Inhibitors and activators for myotoxic phospholipase A2-like toxins from snake venoms - A structural overview.

Snakebite envenomations result in acute and chronic physical and psychological health effects on their victims, leading to a substantial socio-economic burden in tropical and subtropical countries. Local necrosis is one of the serious effects caused by envenomation, primarily induced by snake venoms from the Viperidae family through the direct action of components collectively denominated as myotoxins, including the phopholipase A2-like (PLA2-like) toxins. Considering the limitations of antivenoms in preventing the rapid development of local tissue damage caused by envenomation, the use of small molecule therapeutics has been suggested as potential first-aid treatments or as adjuvants to antivenom therapy. In this review, we provide an overview of the structural interactions of molecules exhibiting inhibitory activity toward PLA2-like toxins. Additionally, we discuss the implications for the myotoxic mechanism of PLA2-like toxins and the molecules involved in their activation, highlighting key differences between activators and inhibitors. Finally, we integrate all these results to propose a classification of inhibitors into three different classes and five sub-classes. Taking into account the structural and affinity information, we compare the different inhibitors/ligands to gain a deeper understanding of the structural basis for the effective inhibition of PLA2-like toxins. By offering these insights, we aim to contribute to the search for new and efficient inhibitor molecules to complement and improve current therapy by conventional antivenoms.

Identification of purinergic system components in the venom of Bothrops mattogrossensis and the inhibitory effect of specioside extracted from Tabebuia aurea.

Snake bites are a severe problem in the countryside of Brazil and are usually attributed to snakes of the genera Bothrops, Crotalus, and Lachesis. Snake venom can release ectoenzymes and nucleotidases that modulate the purinergic system. In addition to serum therapy against snake poisoning, medicinal plants with anti-inflammatory activities, such as Tabebuia aurea, is empirically applied in accidents that occur in difficult-to-access areas. This study aimed was to verify the presence and activity of nucleotidases in the crude venom of Bothrops mattogrossensis (BmtV) in vitro and characterize the modulation of purinergic components, myeloid differentiation, and inflammatory/oxidative stress markers by BmtV in vivo and in vitro. Moreover, our study assessed the inhibitory activities of specioside, an iridoid isolated from Tabebuia aurea, against the effects of BmtV. Proteomic analysis of venom content and nucleotidase activity confirm the presence of ectonucleotidase-like enzymes in BmtV. In in vivo experiments, BmtV altered purinergic component expression (P2X7 receptor, CD39 and CD73), increased neutrophil numbers in peripheral blood, and elevated oxidative stress/inflammatory parameters such as lipid peroxidation and myeloperoxidase activity. BmtV also decreased viability and increased spreading index and phagocytic activity on macrophages. Specioside inhibited nucleotidase activity, restored neutrophil numbers, and mediate the oxidative/inflammatory effects produced by BmtV. We highlight the effects produced by BmtV in purinergic system components, myeloid differentiation, and inflammatory/oxidative stress parameters, while specioside reduced the main BmtV-dependent effects.

Scorpion-Induced Acute Coronary Syndrome: A Stinging Complication.

The Tityus trinitatis, a black scorpion species endemic to the fauna of Trinidad, has been implicated in envenomation with devastating clinical sequelae such as acute pancreatitis and major adverse cardiovascular events. We present the first in-Caribbean case of a 59-year-old Caribbean South Asian male with human immunodeficiency virus who presented with a non-ST-segment-elevation acute coronary syndrome after being stung, which was managed with comprehensive, guideline-directed medical therapy. The clinician should be cognizant of scorpion-induced acute coronary syndrome (ACS) as a potential sequela of envenomation and its clinical management.

Long-term disability after cerebral ischemic stroke following a Bothrops atrox snakebite in the Brazilian Amazon.

