A longitudinal study of the blood and urine metabolome of Vipera berus envenomated dogs.

Envenomation of dogs by the common European adder (Vipera berus) is associated with high morbidity. The cytotoxic venom of Vipera berus contains enzymes with the potential to cause acute kidney injury, among other insults, however robust biomarkers for such effects are lacking. A prospective observational follow-up study of naturally envenomated dogs and controls was conducted to fill knowledge gaps regarding canine Vipera berus envenomation, attempt to identify novel biomarkers of envenomation and related kidney injury, and elucidate potential long-term effects. Blood and urine samples were analyzed with a global metabolomics approach using liquid chromatography-mass spectrometry, uncovering numerous features significantly different between cases and controls. After data processing and feature annotation, eight features in blood and 24 features in urine were investigated in order to elucidate their biological relevance. Several of these are associated with AKI, while some may also originate from disturbed fatty acid ß-oxidation and soft tissue damage. A metabolite found in both blood and a venom reference sample may represent identification of a venom component in case dogs. Our findings suggest that envenomated dogs treated according to current best practice are unlikely to suffer permanent injury.

Pit Viper Envenomation in Two Pregnant Bitches.

Snake envenomation is relatively common in small animals, particularly in endemic areas. Effects and outcomes of envenomation during pregnancy are poorly described in humans and more so in veterinary patients. Two young pregnant female dogs presented to a university teaching hospital with a history of acute soft tissue swelling and bleeding. History, physical examination findings, and diagnostics were consistent with envenomation by crotalid snakes. Medical management of one of the dogs included administration of antivenin. Both dogs survived envenomation with minimal complications and went on to whelp without complications, and all fetuses survived. This is the first description of the management of pit viper envenomation in pregnant dogs.

The establishment and evaluation of a swine model of deinagkistrodon acutus snakebite envenomation.

OBJECTIVE: To establish a preclinical large-animal model of Deinagkistrodon acutus snakebite envenomation and evaluate its feasibility. METHODS: The venom of D. acutus (0 mg/kg, 1 mg/kg, 2 mg/kg, 5 mg/kg, or 10 mg/kg) was injected into the left biceps femoris of 11 male pigs. Then, the circumferences of the limbs were regularly measured, and changes in muscle injury biomarkers, blood parameters, coagulation function, vital organ function and injury biomarkers were regularly detected. At 24 h after venom injection, the animals were euthanized, and the pathological damage to the vital organs mentioned above was evaluated. RESULTS: The two pigs receiving 10 mg/kg and 5 mg/kg snake venom died at 8 h and 12 h after injection, respectively. The remaining pigs were equally divided into 0 mg/kg, 1 mg/kg, and 2 mg/kg snake venom groups, and all of them survived to 24 h after injection. Compared with the pigs receiving 0 mg/kg snake venom, the pigs receiving 1 mg/kg or 2 mg/kg snake venom exhibited significant abnormities, including limb swelling; increased muscle injury biomarker creatine kinase (CK) and coagulation function indicators prothrombin time and D-dimer; and decreased blood routine indicator platelet and coagulation function indicator fibrinogen. Moreover, significant abnormalities in myocardial and cerebral function and injury biomarkers in the heart, brain, liver, kidney and intestine were also observed. In particular, the abnormalities mentioned above were significantly obvious in those pigs receiving 2 mg/kg snake venom. Pathological evaluation revealed that the morphology of muscle, heart, brain, liver, kidney, and intestine in those pigs receiving 0 mg/kg snake venom was normal; however, pathological damage was observed in those pigs receiving 1 mg/kg and 2 mg/kg snake venom. Similarly, the pathological damage was more severe in those pigs receiving 2 mg/kg snake venom. CONCLUSION: The intramuscular injection of 2 mg/kg D. acutus venom seems to be an optimal dose for examining the preclinical efficacy of existing and novel therapeutics for treating D. acutus envenomation in pigs.

Evaluation of venom diversity and antivenom quality from the venom of long-term captive vs recently wild captured Pseudocerastes persicus snake: An In vitro and In vivo study.

