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Cardiac complications following snakebites are uncommon but fatal. Here, we discuss a case of a snakebite that led to acute myocardial infarction (AMI). Forty-five-year-old male presented to the emergency room with snakebite on the right middle finger. He was given symptomatic treatment and admitted for observation. His vital signs and initial investigations were normal except for the white blood count that was high. During observation, he developed vomiting and bradycardia. He was diagnosed with a right bundle branch block on ECG. The patient developed chest pain after a few hours and was diagnosed with AMI on ECG. The toxicology team started antivenom therapy. His troponin kept rising initially but later started coming down without percutaneous intervention (PCI). He was treated successfully with antivenom therapy and discharged.

Snakebite envenoming has killed about 138000 people and maimed 400,000 victims annually. WHO has designated this medical problem as one of the most neglected tropical diseases for which effective, affordable antivenoms (AVs) are urgently needed. Production of potent AV against neurotoxic venoms was difficult and was thought to be due to the low immunogenicity of the postsynaptic neurotoxins (PSNT) which cause death in the victims. However, it was showed that the use of ineffective adjuvant in the immunization of horse was the root cause. The highly effective Freund adjuvant (FA) causes severe local reactions and could not be used. A novel immunization protocol termed ‘low dose low volume multi-site’ was tested and shown to obliterate the local side effect and allow for the safe use of FA in horse. The immunization protocol led to the production of 7 highly potent monovalent AVs, and 2 potent polyvalent AVs, one against 4 neurotoxic venoms and another against 3 hematotoxic venoms. These AVs allow the treatment of snakebite victims without the need to identify the culprit snakes. Furthermore, we have tested a novel immunization strategy using ‘Diverse toxin repertoire’ of 12 Asian elapid toxin fractions. The resulting antiserum effectively neutralized at least 36 elapid venoms of 28 species encompassing 10 genera and from 20 countries on 4 continents, and most likely all the elapid neurotoxic snake venoms. These results indicate that effective universal antivenom against all elapid neurotoxic venoms of the world can be produced and save numerous lives.

Snakebite is a life-threatening medical emergency, and globally responsible for millions of deaths. In snakebites accidents only deaths are not a concern, it leads to more morbidities. Due to scanty healthcare facilities in rural areas of India, many people seek alternative treatment available in ethnic practices. Tamarindus Indica (TI) plant is rich in medicinal value and used to treat many diseases including snakebite treatment traditionally. In view of this TI seed coat extract (TISCE) was evaluated for antivenom activity. The phytochemical screening of TISCE was performed to understand its chemical composition. TISCE was evaluated for antivenom activity against Indian cobra venom (ICV), common krait venom (CKV), Russells viper venom (RVV), and saw-scaled viper venom (SCV) for phospholipase A2 (PLA-2), haemorrhagic in vitro and in vivo, procoagulant, proteolytic activity, and lethality studies. TISCE majorly contains saponins, glycosides, alkaloids, and phenolic compounds. Minimum indirect haemorrhagic dose (MIHD) observed for ICV (12.5 µg), CKV (5.0 µg),RVV (10.0 µg), and SVV (12.5 µg). TISCE inhibits the procoagulant activity of all venoms at a concentration of 18.0 µg. It also shows the neutralization of proteolytic enzymes of venom in a dose-dependent manner. A pre-incubated mixture containing five lethal dose 50 (LD50) of venom and TISCE was injected intravenously, all mice survived as venom neutralized by TISCE. The present study demonstrates the ability of TISCE to neutralize snake venom using suitable in vivo and in vitro methods. Further studies required to unravelling the specific active chemical constituent of TISCE that may used as novel alternative snakebite treatment. TISCE was able to prolong the deaths during the simulation study and may be used in the topical pharmaceutical formulation that will reduce local venom reactions causing much morbidity, which will collectively with Anti-snake venom (ASV), used to treat envenomed patients more effectively.

Ми наводимо клінічний випадок укусу змії в дівчинки 8 років, яка була госпіталізована в реанімаційне відділення Тернопільської обласної дитячої клінічної лікарні. Особливістю наведеного клінічного випадку є домінування больового синдрому та виражений лімфостаз у місці укусу, відсутність системного ураження. Необхідно підвищити настороженість населення щодо можливих укусів змій. Особливо небезпечними є укуси для дітей у зв’язку з тим, що вони багато часу проводять босоніж на відкритому повітрі.

Snakebite envenomation (SBE) is a neglected One Health issue that overwhelmingly affects people living in rural and impoverished regions of Africa and Asia. Information on SBE is scarce in Rwanda; thus, our objectives were to 1) describe the demographics of SBE patients seeking hospital care, 2) evaluate physician adherence to national treatment guidelines, and 3) assess availability of snake antivenom at hospitals in Rwanda. To achieve these goals, we obtained national data on animal bites/stings and visited every district and provincial hospital in Rwanda to obtain physical records of SBE patients treated in 2017 and 2018. Hospital pharmacies were assessed for antivenom availability. We identified snakes as the second leading cause of animal bites, after dogs, among patients who sought hospital care in 2017 and 2018. Of 363 SBE patients, the highest number of cases occurred among children (< 18 years; 32%) and young adults (18–30 years; 33%), females (61%), farmers (82%), and those living in Eastern Province (37%). Overall, physician adherence to treatment guidelines was 63%. Prescriptions of vitamin K and antivenom were low (4% and 13%, respectively), and only 8% of hospital pharmacies had antivenom in stock throughout the study period. The antivenom stocked was an Indian generic suited for Asian snakes. This minimum estimate of hospitalization cases does not include individuals who died in communities or sought care outside the formal sector. Our study highlights the need to map incidence, risk factors, and patient experiences to mitigate human–snake conflicts and improve patient outcomes.

