Towards better antivenoms: navigating the road to new types of snakebite envenoming therapies

Abstract Snakebite envenoming is a significant global health challenge, and for over a century, traditional plasma-derived antivenoms from hyperimmunized animals have been the primary treatment against this infliction. However, these antivenoms have several inherent limitations, including the risk of causing adverse reactions when administered to patients, batch-to-batch variation, and high production costs. To address these issues and improve treatment outcomes, the development of new types of antivenoms is crucial. During this development, key aspects such as improved clinical efficacy, enhanced safety profiles, and greater affordability should be in focus. To achieve these goals, modern biotechnological methods can be applied to the discovery and development of therapeutic agents that can neutralize medically important toxins from multiple snake species. This review highlights some of these agents, including monoclonal antibodies, nanobodies, and selected small molecules, that can achieve broad toxin neutralization, have favorable safety profiles, and can be produced on a large scale with standardized manufacturing processes. Considering the inherent strengths and limitations related to the pharmacokinetics of these different agents, a combination of them might be beneficial in the development of new types of antivenom products with improved therapeutic properties. While the implementation of new therapies requires time, it is foreseeable that the application of biotechnological advancements represents a promising trajectory toward the development of improved therapies for snakebite envenoming. As research and development continue to advance, these new products could emerge as the mainstay treatment in the future.

Neutralization of toxic activities of Bothrops asper snake venom by ethnomedicinal plants used in Central America, with emphasis in Guatemala: a review / Neutralización de actividades tóxicas del veneno de la serpiente Bothrops asper por plantas etnomedicinales utilizadas en Centroamérica, con énfasis en Guatemala: Revisión

There are few scientific studies that explore the use of medicinal plants for snakebite envenoming in Central America, although plant-based therapies have been traditionally used in the region. This work reviews the studies conducted in Central America to assess the ability of extracts obtained from plants of local ethnomedical use to inhibit toxic activities of the venom of Bothrops asper, the snake responsible for approximately half of the snakebite envenomings in these countries. The search prioritized the description of the plants used in Guatemala, since most of the studies described in this work were conducted in that country, although references to other countries are included. Information concerning secondary metabolites and other pharmacological activities of these plant species, relevant to the treatment of snakebites, was also described. The literature search was conducted in the Google Scholar, PubMed and Scopus databases and completed with locally available literature. It was found that extracts of 12 plant species inhibited the hemorrhagic effect of the venom and three neutralized the edema-forming activity, while inhibition of proteolytic and phospholipase A2 (PLA2) activities was achieved by three and one plant species, respectively. Only Brownea rosa-de-monte was able to effectively counteract the in vitro coagulant effect of the venom. Some plant extracts screened in Guatemala demonstrated procoagulant or anti-thrombin intrinsic effects that might aggravate the coagulopathy induced by the venom. These findings underscore the need of carrying out scientific studies aimed to validate the inhibitory potential of Central American plant extracts and their metabolites against B. asper venom.

Pocos estudios científicos han explorado el uso de plantas medicinales para el tratamiento del envenenamiento ofídico en Centroamérica, a pesar de que las terapias basadas en plantas son de uso tradicional en la región. Este trabajo recopiló información sobre los estudios realizados en Centroamérica para evaluar la capacidad de extractos de plantas de uso etno-médico para inhibir las actividades tóxicas del veneno de Bothrops asper, la serpiente responsable de aproximadamente la mitad de los envenenamientos ofídicos en Centroamérica. La búsqueda priorizó la descripción de plantas utilizadas en Gua-temala, ya que la mayoría de los estudios aquí descritos fueron realizados en ese país. También se incluyó la descripción de los metabolitos secundarios y otras actividades farmacológicas de las especies evaluadas, que podrían explicar su uso como antiofídicos. La búsqueda de literatura se realizó en las bases de datos de Google Scholar, PubMed, Scopus, y se completó con literatura disponible localmente. Se determinó que 12 extractos de plantas inhibieron el efecto hemorrágico del veneno y tres el efecto edematígeno; la actividad proteolítica fue inhibida por extractos de tres especies y la fosfolipasa A2 (PLA2) por una especie. Solamente Brownea rosa-de-monte demostró inhibir efectivamente el efecto coagulante del veneno in vitro. Algunos extractos de las plantas tamizadas en Guatemala demostraron efectos procoagulantes o anti-trombina intrínsecos, que podrían agravar las alteraciones inducidas por el veneno en la coagulación. Estos hallazgos enfatizan la necesidad de validar el potencial de extractos de plantas centroamericanas y sus metabolitos secundarios para neutralizar el veneno de B. asper.

