Dissertations / Theses on the topic 'Snakebites'

I used surgically implanted miniature radio-transmitters to conduct a broad behavioural ecology study of the eastern brownsnake, Pseudonaja textilis, a large (to 2 m), slender, fast-moving elapid snake responsible for most snakebite fatalities in Australia. In order to minimise trauma to the snake, I modified anaesthesia (use of nitrous oxide to relax the animal prior to induction of surgical—level anaesthesia with halothane); implantation techniques (reliance on “blunt” dissection rather than cutting of tissues after the initial incision; placement of antenna in the peritoneal cavity rather than subcutaneously; anchoring the transmitter in place to avoid slippage in a position anterior to the incision), and removal (use of a "disposable" silicon casing to eliminate problems associated with tissue adhesion to the antenna). Comparisons of changes in body mass of telemetered versus non— telemetered snakes indicated that the transmitters had no detectable effects on growth rate, even in a drought year when such effects might be most obvious. Encounters between humans and dangerously venomous snakes put both participants at serious risk, so the determinants of such encounters warrant attention. I set out to identify factors influencing the probability that a human walking in agricultural land near the town of Leeton (in the Murrumbidgee Irrigation Area in south-eastem Australia) would come into close proximity to a brownsnake. My study area is typical of many of the agricultural landscapes occupied by B. texiis. Over a three-year period, I walked regular transects to quantify the number and rate of snake encounters, and the proportion of snakes above-ground which could be seen. The rate of encounters depended upon a series of factors, including season, time of day, habitat type, weather conditions (wind and air temperature) and shade of the observer’s clothing (light versus dark).

Os acidentes causados por serpentes peçonhentas são considerados um problema de saúde pública no Brasil, e é muito importante que sejam feitos mais estudos para um melhor conhecimento desse agravo. O objetivo deste trabalho é descrever as características clínicas e epidemiológicas que foram observados no Hospital de Doenças Tropicais de Araguaína, Estado do Tocantins, Brasil, que é uma unidade de saúde que cuida de pacientes que sofrem de doenças tropicais, no período de 2007 a 2009. Foram estudados 556 indivíduos e as características mais comuns observadas foram: sexo masculino, idade entre 19-40 anos, picada em membros inferiores e os ferimentos causados por serpentes do gênero Bothrops. Os sinais e sintomas mais freqüentes foram dor, edema e hemorragia. A manifestação sistêmica mais observada foi alteração da coagulação sanguínea. As complicações mais freqüentes foram abscesso, insuficiência renal aguda, necrose e infecção bacteriana. Os principais microorganismos identificados foram Morganela morganii (17,1%), Pseudomonas aeruginosa (14,6%) e Staphylococcus epidermidis (4,9%). Esta flora bacteriana foi semelhante às descritas no veneno e na boca das serpentes por outros pesquisadores. Com base nos resultados dos testes de suscetibilidade sugere-se a continuidade no uso de ciprofloxacin para o tratamento desses abscessos que não respondem à simples drenagem. O conjunto dos resultados obtidos representa um completo levantamento da atual situação dos acidentes envolvendo serpentes no estado do Tocantins e arredores e certamente contribuirá para o aprimoramento das ações de combate aos problemas de Saúde Pública da região Norte.
Accidents caused by venomous snakes are considered a public health problem in Brazil, and it is very important that more studies be done to a better understanding of this injury. The aim of this paper is to describe the clinical and epidemiological characteristics that were observed in the patients at the Hospital for Tropical Diseases in Araguaina, Tocantins State, Brazil, during the last three years. We have studied 556 individuals and the most common features were: male, aged 19-40 years, stinging in his legs and injuries caused by Bothrops snakes. Signs and symptoms were pain, swelling and bleeding. The most observed systemic manifestation was alteration of blood coagulation. The most frequent complications were abscess, acute renal necrosis and bacterial infection and the main microorganisms identified were Morganela morganii (17.1%), Pseudomonas aeruginosa (14.6%) and Staphylococcus epidermidis (4.9%). The bacterial flora was similar to those described in the mouth of snakes by other researchers. The susceptibility tests results suggest the continuity in the use of ciprofloxacin for the treatment of abscesses that do not respond to simple drainage. The set of results represents a complete survey of the current situation of accidents involving snakes in the state of Tocantins and the surrounding area and will certainly contribute to the improvement of actions to combat public health problems in the North region of Brazil.

