Beef herd poisoning due to ingestion of tansy ragwort in southwestern Ontario

Abstract

Deaths attributed to Senecio jacobaea were investigated. The animal presented was a mature bull that was lethargic and dragging its feet. The bull was euthanized and 3 other cows died. Significantly, this disease has not been documented in Ontario before, and clinical signs of icterus or hepatoencephalopathy were not observed.

On the evening of June 12, 2006 (Day 0), the owner of a small cross-bred 25-head cow-calf herd phoned the Ontario Veterinary College to discuss a lethargic bull. The owner requested a farm visit to examine his bull, which was lying down excessively and had been uninterested in the cow herd for the past 4 wk. The herd was turned out to pasture during the last week of April; approximately 1 mo ago, it was moved to a new pasture. The 1st visit to the farm was made on Day 1.

Case description

A 5-year-old, red cross-breed bull was presented for examination. The bull had been purchased at auction as a yearling and had never left the farm. He had no record of vaccinations, deworming, or previous treatments.

From general inspection, the bull was standing, was in poor body condition (body condition score 3/9), had bilateral symmetrical ventral abdominal swelling, and held his ears low (depressed), but he was responsive and aware of the presence of the clinician. His respiratory rate was 16 breaths/min. As the clinician moved around the bull, staining of the tail head with dark feces was noted, but no other areas with swelling, edema, or abnormalities were noted, until the bull began to ambulate. With slow deliberate movements, the bull was consistently unable to pick up the toe of either the right or the left hind foot. The gait could not be explained by a localized lameness or classified as ataxic.

On physical examination, the bull had a rectal temperature of 38.9°C and heart rate of 84 beats/min, which was of normal rhythm but faint and very difficult to hear. A menance response was present. There were no oral erosions or ulcers and no nasal discharge. The sclera appeared normal and auscultation of the lungs was unremarkable. Ruminal contractions were absent. Thorough percussion and auscultation on both sides of the abdomen did not identify any abnormalities, but fluid was noted on succusion of the abdomen. On rectal examination, the most marked abnormality was scant feces and frank blood was present on the rectal sleeve. As rectal palpation was completed, the bull strained and prolapsed the rectum, revealing a markedly hyperemic rectal mucosa with bleeding.

Based on the physical examination findings and history, diagnostic hypotheses included peritonitis, pericardial effusion, gastrointestinal parasitism, and infection with Bovine viral diarrhea virus. The decision to do further diagnostic tests was delayed until the owner returned home, but the prognosis for return to function as a breeding bull was poor to guarded. Diagnostic hypotheses discussed with the owner at this time did not include encephalopathies or nervous system diseases attributable to toxicities, based on the physical examination findings and the fact that disease in this herd seemed confined to the chronic condition of this bull.

On Day 3, a mature yellow brockle-face cross-bred cow was found dead on the farm. This cow had no previous history of disease or record of treatments, but in retrospect, the owner reported that this cow appeared to have a similar attitude to the bull examined 48 h previously. The signs of lethargy and depression had a 2-day progression. The cow was submitted for routine postmortem examination at the Ontario Veterinary College. On gross examination, the body condition, fat stores, and hydration of the carcass were adequate. There was marked mesenteric edema, extensive abomasal edema, and marked diffuse omental hemorrhage extending to the caudal flexure of the duodenum. The heart was mottled on cut surfaces, particularly in the right ventricle. The liver was of normal size; an enhanced reticular pattern was evident on cut surface. The gall bladder was markedly enlarged. The ruminal contents appeared normal, but the contents of the small and large intestines were watery. One tentative diagnosis based on the gross examination was blue-green algae poisoning; samples from liver, heart, lung, spleen, and kidney were preserved in formalin and frozen and then sent for histopathologic examination and virologic study. No ruminal or gastrointestinal contents were saved.

On Day 7, a 2nd mature cow was found dead on pasture with no previous clinical signs or treatment. On Day 8, the cow was submitted for routine postmortem, but the carcass was too severely autolyzed for any gross lesions to be observed or diagnosis obtained.

