Arsenic has different forms and can occur naturally in plants and soil at low levels, but most poisonings occur from exposure to arsenic modified for pesticidal use. Arsenic toxicosis is an uncommon condition in cattle and has a generally grave prognosis, often resulting in death by cardiovascular collapse before clinical signs are observed. Acute arsenic poisoning occurs within 3-12 hours after ingestion, and clinical signs may include ataxia, mucoid or haemorrhagic diarrhoea, recumbency, convulsions, weakness, dehydration and death. Successful treatment is rarely reported2.
In September 2019, the Emergency Animal Disease Hotline was notified of sudden deaths in 10 cattle from an at-risk group of 60 mixed-breed and mixed-age heifers. The stock were in good condition, with a large amount of feed available, including ryegrass and volunteer wheat. The paddock contained small amounts of capeweed and clover and an old house and piggery site, with piles of discarded materials. Treated wooden posts, wire and corrugated iron remained, along with a 40-year-old dip site. The history of chemical use in the dip was unknown. The heifers had been in this paddock for at least six weeks.
The herd was removed from the paddock with the old house and piggery site as soon as the mortalities were discovered. Examination of 10 dead animals showed various stages of decomposition, with a suspected time of death of over 48 hours. Affected animals were mostly joined 24-month old heifers due to calve in May 2020, and some unjoined 15-month-old heifers. The deaths were scattered across the paddock, with one animal found in an adjacent paddock into which the herd was moved. Due to advanced decomposition samples were not taken from the dead cattle.
One heifer showed significant clinical signs, including pyrexia (40.3°C), staggers, generalised incoordination, injected mucous membranes and a prolonged capillary refill time (>2 seconds). Mentation and cranial nerve exam were normal (palpebral reflex, menace response, jaw and tongue tone). This animal was euthanised in the field for necropsy.
Post mortem examination revealed no gross abnormalities. Fresh samples were collected for laboratory submission.
Another mildly affected animal was observed at a distance displaying swaying hindlimb ataxia. No other signs noted.
Arsenic was found in the liver with levels of 7.9 mg/kg of wet weight (Ref. <1mg/kg). Kidney lead levels were examined and were under 0.5 μmol/kg wet weight (Ref. <2.0 μmol/kg). A chemical residue report was done and showed all pesticides were under the limit of reporting, including organochlorine, organophosphorus, synthetic pyrethroid type pesticides, selected fungicides, and other pesticide types.
Blood work from the euthanised animal revealed a mild erythrocytosis (12.59 (5-10)x1012/L), mild hyperhaemoglobinaemia (196 (80-150) g/L), degenerate neutrophilia (9.04 (0.6-4.0)x109/L) and lymphopaenia (1.93 (2.5-7.5) x109/L), slightly icteric plasma, severe elevation in CK (104,317 (<300) U/L), AST (1,384 (<130) U/L) and GLDH (317 (6.1-13.3), marked elevation in GGT (113 (<30) U/L) U/L), mild hyperbilirubinaemia (11 (<10) μmol/L), azotaemia (blood urea 15.4 (5.8-9.0) mmol/L), creatinine 306 (81-125) μmol/L), hyperalbuminaemia (34 (28-32) g/L), hypoglycaemia (2.9 (3.2-4.0) mmol/L), hypocalcaemia (1.76 (2.0-3.0) mmol/L), hyperphosphataemia (2.57 (1.35-2.36) mmol/L), and severe hyperkalaemia (9.5 (4.0-6.1) mmol/L).
Histological findings showed damage to the liver, kidneys, muscle and brain. The liver had severe centrilobular hepatocellular degeneration with focal necrosis and perivascular neutrophilic infiltration. The kidneys had moderate multifocal cortical tubular dilation and degeneration, medullary vascular congestion and parenchymal neutrophilic infiltration. The muscle had moderate multifocal fibre degeneration and fragmentation. The brain had haemorrhagic lesions, but no other changes in the parenchyma.
Differential diagnoses for sudden death in this outbreak included toxicosis due to an organophosphate, plant or heavy metal, polioencephalomalacia (due to thiamine deficiency), bacterial meningitis (listeriosis), blackleg (caused by Clostridium chauvei) or black disease (Clostridium novyi), vitamin A deficiency, grass tetany (unlikely as heifers had not calved recently), and salt poisoning. Diseases that were excluded were lead toxicity, chlamydiosis (Chlamydophila pecorum, serology titres were negative), and clostridial diseases (the cattle had been previously vaccinated for clostridial diseases either in February or June 2019).
The pathophysiology of arsenic toxicosis depends on the form of arsenic involved. Inorganic arsenic compounds, the form historically found in livestock dips, block the citric acid cycle, reducing energy metabolism and causing damage to metabolically active organs like the liver, kidneys, gastrointestinal tract epithelium and the heart1. The compounds also affect the vasculature, causing vascular wall necrosis, transudation of plasma, haemorrhage, diarrhoea, decreased blood volume, dehydration and shock.