Toxicological, enzymatic, and immunochemical characterization of Bothrops asper (Serpentes: Viperidae) reference venom from Panama / Caracterización toxicológica, enzimática e inmunoquímica del veneno de referencia de Bothrops asper (Serpentes: Viperidae) de Panamá

Introduction: It is estimated that 2 000 snakebites occur in Panama every year, 70 % of which are inflicted by Bothrops asper. Objective: To determine the biochemical and toxicologic effects and to assess the immunochemical characteristics of a reference pool of B. asper venom representative of Panama. Methods: The reference venom was prepared as a homogeneous mixture of the venoms obtained from 78 adult snakes collected in four geographic areas of Panama. Enzymatic and toxicological activities were assessed. The electrophoretic pattern was studied by SDS-PAGE. Immunoreactivity of various antivenoms was analyzed by Western blot. Results: B. asper reference venom has lethal, hemorrhagic, myotoxic, edema-forming, coagulant, defibrinating, proteinase and phospholipase A2 activities. SDS-PAGE showed the presence of protein bands with molecular weights ranging from 8 to 70 kDa, with the presence of predominant bands at ≈ 15 kDa and ≈ 30 to 66 kDa, which likely correspond to phospholipases A2 and metalloproteinases, respectively. Immunoblotting showed a high degree of recognition by various antivenoms, especially by antivenoms from Colombia and Costa Rica. Conclusions: Following recommendations by the World Health Organization, this reference venom of B. asper of Panama will become a useful tool for the preclinical evaluation of antivenoms distributed in this country.

Introducción: Se estima que 2 000 mordeduras de serpiente ocurren en Panamá cada año, el 70 % de las cuales son infligidas por Bothrops asper. Objetivo: Determinar los efectos bioquímicos y toxicológicos y evaluar las características inmunoquímicas del veneno de referencia de B. asper representativo de Panamá. Métodos: El veneno de referencia se preparó como una mezcla homogénea de los venenos obtenidos de 78 serpientes adultas recolectadas en cuatro áreas geográficas de Panamá. Se evaluaron las actividades enzimáticas y toxicológicas. El patrón electroforético se estudió mediante SDS-PAGE. La inmunoreactividad de varios antivenenos se analizó mediante transferencia de Western. Resultados: El veneno de referencia de B. asper tiene actividades letales, hemorrágicas, miotóxicas, formadoras de edema, coagulantes, desfibrinante, proteolítica y de fosfolipasa A2. El análisis de SDS-PAGE mostró la presencia de bandas de proteínas con pesos moleculares que varían de 8 a 70 kDa, con la presencia de bandas predominantes a ≈ 15 kDa y ≈ 30 a 66 kDa, que probablemente corresponden a fosfolipasas A2 y metaloproteinasas, respectivamente. La inmunotransferencia mostró un alto grado de reconocimiento por varios antivenenos, especialmente por antivenenos de Colombia y de Costa Rica. Conclusiones: Siguiendo las recomendaciones de la Organización Mundial de la Salud, este veneno de referencia de B. asper de Panamá se convertirá en una herramienta útil para la evaluación preclínica de antivenenos distribuidos en este país.

Inhibición de las actividades proteolítica y fosfolipasa A2 del veneno de Bothrops asper por el extracto etanólico de Neurolaena lobata (L) Cass / Inhibition of proteolytic and phospholipase A2 activities of Bothrops asper venom by the ethanolic extract of Neurolaena lobata (L) Cass

Neurolaena lobata es utilizada tradicionalmente en Centroamérica para tratar la mordedura de serpiente, pero su efectividad para contrarrestar el envenenamiento producido por Bothrops asper ha sido poco estudiada. Se evaluó la capacidad del extracto etanólico de sus hojas para inhibir las actividades proteolítica, fosfolipasa A2 (PLA2; evaluada como hemólisis indirecta) y coagulante del veneno in vitro. El material vegetal fue colectado en Izabal, Guatemala, secado, se hicieron extracciones con etanol y se evaluó la presencia de actividades proteolítica, PLA2 y coagulante in-trínsecas en ensayos de concentración-actividad. Los efectos inhibitorios de la actividad proteolítica y PLA2 del veneno se evaluaron después de pre-incubar concentraciones variables del extracto con concentraciones fijas de veneno. La inhibición de la actividad coagulante del veneno no fue evaluada porque el extracto presentó actividad anticoagulante intrínseca dependiente de la concentración. El extracto inhibió completamente las actividades proteolítica (CE50 = 15.7 µg/µl) y PLA2 (CE50 = 32.5 µg/µl) del veneno. El análisis fitoquímico utilizando ensayos macro y semimicrométricos de cromatografía en capa fina, demostró la presencia de flavonoides, cumarinas, saponinas, taninos, sesquiterpenlactonas y aceites esenciales en el extracto. Su efecto sobre las proteínas del veneno se evaluó por electroforesis SDS-PAGE, mostrando cambios en el patrón electroforético atribuidos a la formación de complejos moleculares con los metabo-litos del extracto. Los resultados indican que el extracto podría inhibir los efectos tóxicos del veneno inducidos por las metaloproteinasas dependientes de zinc (SVMPs) y PLA2s, pero podría afectar las alteraciones en la coagulación, coadyuvando en la desfibrinogenación inducida por el veneno.