A histopathological report was available on the morning of Day 8 from the cow that had died on Day 3. Histopathologic examination had revealed hepatic portal areas with marked ductulization and periacinar areas with moderate congestion. A 2- to 3-fold anisokaryosis and megalocytosis of hepatocytes was observed. Both the large and small intestines exhibited the serosal edema observed grossly, and the marked abomasal edema was confirmed histopathologically. The final diagnosis was toxic hepatopathy consistent with pyrrolizidine alkaloidosis.

On Day 8, the farm pastures were examined to identify any plants that would be associated with pyrrolizidine alkaloidosis. The current pasture that the remaining cows and bull were grazing contained a plant that appeared to be preflowering Senecio jacobaea (tansy ragwort). This plant was spread throughout the low areas of the pasture at a density estimated to be 3 to 5 plants/m². A similar density of the plant was observed in the adjacent pasture where the cows had been pastured initially. The owner was contacted that evening to discuss the presumptive diagnosis, the identification of the plant in the pasture, and the high likelihood of a similar diagnosis in the bull examined 8 d ago. Euthanasia of the bull was discussed.

On Day 9, the Herbarium of the University of Guelph was contacted to confirm the identification of the plant. The plant obtained from the pasture was confirmed as S. jacobaea [personal communication — Carole Ann LaCroix; Curator of Phanerogam collection, Herbarium Administration and Invasive Alien Plant Program (OIPIS)]. Later that same day, the owner agreed that with confirmation of the plant, the bull should be euthanized. On Day 10, the bull was sedated with 100 mg xylazine (Rompun; Bayer Animal Health Division, Toronto, Ontario) and antemortem blood samples were collected prior to euthanasia (Euthanyl; Bimeda-MTC Animal Health, Vetroquinol Canada, Lavaltrie, Quebec). On postmortem examination, the bull had a severe hepatopathy and lesions consistent with pyrrolizidine alkaloidosis. The pleural cavity contained 1–2 L of serosanguinous fluid, and the peritoneal cavity contained several liters of clear fluid. The omental and mesenteric tissues were edematous and had petechial hemorrhages. There was severe mucosal edema of the abomasum, and the gall bladder was distended to approximately 30 cm × 20 cm × 20 cm. The liver was of regular size, had an irregular capsular surface, was firm on palpation, and had a marked reticular pattern on cut surface.

Interpretation of the antemortem blood analysis was considered unremarkable, given the presumptive diagnosis and the chronicity of disease in the bull (Table 1). On serum biochemical analysis, hypomagnesemia was observed, and there was a mild hypoproteinemia and a marked hypoglobulinemia (Table 1). Levels of alkaline phosphatase and creatine kinase (Table 1) were attributed to the historical bouts of recumbency. Liver enzymes were surprisingly unchanged. There was pronounced hyperbilirubinemia (Table 1), mostly free, not conjugated, bilirubin.

Table 1.

Selected serum chemical and whole blood cell count results collected from the index case animal diagnosed with pyrrolizidine alkaloidosis

Sample	Test	Units	Result	Reference Interval
EDTA blood (complete blood cell count)	WBC	109/L	10.2	5.05	13.3
	RBC	1012/L	6.0	4.9	7.5
	Hemoglobin	g/L	120	84	120
	Total solids protein	g/L	65	60	80
	Hematocrit	L/L	0.31	0.21	0.30
	Lymphocytes	109/L	2.04	1.8	8.1
	Seg neutrophil	109/L	7.14	1.7	6.0
	Monocytes	109/L	0.71	0.1	0.70
Serum biochemistry	Magnesium	mmol/L	0.70	0.82	1.30
	Total protein	g/L	63	66	86
	Globulin	g/L	46	30	53
	Alk phosphatase	U/L	235	25	127
	Creatinine kinase	U/L	2084	44	211
	Gamma GT	U/L	20	11	51
	GLDH	U/L	7	3	45
	Total bilirubin	μmol/L	66	0	3

EDTA = ethylenediamine-tetraacetic acid, WBC = white blood cells, RBC = red blood cells, Alk = alkaline, GT = glutamyl transpeptidase, GLDH = glutamate dehydrogenase

One further animal died naturally on the evening of Day 15. Similar to all previous cow deaths, this cow was not examined antemortem, and there were no previous treatments or notable clinical signs observed by the owner. This animal was submitted for postmortem examination on Day 16. Gross findings were again consistent with pyrrolizidine alkaloidosis toxicity. This animal did exhibit some minimal jaundice throughout the carcass.

