Comparative study of the in vivo toxicity and pathophysiology of envenomation by three medically important Egyptian snake venoms.

Snakebite envenomation is a serious medical problem in many developing tropical and subtropical countries. Envenomation is registered by the World Health Organization as a neglected tropical disease due to critical shortages in the production of antivenom. Envenomation causes more than 100,000 deaths annually. Snakebites result in several effects to include edema, blistering, hemorrhage, necrosis and respiratory paralysis. Antivenom is the preferred treatment for the systemic effects of snakebite envenomation, though these are often ineffective in neutralizing venom toxin-induced local tissue damage. To effectively treat snakebites, it is important to determine the lethal potency and pathophysiological effects induced by specific snake venoms. In the current study, we compared the lethality, and the hemorrhagic and dermonecrotic activities of venoms from three snakes in Egypt that are the primary causes of local tissue necrosis. Our data show that the intraperitoneal median lethal doses (LD50) for Cerastes cerastes, Echis carinatus and Naja nigricollis venoms are 0.946, 1.744 and 0.341 mg/kg mouse body weight, respectively. These results indicated that N. nigricollis venom is the most toxic and significantly accelerated the time of death compared to the other two venoms. However, no hematoma or associated edema appeared upon sub-plantar injection of N. nigricollis venom into the mice hind paw. Two hours following intradermal injection of C. cerastes and E. carinatus venoms, macroscopic analysis of the inner surface of mouse skin showed severe hemorrhagic lesions, whereas only insignificant hemorrhagic lesion appeared in mice injected with the highest dose of N. nigricollis venom. Furthermore, the minimum necrotic doses (MND) for the same venoms were 43.15, and 70.87 µg/mouse, or not observed in the case of N. nigricollis venom, respectively. These LD50 values and pathophysiological results can be used to guide development of antivenom against bites by these dangerous Egyptian snakes.

Clinical Features, Bacteriology, and Antibiotic Treatment Among Patients with Presumed Naja Bites in Vietnam.

INTRODUCTION: Clinical and bacteriological features of cobra (Naja) bites are still relatively unknown in Vietnam. This study aimed to characterize the clinical and bacteriological characteristics of local wounds in patients with presumed Naja spp bite, as well as their antibiotic treatment. METHODS: A cross-sectional study was performed on presumed Naja bite patients who were admitted to Bach Mai Hospital in Hanoi, Vietnam. In vitro bacterial isolation, blood tests, and lesion measure were conducted, and antibiotic susceptibilities of localized bite wounds were assessed. The Mann-Whitney test was used to examine the difference in clinical characteristics between patients experiencing presumed Naja atra bites and Naja kaouthia bites. Data are presented as percentages or median with interquartile range, as appropriate. Statistical significance was accepted at P<0.05. RESULTS: Among 46 patients, all had typical clinical features of Naja bite. The median bite-to-hospital time was 6 h (interquartile range 4.0-11.3). The dominant organisms isolated from local wounds were Morganella morganii (11/36) and Enterococcus faecalis (25/36). All cultures were susceptible to ciprofloxacin. No difference was found with regard to pain, swelling circumference, swelling spread, or necrotic area between patients bitten by presumed Naja atra and Naja kaouthia (P>0.05). CONCLUSIONS: Wound necrosis and infection were important clinical issues in presumed Naja spp snake bites. Morganella morganii and Enterococcus faecalis were dominant in local wound swabs of such cases. Ciprofloxacin should be an effective first-line antibiotic for patients with presumed Naja bite.

Snakebite accidents in Rio Grande do Norte state, Brazil: Epidemiology, health management and influence of the environmental scenario.