Neurolaena lobata has been used by traditional healers in Central America to treat snakebite, but its ability to neutralize Bothrops asper envenomations needs to be proved. This study evaluated the inhibitory potential of the ethanolic extract of the leaves of N. lobata against proteolytic, phospholipase A2 (PLA2) and coagulant activities of the venom in vitro. Leaves were collected in Izabal, Guatemala, dried, extracted with ethanol and concentration-response assays were conducted to detect intrinsic proteolytic, PLA2 (evaluated as indirect hemolysis) and coagulant activities. Assays for anti-proteolytic and anti-PLA2 activities were performed after pre-incubation of several amounts of extract with a fixed concentration of venom. Inhibition assay for the coagulant effect of the venom was not tested because pre-incubation of thrombin with the extract prolonged the clotting time of plasma in a concentration-dependent manner. Proteolytic (EC50 = 15.7 µg/µl) and PLA2 (EC50 = 32.5 µg/µl) activities of the venom resulted completely inhibited by the extract. Phytochemical profiles, determined by micrometric assays and semi microanalysis by thin layer chro-matography, showed the presence of flavonoids, coumarins, saponins, tannins, sesquiterpene lactones and essential oils in the extract. SDS-PAGE was used to assess the action of the extract on the venom proteins. Results showed changes in the electrophoretic profile, probably due to the formation of insoluble complexes with plant specialized metabolites. These findings demonstrated that the extract could be able to inhibit toxic effects triggered by zinc-dependent snake venom metalloproteinases (SVMPs) y PLA2s but might aggravate the alterations induced by the venom in coagulation.

Avaliação do uso de soros antivenenos na emergência de um hospital público regional de Vitória da Conquista (BA), Brasil / Evaluation of the use of antivenom sera in the emergency service of a regional public hospital in Vitória da Conquista (BA), Brazil

Resumo O presente estudo tem como objetivo caracterizar o perfil epidemiológico de vítimas de acidentes escorpiônicos e ofídicos e avaliar a adequação das prescrições de soros antivenenos. Estudo transversal cujas fontes de dados foram as fichas de notificação de acidentes por animais peçonhentos do Sistema de Informação de Agravos de Notificação no município de Vitória da Conquista (BA), Brasil. Foram incluídas as informações de acidentes escorpiônicos ou ofídicos no período entre julho de 2016 e junho de 2017 atendidos no município. Os dados obtidos e as variáveis de interesse foram analisadas de acordo com as perguntas deste estudo. No período observado foram atendidas 293 vítimas de acidentes por animais peçonhentos. Destas, 149 (50,9%) foram homens e 114 (38,9%) possuíam entre 20 a 59 anos. Foram 235 (80,9%) casos de escorpionismo e 58 (19,1%) de ofidismo. Destes, 203 (69,3%) foram classificados como leves e em 200 (68,5%) casos foi prescrita soroterapia para estes pacientes. Quanto à adequação das prescrições, 172 (59,7%) foram julgadas inadequadas e destas, o uso de número de ampolas acima do indicado foi a mais frequente. A prescrição inapropriada de soros antivenenos ocorreu em aproximadamente em 60% dos casos avaliados. Apesar disso, a maioria dos acidentes foi classificada como leve, em homens jovens.

Abstract This study aims to characterize the epidemiological profile of victims of scorpion and snakebite envenomations and to evaluate the adequacy of antivenom sera prescriptions. This is a cross-sectional study whose data sources were the envenomation notification information sheets of the Notifiable Diseases Information System in the city of Vitória da Conquista (BA), Brazil. We included information on scorpion or snakebite envenomations attended in the municipality in the period between July 2016 and June 2017. The data obtained and the variables of interest were analyzed according to the questions of this study. In the observed period, 293 victims of envenomations were treated. Of these, 149 (50.9%) were men, and 114 (38.9%) were 20-59 years old. In total, 235 (80.9%) cases of scorpionism and 58 (19.1%) of ophidism were reported. Of these, 203 (69.3%) were classified as mild, and in 200 (68.5%) cases, serum therapy was prescribed for the patients. Regarding the adequacy of the prescriptions, 172 (59.7%) were considered inadequate, and of these, the use of some vials above than indicated was the most frequent. The inappropriate prescription of antivenom sera occurred in approximately 60% of the evaluated cases. Despite this, most accidents were classified as mild - in young men.