Bothrops atrox envenomations in the Brazilian Amazon are responsible for a number of local and systemic effects. Among these, stroke presents the worst prognosis for the patient since it may evolve into disabilities and/or premature death. This complication is caused by coagulation disorders and generates hemorrhagic and thrombotic conditions. This study presents a case report of a 54-year-old female patient who presented extensive cerebral ischemia after a B. atrox envenomation that occurred in the state of Amazonas, Brazil. The patient was hospitalized for 102 days, which included a stay in the intensive care unit. Clinical and laboratory findings indicated a thrombogenic coagulopathy. On discharge, the patient had no verbal response, partial motor response, and right hemiplegia. The assessment carried out four years after discharge evidenced incapacitation, global aphasia and bilateral lower and upper limbs showed hypotrophy with a global decrease in strength. Ischemic stroke is a possible complication of B. atrox snakebites even after antivenom treatment, with the potential to cause debilitating long-term consequences.

Clinical outcomes in a murine model after envenoming by the Amazonian scorpions Tityus strandi and Tityus dinizi.

The Brazilian Amazon is home to a rich fauna of scorpion species of medical importance, some of them still poorly characterized regarding their biological actions and range of clinical symptoms after envenoming. The Amazonian scorpion species Tityus strandi and Tityus dinizi constitute some of the scorpions in this group, with few studies in the literature regarding their systemic repercussions. In the present study, we characterized the clinical, inflammatory, and histopathological manifestations of T. strandi and T. dinizi envenoming in a murine model using Balb/c mice. The results show a robust clinical response based on clinical score, hyperglycemia, leukocytosis, increased cytokines, and histopathological changes in the kidneys and lungs. Tityus strandi envenomed mice presented more prominent clinical manifestations when compared to Tityus dinizi, pointing to the relevance of this species in the medical scenario, with both species inducing hyperglycemia, leukocytosis, increased cytokine production in the peritoneal lavage, increased inflammatory infiltrate in the lungs, and acute tubular necrosis after T. strandi envenoming. The results presented in this research can help to understand the systemic manifestations of scorpion accidents in humans caused by the target species of the study and point out therapeutic strategies in cases of scorpionism in remote regions of the Amazon.

Potential Biotechnological Applications of Venoms from the Viperidae Family in Central America for Thrombosis.

Central America is home to one of the most abundant herpetofauna in the Americas, occupying only 7% of the continent's total area. Vipers and lizards are among the most relevant venomous animals in medical practice due to the consequences of envenomation from the bite of these animals. A great diversity of biomolecules with immense therapeutic and biotechnological value is contained in their venom. This paper describes the prominent leading representatives of the family Viperidae, emphasizing their morphology, distribution, habitat, feeding, and venom composition, as well as the biotechnological application of some isolated components from the venom of the animals from these families, focusing on molecules with potential anti-thrombotic action. We present the leading protein families that interfere with blood clotting, platelet activity, or the endothelium pro-thrombotic profile. In conclusion, Central America is an endemic region of venomous animals that can provide many molecules for biotechnological applications.

Fatal Africanized bee attack in captive non-human primates (Saimiri ustus and Sapajus libidinosus).

Bee stings (BS) are a life-threatening issue and a growing concern for public health and animals in the Americas. We describe the clinical, pathological, and ultrastructural findings of a massive lethal bee attack in two non-human primates (NHPs). Both animals showed BS scattered throughout the skin, surrounded by a local reaction, diffuse pulmonary congestion, edema, hemorrhage, and remarkable degeneration and necrosis of renal epithelial cells from the proximal and distal tubules, characterizing a systemic bee envenomation reaction.

Scorpion sting envenomation outbreak in Mexico. Strategies for prevention and control.

In Mexico occurs 25% of all worldwide cases of scorpion sting envenomation (SSE). An outbreak of SSE was identified in Villa Unión, Sinaloa, Mexico. The objective of this study is to describe the outbreak, and prevention and control strategies implemented. The design was a cross-sectional study. Eligibility criteria included confirmed cases (n = 425) identified from the date the outbreak was recognized (from November 08, 2023 to July 10, 2023). The cases from Villa Unión (n = 231) were included for the analysis of epidemiological and clinical findings. The research followed the recommendations of the Initiative Reporting of studies Conducted Using Observational Routinely collected Data (RECORD). Of the total cases (n = 425), 398 (93.6%) were from the municipality of Mazatlán, and 231 (58%) were from Villa Unión. The incidence rate was 13.64 per 1000 persons. The average cases per week was 51.5(SD ± 12). The male-to-female ratio was 3:4, the average age was 30.7(SD ± 19) years. Most of cases occurred in the 25-44 age group. The sting occurred mostly inside houses (n = 200, 86.5%). The predominant symptoms were local pain (95.2%), and local paresthesia (75.8%). The Case fatality rate was 0%. Implementation of prevention and control strategies based on field epidemiological research and scientific evidence are necessary to reduce the incidence and prevent fatal complications.

