Snake Antivenom Research Articles

Awareness of Indian medical practitioners about snakebite and its management – Is there a need to re-evaluate medical training?

Background: Snakebite envenomation is an important cause of morbidity and mortality worldwide, with India contributing to the majority of cases. Effective management is important to mitigate the impact of the condition. Medical practitioners dealing with snakebite victims need to be thoroughly aware of the current guidelines to provide effective care.Objectives: The aim of this study is to determine the knowledge and awareness of Indian medical practitioners about the current guidelines regarding the management of snakebite and their opinion about the cogency of their undergraduate medical training regarding the subject.Materials and Methods: Allopathic practitioners currently practicing in India were administered a pretested questionnaire to assess their knowledge about epidemiology, diagnosis, and the treatment of snakebite.Results: Of the 143 practitioners in the study, 79.4% underestimated the burden of morbidity due to snakebite in India. About 6.8% had correct knowledge about the number of species of the highest medical importance. About 52.2%, 91.7%, and 20.2% were aware of the common presentation of Common Krait, other neurotoxic elapids (e.g., Indian Cobra) and Viper envenomation, respectively. About 32.6% had correct knowledge about the management of adverse reactions to anti-snake venom. About 72.3% responded that their undergraduate medical education was inadequate to deal with snakebite and 91.4% responded that the topic of snakebite needs more emphasis at the undergraduate level.Conclusions:The current undergraduate medical education in India, about the management of snakebite is limited to outdated concepts or those gained from Western literature, leading to gaps in knowledge in several key areas. A clinically oriented approach suited to the Indian scenario needs to be emphasized.

Neutralizing potential of Rauvolfia serpentina root extract against Naja naja venom

Snake bites are a serious health hazard occurs throughout the world especially in tropical countries like India. Anti-Snake Venom Serum is the only remedy available to treat snake bite victims successfully till date. Infusion of ASV may lead to adverse reactions ranging from severe itching of the skin, hives to potentially serious allergic reactions. Considering all above difficulties research workers all over the world is constantly in search of a cheap and readily available easy formulate remedy for treating snake bite victims. In present study aqueous extract of Rauvolfia serpentina root was checked for the antidote properties against Naja naja venom by in vitro and in vivo methods. Various in vitro neutralization tests like Acetyl cholinesterase, Protease and ATPase activity of Naja naja venom were carried out and the root extract was neutralized all the toxic effects induced by the venom. The in vivo assessment of venom lethality (LD50) of Naja naja venom was found to be 0.301 µg. The aqueous root extract was effectively neutralized the venom lethality and effective dose (ED50) was found to be 12.88 mg/ 3LD50 of Naja naja venom. LC-MS analysis from root extract of Rauvolfia serpentina was done for confirmation of the bioactive compounds.

Role of Adrenaline Premedication in Reducing Anti-Snake Venom Induced Adverse Reactions in Children

Role of Adrenaline Premedication in Reducing Anti-Snake Venom Induced Adverse Reactions in Children

Recombinant antibodies against Iranian cobra venom as a new emerging therapy by phage display technology.

Background:The production of antivenom from immunized animals is an established treatment for snakebites; however, antibody phage display technology may have the capacity to delivery results more quickly and with a better match to local need. Naja oxiana, the Iranian cobra, is a medically important species, responsible for a significant number of deaths annually. This study was designed as proof of principle to determine whether recombinant antibodies with the capacity to neutralize cobra venom could be isolated by phage display.Methods:Toxic fractions from cobra venom were prepared by chromatography and used as targets in phage display to isolate recombinant antibodies from a human scFv library. Candidate antibodies were expressed in E. coli HB2151 and purified by IMAC chromatography. The selected clones were analyzed in in vivo and in vitro experiments. Results:Venom toxicity was contained in two fractions. Around a hundred phage clones were isolated against each fraction, those showing the best promise were G12F3 and G1F4. While all chosen clones showed low but detectable neutralizing effect against Naja oxiana venom, clone G12F3 could inhibit PLA2 activity. Conclusion:Therefore, phage display is believed to have a good potential as an approach to the development of snake antivenom.