Amaç: Bu çalışmada; acil servise yılan ısırması ile başvuran hastalarda kullanılan iki tip polivalan yılan antivenomun etkinliğinin karşılaştırılması ve olası lokal ve sistemik yan etkilerin belirlenmesi amaçlanmıştır.Gereç ve Yöntem: Bu retrospektif çalışmaya yılan ısırması şikayeti olan 30 hasta dahil edildi. Hastalar aldıkları antivenom tipine (PoliseraTM veya PolivalanTM) göre gruplandırıldı. Hastaların demografik özelliklerinin yanı sıra, vital bulguları, lokal doku bulguları ve laboratuvar parametreleri standart veri formuna kaydedildi. Her grupta kaç vial yılan anti serumu kullanıldığı, kaç kez ek doz venom ihtiyacı olduğu; antivenoma karşı herhangi bir reaksiyon gelişip gelişmediği kaydedildi.Bulgular: Çalışmaya 30 hasta dahil edildi. 16 hastaya Polisera TM (Grup 1) yılan antivenomu, 14 hastaya PolivalanTM (Grup 2) yılan antivenomu verildi. Grup 1'deki hastalara ortalama 9.1±7.3 vial antivenom verilirken, Grup 2'deki hastalara ortalama 11.6±12.7 vial verildi. PolivalanTM antivenom alan grupta daha fazla alerjik reaksiyon-ürtiker, ateş ve selülitgözlendi.Sonuç: Pirojen kontaminasyonu, üretimden kaynaklanan farklı metodolojiler ve ambalaj farklılıkları aynı doz ve içeriğe sahip antivenom ürünlerinde bile farklı etkilere ve yan etkilere neden olabilir., Purpose: In this study; we aimed to compare the effectiveness of the two types of polyvalent snake antivenom and to determine the possible local and systemic reactions in patients who admitted to the emergency department with snake bite.Materials and Methods: We performed this retrospective study on 30 patients who complained of snakebite. We grouped the patients according to the antivenom type (PoliseraTM or Polivalan TM) which they received. Demographic characteristics of the patients, vital signs, local tissue findings, and laboratory parameters were recorded in the standard data form. The following data were also recorded; the number of vials of snake antivenom used in each group, additional doses of venom were administered, and whether any local or systemic reaction to antivenom has developed or not.Results: Thirty patients were included in the study. 16 patients were administered PoliseraTM (Group 1) snake antivenom and 14 patients were administered Polivalan TM (Group 2) snake antivenom. Patients in Group 1 were given an average of 9.1±7.3 vials, while patients in Group 2 were given an average of 11.6±12.7 vials. More allergic reactions-urticaria, fever, and cellulite were observed in the group receiving PolivalanTM antivenom.Conclusion: Different methodologies arising from the production of antivenom, pyrogen contamination, and differences in packaging can cause different effects and side effects even in products with the same dose and antivenom content.

BACKGROUND This report describes 17 cases of red-bellied black snake envenomation (RBBS; Pseudechis porphyriacus) in dogs in south-eastern Queensland. Patients were prospectively enrolled for the treatment with a new tiger-brown snake antivenom 8000 units, (TBAV; Padula Serums Pty Ltd, VIC, Australia). CASE REPORT Clinical diagnosis of RBBS envenomation was made by either snake venom detection kit, snake identification using scale counting, or owner observed dog-snake interaction in patients with clinical signs of envenomation. An RBBS venom antigen sandwich ELISA was used to retrospectively quantify venom levels in frozen serum and urine. Mechanical ventilation was required in 11% (2/17) patients, whole blood transfusion in 12% (2/17), tissue swelling at the bite site occurred in 53% (9/17) and facial palsy in 12% (2/17). One dog was euthanised, and overall, 94% (16/17) survived to hospital discharge. Clinicopathological changes pre-TBAV included variable haemolysis, increased CK, pigmenturia and mildly prolonged active clotting time with a median of 134 s (n = 13, range 91-206 s). Haematological profiles post envenomation revealed anaemia (6/6) and spherocytosis (5/5), which resolved without the use of corticosteroids. Pre-TBAV, median RBBS venom antigen concentration was 22.6 ng/mL (n = 15, range 2-128) in serum and 58 ng/mL (range 1-452) in urine; RBBS venom antigen was undetectable in serum post-TBAV in all patients. CONCLUSION Some RBBS envenomed dogs required, critical care including mechanical ventilation, blood transfusion, additional antivenom and prolonged hospitalisation. TBAV was effective with excellent prognosis despite stated specificity for tiger and brown snake.