Hemoperitoneum after a Bothrops snakebite: Case report.

Snakebites are frequent in tropical countries. Brazil has an average of 27,000 cases per year, with a fatality rate of 0.5%, and the Bothrops genus is the most common causative agent, accounting for about 70-90% of the accidents. This report describes a case of human envenomation by a juvenile Bothrops jararaca snake in São Paulo, Brazil, in a 71 years-old man, previously healthy. He presented a life-threatening envenomation, which developed to severe hypotension, acute kidney injury and extensive peritoneal hemorrhage. The hemoperitoneum was diagnosed due to persistent hypotension associated with anemia, pain and gastrointestinal complaints. Abdominal Computed Tomography scans showed a moderate to large amount of presumable hematic material inside the abdominal cavity, predominantly in the perihepatic and perisplenic spaces. The intra-abdominal hemorrhage was not surgically addressed, and the patient was discharged 5 days after hospitalization, with the progressive absorption of the hemoperitoneum. Systemic bleeding is one of the complications and main causes of death in Bothrops envenomations. Acute peritoneal hemorrhage is one of these serious complications that must be carefully addressed since its management must take into account the risk of bleeding caused by toxins that affect hemostasis. The case described highlights the importance of early diagnosis and adequate management of this potentially fatal complication in snakebites.

First case of envenomation in humans caused by the banded cat-eyed snake Leptodeira annulata (Linnaeus, 1758) (Squamata: Dipsadidae) in Brazil

ABSTRACT A 22-year-old female researcher was bitten by a Leptodeira annulata on the index finger of the left hand during a contention activity. After removing the snake, a little bleeding and redness was observed in the bite region, accompanied by fang marks. Thirty minutes later, edema had progressed to the dorsum of the hand. After four hours, edema persisted, but the bitten area was slightly whitened. Treatment consisted of antibiotics and anti-inflammatory drugs. The edema resolved completely and disappeared after 48 hours. Overall, this report presents the first case of envenomation in humans caused by Leptodeira annulata in Brazil.

Identification of purinergic system components in the venom of Bothrops mattogrossensis and the inhibitory effect of specioside extracted from Tabebuia aurea

Snake bites are a severe problem in the countryside of Brazil and are usually attributed to snakes of the genera Bothrops, Crotalus, and Lachesis. Snake venom can release ectoenzymes and nucleotidases that modulate the purinergic system. In addition to serum therapy against snake poisoning, medicinal plants with anti-infammatory activities, such as Tabebuia aurea, is empirically applied in accidents that occur in difcult-to-access areas. This study aimed was to verify the presence and activity of nucleotidases in the crude venom of Bothrops mattogrossensis (BmtV) in vitro and characterize the modulation of purinergic components, myeloid diferentiation, and infammatory/oxidative stress markers by BmtV in vivo and in vitro. Moreover, our study assessed the inhibitory activities of specioside, an iridoid isolated from Tabebuia aurea, against the efects of BmtV. Proteomic analysis of venom content and nucleotidase activity confrm the presence of ectonucleotidase-like enzymes in BmtV. In in vivo experiments, BmtV altered purinergic component expression (P2X7 receptor, CD39 and CD73), increased neutrophil numbers in peripheral blood, and elevated oxidative stress/infammatory parameters such as lipid peroxidation and myeloperoxidase activity. BmtV also decreased viability and increased spreading index and phagocytic activity on macrophages. Specioside inhibited nucleotidase activity, restored neutrophil numbers, and mediate the oxidative/infammatory efects produced by BmtV. We highlight the efects produced by BmtV in purinergic system components, myeloid diferentiation, and infammatory/oxidative stress parameters, while specioside reduced the main BmtV-dependent efects.