Ofidismo en el Paraguay: distribución geográfica, alteraciones fisiopatólogicas y necesidad de la preparación de un veneno de referencia nacional

El accidente ofídico en el Paraguay es un evento frecuente que reviste gravedad si la serpiente asociada pertenece a las familias Viperidae y Elapidae, particularmente en los departamentos fronterizos con el Brasil, en donde afecta principalmente a hombres en actividades agrícolas entre los 20 y 40 años de edad. El oriente del Paraguay, junto con el sudeste del Brasil, ha sido identificado como una de las áreas de mayor incidencia de ofidismo en todo el Neotrópico. Se presenta una revisión de la problemática desde el punto de vista epidemiológico y fisiopatológico, conjuntamente con la distribución de las especies de potencial importancia médica de los géneros Bothrops y Micrurus. Se plantea la necesidad de elaborar un veneno de referencia nacional que represente las especies asociadas a los envenenamientos severos y que permita la evaluación de la capacidad neutralizante de antídotos foráneos, así como la eventual preparación de un antiveneno nacional.

Can the methanolic extract of Andrographis paniculata be used as a supplement to anti-snake venom to normalize hemostatic parameters: A thromboelastographic study

Ethnopharmacological relevance of Andrographis paniculataThe whole plant (including leaves and roots) is used in traditional Ayurveda and Siddha medicine to treat various clinical conditions such as fever, respiratory tract infections, colic pain, liver disorders, diabetes, hypertension, and inflammation. It is also used as an antidote for snake-bite, poisonous bites of insects and recommended as a dietary supplement to boost immunity. Aim of the studyIn-vitro thromboelastographic evaluation of the efficacy of methanolic extract of Andrographis paniculata (MAP) and polyvalent anti-snake venom (ASV) in neutralizing the Naja naja (N.N) venom-induced changes in hemostatic parameters. Materials and methodsThromboelastographic evaluation of hemostatic parameters was initiated by adding 3μg N.N venom to citrated whole blood from healthy volunteers. The effect of different concentrations of ASV and MAP in neutralizing the toxicity of N.N venom were studied in two groups. In group 1 experiments, citrated whole blood (340μl) was mixed with N.N venom (3μg), immediately followed by successive addition of ASV (5μl, 8μl and 15μl) or MAP (15μg, 30μg, 60μg and 120 μg) or combination of ASV and MAP (3μl ASV+30μg MAP and 3μl ASV+60μg MAP). In group 2 experiments, N.N venom was incubated with whole blood for 90 minutes at 37°C, followed by successive addition of ASV (5μl, 10μl, and 15μl) or MAP (30μg and 60μg) or combination of ASV and MAP (5μl ASV+30μg MAP and 5μl ASV+60μg MAP). ResultIn Group 1 experiments, N.N venom caused significant (p<0.05) increase in R-time, K-time, LY30% and a decrease in angle and MA. Optimum effect on hemostatic parameters was observed at a concentration of 8μl ASV, where all the deleterious effects of the venom were completely reversed. Similarly, the addition of MAP to the assay system could reproduce results as ASV, in reversing the deleterious effects of the venom. This occurred in a concentration-dependent manner, from 15μg-60μg, with the optimum results at 60μg. When ASV concentration was reduced to 3μl and supplemented with MAP (30μg or 60μg), the positive supplementary effect of MAP was demonstrated.In Group 2 experiments, N.N venom caused significant (p<0.05) changes in all TEG parameters, with most deleterious changes observed in MA and LY30% compared to Group 1 experiments. ASV when added in increasing concentrations (5-15μl), had beneficial effects only on K-time, angle, and MA. When added together with ASV, MAP (30μg or 60μg) could significantly (p<0.05) supplement the effect of ASV (5μl) in improving R-time, K-time, and angle. ConclusionThis in-vitro study demonstrates the effectiveness of MAP as a supplement to ASV in combating the deleterious effects of N.N venom on hemostasis. However, further in-vivo experiments in animal models are required to substantiate these effects.