Envenenamientos por mordedura de serpiente en Guatemala: revisión de literatura / Snakebite envenomings in Guatemala: literature review

El accidente ofídico es una enfermedad tropical desatendida que ocasiona un problema de salud pública en el mundo, siendo una de las principales causas de morbilidad y mortalidad en las áreas empobrecidas de América Latina. En Guatemala se distribuyen 23 especies de serpientes venenosas de importancia médica. La composición de los venenos es compleja y diversa, resultando en una variedad de manifestaciones clínicas. Los departamentos con mayor incidencia de ofidismo son Petén, Alta Verapaz, Quiché, Escuintla e Izabal. Estos accidentes afectan más a hombres que a mujeres, siendo la mayoría agricultores; el rango de edad más comprometido es de 10-19 años y principalmente ocurren en miembros inferiores. El tiempo medio que tarda la víctima en llegar al hospital es de 5.6 h, siendo el retraso en la atención médica, un factor de riesgo para severidad y mortalidad. Los servicios de salud en ocasiones no cuentan con recursos idóneos para atender a las víctimas, brindando tratamiento sintomático. Simultáneamente, el tratamiento empírico tiene gran aceptación, sin embargo, los resultados de investigaciones realizadas con algunas plantas de uso común en casos de ofidismo, concluyeron que no es recomendable su uso aislado en el tratamiento del envenenamiento. Dada la falta de información se debe promover más investigación sobre el ofidismo en el país, siendo indispensable la elaboración de una ficha de reporte obligatoria. Además, deben elaborarse guías de tratamiento e identificación de serpientes para uso del personal médico, incluyendo programas de educación a nivel comunitario.

Snakebite envenoming is a neglected tropical disease that causes a public health problem in the world, being one of the main causes of morbidity and mortality in impoverished areas of Latin America. 23 species of poi-sonous snakes of medical importance are distributed in Guatemala. The composition of venoms is complex and diverse, resulting in a variety of clinical manifestations. The departments with the highest incidence of snakebites are Petén, Alta Verapaz, Quiché, Escuintla and Izabal. These accidents affect more men than women, the majo-rity being farmers; the most compromised age range is 10-19 years and they mainly occur in the lower limbs. The average time it takes for the victim to reach the hospital is 5.6 hours, with delay in medical care being a risk factor for severity and mortality. Health services sometimes do not have adequate resources to care for victims, providing symptomatic treatment. Simultaneously, empirical treatment is widely accepted, however, the results of research carried out with some plants commonly used in cases of envenoming concluded that their isolated use is not recommended in the treatment. Given the lack of information, more research on snakebite envenoming in the country should be promoted, making the preparation of a mandatory report form essential. In addition, snake identification and treatment guides should be developed for use by medical personnel, including education pro-grams at the community level.

Mordedura de Phalotris lemniscatus (Duméril, Bibron & Duméril, 1854) (Squamata, Dipsadidae) en Uruguay / Phalotris lemniscatus (Duméril, Bibron & Duméril, 1854) (Squamata, Dipsadidae) bites in Uruguay

Phalotris lemniscatus es la única especie representante del género Phalotris en Uruguay. Esta especie tiene una amplia distribución que incluye Uruguay, Rio Grande do Sul en Brasil y el norte de Argentina que se extiende a las áreas fronterizas con Bolivia y Paraguay. Aunque este ofidio no es agresivo, se registraron dos accidentes en Uruguay en los que se observó acción local y sistémica del veneno. Los mismos ocurrieron en las manos después de manipulación excesiva y prolongada de los ejemplares. Localmente presentaron edema leve, pero en términos sistémicos el veneno de Phalotris causó alteraciones en la coagulación. Los pacientes se recuperaron totalmente después de 3 días. Serán necesarios más estudios para establecer una terapia adecuada para los envenenamientos graves provocados por esta especie.

Phalotris lemniscatus is the only species representative of Phalotris genus in Uruguay. This species has a wide distribution that includes Uruguay, Rio Grande do Sul in Brazil and northern Argentina extending to the areas bordering Bolivia and Paraguay. Although this snake is not aggressive, there were two snakebite accidents in Uruguay. They occurred on the hands after excessive and prolonged handling of the specimens. Locally they showed mild edema, but in systemically Phalotris venom caused alterations in blood coagulation. The patients recovered completely after 3 days. More studies will be required to establish an adequate therapy for Phalotris severe envenomations.

