A Bite by Shaw's Short Sea Snake (Hydrophis curtus): A Case of Mild Myotoxicity or a Dry Bite?

Although sea snakes (Elapidae) are commonly encountered by fishermen, accurately authenticated envenomings by them are uncommon in clinical literature. We report an authenticated case of Shaw's short, or spine-bellied, sea snake (Hydrophis curtus) bite in a young fisherman from northern Sri Lanka. The patient had clinical and biochemical evidence of mild transient myotoxicity but no evidence of neuromuscular paralysis or significant renal injury. Consideration of the clinical manifestations suggests either a mild envenoming or a dry bite. The patient completely recovered without any antivenom therapy and was discharged on the fourth day. Prolonged observation may be beneficial to exclude complications of sea snake envenoming.

The banded colour patterns of sea snakes discourage attack by predatory fishes, enabling Batesian mimicry by harmless species.

The evolution of bright 'warning' colours in nontoxic animals often is attributed to mimicry of toxic species, but empirical tests of that hypothesis must overcome the logistical challenge of quantifying differential rates of predation in nature. Populations of a harmless sea snake species (Emydocephalus annulatus) in New Caledonia exhibit colour polymorphism, with around 20% of individuals banded rather than melanic. Stability in that proportion over 20 years has been attributed to Batesian mimicry of deadly snake species by banded morphs of the harmless taxon. This hypothesis requires that banded colours reduce a snake's vulnerability to predation. We tested that idea by pulling flexible snake-shaped models through the water and recording responses by predatory fish. Black and banded lures attracted similar numbers of following fish, but attacks were directed almost exclusively to black lures. Our methods overcome several ambiguities associated with experimental studies on mimicry in terrestrial snakes and support the hypothesis that banded colour patterns reduce a non-venomous marine snake's vulnerability to predation.

Electrostatic resistance to alpha-neurotoxins conferred by charge reversal mutations in nicotinic acetylcholine receptors.

The evolution of venom resistance through coevolutionary chemical arms races has arisen multiple times throughout animalia. Prior documentation of resistance to snake venom α-neurotoxins consists of the N-glycosylation motif or the hypothesized introduction of arginine at positions 187 at the α-1 nicotinic acetylcholine receptor orthosteric site. However, no further studies have investigated the possibility of other potential forms of resistance. Using a biolayer interferometry assay, we first confirm that the previously hypothesized resistance conferred by arginine at position 187 in the honey badger does reduce binding to α-neurotoxins, which has never been functionally tested. We further discovered a novel form of α-neurotoxin resistance conferred by charge reversal mutations, whereby a negatively charged amino acid is replaced by the positively charged amino acid lysine. As venom α-neurotoxins have evolved strong positive charges on their surface to facilitate binding to the negatively charged α-1 orthosteric site, these mutations result in a positive charge/positive charge interaction electrostatically repelling the α-neurotoxins. Such a novel mechanism for resistance has gone completely undiscovered, yet this form of resistance has convergently evolved at least 10 times within snakes. These coevolutionary innovations seem to have arisen through convergent phenotypes to ultimately evolve a similar biophysical mechanism of resistance across snakes.

Myalgia as a Symptom of Envenomation by the Eastern Coral Snake, Micrurus Fulvius: A Case Report.

We present the case of a patient who developed myalgia as the primary symptom of envenomation by the eastern coral snake, Micrurus fulvius. The patient was evaluated and treated in the emergency department. Physical examination did not demonstrate any neuromuscular abnormalities. On consultation with the poison control center, the patient's myalgia was determined to be an effect of envenomation, and 5 vials of North American coral snake antivenin were administered. The patient was admitted to the intensive care unit where his symptoms resolved. He was discharged the following day after remaining asymptomatic for 24 h.

Assessing the Binding of Venoms from Aquatic Elapids to the Nicotinic Acetylcholine Receptor Orthosteric Site of Different Prey Models.