Improvement of Naja haje snake antivenom production using gamma radiation and a biotechnological technique

This study aimed to improve antivenom production using gamma radiation and calcium phosphate nanoparticles (CPN) as adjuvant. Toxicological and immunological properties of the Naja haje venom before and after exposure to radiation were estimated. The immune response of immunized rabbits was evaluated. Toxicity of irradiated venom was reduced six times as compared to native venom. Moreover, no change in antigenic reactivity between native and irradiated venoms. Serum titer produced with irradiated venom loaded on CPN showed highest titer and neutralization capacity as compared to other sera. Thus, irradiation and nanoparticles adjuvant could be a new approach for snake antivenom production.

Anti-Ophidian Properties of Herbal Medicinal Plants: Could it be a Remedy for Snake Bite Envenomation?

Snake bite envenoming causes high rates of morbidity and mortality and is one of the serious health-related concerns all over the globe. Around 3200 species of snakes have been discovered till date. Amid these species, about 1300 species of snakes are venomous. On account of its severity, World Health Organization (WHO) recently included snakebite envenoming in the list of neglected tropical diseases. Immunotherapy has partially solved the issues related to snakebite envenomation. However, it is associated with numerous adverse effects, due to which alternative treatment strategies are required for the treatment of snakebite. Traditionally, a large repository of herbal medicinal plants is known to possess activity against snake venom. An exploration of the therapeutic benefits of these medicinal plants used for the treatment of snakebites reveals the presence of various potential phytochemicals. The aim of the present review is to provide an outline regarding poisonous snakes all over the world, various compositions of snake venom, adverse effects related to anti-snake venom and numerous medicinal plants used for the anti-ophidian activity.

Risk factors associated with snake antivenom reaction and the role of skin test

Antivenom reactions are a common complication of snake antivenom. This study aimed to identify predicators of antivenom reaction and the involvement of antivenom skin test in antivenom reaction development. This retrospective cohort study was conducted in six medical institutions in Taiwan. Data were extracted from the Chang Gung Research Database (CGRD) from January 2006 to December 2016. The association between antivenom reaction and patient demographics, type and dose of antivenom, and skin test results was analyzed. The study enrolled 799 patients, including 219 who developed antivenom reactions. Compared to patients receiving both freeze-dried hemorrhagic (FH) and freeze-dried neurotoxic (FN) antivenom, those administered a single type had a lower antivenom reaction risk (adjusted odds ratios [aORs]: 0.5 and 0.4, 95% confidence interval [CI]: 0.35–0.74 and 0.24–0.69, FH and FN respectively). Patients administered a higher antivenom dose (≥ 5 vials) had higher antivenom reaction risk (aOR: 1.8, 95% CI: 1.23–2.76). A positive skin test result was also associated with antivenom reaction (aOR: 16.7, 95% CI: 5.42–51.22). The skin test showed high specificity (98.5%, 95% CI: 97.49%–99.83%) but low sensitivity (17.5%, 95% CI: 10.74%–24.18%). The antivenom skin test should be abolished because of the extremely low sensitivity and possible misinterpretation of results because of the limitation of this examination.

Therapeutic Management of Snake Bite in a Rottweiler Dog

M Snakebite cases are more common in horses and dogs when compared to other animals such as cattle, sheep, and goats. Snake envenomation can be difficult to diagnose if the incident was not witnessed. Clinical signs may vary greatly depending on the species of snake involved, and the quantity and toxicity of the venom injected. Dogs are commonly presented with extensive edematous swelling, severe pain, ecchymosis, and discoloration of the skin in the affected area within several hours after the bite (Garg, 2002) The animals exhibit various symptoms like cardio-pulmonary dysfunction, local tissue damage, blood coagulation defects, ataxia etc, depending on type of snake bite (Bhardwaj, 2011). Systemic signs can vary and may include hypotension, shock, cardiac arrhythmias, bleeding disorders, ptyalism, nausea, vomiting, respiratory distress, mental confusion, rhabdomyolysis, and acute renal failure (Ananda et al., 2009). The snake bite with envenomation is a true emergency, and it needs rapid examination and prompt appropriate treatment. The current paper reports on the successful use of antihistamine together with anti-snake venoms, fluids, corticosteroids, and antibiotics with no untoward effects in a snake-bitten dog.