OBJECTIVES: Brazil is home to large variety of snake species, of which about 17% are venomous. A large proportion of reported snakebite accidents in the country take place in northeast Brazil. We aimed to analyse the epidemiology of snakebites as a public health concern in Rio Grande do Norte state. METHODS: A retrospective epidemiologic analysis was performed using data from the Brazilian Case Registry Database pertaining to the period 2007-2016, and considering environmental climate characteristics as an influential factor. RESULTS: A number of 3909 cases were reported in total. Among those cases, 58% involved venomous species and more than 80% of these were caused by Bothrops species. An association between environmental characteristics and the incidence of reported cases was found. The Borborema Potiguar region was the most affected area. Apart from that, deficiencies in managing the victims were described. CONCLUSION: This study highlights snakebite accidents as a public health concern in Rio Grande do Norte state. Snake bites are most likely being influenced by climate change and human activities. Continuous training of involved medical personnel could help optimise patient care and avoid under reporting in the accident reporting system.

OBJECTIFS: Le Brésil abrite de très nombreuses espèces de serpents, dont environ 17% sont venimeuses. Une grande partie des accidents rapportés de morsures de serpent dans le pays ont lieu dans le nord-est du pays. Notre objectif était d'analyser l'épidémiologie des morsures de serpents en tant que problème de santé publique dans l'Etat du Rio Grande do Norte. MÉTHODES: Une analyse épidémiologique rétrospective a été réalisée à l'aide des données de la Base de Données du Registre Brésilien des cas couvrant la période 2007-2016 et prenant en compte les caractéristiques climatiques de l'environnement comme facteur d'influence. RÉSULTATS: 3.909 cas au total ont été rapportés. 58% concernaient des espèces venimeuses et plus de 80% d'entre elles étaient causées par l'espèce Bothrops. Une association entre les caractéristiques environnementales et l'incidence des cas rapportés a été mise en évidence. La région de Borborema Potiguar était la plus touchée. Outre cela, les déficiences dans la prise en charges des victimes ont été décrites. CONCLUSION: Cette étude souligne que les accidents causés par des morsures de serpent constituent un problème de santé publique dans l'Etat de Rio Grande do Norte. Les morsures de serpents sont très probablement influencées par les changements climatiques et les activités humaines. La formation continue du personnel médical impliqué pourrait aider à optimiser les soins prodigués aux patients et à éviter une sous-notification dans le système de notification des accidents.

Snakebites Treated in North Carolina Emergency Departments, October 2013-September 2015.

INTRODUCTION: North Carolina (NC) is home to more than 30 species of indigenous venomous and nonvenomous snakes. Snakebites can cause debilitating and potentially fatal injuries. However, there is a lack of current information available describing the incidence of snakebites in NC. Therefore, we performed this study of snakebites treated in NC emergency departments (EDs) using the statewide syndromic surveillance system, the North Carolina Disease Event Tracking and Epidemiologic Collection Tool (NC DETECT). METHODS: This was a descriptive epidemiologic study characterizing NC ED visits collected by NC DETECT between October 1, 2013 and September 30, 2015 with an assigned International Classification of Diseases, 9th Revision, Clinical Modification code or keyword indicating a snakebite. RESULTS: Over the 2-year period, the absolute count of snakebite-related ED visits was 2080 visits with an incidence rate of 10.4 visits per 100 000 person-years (95% confidence interval: 10.0-10.9). The frequency of snakebite was highest during the summer months and evening hours. Men had higher incidence rates of snakebite-related ED visits than women, and residents of the Coastal Plain geographic region of NC had higher incidence rates than persons in other regions. CONCLUSIONS: The current study indicated that snakebites are common injuries treated at NC EDs, with a strong seasonal and geographic component. Additional research is needed to further characterize the circumstances associated with snakebites for the development of preventive measures and public health education.

THE FIRST REPORT OF A CROTALID ENVENOMATION IN A DOMESTICATED FERRET ( MUSTELA FURO) AND SUCCESSFUL TREATMENT WITH A NOVEL F(AB')2 ANTIVENOM.

