Managing scorpion envenomations: A Gabes emergency department case study of 60 patients.

INTRODUCTION: Scorpion envenomation constitutes a major public health issue in Tunisia, especially in arid regions such as the Gulf of Gabes. It is necessary to understand the epidemiological and clinical characteristics of this condition and the importance of early management. AIM: This study aims to assess the epidemiological and clinical profile of patients admitted to the emergency department of Gabes University Hospital for scorpion envenomation, as well as the timing of management and intra-hospital evolution. METHODS: A retrospective descriptive study of 60 patients admitted for scorpion envenomation to the Acute Assessement unit at the Emergency Department of the Gabes University Hospital from January 2020 to January 2023. RESULTS: The average age was 35 years [1-85 years]. A slight male predominance (51.7%) was noted. Patients with chronic somatic diseases accounted for (25%) of our series. The predominant scorpion species was Androctonus australis (71.7%). The majority of incidents occurred during the nighttime (71.7%). Most patients were of rural origin (58.3%). The most common sting sites were the lower limbs (48.8%) and upper limbs (36.7%). Scorpion envenomation stages at admission were: Stage I (3.3%), Stage II (83.3%), and Stage III (8.33%). The average time to management was 2 hours. Patients classified as Stage II at admission or afterward were seen after an average of 3 hours. Patients initially classified as Stage III were seen after an average of 3 hours and 30 minutes, and those classified as Stage III during the hospitalization were seen after an average of 4 hours. The average time to management for patients transferred from the Emergency Department to the Intensive Care Unit was 4 hours. CONCLUSION: This study highlights the importance of early management of scorpion envenomation.

[Snakebite in Switzerland - a potentially life-threatening event?] / Schlangenbiss im Glarnerland ­ ein potenziell lebensbedrohliches Ereignis?

INTRODUCTION: A 39-year-old healthy patient accidentally stepped barefoot on an adder and was then bitten into the foot. After initially only local complaints, severe systemic symptoms developed within 10-15 minutes with swelling of the lips and soft palate, recurrent vomiting, bradycardia, weakly palpable peripheral pulse, hypotension, dyspnea and intermittent somnolence. The potentially life-threatening consequences of this severe poisoning could be avoided by using adequate emergency measures and immediate intravenous administration of antivenin.

Novel insights into the application of recombinant mutated phospholipases D as antigens for developing new strategies against Loxoscelism.

Loxoscelism is the pathological condition triggered by a brown spider bite. The venom of these spiders is rich in phospholipases D (PLDs), which can induce virtually all local and systemic manifestations. Recombinant mutated PLDs from clinically relevant Loxosceles species in South America have been investigated as potential antigens to develop novel therapeutic strategies for loxoscelism. However, certain gaps need to be addressed before a clinical approach can be implemented. In this study, we examined the potential of these recombinant mutated PLDs as antigens by testing some variations in the immunization scheme. Furthermore, we evaluated the efficacy of the produced antibodies in neutralizing the nephrotoxicity and sphingomyelinase activity of brown spider venoms. Our findings indicate that the number of immunizations has a greater impact on the effectiveness of neutralization compared to the amount of antigen. Specifically, two or three doses were equally effective in reducing dermonecrosis and edema. Additionally, three immunizations proved to be more effective in neutralizing mice lethality than one or two. Moreover, immunizations mitigated the signs of kidney injury, a crucial aspect given that acute renal failure is a serious systemic complication. In vitro inhibition of the sphingomyelinase activity of Loxosceles venoms, a key factor in vivo toxicity, was nearly complete after incubation with antibodies raised against these antigens. These findings underscore the importance of implementing an effective immunization scheme with multiple immunizations, without the need for high antigen doses, and enhances the spectrum of neutralization exhibited by antibodies generated with these antigens. In summary, these results highlight the strong potential of these antigens for the development of new therapeutic strategies against cutaneous and systemic manifestations of loxoscelism.

Frequency, geographical distribution, clinical characteristics, antivenom utilisation and outcomes of King Cobra (Ophiophagus hannah) bites in Malaysia.

