Snakebites affect millions of people worldwide. The majority of research and management about snakebites focus on venom and antivenom, with less attention given to snake ecology. The fundamental ...factor in snakebites is the snakes' defensive biting behavior. Herein we examine the effects of environmental variables (temperature, time of day, and human stimulus) and biological variables (sex and body size) on the biting behavior of a medically significant pit viper species in Brazil, Bothrops jararaca (Viperidae), and associate it with the epidemiology of snakebites. Through experimental simulations of encounters between humans and snakes, we obtained behavioral models applicable to epidemiological situations in the State of São Paulo, Brazil. We found a significant overlap between behavioral, morphological, environmental, and epidemiological data. Variables that increase snakebites in epidemiological data also enhance the tendency of snakes to bite defensively, resulting in snakebites. We propose that snakebite incidents are influenced by environmental and morphological factors, affecting the behavior of snakes and the proportion of incidents. Thus, investigating behavior of snakes related to snakebite incidents is a valuable tool for a better understanding of the epidemiology of these events, helping the prediction and, thus, prevention of snakebites.
Snakebite is a major public health problem in Eswatini and serious envenomations can be responsible for considerable morbidity and mortality if not treated correctly. Antivenom should be administered ...in hospital in case of adverse reactions and any delays due to distance, transport, costs, antivenom availability and cultural beliefs can be critical. Myths and superstition surround snakes, with illness from snakebite considered a supernatural phenomenon best treated by traditional medicine since healers can explore causes through communication with the ancestors. Traditional consultations can cause significant delays and the remedies may cause further complications. Four rural focus group discussions were held in varying geographical regions to establish why people may choose traditional medicine following snakebite. The study revealed four themes, with no apparent gender bias. These were 'beliefs and traditions', 'logistical issues', 'lack of knowledge' and 'parallel systems'. All snakes are feared, regardless of geographical variations in species distribution. Deep-seated cultural beliefs were the most important reason for choosing traditional medicine, the success of which is largely attributed to the 'placebo effect' and positive expectations. Collaboration and integration of the allopathic and traditional systems assisted by the regulation of healers and their methods could improve future treatment success. The plight of victims could be further improved with more education, lower costs and improved allopathic facilities.
Snakes have been important ambush predators of both primates and human hunter-gatherers throughout their co-evolutionary history. Viperid snakes in particular are responsible for most fatal venomous ...snakebites worldwide and thus represent a strong selective pressure. They elicit intense fear in humans and are easily recognizable thanks to their distinctive morphotype. In this study, we measured skin resistance (SR) and heart rate (HR) in human subjects exposed to snake pictures eliciting either high fear (10 venomous viperid species) or disgust (10 nonvenomous fossorial species). Venomous snakes subjectively evaluated as frightening trigger a stronger physiological response (higher SR amplitude) than repulsive non-venomous snakes. However, stimuli presented in a block (more intense stimulation) do not trigger a stronger emotional response compared to sequentially presented stimuli (less intense stimulation). There are significant interindividual differences as subjects with high fear of snakes confronted with images of viperid snakes show stronger, longer-lasting, and more frequent changes in SR and higher HR compared to low-fear subjects. Thus, we show that humans demonstrate a remarkable ability to discriminate between dangerous viperids and harmless fossorial snakes, which is also reflected in distinct autonomous body responses.
Snake venom contains a cocktail of compounds dominated by proteins and peptides, which make up the toxin. The toxin components of snake venom attack several targets in the human body including the ...neuromuscular system, kidney and blood coagulation system and cause pathologies. As such, the venom toxins can be managed and used for the treatment of these diseases. In this regard, Captopril used in the treatment of cardiovascular diseases was the first animal venom toxin‐based drug approved by the US Food and Drug Administration and the European Medicines Agency. Cancers cause morbidity and mortality worldwide. Due to side effects associated with the current cancer treatments including chemotherapy, radiotherapy, immunotherapy, hormonal therapy and surgery, there is a need to improve the efficacy of current treatments and/or develop novel drugs from natural sources including animal toxin‐based drugs. There is a long history of earlier and ongoing studies implicating snake venom toxins as potential anticancer therapies. Here, we review the role of crude snake venoms and toxins including phospholipase A2, L‐amino acid oxidase, C‐type lectin and disintegrin as potential anticancer agents tested in cancer cell lines and animal tumour models in comparison to normal cell lines. Some of the anti‐tumour activities of snake venom toxins include induction of cytotoxicity, apoptosis, cell cycle arrest and inhibition of metastasis, angiogenesis and tumour growth. We thus propose the advancement of multidisciplinary approaches to more pre‐clinical and clinical studies for enhanced bioavailability and targeted delivery of snake venom toxin‐based anticancer drugs.