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Recently the World Health Organization reclassified the snakebites as Neglected Tropical Disease. This problem mainly affects economically active age groups of rural populations in poor or in developing countries in tropical regions. Despite the low mortality rate associated with this type of accident in Brazil, one of the largest estimates of occurrence was attributed to the country. The epidemiological profile is widely known in several Brazilian regions, but little was inferred about factors associated with the occurrence of snakebites in the country. In order to analyze the spatial distribution of snakebites caused by snakes of the Elapidae and Viperidae families in the Brazilian municipalities between 2007 and 2015, we associate the number of snakebites with variables related to human factors (Area of the Municipality, Population, Agricultural Production, Municipal Human Development Index and Gross Domestic Product) and environmental factors (Species Richness, Remnant Area of Native Vegetation, Altitude and Climate). The records of notifications were obtained from the database of the Ministry of Health's Information and Notification System of Injuries. The average annual incidence rate for the time series analyzed was calculated. The association between the number of snakebites and factors analyzed was tested through Multiple Linear Regression Analysis by an OLS (Ordinary Least Square) model, evaluating the spatial autocorrelation in the model residues by the Moran Index. The variance partition was performed to evaluate the isolated effect of the different factors (environmental, human and spatial) on the variation of the accident data. Data were analyzed at national and regional scales. The average annual incidence for the period was 12.1/100,000 inhabitants. The North and Midwest regions presented the highest incidence, followed by the Northeast, South and Southeast regions, respectively. The OLS model indicated association more than 50% between snakebites data and variables tested, with the highest contribution of human factors followed the spatial effect and lower contribution of environmental factors in all scales. The model showed higher suitability especially for regions with the highest incidence rate, indicating differences in the composition of the most important variables in each region. However, it is possible to infer that in the analysis period, human factors contributed most heavily to the occurrence of snakebites in Brazil, followed by the spatial effect on the distribution of these snakebites and minor contribution of environmental factors. Clearly, the demographic density linked to type of occupation and climatic conditions may favor the increase of snakebites in the country, and different regional characteristics can clarify the disparity in the incidence rate among the Brazilian regions.
Recentemente os acidentes ofídicos foram reclassificados pela Organização Mundial da Saúde como Doença Tropical Negligenciada. Esse problema atinge principalmente grupos etários economicamente ativos de populações rurais em países pobres ou em desenvolvimento nas regiões tropicais. Apesar do baixo índice de mortalidade associado a esse tipo de acidente no Brasil, uma das maiores estimativas de ocorrência foi atribuída ao país. O perfil epidemiológico é amplamente conhecido nas diversas regiões brasileiras, porém, pouco se inferiu sobre fatores associados à ocorrência de acidentes ofídicos no país. Assim, com o objetivo de analisar a distribuição espacial dos acidentes causados por serpentes das famílias Elapidae e Viperidae, registrados para os municípios brasileiros entre os anos de 2007 e 2015, associamos o número de acidentes ofídicos, obtidos na base de dados do Sistema de Informação e Notificação de Agravos do Ministério da Saúde, com variáveis ligadas a fatores humanos e ambientais considerando o efeito espacial na distribuição dos dados. A taxa de incidência média anual foi calculada para elaboração do mapa de distribuição nacional e regional da incidência no período analisado. A associação entre o número de acidentes e fatores analisados foi testada através de Análise de Regressão Linear Múltipla OLS (Ordinary Least Square), avaliando a autocorrelação espacial nos resíduos do modelo pelo Índice de Moran. A partição de variância foi realizada para avaliar o efeito isolado dos diferentes fatores sobre a variação do número de acidentes. A incidência média anual para o período foi de 12,1/100.000hab. As regiões Norte e Centro-Oeste apresentaram as maiores incidências, seguidas pelas regiões Nordestes, Sul e Sudeste, respectivamente. O modelo OLS indicou associação superior a 50% entre dados de acidentes e variáveis testadas, com maior contribuição dos fatores humanos seguidos do efeito espacial e menor contribuição dos fatores ambientais em todas as escalas analisadas. O modelo mostrou maior adequação principalmente para as regiões com maior taxa de incidência, indicando diferenças na composição das variáveis mais importantes em cada região. Contudo, é possível inferir que no período analisado, fatores humanos contribuíram mais fortemente para a ocorrência de acidentes ofídicos no Brasil, seguidos do efeito espacial sobre a distribuição desses acidentes e menor contribuição dos fatores ambientais. Especialmente, o adensamento demográfico ligado ao tipo de ocupação e condições climáticas podem favorecer o aumento de acidentes ofídicos no país e diferentes características regionais podem esclarecer a disparidade na taxa de incidência entre as regiões brasileiras.

Snakebite disproportionally affects children living in impoverished rural communities. The WHO has recently reinstated snakebites on its list of Neglected Tropical Diseases and launched a comprehensive Strategy for the Prevention and Control of Snakebite Envenoming. In the first of a two paper series, we describe the epidemiology, socioeconomic impact and key prevention strategies. We also explore current challenges and priorities including the production and distribution of safe and effective antivenom.
Revisión por pares

The epidemiology of snakebite injury in the Amazonian regions of Ecuador Introduction: Morbidity and mortality from snakebite envenomations is a major public health issue in remote areas of under-developed countries. Several attempts have been made to approximate the impact of snakebites worldwide, however these are assumed to be underestimations due to the lack of documentation on the local level. Ecuador's Amazonian region lacks a comprehensive community-based surveillance system, however it is unique in that an aero-medical transport system is in place to transfer the patients requiring hospitalization to one of the five urban medical centers. Beginning in 1998, Servicio Aéreo Misional (SAM), one of the two transport companies serving three of the rural provinces, began documenting flight data including the demographics of patients and their diagnoses. Methods: The SAM database was used to conduct a retrospective study to describe the incidence, patient demographics and geographic location of snakebite injuries in three rural provinces of Ecuador. SPSS was used for frequencies and Chi squares analyses. Results: In the years 2003 to 2005 there were a total of 1,340 aero-medical transports in this region. Of those, snakebite injuries constituted 4.2% of all medical diagnoses. The majority of snakebites occurred in males (p=0.027) aged 10-29 (p<0.001) and were concentrated in the low-lying areas of the province of Morona-Santiago. Discussion: These results describe the distribution of snakebites; efforts are now underway to identify the risk factors involved in this patient population. This information would then be used to optimize prevention and treatment.

Antivenom is the only effective treatment against the systemic effects of snakebite and is currently developed by a century-old immunisation protocol that aims to generate IgGs capable of binding and neutralizing most (if not all) of the venom toxins. However, snake venoms comprise more than a hundred proteins and peptides that exhibit a significant diversity in terms of isoform complexity, toxicity and immunogenicity. Therefore, antivenom doesn’t take into account the representation of venom toxins and contains therapeutically redundant IgGs to non-toxic venom components, and a lack of high titre IgGs to highly toxic, but weakly immunogenic components. The usual consequence of the century old immunisation protocol is the need to administer large volumes to achieve venom-neutralisation in an envenomed patient, which greatly increases the risk of antivenom-induced adverse effects and reduces its affordability. The Alistair Reid Venom Research Unit has pioneered a new approach using the rationale of generating venom toxin‐specific antibodies on the basis that an antivenom that only targets the most pathogenic toxin groups would be predicted to overcome these issues by improving the clinical efficacy of the treatment. Based upon preliminary work illustrating extensive cross‐specific and cross‐generic reactivity of a toxin‐specific antibodies generated against some of the most pathogenic toxin groups of venoms from medically-important species, the overarching aim of the work described in this thesis was to extended this toxin-specific antivenom approach with a view to ultimately generating a therapy against all the African species of the Echis genus. In order to overcome the high isoform diversity known for most of the pathologically-important venom toxin groups, we conducted a bioinformatic interrogation of the venom gland transcriptomes of Echis ocellatus, Echis pyramidum leakeyi and Echis coloratus for five major target toxin groups: Phospholipases A2 (PLA2), Serine proteases (SP) C-type lectins (CTLs), Metalloproteinases (SVMPs) and Disintegrins that identified epitopes on the basis of i) sequence conservation, ii) antigenicity, (iii) surface exposure and (iv) coverage across the EST data. Resultant sequences were synthesised as epitope-strings and subsequently delivered as DNA and recombinant proteins immunogens that in a proteic form successfully generated antibodies capable of binding to a number of reduced venom proteins in a cross-reactive manner, suggesting the presence of specific and generic shared epitopes of importance. The results obtained in this study helped identifying key elements of the toxin-specific approach for the design of antivenoms and highlighted the need to elucidate several aspects of the molecular interaction of the raised antibodies against the target venom proteins, in order to have an accurate approach to their binding in a native state. In addition, the study successfully approached venom glycosylation, and aspect that hasn’t been studied in detail and came apparent during the progress of the toxin specific antivenom gave light in the future stages of its development.

