Spontaneously arising disease
Pathology of Fatal Australian Black Snake (Pseudechis sp) Envenomation in Two Adult Dogs

https://doi.org/10.1016/j.jcpa.2021.04.009Get rights and content

Summary

Black snakes (Pseudechis spp) are a genus of venomous Australian elapid snakes that can cause major clinical envenomation in companion animals, which may be fatal, even with appropriate antivenom treatment. Despite its clinical significance, there is little published information on the pathology of black snake envenomation. We report the gross and microscopic lesions associated with black snake envenomation in two dogs, one with a definitive immunological species identification of red-bellied black snake (RBBS; Pseudechis porphyriacus), the other with a black snake immunotype on a venom detection kit. Both dogs were located in a geographical area where the RBBS is found. The prominent gross findings in both cases included icterus, localized facial oedema in the region of the presumed bite wound, pigmenturia and multicavitary serosanguineous effusions. Histopathology of the confirmed RBBS case revealed acute renal tubular necrosis with haemosiderosis, marked splenic haemosiderosis and centrilobular to midzonal hepatocellular necrosis with severe cholestasis. Defining the spectrum of lesions of elapid snake envenomation improves understanding of the pathogenesis, which may lead to improved patient outcomes and post-mortem diagnosis.

Introduction

Snake envenomation of companion animals is a common occurrence in Australia, a country renowned for a large population of native venomous snakes (Padula et al, 2018; Boller et al, 2020). Most of Australia's venomous snakes belong to the family Elapidae, within which five major genera contain the highly venomous snakes of medical and veterinary importance. The nomenclature of elapid snakes in Australia can be misleading, with common names differing between geographic regions, and names often referring to colours that in reality can vary widely between and within species (Shea, 1999). The term ‘black snakes’ refers to snakes of the genus Pseudechis, of which there are six species recorded in Australia, all with specific and often overlapping geographic distributions (Shea, 1999). The red-bellied black snake (RBBS; Pseudechis porphyriacus) is the most common black snake species to cause envenomation in companion animals in the regions where it occurs. It is widely distributed along most of the east coast and into south-eastern Australia, including along the Murray River in South Australia (Shea, 1999). In a survey of veterinary clinics in New South Wales, the RBBS accounted for nearly 45% of all envenomation cases presenting for treatment (Heller et al, 2005). Other common black snake species include the blue-bellied black snake (BBBS; Pseudechis guttatus), also known as the spotted black snake, and the mulga snake (Pseudechis australis), which is alternatively known as the King Brown snake, a misnomer that may lead one to incorrectly assume it is of the brown snake genus Pseudonaja (Shea, 1999). There are few published reports of the latter two species causing envenomation in companion animals.

Like all snake venoms, that of Australian black snakes contains a mixture of proteins with diverse functions, and the exact constituents vary between species (Fry, 1999). RBBS venom has haemolytic (Vaughan et al, 1981), myotoxic (Mebs and Samejima, 1980), neurotoxic (Hart et al, 2013), anticoagulant (Lane et al, 2011) and procoagulant effects (Tan and Ponnudurai, 1990; Lane et al, 2011). These toxic actions are reflected in the clinical syndrome of RBBS envenomation in companion animals, which can include local bite site swelling, hypersalivation, collapse, anaemia with haemolysis and spherocytosis, increased serum creatine kinase (CK) activity, coagulopathy and pigmenturia (Heller et al, 2006; Padula and Winkel, 2016; Lenske et al, 2018; Finney et al, 2020). Less commonly, RBBS envenomation can be associated with severe neurotoxicity presenting primarily as paresis and paralysis (Padula and Leister, 2017a), although this is more frequently reported with envenomation by other Australian elapids such as the eastern brown snake (Pseudonaja textilis) and tiger snake (Notechis scutatus) (Indrawirawan et al, 2014; Padula and Leister, 2017b).

Published clinical information on Australian black snake envenomation in companion animals has been growing in recent years. However, there remains a lack of knowledge regarding the associated pathology, with only one case report describing necropsy findings in a dog (Heller et al, 2006) and another briefly describing lesions in a captive wolf (Portas and Montali, 2007). The aim of the current report is to document the gross and microscopic lesions associated with fatal Australian black snake envenomation in two dogs, including changes that have not been previously described.

The first case, located in South-East Queensland, was an 8-year-old, entire female Staffordshire Bull Terrier with acute onset of vomiting, pigmenturia and lethargy. The owners found a dead, mauled snake in the yard and described the snake as being black with a pink belly, consistent with a RBBS. On presentation to a referral veterinary hospital, the dog was dull and reluctant to move with painful muscles, and clinical workup revealed severe haemolytic anaemia (packed cell volume 9%, reference interval [RI] 35–50%; and haemolysed serum) and pigmenturia. A clinical diagnosis of RBBS envenomation was made, and the patient was hospitalized and treated intensively for approximately 3 days. Treatment during the hospitalization period included 8,000 IU tiger-brown snake antivenom, two blood transfusions, Hartmann's intravenous fluid therapy, fentanyl and methadone analgesia, mannitol and the antiemetic maropitant. Further serum analysis revealed severe azotaemia (creatinine 468 μm/l, RI 40–140 μm/l; urea 34.6 mmol/l, RI 2.5–9.0 mmol/l), hyperbilirubinaemia (27 μm/l, RI 0–10 μm/l), hypoalbuminaemia (17 g/l, RI 22–26 g/l) and elevated CK activity (2,706 U/l, RI 0–400 U/l). Despite intensive treatment, the patient became anuric and died. The interval between presentation to the clinic and death was approximately 70 h. The presence of RBBS venom in ante-mortem serum was confirmed retrospectively using a venom antigen-specific sandwich ELISA as described (Padula and Winkel, 2016). The carcass was stored at 2°C until necropsy 5 days later.

