Highlight: We report a case of Stromatopelma calceatum envenoming with magnetic resonance imaging-confirmed venom-induced fasciitis in a French legionnaire deployed to C & ocirc;te d'Ivoire. Outcome was favourable following symptomatic treatment.

The Wilderness Medical Society convened an expert panel to develop a set of evidence-based guidelines for the prevention and treatment of North American pit viper envenomations, and this serves as an update to the initial guidelines. We present a review of pertinent pathophysiology and discuss prevention measures and therapeutic management. Graded recommendations are made regarding each treatment and its role in management. This significant update to the prior guidelines includes a discussion of F(ab')2 antivenom treatment, which was not previously approved by the Food and Drug Administration. These guidelines should assist in clinical decision making, but a cookbook approach is often insufficient, because each patient is unique and may respond differently to therapeutics. Physicians must use their experience and frequent clinical assessments to apply these recommendations to their individual patients. Consultation with a local toxicologist familiar with envenomations or a poison control center is recommended to assist in patient management. These guidelines are for crotaline snakes native to the United States and Canada and should not be applied to other snake species or geographic regions. Coral snake envenomations result in fewer serious side effects (<3% of victims) and account for only 1 to 3% of all snakebites reported in the United States and Canada. Due to the differences in management, coral snakes are not covered in these guidelines. This is an updated version of the guidelines published in 2015.

The clinical evolution and management of a 22-yr-old male envenomed by a captive female inland taipan, Oxyuranus microlepidotus (McCoy, 1879), Elapidae, at a public educational reptile exhibit (Florida, USA) is reported. The patient was bitten (quick 'bite and release') in the right hand between digits #3 and 4 while performing captive maintenance. The victim did not attempt any first aid, but urgently presented to the local hospital within 25 mins post-bite. The patient had an unremarkable medical/surgical history including no previous envenoming/treatment with antivenom. Within approximately 5 mins post-bite he reported experiencing transient loss of consciousness/syncope, altered sensorium, nausea, dull headache, weakness, and "severe" bite site pain. Laboratory investigations revealed profound defibrinating coagulopathy including thrombocytopenia; there was only mildly elevated creatine kinase and renal function remained within normal limits. The patient's clinical evolution included cranial nerve palsies manifested as dysconjugate gaze, persistent, but minor, bite site bleeding, asthenia and reported myalgia as well as prolonged intense bite site pain. He was successfully and uneventfully treated with four vials of Australian polyvalent antivenom and one vial of taipan monovalent; all were expired products with expiration dates ranging from one month to 38 years. Effective antivenom therapy might have been achieved with only 2, possibly 3 vials; however, concerns about reduced efficacy of the long-expired antivenom (4/5 vials were expired 18-38 years) and persistent bite site bleeding/pain contributed to the provision of the additional vials. The patient recovered sufficiently for discharge in 48 h; there were no sequelae. There have been approximately 12 formally documented cases of O. microlepidotus envenoming and selected, detailed examples of these are briefly considered and compared with the clinical evolution of our patient; patient-centred recommendations for management of Oxyuranus spp. envenoming are discussed. The need for advanced preparedness and an action plan for any institution/collection that contains non-native, medically significant venomous species is emphasised, and a general recommended approach is outlined.

Non-front-fanged snakes (NFFS) have long been overlooked by snake venom research, likely due to most of them being considered non-medically relevant for humans. The paucity of information about composition and activities of NFFS venoms and oral secretions makes it difficult to assess whether a given species can inflict medically significant bites. Here, we provide a review of the information currently available about the symptoms/signs elicited by bites from European NFFS, aiming to offer a foundation for understanding the threat they pose in terms of snakebite. Despite an overall limited amount of available data for most of the considered taxa, the genus Malpolon is notable for its capacity to cause local and systemic envenoming, including neurotoxic symptoms. Bites by other genera like, Hemorrhois, Hierophis, Natrix, Platyceps, Telescopus, and Zamenis are mainly associated with local symptoms, but the extent of their medical significance remains unclear. Our findings suggest that, although bites from European NFFS generally cause only mild effects, the potential occurrence of systemic effects from some species cannot be ruled out. Considering the above, any bite by European NFFS should receive professional medical evaluation in order to ensure patient safety and appropriate management, as well as detailed documentation facilitating construction of an accurate medical risk profile for the species.