Background: Venomous snakebite and its effects are a source of fear for people living in southern Nepal. As a result, people have developed a negative attitude towards snakes, which can lead to human-snake conflicts that result in killing of snakes. Attempting to kill snakes increases the risk of snakebite, and actual killing of snakes contributes to loss of biodiversity. Currently, snake populations in southern Nepal are thought to be declining, but more research is needed to evaluate the conservation status of snakes. Therefore, we assessed attitudes, knowledge, and awareness of snakes and snakebite by Chitwan National Park's (CNP) buffer zone (BZ) inhabitants in an effort to better understand challenges to snake conservation and snakebite management. The results of this study have the potential to promote biodiversity conservation and increase human health in southern Nepal and beyond. Methods: We carried out face-to-face interviews of 150 randomly selected CNP BZ inhabitants, adopting a cross-sectional mixed research design and structured and semi-structured questionnaires from January-February 2013. Results: Results indicated that 43 % of respondents disliked snakes, 49 % would exterminate all venomous snakes, and 86 % feared snakes. Farmers were the most negative and teachers were the most ambivalent towards snakes. Respondents were generally unable to identify different snake species, and were almost completely unaware of the need of conserve snakes and how to prevent snakebites. Belief in a snake god, and the ability of snakes to absorb poisonous gases from the atmosphere were among many superstitions that appeared to predispose negativity towards snakes of BZ residents. Conclusion: People with predisposed negativity towards snakes were not proponents of snake conservation. Fear, negativity, ambivalence towards, and ignorance about, snakes and the need for snake conservation were strong indicators of the propensity to harm or kill snakes. It seems that if wanton killing of snakes continues, local snake populations will decline, and rare and endangered snake species may even become locally extirpated. Moreover, inappropriate perception and knowledge about snakes and snakebites may put BZ people at increased risk of venomous snakebite. Therefore, intensive, pragmatic educational efforts focused on natural history and ecology of snakes and prevention of snakebite should be undertaken in communities and at schools and universities.

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O envenenamento ofídico, dentre os acidentes com animais peçonhentos é o mais importante deles, pela sua frequência e gravidade. No Brasil, as serpentes do gênero Bothrops são responsáveis por 90 % dos acidentes ofídicos. Os extratos vegetais apresentam uma diversidade de moléculas com diversas ações farmacológicas. As espécies de Clusia são de grande interesse paisagístico, porém duas espécies deste gênero, C. torresii Standl. e C. palmana Standl. apresentam propriedades antiofídicas contra o veneno de B. asper. O objetivo do nosso trabalho foi avaliar as propriedades antiofídicas da espécie Clusia fluminensis Planch & Triana, utilizando diferentes partes vegetais e solventes de diferentes polaridades para o preparo dos extratos, assim como uma benzofenona isolada do extrato hexânico da flor, frente atividades biológicas do veneno de B. jararaca. Ensaios in vitro mostraram que os extratos hexânicos e metanólicos das folhas e frutos, na proporção de 1:50 (veneno:extrato) foram capazes de inibir 100 % a atividade proteolítica do veneno de B. jararaca (9 μg/mL), usando-se azocaseína como substrato; com exceção do extrato hexânico do caule e da benzofenona que inibiram cerca de 50 %. Na atividade hemolítica do veneno de B. jararaca (88 μg/mL), a inibição foi de 40 %, nas proporções de 1:10 e 1:20. Por outro lado, os extratos nestas mesmas proporções não foram capazes de neutralizar a coagulação do plasma induzida pelo veneno de B. jararaca (22 μg/mL), de forma significativa. Em ensaios in vivo (atividade hemorrágica) apenas o extrato acetônico do fruto, na proporção de 1:20, foi capaz de reverter totalmente a hemorragia causada pelo veneno de B. jararaca (16,7 μg/g). Sendo assim, nossos resultados mostram que a planta C. fluminensis pode ser uma fonte de moléculas com propriedades antiofídicas, especificamente contra o veneno de B. jararaca, e que este efeito neutralizante está diretamente relacionado a parte do vegetal e a polaridade do solvente utilizado na extração, Além disso podemos concluir que a benzofenona não é responsável, isoladamente, pelos resultados obtidos
Snake venom poisoning, among accidents with venomous animals is the most important of them, by their frequency and severity. In Brazil, Bothrops are responsible for 90 % of snake bites. The plant extracts have a variety of molecules with several pharmacological actions. Clusia species are of great landscape interest, but two species of this genus, C. torresii Standl. and C. palmana Standl. have properties against snake venom B. asper. The aim of our study was to evaluate the antivenom properties the species Clusia fluminensis Triana & Planch, using different plant parts and solvents of different polarities for the preparation of extracts, as well as a benzophenone isolated from the hexane extract of the flower, against biological activity of the venom of B. jararaca. In vitro assays showed that the hexane and methanolic extracts of leaves and fruits at a ratio of 1:50 (venom: extract) were able to inhibit 100 % proteolytic activity of the venom of B.jararaca (9μg/mL), using azocaseíne as substrate, with the exception of hexanic extract from stem and benzophenone which inhibited about 50 %. In the hemolytic activity of the venom of B. jararaca (88 μg/mL), inhibition was 40 %, the proportions of 1:10 and 1:20. On the other hand, the same proportions in these extracts were not able to neutralize the plasma coagulation induced by the venom of B. jararaca (22 μg/mL) significantly. In vivo assays (hemorrhagic activity) only the acetone extract of the fruit was able to totally reverse bleeding caused by the venom of B. jararaca (16,7 μg/g). Thus, our results show that the plant C. fluminensis can be a source of molecules with neutralizing properties of snake venom, specifically against the venom of B. jararaca, and that the neutralizing effect is directly related to part of the plant and the polarity of the solvent used in extraction, we can also conclude that benzophenone is not responsible alone for the results

