A paper submitted to The University of Arizona College of Medicine - Phoenix, History of Medicine course.

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / The standard treatment for rattlesnake envenomation (RSE) is antivenom. The clinical course of patients treated with antivenom is well described. Prior to 2000, only a whole IgG AV (IgGAV) associated with high rates of hypersensitivity reactions (HSS) was available to treat RSE. Since 2000, Crotalidae Polyvalent Immune Fab (FabAV), which has a better safety profile than IgGAV, has been primarily used. Patients with RSE may not be treated with AV for a variety of reasons including history or perceived risk of HSS, patient refusal, drug shortage, or clinical impression that AV is not indicated. Research Question: What outcomes are associated with moderate to severe RSEs treated without antivenom?

Class of 2009 Abstract / OBJECTIVES: The study’s purpose was determining the economic impact of recurrent coagulopathy with crotaline envenomation using the current standard of care, crotalinae polyvalent immune Fab antivenom (CroFab), and to establish a model of pharmacoeconomic assessment for future studies. METHODS: A recurrent coagulopathy cost assessment tool was designed that included payer and patient costs. This system used medical and billing references, government and business websites, published studies, and average costs for major variables affecting costs of recurrent coagulopathy to the payer and patient. RESULTS: Of the 42 subjects screened during the study period, 13 were eligible, and 5 chose to participate. On average, lab results were the most significant cost to payers ($247.25). No subject required additional vials of CroFab as a result of recurrent coagulopathy and therefore this was the least costly parameter. There were no correlation between lab costs, doctor visits, or ER visits. Lost wages were the highest cost to patients, with an average of $880.85. Household help and child care were the least costly parameters in this study group. The loss to follow-up was a substantial barrier to obtaining the projected number of study subjects. CONCLUSIONS: A major limitation of this study is the small sample size. Therefore, only generalizations can be made by analyzing the data in regards to the true costs of recurrent coagulopathy to patients and payers. Future pharmacoeconomic studies regarding average costs related to crotaline envenomation should consider experimental mortality a significant barrier to obtaining significant results.

Submitted by Rosana Amâncio (rosana.amancio@ufcg.edu.br) on 2018-07-12T15:42:24Z No. of bitstreams: 1 ALUSKA VIEIRA TAVARES - DISSERTAÇÃO PPGCNBio 2016..pdf: 3420076 bytes, checksum: 285c96d7eef3fab2a5f91adabb044549 (MD5) / Made available in DSpace on 2018-07-12T15:42:24Z (GMT). No. of bitstreams: 1 ALUSKA VIEIRA TAVARES - DISSERTAÇÃO PPGCNBio 2016..pdf: 3420076 bytes, checksum: 285c96d7eef3fab2a5f91adabb044549 (MD5) Previous issue date: 2016-07-20 / CNPq / O acidente ofídico é um problema de saúde pública negligenciado em países tropicais e subtropicais. Este estudo é uma investigação transversal das características epidemiológicas dos acidentes ofídicos no estado do Rio Grande do Norte, Nordeste do Brasil, de 2007 a 2014.Os dados foram coletados na Secretaria de Saúde do Rio Grande do Norte, utilizando o banco de dados do Sistema de Informação de Agravos de Notificação. Um total de 3.019 casos foram analisados. Os acidentes foram notificados em 163 municípios do estado, com maior incidência nos pequenos municípios localizados na região central. Os casos ocorreram em todos os meses dos anos investigados, com maior frequência entre março e agosto. A maioria dos casos envolveu homens com idade entre 20 e 59 anos, trabalhadores e residentes rurais, com baixa escolaridade e raça parda. Os casos ocorreram com maior frequência em áreas rurais. Houve predomínio de acidentes com serpentes do gênero Bothrops. As picadas acometeram principalmente as extremidades dos membros. A maioria das vítimas recebeu assistência médica entre 1 e 3 horas após o acidente. Os casos foram prevalentemente classificados como leves e progrediram para cura. Foram notificados 13 óbitos. A maioria das vítimas realizou o teste do tempo de coagulação e fez uso da soroterapia. As principais manifestações locais foram dor e edema. As principais manifestações sistêmicas foram vagais e neuroparalíticas. As complicações locais mais frequentes foram a infecção secundária e o déficit funcional. Quanto às complicações sistêmicas exibiu-se, sobretudo, a insuficiência renal e o edema generalizado. O perfil epidemiológico dos acidentes ofídicos no Rio Grande do Norte é semelhante aqueles observados em outros estados do Nordeste Brasileiro. Esses acidentes podem ser considerados como um problema de saúde pública no estado, devido à elevada frequência e ampla distribuição espacial dos casos. Isso revela a necessidade de desenvolver políticas públicas regionais, visando o controle preventivo desses acidentes, bem como o aprimoramento do atendimento médico das vítimas. / The snakebite is a neglected public health problem in tropical and subtropical countries. This study is a transversal investigation of the epidemiological characteristics of snakebites in the state of Rio Grande do Norte, Northeastern Brazil, from 2007 to 2014. Data was collected from the Injury Notification Information System database of the Health Department of Rio Grande do Norte. A total of 3,019 cases were analyzed. Snakebite cases were reported in 163 municipalities in the state, with the highest incidence in small municipalities in the central region. Snakebites occurred in every month of the year investigated, more frequently between March and August. Most cases involved men aged 20 to 59 years, workers and rural residents with low education level and mulattos. The cases occurred more frequently in rural areas. There was a predominance of envenoming involving Bothrops snakes. The bites mainly reached the extremity of the limbs. Most of the victims received medical assistance between 1 and 3 hours after the accident. The cases were mainly classified as mild and progressed to cure. 13 deaths have been reported. Most of the victims made the blood-clotting time test and made use of antivenom. The main local reactions were pain and swelling. The main systemic reactions were vagal and neuroparalytic. The most frequent local complications were infection secondary and functional deficit. As for systemic complications showed especially renal insufficiency and generalized edema. The epidemiological profile of snakebites in Rio Grande do Norte is similar to those observed in other states of the Brazilian Northeast. Snakebite may be considered as a public health problem in the state, due to the high frequency and high spatial distribution of the cases. This reveals the need to develop regional public policies aimed at preventive control of such injury, as well as medical care enhancement of the victims.