Snakebite envenomation remains an important, yet a neglected public health issue in most tropical and subtropical countries. Underdeveloped medical infrastructure, suboptimal medical services, poor documentation and failure to make snake-related injury a mandatory notifiable disease are important contributing factors. The King Cobra (Ophiophagus hannah) is a medically significant species encountered in Malaysia however, there have been few publications from the clinical perspective. The objectives of this study were to determine the frequency of King Cobra related injuries, geographical distribution, clinical presentation, type and frequency of antivenom utilization and the management outcome. This is a cross-sectional study of confirmed King Cobra related injuries consulted to Remote Envenomation Consultation Services (RECS) from 2015 to 2020. Data were extracted from the RECS database and descriptively analyzed. A total of 32 cases of King Cobra bite were identified. Most cases were from Peninsular Malaysia with the most frequent from the state of Pahang (n = 9, 28.1%). Most patients got bitten while attempting to catch or play with the snake (68.8%). Signs and symptoms of envenomation were documented in 24 (75.0%) cases and the most frequent systemic manifestation was ptosis (n = 13, 40.6%). Tracheal intubation and ventilatory support were required in 13 (40.6%) patients. Antivenom was administered to 22 (68.8%) patients with most (25.0%) receiving 10 vials (1 dose). The commonest antivenom used was monospecific King Cobra antivenom (50.0%) from Thai Red Cross. There was one death documented due to complications from necrotizing fasciitis and septicemia. Public awareness of the dangers and proper handling of King Cobras needs to be emphasised. Timely administration of the appropriate antivenom is the definitive treatment and leads to favorable outcomes.

The critical time period for administering antivenom: golden hours and missed opportunities.

INTRODUCTION: Antivenom is widely accepted as an effective treatment for snake envenomation. This is despite very limited evidence supporting clinical effectiveness for major envenomation syndromes, and is mainly based on pre-clinical studies and observational studies without control groups. EFFECTIVENESS OF EARLY ANTIVENOM: Although antivenom exhibits efficacy by binding to snake toxins and preventing toxic injury in animals if pre-mixed with venom, this efficacy does not always translate to clinical effectiveness. There are many irreversible venom mediated effects that antivenom cannot neutralise or reverse, such as pre-synaptic neurotoxicity and myotoxicity. Fortunately, early antivenom appears to prevent some of these. PRACTICALITIES OF ADMINISTERING ANTIVENOM EARLY: With good evidence that early antivenom prevents some envenomation syndromes, the time between bite and antivenom administration must be reduced. This requires improving the initial assessment of snakebite patients, and improving early decision making based on clinical effects. CONCLUSION: Until there are improved, simplified, easy to use, rapid and inexpensive tests, whether available in the laboratory or preferably at the bedside that identify systemic envenomation, the key to early antivenom administration is early assessment and decision making based on systemic symptoms, including nausea, vomiting, headache and abdominal pain.

An indigenously developed tele-ICU model to treat severe cases of envenomation in remote regions in India.

In cases of severe envenomation due to snakebites, patients require antivenom, intensive care management, including respiratory support, haemodynamic monitoring and renal replacement therapy. Early recognition and treatment of complications such as acute kidney injury, rhabdomyolysis and coagulopathy are important to improve outcomes.Tele-ICU models can play a critical role in providing access to critical care expertise and nuanced support to remote healthcare facilities that may not have the necessary resources or expertise to manage complex cases of envenomation. With the help of telemedicine technology, remote intensivists can provide timely guidance on diagnosis and ongoing management, improving the quality of care and outcomes for patients. We discuss two patients in resource-constrained regions of India with severe envenomation who were managed with tele-ICU support.

Comparison of the intrageneric neutralization scope of monospecific, bispecific/monogeneric and polyspecific/monogeneric antisera raised in horses immunized with sub-Saharan African snake venoms.

