Suspected envenomation by the common European adder (Vipera berus berus) in 28 horses in Finland.

Vipera berus berus is the only venomous snake present in the Nordic countries and cases of envenomation in horses are reported during the warmer months. Little is known about the presentation, treatment and survival of horses with common European adder envenomation. Clinical and laboratory findings, treatment and outcome are reported for 28 horses admitted to Helsinki University Equine Hospital in 2008-2023 due to suspicion of snake bite. Eleven of these horses received antivenom treatment. Other common treatments included non-steroidal anti-inflammatories (22/28), antimicrobials (19/28), intravenous fluid therapy (11/28), corticosteroids (9/28) and local treatment (11/28). All horses survived until discharge. No difference was detected in the length of hospital stay between horses with moderate envenomation that had or had not received antivenom treatment. Horses with moderate envenomation are more likely to receive antivenom treatment and require longer hospital stay than horses with mild envenomation. Antivenom treatment is not associated with shorter hospital stay. Little evidence supports the use of corticosteroids and antibiotics in treatment of envenomation. Studies with larger numbers of animals are warranted to evaluate the effect of treatment, including administration of antivenom, on long-term outcome and survival from envenomation.

What drives the risk of being bitten by a viper? A fine spatial scale study in western France.

Previous studies on viper bites in France have focused on clinical consequences of envenomation, efficacy of antivenom and epidemiology of bites. Herein, we wanted to clarify temporal and spatial patterns in bite incidence using a fine spatial scale (municipality level). We focused on viper bites recorded over the last 10 years in 4 regions of western France. We addressed the determinants of bite occurrence and number of bites considering the following variables: predicted probability of viper presence, species (V. aspis or V. berus), climatic data, tourism function rate, soil transformation and landscape use. 703 bite cases were retained with significant disparities between areas. Bites occurred either during a garden-related activity (339 cases, 51.2%) or during an activity in the countryside (300 cases, 45.3%). The probability of presence of a viper at the municipality level positively influenced the risk of being bitten (multiplied by 3 for a variation in probability of 0.25 from 0.5) but varied between species (lower in V. berus than V. aspis). Artificial land development had a positive effect on bite risks. Finally, a tourism function rate above 50 beds/100 inhabitants was strongly associated with an increase in the risk of occurrence and frequency of bites. Overall, viper bites recorded in our study were concentrated on the south coastline of Pays de la Loire region. The coastal towns are significant areas of tourist attraction and are located close to preserved semi-natural landscapes that provide favorable habitats for vipers. This convergence may favor human/wildlife encounters.

First step in assessment of VipGrade®, a computerized clinical decision system to assess Vipera envenomation grading: a single-center interrater reliability study.

METHODS: We conducted a retrospective review of Vipera spp. snakebite cases registered by the PCC of Bordeaux, France, between January 1, 2018, and December 31, 2020, evaluating the agreement between VipGrade® assessments, toxicologists' assessments, and current guidelines. RESULTS: 133 patients with Vipera aspis snakebites were included. There was 100% agreement in severity grading by PCC guidelines and VipGrade®. However, grading by toxicologists and VipGrade® diverged in 19 cases (85% agreement; κ = 0.80; 95% CI: 0.71 to 0.87). CONCLUSIONS: The VipGrade® tool's grading reflects current PCC guidelines, which are authoritative in France, and may allow for a more rapid and standardized determination of management and follow-up of viper-bitten patients. It should be noted, however, that the more complex and dynamic aspects of management are not included in VipGrade®. Its purpose is to supplement, not replace, the advice of the PCC's clinical toxicologists, and this advice should be sought whenever a viper bite is encountered in clinical practice.

Neurotoxicity and Other Clinical Manifestations of a Common European Adder (Vipera berus) Bite in Romania.