Snakebite envenomation is a life-threatening condition and antivenoms are used as the most effective treatment. Venom obtained from snakes in long-term captivity showed some variations in comparison to the venom of the wild snakes. The objective of this study is to compare the venom of the Pseudocerastes persicus under long-term captivity and wild conditions as well as the antivenom obtained from these venoms. We have analyzed venom samples and produced trivalent antivenoms using the venom of long-term captive (LTC) or recently wild-captured (RWC) Pseudocerastes persicus, and RWC Macrovipera lebetina, and Echis carinatus. The HPLC analysis revealed that the RWC snakes' venom had three peaks that were not present in the LTC snake's venom. Further analysis using MALDI-TOF and MS/MS showed that the fraction with a retention time (RT) of 14 min contained a toxin from the Kunitz-type serine protease inhibitor (KUT) class, while the fraction with RT 21 a peptide identified within the snake venom metalloproteinase (SVMP) class. The third peak was identified as a sphingolipid. Interestingly, the in vivo preclinical tests showed no significant differences in the effectiveness of the antivenoms. which could be due to the cross-immunogenicity or cross-reactivity between different toxins in the venom. According to our results, small variations in the venom composition of a species do not lead to a decrease in the efficacy of the polyvalent antivenom.

Snake Envenomation.

Snakebite envenomation (SBE) in horses can have devastating outcomes. Tissue damage, cardiotoxicity, coagulopathy, and neurotoxicity can be concerns with SBE. Understanding the actions of venom components is important in developing a successful treatment plan. Antivenom is the mainstay of treatment. Long-term deleterious effects can occur including cardiac dysfunction and lameness.

The challenge in detecting risk areas of snakebite when case rates are low: the case of Amazonian coral snakes.

Identifying risk areas for envenomation by animals is relevant for public health, such as strategic distribution of antivenoms. Coral snakes are highly diverse in the Amazon, inhabit natural and human-modified environments, and the outcome of the cases tends to be serious and potentially lethal due to their neurotoxic venom. By integrating species' geographical records and environmental variables, we used species distribution modeling to predict the distribution of coral snake species in the Brazilian Amazonia. We analyzed the relationship between the predicted distribution of coral snake species, along with envenomation data in the region, to propose actions to reduce the number of cases and to provide tools for a better policy of public health. We conclude that the entire Amazon shows high environmental suitability for coral snakes, and such suitability explains little about the incidence of cases. This is probably due to the low human density in the Amazon and to coral snake traits such as secretive habits and non-agressive behavior. Differently from other venomous snakes, the scenario regarding coral snakebites precludes the detection of prominent geographical areas of concern and demands a broad and equitable availability of health centers throughout Amazonia and along other areas of occurrence of the genus Micrurus.

Serum Cholesterol Concentration on Admission in 415 Dogs Envenomated by Daboia (Vipera) palaestinae as a Marker of Envenomation Severity and Outcome-A Retrospective Study.

Daboia (Vipera) palaestinae (Dp), accounts for most envenomations in humans and dogs in Israel. In humans envenomed by Dp, serum cholesterol concentration (sChol) is inversely correlated with envenomation severity. This study examined the utility of sChol upon admission in dogs envenomed by Dp as an envenomation severity and outcome marker. Data upon admission, including sChol, were retrospectively collected from the medical records of dogs with proven Dp envenomation. The study included 415 dogs. The mortality rate was 11%. The heart rate upon admission was higher in non-survivors than in survivors. Signs of bleeding or hematoma and circulatory shock signs were more frequent among non-survivors compared to survivors. sChol, the platelet count, and serum albumin concentration (sAlb) were lower, while serum creatinine concentration was higher among non-survivors. sChol and sAlb were moderately, positively, and significantly correlated. sChol was significantly, negatively, albeit weakly, correlated with the length of hospitalization and the heart rate. sChol was lower in dogs admitted >12 h post-envenomation than in those admitted later. In dogs, sChol upon admission is a potential marker of severity and outcome of Dp envenomation. The platelet count, sAlb, and sCreat might also be potential markers.

Snakebite Envenoming in Avian Species: A Systematic Scoping Review and Practitioner Experience Survey.