The evolution of an aquatic lifestyle from land dwelling venomous elapids is a radical ecological modification, bringing about many evolutionary changes from morphology to diet. Diet is an important ecological facet which can play a key role in regulating functional traits such as venom composition and prey-specific targeting of venom. In addition to predating upon novel prey (e.g., fish, fish eggs and invertebrates), the venoms of aquatic elapids also face the challenge of increased prey-escape potential in the aquatic environment. Thus, despite the independent radiation into an aquatic niche on four separate occasions, the venoms of aquatic elapids are evolving under convergent selection pressures. Utilising a biolayer interferometry binding assay, this study set out to elucidate whether crude venoms from representative aquatic elapids were target-specific to the orthosteric site of postsynaptic nicotinic acetylcholine receptor mimotopes of fish compared to other terrestrial prey types. Representatives of the four aquatic lineages were: aquatic coral snakes representative was Micrurus surinamensis;, sea kraits representative was Laticauda colubrina; sea snakes representatives were two Aipysurus spp. and eight Hydrophis spp; and water cobras representative was Naja annulata. No prey-specific differences in crude venom binding were observed from any species tested, except for Aipysurus laevis, which showed slight evidence of prey-potency differences. For Hydrophis caerulescens, H. peronii, H. schistosus and M. surinamensis, there was a lack of binding to the orthosteric site of any target lineage. Subsequent testing on the in vitro chick-biventer cervicis muscle preparation suggested that, while the venoms of these species bound postsynaptically, they bound to allosteric sites rather than orthosteric. Allosteric binding is potentially a weaker but faster-acting form of neurotoxicity and we hypothesise that the switch to allosteric binding is likely due to selection pressures related to prey-escape potential. This research has potentially opened up the possibility of a new functional class of toxins which have never been assessed previously while shedding light on the selection pressures shaping venom evolution.

First Authenticated Case of a Bite by Rare and Elusive Blood-Bellied Coral Snake (Calliophis haematoetron).

Blood-bellied coral snake (Calliophis haematoetron) is a recently discovered forest-dwelling species of elapid hitherto known from 3 specimens found from central Sri Lanka. Herein we describe the first authenticated case of blood-bellied coral snakebite. The victim, an 11-mo-old infant who received the bite while handling the snake at her home, had mild transient swelling at the bite site. The patient had no clinical or laboratory evidence of systemic envenoming. We highlight the importance of clinicians being aware of the occurrence of this potentially medically important elapid snake in anthropogenic habitats.

Management of Snakebites in the Upper Extremity.

Encounters with venomous snakes can lead to substantial morbidity or mortality if managed inappropriately. Medical management is the mainstay of treatment, but surgery may be necessary in rare cases. The hand surgeon should be well versed in the types of venomous snakes, the mechanism of action of venom, and the management of these injuries, given the frequency of hand envenomation. The indications for surgery are not well established and rely on clinical judgment and practitioner's experience. An understanding of previously reported outcomes and an algorithmic approach to treatment will help improve patient care and avoid complications.

Venom Proteomics of Indonesian King Cobra, Ophiophagus hannah: Integrating Top-Down and Bottom-Up Approaches.

We report on the first application of top-down mass spectrometry in snake venomics. De novo sequence tags generated by, and ProSight Lite supported analysis of, combined collisional based dissotiations (CID and HCD) recorded in a hybrid LTQ Orbitrap instrument in data-dependent mode identified a number of proteins from different toxin families, namely, 11 three-finger toxins (7-7.9 kDa), a Kunitz-type inhibitor (6.3 kDa), ohanin (11.9 kDa), a novel phospholipase A2 molecule (13.8 kDa), and the cysteine-rich secretory protein (CRISP) ophanin (25 kDa) from Indonesian king cobra venom. Complementary bottom-up MS/MS analyses contributed to the completion of a locus-resolved venom phenotypic map for Ophiophagus hannah, the world's longest venomous snake and a species of medical concern across its wide distribution range in forests from India to Southeast Asia. Its venom composition, comprising 32-35 proteins/peptides from 10 protein families, is dominated by α-neurotoxins and convincingly explains the main neurotoxic effects of human envenoming caused by king cobra bite. The integration of efficient chromatographic separation of the venom's components and locus-resolved toxin identification through top-down and bottom-up MS/MS-based species-specific database searching and de novo sequencing holds promise that the future will be bright for the field of venom research.