A case report of a domesticated ferret ( Mustela furo) envenomated by a presumptive rattlesnake ( Crotalus sp.) treated successfully and safely with the novel Fab (2') North American Snake Antivenom (Veteria Labs). The ferret presented with clinical signs of depressed mentation and facial edema following a rattlesnake ( Crotalus sp.) bite. It developed hypotension, thrombocytopenia, and ecchymosis following the envenomation. It was treated with Fab (2') antivenom and given supportive care including crystalloid fluids and analgesia to resolution of clinical signs. This is the first documented case of rattlesnake envenomation in this species. This case supports the efficacy and short-term safety of this Fab (2') antivenom in this species without the use of antihistamines or glucocorticoids. This report also addresses the current standards of care with thorough review of the literature involving rattlesnake envenomation in zoological species.

Clinically Significant Envenomation From Postmortem Copperhead (Agkistrodon contortrix).

Over 14,000 copperhead (Agkistrodon contortrix) bites were reported to United States poison centers between 1983 and 2008, and 1809 cases were reported to poison centers in 2014. The copperhead is primarily found in the southeastern United States and belongs to the pit viper subfamily Crotalinae, which also includes the water moccasin (Agkistrodon piscivorus) and rattlesnakes (Crotalus and Sistrurus genera). Postmortem rattlesnakes have been reported to cause clinically significant envenomation; we report a case of a postmortem copperhead causing clinically significant envenomation after inadvertent puncture with the deceased copperhead fang. The copperhead was transected twice, leaving the snake in 3 separate pieces. While handling the snake head, an inadvertent puncture occurred on the right index finger followed by pain and swelling in the affected extremity necessitating antivenom administration. Care should be taken when handling deceased pit vipers due to the continued risk of envenomation.

Snakebite by the Shore Pit Viper (Trimeresurus purpureomaculatus) Treated With Polyvalent Antivenom.

Although snakebites are uncommon, there are several species of medically important venomous snakes native to Singapore. We present a case of envenoming by the shore pit viper (Trimeresurus purpureomaculatus) that showed clinical improvement when treated with the Indian (Haffkine) polyvalent antivenom. A 40-year-old man was bitten on his right hand by a snake, which was identified through photos and his description to be a shore pit viper, which is native to the local mangrove area. Severe swelling and pain developed immediately after the bite, which progressed up the arm. Because of the progression of local swelling, antivenom was started. He was given a total of 6 vials (60 mL) of polyvalent antivenom, with the first vial started 3 hours after the bite. He showed clinical improvement within 24 hours. His subsequent recovery was uneventful, with no other complications as a result of envenomation or antivenom use. Severe envenoming by the shore pit viper can lead to marked local effects such as extensive swelling and tissue necrosis. Antivenom is indicated in the presence of severe local envenomation. Antivenom against the shore pit viper is however not available locally. The Indian (Haffkine) polyvalent antivenom contains antibodies against 4 common venomous snakes in India, namely the Indian cobra, common krait, Russell's viper, and sawscaled viper. The improvement seen in this patient suggests possible cross-neutralizing activity of the Indian vipers' antivenom against the local shore pit viper venom. Further in vivo and in vitro studies should be performed to verify this clinical case.

Estimating the Burden of Snakebite on Public Hospitals in KwaZulu Natal, South Africa.