Peixes peçonhentos da bacia hidrográfica do Rio Paraná: aspectos ecológicos e toxinológicos de interesse em saúde

Aquatic ecosystems have a vast diversity of fauna and flora associated with them. Notably, rivers are of great social, economic, and environmental importance. The Paraná River basin comprises a river system used for energy production, recreation, production and consumption of fish resources. In addition, there is a record of a diverse fauna of venomous fish in this region which, due to their close proximity to the population, results in accidents known as ichthyism. Although these accidents are not lethal, they have a high morbidity rate and serious occupational consequences. Their main symptoms are intense pain, edema, and slow- healing lesions that can result in tissue necrosis. Albeit frequent, these accidents are underreported, making it difficult to map and treat them. Therefore, the aim of this study is to expand the knowledge about venomous fish by characterizing the venomous species found in the Paraná River with the potential to cause accidents. The venom and mucus samples were collected by the Taxonomy of Venomous Animals Laboratory - Toxicological Information and Assistance Center of Paraná and sent to the Immunoregulation Unit of the Applied Toxinology Laboratory of the Butantan Institute for analysis. The venoms were extracted by scraping the epithelium covering the spines and stingers and scraping the mucus covering the animal's body, and the supernatant was obtained by centrifugation. Proteins were quantified using the Bradford method and the protein profile was analyzed using polyacrylamide gel electrophoresis. A total of 133 individuals were collected, distributed among 19 species and 6 families (Auchenipteridae, Doradidae, Loricariidae, Pimelodidae, Cichlidae, and Myliobatiformes). The Pimelodidae family presented the highest species richness, with seven species in total. In addition, seven species collected occur outside their natural distribution area, with Pterodoras granulosus being the most abundant among all the samplings. The Auchenipteridae and Pimelodidae families have similar protein profiles, notably at 68, 38, 28, and 14 kDa in the stinger samples, although they vary for mucus. The Doradidae family, despite having two species from the same family (Pterodoras granulosus and Oxydoras kneri), did not show similarities in the protein pattern. The Cichlidae, with two families, showed only two similar bands (62 and 38 kDa). The expansion of venomous fish habitats can occur due to hydrological and limnological changes, such as river damming. Although it was expected that individuals from the same family would present similar protein profiles, this was not verified in the samples analyzed, suggesting greater diversity in the composition and types of venom. This work is the first endeavor towards notification and biochemical knowledge about fish species with the potential to cause accidents in the Paraná River basin and provides a better understanding of the ecological and toxicological characteristics of these animals.