Arsenic toxicosis lesions are commonly found in the abomasum, but in this case no gross lesions were observed and the abomasum was not examined histologically. Other common findings for arsenic toxicosis not observed in this animal are pulmonary oedema, haemorrhage of the cardiac serosa and peritoneum.
Histopathological lesions of the liver, kidney and skeletal muscle were consistent with an acute toxicosis affecting tissues with a high metabolic activity. These findings were consistent with the elevated arsenic level in the fresh liver. It is likely the brain haemorrhages seen on the histopathology were a result of euthanasia via gunshot as opposed to the arsenic toxicosis, as there was no evidence of vascular wall necrosis. Despite the profound ataxia, it is possible for histopathological lesions to be absent in the central nervous system with some sudden death conditions (e.g. lead toxicosis), suggesting the ataxia is due to functional changes. Prior to confirmation of elevated arsenic, hepatic encephalopathy was considered, rather than a primary neural disorder. In one study of 156 cases of acute arsenic toxicosis, Bertin et al. (2013) reported ataxia as a clinical sign in 29% of cases, and interestingly, diarrhoea was reported in 33% of cases, which was not apparent in this case.
The markedly elevated CK and AST could have been related to a primary myopathy, however there would likely be considerable muscle damage secondary to the neurological signs. Liver damage was indicated by the marked elevation in GLDH and AST, indicating hepatocellular damage and the marked elevation in GGT, mild hyperbilirubinaemia and slight icteric plasma appearance, indicating cholestasis. The azotaemia could have been a combination of renal (from acute kidney injury) and pre-renal (from hypovolaemia due to dehydration) which is supported by the erythrocytosis, hyperhaemoglobinaemia and hyperalbuminaemia. The hyperkalaemia could have been due to prolonged storage of blood (>6 hours) without separation of serum or plasma, or it may have occurred as a result of acute kidney injury, as could the hyperphosphataemia and hypocalcaemia1.
A spinal cord sample was submitted for bacteriology in case this mass mortality event was not due to a toxicity. It returned with a sparse mixed growth, including Mannheimia haemolytica, which may have either been an incidental finding in this animal or the sample may have been contaminated. Neural tissues are not a common place for M. haemolytica to be found, but it is ubiquitous in the environment and often endogenous to the respiratory and gastrointestinal tracts. The positive culture of M. haemolytica in this case is therefore unlikely to be related to the mass mortality event.
The surviving affected heifer showing mild clinical signs was prescribed oxytetracycline (30 mg/kg IM, Alamycin LA300, Norbrook) and meloxicam (0.5 mg/kg SC, Metacam 20, Boehringer Ingelheim) as interim treatment while awaiting laboratory results.
In this investigation, samples were not taken from the deceased animals. At this stage, arsenic toxicosis had not been a major differential, and due to advanced decomposition it was deemed samples collected would be of limited diagnostic value. However, arsenic could have been detected in decomposing tissues, specifically the liver, and testing may have strengthened the diagnosis of acute arsenic toxicosis.
Maximum Residue Limits have not been established for arsenic by the Food Standards Australia New Zealand (FSANZ). The (draft) NSW DPI procedure ‘Chemical Residues in Stock – Part 14 – Managing Residue Aspects of Arsenic Poisoning In Stock’ was followed in managing this case. The landholder was specifically advised to withhold exposed stock from slaughter for a minimum of 72 days after last exposure to the suspected source of arsenic. Should the landholder have wished to consider slaughter for human consumption before the 72 days, further testing would have been required. All heifers in the group were permanently identified and their RFID tags recorded.
Preventing cattle access to contaminants is the best way to reduce the risk of future cases of arsenic toxicosis. The producer was advised to work with the appropriate authorities to identify the source of arsenic and develop a management plan to reduce the risk of future outbreaks. Most likely, the arsenic originated from the discarded posts from the house, or the old dip site, where soil may have been disturbed.
The timing of the arsenic toxicosis outbreak in this case is curious. The cattle had supposedly had access to the contaminated paddock for the six weeks prior to the sudden death event, yet acute poisonings reportedly occur within 12 hours of arsenic ingestion2,. Some theories are that the cattle were not grazing or accessing the areas contaminated with arsenic until recently, that a precipitating event may have caused soil disturbance and brought up arsenic residues, or that increased arsenic uptake from the soil by growing plants caused the cattle to ingest toxic doses1,.
Environmental arsenic contamination and risk can be managed according to site specifics through water management, soil amendments, fertilisation practices, plant breeding approaches, or more simply prevention of access to contaminated areas. Removing all soil contaminated by arsenic would require core sampling at different soil depths to establish the extent of contamination, and this option may not be feasible if contamination is extensive. Preventing access to the suspected contaminated site by exclusion fencing might be a viable option in this situation. Overall, this case highlights the importance of assessing the risk of potential contaminants in paddocks that were historically used for different purposes than grazing.
Elizabeth Macarthur Agricultural Institute Veterinary Pathology team for tissue examination, testing and interpretation.