Snakebite envenoming in avian species is infrequently reported in the veterinary literature, although perhaps not as rarely as recent publications suggest. A systematic scoping review was performed on the topic using PubMed and Google Scholar, 21 veterinary textbooks, and 139 conference proceedings. A practitioner experience survey was also performed, with recruitment from Facebook groups for exotic animal practitioners and professional organization email listservs. Only 31 texts met our inclusion/exclusion criteria, which meant they described clinicopathologic signs of snakebite envenomation in avian species, the treatment of snakebite envenomation in avian species, or expanded the geographic range or the number of captive avian and snake species involved. Reports included approximately 15-20 different species of both snakes and birds worldwide; however, no reports described clinicopathologic signs of naturally occurring snakebites from Asia, Australasia, or Europe. The few responses from our practitioner experience survey suggest that snakebite envenomation may be more common than previously reported. Clinical signs of snake envenomation in birds appear to depend on the snake species involved but often include local swelling and subcutaneous edema or hemorrhage with paired fang marks; weakness, bleeding, neurologic deficits, and death may follow. A wide variety of treatment protocols have been used to counter snakebite envenomation in birds, including the successful use of antivenom. Based on this body of evidence, much remains to be learned about snakebite envenomation of birds, particularly about the efficacy of different treatment protocols.

Clinical features and management of snake bites in 70 dogs in Korea.

BACKGROUND: Snakebites remain a devastating and life-threatening environmental hazard. While the management of snakebites has been well described in humans, few clinical data and guidelines exist for dogs, especially in Korea. OBJECTIVES: This retrospective study evaluated the clinical features of 70 dogs with snakebite wounds in Korea. METHODS: The medical records of 72 dogs that presented to three animal hospitals from June 2008 to July 2021 were reviewed; among these, 70 dogs that met the inclusion criteria were enrolled. Their signalment, history, clinical signs, physical examination, blood analysis, treatment, and prognosis were also evaluated. RESULTS: Of 70 dog owners, 35 (50%) witnessed the bite, with a mean time between bite and hospital presentation of 9.7 ± 4.1 h in 58 dogs. Blood smears were evaluated in 45 dogs, of which 28 (62%) showed echinocytosis. Anemia and acute kidney injury were found in 21 (29%) and 2 dogs (3%), respectively. A total of 37 dogs (53%) were hospitalized, 5 (7%) of which died. CONCLUSIONS: The most significant finding was the high prevalence of echinocytosis. The data from this retrospective study could inform the management of dogs bitten by snakes in Korea.

Screening and identification of differential metabolites in serum and urine of bamaxiang pigs bitten by trimeresurus stejnegeri based on UPLC-Q-TOF/MS metabolomics technology.

Trimeresurus stejnegeri is one of the top ten venomous snakes in China, and its bite causes acute and severe diseases. Elucidating the metabolic changes of the body caused by Trimeresurus stejnegeri bite will be beneficial to the diagnosis and treatment of snakebite. Thus, an animal pig model of Trimeresurus stejnegeri bite was established, and then the metabolites of serum and urine were subsequently screened and identified in both ESI+ and ESI- modes identified by ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS) methods. There are 9 differential metabolites in serum, including Oleic acid, Lithocholic acid, Deoxycholic acid, Hypoxanthine, etc. There are 11 differential metabolites in urine, including Dopamine, Thiocysteine, Arginine, Indoleacetaldehyde, etc. Serum enrichment pathway analysis showed that 5 metabolic pathways, including Tryptophanuria, Liver disease due to cystic fibrosis, Hartnup disease, Hyperbaric oxygen exposure and Biliary cirrhosis, the core metabolites in these pathways, including deoxycholic acid, lithocholic acid, tryptophan and hypoxanthine, changed significantly. Urine enrichment pathway analysis showed that 4 metabolic pathways, including Aromatic L-Amino Acid Decarboxylase, Vitiligo, Blue Diaper Syndrome and Hyperargininemia, the core metabolites in these pathways including dopamine, 5-hydroxyindole acetic acid and arginine. Taken together, the current study has successfully established an animal model of Trimeresurus stejnegeri bite, and identified the metabolic markers and metabolic pathways of Trimeresurus stejnegeri bite. These metabolites and pathways may have potential application value and provide a therapeutic basis for the treatment of Trimeresurus stejnegeri bite.