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Introduction: Snakebites in some countries are among the 10 leading causes of death and heterologous antivenom is the only effective treatment for over 100 years. However, problems in its production and control until now have not been fully resolved and early and late adverse reactions are common serotherapy. In most case reports, clinical and laboratory findings are related to the subject that had been chopped and received antivenom, so there is the question whether the changes are related only to the action of the venom and also the action of the serum. Studies report evidence that excessive amounts of antivenom are in use, resulting in a high incidence of reactions. Therefore, this study aimed to evaluate the effect of different antivenoms on liver function in Wistar rats. One hundred and fifty animals were distributed in five groups as follows: group 1 (G1) - received anticrotalic serum for human use; group 2 (G2) - antivenom for human use; group 3 (G3) - serum antibothropic-crotalic for human use; group 4 (G4) - serum antibothropic-crotalic for veterinary use; group 5 (G5 control) - received saline. Serum dosage of alanine aminotransferase, aspartate aminotransferase, gammaglutamyltransferase, alkaline phosphatase and liver histopathology with 2, 8 and 24 hours was performed. The statistical analyzes were performed using analysis of variance with contrasts using the Tukey method, ANOVA and Kruskal-Wallis. The level of significance was 5%. Results: In the groups treated with antivenom, we observed increased alanine aminotransferase and alkaline phosphatase, no change in aspartate aminotransferase and gammaglutamyltransferase, and congestion, decreased glycogen, vacuolar degeneration, Kupffer cell hyperplasia and centrilobular necrosis in the histopathological analysis. Conclusions: The antivenom used in this assay when administered intraperitoneally, caused hepatic changes in Wistar rats, suggesting new studies related to adequacy in conduct as the dose of serum to be used in snakebite, need to produce higher quality sera and greater safety for patients.
Os acidentes ofídicos em alguns países estão entre as 10 principais causas de morte em seres humanos e a soroterapia heteróloga é o único tratamento eficaz há mais de 100 anos. No entanto, problemas na sua produção e controle até hoje não foram totalmente resolvidos e reações adversas precoces e tardias à soroterapia são comuns. Na maioria dos relatos de caso, os achados clínicos e laboratoriais estão relacionados ao sujeito que já havia sido picado e recebido a soroterapia, assim fica a dúvida se as alterações só estão relacionadas à ação do veneno ou também a ação do soro. Estudos relatam evidências que quantidades excessivas de antiveneno estão sendo utilizadas, resultando em uma elevada incidência de reações. Desta forma, este estudo teve como objetivo avaliar a ação de diferentes antivenenos sobre a função hepática em ratos Wistar. Cento e cinqüenta animais foram distribuídos em cinco grupos como se segue: grupo 1 que receberam soro anticrotálico para uso humano; grupo 2 que receberam soro antibotrópico para uso humano; grupo 3 que receberam soro antibotrópico-crotálico para uso humano; grupo 4 que receberam soro antibotrópico-crotálico para uso veterinário; grupo 5 que receberam solução fisiológica. Foi realizado dosagem sérica de alaninoaminotransferase, aspartato aminotransferase, gama glutamiltransferase , fosfatase alcalina e histopatologia do fígado com 2, 8 e 24 horas. Os testes estatisticos utilizados foram de análise de variância com contrastes pelo método de Tukey, Anova e Kruskal-Wallis. O nível de significância adotado foi de 5%. Nos grupos tratados com antiveneno, observou-se aumentou de alanino aminotransferase e da fosfatase alcalina, ausência de alteração de aspartato aminotransferase e gama glutamiltransferase , além de congestão, diminuição de glicogênio, degeneração vacuolar, hiperplasia das células de Kupffer e necrose centrolobular na análise hitopatológica. Os antivenenos utilizados neste ensaio, quando administrados por via intraperitoneal, na dose de 2 mL, causaram alterações hepáticas em ratos Wistar, sugerindo assim novos estudos relacionados a adequação da conduta quanto a dose de soro a ser usada no acidente ofídico, necessidade de produção de soros de maior qualidade e de maior segurança aos pacientes.

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Venomous animals accidents are of great importance in any Country especially due to the significant number of people involved and the relevance of these accidents. There is an annual average of 24,000 snakebite accidents in Brasil and from these 1% are related to the genus Micrurus, which represents the true coralsnakes. In this study I evaluated the biological aspects of the accidents caused by coralsnakes in Brasil, including aspects related to municipality, sex and age of the patients, time between the accident and the first medical evaluation and biological and toxinological diversity. I analyzed 787 reports available in the SINAN electronic system, from 2007 to 2010. According to the data, 691 patients were discharged as totally healed, three died, and 93 were reported as no data available. The majority of the accidents were reported from the northeast region (52%). The time between 0 and 3 hours for the first medical evaluation is a general rule for the whole Country which contributes for a satisfactory result of the treatment. The clinical cases available in the literature show that the coralsnake envenomation may or may not present symptoms, however the administration of the anti-coralsnake serum is recommended in all cases as all are considered as grave. From the 27 described species of coralsnakes for Brasil 20 occur in the northern region and, among them, nothing is known about the venom composition of at least 13 species. In a long term this might become a problem as the immunization pool for antivenin production is based only in three species. The study of biology and natural history of this group is important to facilitate the maintenance of these animals in captivity. It is also necessary to evaluate the antigenic pool and verify the efficacy of the antivenin against all species.
Os acidentes por animais peçonhentos têm grande importância médico sanitária no país. No Brasil ocorre uma média anual de 24.000 acidentes com serpentes peçonhentas, desses, 1% com o gênero Micrurus, representado pelas cobras corais verdadeiras. Neste trabalho foram avaliados os aspectos biológicos dos acidentes causados por cobras corais no Brasil, incluindo aspectos relacionados com o município e região brasileira, sexo e faixa etária dos acidentados, tempo decorrido entre o acidente e o atendimento, diversidade biológica e toxinológica. Foram analisadas as informações de 787 notificações disponíveis no sistema eletrônico do SINAN, no período de 2007 a 2010. De acordo com os dados, 691 pacientes foram liberados totalmente curados, três vieram a óbito, e 93 não há informação. A maioria dos acidentes foram registrados na região Nordeste do país (52%). O intervalo de zero a três horas entre acidente e atendimento, prevalece em alta para todas as regiões, o que contribui para um resultado satisfatório do tratamento. Os casos clínicos disponíveis na literatura mostram que o envenenamento elapídico pode apresentar sintomatologia ou não, porém a administração do soro antielapídico é recomendada em todos os casos, pois todos são considerados graves. Das 27 espécies de cobras corais descritas para o Brasil, 20 ocorrem na região norte, dentre elas, não se conhece o veneno de 13 espécies. A longo prazo esse pode ser um problema diante do pool de imunização para a produção de soro, que é composto por somente três espécies. O estudo da biologia e história natural desse grupo é importante para facilitar a manutenção desses animais em cativeiro. É necessário também, a avaliação do pool antigênico para verificar a eficácia do antiveneno para todas as espécies.