Sea snake harvest in the gulf of Thailand.

Conservation of sea snakes is virtually nonexistent in Asia, and its role in human-snake interactions in terms of catch, trade, and snakebites as an occupational hazard is mostly unexplored. We collected data on sea snake landings from the Gulf of Thailand, a hotspot for sea snake harvest by squid fishers operating out of the ports of Song Doc and Khanh Hoi, Ca Mau Province, Vietnam. The data were collected during documentation of the steps of the trading process and through interviewers with participants in the trade. Squid vessels return to ports once per lunar synodic cycle and fishers sell snakes to merchants who sort, package, and ship the snakes to various destinations in Vietnam and China for human consumption and as a source of traditional remedies. Annually, 82 t, roughly equal to 225,500 individuals, of live sea snakes are brought to ports. To our knowledge, this rate of harvest constitutes one of the largest venomous snake and marine reptile harvest activities in the world today. Lapemis curtus and Hydrophis cyanocinctus constituted about 85% of the snake biomass, and Acalyptophis peronii, Aipysurus eydouxii, Hydrophis atriceps, H. belcheri, H. lamberti, and H. ornatus made up the remainder. Our results establish a quantitative baseline for characteristics of catch, trade, and uses of sea snakes. Other key observations include the timing of the trade to the lunar cycle, a decline of sea snakes harvested over the study period (approximately 30% decline in mass over 4 years), and the treatment of sea snake bites with rhinoceros horn. Emerging markets in Southeast Asia drive the harvest of venomous sea snakes in the Gulf of Thailand and sea snake bites present a potentially lethal occupational hazard. We call for implementation of monitoring programs to further address the conservation implications of this large-scale marine reptile exploitation.

Epidemiology and characteristics of coral snake bites reported to the National Poison Data System (2006‒2022).

Objectives: North American coral snake envenomations can result in life-threatening neurotoxicity. Their bites are relatively rare, making large studies difficult. Using the National Poison Data System (NPDS), we sought to investigate the epidemiological trends and clinical outcomes associated with North American coral snake bites over a 17-year period. Methods: NPDS cases involving coral snakes from January 1, 2006, to December 31, 2022, were analyzed. Data collected included patient age, date, geographic location, clinical effects, treatments administered, and medical outcomes including incidence of "dry bites" (non-envenomation) and death. Results: During the 17-year period, a total of 1374 cases were reported and analyzed. Cases included adults (≥ 20 years), accounting for 80% (n = 1107), and pediatric patients (≤19 years), accounting for 20% (n = 267) of total cases. Out of 50 US states and District of Columbia, 20 states reported cases. Florida and Texas accounted for 90.5% of all bites (n = 1243) with April being the month with the most reported cases (n = 184). The most bites (n = 96) were reported in 2008 and the fewest (n = 69) in 2016. Male patients predominated for both pediatric (75.7%, n = 202) and adult cases (75.3%, n = 834). Moderate to major clinical outcomes were documented in approximately 30% of total cases; with no reported deaths. Moderate effect is defined as the patient exhibited symptoms as a result of the exposure that were more pronounced, more prolonged, or more of a systemic nature than minor symptoms. Major effect was defined as the patient exhibited symptoms as a result of the exposure that were life threatening or resulted in significant residual disability or disfigurement. The three most reported clinical effects were wound/sting, dermal irritation/pain, and edema. Antivenom was administered in 21% (n = 286) of total cases and 37% (n = 511) of patients were admitted to a critical care unit. Dry bites occurred in 7% (n = 100) of total cases. Conclusion: Coral snake bites were rare, but consistently reported. While bites were associated with significant morbidity in adult and pediatric patients, there were no deaths reported. Antivenom use declined over the study period but was not associated with an increase in morbidity. An increased incidence of intubations was seen in association with decreased antivenom use.

Novel phylogenomic inference and 'Out of Asia' biogeography of cobras, coral snakes and their allies.