Hemorrhagic stroke following viper bites and delayed antivenom administration: three case reports from the Western Brazilian Amazon

Abstract Snakebites were included by the World Health Organization in their list of neglected diseases. In Latin America, most snakebites are caused by species of the Viperidae family, notably by the genus Bothrops. Bothrops atrox accounts for 90% of the cases of envenoming in the Brazilian Amazon. In this report, we present a series of three cases of snakebites that evolved with hemorrhagic stroke due to delays in the access to antivenom in the Brazilian Amazon, being fundamental for diagnosis to validate the clinical suspicion and make decisions that would improve the treatment and prognosis of the patients.

Envenomation by an opisthoglyphous snake, Erythrolamprus aesculapii (Dipsadidae), in southeastern Brazil

Abstract Snakebites by aglyphous or opisthoglyphous snakes are common in Brazil. We report a case of snakebite by the opisthoglyphous Erythrolamprus aesculapii. The victim presented with pain, edema, and bleeding at the bite site, along with erythema, similar to a Bothrops envenomation. In this type of snakebite, if the snake is not brought to the hospital, the victim may receive unnecessary serum therapy, with the risk of adverse reactions to the antivenom. The possibility of reducing after-effects with anti-inflammatory drugs and early antibiotic therapy for secondary infection need to be further investigated, preferably in multicenter studies, while observing good clinical practice.

Epidemiological study of snakebite cases in Brazilian Western Amazonia

Abstract INTRODUCTION Brazil has the largest number of snakebite cases in South America, of which the large majority is concentrated in the Midwest and North. METHODS In this descriptive observational study, we assessed the epidemiological and clinical snakebite cases referred to the Centro de Medicina Tropical de Rondônia from September 2008 to September 2010. RESULTS We followed up 92 cases from admission until discharge, namely 81 (88%) men and 11 (12%) women, with a mean age of 37 years, and mainly from rural areas (91.3%). The snakebites occurred while performing work activities (63%) during the Amazon rainy season (78.3%). The vast majority of individuals presented from the Porto Velho microregion (84.7%). Approximately 95.6% of the snakebites were caused by snakes of the genus Bothrops, followed by two lachetics and two elapidics cases. Surgery was performed in 10 cases (9 fasciotomies in the lower limb and 1 amputation). No deaths were reported in this study, but 4 cases (4.3%) developed sequelae in the lower limb. CONCLUSIONS This study can contribute to a better understanding of envenomation in the state of Rondônia and thus can be useful for identifying real conditions that can increase the incidence of snakebites in this region. Moreover, the study results can serve as a basis for improving educational campaigns designed to prevent these types of snakebites, as well as for preserving snakes.

Preclinical efficacy against toxic activities of medically relevant Bothrops sp. (Serpentes: Viperidae) snake venoms by a polyspecific antivenom produced in Mexico / Eficacia de un antiveneno poliespecífico producido en México para neutralizar, a nivel preclínico, las actividades tóxicas de venenos de Bothrops sp (Serpentes: Viperidae) de importancia médica

Abstract:The assessment of the preclinical neutralizing ability of antivenoms in Latin America is necessary to determine their scope of efficacy. This study was aimed at analyzing the neutralizing efficacy of a polyspecific bothropic-crotalic antivenom manufactured by BIRMEX in Mexico against lethal, hemorrhagic, defibrinogenating and in vitro coagulant activities of the venoms of Bothrops jararaca (Brazil), B. atrox (Perú and Colombia), B. diporus (Argentina), B. mattogrossensis (Bolivia), and B. asper (Costa Rica). Standard laboratory tests to determine these activities were used. In agreement with previous studies with bothropic antivenoms in Latin America, a pattern of cross-neutralization of heterologous venoms was observed. However, the antivenom had low neutralizing potency against defibrinogenating effect of the venoms of B. atrox (Colombia) and B. asper (Costa Rica), and failed to neutralize the in vitro coagulant activity of the venom of B. asper (Costa Rica) at the highest antivenom/venom ratio tested. It is concluded that, with the exception of coagulant and defibrinogenating activities of B. asper (Costa Rica) venom, this antivenom neutralizes toxic effects of various Bothrops sp venoms. Future studies are necessary to assess the efficacy of this antivenom against other viperid venoms. Rev. Biol. Trop. 65 (1): 345-350. Epub 2017 March 01.