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This study evaluated the effects of the venom from Crotalus durissus terrificus and snakebite serum on the clinical signs and liver function in 120 Wistar rats by performing physical examinations, laboratory and histopathology tests. The animals were divided into four experimental groups of thirty animals in each group. The control group (C) - received only solution of sodium chloride 0.9%; Group venom (V) - received 1mg/kg venom; Group snakebite serum (S) - received the indicated dose snakebite serum to neutralize the poison; Poison and serum group (VS) - received venom and the snakebite serum six hours later. The clinical evaluation and specimen obtained for laboratory and histological examinations were performed at time 2 hours, 8 hours and 24 hours in all groups. It was observed for the S Group elevation of serum enzyme alkaline phosphatase (FA), inflammatory reaction, changes in Kupffer cells, necrosis and hyaline degeneration; Group V heart rate decrease over time, increase in rectal temperature (TR), increased FA, increase of serum aspartate aminotransferase (AST), inflammatory infiltrate, changes in Kupffer cells, necrosis and hyaline degeneration; Group VS increased TR and also respiratory rate, elevated serum FA, AST and alanine aminotransferase (ALT), inflammatory reaction, changes in Kupffer cells, necrosis and hyaline degeneration. The results indicate that the venom and snakebite serum alter the clinical parameters and cause liver damage at the doses and times studied. However, further studies with the venom and antivenom to be able to understand the effect of time and changes in the percentage contribution of hepatotoxicity in serum isolated. In addition, to investigate the need for additional treatments to protect the liver.
Este estudo avaliou os efeitos hepatotóxicos do veneno de Crotalus durissus terrificus e soro antiofídico em 120 ratos Wistar, através da realização de exames físico, laboratorial e histopatológico. Os animais foram divididos em quatro grupos experimentais, com trinta animais em cada grupo, sendo: grupo controle (C) - recebeu solução de cloreto de sódio 0,9%; grupo veneno (V) - recebeu veneno crotálico 1mg/Kg; grupo soro antiofídico (S) - recebeu soro antiofídico na dose indicada para neutralizar o veneno; grupo veneno e soro (VS) - recebeu veneno crotálico e após 6 horas o soro antiofídico. A avaliação clínica e a colheita de material para exames laboratorial e histopatológico do fígado foram realizadas nos momentos 2 horas (n=10), 8 horas (n=10) e 24 horas (n=10) para todos os grupos. Observou-se para o grupo S elevação sérica da enzima fosfatase alcalina (FA), infiltrado inflamatório, alterações nas células de Kupffer, necrose e degeneração de hialina; Grupo V diminuição da frequência cardíaca no decorrer do tempo, aumento na temperatura retal (TR), elevação da FA, elevação sérica da aspartato aminotransferase (AST), infiltrado inflamatório, alterações nas células de Kupffer, necrose e degeneração de hialina; Grupo VS aumento da TR e na frequência respiratória, elevação sérica da FA, elevação sérica da AST, elevação sérica da alanina aminotransferase (ALT), infiltrado inflamatório, alterações nas células de Kupffer, necrose e degeneração de hialina. Os resultados encontrados indicam que o veneno crotálico e o soro antiofídico, associados ou não, alteram os parâmetros clínicos e provocam danos hepáticos nas doses e momentos estudados. No entanto, são necessários novos estudos com o veneno crotálico e a soroterapia para que se possa entender o efeito do tempo nas alterações e a porcentagem de contribuição do soro isolado na hepatotoxicidade. Além disso, investigar a necessidade de tratamentos complementares para a proteção hepática.