Most cases of envenomation by common European vipers (Vipera berus) have not been reported to have neurotoxic manifestations. However, these manifestations have been demonstrated in some cases of envenomation by subspecies of V. berus, found in the Carpathian Basin region of south-eastern Europe. Here, we report the case of a 5-year-old girl from the south of Romania who presented symptoms of neurotoxicity, as well as other systemic and local symptoms, after being bitten by an adder of the V. berus subspecies. Treatment consisted of monovalent antivenom, a corticosteroid, and prophylactic enoxaparin. Neurotoxic manifestations of envenomation as well as other local and systemic symptoms improved within 5 days of treatment. The presented case shows that venom from V. berus subspecies found in the Carpathian Basin can have neurotoxic effects. This case also confirmed the efficacy of monospecific antivenom treatment in bringing about rapid and complete remission, following envenomation.

Intravenous Vipera berus Venom-Specific Fab Fragments and Intramuscular Vipera ammodytes Venom-Specific F(ab')2 Fragments in Vipera ammodytes-Envenomed Patients.

Vipera ammodytes (V. ammodytes) is the most venomous European viper. The aim of this study was to compare the clinical efficacy and pharmacokinetic values of intravenous Vipera berus venom-specific (paraspecific) Fab fragments (ViperaTAb) and intramuscular V. ammodytes venom-specific F(ab')2 fragments (European viper venom antiserum, also called "Zagreb" antivenom) in V.ammodytes-envenomed patients. This was a prospective study of V.ammodytes-envenomed patients that were treated intravenously with ViperaTAb or intramuscularly with European viper venom antiserum that was feasible only due to the unique situation of an antivenom shortage. The highest venom concentration, survival, length of hospital stay and adverse reactions did not differ between the groups. Patients treated with intravenous Fab fragments were sicker, with significantly more rhabdomyolysis and neurotoxicity. The kinetics of Fab fragments after one or more intravenous applications matched better with the venom concentration in the early phase of envenomation compared to F(ab')2 fragments that were given intramuscularly only on admission. F(ab')2 fragments given intramuscularly had 25-fold longer apparent total body clearance and 14-fold longer elimination half-time compared to Fab fragments given intravenously (2 weeks vs. 24 h, respectively). In V.ammodytes-envenomed patients, the intramuscular use of specific F(ab')2 fragments resulted in a slow rise of antivenom serum concentration that demanded their early administration but without the need for additional doses for complete resolution of all clinical signs of envenomation. Intravenous use of paraspecific Fab fragments resulted in the immediate rise of antivenom serum concentration that enabled their use according to the clinical progress, but multiple doses might be needed for efficient therapy of thrombocytopenia due to venom recurrence, while the progression of rhabdomyolysis and neurotoxic effects of the venom could not be prevented.

Snake bites by European vipers in Mainland France in 2017-2018: comparison of two antivenoms Viperfav® and Viperatab®.

Context: Today, immunotherapy with Fab or F(ab')2 fragments is considered as a gold standard treatment for patients bitten by vipers. We compared the efficiency of two antivenoms, Viperfav® and Viperatab®, in mainland France in 2017-2018 with data provided by the French poison control centre (PCC).Methods: Patients with a moderate (2a and 2b) or severe (3) envenomation after a European viper bite and treated with immunotherapy were included and the markers chosen were the risk of post-antivenom treatment worsening, duration of hospital stay and persistent functional discomfort on day 15. Statistical studies were based on multivariate data analysis.Results: Two hundred and ninety-seven cases were recorded. One hundred and eighty-two (61.3%) patients received Viperfav® and 115 (38.7%) received Viperatab®. Compared to Viperfav®, use of Viperatab® significantly increased the risk of post-antivenom treatment worsening (OR* 12.05; 95%CI [3.11; 46.70]; p < .001). No significant difference between these antivenoms was recorded with respect to the duration of hospital stay and persistent functional discomfort on day 15. Viperfav® and Viperatab® have a similar tolerance (p > .21). Otherwise, duration of hospitalisation was significantly increased by a delay of immunotherapy infusion of more than 12 h (OR 2.70; 95%CI [1.45-5.06]; p = .002) or a preventive administration of LMWH (OR 6.55; 95%CI [1.58-27.13]; p=.02).Discussion: While Viperfav® and Viperatab® have a similar tolerance, our data show that Viperatab® was associated with a higher risk of post-antivenom treatment worsening compared to Viperfav®. Furthermore, this study confirms that the antivenom should be used as soon as possible. Indeed, patients receiving the immunotherapy infusion from the grade 2b presented significantly more frequent exacerbated symptoms (OR 3.99; 95%CI [1.16-13.73]; p=.028) after the antivenom infusion compared to grade 2a group.Conclusions: Whereas no significant difference between these antivenoms was recorded with respect to the duration of hospital stay and persistent functional discomfort on day 15, use of Viperatab®, compared to Viperfav®, significantly increased the risk of post-antivenom treatment worsening (OR* 12.05; 95%CI [3.11; 46.70]; p < .001). Taken together, these data show that Viperfav® is the treatment of choice for the management of snake bites in France.