Estimation of evolutionary relationships among lineages that rapidly diversified can be challenging, and, in such instances, inaccurate or unresolved phylogenetic estimates can lead to erroneous conclusions regarding historical geographical ranges of lineages. One example underscoring this issue has been the historical challenge posed by untangling the biogeographic origin of elapoid snakes, which includes numerous dangerously venomous species as well as species not known to be dangerous to humans. The worldwide distribution of this lineage makes it an ideal group for testing hypotheses related to historical faunal exchanges among the many continents and other landmasses occupied by contemporary elapoid species. We developed a novel suite of genomic resources, included worldwide sampling, and inferred a robust estimate of evolutionary relationships, which we leveraged to quantitatively estimate geographical range evolution through the deep-time history of this remarkable radiation. Our phylogenetic and biogeographical estimates of historical ranges definitively reject a lingering former 'Out of Africa' hypothesis and support an 'Out of Asia' scenario involving multiple faunal exchanges between Asia, Africa, Australasia, the Americas and Europe.

Identification of antigenic proteins from the venom of Malaysian snakes using immunoprecipitation assay and tandem mass spectrometry (LC-MS/MS).

Snake envenomation poses a significant risk to Malaysians and country visitors. Malaysia witnesses an estimated 650 snake bites per 100,000 population annually. The primary treatment for snake envenomation involves administering antivenom derived from horses, despite its drawbacks, such as anaphylactic reactions and serum sickness. Identifying the venom proteome is crucial for understanding and predicting the clinical implications of envenomation and developing effective treatments targeting specific venom proteins. In this study, we employ an immunoprecipitation assay followed by LC-MS/MS to identify antigenic proteins in five common venomous snakes in Malaysia compassing of two families which are pit vipers, (Calloselasma rhodostoma and Cryptelytrops purpureomaculatus) and cobras (Ophiophagus hannah, Naja kaouthia, and Naja sumatrana). The immunoprecipitation assay utilises a 2 % agarose gel, allowing antigenic proteins to diffuse and bind with antibodies in the antivenom. The antivenom utilised in this research was procured from the Queen Saovabha Memorial Institute (QSMI), Thailand, including king cobra antivenom (KCAV), cobra antivenom (CAV), Malayan pit viper antivenom (MPAV), Russell's viper antivenom (RPAV), hematopolyvalent antivenom (HPAV), neuropolyvalent antivenom (NPAV), banded krait antivenom (BKAV), and Malayan krait antivenom (MKAV). The protein identified through these interactions which are exclusive to the cobras are three-finger toxins (3FTXs) while snake C-type lectins (Snaclecs) are unique to the pit vipers. Common protein that are present in both families are L-amino acid oxidase (LAAO), Phospholipase A2 (PLA2), and snake venom metalloproteinase (SVMP). Identifying these proteins is vital for formulating a broad-spectrum antivenom applicable across multiple species.

Neurotoxic snakebites in Africa: Clinical implications, therapeutic strategies, and antivenom efficacy.

Snakebite is a significant health concern in Africa, particularly due to neurotoxic envenomation which can lead to neuromuscular paralysis and respiratory failure. In Nigeria, snakes from the Elapidae family are a notable cause of envenomation cases, though these incidents are underreported. This review examined case reports of neurotoxic envenomation in Africa, highlighting the clinical impacts and the efficacy of available antivenoms. Preclinical studies showed that the polyvalent antivenom from the South African Institute for Medical Research (SAIMR) was highly effective against neurotoxicity with a protective efficacy (R) of 1346.80 mg/mL, while clinical assessment emphasized the need for high-dose antivenom therapy along with supportive measures like mechanical ventilation. Unlike hemorrhagic envenomation, where antivenom promptly resolves bleeding, neurotoxic cases often require additional interventions. The review underscores the necessity for tailored approaches in antivenom therapy to address the complexities of neurotoxic snakebites and reduce their public health burden in Africa.

VenomCap: An exon-capture probe set for the targeted sequencing of snake venom genes.