ResumenEs necesario estudiar a nivel preclínico la capacidad neutralizante de los antivenenos producidos en América Latina, para conocer su espectro de cobertura. En este estudio se analizó la eficacia preclínica de un antiveneno poliespecífico botrópico-crotálico producido por BIRMEX, en México, para neutralizar los efectos letal, hemorrágico, desfibrinogenante y coagulante in vitro de los venenos de Bothrops jararaca (Brasil), B. atrox (Perú y Colombia), B. diporus (Argentina), B. mattogrossensis (Bolivia) y B. asper (Costa Rica). Se emplearon metodologías de laboratorio estándar en los análisis. En consonancia con estudios anteriores con diversos antivenenos botrópicos en América Latina, se observó un amplio patrón de neutralización de estos venenos heterólogos en la mayoría de los efectos estudiados. Sin embargo, el antiveneno mostró una baja capacidad neutralizante contra el efecto desfibrinogenante de los venenos de B. atrox (Colombia) y B. asper (Costa Rica) y no neutralizó la actividad coagulante in vitro del veneno de B. asper (Costa Rica) a la máxima razón antiveneno/ veneno empleada.

Snakebite cases in the municipalities of the State of Paraiba, Brazil

Introduction This study investigated the epidemiological and clinical profile of snakebite cases reported from 2007 to 2012 in the municipalities of the Curimataú region, State of Paraíba, in northeastern Brazil. Methods Data were collected from the Health Department of the State of Paraíba using the Injury Notification Information System data banks of the Health Ministry. Results A total of 304 snakebite cases were studied. The cases occurred most frequently from April to June. The genera Bothrops, Crotalus, and Micrurus were responsible for 74.6%, 6.2%, and 1.3% of cases, respectively. Snakebite cases predominated in males living in rural areas and between 10 and 19 years old. The highest incidence of bites occurred on the feet. The majority of the victims received medical assistance within 1 to 3h after being bitten. With regard to severity, 48% of the cases were classified as mild, 26% as moderate, and 2.6% as severe. Successful cures predominated, and no deaths were reported. The average antivenom ampoule dose used for the treatment in some snakebite cases was lower than that recommended by the Health Ministry. Conclusions Although our results show that Paraíba has a good level of medical care, there are serious deficiencies in recording snakebite information. These data indicate the need to improve the recording process for snakebite cases. Further training for health professionals seems to be necessary to optimize their skills in treating snakebite victims. .

Efecto inhibitorio de extractos de Renealmia alpinia Rottb. Maas (Zingiberaceae) sobre el veneno de Bothrops asper (mapaná) / Evaluation of the inhibitory effect of extracts from leaves of Renealmia alpinia Rottb. Maas (Zingiberaceae) on the venom of Bothrops asper (mapaná)

Introducción. La medicina tradicional es una invaluable fuente de investigación de nuevos remedios como complemento para el tratamiento del accidente ofídico, considerado como un grave problema de salud pública a nivel mundial. Objetivo. Este trabajo de investigación pretende comprobar la capacidad de neutralizar los efectos hemorrágicos, coagulantes y proteolíticos, de los extractos de hojas de Renealmia alpinia, usada tradicionalmente por los indígenas del Chocó (Colombia) contra la mordedura de la serpiente Bothrops asper, causante de la gran mayoría de los accidentes ofídicos en nuestro país. Materiales y métodos. Se llevaron a cabo ensayos de toxicidad aguda y de actividad analgésica in vivo de R. alpinia. Además, se hicieron ensayos in vitro sobre inhibición de las actividades coagulante, hemolítica y proteolítica del veneno de B. asper. Resultados. El presente estudio demuestra que R. alpinia no produce efectos tóxicos en animales de experimentación; además, presenta efectos analgésicos in vivo y antiofídicos in vitro,y protege contra los efectos letales del veneno de B. asper, in vivo. Conclusión. Renealmia alpinia puede ser una buena alternativa terapéutica como complemento al tratamiento con antiveneno en el accidente ofídico, por sus efectos analgésicos y antiofídicos.

Introduction. Traditional medicine is an invaluable source of research into new medicines as a supplement for the treatment of snakebite, considered as a serious public health problem worldwide. The extracts of the medicinal plant, Renealmia alpina, have been used traditionally by indigenous people of Chocó (Colombia) against Bothrops asper snakebite, a snake responsible for the majority of snakebite accidents in Colombia. Objective. The ability of extracts of R. alpinia leaves was tested for its ability to neutralize the hemorrhagic, coagulant and proteolytic effects of the snakebite venom of B. asper. Materials and methods. The acute toxicity tests and analgesic activity of R. alpina were evaluated in vivo. In addition, tests were undertaken in in vitro conditions to demonstrate inhibition of coagulant, haemolytic and proteolytic activity of the B. asper venom. Results. Renealmia alpinia extracts had no toxic effects in experimental animals and also provided analgesic and antiophidian effects and protection against the lethal effects of the venom of B. asper. Conclusion. Renealmia. alpinia was an effective therapeutic alternative in association with antivenom treatment in the event of a B. asper snakebite accident. It was demonstrated to protect against the lethal effects and provided analgesic properties as well.