Vipera berus berus Venom from Russia: Venomics, Bioactivities and Preclinical Assessment of Microgen Antivenom.

The common European adder, Vipera berus berus, is a medically relevant species, which is widely distributed in Russia and thus, is responsible for most snakebite accidents in Russia. We have investigated the toxic and enzymatic activities and have determined the proteomic composition of its venom. Phospholipases A2 (PLA2, 25.3% of the venom proteome), serine proteinases (SVSP, 16.2%), metalloproteinases (SVMP, 17.2%), vasoactive peptides (bradykinin-potentiating peptides (BPPs), 9.5% and C-type natriuretic peptides (C-NAP, 7.8%), cysteine-rich secretory protein (CRISP, 8%) and L-amino acid oxidase (LAO, 7.3%) represent the major toxin classes found in V. b. berus (Russia) venom. This study was also designed to assess the in vivo and in vitro preclinical efficacy of the Russian Microgen antivenom in neutralizing the main effects of V. b. berus venom. The results show that this antivenom is capable of neutralizing the lethal, hemorrhagic and PLA2 activities. Third-generation antivenomics was applied to quantify the toxin-recognition landscape and the maximal binding capacity of the antivenom for each component of the venom. The antivenomics analysis revealed that 6.24% of the anti-V. b. berus F(ab')2 molecules fraction are toxin-binding antibodies, 60% of which represent clinically relevant antivenom molecules.

European viper envenomation recorded by French poison control centers: A clinical assessment and management study.

INTRODUCTION: Immunotherapy is the gold standard treatment for patients bitten by European vipers in France; it significantly decreases morbidity, frequency and severity of complications and length of stay. A national prospective study was performed by all Poison Control Centers (PCC) to validate the emergency protocol for viper envenomations. METHODS: This prospective study included all cases of viper bites in France, treated or not with Viperfav(®) in 2013. RESULTS: In 2013, 277 cases of viper bites were collected: ratio M/F 2.1; mean aged 43 years (<15 years 25% 15-65 63% > 65 12%). The final severity was divided into 68 grades 0, 58 grades I, 62 grades IIA, 71 grades IIB and 18 grades III. One death was reported. Five patients had neurological signs. For the 114 patients who received Viperfav(®), all systemic signs disappeared in 5 h and in 24 h for biological and neurological signs. No severe anaphylactic reaction with Viperfav(®) was reported. Late Viperfav(®) administration increased the risk of functional impairment 15 days after the bite (OR = 3.21 p = 0.043). The administration of Low Molecular Weight Heparin (LMWH) increased the frequency of functional impairment to 15 days after the bite (OR = 6.38 p = 0.064), although Viperfav(®) was given in the first 18 h. DISCUSSION: This study confirms the efficiency, safety and recommendation of an early administration of a single dose of Viperfav(®), LMWH should not be used. It also shows the extension of neurotoxic venom of vipers in France.