Snake envenomation in cats and its detection by rapid immunoassay

Objective To determine the usefulness of a snake venom detection kit (SVDK) in the management of envenomed cats.
Design A clinical study.  

Animals

Twenty-two cats were investigated.
Procedure Cats injected subcutaneously with approximately 0.25 or 1.0 lethal dose (LD) of tiger snake venom or 1 or 4 LD of brown snake venom were observed for clinical symptoms of envenomation at intervals over the ensuring 24 to 48 hours(h). Blood and urine samples were taken at regular intervals and assayed in a quantitative laboratory assay for snake venoms. Selected samples were assayed in parallel in a rapid, semi-quantitative SVDK.
Results The studies showed that it was important to estimate the elapsed time from envenomation to presentation. If this time was less than 8 h, blood was the most appropriate sample and a negative result should exclude serious envenomation. If the elapsed time exceeded 8 h, it was essential that urine be sampled. Venom levels in urine were high at 8 h and approached the level of test sensitivity over 24 to 48 h; however by this time clinical signs were obvious in endangered cats.  

Conclusions

Careful use of the SVDK is a valuable aid in the management of a potentially envenomed cat.     

Myotoxicity and nephrotoxicity of common tiger snake (Notechis scutatus) venom in the dog

SUMMARY The myotoxicity and neurotoxicity of common tiger snake (Notechis scutatus) venom are major factors in the pathogenesis of envenomation in the dog. Histological examination of the tissues of experimentally envenomed dogs has demonstrated the importance of muscle damage in affecting the clinical syndrome of tiger snake envenomation. Within one hour of injection of the venom into dogs, there was selective involvement of some muscles. Cardiac and smooth muscles were not significantly affected. The severity of myofibre damage was influenced by the amount of venom injected. Immobilisation under general anaesthesia resulted in significant protection against the myotoxic effects of high doses of venom. Lesions in the kidneys of experimentally envenomed dogs were acute tubular necrosis and the variable presence of a small amount of proteinaceous material in tubules. These lesions, which were similar to those in cases of natural snake bite, were indicative of a direct nephrotoxic effect, which could be complicated by the effects of myoglobinuria. These findings emphasise the need for supportive treatment aimed at maintenance of renal function in the treatment of dogs suffering from tiger snake envenomation.     

The diagnosis and management of snakebite in dogs--a southern African perspective

Cases of snakebite envenomation are frequently presented to veterinary practitioners in southern Africa. Despite this, no published guidelines exist on how this medical emergency should be managed. Southern African snake venoms can be classified into 3 main types based on the main mechanism of venom action and clinical presentation. A polyvalent antivenom is manufactured in South Africa and contains antibodies against the most important southern African snake venoms. The cytotoxic venoms are represented mainly by the puff-adder (Bitis arietans), Mozambique spitting cobra (Naja mossabica), black-necked spitting cobra (Naja nigricollis) (in the Western Cape and Namibia) and the stiletto snake (Atractaspis bibronii). These venoms may cause dramatic local swelling, high morbidity and low mortality and infrequently require the use of antivenom for survival (the only cytotoxic venoms used to prepare the antivenom are the puff-adder and Mozambique spitting cobra). The neurotoxic venoms (represented chiefly by the non-spitting cobras and mambas) cause high mortality due to rapid onset of paresis and require antivenom and mechanical ventilatory support which is life-saving. The boomslang (Dispholidus typus) and the vine snake (coagulopathic venom) rarely bite humans but dogs may be bitten more frequently. These venoms cause a consumption coagulopathy and successful treatment of boomslang bites requires the use of snake species-specific monovalent antivenom. There is no antivenom available for treating vine snake (Thelotornis capensis), berg adder (Bitis atropos), night adder (Causus spp.), stiletto snake and other lesser adder bites. There are some important differences between the way snakebites are managed in humans and dogs.     

Some toxicity thresholds for the clinical effects of common tiger snake (Notechis scutatus) envenomation in the dog

SUMMARY Common tiger snake (Notechis scutatus) venom was administered experimentally to dogs at doses from 0.25 lethal dose (LD) to 20 LD. Haemolysis and increased creatine kinase values occurred rapidly after injection of sublethal (subparalytic) doses, but the clotting time of blood was extended and blood became incoagulable only when dogs were dosed with 10 LD or more of venom. Haemolysis, although of a low threshold of toxicity, was not severe and should not greatly affect the lethality of the venom. Coagulopathy is a sign that the dog has been lethally envenomed and will need to be given antivenom if skeletal muscle paralysis is to be overcome.     