Class of 2016 Abstract and Report / Objectives: The purpose of this study was to assess trends in the anatomical bite location, circumstances, and legitimacy of rattlesnake envenomations managed by the Arizona Poison and Drug Information Center (APDIC) between the years of 2002 to 2014. Methods: The Institutional Review Board approved this retrospective database analysis in which deidentified patient case information was extracted from the APDIC electronic medical record database. Descriptive and demographic variables collected included: age, gender, anatomical bite location, circumstance, and alcohol involvement. Variables were analyzed by student researchers to determine the legitimacy. Researchers compared demographic variables by year and month to assess for trends. Results: A total of 1,738 rattlesnake envenomations were analyzed for the 13 year study period. The number of cases per year varied, but not significantly, p=0.069. A statistically significant (p<0.005) upward trend in average age occurred. No significant difference in cases involving females was found between study years (p=0.171). Alcohol involvement was not statistically significant, p=0.46. An upward trend (p<0.005) in legitimate rattlesnake envenomations was demonstrated. Conclusions: Envenomations from 2002 to 2014, showed an upward trend in age, but similar distribution of gender. An increasing number of envenomations were determined to be legitimate, possibly related to the increasing number occurring to the foot/ankle, as well as the increasing number related to gardening and walking outside/taking out the trash. This trend may also be due to the lack of adequate data related to alcohol involvement.