For more than a century, concerns about the medical significance of Montpellier snakes, Malpolon spp. (Psammophiidae, Psammophiinae) have been expressed by herpetologists and toxinologists. Although some of the opinions have suggested that the most familiar species, the Western Montpellier snake, Malpolon monspessulanus, poses a significant medical risk, only a few detailed, formally documented reports have been published that describe effects in humans. Two reports support a rare risk of systemic envenoming (cranial nerve palsies) after prolonged bites by M. monspessulanus. Relevantly, there has been only one previous report describing a bite by the Eastern Montpellier snake, Malpolon insignitus. Reported here are the effects of a bite inflicted by a 1.1-meter female Malpolon insignitus fuscus in Alborz Province, Iran. The 40-yr-old male victim was handling the snake while preparing to photograph it when he was bitten on the right wrist. The snake remained attached for approximately 40-seconds during which it repeatedly advanced its jaws. The bite caused moderate local envenoming that featured moderate but reportedly notably uncomfortable sharp pain, moderate edema, erythema and pruritis; wound site bleeding was transient and proportional. Full resolution required 5-days; there were no sequelae. The clinical evolution included signs/symptoms consistent with Type I hypersensitivity and subtype Type IV hypersensitivity. Detailed reports of medically significant bites by Malpolon spp. are briefly reviewed and the evidence for medical significance of the genus is evaluated. Management of envenoming by Malpolon spp. is supportive only; almost all victims with qualified medical review have developed only local envenoming that is often mild-moderate. Notably rare systemic effects, e.g., neurotoxicity so far limited to non-progressive cranial nerve palsies, should prompt airway protection, ICU admission, and consultation as indicated. Future study of Malpolon venoms and formal documentation of their bites should increase the evidence quality for the medical risk profile of the genus.

We read with interest the paper entitled, "A Retrospective Observational Study of Mangrove Pit Viper Envenomation Presented to Selangor Middle Zone Cluster Hospitals in Malaysia", authored by Chan and colleagues (Toxicon 249, 108086), but have concerns about some of its content. First, the authors claim that: "All patients recruited were diagnosed with mangrove pit viper bite based on either real snake specimen or photographic evidence that enabled species identification clinically (Fig. 1)". However, there is no specific record of the person(s) or expert service who formally provided presumably qualified identification of the specimens and/or images of those assigned responsibility for envenoming. This is an important consideration and should at least be stated under "Limitations", or if there were, stated under "Acknowledgement". The study contains several flaws and misleading assertions, particularly regarding antivenom use and some of the reported clinical observations, and gives an inadequate account of what is published on this interesting species, the recent revisions to its taxonomy, and the clinical effects of envenoming. Below, we have provided comments on the most important of these because they conceivably could impact management of envenomed patients.

The genus Latrodectus (Araneae: Theridiidae) consists of 35 widow spider species with global distribution. Envenoming by medically important species, latrodectism, commonly features bite site erythema and diaphoresis, variably severe pain that may be persistent, myalgia/cramping and/or myoclonus, autonomic symptoms, abdominal distress; severe envenoming can be prolonged and include serious effects such as oliguria, hypertension and, rarely, myocarditis/myocardial injury. Red-back spiders (Latrodectus hasselti) are the most common cause of envenoming in Australia and can cause the spectrum of effects noted for other medically important widow spiders. A 34-yr-old woman with a history of previous L. hasselti envenoming and treatment with antivenom was envenomed in her left ankle by a verified L. hasselti (hiding in her boot) while attending an appointment with her primary care physician. She reported some of the common effects of latrodectism including severe, prolonged pain, bite site diaphoresis, and malaise; however, she also developed marked edema that involved the entire left foot. She also exhibited mild hypertension and autonomic/non-specific effects limited to nausea, headache, and anxiety. She was effectively treated with red-back spider antivenom (a total of 4 ampoules) and supportive care; full resolution of the edema required almost 5 days. The uncommon clinical evolution of L. hasselti local envenoming observed in this patient may have been caused by a mixed picture of venom-induced effects and Type I hypersensitivity, but alternatively could be a rare, solely venom-induced manifestation. While provision of patient-centred care for anyone envenomed by Latrodectus spp. requires careful history collection and assessment of comorbidities, differentiation of atopic and direct venom effects may be challenging in some envenomed patients with established complex allergy history.