Galactose-α-1,3-galactose (alpha-gal) allergy: first pediatric case in a series of patients in Spain

Introduction and ObjectivesAllergy to galactose-α-1,3-galactose (alpha-gal) is a peculiar form of food allergy generally manifesting as an anaphylactic reaction hours after mammalian meat consumption, due to the presence of specific IgE against this oligosaccharide. In addition, immediate anaphylaxis may develop after exposure to other sources of alpha-gal, such as monoclonal antibody cetuximab, vaccines, plasma expanders or anti-snake venoms. Sensitization to alpha-gal has also been implicated in the rapid degeneration of biological valve implants, and recognized as a cause of occupational disease in cattle raisers. The implication of tick bites in this type of sensitization has been accepted by all the research groups dedicated to this disease. Patients and methodThe present study describes the clinical and sensitization characteristics of 39 patients diagnosed with alpha-gal allergy in the hospitals of our province (Lugo, Monforte de Lemos and Burela, Spain). ResultsMost patients were middle-age males. Of note, is the fact that the series includes the first pediatric patient reported in Spain to date. The predominant clinical manifestations were urticaria or delayed anaphylaxis after consumption of mammalian meat. Seventy-four percent of the patients reported having suffered a previous tick bite, and the clinical presentation of anaphylaxis was significantly more prevalent in those with a persistent local reaction following the bite than in those with no such reaction (p = 0.032). ConclusionsA review is also made of the disorder which, due to its variable clinical expression, is referred to as alpha-gal syndrome. The study concludes that a diagnosis of alpha-gal allergy should be considered in patients with urticaria-anaphylaxis of uncertain origin or manifesting after the administration of vaccines or products of bovine/porcine origin.

Retrospective evaluation of Micrurus fulvius (Eastern coral snake) envenomation and the use of mechanical ventilation in dogs and a cat (2011-2016): 8 cases.

To describe the use of mechanical ventilation (MV) in the management of Eastern coral snake envenomation in 7 dogs and a cat. Retrospective study (2011-2016). University teaching hospital. Seven dogs and 1 cat receiving MV for ventilatory failure secondary to Eastern coral snake envenomation. None. The medical records of 8 animals that received MV following Eastern coral snake envenomation were reviewed. Data collected included signalment, time to veterinary assessment, physical and laboratory characteristics at arrival, clinical course during hospitalization, management including antivenom administration, MV settings, duration of ventilation, length of hospitalization, cost of care, and survival to discharge. The mean ± SD age was 4 ± 3.2 years. Median (range) time to onset of clinical signs was 30 (5-240) minutes. Coral snake antivenom was administered to 7 of the 8 animals following arrival at a median (range) of 30 (5-90) minutes. All animals had progressive hypoventilation and received MV, specifically volume controlled, synchronized intermittent mandatory ventilation with pressure support. The median (range) duration of MV was 58 (25-84) hours and the median (range) duration of hospitalization was 8.2 (6-11) days. Ventilator associated complications occurred in all animals, but overall outcome was excellent with 7 of 8 surviving to discharge. No dog, but the 1 cat, had an adverse reaction to antivenom. Ventilatory failure secondary to Eastern coral snake envenomation necessitating MV carries an excellent prognosis and is better than reported for other causes of lower motor neuron disease. Successful response to ventilation was achieved even with associated complications being common in this cohort of animals.

Australian snake antivenom dosing: What is scientific and safe?

Because the median dose of one vial 'clears the blood of circulating venom', the authors of the Australian Snakebite Project recommend restriction of antivenom to one vial for all envenomated victims. This is neither scientific nor safe. Methodological flaws in the case series include limited detection of venom toxins and misinterpretation of data. The recommendation fails to consider larger doses of venom than that neutralised by one vial of antivenom. Although one vial may be adequate for minor envenomation, the initial dose should be two vials with more on a clinical basis.

Perspective on the Therapeutics of Anti-Snake Venom.