Venenos de serpiente: de la investigación al tratamiento / Snake venoms: from research to treatment

El presente trabajo ofrece una breve visión de cómo se ha enfrentado el problema del ofidismo en Costa Rica, y en especial, de cómo la investigación científica y tecnológica ha contribuido a tal fin. Se resumen los orígenes de la lucha antiofídica en el país y de la creación del Instituto Clodomiro Picado en la Universidad de Costa Rica, en 1970. Se describen las primeras etapas de su labor y la evolución de distintas líneas de investigación sobre serpientes, venenos y antivenenos, que por espacio de cuatro décadas han contribuido a que en el país y en la región centroamericana, existan recursos terapéuticos adecuados y suficientes para enfrentar el ofidismo.

Accidents caused by Bothrops and Bothropoides in the State of Paraiba: epidemiological and clinical aspects / Acidentes causados por serpentes dos gêneros Bothrops e Bothropoides no Estado da Paraíba: aspectos clínicos e epidemiológicos

INTRODUCTION: Bothrops and Bothropoides snakes cause 70 percent of the ophidic accidents in Brazil. The species that cause ophidic accidents in State of Paraíba are Bothropoides erythromelas, Bothrops leucurus and Bothropoides neuwiedi. METHODS: This is a prospective and transverse study, following a quantitative approach of accidents involving Bothrops and Bothropoides admitted to the Toxicological Assistance and Information Centers of Campina Grande and João Pessoa (Ceatox-CG and Ceatox-JP), aimed at identifying the epidemiological and clinical profile of such accidents. All of the patients admitted had medical diagnoses and were monitored at Ceatox-CG or Ceatox-JP. RESULTS: The genera Bothrops and Bothropoides caused 91.7 percent of the ophidic accidents reported. Snake bites were frequent in men (75.1 percent), rural workers (65.1 percent), literate individuals (69 percent) between 11 and 20 years-old (21.7 percent), and toes the most common area attacked (52.7 percent). Most (86.6 percent) patients were admitted within 6 hours after the accident/bite, with a predominance of mild cases (64.6 percent). The annual occurrence in Paraíba was 5.5 accidents/100,000 inhabitants and lethality was 0.2 percent. CONCLUSIONS: Positive changes in the profiles of these accidents were verified, such as the non-application of inadequate solutions, including the use of tourniquet, coffee grounds, garlic, suction and/or cutting the bitten area. Moreover, the Itinerant Laboratory project, linked to Paraíba State University in partnership with Ceatox-CG, has contributed positively, providing several cities of the state with information regarding the prevention of accidents involving venomous animals. The local press has also contributed, reporting the educational work developed by the centers.

INTRODUÇÃO: As serpentes Bothrops e Bothropoides são responsáveis por 70 por cento dos acidentes ofídicos ocorridos no Brasil. As espécies causadoras de acidentes na Paraíba são Bothropoides erythromelas, Bothrops leucurus e Bothropoides neuwiedi. MÉTODOS: Tratou-se de um estudo prospectivo e transversal, com abordagem quantitativa dos acidentes botrópicos e botropóidicos atendidos e registrados pelos Centros de Assistência e Informação Toxicológica de Campina Grande e João Pessoa (Ceatox-CG e Ceatox-JP), com o objetivo de conhecer o perfil epidemiológico e clínico deste agravo. Todos os pacientes atendidos tiveram diagnóstico médico e acompanhamento pelos Ceatox CG e JP. RESULTADOS: Os gêneros Bothrops e Bothropoides foram responsáveis por 91,7 por cento dos acidentes ofídicos notificados. Atingindo frequentemente o sexo masculino (75,1 por cento), trabalhadores rurais (65,1 por cento), alfabetizados (69 por cento) e na faixa etária entre 11 a 20 anos (21,7 por cento), os dedos dos pés foram as regiões anatômicas mais acometidas (52,7 por cento). A maioria (86,6 por cento) dos pacientes foi atendida em até 6 horas após o acidente/picada com predominância de casos leves (64,6 por cento). A incidência anual no estado foi 5,5 acidentes/100.000 habitantes e a letalidade 0,2 por cento. CONCLUSÕES: Verificaram-se mudanças positivas no perfil desses acidentes, como a não utilização de medidas consideradas inadequadas (uso de torniquetes, borra de café, alho, incisão com sucção e outras). Além disso, o projeto Laboratório Itinerante, ligado a Universidade Estadual da Paraíba em parceria com o Ceatox-CG, tem contribuído positivamente, levando a várias cidades do estado informações sobre prevenção e tratamento dos acidentes causados por animais peçonhentos. A imprensa local também tem contribuído, divulgando esse trabalho educativo.