OBJECTIVE: We propose a formula as a means to estimate the number and incidence of snakebites treated per annum in KwaZulu Natal (KZN), South Africa. METHODS: Using an unvalidated formula that includes an antivenom ratio, we crudely estimated the total number of snakebite presentations in KZN. Using antivenom supply data from the central pharmacy, we stratified a sample of 6 hospitals that were surveyed to establish an antivenom ratio, that is, the total number of patients receiving antivenom to the total number of snakebite presentations at hospitals. The antivenom ratio and the average number of antivenom vials for treated snakebites were incorporated into a formula to crudely estimate the number of snakebite presentations. This was then applied to all public hospitals and districts in the region. RESULTS: Seventy-eight percent of public hospitals were included. The mean antivenom ratio derived from the sample hospitals indicated that 12% (95% CI, 10-14%) of snakebite presentations received antivenom. We estimated an annual total of 1680 (95% CI, 1193-2357) snakebite presentations to hospitals. Two thirds of cases (1109 of 1680) were in the low-lying subtropical coastal region. Few cases were in the higher, cooler regions of KZN (87 of 1680) or the metropolitan city of Durban (93 of 1680). The overall incidence for KZN was 16/100,000. The estimated cost of snakebite in KZN was between $1,156,930 and $2,827,848. CONCLUSIONS: We propose an alternative method to estimate the annual number of snakebite presentations to hospitals.

Management of a Pediatric Snake Envenomation After Presentation With a Tight Tourniquet.

We describe an illustrative case of pediatric snake envenomation presenting with a tightly wound tourniquet. A 10-year-old boy presented after a snake bite to the right calf. A tourniquet was in place just below the right knee. The species of snake was unknown. The patient was hemodynamically stable, but the entirety of the right leg distal to the tourniquet was discolored. Over concern for a potential venom bolus effect upon tourniquet removal, the decision was made to start a crotaline Fab antivenom infusion and gradually loosen the tourniquet. The patient tolerated the infusion and removal of the tourniquet without signs of anaphylaxis or decompensation. Dynamic improvements were observed in the right leg and wound site that appeared to be the result of vascular congestion. Tourniquets are generally not recommended for snakebites; however, if a tourniquet is already placed, we avoid removal until prepared to manage acute toxicity or immediate hypersensitivity.

Marked Hypofibrinogenemia and Gastrointestinal Bleeding After Copperhead (Agkistrodon contortrix) Envenomation.

Compared with other crotaline envenomations, copperhead envenomations have historically been reported as having less severe hematologic venom effects and rarely hemorrhage. We report a case of clinically significant gastrointestinal bleeding after a copperhead (Agkistrodon contortrix) envenomation. A 52-year-old woman with a history of systemic lupus erythematosus was bitten on her right medial ankle after which hypofibrinogenemia and hematochezia developed. The symptoms resolved after repeated administration of Crotalidae polyvalent immune Fab (ovine) antivenom. She was discharged without further complications 2 days later. Although copperhead envenomations are classically considered less severe than other crotaline envenomations, this case demonstrates the potential of the venom to produce clinically significant hematologic effects.

Neurological Involvement and Hepatocellular Injury Caused by a Snake With Hematotoxin Envenomation.

Venomous snakes with hematotoxin-Russell's viper (Daboia spp), Malayan pit viper (Calloselasma rhodostoma), and green pit viper (Cryptelytrops albolabris and C macrops, previously named Trimeresurus spp) are commonly found in Thailand. Coagulation factor activation, thrombocytopenia, hyperfibrinolysis, and disseminated intravascular coagulation are the main mechanisms of hemorrhaging from these snake bites. The neurological involvement and hepatocellular injury after Russell's viper bites were reported in Sri Lanka, but there is no report from Southeast Asia. This case was a 12-year-old hill tribe boy who had ptosis and exotropia of the left eye, respiratory distress, and prolonged venous clotting time, prothrombin time, and activated partial thromboplastin time; low fibrinogen and platelet count; and transaminitis after being bitten by a darkish-colored snake. He did not respond to antivenom for cobra, Malayan pit viper, or Russell's viper. However, his neurological abnormalities, respiratory failure, and hepatocellular injury improved, and coagulopathy was finally corrected after receiving antivenom for green pit viper. The unidentified snake with hematotoxin was alleged for all manifestations in this patient.

Incidence and characteristics of snakebite envenomations in the New York state between 2000 and 2010.