BACKGROUND: Snakebite envenomation inflicts a high burden of mortality and morbidity in sub-Saharan Africa. Antivenoms are the mainstay in the therapy of envenomation, and there is an urgent need to develop antivenoms of broad neutralizing efficacy for this region. The venoms used as immunogens to manufacture snake antivenoms are normally selected considering their medical importance and availability. Additionally, their ability to induce antibody responses with high neutralizing capability should be considered, an issue that involves the immunization scheme and the animal species being immunized. METHODOLOGY/PRINCIPAL FINDINGS: Using the lethality neutralization assay in mice, we compared the intrageneric neutralization scope of antisera generated by immunization of horses with monospecific, bispecific/monogeneric, and polyspecific/monogeneric immunogens formulated with venoms of Bitis spp., Echis spp., Dendroaspis spp., spitting Naja spp. or non-spitting Naja spp. It was found that the antisera raised by all the immunogens were able to neutralize the homologous venoms and, with a single exception, the heterologous congeneric venoms (considering spitting and non-spitting Naja separately). In general, the polyspecific antisera of Bitis spp, Echis spp, and Dendroaspis spp gave the best neutralization profile against venoms of these genera. For spitting Naja venoms, there were no significant differences in the neutralizing ability between monospecific, bispecific and polyspecific antisera. A similar result was obtained in the case of non-spitting Naja venoms, except that polyspecific antiserum was more effective against the venoms of N. melanoleuca and N. nivea as compared to the monospecific antiserum. CONCLUSIONS/SIGNIFICANCE: The use of polyspecific immunogens is the best alternative to produce monogeneric antivenoms with wide neutralizing coverage against venoms of sub-Saharan African snakes of the Bitis, Echis, Naja (non-spitting) and Dendroaspis genera. On the other hand, a monospecific immunogen composed of venom of Naja nigricollis is suitable to produce a monogeneric antivenom with wide neutralizing coverage against venoms of spitting Naja spp. These findings can be used in the design of antivenoms of wide neutralizing scope for sub-Saharan Africa.

Aquatic Antagonists: Scorpionfish Envenomation.

Scorpionfish are among the most venomous creatures found in American and Caribbean seas. Their envenomation is responsible for considerable morbidity and socioeconomic burden associated with marine animal injuries. Avoiding physical contact with scorpionfish through proper identification prevails as the chief prevention method for stings. This article discusses common features of scorpionfish as well as the clinical presentation and treatment options following exposure to its toxins.

Oxidative stress and changes in hematological and biochemical biomarkers in Crotalus durissus terrificus (South American rattlesnake) venom-induced acute kidney injury in rats / Estrés oxidativo y alteraciones en biomarcadores hematológicos y bioquímicos en lesión renal aguda inducida por el veneno de Crotalus durissus terrificus (cascabel de America del Sur) en ratones

Abstract Acute kidney injury (AKI) is the major cause of mortality following bites by the South American rattlesnake Crotalus durissus terrificus. We investigated the early onset of Crotalus durissus terrificus venom-induced AKI in rats within 2 h of venom injection and its attenuation by antivenom. Several biomarkers were used to monitor AKI in the absence or presence of antivenom. Male Wistar rats were divided into five groups (n=5 each): G1, rats injected with saline (control); G2, rats injected with venom (6 mg kg-1, intraperitoneally) and euthanized after 2 h to evaluate AKI; G3 and G4, rats injected with 0.9% sterile saline or antivenom 2 h after venom, respectively, and monitored until death or up to 24 h post-venom, and G5, rats injected with antivenom alone and monitored for 24 h. Blood, urine and renal tissue samples were collected immediately after death to assess oxidative stress, hematological and biochemical alterations, and renal histological damage. Venom caused AKI within 2 h (G2) that persisted for up to 8.2 ± 1.6 h (G3), as confirmed by increases in blood urea, creatinine, and renal proteinuria; these increases were attenuated by antivenom. There were no changes in blood protein concentrations in G2 and G3, whereas there were increases in blood reduced glutathione, glutathione peroxidase, and plasma TBARS (but not in catalase) that were attenuated to varying extents by antivenom. There were no marked changes in platelets or leukocytes, but an increase in erythrocytes after 8.2 h with venom alone was attenuated by antivenom. Renal glomerular and tubular damage was greatest after 2 h post-venom groups alone was attenuated by antivenom. Renal glomerular and tubular damage was greatest after 2 h post-venom and declined thereafter. Venom caused early-onset AKI, with variable effects on lipid peroxidation and oxidative stress. Antivenom attenuated the AKI, as shown by the decrease in blood urea and the normalization of proteinuria, without protecting against lipid peroxidation.