The snakebite is a public health problem worldwide, especially in tropical countries. The objective of this study was to investigate the mechanisms involved in the effect of hydroethanolic extract of the stem bark Abarema cochliacarpos (EAc) in muscle injury induced by Bothrops leucurus. Male swiss mice were used (28-32g ; n= 6 groups), where they received perimuscular injection Bothrops leucurus venom (BlV 1 mg/Kg/paw Volume 50 ìl) the right hind limb, treated orally (po), with vehicle (saline) or EAc (100, 200 or 400 mg / kg). In the mechanical hypernociception animals were evaluated in time 2, 4 and 6 hours using digital analgesymeter (von Frey). Edema activity in the animals were evaluated at 15, 30, 60 and 90 minutes, using a digital caliper. Have motor activity was assessed by the rota -rod test and the animals were evaluated at 1, 3 and 7 days. Histological evaluation extensor digitorum longus muscle (EDL) was isolated, removed, fixed, paraffin emblocado (Optical Microscopy) and resin (Electron Microscopy) and cut. Tissues were stained with hematoxylin and eosin and observed under optical and electron microscopy and subsequently photographed. The experimental protocols were approved by the ethical committee for animal research at UFS (CEPA: 61/12). The results were analyzed using followed by Student.s t-test. The treatment orally with EAc (400 mg / kg ) inhibited mechanical hypernociception (2h 5.1 ± 0.76, 5.70 ± 0.65 4h, 6h 5.93 ± 0.49, (p < 0, 05) compared with the BlV venom group (2h 2.08 ± 0.33; 4h 2.28 ± 0.18; 6h 2.52 ± 0.24). The inhibition of edema was also seen in activity with EAc (400 mg / kg) (15 min 15.35 ± 0.27; 30 min 12.63 ± 0.69; 60 min 9.38 ± 0,29 and 90 min 6.83 ± 0.66, p < 0.05) compared with the BlV venom group (15 min 29.7 ± 0.17; 30 min 25.8 ± 0.26; 60 min 20.15 ± 0.24 and 90 min 14.76 ± 0.21). Regarding motor activity, the EAc (400 mg / kg) preserved motor ability (1day 83.22 ± 0.46; 3 days 98.02 ± 0.20 and 7 days 119.24 ± 0.48, p < 0.05) compared to the BlV venom group (1 day 20.03 ± 0.26, 3 days 35.22 ± 0.36 and 7 days 111.21 ± 0.18). Histological analysis showed an protection of muscle injury after administration of EAc (400 mg / kg), maintaining muscle fibers. Our results demonstrated that EAc inhibited the harmful effects of the venom, suggesting that this compound has biotechnological potential in adjuvant treatment of snakebite.
O ofidismo e um problema de saude publica em todo o mundo, especialmente nos paises tropicais. O objetivo deste trabalho foi de investigar os mecanismos envolvidos no efeito do extrato hidroetanolico da entrecasca da Abarema cochliacarpos (EAc) (popularmente conhecida como gbarbatimao h) na lesao muscular induzida pelo veneno de Bothrops leucurus (BlV). Foram utilizados camundongos Swiss machos (28-32 g; n=6 por grupo), que receberam injecao perimuscular do veneno Bothrops leucurus (BlV . 1 mg/Kg/pata . Volume 50 Êl) no membro posterior direito, tratados por via oral (v.o.), com veiculo (solucao salina) ou EAc (100, 200 ou 400 mg/kg). Na hipernocicepcao mecanica os animais foram avaliados nos tempos 2, 4 e 6 horas, utilizando o analgesimetro digital (Von Frey). Na atividade edematogenica os animais foram avaliados nos tempos 15, 30, 60 e 90 minutos, utilizando o paquimetro digital. Ja atividade motora foi avaliada pelo teste de rota-rod e os animais foram avaliados em 1, 3 e 7 dias. Na avaliacao histologica o musculo Extensor digitorum longus (EDL) foi isolado, retirado, fixado, emblocado com parafina (Microscopia optica) e resina (Microscopia eletronica) e cortados. Os tecidos foram corados com hematoxilina- eosina e observados ao microscopio optico e eletronico e posteriormente fotografados. Os protocolos experimentais foram aprovados pelo comite de etica em pesquisa com animais da UFS (CEPA: 61/12). Os resultados foram analisados utilizando o teste Student.S t-test. O tratamento, por v.o, com EAc (400 mg/Kg) inibiu a hipernocicepcao mecanica, (2h 5,1 }0,76; 4h 5,70 }0,65; 6h 5,93 }0,49; p<0,05) quando comparados aos animais do grupo BlV (veneno) (2h 2,08 }0,33; 4h 2,28 }0,18; 6h 2,52 }0,24). A inibicao tambem foi verificada na atividade edematogenica, com EAc (400 mg/kg), (15 min. 15,35 }0,27; 30 min. 12,63 }0,69; 60 min. 9,38 }0,29 e 90 min. 6,83 }0,66; p<0,05), quando comparados aos animais do grupo BlV (veneno) (15 min. 29,7 }0,17; 30 min. 25,8 }0,26; 60 min. 20,15 }0,24 e 90 min. 14,76 }0,21). Quanto a atividade motora, o EAc (400 mg/Kg) preservou a capacidade motora (1 dia 83,22 }0,46; 3 dias 98,02 }0,20 e 7 dias 119,24 }0,48; p<0,05), comparados ao grupo BlV (veneno) (1 dia 20,03 }0,26; 3 dias 35,22 }0,36 e 7 dias 111,21 }0,18). Na analise histologica verificou-se uma protecao da lesao muscular apos administracao do EAc (400 mg/Kg), preservando as fibras musculares. Nossos resultados demonstraram que o EAc inibiu os efeitos nocivos do veneno, sugerindo que este composto apresenta potencial biotecnologico no tratamento coadjuvante do ofidismo.

The author wrote a dissertation for the Mmed Sc degree entitled The Clinical Natural History of Snakebite in Southern Africa, which dealt with the epidemiology of snakebite and the clinico-pathological events in snakebite victims. This thesis is a sequel on the management of snakebite victims. Publications on the overall management of snakebite in the Southern African region that include original scientific research are those of F.W. Fitzsimons (1912), F.W. Fitzsimons (1929) (assisted by V.F.M. Fitzsimons), P.A. Christensen (1955, 1966, 1969) and Christensen & Anderson (1967). Subsequent books, pamphlets and journal articles have rehashed this knowledge or advocated methods of treatment developed in other countries. An example of the latter is the pressure immobilisation prehospital measure advocated for snakebites in Australia (Sutherland et aL, 1979, 1981, 1995), which I regard as benefiting less than 1% of snakebite victims here and being deleterious in most cases. In view of the paucity of research done in Southern African in recent years, many questions remain unanswered, and some strongly held views are without logical or scientific foundation. Most of these questions arose prior to the writing of this thesis, and others arose when the data were analysed. The following are some questions on the management of snakebite that have still have to be addressed. Is vaccination against snakebite possible and practical? Are folk and traditional remedies advantageous or deleterious? How commonly are they used? Immobilisation of the bitten part and the patient is an internationally recognised aid measure, but is this relevant to the Southern African situation? Tourniquet use in the case of necrotising venoms is considered to aggravate or precipitate necrosis. Does immediate active movement following a bite ameliorate or prevent necrosis without increasing mortality? The majority of clinicians recommend antibiotic prophylaxis, but is this necessary for all snakebites, against which bacteria should antibiotics be administered, and what is the source of these bacteria? Should antivenom be administered to all snakebite victims: for species-specific bites, only if envenomation is present, for severe envenomation, or not at all? Acute adverse reactions to South African manufactured snakebite antivenom has been variously recorded as less than 1% (Visser & Chapman 1978) up to 76% (Moran et al., 1998). What is the truth? Is syndromic management of snakebite efficacious or is it essential to identify the particular snake species? Is the present liberal use of fasciotomy necessary? Is there an optimum time to debride necrotic areas and is surgery necessary at all? Is paresis or paralysis due to neurotoxic envenomation always the result of a post-synaptic block? Would such a block respond to neostigmine or prostigmine in a similar way to post-synaptic anaesthetic muscle relaxants? Is heparin of value when procoagulant toxins induce a consumption coagulopathy? Do fibrinstabilising agents or fibrinolytics have a role? Does the management of pregnant snakebite patients differ from that of non-pregnant patients? Is snake venom teratogenic? Does snake venom ophthalmia frequently lead to blindness? Are steroids, NSAIDs and antihistaminics, which are commonly used in the management of snakebite, of proven value? This thesis attempts to answer these questions and more, and comprises six sections. The first section deals with pre-hospital management, the second with infection which may occur at the bite site wound, the third with SAIMR snakebite antivenom, the fourth with the three envenomation syndromes, the fifth with snakebite in pregnancy, venom ophthalmia and other treatment modalities, and the sixth section includes a summary, appendix and references. Unless otherwise stated, the materials and methods of each chapter are based on 336 snakebite victims admitted to Eshowe Hospital, KwaZulu-Natal, from January 1990 - July 1993 and other victims treated by the author, the data of which have been prospectively maintained. This has been an ongoing process up to the present time.
Thesis (MMedSc.)-University of Natal, 2000.