In 2017, the second national reference standard (NRS) for Gloydius snake venom was established to replace the first NRS for Gloydius snake venom. In connection with the second venom NRS, a candidate for the first NRS for Gloydius snake antivenom was produced in 2017. In this study, the qualification of the candidate was estimated and the potency was determined by a collaborative study. The potency (anti-lethal titer and anti-hemorrhagic titer) of the candidate was determined by measuring the capability of the antivenom to neutralize the lethal and hemorrhagic effects of the second NRS for Gloydius snake venom, which was calibrated against the regional reference standard for Gloydius snake antivenom established in 2006. Two Korean facilities contributed data from 20 independent assays. Subsequently, one foreign national control research laboratories participated in this collaborative study. The general common potency of the anti-lethal and anti-hemorrhagic titers was obtained from the results of a total of 25 tests performed at three facilities. According to the results of the present study, the candidate preparation showed good quality and is judged to be suitable to serve as the first NRS for Gloydius snake antivenom with the following potency: an anti-lethal titer of 3100 unit (U) (95% confidence interval 2991–3276 U) and anti-hemorrhagic titer of 3000 U (95% confidence interval 2849–3159 U). In conclusion, the first NRS for Gloydius snake antivenom was established in this study. This reference standard will be used routinely for quality control of a snake antivenom product by manufacturer in Korea, which also can be used for national quality control, including a national lot-release test of the snake antivenom product.

Ersan, Eylem (Balikesir Author), GİRİŞ ve AMAÇ: Bu çalışmanın amacı, acil servis hekimlerinin yılan ısırıklarına karşı yaklaşımını değerlendirmektir. YÖNTEM ve GEREÇLER: Bu çalışma acil serviste çalışan hekimlerin demografik özellikleri, çalışma yerleri ve sürelerini, yılan ısırıkları ile karşılaşıp karşılaşmadıklarını, antivenom kullanıp kullanmadıkları, antivenom kullanma şekillerini, tedavi yaklaşımı ve deneyimlerini araştıran bir anketten oluşmaktadır. BULGULAR: Çalışmaya 611 hekim katıldı. Hekimlerin 71.4%’ü (n=436) daha önce yılan ısırığı hastasına müdahale ederken, bu oran 42.0 % (n=183) ile en fazla acil tıp uzmanlarında (ATU) idi (p, INTRODUCTION: The aim of this study is to investigate the attitudes of emergency physicians towards snakebites. METHODS: This study includes a questionnaire aiming to examine emergency physicians’ knowledge, skills and experience regarding snakebites as well as demographic characteristics. It also aims to identify the causes of shortcomings in the management of emergency department (ED). RESULTS: A total of 611 physicians participated in the study. 71.4% of physicians (n = 436) experienced snakebite cases before. Emergency medicine specialists (EMS) had the highest rate 42.0% (n = 183) (p

The lethality neutralization assay in mice is the gold standard for the evaluation of the preclinical efficacy and specification fulfillment of snake antivenoms. However, owing to the animal suffering involved, this assay is a candidate to be replaced by in vitro alternatives or, at least, improved by the reduction of the number of animals used per experiment, the introduction of analgesia, and the refinement of the test. Since these tests are usually run for 24 or 48 h, one possibility to refine it is to shorten the endpoint observation time of the assay and so limiting the duration of suffering. To assess the effect of this modification of the standard procedure on the analytical properties of the assay, we compared the median lethal dose (LD50) and median effective dose (ED50) values, estimated through observation times of 6, 24 and 48 h. We used African and Latin American snake venoms and several batches of two polyspecific antivenoms. A significant correlation was found between LD50 and ED50 values estimated at the three observation times. Although some LD50 and ED50 values were significantly different at these time points, results of 6 h were robust enough to be used in the characterization of new antivenoms, the verification of specification compliance, and the parallel comparison of formulations. Our observations support the modification of the standard procedures used for assessing neutralizing ability of antivenoms by carrying out the observations at 6 h instead of 24 or 48 h, with the consequent reduction in the suffering inflicted upon mice during these assays. However, the shortening of the observation time in the lethality tests must be validated for each venom and antivenom before its introduction in the routine procedures., Graphical abstract Image 1, Highlights • The lethality neutralization assay in mice is the gold standard for the preclinical evaluation of snake antivenoms. • This assay is a candidate to be improved by the 3Rs philosophy (i.e., replacement, reduction and refinement). • The effect of the reduction of the endpoint observation time on the analytical properties of the test was assessed. • A significant correlation was found between LD50 and ED50 values estimated at 6 h and 24 or 48 h. • A 6-h observation time limits the duration of the suffering without reducing the analytical quality of the test.

In Uruguay, around 60 cases of snakebite accidents occur every year that need to be treated with specific antivenom. They are caused by two snakes of Bothrops genus: Bothrops alternatus and Bothrops pubescens. Snakebite accidents are mandatory notification events, allowing the acquisition of an accurate registry and a fluent communication with the health care services. The aim of this study is to analyze and report the doses administered to achieve the neutralization of the venom and the adverse reactions caused by snake antivenoms used in Uruguay in 2018, when a change was made in the type of antivenom available. In this year, Uruguay started to use the BIOL® antivenom (lyophilized) and this use coexists with traditional antivenom liquid forms (Vital Brazil and Malbran). The number of patients treated with heterologous BIOL® antivenom were 28 and the ones treated with heterologous solutions Malbran and Vital Brazil antivenoms were 21. The initial dose of BIOL antivenom was 8 vials instead of 4 vials regularly used with the others antivenoms and it achieved the neutralization of most cases (27/28 cases). Early adverse reactions were detected in 4 patients (3 in children) treated with BIOL antivenom and there were no adverse reactions in those treated with Malbran or Vital Brazil antivenoms. Lyophilized antivenom BIOL is being used widely in Uruguay without major complications.