Post-mortem examination revealed extensive pathology, including diffuse severe icterus (Fig. 1), with dependant ventral subcutaneous oedema. Locally extensive subcutaneous oedema was present on the left side of the face, markedly expanding the soft tissues in the region of the left lip commissure and extending ventrally to the submandibular region. This localized subcutaneous oedema may have been the site of the snake bite, although no puncture wounds were observed. The peritoneal, pleural and pericardial spaces contained serofibrinous effusions, with 400 ml, 150 ml and 100 ml of fluid, respectively (Fig. 1). The liver was diffusely yellow–green tinged with a subtle, generalized, exaggerated reticular pattern, suggestive of cholestasis and zonal necrosis. The kidneys were bilaterally and uniformly dark red to black in colour, indicating severe pigmenturia (Fig. 2). The colon contained tarry, black melaena, and the lungs were diffusely heavy and wet, leaking serosanguineous foamy fluid on cut surface, indicative of pulmonary oedema.

Histopathology was performed on liver, spleen, lung, heart, kidney, bladder, adrenal glands, stomach, jejunum, colon, gracilis muscle, sciatic nerve, cervical spinal cord and brain (including cerebellum, brainstem, cerebrum, hippocampus and thalamus). Tissues were fixed with 10% neutral buffered formalin and stained with haematoxylin and eosin (HE). Microscopic examination of the kidney revealed severe, acute tubular necrosis affecting approximately 80% of the proximal and distal tubules (Fig. 3). Severe haemosiderosis was present, with frequent degenerate and necrotic tubular epithelial cells containing intracytoplasmic haemosiderin, confirmed with Perl's Prussian blue stain (Fig. 4). There was also mild interstitial haemorrhage in the kidney. In the liver, there was severe, acute, centrilobular to midzonal, submassive hepatocellular necrosis with severe cholestasis. Cholestasis was characterized by generalized distension of bile canaliculi with yellow pigment, confirmed to be bile on Hall's bilirubin staining. Occasional deposits of haemosiderin were noted in the liver with Perl's Prussian blue stain. Further histopathological findings included multifocal cortical necrosis affecting approximately 10% of the adrenal gland, extensive haemosiderin in the spleen, moderate high-protein alveolar oedema in the lung and mild acute injury in the gracilis muscle characterized by dissolution of Z-lines and hypertrophy of satellite cell nuclei.

The second case was an 8-year-old, male neutered Rhodesian Ridgeback that had been referred to a specialist veterinary hospital in South-East Queensland for treatment of presumed snake envenomation the previous day. The dog arrived in respiratory distress, the upper lip was swollen with visible purulent puncture wounds and dark red–brown urine was dripping from the prepuce, indicating pigmenturia. On examination, SpO2 was 84% (normal >95%), all lung fields sounded dull on auscultation, the dog was slightly hypothermic (37.9°C), not anaemic (packed cell volume 35%, RI 35–50%), but the serum was haemolysed. A commercially available snake venom detection kit (SVDK; Seqirus, Parkville, Victoria, Australia) performed on urine was positive for black snake venom immunotype. Intensive treatment commenced, including two doses of 7,000 IU tiger-brown snake antivenom, Hartmann's intravenous fluid therapy, antibiotics (metronidazole and cephalothin), mannitol, a gastroprotectant (esomeprazole), an antiemetic (maropitant) and intranasal oxygen progressing to mechanical ventilation, maintained under anaesthetic with a constant rate infusion of propofol, fentanyl and midazolam. Despite intensive treatment for approximately 16 h, the patient deteriorated and was euthanized. The carcass was stored at 2°C until necropsied approximately 24 h later.

On gross examination, the adipose tissue was moderately icteric. There was a marked pleural and peritoneal effusion, with 400 ml and 700 ml of serosanguineous fluid in each cavity, respectively. The kidneys were bilaterally dark red to almost black on cut surface, which was interpreted as pigmenturia, and the liver was diffusely mottled orange–tan.

Histopathology was limited to the liver, due to submission of the case through a pro bono veterinary student teaching stream. Histopathology revealed generalized congestion of the sinusoids (Fig. 5) and accumulation of intracytoplasmic, yellow–brown granular pigment in Kupffer cells. The pigment stained positive for iron with Perl's Prussian blue stain, which is consistent with haemosiderin.

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Discussion

Black snake envenomation is infrequent in humans compared with envenomation by other elapid snake species and accounted for only 20% of cases over a period of 10 years, with no deaths during that time (Johnston et al, 2017). In contrast, companion animals in regions with a high prevalence of black snakes are at risk of serious disease and death (Heller et al, 2006; Finney et al, 2020) despite antivenom and intensive treatment, as documented by the two cases presented here.

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Acknowledgments

The authors wish to thank Graham Panzram, Jo Gordon and Michael Cobbin for technical assistance, and Jingyan Zhang for assistance with the necropsy and initial report of the second case.

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