Resumen La injuria o lesión renal aguda (LRA) es la mayor causa de mortalidad debido a las mordeduras por cascabeles Crotalus durissus terrificus. Se estudió la instalación precoz de LRA, en ratas, inducida por el veneno de Crotalus durissus terrificus después de 2 h de su inoculación y la atenuación por el antiveneno. Se utilizaron diversos biomarcadores para monitorear LRA en ausencia o presencia del antiveneno. Ratas Wistar machos fueron divididos en 5 grupos (n=5 por grupo): G1, ratas inoculadas con solución salina (control); G2, ratas inoculadas con veneno (6 mg kg-1 dosis, vía intraperitoneal), y sacrificadas después de 2 h para evaluar LRA; G3 y G4, ratas inoculadas con 0.9% de solución salina esterilizada o antiveneno luego de 2 h después de inoculado el veneno, respectivamente, y monitoreadas hasta su muerte o hasta 24 h después de inoculado el veneno; y G5, ratas inoculadas con antiveneno solo y monitoreadas durante 24 h. Las muestras de sangre, orina, y tejido renal fueron colectadas inmediatamente después de la muerte de los animales para evaluar estrés oxidativo, alteraciones hematológicas y bioquímicas, y daño histológico renal. El veneno causó LRA dentro de las 2 h (G2) persistiendo durante más de 8,2 ± 1,6 h (G3), estando esto confirmado por el incremento de urea sanguínea, creatinina, y proteinuria renal; estos aumentos disminuyeron con la aplicación del antiveneno. No se observaron alteraciones en las concentraciones de proteínas sanguíneas en G2 y G3, mientras que se encontraron incrementos en glutatión reducido sanguíneo, glutatión peroxidasa y TBARS plasmática (pero no en catalasa), que disminuyeron con la aplicación del antiveneno aunque en diferente grado. No ocurrieron alteraciones marcadas de plaquetas o leucocitos, mientras que el aumento de glóbulos rojos observado luego de 8,2 h de la inoculación con veneno, disminuyó con el antiveneno. El daño renal glomerular y tubular fue más importante luego de 2 h de la inoculación con veneno y posteriormente disminuyó. El veneno causó LRA precoz a las 2 h, con efectos variables sobre la peroxidación lipídica y el estrés oxidativo. El antiveneno redujo el daño renal, conforme lo demostrado por la disminución en la urea sanguínea y por la normalización de la proteinuria, aunque no se observó protección contra la peroxidación lipídica.

Crotalidae Polyvalent Immune Fab and Cost-Effective Management of Hospital Admissions for Snakebites.

BACKGROUND: Venomous snakebites are a common clinical scenario in the Southeastern United States. CroFab® (Crotalidae Polyvalent Immune Fab (Ovine), BTG, Wales, UK) antivenom is indicated in cases involving pit vipers and is known to be expensive. The treatment protocol for snakebites is based on clinically subjective measures triggering the application, or escalation of, antivenom administration. The purpose of this study is to characterize the use of CroFab at our institution and to evaluate the impact of its use regarding cost and overall outcomes. We suspect that it is often used but potentially less often needed. We hypothesized that CroFab use was associated with increased length of stay (LOS) without an observed difference in patient outcomes. MATERIALS AND METHODS: A retrospective chart review of snakebite patients at our level-1 trauma center from 2000 to 2016 was performed. Snakebite location, snake species, number of vials of CroFab administered, hospital LOS, intensive care unit (ICU) LOS, and complications were identified for each patient. Patients were divided into CroFab (C) and no CroFab (NC) groups. RESULTS: One hundred ninety patients with venomous snakebites were included. 53.7% of patients received CroFab. There was no difference in the complication rate of C versus NC groups, (P = .1118). CroFab use was associated with longer hospital LOS (P < .0001) and ICU LOS (P < .0001). DISCUSSION: CroFab use was associated with increased LOS in our patient population. There was no difference in observed outcomes between the C and NC groups. These findings imply that CroFab is potentially over-used in our patient population.