Snakebite envenomation is a life-threatening disease that was recently re-included as a neglected tropical disease (NTD), affecting millions of people in tropical and subtropical areas of the world. Improvement in the therapeutic approaches to envenomation is required to palliate the morbidity and mortality effects of this NTD. The specific therapeutic treatment for this NTD uses snake antivenom immunoglobulins. Unfortunately, access to these vital drugs is limited, principally due to their cost. Different ethnic groups in the affected regions have achieved notable success in treatment for centuries using natural sources, especially plants, to mitigate the effects of snake envenomation. The ethnopharmacological approach is essential to identify the potential metabolites or derivatives needed to treat this important NTD. Here, the authors describe specific therapeutic snakebite envenomation treatments and conduct a review on different strategies to identify the potential agents that can mitigate the effects of the venoms. The study also covers an increased number of literature reports on the ability of natural sources, particularly plants, to treat snakebites, along with their mechanisms, drawbacks and future perspectives.

Use of Snake Antivenom and Clinical Outcomes in Snake Envenomation: A Retrospective Study in a Tertiary Hospital in Penang, Malaysia

Backgrounds: Snake antivenom (SAV) is the definitive treatment for snake envenomation. But SAVs are specific, expensive and limited in supply. SAVs also come with risk of adverse reactions. Hence, this study was conducted to assess the use of SAV, adverse reactions to SAV and its clinical outcomes in snakebite patients. Methods: This was a retrospective study. Medical records of snakebite patients for the period from January 2014 to September 2017 were reviewed and study data was extracted. Clinical outcomes were measured by mortality rate in those receiving SAV. Results: Among 165 subjects, only 9 patients (5%) were treated with SAV after presenting with envenomation symptoms in which five cases with identified snakes were given monovalent SAV namely pit viper (two cases), king cobra, sea snake and cobra with one case each. Meanwhile, three cases of unidentified snake received polyvalent SAV and one case received pit viper SAV. Most of the patients (8/9, 88.9%) received SAV within 24 hours after snakebite. The average time gap to first administration was 7.23 hours. In patients receiving SAV, six out of 9 cases required two to four vials of SAV. All the patients receiving SAV did not encounter any adverse effects except a child who had pyrogenic reaction. All patients survived without significant morbidity at discharge. The total cost of SAV for the 9 patients was US$ 24,082.68. Conclusion: From this study, the incidence of snakebites requiring SAV was low. Low incidences of adverse effects and no mortality were observed in patients receiving SAV.

Clinical implications of convergent procoagulant toxicity and differential antivenom efficacy in Australian elapid snake venoms

Australian elapid snakes are some of the most venomous snakes in the world and are unique among venomous snakes in having mutated forms of the blood clotting factor X in an activated form (FXa) as a key venom component. In human bite victims, an overdose of this activated clotting enzyme results in the systemic consumption of fibrinogen due to the large amounts of endogenous thrombin generated by the conversion of prothrombin to thrombin by venom FXa. Within Australian elapids, such procoagulant venom is currently known from the tiger snake clade (Hoplocephalus, Notechis, Paroplocephalus, and Tropidechis species), brown/taipan (Oxyuranus and Pseudonaja species) clade, and the red-bellied black snake Pseudechis porphyriacus. We used a STA-R Max coagulation analyser and TEG5000 thromboelastographers to test 47 Australian elapid venoms from 19 genera against human plasma in vitro. In addition to activity being confirmed in the two clades above, FXa-driven potent procoagulant activity was found in four additional genera (Cryptophis, Demansia, Hemiaspis, and Suta). Ontogenetic changes in procoagulant function was also identified as a feature of Suta punctata venom. Phylogenetic analysis of FX sequences confirmed that snake venom FXa toxins evolved only once, that the potency of these toxins against human plasma has increased in a stepwise fashion, and that multiple convergent amplifications of procoagulant activity within Australian elapid snakes have occurred. Cofactor dependence tests revealed all procoagulant venoms in our study, except those of the tiger snake clade, to be highly calcium-dependent, whereas phospholipid dependence was less of a feature but still displayed significant variation between venoms. Antivenom testing using CSL Tiger Snake Antivenom showed broad but differential cross-reactivity against procoagulant venoms, with P. porphyriacus and S. punctata extremely well neutralised but with Cryptophis, Demansia, and Hemiaspis less well-neutralised. The relative variation was not in accordance to genetic relatedness of the species used in antivenom production (Notechis scutatus), which underscores a fundamental principle that the rapid evolution characteristic of venoms results in organismal phylogeny being a poor predictor of antivenom efficacy. Our results have direct and immediate implications for the design of clinical management plans in the event of snakebite by such lesser known Australian elapid snake species that have been revealed in this study to be as potent as the better studied, and proven lethal, species.