Orientadora: Profa Dra Carlos Alberto Silva / Dissertação (mestrado) - Universidade Federal do ABC, Programa de Pós-Graduação em Biotecnociência, 2016. / No Brasil a especie com maior numero de registros de acidentes ofidicos e a serpente Bothrops jararaca (Bj). Os efeitos causados pelo envenenamento amplamente caracterizados sao inflamacao no local, edema, necrose tecidual no local da picada e, acoes sistemicas, como hemorragia, coagulopatia e hipotensao arterial. Os efeitos observados ocorrem em funcao da presenca de metaloproteinases, fosfolipase, disintegrinas e peptideos biologicamente ativos presentes no veneno. Apesar disso, nao ha relatos na literatura sobre os eventuais efeitos do envenenamento no sistema reprodutor masculino de pacientes acidentados. Assim, em linhas gerais, o presente estudo visa avaliar os efeitos de componentes presentes no veneno de Bj sobre o testiculo de camundongos. Animais machos (n=6 por grupo) com 2 meses de idade, com peso entre 30 e 35 g foram separados em dois grupos. No primeiro grupo, estao os animais tratados com fracao peptidica (FP), solucao contendo componentes presentes no veneno de Bj com peso molecular inferior a 10 KDa, via intratesticular (i.t) na dose de 5¿Êg diluida em 20 ¿ÊL de solucao salina em dose unica, enquanto que o outro grupo recebeu FP com concentracao de 5¿Êg diluida em 20 ¿ÊL de solucao salina durante 15 dias via intraperitoneal (i.p). Apos o periodo de tratamento, os animais foram eutanasiados e tiveram os testiculos fixados e submetidos a analises morfologica e morfotmetrica. Posteriormente, um outro grupo de animais (n=6) foi tratado via intramuscular, e fragmentos de musculo e testiculo foram submetidos a analise por FT-Raman. Os resultados mostraram que a FP, quando injetada via i.p ou via i.t, provocam intensas alteracoes no epitelio seminifero. Ainda, a FP promoveu o aumento na quantidade de alguns tipos celulares (Espermatocito paquiteno; Espermatide circular; e Figuras meioticas) com papel importante na espermatogenese quando tratados via i.p, e diminuicao no numero de celulas germinativas (Esermatocito paquiteno; Espermatide circular; Espermatogonia tipo B; e Espermatocito zigoteno) durante os estadios de espermiogenese quando tratados via i.t., sendo que os valores de celulas obtidas apresentam diferencas estatisticas com valor de p<0,05. Para avaliar os efeitos toxicologicos do veneno sobre o testiculo, foi empregada a tecnica FT-Raman, que se mostrou efetiva na caracterizacao do envenenamento analisando fragmentos de musculo estriado esqueletico, assim como, pelas analises morfologica do musculo e niveis sericos de creatino quinase. Entretanto, quando aplicada a tecnica FT-Raman na analise de testiculo, nao foi possivel identificar alteracoes que evidenciaram a acao toxicologica do veneno sobre este orgao. Apesar disso, analise dos espectros pelo estudo dos componentes principais, verificou-se diferencas no grupo tratado com veneno botropico em relacao ao controle. Assim, os dados obervados abrem possibilidades de estudo utilizando outras tecnicas para avaliar niveis de expressao de proteinas importantes que indicam eventuais comprometimentos da espermatogenese. / The Bothrops jararaca snake shows the highest number of accidents recorded by the health ministry in Brazil. The effects caused by envenomation can be characterized by edema, tissue necrosis in the local bite and, systemic actions, such as bleeding, coagulopathy and hypotension. These effects are caused by metalloproteinases, phospholipase, disintegrins andbiologically active peptides present in the venom. However, there are no reports in the literature. In the present study, we evaluated if the envenomation effects induced via i.m cause changes on the testis functionality. Male animals at 2 months of age and weighing between 30g and 35g, were divided into 2 groups. The first one received peptide fraction (FP), solution containing components present in Bj venom with a molecular weight below 10 kDa, with dose about 5ìg diluted in 20ìL of saline solution, via intratestis (i.t) in single dose, while the second group received FP 5ìg diluted in 20ìL of saline solution via intraperitoneal (i.p) once a day, during 15 days. Subsequently another group of animals was poisoned, so induced via intramuscular, and testis and muscle were collected after 24h of treatment, and the fragments were subjected to analysis by FT-Raman. FP affected the seminiferous epithelium structure in the groups treated via i.p. and via i.t. Quantitative analysis of seminiferous epithelium showed an increase of some cell types (Spermatocyte pachytene; Spermatid circular; and Meiotic figures) with an important role in spermatogenesis when treated via i.p., and decrease in the number of germ cells (Spermatocyte pachytene; Spermatid circular; Spermatogonia type B, and Spermatocyte zygotene) during the stages of spermatogenesis when treated via i.t. The differences of number of germ cells obtained between the groups show statistical diference with p value <0.05. To evaluate the toxicological effects of the poison on the testis, we used the FT-Raman. The technique was effective in muscle fragments analyses. confirming morphology analysis and the level of creatine kinase, however, when applied the FT-Raman technique in testicular analysis was not possible to identify changes that can complete toxicological poison action on this body as to derail matured germ cells, although further analysis of the spectra, which uses key components, showed differences, opening possibilities to invest time in different analyzes that can prove or disprove this hypothesis.