博士
國立臺灣大學
毒理學研究所
90
Climatically speaking, Taiwan is situated right at the joint of the tropical and subtropical regions. The weather here is thus quite warm and wet with lots of rainfall throughout the year. With abundant food available around, plus complicated, luxuriant vegetation and greatly varied geography, many different varieties of snakes thrive in Taiwan. Among them there are six major venomous snakes, i.e. Naja atra(Cobra), Bungarus multicinctus(BM), Trimeresurus mucrosquamatus(TM), T. stejnegeri(TS), Deinagkistrodon acutus and Daboia russelli siamensis(Russell’s viper, RV). Basic studies on snake venoms started quite early and are plenty, but researches on clinical diagnosis and managements are rather scarce. There are still many unsolved problems in clinical diagnosis and therapeutic treatments of venomous snakebites. In this thesis study, we looked back into relevant literature and made use of clinical cases analyses, patients blood snake venom analyses, pathologic examinations, antivenom clinical trial, and animal tests to shed some light on the clinical toxicology of Taiwan venomous snakes envenoming. We retrospectively analyzed 286 snakebite cases treated by Taichung Veterans General Hospital and some reported epidemiological data of venomous snakebites of the past 30 years. We found that there were geographic differences in the incidence of various venomous snakebites in Taiwan, and they seemed to be related to the common living environments shared by human beings and venomous snakes. Throughout Taiwan, TM caused the most common venomous snakebites in average. Locally, bites by DA and RV were more common in southern and eastern Taiwan, while cobra snakebites frequently occurred in central Taiwan. In general, immediate treatment with antivenom could greatly lower the mortality of venomous snakebite cases. However, in the case of bites by BM, it is also essential to keep the patient alive by protecting his airway. From case studies of cobra snakebites, we found that its early clinical symptoms were very similar to that caused by other venomous snakes, so called “hemorrhagic” species. Some objective methods are necessary to get accurate diagnosis. Cobra snakebite mainly causes local reddening and swelling and tissue necrosis, and the necrosis lesions were vulnerable to infection by Gram-negative bacteria. Only about 5% of the bitten patients showed the typical symptoms and signs of neuromuscular junction block paralysis. In order to diagnose accurately or be able to identify Formosan cobra snakebites, we made use of an enzyme-linked immunosorbent assay (ELISA) to detect the venom in the bitten patients. The detecting limit of this method is close to 1 ng/ml, which is highly sensitive and very characteristic. A patient bitten by cobra usually has higher blood venom level if he shows systemic symptoms and/or signs or presents with apparent necrosis of local tissue. Adequate antivenom therapy given soon enough can lighten the complication of tissue necrosis. The ELISA method can easily differentiate the cobra bite case from bites by hemorrhagic species, and it can also monitor the kinetic change of cobra venom in the patient’s blood. Bites by Russell’s viper are extremely rare and are restricted to the southeastern part of Taiwan. There has been a lack of specific or unique antivenom for this kind of bites. The venom of Russell’s viper contains several toxins affecting blood-clotting mechanism aside from other cytotoxic components. Patients bitten by Russell’s viper usually display slight local symptoms of reddening, swelling and necrosis. However, in cases of systemic envenoming, severe symptoms such as serious coagulopathy, hemolysis, rhabdomyolysis, acute renal failure, increase in capillary permeability, and systemic vascular thrombotic occlusions, start to show up. Systemic vascular thrombotic occlusions seem to be the most prominent difference between Russell’s viper snakebites in Taiwan and those in other Asian countries. The procoagulants and endothelial toxins in the venom plus the contraction of blood vessels after systemic envenoming are probably the pathophysiology of systemic vascular thrombotic occlusions. Besides, the Formosan Russell’s viper snakebites present rather obviously renal toxicity and hemotoxic effects. From the results of animal studies, we found that the earlier we administered antivenom, the less damage the animal’s vital organs would suffer. After antivenom treatment within 8 hours after snakebites, blood clotting ability would return to normal in about 24 hours. If the antivenom treatment was given later than 8 hours after the poisoning, it seemed to be unable to prevent the renal failure in the animal later. In order to strengthen the effectiveness of the Russell’s viper antivenom, we conducted a clinical trial and deployed the specific antivenom at hospitals in the area where Russell’s viper snakebites frequently occurred. We found that the patient would suffer a much lighter overall poisoning expression with shorter symptom-manifesting period if the antivenom was administered 3~6 hours after the snake bite. The blood clotting ability would return to normal anywhere from 11 hours to 2 days after the antivenom treatment. Furthermore, the renal toxicity was also relatively less extensive, and the renal function recovered much faster. In general, the results of the trial showed that the Russell’s viper antivenom was safe and effective. Finally, we used ELISA method to look into the similarities and discrepancies of immunological properties among different kinds of snake venom. We found that only about 2%~7% similarity in immunological properties was noted between those of TM and TS. Comparatively, Russell’s viper venom from Taiwan, Thailand and India showed more immunological similarities. It means that the ELISA method and specific antivenom produced here in Taiwan for Formosan Russell’s viper can also be applied to diagnose and treat bites by Thai or Indian Russell’s viper. In summary, this study in Taiwan venomous snakebite shows that the most common clinical manifestations of cobra snakebites include only localized reddening and swelling and tissue necrosis, while the supposed neurotoxic phenomena of neuromuscular junction block and difficulty in breathing are quite rare, found only in about 5% of all cases. Therefore, people would easily be misled in the diagnosis by looking for neurotoxic symptoms. In addition, most cobra bite cases would mistakenly be diagnosed as TM bites due to their predominance in local appearance. With this newly established ELISA method, we can not only affirmatively identify cobra snake bites, but also know the close relationship between patient blood venom concentration and the tissue damages. In addition, we are the first to report that in the case of Russell’s viper bites, principal clinical symptoms include systemic vascular thrombotic occlusion and renal toxicity, and this is the first incidence that an antivenom was proven effective for treating bites by Russell’s viper in Taiwan. We hope our efforts can contribute to the clinical diagnosis and treatment of cobra and Russell’s viper bites in Taiwan and their efficiency be improved substantially.