Background: Snakebite is one of the major causes of morbidity and mortality in India, particularly in rural regions. Of the 57 known venomous species of snakes in India, the 4 most dangerous snakes are the cobra, the common krait, the Russell viper, and the saw-scaled viper. Of these, the snakes commonly implicated with neurotoxicity are the cobra and the common krait—both elapidae. Acute neuromuscular weakness with respiratory system involvement is the most lethal neurotoxic effect. Case Report: A 24-year-old female was brought to the emergency department in an unresponsive state with a history of snakebite on the left foot. The patient was intubated, mechanically ventilated, and promptly started on snake antivenom and anticholinesterase agents. The patient improved significantly and was extubated. On day 6, she developed blurred vision and slurred speech. She was diagnosed with bilateral optic neuropathy and treated with repeat snake antivenom and steroids. She improved significantly and was discharged on day 14. Conclusion: When a person is bitten by a venomous snake, antivenom is the mainstay of treatment, but clinicians must also consider possible reactions and complications. Optic neuritis following a snakebite is rare but does occur. The prognosis is generally good if clinical suspicion for such a complication is strong, the snake is identified, and the patient receives timely treatment with steroids.

Objetiva-se com este trabalho revisar estudos quanto aos acidentes ofídicos em Minas Gerais, traçando o perfil epidemiológico neste Estado, além de caracterizar os animais peçonhentos serpentes, tipos e gêneros, sinais e sintomas de sua inoculação, e aspectos clínicos e tratamento desse agravo. Foi realizada uma revisão narrativa da literatura com pesquisa bibliográfica nas bases de dados MedLine e SciELO. Pode-se constatar que as serpentes brasileiras de interesse de saúde pública são as das famílias Viperidae e Elapidae, e os acidentes ofídicos dividem-se em: botrópicos (serpentes gênero Bothrops), crotálicos (serpentes gênero Crotalus), laquéticos (serpentes gênero Lachesis) e elapídicos (serpentes gênero Micrurus). O diagnóstico da vítima de acidente ofídico é baseado nas alterações clínico-laboratoriais e na identificação do tipo de serpente, mas raramente a vítima leva para o hospital o animal que o causou a picada para que os profissionais de saúde possam identificar a espécie e realizar o tratamento mais adequado para cada tipo de veneno. A soroterapia é realizada para manter a normalidade do paciente e prevenir o agravamento dos sintomas. E de acordo com os estudos revisados referentes ao perfil epidemiológico do Estado de Minas Gerais, pode-se constatar que a maioria dos acidentes ocorreu com serpentes do gênero Bothrops, seguidos pela Cotralus, em zonas rurais durante atividade laboral ou lazer, geralmente em indivíduos do sexo masculino com idades entre 20 e 50 anos, em meses quentes e chuvosos, tendo como membros mais atingidos os pés e pernas. A maioria das vítimas procurou por atendimento médico dentro de uma a três horas, recebendo o soro antiofídico, com poucos óbitos e complicações. Tais resultados mostram-se de acordo com outros estudos na literatura médico-científica. The objective of this work is to review studies regarding ophidian accidents in Minas Gerais, tracing the epidemiological profile in this State, besides characterizing the venomous animals snakes, types and genus, signs and symptoms of their inoculation, and clinical aspects and treatment of this disease. A literature review was performed with bibliographic research in the MedLine and SciELO databases. It is possible to observe that the Brazilian snakes of public health interest are those of the families Viperidae and Elapidae, and the ophidian accidents are divided into: snakes genus Bothrops, snakes genus Crotalus, snakes genus Lachesis and snakes genus Micrurus. The diagnosis of the victim of snakebite is based on clinical-laboratory changes and identification of the snake type, but rarely does the victim take the animal that caused the snake to the hospital so that health professionals can identify the species and perform the treatment for each type of venom. Serotherapy is performed to maintain patient normality and prevent worsening of symptoms. According to the revised epidemiological profile of the State of Minas Gerais, most of the accidents occurred with Bothrops snakes, followed by Cotralus, in rural areas during work or leisure, usually in males between the ages of 20 and 50, in hot and rainy months, with the feet and legs most affected. Most of the victims sought medical attention within one to three hours, receiving snake antivenom serum, with few deaths and complications. These results are shown in accordance with other studies in the medical-scientific literature. El objetivo de este trabajo es revisar estudios sobre mordeduras de serpientes en Minas Gerais, trazando el perfil epidemiológico en este estado, además de caracterizar las serpientes venenosas, tipos y géneros, signos y síntomas de su inoculación, y aspectos clínicos y de tratamiento de esta enfermedad. Se realizó una revisión narrativa de la literatura con una búsqueda bibliográfica en las bases de datos MedLine y SciELO. Se puede observar que las serpientes brasileñas de interés para la salud pública son las de las familias Viperidae y Elapidae, y las mordeduras de serpientes se dividen en: bothrops (serpientes bothrops), crotalus (serpientes Crotalus), lachetics (serpientes Lachesis) y elápidos (serpientes género Micrurus). El diagnóstico de las víctimas de mordeduras de serpientes se basa en alteraciones clínico-laboratoriales e identificación del tipo de serpiente, pero rara vez la víctima lleva al animal que le provocó la mordedura al hospital para que los profesionales de la salud identifiquen la especie y realicen el tratamiento más adecuado para la misma. cada tipo de veneno. La seroterapia se realiza para mantener la normalidad del paciente y evitar el empeoramiento de los síntomas. Y de acuerdo con los estudios revisados ​​que se refieren al perfil epidemiológico del Estado de Minas Gerais, se puede ver que la mayoría de los accidentes ocurrieron con serpientes del género Bothrops, seguido de Cotralus, en áreas rurales durante actividades laborales o de ocio, generalmente en individuos de los varones con edades comprendidas entre 20 y 50 años, en meses cálidos y lluviosos, siendo los miembros más afectados los pies y piernas. La mayoría de las víctimas buscaron atención médica dentro de una a tres horas, recibieron antiveneno, con pocas muertes y complicaciones. Tales resultados concuerdan con otros estudios de la literatura médico-científica.