A bite by the emerald snake, Hapsidophrys smaragdinus Schlegel, 1837 (Colubridae, Colubrinae) causing atopic eczema with comments on the formal documentation of non-front-fanged snakebites.

The mixed quality evidence about non-front-fanged snake bites has included unsupported speculation and presumption; the possible role of atopy and/or primary hypersensitivity have often been prematurely discounted. Described is a medically insignificant bite by a captive African emerald snake, Hapsidophrys smaragdinus Schlegel, 1837 (Colubridae, Colubrinae) that caused the development of moderate Type IV hypersensitivity; the 44-year-old male victim experienced persistent pruritis and an erythematous bite site maculopapular dermatitis that slowly resolved and required 6 days for full resolution. The victim had received several previous medically insignificant bites from non-front-fanged snakes. Brief comparison is made with a previously reported case consistent with a mixed clinical picture of local mild envenoming and hypersensitivity from a bite by another colubrine, the coin snake (Hemmorhois nummifer). This case highlights slowly accumulating evidence supporting the risk of acquired and primary hypersensitivity to some snakebites in susceptible individuals. In order to provide accurate medical risk profiles for less-known snake species it is essential that the case of any patient developing acute or delayed effects from bites by these species is formally documented. The need for further attention to atopic risks, especially in private collectors, is emphasised with consideration of venom/other ophidian product-induced anaphylaxis.

A Retrospective Evaluation of Snake Envenomation in Dogs in South Korea (2004-2021).

Snake envenomation is a medical emergency capable of causing local and systemic complications. However, information on venomous snakebite in dogs in South Korea is scarce. In this study, fifty-nine dogs treated at a private veterinary clinic from 2004 to 2021 were retrospectively studied. The aim was to characterize the demographics, elapsed time between snakebite and veterinary clinic presentation, laboratory findings, clinical signs, treatments, adverse reactions to antivenom, and prognosis of venomous snakebite. Snakebite was mostly observed between 12 p.m. and 5 p.m. from April to October. On the days of envenomation, the weather conditions were mostly cloudy, followed by rain/precipitation, and least frequently fair weather. Grassland was the most common incident location, and leashed dog walking was the most frequent activity when snakebite occurred. The main local symptoms were edema, hemorrhagic discharge, cutaneous erythema, ulceration, and necrosis. Major systemic clinical signs were tachypnea, tachycardia, altered mentation, ptyalism, and hypotension. Based on the time interval between snakebite and presentation at the veterinary clinic, two groups were defined: <4 h (Group 1, 49.2%) and ≥4 h (Group 2, 50.8%). Systemic inflammation was more frequently observed in Group 2. The level of C-reactive protein at presentation (p = 0.036) and the highest-level during hospitalization (p = 0.023) were significantly elevated in Group 2 (≥4 h). The dogs in Group 2 displayed more frequent muscle damage (increased creatine kinase) than the dogs in Group 1, and a higher level of creatine kinase was associated with delayed (≥4 h) presentation after snakebite (p = 0.003). All of the dogs were treated symptomatically, and 34 dogs (58%) received antivenom. Treatment with antivenom showed no adverse reactions in this study. All of the treated dogs recovered. One dog was euthanized without any treatment due to respiratory distress, hypotension, and cost constraints. In conclusion, this study provides baseline information on venomous snakebite in dogs in South Korea. The prognosis was excellent, especially when the dogs were treated within 4 h.

In vitro evaluation of canine whole blood with the addition of Crotalus atrox (Western Diamondback Rattlesnake) venom and antivenom using thromboelastography.