Snake venom contains toxins that attack different organs in the body. These toxins cause local and systemic pathologies. Ever since the approval of first snake venom‐based drug Captopril used in the treatment and management of cardiovascular diseases, there are ongoing researches towards the use of snake venom for the treatment of other diseases including cancer. Here, we have reviewed studies that reported the role of several snake venom and venom toxins including phospholipase A2, three‐finger toxins, L‐amino acid oxidase and disintegrin as potential anticancer agents.
Oligoclonal mixtures of broadly-neutralizing antibodies can neutralize complex compositions of similar and dissimilar antigens, making them versatile tools for the treatment of e.g., infectious ...diseases and animal envenomations. However, these biotherapeutics are complicated to develop due to their complex nature. In this work, we describe the application of various strategies for the discovery of cross-neutralizing nanobodies against key toxins in coral snake venoms using phage display technology. We prepare two oligoclonal mixtures of nanobodies and demonstrate their ability to neutralize the lethality induced by two North American coral snake venoms in mice, while individual nanobodies fail to do so. We thus show that an oligoclonal mixture of nanobodies can neutralize the lethality of venoms where the clinical syndrome is caused by more than one toxin family in a murine challenge model. The approaches described may find utility for the development of advanced biotherapeutics against snakebite envenomation and other pathologies where multi-epitope targeting is beneficial.
The Middle East and Northern Africa, collectively known as the MENA region, are inhabited by a plethora of venomous animals that cause up to 420,000 bites and stings each year. To understand the ...resultant health burden and the key variables affecting it, this review describes the epidemiology of snake, scorpion, and spider envenomings primarily based on heterogenous hospital data in the MENA region and the pathologies associated with their venoms. In addition, we discuss the venom composition and the key medically relevant toxins of these venomous animals, and, finally, the antivenoms that are currently in use to counteract them. Unlike Asia and sub-Saharan Africa, scorpion stings are significantly more common (approximately 350,000 cases/year) than snakebites (approximately 70,000 cases/year) and present the most significant contributor to the overall health burden of envenomings, with spider bites being negligible. However, this review also indicates that there is a substantial lack of high-quality envenoming data available for the MENA region, rendering many of these estimates speculative. Our understanding of the venoms and the toxins they contain is also incomplete, but already presents clear trends. For instance, the majority of snake venoms contain snake venom metalloproteinases, while sodium channel-binding toxins and potassium channel-binding toxins are the scorpion toxins that cause most health-related challenges. There also currently exist a plethora of antivenoms, yet only few are clinically validated, and their high cost and limited availability present a substantial health challenge. Yet, some of the insights presented in this review might help direct future research and policy efforts toward the appropriate prioritization of efforts and aid the development of future therapeutic solutions, such as next-generation antivenoms.
There is a clear, unmet need for effective, lightweight, shelf-stable and economical snakebite envenoming therapies that can be given rapidly after the time of a snake's bite and as adjuncts to ...antivenom therapies in the hospital setting. The sPLA2 inhibitor, LY315920, and its orally bioavailable prodrug, LY333013, demonstrate surprising efficacy and have the characteristics of an antidote with potential for both field and hospital use.
The efficacy of the active pharmaceutical ingredient (LY315920) and its prodrug (LY333013) to treat experimental, lethal envenoming by
(Eastern coral snake) venom was tested using a porcine model. Inhibitors were administered by either intravenous or oral routes at different time intervals after venom injection. In some experiments, antivenom was also administered alone or in conjunction with LY333013.
14 of 14 animals (100%) receiving either LY315920 (intravenous) and/or LY333013 (oral) survived to the 120 h endpoint despite, in some protocols, the presence of severe neurotoxic signs. The study drugs demonstrated the ability to treat, rescue, and re-rescue animals with advanced manifestations of envenoming.
Low molecular mass sPLA2 inhibitors were highly effective in preventing lethality following experimental envenoming by
. These findings suggest the plausibility of a new therapeutic approach to snakebite envenoming, in this example, for the treatment of a coral snake species for which there are limitations in the availability of effective antivenom.
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