Background When snake breeders are bitten by rare snakes, deciding whether to administer snake antivenom can be challenging. Case Presentation A 50‐year‐old man was bitten on the right finger by Boiruna maculata. The next day, his right upper limb exhibited pronounced local manifestations of envenomation. At the first consultation, a dark purple bleeding spot and a necrotic site were present under the fang marks at the bitten finger and his affected limb showed extensive swelling and redness. Snake antivenom was not administered because it was difficult to identify the snake and obtain the antivenom. We performed the pressure immobilization technique to his limb. The patient’s symptoms peaked in severity on the second day of illness. He was discharged with marked improvement. Conclusions We have experienced a case of snakebite envenomation by Boiruna maculata., We have experienced a case of snakebite due to Boiruna maculata, and it has been reported that antitoxin serum treatment was performed on snakes of the same species. Our case illustrates that not all such snakebites necessarily require antivenom.

In the current global emergency due to SARS-CoV-2 outbreak, passive immunotherapy emerges as a promising treatment for COVID-19. Among animal-derived products, equine formulations are still the cornerstone therapy for treating envenomations due to animal bites and stings. Therefore, drawing upon decades of experience in manufacturing snake antivenom, we developed and preclinically evaluated two anti-SARS-CoV-2 polyclonal equine formulations as potential alternative therapy for COVID-19. We immunized two groups of horses with either S1 (anti-S1) or a mixture of S1, N, and SEM mosaic (anti-Mix) viral recombinant proteins. Horses reached a maximum anti-viral antibody level at 7 weeks following priming, and showed no major adverse acute or chronic clinical alterations. Two whole-IgG formulations were prepared via hyperimmune plasma precipitation with caprylic acid and then formulated for parenteral use. Both preparations had similar physicochemical and microbiological quality and showed ELISA immunoreactivity towards S1 protein and the receptor binding domain (RBD). The anti-Mix formulation also presented immunoreactivity against N protein. Due to high anti-S1 and anti-RBD antibody content, final products exhibited high in vitro neutralizing capacity of SARS-CoV-2 infection, 80 times higher than a pool of human convalescent plasma. Pre-clinical quality profiles were similar among both products, but clinical efficacy and safety must be tested in clinical trials. The technological strategy we describe here can be adapted by other producers, particularly in low- and middle-income countries.

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.

Bungarus multicinctus, the Chinese krait, is a highly venomous elapid snake which causes considerable morbidity and mortality in southern China. B. multicinctus venom contains pre-synaptic PLA2 neurotoxins (i.e., &beta, bungarotoxins) and post-synaptic neurotoxins (i.e., &alpha, bungarotoxins). We examined the in vitro neurotoxicity of B. multicinctus venom, and the efficacy of specific monovalent Chinese B. multicinctus antivenom, and Australian polyvalent elapid snake antivenom, against venom-induced neurotoxicity. B. multicinctus venom (1&ndash, 10 &mu, g/mL) abolished indirect twitches in the chick biventer cervicis nerve-muscle preparation as well as attenuating contractile responses to exogenous ACh and CCh, but not KCl. This indicates a post-synaptic neurotoxic action but myotoxicity was not evident. Given that post-synaptic &alpha, neurotoxins have a more rapid onset than pre-synaptic neurotoxins, the activity of the latter in the whole venom will be masked. The prior addition of Chinese B. multicinctus antivenom (12 U/mL) or Australian polyvalent snake antivenom (15 U/mL), markedly attenuated the neurotoxic actions of B. multicinctus venom (3 &mu, g/mL) and prevented the inhibition of contractile responses to ACh and CCh. The addition of B. multicinctus antivenom (60 U/mL), or Australian polyvalent snake antivenom (50 U/mL), at the t90 time point after the addition of B. multicinctus venom (3 &mu, g/mL), did not restore the twitch height over 180 min. The earlier addition of B. multicinctus antivenom (60 U/mL), at the t20 or t50 time points, also failed to prevent the neurotoxic effects of the venom but did delay the time to abolish twitches based on a comparison of t90 values. Repeated washing of the preparation with physiological salt solution, commencing at the t20 time point, failed to reverse the neurotoxic effects of venom or delay the time to abolish twitches. This study showed that B. multicinctus venom displays marked in vitro neurotoxicity in a skeletal muscle preparation which is not reversed by antivenom. This does not appear to be related to antivenom efficacy, but due to the irreversible/pseudo-irreversible nature of the neurotoxins.