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.

Evaluation of Protection by Caffeic Acid, Chlorogenic Acid, Quercetin and Tannic Acid against the In Vitro Neurotoxicity and In Vivo Lethality of Crotalus durissus terrificus (South American Rattlesnake) Venom.

Systemic envenomation by Crotalus durissus terrificus (South American rattlesnake) can cause coagulopathy, rabdomyolysis, acute kidney injury, and peripheral neuromuscular blockade, the latter resulting in flaccid paralysis. Previous studies have shown that plant products such as tannic acid and theaflavin can protect against the neuromuscular blockade caused by C. d. terrificus venom in vitro. In this work, we used mouse-isolated phrenic nerve-diaphragm preparations to examine the ability of caffeic acid, chlorogenic acid, and quercetin to protect against C. d. terrificus venom-induced neuromuscular blockade in vitro. In addition, the ability of tannic acid to protect against the systemic effects of severe envenomation was assessed in rats. Preincubation of venom with caffeic acid (0.5 mg/mL), chlorogenic acid (1 mg/mL), or quercetin (0.5 mg/mL) failed to protect against venom (10 µg/mL)-induced neuromuscular blockade. In rats, venom (6 mg kg-1, i.p.) caused death in ~8 h, which was prevented by preincubation of venom with tannic acid or the administration of antivenom 2 h post-venom, whereas tannic acid given 2 h post-venom prolonged survival (~18.5 h) but did not prevent death. Tannic acid (in preincubation protocols or given 2 h post-venom) had a variable effect on blood creatinine and urea and blood/urine protein levels and prevented venom-induced leukocytosis. Tannic acid attenuated the histological lesions associated with renal damage in a manner similar to antivenom. The protective effect of tannic acid appeared to be mediated by interaction with venom proteins, as assessed by SDS-PAGE. These findings suggest that tannic acid could be a potentially useful ancillary treatment for envenomation by C. d. terrificus.

Observation of Bothrops atrox Snake Envenoming Blister Formation from Five Patients: Pathophysiological Insights.

In the Brazilian Amazon, Bothrops atrox snakebites are frequent, and patients develop tissue damage with blisters sometimes observed in the proximity of the wound. Antivenoms do not seem to impact blister formation, raising questions regarding the mechanisms underlying blister formation. Here, we launched a clinical and laboratory-based study including five patients who followed and were treated by the standard clinical protocols. Blister fluids were collected for proteomic analyses and molecular assessment of the presence of venom and antivenom. Although this was a small patient sample, there appeared to be a correlation between the time of blister appearance (shorter) and the amount of venom present in the serum (higher). Of particular interest was the biochemical identification of both venom and antivenom in all blister fluids. From the proteomic analysis of the blister fluids, all were observed to be a rich source of damage-associated molecular patterns (DAMPs), immunomodulators, and matrix metalloproteinase-9 (MMP-9), suggesting that the mechanisms by which blisters are formed includes the toxins very early in envenomation and continue even after antivenom treatment, due to the pro-inflammatory molecules generated by the toxins in the first moments after envenomings, indicating the need for local treatments with anti-inflammatory drugs plus toxin inhibitors to prevent the severity of the wounds.

Case Report: Anaphylactoid Shock Associated with Snakebite Envenoming in Portugal.

Although rare in Portugal, snakebite envenoming entails severe morbidity and mortality. We present the case of a 65-year-old woman bitten on her leg in a northern coastal region in Portugal, on a walk during the COVID-19 pandemic lockdown. Despite first looking for help at the nearest pharmacy, she developed anaphylactoid shock and was promptly driven to a tertiary hospital, where antivenom was administered in a timely manner under close monitoring. Prophylactic antibiotics were started and maintained based on elevated inflammatory markers and signs of wound inflammation. She evolved favorably, with rapid weaning of vasopressors and resolution of end-organ dysfunction. This case highlights the importance of prompt recognition and describes crucial steps in envenomation management in a country where snakebite is infrequent, but potentially fatal.

Investigating myotoxicity following Australian red-bellied black snake (Pseudechis porphyriacus) envenomation.