We describe species richness patterns of venomous snakes in Iran in order to produce snakebite risk prediction maps and identify gaps in regional health care centers capable of managing snakebites. We digitized distribution maps from the literature, Global Biodiversity Information Facility (GBIF), and the results of our own field studies of 24 terrestrial venomous snake species (including 4 endemic to Iran). Species richness patterns were associated with eight environmental factors. The variables have been extracted from the WorldClim dataset (bio12 = annual precipitation, bio15 = precipitation seasonality, bio17 = precipitation of the driest quarter, bio2 = mean diurnal range, bio3 = isothermality (bio2/bio7), bio4 = temperature seasonality, bio9 = mean temperature of the driest quarter and slope). Based on spatial analyses, species richness in Iran is highly affected by three environmental variables (bio12, 15, and 17) associated with precipitation. The relationship patterns among these predictors and species richness were strong and linear. The hotspot regions for venomous snakes species are concentrated on the western to southwestern and north to northeastern regions of Iran, which is partially consistent with the known Irano-Anatolian biodiversity hotspot. Because of the high number of endemic species and climatic conditions on the Iranian Plateau, the venoms of snakes distributed in those areas may contain novel properties and components.

In Iran, there are approximately 4500-6500 snakebites per year, but fortunately only 3-9 of these are fatal. However, in some population centers such as Kashan city (Isfahan Province, central Iran), approximately 80% of snakebites are attributed to "non-venomous" snakes that are often comprised of several species of non-front-fanged snakes (NFFS). NFFS comprise a diverse group that constitute approximately 2900 species belonging to an estimated 15 families. We report here two cases of local envenoming from H. ravergieri, and one from H. nummifer that occurred in Iran. The clinical effects consisted of local erythema, mild pain, transient bleeding and edema. Two victims experienced progressive local edema that distressed the victims. The medical team's unfamiliarity with snakebites contributed to the incorrect clinical management of one victim including the contraindicated, ineffective provision of antivenom. These cases provide further documentation about local envenoming caused by these species, and also emphasize the need for regional medical personnel to receive increased training in order to improve familiarity with the local snake fauna and evidence-based snakebite management.

The mixed quality evidence about non-front-fanged snake bites has included unsupported speculation and presumption; the possible role of atopy and/or primary hypersensitivity have often been prematurely discounted. Described is a medically insignificant bite by a captive African emerald snake, Hapsidophrys smaragdinus Schlegel, 1837 (Colubridae, Colubrinae) that caused the development of moderate Type IV hypersensitivity; the 44-year-old male victim experienced persistent pruritis and an erythematous bite site maculopapular dermatitis that slowly resolved and required 6 days for full resolution. The victim had received several previous medically insignificant bites from non-front-fanged snakes. Brief comparison is made with a previously reported case consistent with a mixed clinical picture of local mild envenoming and hypersensitivity from a bite by another colubrine, the coin snake (Hemmorhois nummifer). This case highlights slowly accumulating evidence supporting the risk of acquired and primary hypersensitivity to some snakebites in susceptible individuals. In order to provide accurate medical risk profiles for less-known snake species it is essential that the case of any patient developing acute or delayed effects from bites by these species is formally documented. The need for further attention to atopic risks, especially in private collectors, is emphasised with consideration of venom/other ophidian product-induced anaphylaxis.