碩士
元培醫事科技大學
醫務管理系碩士班
107
It is estimated that about 6 kind of 23 snake species are clinically common in Taiwan. The treatment of snake bites is mainly treated with neutralizing anti-venom serum injection. The purpose of this study is to compare the cases of snake bites with ICD-9CM and ICD10CM in one regional teaching hospital in Taoyuan from 2011 to 2017. The hospitalization of patients with snake bites, the hospital anti-venom serum usage and personal background were analyzed for epidemiological analysis. The key findings showed as follows. First, patients with snake bites are 41 to 60 years old, in agricultural ovccupation who were mainly males and majority of them were bitten by T. stejnegeri and P. mucrosquamatus, the bite is mostly hand. Secod, the medical treatment of snake bite case mostly used antivenin of TR. mucrosquamatus, and more than 60% of patients used tetanus treatment. Third, all blood biochemical value of the case of snake bite in the normal range. Forth, the determinants of WBC number included age, the bite time, occupation and whther serum had been injected. The attributes associated with Hb values were age and gender. It is recommended to study the follow-up complications or detailed treatment. Interactions such as interactions were explored in order to obtain an epidemiological analysis of more complete snake bites.

Bibliography: leaves 515-531
The Brooklyn Papyrus (47.218.48 and 47.218.85) is the handbook of the Priests of Serqet who were called upon to treat snakebite victims in ancient Egypt. The first part of the Brooklyn Papyrus describes various snakes encountered by the ancient Egyptians, and the effects of the bites of these snakes. The second part of the Papyrus contains the numerous treatments that were used to treat the snakebite victims. The primary question of the thesis is to address how the ancient Egyptians treated snakebite victims; and if it is possible to identify the snakes that they encountered, as treatment often hinges on this identification. Additional questions are addressed, namely: What is the Brooklyn Papyrus exactly and what is its background? How does the Brooklyn Papyrus compare to the well-known ancient Egyptian medical papyri? How does the snakebite treatment of the ancient Egyptians compare to that of today’s treatment protocol? In order to answer these questions, this thesis provides my transliteration of the hieroglyphic writing into Latin script, and my translation into English, based on the hieratic to hieroglyphic transliteration done by Serge Sauneron in the late 1960s, and published in 1989 as Un Traité Egyptien d’Ophiologie. The primary aim of this thesis is to provide a transliteration and full English translation of the Brooklyn Papyrus, as none is currently available. It is clear that from the translation that one can discover exactly how snakebite was treated in ancient Egypt: what medicinal ingredients were used and how the patient was treated. Furthermore, from the text describing the snakes and the effects of their bites, one can indeed attempt to identify the species of snakes. It is also apparent from the Brooklyn Papyrus that the ancient Egyptians did recognise and accurately describe many effects of snakebite on the human body, as well as the different types of bite wounds: and they also understood the importance of being able to identify a species of snake as it very often impacted on the treatment to be prescribed—exactly as snakebite treatment is considered in medicine today
Biblical and Ancient studies
D. Litt. et Phil. (Ancient Near Eastern Studies)

碩士
國立臺灣大學
生化科學研究所
96
The snake venom metalloproteinases (SVMPs) are abundant in snake venoms and have been considered as the key toxins involved in snake venom-induced pathogenesis, such as hemorrhage, edema and mortality. According to their primary structures, SVMPs can be classfied into three categories. Here I cloned a novel P-III class SVMP from the cDNA prepared from the Walterinnesia aegyptia venom glands and determined its cDNA sequence and full amino acid sequence. By phylogenetic analysis this P-III was found to be a non-hemorrhagic SVMP, and is most similar to the P-III SVMPs from Asian and African cobra venom. Since 1970, Chinese researchers have developed the First-Aid Kit injecting trypsin solution to the bite area for snakebite treatments.The treatment has been ineffective against viper’s snakebites, Here I tried to find better protease to replace trypsin for snakebite treatment. I also looked into possible improvement of the non-antiserum or preliminary snakebite treatment. For in vitro analyses using SDS-PAGE, I have chosen crude venom of three medically important species as the substrates : Calloselasma rhodostoma, Crotalus viridis viridis and Naja atra, and compared the efficiencies of trypsin and Subtilisin Carlsberg (STC) to degrade these venom. Results of these in vitro experiments showed that STC was better than trypsin in the hydrolysis of snake venom, especially when was also included EDTA. Besides, we found that SVMPs in viper snake venom were rather resistant to trypsin digestion. Furthermore, we used mice as a model to study the pain level and protection effect of STC and EDTA after injecting C. rhodostoma venom (CRV). It was found that SVMPs in CRV may be the source of pain. When first aid treatment by EDTA together with various level of STC was given within 15 min after envenomation, the lethality of venom was reduced, and skin necrosis and pain level of the mice were reduced when EDTA and/or STC was given within 5 min after the venom injection. These data confirm that the first-aid treatment have potential to be useful for snakebite treatment. Further refinement of antidose, e.g. EDTA and lower dose of STC; or EDTA plus hyaluronidase inhibitor.