OBJECTIVE: We sought to evaluate the incidence of reported venomous snakebites in the state of New York between 2000 and 2010. METHODS: Data were collected retrospectively from the National Poison Data System (NPDS) and then reviewed for species identification and clinical outcome while using proxy measures to determine incidence of envenomation. RESULTS: From 2000 to 2010 there were 473 snakebites reported to the 5 Poison Control Centers in the state of New York. Venomous snakes accounted for 14.2% (67 of 473) of these bites. Only 35 bites (7%) required antivenom. The median age of those bitten by a venomous snake was 33. Most victims were male. CONCLUSIONS: Although not rare, venomous snakebites do not occur commonly in New York State, with a mean of just 7 bites per year; fortunately most snakebites reported are from nonvenomous snakes. Yet even nonvenomous bites have the potential to cause moderately severe outcomes. Medical providers in the state should be aware of their management.

Adder bite on eyelid along with retained intraorbital fangs.

PURPOSE: Snake bite to the eye is a rare event. Most cases reported in the literature are due to boa constrictor bites. This is a rare case of snake bite from a common adder (Vipera berus) to the ocular adnexa along with a retained intraorbital tooth. METHOD: A 57-year-old man presented with a history of being bitten by an adder in the left eye upper lid 12 days previously while bending down to pick up a log at his farm. He developed a firm, tender lump in the medial part of his left upper eyelid. RESULT: A CT scan revealed an extraconal curved calcific dense foreign body, about 5 mm in length consistent with adder's tooth in the superomedial part of left orbit. CONCLUSION: There are few reports of adder bites on face, ear and neck. We report a rare case of adder bite on eyelid along with retained intraorbital fangs and its clinical outcome.

Purification, characterization, and chemical modification of neurotoxic peptide from Daboia russelii snake venom of India.

Comprehensive knowledge of venom composition is very important for effective management of snake envenomation and antivenom preparation. Daboia russelii venom from the eastern region of India is the most neurotoxic among the four venom samples investigated. From the eastern D. russelii venom sample, neurotoxic peptide has been purified by combined method of ion exchange gel permeation chromatography and reversed phase high performance liquid chromatography. Molecular weight of Daboia neurotoxin III (DNTx-III) found to be 6,849 Da (as measured on matrix-assisted laser desorption/ionisation-time of flight mass spectrometer), and N-terminal amino acid sequences is I K C F I T P D U T S Q A. Approximate LD50 dosage was 0.24 mg/kg body weight. It produced concentration- and time-dependent inhibition of indirectly stimulated twitches of Rana hexadactyla sciatic nerve gastrocnemius muscle preparations. Chemical modification of DNTx-III tryptophan residue(s) reduced the twitch height inhibition property of toxin, signifying the importance of tryptophan residues for the neurotoxic function. This type of neurotoxic peptide is unique to east Indian regional D. russelii venom.

Visual loss with inner retinal dysfunction, after snake bite: two case reports.

PURPOSE: To report two cases of visual loss following snake bite. METHOD: Retrospective review of medical records including history, examination finding, fundus details and investigation reports (visual field, electroretinogram, visual evoked potential and optical coherence tomogram) at two centers. RESULT: Two cases of snake bite presented to us with reduction of vision at 1 and 3 months after the incident. The subnormal b wave and abnormal pattern electroretinography in one case pointed at inner retinal dysfunction and neurotoxicity as the cause of visual loss in an apparently normal-looking fundus. The electronegative b wave in the other gave us a clue that the optic atrophy was consecutive (secondary to inner retinal dysfunction due to central retinal artery occlusion). CONCLUSION: When presented late, diagnosis of visual loss secondary to snake bite becomes difficult and puzzling due to the absence of classical findings. Electrophysiological tests in such cases give us important clue to reach at a definite diagnosis.

BITES study: A qualitative analysis among emergency medicine physicians on snake envenomation management practices.