Background: Trimeresurus stejnegeri stejnegeri bite induces tissue swelling, pain, thrombocytopenia, rhabdomyolysis, and acute renal failure. However, the incidence of coagulopathy, factors associated with wound necrosis, and the appropriate management of this condition have not been well characterized yet. Materials: This study included patients bitten by T. s. stejnegeri that were admitted to the study hospitals from 2001 to 2016. Patient characteristics, laboratory data, and management approaches were compared in victims with and without wound necrosis. Results: A total of 185 patients were evaluated: three patients (1.6%) were asymptomatic; whereas tissue swelling and pain, local ecchymosis, wound necrosis, coagulopathy, thrombocytopenia, rhabdomyolysis, and renal impairment were present in 182, 53, 13, 15, 10, 1, and 3 patients, respectively. One patient died from coagulopathy and hemorrhagic shock. Antivenom was administered to all envenomed patients at a median time of 1.8 h after the bite. The median total dose of antivenom was five vials. Chi-square analysis showed that bitten fingers, using cold packs during first aid, presence of bullae or blisters, lymphangitis or lymphadenitis, local numbness and suspected infection to be significantly associated with wound necrosis. After adjustment using a multivariate logistic regression model, only cold packs as first aid, bulla or blister formation, and wound infection remained significant. Conclusions: The main effects of T. s. stejnegeri envenomation are tissue swelling, pain, and local ecchymosis. We do not recommend the use of cold packs during first aid to reduce wound pain, as this may be a risk factor for wound necrosis. In addition, patients with bulla or blister formation should be carefully examined for subsequent wound necrosis. Antiplatelet use may worsen systemic bleeding. No severe rhabdomyolysis or renal failure was observed in this large case series, we therefore considered that they were not prominent effects of T. s. stejnegeri bite.

In the field of antivenom research, development, and manufacture, it is often advised to follow the World Health Organization’s (WHO) guidelines for the production, control, and regulation of snake antivenom immunoglobulins, which recommend the use of preincubation assays to assess the efficacy of snakebite therapeutics. In these assays, venom and antivenom are mixed and incubated prior to in vivo administration to rodents, which allows for a standardizable comparison of antivenoms with similar characteristics. However, these assays are not necessarily sufficient for therapeutics with significantly different pharmacological properties than antibody-based antivenoms, such as small molecule inhibitors, nanoparticles, and other modalities. To ensure that the in vivo therapeutic utility of completely novel toxin-neutralizing molecules with no history of use in envenoming therapy and variable pharmacokinetics is properly evaluated, such molecules must also be tested in preclinical rescue assays, where rodents are first challenged with appropriate doses of venoms or toxins, followed by the administration of neutralizing modalities after an appropriate time delay to better mimic the real-life scenarios faced by human snakebite victims. Such an approach takes the venom (or toxin) toxicokinetics, the drug pharmacokinetics, and the drug pharmacodynamics into consideration. If new modalities are only assessed in preincubation assays and not subjected to evaluation in rescue assays, the publication of neutralization data may unintentionally misrepresent the actual therapeutic efficacy and suitability of the modality being tested, and thus potentially misguide strategic decision making in the research and development of novel therapies for snakebite envenoming Villum Foundation/[Project 00025302]//Dinamarca BioPorto Diagnostics A/S/[]//Dinamarca UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP)

Received:03-02-2020 Approved:03-27-2020 While acting as the bishop of Costa Rica (1880-1901), Bernardo Augusto Thiel, a multifaceted German priest, did not restrict himself solely to his demanding ecclesiastic activities, but also became involved in issues related to ethnography, linguistics, anthropology, history and demography. This paper reveals that he was also interested in biological sciences, as is shown in a myriad of notes regarding flora and fauna, in field accounts written during his evangelization journeys through indigenous territories. In addition, he kept a collection of archaeological objects and birds, including Iridophanes pulcherrimus aureinucha, collected in Ecuador and later described as a new subspecies to science. Finally, he promoted actions for developing a botanical snake antivenom, and vehemently expressed concerns about deforestation that was already taking place in Costa Rica. Recibido: 02-03-2020 Aprobado: 27-03-2020 Durante su mandato como obispo de Costa Rica (1880-1901), el polifacético sacerdote alemán Bernardo Augusto Thiel no se limitó a sus exigentes funciones eclesiásticas, sino que incursionó en la etnografía, la lingüística, la antropología, la historia y la demografía. En el presente artículo se documenta una faceta más, referida a las ciencias biológicas. Ello se manifestó en numerosas anotaciones acerca de la flora y la fauna en sus crónicas de viaje, escritas durante sus jornadas de evangelización en territorios indígenas. Además, tuvo una colección de objetos arqueológicos y de aves, entre las que figuró Iridophanes pulcherrimus aureinucha, recolectada en Ecuador y después descrita como una subespecie nueva para la ciencia. Finalmente, impulsó acciones para el desarrollo de un medicamento antiofídico de origen vegetal, y expresó con vehemencia su preocupación por la deforestación que ya se percibía en el país.