Ecossistemas aquáticos possuem vasta diversidade associada, apresentando alto grau de importância social, econômica e ambiental, e os ambientes fluviais contemplam diversos animais e espécies vegetais que usufruem e dependem de suas propriedades para a sobrevivência, apresentando assim alto grau de endemismo. A bacia do Rio Paraná compreende um grande sistema fluvial utilizado para recreação, produção e consumo de recursos pesqueiros e produção de energia por uma das principais hidrelétricas do país, Itaipu Binacional. Devido às suas particularidades, a bacia do Rio Paraná possui registros de uma grande diversidade da fauna de peixes peçonhentos que, por estar em áreas próximas à população, resulta em acidentes denominados de ictismo. Essas ocorrências, apesar de apresentarem baixa letalidade, têm alta morbidade e sérias consequências ocupacionais, cujos principais sintomas são dor intensa, edema e lesões de lenta cicatrização que podem resultar em necrose tecidual da região afetada. Apesar de frequentes, tais acidentes são subnotificados, dificultando seu mapeamento e tratamento. Assim, o objetivo deste trabalho foi expandir o conhecimento sobre peixes peçonhentos, através da caracterização das espécies peçonhentas encontradas no Rio Paraná com potencial de causarem acidentes. As amostras de peçonha e muco foram coletadas pelo Laboratório de Taxonomia de Animais Peçonhentos - Centro de Informações e Assistência Toxicológica do Paraná e encaminhadas à Unidade de Imunorregulação do Laboratório de Toxinologia Aplicada do Instituto Butantan para análise. A extração das peçonhas ocorreu por raspado do epitélio que recobre espinhos e ferrões e raspado do muco que recobre o corpo do animal, obtendo-se sobrenadante através de centrifugação. A quantificação de proteínas se deu pelo método de Bradford e o perfil eletroforético foi analisado através de eletroforese em gel de poliacrilamida. Ao todo foram coletados 133 indivíduos, distribuídos em 19 espécies e 6 famílias (Auchenipteridae, Doradidae, Loricariidae, Pimelodidae, Cichlidae e Myliobatiformes). A família Pimelodidae apresentou maior riqueza com sete espécies ao todo. Além disso, sete espécies capturadas ocorrem fora de sua área de distribuição natural, sendo Pterodoras granulosus a mais abundante entre a soma de todas as coletas. As famílias Auchenipteridae e Pimelodidae possuem semelhanças no perfil de proteínas, notadamente em 68, 38, 28 e 14 kDa, nas amostras de espinhos, embora variando para muco. A família Doradidae, apesar de possuir duas espécies de mesma família (Pterodoras granulosus e Oxydoras kneri), não apresentou semelhanças no padrão de proteínas. Os Cichlidae, com duas famílias, apresentaram apenas duas bandas semelhantes (62 e 38 kDa). A expansão de habitats dos peixes peçonhentos pode ocorrer por alterações hidrológicas e limnológicas, como o represamento do rio. Apesar de esperado que indivíduos de mesma família apresentassem perfis proteicos semelhantes, isso não foi verificado, sugerindo maior diversidade de quantidades e tipos de peçonha. Este trabalho é o primeiro passo para a notificação e conhecimento bioquímico sobre as espécies de peixes com potencial de causarem acidentes e possibilita o maior entendimento acerca das características ecológicas e toxicológicas desses animais.

Lesiones por Raya de Río: Acerca de tres casos en el Río de la Plata, Argentina / Injuries caused by River Stingrays:About three cases in the Río de la Plata ("River Plate") river, Argentina

Resumen Las rayas del género Potamotrygon son peces con forma dorsoventral aplanada. Son animales tranquilos, que solo atacan al ser agredidos o amenazados. Poseen en su cola estructuras punzantes, conocidas como espinas, envueltas por una vaina tegumentaria con tejidos secretores de componentes tóxicos. Suelen permanecer quietos en aguas superficiales, ocultos bajo arena o barro, lo que facilita su contacto accidental con humanos, con la probable generación de lesiones, al utilizar su cola hacia arriba y adelante en forma de látigo. Las lesiones son más frecuentes en hombres, en los meses estivales y en los miembros inferiores, seguidos por los miembros superiores. La lesión se asocia a dolor urente, casi inmediato y de gran intensidad, por el efecto traumático generado por las espinas, la persistencia de las mismas o sus fragmentos y por el efecto químico generado por sus toxinas. En ocasiones se asocia a la formación de necrosis y úlceras profundas o reacción granulomatosa por cuerpo extraño, con requerimientos de desbridamiento quirúrgico. Las lesiones fatales son infrecuentes y pueden resultar de una lesión torácica penetrante, laceraciones cervicales, compromiso de vía aérea, heridas vasculares o infecciones. Se deben realizar estudios de imágenes para evidenciar restos de la espina. La herida debe ser higienizada y se debe retirar la espina o sus fragmentos a la brevedad y sumergir el área lesionada en agua tan caliente como el paciente pueda tolerar, por 30 a 90 minutos, buscando disminuir el dolor y generar vasodilatación, junto con la analgesia y cobertura antibiótica y antitetánica. Se presentan tres casos de pacientes con lesiones por raya de río, dos de ellos por Potamotrygon brachyura, especie endémica del río de La Plata y el tercero por una raya no identificada. Se expone además una revisión bibliográfica a fin de remarcar la importancia de su diagnóstico temprano y su correcto abordaje.