INTRODUCTION: Antivenom is currently considered standard treatment across the full spectrum of severity for snake envenomation in the United States. Although safe and effective antivenoms exist, their use in clinical practice is not universal. OBJECTIVE: This study explored physicians' perceptions of antivenom use and experience with snake envenomation treatment in order to identify factors that influence treatment decisions and willingness to administer. METHODS: We conducted a qualitative study including in-depth interviews via online video conferencing with physicians practicing in emergency departments across the United States. Participants were selected based on purposive sampling methods. Data analysis followed inductive strategies, conducted by two researchers. The codebook and findings were discussed within the research team. FINDINGS: Sixteen in-depth interviews with physicians from nine states across the US were conducted. The participants' specialties include emergency medicine (EM), pediatric EM, and toxicology. The experience of treating snakebites ranged from only didactic education to having treated over 100 cases. Emergent themes for this manuscript from the interview data included perceptions of antivenom, willingness to administer antivenom and influencing factors to antivenom usage. Overall, cost-related concerns were a major barrier to antivenom administration, especially in cases where the indications and effectiveness did not clearly outweigh the potential financial burden on the patient in non-life- or limb-threatening cases. The potential to decrease recovery time and long-term functional impairments was not commonly reported by participants as an indication for antivenom. In addition, level of exposure and perceived competence, based on prior education and clinical experience, further impacted the decision to treat. Resources such as Poison Center Call lines were well received and commonly used to guide the treatment plan. The need for better clinical guidelines and updated treatment algorithms with clinical and measurable indicators was stated to help the decision-making process, especially among those with low exposure to snake envenomation patients. CONCLUSIONS: A major barrier to physician use of antivenom is a concern about cost, cost transparency and cost-benefit for the patients. Those concerns, in addition to the varying degrees of awareness of potential long-term benefits, further influence inconsistent clinical treatment practices.

Utilization of thromboelastograms in management of Crotalus adamanteus envenomation.

BACKGROUND: Crotalinae (pit viper) envenomations are frequently encountered in North American emergency departments. Cases can be complicated by ambiguity in initial species identification as well as timing and duration of current antivenin treatment. Recently, thromboelastography (TEG) has emerged as an enhanced real-time monitoring parameter for snake envenomations that may aid in management of venom-induced consumptive coagulopathy. CASE: A 61-year-old snake handler presented with severe coagulopathy and hypofibrinogenemia following envenomation from her pet eastern diamondback rattlesnake (Crotalus adamanteus). Her coagulopathy transiently improved with Crotalidae Polyvalent Immune Fab (Ovine) (FabAV) but would repeatedly rebound following cessation of antivenin over the next 10 days. Serial TEGs were successfully utilized to identify and corroborate fibrinolysis while predicting clot formation prior to routine coagulation studies. DISCUSSION: Traditional coagulation parameters have not always been ideal when treating severe coagulopathy from pit viper envenomations and may not identify active fibrinolysis for several hours. In this case of C. adamanteus envenomation, TEG proved to be useful in demonstrating improvements in clotting function prior to standard laboratory measures, which further guided antivenin therapy.

Trends in snakebite deaths in India from 2000 to 2019 in a nationally representative mortality study.

The World Health Organization call to halve global snakebite deaths by 2030 will require substantial progress in India. We analyzed 2833 snakebite deaths from 611,483 verbal autopsies in the nationally representative Indian Million Death Study from 2001 to 2014, and conducted a systematic literature review from 2000 to 2019 covering 87,590 snakebites. We estimate that India had 1.2 million snakebite deaths (average 58,000/year) from 2000 to 2019. Nearly half occurred at ages 30-69 years and over a quarter in children < 15 years. Most occurred at home in the rural areas. About 70% occurred in eight higher burden states and half during the rainy season and at low altitude. The risk of an Indian dying from snakebite before age 70 is about 1 in 250, but notably higher in some areas. More crudely, we estimate 1.11-1.77 million bites in 2015, of which 70% showed symptoms of envenomation. Prevention and treatment strategies might substantially reduce snakebite mortality in India.