OBJECTIVES: To compare the efficacy of 2 equine-origin antivenom products on correction of coagulation abnormalities noted on thromboelastography (TEG) caused by Crotalus atrox venom in vitro. DESIGN: Prospective in vitro controlled study. SETTING: Veterinary teaching hospital. ANIMALS: Six healthy dogs. INTERVENTIONS: Blood from each dog was used for 4 separate kaolin-activated TEG analyses: A negative control (blood-saline) and positive control (blood-Crotalus atrox venom) were used to assess the dog's normal coagulation and the effect of venom on TEG parameters. Thromboelastographic analyses were then run with blood, venom, and either Argentinian or North American antivenom. All TEG analyses from each dog were compared for efficacy. MEASUREMENTS AND MAIN RESULTS: The mean R values between the North American antivenom and negative controls were not significantly different (P = 0.681), but were significantly different (P = 0.024) between the Argentinian antivenom and negative controls. The mean fibrinolysis values measured 30 minutes after maximum amplitude achieved between the North American antivenom and negative controls were not significantly different (P = 0.198), but were significantly different (P < 0.001) between the Argentinian antivenom and negative controls. The mean K values between the Argentinian antivenom and negative controls were not significantly different (P = 0.274), but were significantly different (P = 0.043) between the North American antivenom and negative controls. CONCLUSIONS: The North American antivenom normalized time to clot formation and fibrinolysis, while the Argentinian antivenom normalized rate of clot formation. Further studies in naturally envenomated patients are necessary to determine if these in vitro results would translate into different clinical outcomes.

Clinico-epidemiology and management of hump-nosed pit viper (Hypnale spp.) bites in dogs.

Human envenoming from the bite of the abundant hump-nosed pit viper (Hypnale spp.) (HNPV) is a frequent occurrence with victims experiencing unpleasant and sometimes life-threatening consequences. Further, clinico-pathology, treatment and management measures in HNPV envenomed dogs are under recognized. Prospective investigations were performed to assess the clinico-pathology and management options for HNPV envenomed dogs brought to the University of Peradeniya's Veterinary Teaching Hospital from January, 2012 to March 2018. We recorded the local and systemic manifestations, hematological and urinary abnormalities of 78 dogs in which HNPV bite had been witnessed by the owner. Mild swelling, extensive swelling, hemorrhagic blistering and hemorrhagic bullae at the site of bite were observed in 59%, 31%, 6% and 4% of the dogs, respectively. Some dogs were subjected to surgical excision of necrotized tissue including limb amputation. We observed the following systemic clinical effects in envenomed dogs: neurotoxicity (13%), acute kidney injury (AKI) (14%) and coagulopathy (16%). All dogs showed leukocytosis with mean white blood cell count of 25.25 × 103/µL. Mild anemia and thrombocytopenia were detected in 29% of the dogs. There was a significant correlation between extent of local tissue injuries with length of hospitalization (LH). The mean time of coagulopathy observed was 21.3 h (IQR: 8-48 h). In coagulopathic dogs, there was a strong correlation between LH and extent of local tissue injury (rs = 0.7751, P < 0.0001); LH and whole blood clotting time(CT) (rs = 1.0, P < 0.0001); PT and aPTT (rs = 0.4712, P < 0.001). LH was significantly correlated with the development of AKI (p = 0.0013). Lack of specific antivenom (AVS) for HNPV envenoming provided an opportunity to study the remaining treatment options. Therefore, the study allowed the identification of local and systemic effects, hematological abnormalities, possible supportive treatments and drawbacks of management measures for envenomed dogs.

Crotalid Polyvalent F(ab)2 Antivenom Treatment in a Red-Tailed Hawk (Buteo jamaicensis).

Envenomation in avian species can result in death, with few cases of successful treatment described. A juvenile, wild-caught, intact female red-tailed hawk (Buteo jamaicensis) used in falconry was presented for emergency evaluation after being bitten by a Northern Pacific rattlesnake (Crotalus oreganus) approximately 2 hours before presentation. On presentation, the bird was quiet, alert, and responsive, with moderate swelling and discomfort of the digits on the right foot. Complete blood count (CBC) and plasma biochemistry abnormalities included a regenerative left shift, severe lymphopenia, and a moderate hypoproteinemia characterized by moderate hypoalbuminemia. Analgesic and antibiotic medications were administered during hospitalization. In addition, 5 mL of VenomVet was administered intravenously with crystalloid fluids over 60 minutes; no adverse effects were noted secondary to infusion. Improvement in the swelling was observed immediately after antivenom administration and nearly resolved within 12 hours. Complete resolution of digital swelling with no discomfort on palpation of that foot was observed 1 week after initial presentation. Blood collected at the 1 week reexamination was submitted for a CBC and plasma biochemistry panel. The results of the CBC revealed a reduced regenerative left shift, increased heterophil count, and a moderate monocytosis; the lymphopenia was resolved. A mild hypoalbuminemia still persisted. Ten months after presentation, the bird was reported to be doing well with no changes in function of the right foot and subsequently released from captivity.

