterson's curse although the author has seen several incidents of chronic liver failure in cattle during the weeks following ingestion of significant amounts of Paterson's curse.
The isolated incidents of liver failure following ingestion of Senecio spp observed by the author also appear to be unusual because on the north cost of NSW sheep are used to clear fireweed from pastures without untoward effects (Glassop pers comm.)
Many animals grazing pastures containing pyrrolizidine alkaloid-bearing plants complete their productive lifetime with little or no obvious ill-effects. A pathologist with the then Regional Veterinary Laboratory at Wagga Wagga commented that he rarely saw any liver from the Riverina which did not have some changes consistent with pyrrolizidine alkaloid poisoning (Glastonbury pers comm.).
There are two distinct clinical syndromes in sheep caused by pyrrolizidine alkaloids. Liver failure is the less common condition. Its occurrence is quite variable. The author has seen it within a few weeks of grazing in lambs on almost pure swards of heliotrope as well as adult sheep on cotton fireweed. He has also observed it in mature sheep where they have not succumbed to the more common chronic copper poisoning syndrome.
Presenting signs are usually weight loss over a period of weeks and less commonly photosensitization. Nervous signs with apparent blindness and aimless wandering are not a feature of the condition in sheep although it is among the more common clinical signs in cattle with chronic pyrrolizidine alkaloidosis.
Morbidity is variable, usually higher with the more rapid onset form where 1-10% of the flock may have obvious clinical changes with mortality in those sheep approaching 100%. In the more chronic condition morbidity is usually below 1% per annum although that is increasing as management of copper stored in affected livers reduces the incidence of chronic copper poisoning.
Chronic copper poisoning usually presents as sudden death with a short clinical course. Most affected animals are found dead although some present as deeply depressed in sternal recumbency with obvious yellowing of the mucosa and red urine; affected animals usually die within hours.
In the Riverina chronic copper poisoning most commonly occurs in the spring when a cold, wet change follows several weeks of fine, warm weather with another spike of incidents during the autumn as feed availability declines.
Morbidity is variable, usually 1-10% or rarely 20% with almost 100% mortality of affected animals.
Sheep which have died of chronic liver failure usually show emaciation with gelatinous subcutaneous oedema of the parts of the head with no wool cover when photosensitization is part of the clinical picture. Jaundice is rare. The liver is usually slightly reduced in size with a granular texture due to fibrosis.
Sheep which have died of chronic copper poisoning have severe jaundice (Figure 1) with butter-yellow body fat (Figure 2), the liver is usually enlarged and sometimes pale but more often dark, the kidneys are swollen and dark blue/black or occasionally green/black (Figure 3) and the urine is deep dark red.
No treatment appears to make any difference to clinically affected sheep: they all die.
There are quite a few strategies to control pyrrolizidine alkaloidosis and as usual an integrated approach using all of them has the most success.
There is a significant difference between sheep breeds in their willingness to eat heliotrope with merinos rarely affected, in fact the author has only seen disease in merinos once and that was in hoggets after their second summer of prolific heliotrope growth. Crossbred sheep are much more likely to be affected. Dorpers appear to love heliotrope but whether it causes disease problems in that breed remains to be seen. Many producers limit their risk of disease by running merino sheep only.
Grazing management works well but at the cost of limiting the value of sheep to control the weeds on cereal paddocks.
Control of the plants with herbicides is often attempted but rarely completely successful. Heliotrope and the Senecio spp are relatively resistant to herbicides although some agronomists in the Riverina are claiming success in controlling heliotrope using tank-mixes of several herbicides.
Spray-graze control of Paterson's does reduce the plant when the paddock is sprayed with MCPA and grazed. This does not produce the poisoning in sheep which one might expect but would be more of a risk with cattle.
Biological control has been fairly successful in recent years. A range of weevils, beetles and moths which infest Paterson's curse have been introduced over the past decade or so and the extensive pure swards of Paterson's curse which were such a feature of the Riverina in the past do not seem to occur these days.
The ideal biological control agent for heliotrope is lucerne (Medicago sativa). It has similar cultural characteristics to heliotrope and heliotrope is extremely uncommon in healthy stands of lucerne. This is, unfortunately, of little help during the cropping phase.
Removing stored copper has been an extremely successful technique in recent decades. Molybdenum has been observed to reduce copper availability and a home brew of sodium molybdate and sodium sulphate has been used extremely successfully to prevent outbreaks of chronic copper poisoning and to almost immediately prevent further deaths in the face of an outbreak. It is difficult to prepare and administer but the results are dramatic with a single treatment. A loose mix of salt, sodium molybdite and sodium sulphate has also had reported success (Radostits et al, 2007).
The legal status of these mixes under stock medicine and chemical residue legislation was unclear.
In the past 12 months due to the efforts of Lee Cook of NSW DPI a permit has been issued for a preparation containing sodium molybdate and sodium sulphate which can be administered either as a drench or a loose mix (APVMA 2010). This product is available to veterinarians only for the treatment of their clients' sheep and can be obtained from Provet Riverina at Wagga Wagga.
Pyrrolizidine alkaloids are important toxic components of many plants and can be a significant problem to sheep production in south-eastern Australia. Several strategies are available to limit the risk of pyrrolizidine alkaloid poisoning. None of them are easy nor is any of them effective by itself. It is possible, however to develop an integrated program which will minimise the effects of these toxins.