Abstract The rays of the Potamotrygon genus are fish with a dorsoventrally flattened shape. They are calm animals that only attack when are provoked or threatened. They have sharp structures in their tail, known as spines, wrapped by a tegumentary sheath with tissues that secrete toxic components. They typically remain still in shallow waters, concealed under sand or mud, which increases accidental human contact. This contact can lead to injuries, as they whip their tail upwards and forwards. Injuries are more common in males during summer months, often affecting lower limbs followed by upper limbs. Injuries are characterized by immediate intense burning pain due to trauma from the spine or its fragments and chemical effects from its toxins. Occasionally, injuries lead to necrosis, deep ulcers, or foreign body granulomatous reactions requiring surgical debridement. Fatal injuries are rare but can result from thoracic penetration, cervical lacerations, airway compromise, vascular wounds, or infections. Imaging studies are necessary to detect spine remnants. Wounds should be cleaned, and spines or fragments removed promptly. The affected area should be immersed in water, as hot as tolerable for 30 to 90 minutes to reduce pain, induce vasodilation, and must supplemented with analgesia, antibiotic coverage, and tetanus prophylaxis. Three cases of river stingray injuries are presented, two from Potamotrygon brachyura, an endemic species of the Rio de la Plata river, and one from an unidentified ray. Additionally, a literature review emphasizes the importance of early diagnosis and proper management.

Scorpion Stings in Minas Gerais (Brazil): A Monocentric Retrospective Study Evaluating All Envenoming Cases of Local Scorpionism.

INTRODUCTION: We aim to provide better insights into the demographic, epidemiological, and seasonal characteristics of scorpion envenomation reported in the Rio Doce Valley, Brazil. METHODS: We conducted this monocentric retrospective descriptive study with data on Investigation Forms of Accidents by Venomous Animals, only envenoming cases of scorpion stings, between January 1, 2017 and December 31, 2020, belonging to the compulsory notification system of the Municipal Hospital of Governador Valadares. RESULTS: There were 3032 accidents, and the male-to-female ratio was 1.17:1 (male, 54%; females, 46%). Accidents occurred every month, but there was an increase in June, July, and October to January. In most cases, the time between the scorpion sting and medical care was between 1 and 3 h (n=1304; 43%). The most frequent clinical and systemic manifestations were pain at the bite site (94%) and vagal symptoms (7%). Cases were mild (n=2750, 91%), moderate (n=221, 7%), and severe (n=56, 2%). Children younger than 10 y constituted the most cases, 522 (17%). There was a significant difference between clinical severity and age (P<0.01). Ten patients developed acute pulmonary edema. Two 4-y-old children died. All severely envenomated patients as well as 74% and 2% of mild and moderately envenomated patients, respectively, received specific scorpion antivenoms. CONCLUSIONS: Scorpion envenomation is of greater severity in children aged <10 y. The clinical presentation includes mainly local pain associated with vagal symptoms. Accidents occur every month, but there was an increase in June, July, and October to January.

A Case Report of Venezuelan Suntiger Tarantula (Psalmopoeus Irminia) Envenomation and Review of Tarantula Exposures.

BACKGROUND: Tarantula envenomations are encountered infrequently but may increase with increased exotic animal ownership. This case report presents the first documented toxicity from a Venezuelan suntiger tarantula (VST), Psalmopoeus irminia, and provides a general framework for approaching patients with tarantula exposures. CASE REPORT: A 35-year-old man presented to an emergency department 4 h after experiencing a bite from his pet VST. He developed erythema, pain, and edema to the bite site on the left thenar eminence that extended proximally. Within 4 h, he developed abdominal pain, nausea, vomiting, throat itching, and tightness. The patient had a blood pressure of 131/105 mm Hg, heart rate of 102 beats/min, 36.6°C, respiratory rate of 20 breaths/min, and SpO2 of 94%. Laboratory evaluations were within normal limits (other than chronically elevated but improved transaminases). The patient received 0.5 mg epinephrine intramuscularly, 50 mg diphenhydramine IV, 20 mg famotidine IV, 0.4 mg ondansetron IV, and 1 L of normal saline for a suspected anaphylactic reaction. Shortly after epinephrine administration, his gastrointestinal and upper airway symptoms resolved. All symptoms resolved within 1 week. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Little is known about VST toxicity. Therefore, providers should rely on a general framework for approaching patients with tarantula exposures. Morbidity from tarantula exposures is mediated by mechanical injury, venom effects, and hypersensitivity reactions. Typical clinical findings include local pain, pruritis, edema, erythema, and burning. Muscle cramping, ophthalmia nodosa, and hypersensitivity reactions may occur. Treatment is primarily supportive and includes decontamination, cool compresses, analgesia, treatment of anaphylaxis, and ophthalmology evaluation if ocular exposure.