Discussion

Pyrrolizidine alkaloidosis is usually a chronic poisoning that inevitably results in death due to hepatic failure. Although the causative lesions develop slowly in most cases, the onset of clinical signs is usually sudden (1). The majority of pyrrolizidine alkaloids (PAs) that are hepatotoxic are esters of 2 amino alcohols, retronecine and heliotridine (1). Pyrrolizidine alkaloids by themselves are not toxic, but once they are ingested, they are metabolized into highly reactive pyrroles. The pyrroles produce cytopathic changes primarily on hepatocyte nuclei, where they inhibit mitosis and cause megalocytosis (1,2). Pyrrolizidine alkaloidosis is caused by many toxic plants, most of which are classified into the plant families Boraginaceae, Fabaceae, and Asteraceae (1). The plants most commonly responsible for disease are tansy ragwort (S. jacobaea), woolly groundsel (S. redellii, S. longilobus), rattleweed (Crotalaria retusa), and seeds of yellow tarweed (Amsinckia intermedia) (3). Mature plants containing PAs are normally avoided by grazing animals, except under drought conditions, as they are very unpalatable. They are usually only ingested in sufficient quantity to cause disease when they are baled or ensiled into stored feed (3). The toxicity of plants containing PAs is not reduced by the process of ensiling, dry hay, or pelleting (1). Flowers of these plants are more toxic than herbage; however, with S. jacobaea, it is the foliage that is most toxic (1).

There are more than 1200 Senecio species, 25 of which have been confirmed to be poisonous (2). One of the most common species in North America is tansy ragwort. This plant is indigenous to Europe and the British Isles, and is commonly found in the western USA (4). It was introduced into the maritime provinces of Canada as a medicinal herb over a century ago (5). One of the first reports of its occurrence in Ontario was associated with poisoning in a horse in 2000 (4). Tansy ragwort occurs sporadically throughout Ontario, primarily in waste places, edges of fields, roadsides, and old gardens (5). Tansy ragwort is a short-lived biennial plant of the sunflower family (6). A low-growing rosette of leaves is produced in the 1st year. Erect stems growing 0.3 to 1.2 m high are produced in the 2nd and often subsequent years (5,6). The daisy-like bright yellow flowers, evident from July through September, produce an abundance of seed that is easily transported by wind, water, and animals. Seeds can lie dormant on the soil surface for 4 to 5 y, or over 20 y if buried. Seeds germinate in both spring and fall to form new rosettes (6).

Once ingested, the toxic PAs inhibit mitosis and result in a hepatopathy from megalocytosis of hepatocytes and hepatic fibrosis, which may be veno-occlusive, resulting in biliary hyperplasia (1). Increased lipoperoxidation, oxidation of non-protein sulfhydryl groups, and oxidative stress in erythrocytes that may contribute to hemolysis have also been attributed to Sencio spp. poisoning (7). Clinical signs are usually consistent with these changes and result from decreased liver function and, as fibrosis becomes progressively worse, impaired hepatic perfusion and portal hypertension. A possible consequence of such liver insufficiency is systemic accumulation of ammonia and other toxic metabolites, resulting in cerebral edema and hepatoencephalopathy (1). Ultrasonographic findings of cows with chronic ragwort poisoning have been reported (2).

Clinical pathologic results usually only provide contributory evidence. Such evidence includes hyperammonemia, hyperbilirubenemia, and hypoalbuminemia (1). The bromosulphalein (BSP) clearance rate is impaired, and serum enzymes are transiently elevated (1). Quantification of serum gamma glutamyl transpeptidase (GGT) and glutamate dehydrogenase (GLDH) has been recommended for early prediction of hepatic injury in cattle grazing Senecio spp. (1). To assess the degree of liver damage in chronic cases, a combination of the BSP clearance test and liver biopsy for histologic examination are regarded as the most practical in cows and horses (1,8). A diagnosis of pyrrolizidine alkaloidosis can only be confirmed with positive identification of pyrrolic metabolites in the blood or liver (1). In cases where exposure to toxic plants has occurred some time previously, only a presumptive diagnosis can be reached.