Snake venoms are complex mixtures of toxic proteins that hold significant medical, pharmacological and evolutionary interest. To better understand the genetic diversity underlying snake venoms, we developed VenomCap, a novel exon-capture probe set targeting toxin-coding genes from a wide range of elapid snakes, with a particular focus on the ecologically diverse and medically important subfamily Hydrophiinae. We tested the capture success of VenomCap across 24 species, representing all major elapid lineages. We included snake phylogenomic probes in the VenomCap capture set, allowing us to compare capture performance between venom and phylogenomic loci and to infer elapid phylogenetic relationships. We demonstrated VenomCap's ability to recover exons from ~1500 target markers, representing a total of 24 known venom gene families, which includes the dominant gene families found in elapid venoms. We find that VenomCap's capture results are robust across all elapids sampled, and especially among hydrophiines, with respect to measures of target capture success (target loci matched, sensitivity, specificity and missing data). As a cost-effective and efficient alternative to full genome sequencing, VenomCap can dramatically accelerate the sequencing and analysis of venom gene families. Overall, our tool offers a model for genomic studies on snake venom gene diversity and evolution that can be expanded for comprehensive comparisons across the other families of venomous snakes.

Neurotoxic snakebite envenomation treated with Philippine cobra antivenom in the eastern Visayas: a descriptive study between 2016 and 2020.

Introduction: There is a significant shortage of observational studies on neurotoxic snakebite envenomation in the Philippines. This lack of data, especially concerning treatment using Purified Cobra Antivenom (PCAV), has prompted the initiation of this foundational study. Methods: The target population included snakebite patients admitted to the Eastern Visayas Medical Center and treated with PCAV between 2016 and 2020. A retrospective chart review was conducted for data collection. The investigation analyzed the hospital stay and patient features of individuals who were administered either lower or higher doses of PCAV. Results: Eighty-two patients were identified during the study. Of these, 27 (33%) were under 20 years of age and 50 (61%) were male. Most patients, totalling 75 (92%) were hailed from rural areas. Of the 82 patients, 59 (72%) received one or two ampoules of PCAV during the course. However, patients who received more than two ampoules had a longer median hospital stay than those who received less than three ampoules [96 h (interquartile range, IQR 66-122) vs. 125 h (IQR 96-218), P = 0.038]. The study reported five in-hospital mortalities (6.1%). Conclusions: The individuals who needed a high dosage of PCAV tended to have more extended hospital stays, yet over 70% of the patient population required a lower dosage. To gain a clearer understanding of the burden of neurotoxic snakebites and determine the optimal PCAV dosage based on disease severity in the area, a more comprehensive, prospective study is recommended.

A confirmed human fatality due to envenomation by the Kunene Coral Snake (Aspidelaps lubricus cowlesi) in Namibia.

Shield-nose and Coral snakes (Aspidelaps spp.) are medium sized venomous snakes found throughout southern Africa. Little is known about the venom of these snakes and its clinical relevance, as human bites are uncommon. Neurological signs and symptoms usually develop following bites by this genus but evaluations of the severity are inconclusive. We report on the first confirmed human fatality by the Kunene Shield-nose Snake (Aspidelaps lubricus cowlesi) in a child. Envenomation by Aspidelaps and other snakes considered lesser-venomous - especially those possessing neurotoxic venom - should be treated with caution as they may result in life-threatening envenomation without established clinical management protocols.

One-Step Affinity Purification of Leucine-Rich α2-Glycoproteins from Snake Sera and Characterization of Their Phospholipase A2-Inhibitory Activities as ß-Type Phospholipase A2 Inhibitors.