Snakebite envenoming in Brazilian children: clinical aspects, management and outcomes.

Snakebite envenoming is currently considered a neglected tropical disease, which affects over 5 million people worldwide, and causes almost 150 000 deaths every year, as well as severe injuries, amputations and other sequelae. Snakebite envenoming in children, although proportionally less frequent, is generally more severe, and represents an important challenge for pediatric medicine, since they often result in worse outcomes. In Brazil, given its ecological, geographic and socioeconomic characteristics, snakebites are considered an important health problem, presenting approximately 30 000 victims per year, approximately 15% of them in children. Even with low snakebite incidence, children tend to have higher snakebite severity and complications due to the small body mass and same venom volume inoculated in comparison to adults, even though, due to the lack of epidemiological information about pediatric snakebites and induced injuries, it is difficult to measure the treatment effectiveness, outcomes and quality of emergency medical services for snakebites in children. In this review, we report how Brazilian children are affected by snakebites, describing the characteristics of this affected population, clinical aspects, management, outcomes and main challenges.

Bothrops atrox mice experimental envenoming treatment using light-emitting diode (led) as an adjunct therapy to conventional serum therapy.

The use of anti-venom is one of the main control measures for snakebite envenoming when applied immediately after the snakebite. Systemic effects of the envenoming are usually reversed; however, neutralization of local effects is hardly achieved. The need for adjuvant therapies associated with serum therapy can improve the treatment for local effects of envenoming, with greater effectiveness in preventing or delaying the progression of damage, reducing the clinical signs and symptoms of victims of snakebites. The purpose of the study was to evaluate the photobiomodulation therapy using LED and/or dexamethasone associated with conventional serum therapy for the treatment of local damage caused by Bothrops atrox envenomation in a murine model. For this, experimental envenoming was carried out in the gastrocnemius muscle of male Swiss mice weighing 18 to 22 g divided into 8 groups of animals, distributed in groups non-treat, treated with anti-bothropic serum, dexamethasone, and LED, or the associated treatments, by intramuscular inoculation of 50 µg of venom or sterile PBS (control). After 30 min, the proposed treatments were administered alone or in combination. After 3 h, blood and muscle samples were collected for myotoxicity, cytotoxicity, histological analysis, and IL-1ß assays. The evaluation of the treatment alone showed that serum therapy is not effective for the treatment of local damage and photobiomodulation demonstrated to be an effective therapy to reduce leukocyte infiltration, hemorrhage, and myotoxicity in experimental envenoming; dexamethasone proved to be a good resource for the treatment of the inflammatory process reducing the leukocyte infiltration. The association of serum therapy, LED, and dexamethasone was the best treatment to reduce the local effects caused by Bothrops atrox venom. All in all, the association of photobiomodulation therapy using LED with conventional serum therapy and the anti-inflammatory drug is the best treatment for reducing the undesirable local effects caused by snakebite accidents involving B. atrox species.

Epidemiological characterization of lonomism in South America.