Clinicopathologic abnormalities associated with snake envenomation in domestic animals

Envenomation of domestic animals by snakes occurs frequently in certain geographic areas. However, reports describing clinical signs, clinicopathologic abnormalities, therapeutic approaches, and outcomes are sparse. This review summarizes various snake families, venom types associated with harmful snakes, and the significant hematologic, hemostatic, and biochemical abnormalities associated with envenomation. Hematologic abnormalities include RBC membrane abnormalities, hemolysis, hemoconcentration, leukogram changes, and platelet abnormalities, specifically thrombocytopenia. Coagulopathies associated with snake envenomation are well described in human medicine, and many studies have demonstrated properties of venoms that lead to both procoagulation and anticoagulation. As expected, similar abnormalities have been described in domestic animals. Biochemical abnormalities are associated with the effects of venom on tissues such as liver, skeletal and cardiac muscle, vascular endothelium, and kidney as well as effects on protein components and cholesterol. This comprehensive review of clinicopathologic abnormalities associated with envenomation and their relationships to characterized venom constituents should be useful both in the diagnosis and management of envenomation and should serve as a foundation for future research in this field.     

Common tiger snake envenomation in dogs and mice—relationship between the amount of venom injected and the onset of clinical signs

SUMMARY Common tiger snake (Notechis scutatus) venom was injected into mice and dogs at various dose rates calculated on the known lethal dose (LD) for each species. The larger the dose of venom, the earlier was the onset of clinical signs and the more rapid and severe the course of the disease in both species. In dogs injected with 32 LD of venom, there was sudden collapse and death in about one hour from the time of injection without recovery from premonitory depression and before mydriasis occurred. Dogs given 5 to 16 LD of venom developed preparalytic signs (vomition, salivation or defaecation) in 5 to 30 min, mydriasis in 2 to 4h, became paralysed and died in about 2.5 to 5 h. When doses of venom of about 1 LD were injected, vomition and salivation occurred within 2 h and mydriasis in about 4 h. The dogs were unable to close the mouth completely despite retention of jaw muscle tone. At the site of injection of venom there was occasional but slight erythema and oedema. Sublethally envenomed dogs did not show preparalytic signs nor did they have general skeletal muscle paralysis. Even at the lowest dose tested (0.25 LD), however, they developed mydriasis and photophobia, which persisted for several days.     

蛇毒神经毒素研究进展

我国的蛇类资源丰富,从理论意义和长远的经济效益考虑,蛇毒的研究是一个很有价值的方向。近年来,随着蛇毒神经毒素结构的确定、理化性质和药理性质的测定及蛇毒神经毒素的临床应用,其在镇痛功能方面表现出的维持时间长、效价高、无耐受性和无成瘾性等特点而倍受关注。蛇毒具有广泛的生物学活性,论文就蛇毒组分中近年来研究较为深入的神经毒素的结构、理化性质、药理作用及其应用等方面进行了综述。     

Snake bites recorded by veterinary practices in Australia

Objective To determine the extent of the snake bite problem in domestic animals, its regional significance and the effects of antivenom treatment.
Design A questionnaire was designed seeking information on the number and type of domestic animals referred, whether treated or untreated, type of snakes and management of the bite.
Procedure The survey form was sent to 10% of veterinary surgeons, selected at random throughout Australia.
Results The response of 106 veterinary surgeons revealed that snake bite in domestic animals is frequent, with an estimated 6200 cases reported annually. Bites were more prominent in rural (78%) than urban areas (22%) with brown, tiger and black snakes accounting for 76%, 13% and 6% of cases, respectively. Cats and dogs were the most frequently reported victims. Ninety-one percent of cats and 75% of dogs survived following the administration of antivenom whereas 66% of cats and 31% of dogs survived without antivenom. Overall, in 33% of cases antivenom was not used, and venom detection kits were used in only 1% of cases. A number of drugs were used in various combinations with or without antivenom and intravenous fluids in the treatment of animals with snake bite, but their role in reducing the severity of envenomations was not assessed.
Clinical implications Antivenom significantly improves the chances of survival of domestic animals bitten by snakes.     