BACKGROUND: Myotoxicity is one of the common clinical manifestations of red-bellied black snake (Pseudechis porphyriacus) envenomation characterised by elevated creatine kinase (CK) concentrations of greater than 1000 U/L. This study aimed to investigate the occurrence of myotoxicity in patients following envenomation. METHODS/PRINCIPAL FINDINGS: Patient characteristics and serial blood samples (timed venom concentrations and CK concentrations, pre- and post- antivenom) from 114 patients (median age 41, 2-90y; 80 male) were extracted from the Australian Snakebite Project database. Patients were categorised into three groups based on peak CK concentrations [no myotoxicity (<1000 U/L), mild (1000-10,000 U/L) and severe (>10,000 U/L)]. The odds of (mild or severe) myotoxicity was lower in patients that received early antivenom (within 6 hours post-bite) compared to those that received late or no antivenom (odd ratio was 0.186; 95% confidence interval, 0.052-0.664). A population pharmacokinetic-pharmacodynamic (PKPD) model was developed to describe the relationship between the time course of venom (a mixture of toxins) and effect (elevated CK). In addition, a kinetic-pharmacodynamic (KPD) model was developed to describe the relationship between time course of a theoretical toxin and effect. Model development and parameter estimation was performed using NONMEM v7.3. No single set of parameter values from either the PKPD or KPD models were found that could accurately describe the time course of different levels of severity of myotoxicity. The predicted theoretical toxin half-life from the KPD model was 11 ± 3.9 hours compared to the half-life of venom of 5.3 ± 0.36 hours. This indicates that the putative causative toxin's concentration-time profile does not parallel that of venom. CONCLUSION: Early antivenom administration reduces the incidence of myotoxicity. The venom concentration profile does not appear to be the driver for myotoxicity following envenomation. Additional factors that affect the sensitivity of the patient to snake venom/toxins must be explored to understand the relationship with myotoxicity.

How beliefs in traditional healers impact on the use of allopathic medicine: In the case of indigenous snakebite in Eswatini.

Snakebite is a major public health problem in Eswatini and serious envenomations can be responsible for considerable morbidity and mortality if not treated correctly. Antivenom should be administered in hospital in case of adverse reactions and any delays due to distance, transport, costs, antivenom availability and cultural beliefs can be critical. Myths and superstition surround snakes, with illness from snakebite considered a supernatural phenomenon best treated by traditional medicine since healers can explore causes through communication with the ancestors. Traditional consultations can cause significant delays and the remedies may cause further complications. Four rural focus group discussions were held in varying geographical regions to establish why people may choose traditional medicine following snakebite. The study revealed four themes, with no apparent gender bias. These were 'beliefs and traditions', 'logistical issues', 'lack of knowledge' and 'parallel systems'. All snakes are feared, regardless of geographical variations in species distribution. Deep-seated cultural beliefs were the most important reason for choosing traditional medicine, the success of which is largely attributed to the 'placebo effect' and positive expectations. Collaboration and integration of the allopathic and traditional systems assisted by the regulation of healers and their methods could improve future treatment success. The plight of victims could be further improved with more education, lower costs and improved allopathic facilities.

Development of a Broad-Spectrum Antiserum against Cobra Venoms Using Recombinant Three-Finger Toxins.

Three-finger toxins (3FTXs) are the most clinically relevant components in cobra (genus Naja) venoms. Administration of the antivenom is the recommended treatment for the snakebite envenomings, while the efficacy to cross-neutralize the different cobra species is typically limited, which is presumably due to intra-specific variation of the 3FTXs composition in cobra venoms. Targeting the clinically relevant venom components has been considered as an important factor for novel antivenom design. Here, we used the recombinant type of long-chain α-neurotoxins (P01391), short-chain α-neurotoxins (P60770), and cardiotoxin A3 (P60301) to generate a new immunogen formulation and investigated the potency of the resulting antiserum against the venom lethality of three medially important cobras in Asia, including the Thai monocled cobra (Naja kaouthia), the Taiwan cobra (Naja atra), and the Thai spitting cobra (Naja Siamensis) snake species. With the fusion of protein disulfide isomerase and the low-temperature settings, the correct disulfide bonds were built on these recombinant 3FTXs (r3FTXs), which were confirmed by the circular dichroism spectra and tandem mass spectrometry. Immunization with r3FTX was able to induce the specific antibody response to the native 3FTXs in cobra venoms. Furthermore, the horse and rabbit antiserum raised by the r3FTX mixture is able to neutralize the venom lethality of the selected three medically important cobras. Thus, the study demonstrated that the r3FTXs are potential immunogens in the development of novel antivenom with broad neutralization activity for the therapeutic treatment of victims involving cobra snakes in countries.