Submitted by Rosana Amâncio (rosana.amancio@ufcg.edu.br) on 2018-07-12T22:28:15Z No. of bitstreams: 1 SANNY DA SILVA FURTADO - DISSERTAÇÃO PPGCNBio 2015..pdf: 2470742 bytes, checksum: 74140118ba1646afd25f965e8611e95a (MD5) / Made available in DSpace on 2018-07-12T22:28:15Z (GMT). No. of bitstreams: 1 SANNY DA SILVA FURTADO - DISSERTAÇÃO PPGCNBio 2015..pdf: 2470742 bytes, checksum: 74140118ba1646afd25f965e8611e95a (MD5) Previous issue date: 2015-07-08 / CNPq / A presente investigação é um estudo retrospectivo sobre as características epidemiológicas dos acidentes por escorpião no estado do Ceará, Nordeste do Brasil, de 2007 a 2013. Os dados foram coletados na Secretaria de Saúde do Ceará, utilizando o banco de dados do Sistema de Informação de Agravos de Notificação. Foi analisado um total de 11134 casos. Os resultados do presente estudo mostram que os acidentes foram distribuídos em todos os meses dos anos investigados, sendo mais frequentes em áreas urbanas. As vítimas foram predominantemente mulheres jovens, com idade entre 20 e 29 anos, sendo que a mão foi a parte do corpo mais atingida pelas picadas. A assistência médica ocorreu, majoritariamente, entre 1 e 3 horas após o acidente. A maioria dos casos foram classificados como leve e progrediram para cura. O envenenamento por escorpião no Ceará é um problema de saúde pública ambiental que deve ser monitorado e controlado durante todo o ano. A capacitação dos profissionais de saúde mostra ser necessária e urgente para melhorar as suas habilidades de coletar e registrar as informações epidemiológicas. Estudos adicionais sobre as relações ecológicas e a estrutura comunitária dos escorpiões da região Nordeste são necessários para conhecer as espécies envolvidas nos acidentes escorpiônicos. / This communication is a retrospective study of the epidemiology of scorpion sting cases recorded from 2007 to 2013 in the State of Ceará, northeastern Brazil. Data was collected from the Injury Notification Information System database of the Health Department of Ceará. A total of 11,134 cases were studied. Cases were distributed over all months of the period studied and occurred mainly in urban areas. Victims were predominantly 20–29 year-old women. Most victims were bitten on the hand and received medical assistance within 1–3 h after being bitten. Cases were mostly classified as mild and progressed to cure. Scorpion envenomation in Ceará is an environmental public health problem that needs to be monitored and controlled throughout the year. Further training for health professionals seems to be necessary to improve their skills in recording epidemiological information. Future studies on the species and community structure of those scorpions existing in the northeast region are necessary to better understand the species involved in the scorpion envenomation.

No description available.

Ce travail avait pour objectif de mieux évaluer les critères intrinsèques d’un antivenin et de son utilisation afin d’être le plus efficace possible dans le traitement des envenimations ophidiennes survenant sur le territoire de France métropolitaine. L’immunothérapie est à ce jour le seul traitement étiologique efficace dans la prise en charge des victimes d’envenimation ophidienne. La qualité des antivenins est un élément clé dans l’efficacité et la tolérance de ces traitements. Pour une efficacité optimale, l’immunothérapie doit être administrée le plus rapidement possible. Il ressort enfin que les caractéristiques des envenimations sont en évolution constante sur le territoire métropolitain : émergence de signes neurotoxiques dans les envenimations vipérines ; développement de l’importation de serpents exotiques. Tous ces éléments incitent à une surveillance spécifique par des structures expertes et spécialisées dans le domaine. / This work aimed to assess antivenom criteria in order to be most effective in the treatment of snake bites occurring in metropolitan France. Immunotherapy is the only effective etiological treatment in snake envenomation, considered as a gold standard. Quality of antivenoms is a key element for effectiveness and safety. Immunotherapy should be administered as soon as possible. Finally, it appears that the characteristics of envenomation are constantly changing on the mainland : emergence of neurotoxic signs in viper envenomation; importation of exotic snakes. All these emerging elements need a specific monitoring by expert and specialized structures in France.