Humoral immune response of patients bitten by the snake Bothrops erythromelas / Resposta imune humoral em pacientes picados pela serpente Bothrops erythromelas

INTRODUCTION: Snake envenomings are a health problem in rural areas of tropical and subtropical countries, but little is known regarding the immune response presented by bitten individuals. The IgM production of patients bitten by Bothrops erythromelas snake was analyzed to identify the effectiveness of treatment in this type of envenomation. METHODS: Bothrops erythromelas venom was submitted to electrophoresis and transferred to a nitrocellulose sheet, following incubation with patients' sera. RESULTS: A 38 KDa protein was detected before and 24 h after therapy. CONCLUSIONS: The result suggests that this protein could be used as a marker for individuals envenomed by Bothrops. erythromelas.

INTRODUÇÃO: Envenenamentos ofídicos consistem problema de saúde pública em áreas rurais de países tropicais e subtropicais, mas pouco sabe-se sobre a resposta imune apresentada pelos indivíduos picados, por isso a avaliação da produção de IgM por pacientes picados por Bothrops erythromelas identificando a eficácia do tratamento nesse tipo de envenenamento. MÉTODOS: O veneno de Bothrops erythromelas foi submetido a eletroforese e transferido para nitrocelulose, seguindo incubação com soro de pacientes. RESULTADOS: Foi observada proteína de 38KDa antes e 24 horas após o tratamento. CONCLUSÕES: Os resultados sugerem que essa proteína poderia ser utilizada como marcador para indivíduos envenenados pela serpente Bothrops erythromelas.

Perfil epidemilógico dos acidentes causados por serpentes venenosas no norte do estado de Minas Gerais, Brasil / Epidemiological profile of accidents caused by venomous snakes in the northern part of the state of Minas Gerais, Brasil

Introdução: os acidentes causados por serpentes venenosas são importante problema de saúde pública devido à sua elevada morbimortalidade. Objetivo: descrever o perfil epidemiológico dos acidentes ofídicos causados por serpentes venenosas no nortedo estado de Minas Gerais. Métodos: foram analisadas informações sobre acidentes ofídicos relativas ao período compreendido entre janeiro de 2002 e dezembro de 2006, por meio de dados obtidos dos bancos SINAN WINDOWS e SINAN NET. Resultados: foram notificados 816 casos; 695 (85%) devidos às serpentes do gênero Bothrops; 334(41%) no primeiro trimestre; 593 (73%) na região de Montes Claros; 701 (86%) na zona rural; 328 (40%) picadas nos pés; 695 (85%) receberam soroterapia; 297 (36%) demoraram uma a três horas, em média, após o acidente, para receberam tratamento; e em 681 (83%) a cicatrização da ferida não apresentou sequelas. Conclusões: os dadosclínico-epidemiológicos permitem reconhecer vários aspectos que possibilitam atitudes médicas de prevenção e abordagem terapêutica adequada ao acidente ofídico no norte de Minas Gerais.

Introduction: the casualties related to venomous snakes are important public health issue due to its high morbidity and mortality. Objective: to describe the epidemiological profile of the casualties due to venomous snakes in the northern part of the State of Minas Gerais. Methods: information about snakebites casualties in the period between January 2002 and December 2006 were analyzed, through database from SINAN WINDOWS and SINAN NET. Results: 816 cases were reported; 695 (85%) due to snakes of the kind Bothrops; 334 (41%) in the first quarter of the year; 593 (73%) in the region of Montes Claros; 701 (86%) in the countryside; 328 (40%) bites on the feet; 695 (85%) received sorotherapy; 297 (36%) took one to three hours on average to receive treatment, and in 681 (83%) wound healing showed no sequels. Conclusions: clinic-epidemiological data allow the recognition of various aspects that enable preventive medical attitudes and appropriate therapeutic approach to snakebite in northern Minas Gerais.

Epidemiology of cobra bite in Manipal, Southern India.

Envenomation by poisonous snakes is considered as an occupational hazard. Cobra bite is commonly encountered in the South Asian countries. The prospective research was conducted in the Department of Forensic Medicine, Kasturba Medical College, Manipal to study the epidemiology, manifestations and treatment of cobra snakebite cases admitted to Kasturba Hospital, Manipal during August 2003 and November 2005. Twenty cases of cobra bite were reported during the study period. The victims of cobra bite predominantly were females. Mean age of victims was 41.9 years. Maximum cases occurred during the summer and pre-monsoon months, during daytime and involved the upper limbs. Ptosis was the chief neurotoxic feature followed by dysarthria. Cellulitis as a complication was observed in most of the cases. Polyvalent Anti Snake Venom (ASV) vials were used as specific treatment. No mortality was reported during the study period.