Observations on blood coagulation after snakebite in dogs and cats

Blood samples from 13 cases of snakebite, 6 in dogs and 7 in cats, were tested for activated partial thromboplastin time (APTT), prothrombin time (PT) and fibrin/fibrinogen degradation products (FDP). Four cases were tested for fibrinogen concentration. Based on the results of a commercially available ELISA test, 9 cases were caused by tiger snakes (Notechis scutatus) and 1 case by a brown snake (Pseudonaja textilis). Three other cases had clinical signs and increased creatine phosphokinase values which suggested tiger snake envenomation. Although the period post-envenomation varied, results indicated a marked prolongation of the APTT and PT in 5 of 6 dogs. Three of these 5 dogs also had increased FDP values and 3 (of 3 examined) were hypofibrinogenaemic. Clinical manifestations of this coagulopathy were: haematoma formation after venepuncture (3 cases), gingival petechiae (1 case) and hyphaema (1 case). In contrast, there was minimal or no prolongation of the APTT and PT values, and no increase in FDP, in all 7 cats. Furthermore, no cat exhibited clinical signs of a coagulopathy.     

Prospective determination of the specificity of a commercial snake venom detection kit in urine samples from dogs and cats

Objective To determine the specificity of a snake venom detection kit in urine samples from dogs and cats presenting to a referral centre for diseases unrelated to snake envenomation. Design Urine was collected from 50 dog and 25 cats presented for investigation and treatment of diseases unrelated to snake envenomation. Urine was collected as a voided sample, by cystocentesis or by catheterisation, and routine urinanalysis was performed. Snake venom testing was performed within 2 h of collection using a commercially available snake venom detection kit, which was observed continuously during the 10-min colour reaction phase for evidence of a visible colour indicating a positive test. Results No false-positive reactions occurred in any sample analysed. Conclusion The snake venom detection kit appears to have 100% specificity for using urine as a test sample.     

Comparative effects of the human protein C activator, Protac, on the activated partial thromboplastin clotting times of plasmas, with special reference to the dog.

The commercial snake venom extract, Protac, is a specific activator of the anticoagulant zymogen, protein C (PC) in human plasma. This specific action has led to its use in developing coagulation-based and amidolytic-based assays for the diagnosis of quantitative and/or qualitative PC deficiency states in human beings. The purpose of the present study was to compare the effects of Protac on the activated partial thromboplastin times (APTT) of human, bovine, equine, and canine plasmas in order to determine the potential value of this venom extract as an activator in functional PC assays in these domestic animal species. As expected, Protac significantly prolonged the APTT of normal human plasma, but had no effect on plasma known to be devoid of PC. Clotting times were prolonged by 34%-214% with concentrations of venom activator ranging from 0.1-1.0 U/mL. Under identical conditions, Protac prolonged the APTT of equine plasma by 11%-98% over control times. Even more dramatic was the inhibitory effect of Protac on the clotting of bovine plasma, extending the APTT more than 3-fold at a venom concentration of 0.1 U/mL. At higher venom concentrations, most bovine plasmas remained unclotted after 300 s (control time 34.1 s). Under similar conditions, the canine APTT was unaffected by Protac, even when the venom concentration was increased to 3 U/mL. In order to determine the reason for the lack in response of canine plasma, the concentration of the APTT reagent was altered (decreased), exposure time of the plasma to the Protac was increased from 2 min to 9 min, and the plasma was diluted to assess for the potential existence of plasma PC inhibitors. Protac caused an unexpected shortening of the APTT when the contact activator reagent was diluted. Increasing the exposure time had no effect. Although a slight prolongation of the canine APTT was detected when the plasma was diluted, the presence of strong plasma PC inhibition was considered an unlikely cause of the lack of significant anticoagulant action. The failure of Protac to exert a strong inhibitory effect on the canine APTT, as well as to generate amidolytic activity, suggests that this venom extract does not stimulate the production of activated PC activity in canine plasma. This may result from molecular differences in the canine PC molecule that prevent the formation of the stoichiometric complex of venom extract, APTT reagent, and canine protein, a complex thought to be essential for the PC-activating function of Protac. Protac may be suitable as an activator of PC in bovine and equine plasmas; however, it appears ineffective in generating anticoagulant activity in canine plasma.     

Intramyocardial haematoma causing right ventricular outflow obstruction after brown snake (Pseudonaja species) envenomation in a dog