Inhibition of snake venom induced sterile inflammation and PLA2 activity by Titanium dioxide Nanoparticles in experimental animals

Sterile inflammation (SI) is an essential process in response to snakebite and injury. The venom induced pathophysiological response to sterile inflammation results into many harmful and deleterious effects that ultimately leads to death. The available treatment for snakebite is antiserum which does not provide enough protection against venom-induced pathophysiological changes like haemorrhage, necrosis, nephrotoxicity and often develop hypersensitive reactions. In order to overcome these hindrances, scientists around the globe are searching for an alternative therapy to provide better treatment to the snake envenomation patients. In the present study TiO2 (Titanium dioxide)-NPs (Nanoparticles) has been assessed for antisnake venom activity and its potential to be used as an antidote. In this study, the synthesis of TiO2-NPs arrays has been demonstrated on p-type Silicon Si < 100 > substrate (∼30 ohm-cm) and the surface topography has been detected by Field-emission scanning electron microscopy (FESEM). The TiO2-NPs successfully neutralized the Daboia russelii venom (DRV) and Naja kaouthia venom (NKV)-induced lethal activity. Viper venom induced haemorrhagic, coagulant and anticoagulant activities were effectively neutralized both in in-vitro and in vivo studies. The cobra and viper venoms-induced sterile inflammatory molecules (IL-6, HMGB1, HSP70, HSP90, S100B and vWF) were effectively neutralised by the TiO2-NPs in experimental animals.

On the Potential of Phytochemical Remedy for Envenomation and the Consequent Endocrinopathy, with a Note on Conservation – A Case Study of Venom Informatics

Envenomation is a serious neglected health issue at the global level that affects millions of people every year. It is highly prevalent among farmers and rural natives and is mainly due to the bite from snakes, spiders, frogs, dogs, wasps, bees, ants, etc. Many plants with antidote potential grow around our backyard without proper recognition and, unfortunately, several of them are under threat of extinction due to human interference and other environmental factors. The sustainable utilization of those antidote herbs can benefit as a life saver to the needy patients. The herbs can also be farmed and used commercially for the pharmaceutical application and incorporated with biotechnology and bioinformatics with a vision of synthesizing antidote drugs with less or no side effects. The objective of the present work is to create awareness among the public for the wise use of wild and local herbs, and their sustainable utilization with a computational case study on laboratory experiments done in two traditional plant based antidotes, selected from literature. The investigation is focused on Daboia russelii venom neutralization via in silico approach which can significantly reduce the time, expense, labour and samples taken. Our approach will add to the conventional non-specific polyvalent anti-snake venom (ASV) with more specific plant-based antidotes.

Assessment of anti-snake venom effects of Acalypha fruticosa leaves against Indian Saw-scaled viper by using envenomed Wistar albino rats

Assessment of anti-snake venom effects of Acalypha fruticosa leaves against Indian Saw-scaled viper by using envenomed Wistar albino rats

Demography, clinical profile, morbidity and mortality pattern of snake bite cases in children: a study at tertiary teaching hospital

Background: Snake bite is one of the important health problems in tropical and sub-tropical countries including India. Most snake bites present without envenomation as most bites are usually due to non-poisonous snakes and even poisonous snakes can control amount of venom injected. Even though mortality is under reported, India accounts for most of deaths due to snake bite.Methods: A hospital based descriptive case study was conducted at Pediatric ward of VIMS Ballari. All children with definite history of snake bite with fang marks or features of local/systemic envenomation were included in study. Demographic parameters, symptomatology and complications were noted down as per pro forma and data was analyzed.Results: Most bites occurred in lower limbs in older children while playing outdoors. Most cases were from rural area. Majority presented with local toxicity followed by hemotoxicity and neuroparalysis. Two children died, one because of respiratory paralysis and other by acute kidney injury.Conclusions: Snake bite is a preventable health problem. By wearing protective shoes and avoiding outdoor sleep many snake bites can be avoided. Early, aggressive but judicious use of antisnake venom is a cornerstone of management.