There is no primary treatment for the disease. All efforts should be focused on identifying other affected animals in the herd to salvage, preventing further exposure, and controlling plants biologically (Tyria jacobeae — cinnabar moth) or chemically (1,5). Tansy ragwort is easily controlled chemically with the herbicide 2,4-D when in the seedling to young rosette stage (5). When the rosettes are large or the plant is in advanced growth with an elongating flower stalk, the herbicide dicamba provides excellent control (5). One of the key control strategies is to prevent the ragwort from going to seed.

The interesting and unique aspects of this case were the chronic nature of the disease in the index case, followed by apparently acute deaths in the subsequent animals. On presentation, the index case had signs consistent with congestive heart failure, but also tenesmus and bloody diarrhea. A primary hepatopathy was not diagnosed initially due to the lack of diagnostic tests performed, but also due to the absence of icterus or jaundice. In cases of sufficient duration, jaundice and generalized edema are usually present (1). The bull did show dragging of the hooves, which has been reported to be a sign associated with death caused by PAs within 2–3 d (1); however, the bull lived until he was euthanized and apparently had been walking in that manner for several weeks. Subsequently, the serum biochemical analysis did exhibit hypoalbuminemia and hyperbilirubinemia; however, serum changes in the important markers of GGT and GDH were not present. In retrospect, this was probably because serum liver enzyme changes precede noticeable histological changes in the liver (1).

On gross postmortem, the lesions identified were consistent with PAs toxicity. However, there is usually hepatomegaly that was not present in any of the 4 animals examined in this outbreak. Hepatic fibrosis, biliary hyperplasia, and abomasal and mesenteric edema were all quite pronounced. It should be noted that an enlarged gall bladder is not pathognomonic for liver disease; the gall bladder is commonly enlarged in cattle with severe anorexia (2).

If signs consistent with an hepatoencephalopathy are present, differential diagnoses for the disease include rabies, lead poisoning, and polioencephalomalacia. In the absence of nervous signs, but when hyposensitivity, weight loss, diarrhea, tenesmus, and abdominal pain, with or without dragging of hooves, are present, differential diagnoses should include hepatopathies due to phytotoxins, mycotoxins, and blue-green algal blooms (cyanophyte toxicity). Common toxic causes of sudden death in cattle include the following: nitropropanol glycosides (Astragalus sp.), canary grass (Phalaris canariensis) toxicity, carbamate toxicity, hydrogen sulfide gas toxicity, nitrate/nitrite toxicity, organophosphate and ionophore toxicity, and blue-green algae (9). The tentative gross postmortem diagnosis on the 1st cow that died naturally was cyanophyte toxicity.

The owner has experienced no further deaths to date. The possibility of performing liver biopsies or serum chemical analyses on the remaining animals to detect other affected animals was limited by financial constraints. The owner was provided with recommendations to immediately remove the animals from the pasture they were on and to spray the pasture with dicamba at the rate of 0.84 L/ac. It was also recommended that this fall and next spring he administer 2,4-D to the pastures at the rate of 1.8 L/ac. The cattle were turned out in late April on a 1st pasture with limited forage and evidence of tansy ragwort growing at a similar rate as in the current pasture. It is hypothesized that for all affected animals in this outbreak, the ingestion of tansy ragwort occurred on this original pasture prior to moving to the current pasture where clinical signs were becoming apparent and death occurred. With the disease presentation (although lacking in jaundice) and postmortem changes observed, the lesions were consistent with chronic exposure. The pasture that the herd was on during this outbreak, although it did contain rosettes, was lush with native grasses as well, and there was no evidence that the rosettes were being grazed. CVJ

Figure 1.

Early flowering stage of Senecio jacobaea as seen on pasture June 28, 2006, where a herd outbreak of pyrollizidine alkaloidosis was diagnosed.

Figure 2.

Photograph of the pasture, and concentration of Senecio jacobaea, where the beef herd was grazing in June 2006, while investigating an outbreak of pyrollizidine alkaloidosis.