O envenenamento humano por Lachesis, embora pouco freqüente, é bastante severo, caracterizado por pronunciado dano tecidual local e efeitos sistêmicos, como hipotensão e bradicardia, tonturas, náuseas, cólicas abdominais e diarréia. A soroterapia é única terapia específica disponível. Entretanto, para muitas plantas é atribuída ação antiofídica. No Norte e Nordeste brasileiro, o suco da fruta (SAm) e o extrato aquoso de folhas (EFAm) de graviola (Annona muricata) são freqüentemente usados pela população local para tratar o envenenamento por Lachesis muta rhombeata. O objetivo deste estudo foi avaliar a letalidade, as alterações de parâmetros hematológicos, bioquímicos, de pressão arterial e processo inflamatório induzidos pela peçonha de L. m. rhombeata (PLmr), bem como a relevância do tratamento com EFAm e SAm no envenenamento. O perfil hematológico mostra uma hemoconcentração inicial seguida de extensa hemólise, evidenciada pela redução do hematócrito, hemoglobina total e contagem global de eritrócitos, não alterado pelos tratamentos. A contagem diferencial de leucócitos revela neutrofilia nas primeiras horas de envenenamento e aumento de linfócitos 24h após a injeção da peçonha, características de processo inflamatório agudo, não influenciado pelos tratamentos. Houve diminuição de albumina e proteínas totais e aumento de uréia, decorrentes do envenenamento. Os valores de AST foram ainda maiores nos animais tratados, mas os aumentos de CK foram reduzidos pelos tratamentos com EFAm e SAm. Houve aumento de TP e TTPA na primeira hora, e diminuição da pressão arterial tempo dependente no envenenamento. O suco intensificou a queda da pressão. Foi observado aumento de IL-6 nas primeiras horas de envenenamento e alterações das proteínas plasmáticas características de processo inflamatório agudo, como esperado em casos de envenenamento. O ensaio de letalidade revela DL50 de 51,0 ± 6,3 mg/kg, para o grupo injetados com a peçonha e sem tratamento; de 56,3 ± 8,5 mg/kg, para o grupo injetado com a peçonha e tratado com SAm e de 62,2 ± 6,8 mg/kg, para o grupo injetado com a peçonha e tratado com EFAm. Concluindo, o quadro clínico do envenenamento laquético foi bem analisado, que era o objetivo principal do trabalho. Avaliou-se também a eficiência do uso popular da graviola (A. muricata) nos acidentes ofídicos com a serpente L. m. rhombeata. De forma geral, os tratamentos com EFAm e com SAm não alteram de forma relevante o quadro clínico do envenenamento, como observado pelos valores semelhantes de DL50. Entretanto, o tratamento com suco parece agravar a hipotensão causada pelo envenenamento e provocar um aumento significativo das transaminases hepáticas. Por outro lado, é possível notar nos animais tratados menores alterações da hemostasia, bem como uma possível proteção contra a miotoxicidade da peçonha. / The human envenomation by Lachesis, although rare, is quite severe, characterized by pronounced local tissue damage and systemic effects, such as hypotension and bradycardia, dizziness, nausea, abdominal cramps and diarrhea. The only specific therapy available is the serum therapy. However, for many plants is attributed antiophidic action. In North and Northeast Brazil, the fruit juice and the aqueous extract of leaves of soursop (Annona muricata) are often used by local population to treat Lachesis muta rhombeata envenomation. The aim of this study was evaluate the lethality, hematological, biochemical, blood pressure, and inflammation parameters induced by L. m. rhombeata snake venom, as well as the relevance of treatment with fruit juice and the aqueous extract of leaves of soursop. The hematological parameters shows an initial hemoconcentration followed by extensive hemolysis, as evidenced by decreased hematocrit, total hemoglobin and total red blood cells count, which were not altered by the treatments. The leukocytes differential count revealed neutrophilia in the early hours after the envenomation and increased lymphocytes 24h after the injection of L. m. rhombeata venom, characteristics of acute inflammatory process, which were not influenced by treatments. There was a decrease of albumin and total proteins and urea increased as a result of the envenomation. The AST concentration were still higher in treated animals, although the increases in CK values were reduced by treatments with leaves extract and soursop juice. There was an increase of prothrombin time and activated partial thromboplastin time during the first hour, and there were time dependent decrease of the blood pressure after the envenomation. The juice intensified the pressure decrease. An increase of IL-6 was observed in the early hours after the envenomation, as well as changes in the profile of plasmatic proteins, characteristic of acute inflammatory process, as expected in cases of snake bite. The lethality assay reveals LD50 of 51,0 ± 6,3 mg / kg for the group injected with venom without treatment; 48,3 ± 8,6 mg /kg for the group injected with venom and treated with juice of A. muricata; and 62,2 ± 6,8 mg/kg for the group injected with venom and treated with leaves extract of A. muricata. In conclusion, the clinical profile of L. m. rhmobeata envenomation was well analyzed, the main goal of this work. The efficiency of the popular use of soursop on envenomation by L. m. rhombeata snakes was also evaluated. In general, treatments with extracts of leaves and soursop juice do not significantly modify the clinical profile of the envenomation, as observed by similar LD50 values. However, treatment with juice seems to worsen the hypotension caused by envenomation and induce a significant increase in AST levels. On the other hand, there are lower changes in hemostasis on treated animals, as well as a possible protection against the myotoxicity of the venom.