A 15-month-old, male neutered Staffordshire Bull Terrier cross was presented to its referring veterinarian collapsed and agonal. He was immediately intubated, manually ventilated, and treatment commenced for presumptive snake envenomation with two vials of Tiger/Multi-Brown Snake Antivenom (minimum 7000 units/vial). The dog was transferred to a referral hospital intubated. Additional diagnostics performed following arrival at the referral hospital included a urine snake venom detection kit test, which was positive for brown snake immunotype. Three additional vials of Tiger/Multi-Brown Snake Antivenom (minimum 7000 units/vial) were administered until the dog was extubated and able to stand. Venom-induced consumptive coagulopathy (VICC) was diagnosed based on prolonged clotting times and scleral haemorrhage. Paroxysms of right ventricular outflow tract (RVOT) origin ventricular arrhythmias were treated with lignocaine and sotalol. Four days after presentation, a new-grade IV/VI systolic heart murmur was auscultated, prompting an echocardiogram. An anechoic and compartmentalised mass measuring 43 mm × 19 mm was visualized within the right ventricular wall at the RVOT, immediately adjacent to the pulmonic valve. The mass was causing a RVOT obstruction. Its appearance was suggestive of an intramyocardial haematoma, most likely secondary to VICC. The dog remained cardiovascularly stable, and treatment consisted of supportive care. Recheck echocardiograms at 2 and 7 weeks after discharge revealed progressive improvement of the intramyocardial mass and resolution of the associated heart murmur. Although intramyocardial haematomas are rare, it should be considered as a differential in dogs that develop a newly diagnosed heart murmur and/or cardiac arrhythmia following brown snake envenomation.     

Elapid snake envenomation in dogs in New South Wales: a review

Elapid snake envenomation in dogs is a commonly occurring yet poorly described clinical entity. Twelve species of dangerously venomous elapid snakes are found in New South Wales that are capable of causing disease in dogs. Geographical distribution of these species varies, as does their venom composition and systemic envenomation syndromes produced in target species. Elapid venom may be divided into the components of prothrombin activating enzymes, lipases and peptidic neurotoxins. Each species of elapid snake may possess venom components that fit any or all of these classifications. The action of these venom components may result in neurotoxic (pre-synaptic and post-synaptic), haemotoxic (red-cell destruction and coagulation disturbance), cardiovascular, myotoxic and secondary nephrotoxic effects. Marked variability may occur in venom composition between and within snake species, resulting in varying toxicity between species and also potentially unreliable clinical syndromes following envenomation. The existence of certain components consistently within the venom of each snake species allows the broad definition of basic pathological processes and clinicopathological changes resulting from snake species-specific envenomation and these are discussed. Diagnosis of snake envenomation is unreliable if based on clinical signs alone and the use of these signs in conjunction with history, physical examination and laboratory investigation, including snake venom detection kits, is recommended. Treatment of systemic envenomation should be undertaken with initial effective first aid and subsequent administration of snake species-specific antivenom.     

Megaoesophagus in adult dogs secondary to Australian tiger snake envenomation

Four cases of megaoesophagus secondary to tiger snake envenomation are reported. History in all cases suggested megaoesophagus was not present prior to snake envenomation. Diagnosis of megaoesophagus was confirmed by thoracic radiography in all cases. One dog died of respiratory failure. The remaining three dogs recovered, with gradual resolution of clinical signs associated with megaoesophagus.     

Hematologic, plasma protein, and biochemical profiles of brown pelicans (Pelecanus occidentalis)

OBJECTIVE: To establish hematologic and biochemical reference values for the brown pelican (Pelecanus occidentalis). ANIMALS: 31 captive, healthy, but permanently disabled pelicans and 35 wild-caught, healthy pelicans from a rehabilitation facility on the east coast of Florida. PROCEDURES: Samples of venous blood were collected from each pelican, and hematologic, plasma biochemical, and electrophoretic protein analyses were performed. Student t-tests were used to compare blood values between captive versus wild-caught, adult male versus adult female, and adult versus juvenile pelicans. RESULTS: Hematologic and electrophoretic values were similar between male and female, adult and juvenile, and captive and wild-caught pelicans. Significant sex differences existed for plasma calcium and triglyceride concentrations. Plasma concentrations of calcium, cholesterol, and CO2 content differed between captive and wild-caught adults. No significant differences were found between wild-caught adult and juvenile pelicans. CONCLUSIONS AND CLINICAL RELEVANCE: Our plasma biochemical results are similar to those of other brown pelicans and confamilial species. Additional studies on seabirds are encouraged, as age, sex, reproductive status, feeding habits, and captivity are important variables for health assessment in this and other aquatic species.     