Lonomism is the envenomation caused by accidental contact with Lonomia caterpillars, and this is a public health priority in South America since it is relatively common but remains underestimated. This study presents an updated and integrative analysis of reliable global data from 1960 to 2020 on the epidemiology of this envenomation in the whole continent. A total of 13,186 notifications were recorded for South America: 13,056 (99.01%) in Brazil, 49 (0.37%) in Argentina, 43 (0.33%) in Colombia, 29 (0.22%) in Venezuela, 6 (0.05%) in Peru and 3 (0.02%) in French Guiana. The number of new locations reporting accidents has increased since the first formally notifications at the middle of the last century. Most of these locations are situated in Brazil, the pioneer in deeply researching the Lonomia genus and its impacts in public health. Most victims were males, in the economically productive age group, and accidental contact occurred more frequently in the upper limbs while doing activities outdoors in urban/rural areas. Regarding the determinants of clinical outcome, countries where patients received delayed medical care were associated with a higher number of moderate and/or severe cases, as well as a higher chance of progressing to death. Additionally, the longer the delay for accessing medical care, the higher the risk of developing systemic complications, thereby increasing the need for specific treatment. Our study also shows that accidents globally occurred more frequently in the summer months and in the beginning of autumn. Although having identified several shortcomings in the documents selected and verified that notifications are strongly biased by public policies adopted by each South American country, this study provides the first comprehensive assessment of lonomism in South America, demonstrating the increase in the number of accidents, and their expansion to other areas of the continent over time. Our findings will undoubtedly help guide the appropriate allocation of resources and implementation of prevention strategies and define priority criteria for epidemiological surveillance of this neglected tropical disease.

An overview of Tityus cisandinus scorpion venom: Transcriptome and mass fingerprinting reveal conserved toxin homologs across the Amazon region and novel lipolytic components.

Tityus cisandinus, a neglected medically important scorpion in Ecuadorian and Peruvian Amazonia, belongs to a complex of species related to the eastern Amazon endemic Tityus obscurus, spanning a distribution of ca. 4000 km. Despite high morbidity and mortality rates, no effective scorpion antivenom is currently available in the Amazon region. Knowledge of the structural/functional relationships between T. cisandinus venom components and those from related Amazonian species is crucial for designing region-specific therapeutic antivenoms. In this work, we carried out the first venom gland transcriptomic study of an Amazonian scorpion outside Brazil, T. cisandinus. We also fingerprinted its total venom through MALDI-TOF MS, which supported our transcriptomic findings. We identified and calculated the expression level of 94 components: 60 toxins, 25 metalloproteases, five disulfide isomerases, three amidating enzymes, one hyaluronidase, and also uncovered transcripts encoding novel lipolytic beta subunits produced by New World buthid scorpions. This study demonstrates the high similarity between T. cisandinus and T. obscurus venoms, reinforcing the existence of a neglected complex of genetically and toxinologically related Amazonian scorpions of medical importance. Finally, we demonstrated the low recognition of currently available therapeutic sera against T. cisandinus and T. obscurus venoms, and concluded that these should be improved to protect against envenomation by Amazonian Tityus spp.

Biological characterization of bristle extract of Lonomia descimoni caterpillar (Lepidoptera, Saturniidae) and effectiveness of Lonomia antivenom to neutralize experimental envenomation in rats.

Contact with Lonomia caterpillars can cause severe envenomation with hemorrhagic syndrome, consumptive coagulopathy, acute renal failure, and death. In Brazil, an antivenom was produced using extracts from L. obliqua caterpillar bristles as antigen and has been used in other countries in South America to treat envenomation caused by distinct species of Lonomia. This study aimed to characterize the activities of toxins from Lonomia descimoni caterpillars found in Colombia and the neutralization of these toxins by the Brazilian Lonomia antivenom. The protein composition and coagulant, phospholipase A2, hyaluronidase, and defibrinogenating activities were evaluated and compared with the same parameters of the L. obliqua bristle extract. Immune recognition and the neutralizing ability of Lonomia antivenom were also determined. The results showed that the L. descimoni bristle extract presented marked differences in electrophoretic and mass spectrometry profiles and had coagulant, phospholipase A2, and hyaluronidase activities significantly less intense than those of the L. obliqua extract. In rats, L. descimoni extract induced coagulopathy and hemoglobinuria when injected by intravenous or intraperitoneal routes. The Lonomia antivenom recognized the toxins in the extract of L. descimoni and reversed the experimental envenomation in rats. Our results indicate that L. descimoni caterpillars possess toxins with weaker activities than those of L. obliqua but with the potential to cause envenomation. Moreover, the Lonomia antivenom recognized and neutralized the toxins in the L. descimoni bristle extract.