A review of 91 canine and feline red-bellied black snake (Pseudechis porphyriacus) envenomation cases and lessons for improved management.

INTRODUCTION: Most cases of red-bellied black snake (RBBS) envenomation in dogs respond favourably to treatment comprising of tiger-brown snake antivenom (TBAV), intravenous fluid therapy, analgesia and, if indicated, mechanical ventilation and/or blood transfusion. However, there remains a subset of patients who develop fatal complications despite intensive treatment and risk factors for these occurring remain unknown. Here we present a retrospective cross-sectional survey of 91 canine and feline RBBS envenomation cases. METHODS: Cases seen between June 2010 and June 2020 were retrieved from the databases of seven practices in South East and coastal Queensland. From the canine case population, logistic regression analysis was performed to assess the impact of potential risk factors at presentation on the likelihood of death. A final multivariable model was developed using a manual backwards elimination approach based on overall likelihood ratio tests and Wald chi-square P-values for each variable. Where model convergence failed due to quasi-complete separation, Firth's penalised maximum likelihood method was implemented. Such separation may occur when an outcome is completely predicted by an explanatory variable in one group. RESULTS: Of the 88 canine cases, 7 died (8.0%), all after prognosis-based euthanasia. Of the three feline cases, one died after unsuccessful resuscitation following cardiopulmonary arrest. Compared to survivors, dogs that died were older, exhibited pigmenturia, received antivenom later and had a higher total plasma protein (TPP), activated clotting time (ACT) and lower packed cell volume (PCV) at presentation.

Rattlesnake envenomation in 2 Visayan warty pigs.

Rattlesnake envenomation is an important cause of morbidity and mortality in humans and animals in the southwestern United States and elsewhere. Two Visayan warty pigs (Sus cebifrons) from a regional zoo were submitted for autopsy after being found dead close to a southern Pacific rattlesnake (Crotalus helleri) in their enclosure. Both pigs had severe regionally extensive cutaneous, subcutaneous, and muscle hemorrhage and edema with myonecrosis. Additionally, both pigs had lesions consistent with puncture wounds within the oral cavity, and one pig had a similar wound on a forelimb. The history, and gross and histologic findings, were consistent with envenomation by rattlesnake bite. There are few documented cases of snakebite envenomation in pigs, and it had been suggested that pigs may have some degree of resistance to envenomation. Our results indicate that warty pigs are susceptible to the action of rattlesnake venom.

In cold blood: Observational descriptive review of Eastern Massasauga rattlesnake bites reported to a single poison center over time.

The Eastern Massasauga rattlesnake (Sistrurus catenatus catenatus) is a pit viper indigenous to the Great Lakes region and the only venomous snake native to Michigan. It is small-to-medium, thick-bodied with dark brown, bow-tie shaped blotches. Its behavior is described as reclusive and docile and it prefers damp habitats. The venom of the Eastern Massasauga is primarily cytotoxic and hemotoxic. Previous literature describes severe coagulopathies following Eastern Massasauga envenomings, with some resulting in death. The objective of this study was to characterize Eastern Massasauga envenomings in humans reported to the Michigan Poison & Drug Information Center from 2003 to 2020, including a description of clinical manifestations, incidence and characterization of coagulopathies, and medical outcome severities. This was a retrospective review of Eastern Massasauga snakebites reported to our state poison center over time. Coagulopathies were classified according to previous toxicological snakebite literature. The degree of envenoming was scored using an institutional guideline, representing a modified version of validated snakebite severity score system. Our longitudinal review demonstrated Eastern Massasauga bites led to clinically significant toxicity, including persistent, recurrent, and late coagulopathies, though with low incidence of bleeding events. Cases typically resolved with use of antivenom. This, to our knowledge, is the largest descriptive case series characterizing Eastern Massasauga snakebites.