Snake bite: coral snakes

North American coral snakes are distinctively colored beginning with a black snout and an alternating pattern of black, yellow, and red. They have fixed front fangs and a poorly developed system for venom delivery, requiring a chewing action to inject the venom. The severity of a coral snake bite is related to the volume of venom injected and the size of the victim. The length of the snake correlates positively with the snakes venom yield. Coral snake venom is primarily neurotoxic with little local tissue reaction or pain at the bite site. The net effect of the neurotoxins is a curare like syndrome. In canine victims there have been reports of marked hemolysis with severe anemia and hemoglobinuria. The onset of clinical signs may be delayed for as much as 10 to 18 hours. The victim begins to have alterations in mental status and develops generalized weakness and muscle fasciculations. Progression to paralysis of the limbs and respiratory muscles then follows. The best flied response to coral snake envenomation is rapid transport to a veterinary medical facility capable of 24 hour critical care and assisted ventilation. First aid treatment advocated in Australia for Elapid bites is the immediate use of a compression bandage. The victim should be hospitalized for a minimum of 48 hours for continuous monitoring. The only definitive treatment for coral snake envenomation is the administration of antivenin (M. fulvius). Once clinical signs of coral snake envenomation become manifest they progress with alarming rapidity and are difficult to reverse. If antivenin is not available or if its administration is delayed, supportive care includes respiratory support. Assisted mechanical ventilation can be used but may have to be employed for up to 48 to 72 hours.     

Comparison of mouse and rabbit model for the assessment of strong PGM-containing oil-based adjuvants

Peptidoglycan monomer (PGM) is an adjuvant active molecule with potential for use in human and veterinary vaccine. PGM's action is short-lived in mammals hence its effects might be limited. Novel PGM-containing oil-based formulations have been developed recently by incorporation of PGM into Montanide ISA720 and ISA206 adjuvants with the aim to prolong and improve immunostimulating activities of PGM. In the present work we studied the efficacy of such novel adjuvant formulations using two different antigens, ovalbumin and snake venom, respectively. Novel formulations were also tested in two experimental models, mice and rabbits. In rabbits the incorporation of PGM into oil-based adjuvants led to overall improvement of antigen-specific IgG response. However, in the mouse model, under experimental conditions used, it was not possible to distinguish differences in antigen-specific IgG response among several strong oil-based adjuvant formulations.     

A case of nutritional secondary hyperparathyroidism in a Siberian tiger cub

A three-month-old female Siberian tiger cub with hindlimb ataxia was referred to the veterinary teaching hospital of Konkuk University. The patient was fed only beef without supplementation of calcium and vitamins after weaning. The tiger was presented with ataxia and back pain on digital palpation. In addition, abnormal gait, reluctance to move, and depressed withdrawal reflex were noted at the neurological examination. The overall osteodystrophic change of the lumbosacral vertebrae was observed on the lateral and ventrodorsal view of radiographic examination. And also PTH level was increased in hormonal assay when compared to that of cat reference range. Based on the results of examinations, nutritional secondary hyperparathyroidism was diagnosed. Clinical signs of this patient were improved after administration of vitamin D and calcium. This case demonstrates that nutritional hyperparathyroidism could be occurred in wild animals raised on a meat diet containing imbalanced calcium and phosphate.     

Effects of various treatments of bovine complement on its lytic efficacy measured by two different tests

Bovine complement was treated with various agents known to activate or inactivate one or more of the cascade components. The treated complement was then assessed for remaining hemolytic activity by a tube titration test and a radial hemolysis method. Divalent cation chelators (EDTA and EGTA); immune complexes prepared with serum and IgM, IgG1, IgG2, and IgA isotypes; smooth and rough lipopolysaccharides and lipid A; hydrazine; zymosan; cobra venom factor and brown recluse spider venom caused depletion of complement as determined in the tube titration test. Immune complexes (prepared with serum); hydrazine; cobra venom factor; EDTA and smooth lipopolysaccharide caused loss of hemolytic activity in the radial hemolysis test. This evidence suggests that the radial hemolysis test assessed complement consumed by the alternate pathway, while the tube titration method measured classical pathway consumption.     

Extradural haematoma secondary to brown snake (Pseudonaja species) envenomation

A 4-year-old Siberian Husky dog was treated with brown snake antivenom by his regular veterinarian after a witnessed episode of brown snake envenomation. The dog was discharged 5 hours post presentation despite an ongoing coagulopathy. The dog was presented to the emergency centre 2 hours later because the owner believed the dog to be in pain. Initial examination revealed an ambulatory but neurologically normal patient with thoracolumbar pain and laboratory evidence of a coagulopathy. Despite correction of the coagulopathy, the signs progressed to bilateral hind limb paresis after approximately 3 hours of hospitalisation, and continued to deteriorate over the next 56 hours to loss of deep pain perception in the right hind limb. Computed tomography imaging identified the presence of an extradural haematoma which was subsequently removed via a hemilaminectomy. Surgical decompression was successful in treating the spinal compression and the dog recovered with minimal complications. To our knowledge this is the first report of extradural haematoma secondary to coagulopathy induced by brown snake envenomation.