Introduction Snakebite envenoming (SBE) is an important occupational and public health hazard especially in sub-Saharan Africa. For optimum management of SBE, adequate knowledge of Snake antivenom (SAV) is very critical among the healthcare practioners in this region. Information related to the knowledge of SAV use in the management of SBE, as well as SAV logistics is scarce among the Health Care Professionals (HCPs) in Nigeria, particularly in the northern region. We therefore aimed to develop, validate and utilize a tool to assess the SAV knowlegde among HCPs in northern Nigeria. We also sought to implement and evaluate an intervention that could improve the SAV knowledge among the HCPs. Methods The proposed study will be conducted in three phases: Phase I will involve the development of the item-pool to be included in the tool, followed by a face, content validity and construct validity. The tool reliability, readability and difficulty index will be determined. Phase II will involve the utilization of the tool to assess baseline SAV knowledge among the HCPs followed by an educational intervention. Multiple Linear Regression analysis will be used to determine the factors associated with SAV knowledge among the HCPs. Lastly, Phase III which will be a repeat of Phase II to assess and evaluate the knowledge after the intervention. Discussion The study design and findings may guide future implementation and streamline the intervention of improving SAV knowledge in HCPs training and practice. Lay Summary Knowledge assessment and educational intervention of snake antivenom among healthcare practitioners in northern Nigeria: a study protocol Snakebite envenoming (SBE) is an important occupational and public health hazard especially in sub-Saharan Africa. For optimum management of SBE, adequate knowledge of snake antivenom (SAV) is very critical among the healthcare practitioners. The baseline knowledge SAV dosage, mode of administration, availability, and logistics is very relevant among healthcare professionals, particularly those that are directly involved in its logistics. It is paramount that SAV is handled and used appropriately. The efforts and advocacy for the availability for more SAV will be in vain if not handled appropriately before they are used. This study protocol aims to develop a tool, to assess SAV knowledge and effects of educational interventions among healthcare professionals (HCPs) in northern Nigeria. This protocol suggests conducting studies in three phases: (a) Development and validation of SAV knowledge assessment tool, (b) Baseline assessment of SAV knowledge assessment tool among HCPs, and (c) Development, implementation and evaluation of an educational intervention to improve SAV knowledge among HCPs in northern Nigeria.

Venomous snakes are a valuable bio-resource for potential therapeutic drug design and development yet are also a major health hazard for society. Snakebite is a globally neglected tropical disease which disproportionately affects the poor and can cause debilitation and death. Snake antivenom is the only recommended treatment for snakebite, yet antivenom efficacy is often untested against many species for which it may be prescribed. In lieu of unethical testing in vivo, venom and antivenom tests in vitro can inform clinicians treating human and pet (domestic and livestock) snakebite victims.Australian venomous snakes (family: Elapidae; subfamily Hydrophiinae) are a specious group of some of the most venomous snakes in the world, whose bites can cause life-threatening coagulopathy (ie. disruption of blood haemostasis). This thesis focuses on Australian elapid venom effects on plasma—primarily human plasma—and the efficacy of currently available antivenoms.Chapter 1 introduces the main concepts and coagulotoxic theme and includes some redundancy with the introductions of individual chapters because all data chapters have either been published as papers or are prepared as such. For this same reason, knowledge gaps are identified within each chapter’s introduction, rather than in Chapter 1. nChapter 2 focuses on the two most coagulotoxic genera within Elapidae: taipans (Oxyuranus) and brown snakes (Pseudonaja). The toxins (FXa:FVa) responsible for the exceptional coagulotoxicity of these venoms are a complex of snake venom Factor Xa, and the cofactor Factor Va. These toxins are homologous to mammalian prothrombinase complex– an enzyme complex which is central to the blood coagulation cascade. The efficacy of a newly developed antivenom was found to be surprisingly specific to the genus of snake in the immunising mixture (Oxyuranus) and largely ineffective against coagulotoxins within similarly related species (Pseudonaja). This likely renders the more affordable, new antivenom an unsuitable solution for snakebite by the eastern brown snake (Pseudonaja textilis) in Papua New Guinea.Chapter 3 broadens the scope of the thesis to include an unprecedented sample size of 47 Australian venoms across 42 species and 19 genera, investigating Australian elapid venom effects on human plasma. This timely research uncovered an additional four genera that contain species with previously unknown potent procoagulant venom. Tiger Snake Antivenom was broadly cross-reactive but varied extensively in relative efficacy across venoms. This chapter also examines the molecular evolution of the prominent coagulotoxin within these venoms—Factor Xa—which revealed a clear, stepwise evolution of increased cleavage region and potency via diversifying selection.nChapter 4 investigates the anticoagulant properties of all currently recognised species of black snakes (Pseudechis) and nine localities of mulga snake (P. australis)– the most widely dispersed and medically significant Pseudechis species. Specifically, this chapter determined the mechanism of anticoagulant action of these venoms, as well as their relative response to Black Snake Antivenom. All venoms demonstrated relatively similar potency and were similarly well-neutralised by antivenom, except for P. colletti, which was well neutralised in subsequent tests by Tiger Snake Antivenom (its prescribed antivenom) and extremely well neutralised by a commercially available phospholipase A2 inhibitor drug, called LY315920 (trade name: Varespladib). Geographical variation was observed for P. australis venoms, with the northern and eastern localities significantly more potent than the western, central, and southern localities. The mechanism of anticoagulant action appears conserved across these localities—and all species within Pseudechis. In contrast to previous speculation, the anticoagulant target in these venoms was determined to be multiple factors within the coagulation cascade, not including FXa, but predominantly inhibition of FVa and its formation with the prothrombinase complex.Chapter 5 extends the anthropomorphic focus of this thesis to prized pets—cats and dogs—investigating the relative susceptibility of these two taxa against a carefully selected group of procoagulant snake venoms which accomplish pathological effects through a range of different molecular mechanisms. An unusual phenomenon uncovered in 1998 inspired this test: while 31% of dogs survive eastern brown snake (P. textilis) bites without antivenom, cats survive more than twice as many bites (66%). As expected, dog plasma was more susceptible to procoagulant snake venoms, with quicker venom-induced clotting times than cats (as well as humans). This physiological susceptibility of dog plasma likely is a major factor contributing to the lower survivability of dogs compared to cats in P. textilis envenomations. Further exacerbating the greater susceptibility of dogs to snakebite is, more than likely, predictable behavioural differences pre– and post-bite, which almost certainly further explain the lower survivability in dogs to snakebite compared to cats.Chapter 6 summarises all results and discusses them regarding clinical implications and antivenom production. The research described in this PhD thesis provides clinicians with greater insight into venom effects of medically significant snakes and lesser known species, as well as antivenom efficacy. This knowledge can inform management treatment plans of envenomed patients in the ongoing struggle to reduce the burden of snakebite on society.nI conclude that Australian elapid venoms have evolved remarkably successful tricks with which to immobilise their prey, and, despite the catastrophic effects they sometimes produce in human snakebite victims, these venoms may help with the development of haemostatic tools and therapeutic drugs to save lives.n