The Snake Study: Survey of National Attitudes and Knowledge in Envenomation.

Despite recent reviews of best practice for the treatment of Australian venomous bites and stings, there is controversy about some aspects of care, particularly the use of antivenom. Our aim was to understand current attitudes and practice in the management of suspected snake envenoming. A single-stage, cross-sectional survey of Australian emergency care physicians who had treated snake envenomation in the previous 36 months was conducted. Hospital pharmacists were also invited to complete a survey about antivenom availability, usage, and wastage in Australian hospitals. The survey was available between 5 March and 16 June 2019. A total of 121 snake envenoming cases were reported, and more than a third (44.6%) of patients were not treated with antivenom. For those treated with antivenom (n = 67), 29 patients (43%) received more than one ampoule. Nearly a quarter of respondents (21%) identified that antivenom availability was, or could be, a barrier to manage snake envenoming, while cost was identified as the least important factor. Adverse reactions following antivenom use were described in 11.9% of cases (n = 8). The majority of patients with suspected envenoming did not receive antivenom. We noted variation in dosage, sources of information, beliefs, and approaches to the care of the envenomed patient.

Influential Factors of Local Tissue Necrosis after Taiwan Cobra Bites: A Secondary Analysis of the Clinical Significance of Venom Detection in Patients of Cobra Snakebites.

Local tissue swelling, inflammation, and wound necrosis are observed in Taiwan cobra bites. Knowledge of the factors influencing local tissue necrosis after cobra bites might improve the cobra bite treatment strategy. Therefore, we aimed to explore the factors influencing local tissue necrosis after cobra bites. This was a retrospective observational cohort study. All patients clinical presentations including serum venom levels for determining the influential factors in this study were obtained from Hung et al.'s previous study. Clinical features, such as bite information, initial swelling, patient presentation time, serum venom levels, and antivenom, use were extracted. The measurement outcome was the development of wound necrosis. The factors influencing wound necrosis were investigated using univariate and logistic regression analyses. The influential factors of local tissue necrosis and their areas under the curve were: initial limb swelling, 0.88; presentation time × serum level, 0.80; initial necrosis, 0.75; patient presentation time, 0.70. Serum venom level alone cannot be used as a predictive factor. The development of tissue necrosis might be associated with the venom factor, time factor, and their interaction. These influential factors can be used in future studies to evaluate antivenom efficacy.

Awareness of the Standard of Care for Snakebite Management Among Physicians in Kerala: A Cross-sectional Study.

Snakebite remains a largely neglected yet important cause of morbidity as well as mortality in Kerala. This study aimed to assess the knowledge about the standard of care for snakebite management among physicians in Kerala. This was a cross-sectional study using a questionnaire-based survey among 110 physicians from Kerala. The overall knowledge levels were assessed using a questionnaire with answers being scored as 0 for wrong answers and as 1 for correct answers. The total knowledge scores for all respondents were calculated, with a maximum possible score of 14 and a minimum possible score of 0. Comparisons were made between subsets of respondents. The questionnaire was administered to 110 physicians who fulfilled the predetermined criteria. The overall mean knowledge score during the study was 10.7 (standard deviation ± 2.9). However, there were certain pitfalls associated with the management of snakebite. In particular, questions about tourniquet use, bringing a dead snake to the physician, and the anti-snake venom test dose had high proportions of incorrect answers. Significantly higher knowledge levels were also observed in certain subgroups. There seems to be varying knowledge gaps associated with various aspects of snakebite management for certain subsets of respondents who are likely to benefit from specific training.