Snakes contain three types of phospholipase A2 (PLA2)-inhibitory proteins in their blood, PLIα, ß, and γ, which protect them from their own venom, PLA2. PLIß is the snake ortholog of leucine-rich α2 glycoprotein (LRG). Since autologous cytochrome c (Cyt c) serves as an endogenous ligand for LRG, in this study, we purified snake LRGs from various snake serum samples using Cyt c affinity chromatography. All purified snake LRGs were found to be dimers linked by disulfide bonds. Laticauda semifasciata and Naja kaouthia LRGs showed no inhibitory activity against L. semifasciata PLA2 and weak inhibitory activity against Gloydius brevicauda basic PLA2. Elaphe climacophora PLIß had weaker inhibitory activity against G. brevicauda basic PLA2 than G. brevicauda and Elaphe quadrivirgata PLIs, which are abundant in blood and known to neutralize G. brevicauda basic PLA2. Protobothrops flavoviridis LRG showed no inhibitory activity against basic venom PLA2, PL-X, or G. brevicauda basic PLA2. Binding analysis of P. flavoviridis LRG using surface plasmon resonance showed very strong binding to snake Cyt c, followed by that to horse Cyt c, weak binding to yeast Cyt c, and no binding to P. flavoviridis PL-X or BPI/II. We also deduced the amino acid sequences of L. semifasciata and P. flavoviridis LRG by means of cDNA sequencing and compared them with those of other known sequences of PLIs and LRGs. This study concluded that snake LRG can potentially inhibit basic PLA2, but, whether it actually functions as a PLA2-inhibitory protein, PLIß, depends on the snake.

Envenomation by Micrurus hemprichii in Brazilian Amazonia: A report of three cases.

Herein, we report three new separate cases of human envenomations by Micrurus hemprichii for the Amazon, which is a biome where envenomations by Micrurus are seldom reported. Two women were bitten after stepping on the snakes and one man was bitten while handling the animal. All cases occurred in the peridomicile, in rural areas. The first case evolved mainly to local symptoms, but the patient was discharged before the identification of the snake and had to be called back for observation before being eventually discharged. In the second case, the patient presented transitory dyspnea and she was discharged after four days in hospital. In the third case, the patient showed only local symptoms, but he was about to receive unnecessary antivenom against coral snakes. Cases like these show the importance of educational problems regarding local venomous snakes in order to avoid bites and to provide the correct hospital treatment. For this, trained professionals in cases involving venomous animals are needed.

Medically important snakes and snakebite envenoming in Iran.

Snakebite is a relatively common health condition in Iran with a diverse snake fauna, especially in tropical southern and mountainous western areas of the country with a plethora of snake species. The list of medically important snakes, circumstances and effects of their bite, and necessary medical care require critical appraisal and should be updated regularly. This study aims to review and map the distributions of medically important snake species of Iran, re-evaluate their taxonomy, review their venomics, describe the clinical effects of envenoming, and discuss medical management and treatment, including the use of antivenom. Nearly 350 published articles and 26 textbooks with information on venomous and mildly venomous snake species and snakebites of Iran, were reviewed, many in Persian (Farsi) language, making them relatively inaccessible to an international readership. This has resulted in a revised updated list of Iran's medically important snake species, with taxonomic revisions of some, compilation of their morphological features, remapping of their geographical distributions, and description of species-specific clinical effects of envenoming. Moreover, the antivenom manufactured in Iran is discussed, together with treatment protocols that have been developed for the hospital management of envenomed patients.

A Case of Cobra Bite Complicated with Basilar Artery Occlusion.

Snakebite is one of the most common complaints related to wilderness medicine. Venomous snakebite manifestation is divided into local and systemic envenomation. For the Elapidae group, the most feared complication is respiratory muscle paralysis due to neurotransmitter malfunction at the neuromuscular junction level which leads to respiratory insufficiency. However, there is a lack of evidence or case report incidence to suggest that it can potentially associate with the development of stroke disorder. We present a rare case of massive posterior circulation infarct in a middle-aged gentleman following a cobra bite. He was brought to our center few hours later following the bite and antivenom was administered. He improved shortly after receiving it. However, he had an abrupt drop in his conscious level several hours later. Noncontrast-enhanced computed tomography (NCCT) brain was performed immediately, but stroke disorder was excluded prematurely. Repeated NCCT imaging which was done 12 h apart showed massive posterior circulation infarction with hydrocephalus. He succumbed to death 3 days later. Given its rarity, the evolution of his clinical condition warrants clinician's early suspicion of potential stroke-related complications that can occur following a cobra bite.