Snake antivenom is the only specific treatment for snakebite envenoming, but life-threatening anaphylaxis is a severe side effect and drawback for the use of these typically mammalian serum products. The present study investigates the hypotheses whether serum IgE antibodies against the epitope galactose-alpha-1,3-galactose (α-gal) located on the heavy chain of non-primate mammalian antibodies are a possible cause for hypersensitivity reactions to snake antivenom. Serum samples from 55 patients with snakebite envenoming were obtained before administration of snake antivenom and tested for serum IgE (sIgE) against α-gal and total IgE. Early anaphylactic reactions (EARs) during the first 3 h after antivenom administration were classified into mild, moderate or severe and correlated with the presence of sIgE against α-gal. Fifteen (27%) out of 55 patients (37 male, 18 female, median 34 years, range 9–90 years) developed EARs after antivenom administration. Eleven, three and one patients had mild, moderate and severe EARs, respectively. Serum IgE against α-gal was detected in 17 patients (31%); in five (33%) out of 15 patients with EARs and in 12 (30%) out of 40 patients without EAR (Odds Ratio = 1.2; 95%-confidence interval: 0.3–4.2) with no correlation to severity. Although the prevalence of serum IgE against α-gal was high in the study population, very high levels of total IgE in the majority of patients question their clinical relevance and rather indicate unspecific sIgE binding instead of allergy. Lack of correlation between α-gal sIgE and EARs together with significantly increased total IgE levels suggest that sIgE against α-gal is not the major trigger for hypersensitivity reactions against snake antivenom., Highlights • Prevalence of serum IgE against α-gal is high in Laotian snakebite victims. • Serum IgE against α-gal is not the major trigger for EARs against snake antivenom. • The rate of EARs against snake antivenom from Thailand is 27%.

Intact or fractionated immunoglobulins are used as snake antivenom to treat snake envenomation. Intravenously administered antivenom binds with snake toxins in the circulation and neutralizes the toxins. Binding of antivenom to venom in the central compartment prevents the distribution of venom to the peripheral tissues and enhances the elimination of venom. Reduction of antivenom concentration in the central compartment is due to both distribution to the peripheral tissues and elimination. Pharmacokinetics of snake antivenom varies among the three different types of immunoglobulins, namely whole IgG, F(ab’)2 and Fab. Pharmacokinetics of F(ab’)2 antivenom is best described by two compartment model with zero order input and linear elimination kinetics. Fab and F(ab’)2 antivenom with smaller molecular masses have a larger volume of distribution than whole IgG antivenom. A biphasic decline of intravenously administered whole IgG and F(ab’)2 antivenom has been observed.

Snakes have fascinated humankind for millennia. Snakebites are a serious medical, social, and economic problem that are experienced worldwide; however, they are most serious in tropical and subtropical countries. The reasons for this are 1) the presence of more species of the most dangerous snakes, 2) the inaccessibility of immediate medical treatment, and 3) poor health care. The goal of this study was to collect information concerning rare, less utilized, and less studied medicinal plants. More than 100 plants were found to have potential to be utilized as anti-snake venom across India. Data accumulated from a variety of literature sources revealed useful plant families, the parts of plants used, and how to utilize them. In India, there are over 520 plant species, belonging to approximately 122 families, which could be useful in the management of snakebites. This study was conducted to encourage researchers to create herbal antidotes, which will counteract snake venom. These may prove to be an inexpensive and easily assessable alternative, which would be of immense importance to society. Plants from families such as Acanthaceae, Arecaceae, Apocynaceae, Caesalpiniaceae, Asteraceae, Cucurbitaceae, Fabaceae, Euphorbiaceae, Lamiaceae, Rubiaceae, and Zingiberaceae are the most useful. In India, experts of folklore are using herbs either single or in combination with others. Keywords: Appraise traditional medicinal plants, Ethnomedicine, India, Snake antivenom