The medical risks of representative nonfront-fanged colubroid snakes (NFFCs) were assessed by critical review of selected cases of bites published from 1875 to 2021. Some previously unpublished cases personally managed by or communicated to one or more of the authors were also included. Using patient-centered quality of evidence criteria, the reviewed cases were ranked A–D. The cases containing sufficient quality information allowing analysis involved approximately 130 taxa, of which only around 32 inflicted medically significant bites. A number of these received low-quality evidence rankings because of numerous flaws and pitfalls in the reports. The majority of these cases involved insignificant or mild local effects (puncture wounds, abrasions, lacerations, limited bleeding, and mild edema). A small number of reports described bites producing moderate local effects that occasionally resulted in persistent symptoms. The life-threatening risks of colubrine genera such as Dispholidus typus and Thelotornis spp. (African bird, twig, tree, or vine snakes) and that of natricids, such as three taxa of Rhabdophis (keelbacks), are well established by clear clinical evidence. Bites from these species cause consumptive coagulopathy and hemorrhagic diathesis, complicated in some cases by acute renal injury. In some cases perpetuated in the literature, fatal consequences of bites inflicted by Tachymenis peruviana (Peruvian slender snake), Philodryas olfersii (Lichtenstein's or South American racer), Oligodon arnensis (banded kukri snake), or Xenodon severus (Amazon false fer-de-lance) were implied without providing any specific information or reasonable clinical evidence supporting these outcomes. Brown tree snakes (Boiga irregularis) have been involved in a large number of bites, but the precise etiology of the serious clinical effects in a few pediatric patients remains unclear. Although there is a verified case of a Malpolon monspessulanus (Montpellier snake) bite causing cranial nerve palsies, there is a very limited number of evidence-based cases on which to evaluate the risks posed by these snakes. Isolated reports of bites by several species of NFFCs have described aberrant effects that were very likely due to alternative etiologies other than the snakebite. Speculation regarding the possible roles of toxins found in oral secretions of nonvenomous lizards (several species of varanids, anguids, agamids, and iguanids) that would support its use as “venom” should be accompanied by nonsensationalist evidence of biological use, e.g., use in acquisition of prey (unlikely) or a defensive role. To date, there is no evidence of medical importance or significance of any saurian oral secretion other than those of the venomous helodermatid lizards, the Gila monster (Heloderma suspectum), and any of the four species of beaded lizards (e.g., Heloderma horridum). Several published cases purporting the life-threatening or even fatal effects of bites by varanid lizards (principally, the Bengal monitor, V. bengalensis, and the desert monitor, V. griseus) have serious flaws such as: limited or no consideration of differential diagnoses that are more likely causes for the described clinical syndrome, absence of formal medical review, and/or insufficient/poor quality clinical evidence. Further consideration of so far unsupported clinical assignment of serious medical risks to these varanids requires very carefully documented, verifiable evidence including formal identification of the envenoming species. Although there is limited information about the epidemiology of bites by most NFFCs, analyses of larger series of documented bites by some species (e.g., the South American racers, P. olfersii and P. patagoniensis, as well as the brown tree snake, B. irregularis) have yielded some significant associations between specific factors/circumstances, and the occurrence of medically significant bites by these species, while other series (e.g., bites by the Pampas snake, Tomodon dorsatus) have reinforced the medical insignificance of bites by other species. Presuppositions about snakes, the effects of snakebites, and individual psychiatric tendencies can significantly impact the victims' response to NFFC bites.

An unknown number of non-front-fanged colubroid snakes possess Duvernoy's venom glands that produce venom released under low pressure (due to a lack of muscular compression of the glands). This is in marked contrast to the highly muscular and thus pressurized glands of front-fanged colubroids such as viperids, elapids, and atractaspidids. While pressurized venom glands release a bolus of stored venom under high pressure (that may exceed 30 psi), non-front-fanged colubroids inoculate or introduce their venom and/or other oral products into wounds produced by maxillary teeth that may be enlarged, posterior or mid-maxillary (in a few studied examples these teeth are just posterior to the anterior-most maxillary teeth), and may or may not be grooved; but unlike those of front-fanged colubroids, they are never canaliculated (e.g., never hollow, or with a lumen). Dispholidus typus (boomslang) and possibly other members of the tribe Dispholidini have limited striated muscle insertion into the gland and thus may be considered to have a partially pressurized venom delivery system. Several hypotheses have been considered that attempt to address the evolution of the venom apparatus and the selection for venom delivery systems. The definition and use of the term “venom” is indicative of the biological use for prey subjugation and/or possibly defense. The clinical effects of ophidian oral secretions do not constitute criteria for use of the term ‘venom’, and terms such as “mildly venomous” are misleading for the same reason. Experimental investigation of a relatively small number of non-front-fanged snake venoms and observations of prey handling in a small variety of species has demonstrated notable prey-specific venom in several species (e.g., brown tree snake, Boiga irregularis , mangrove or gold-ringed cat eye snake, Boiga dendrophila , and Amazon puffing snake, Spilotes sulphureus ). While most studied non-front-fanged species have little or no medical importance, others such as Dispholidus typus , the African twig, bird, or vine snakes, Thelotornis spp., three species of keelbacks, Rhabdophis spp., the Montpellier snake or hooded malpolon, Malpolon monspessulanus , and Lichtensteins' green racer ( Philodryas olfersii ) have medical importance, although serious envenoming by some of these (e.g., M. monspessulanus , and the flower keelback, Rhabdophis ceylonensis ) is rare and there is so far only one well-documented case of each.

Snakebite is an important problem in Myanmar. Regionally, bites by Eastern Russell's vipers, Daboia siamensis (Viperidae, Viperinae), and monocled cobras, Naja kaouthia are considered medically important, but those categorised as "green snake" bites are not. However, these may include bites by green pit vipers, Trimeresurus spp. (Viperidae, Crotalinae) for which no antivenom is available in Myanmar. Elsewhere in Southeast Asia, these snakes are reported to cause local and systemic envenoming. As part of the Myanmar Snakebite Project, prospective case data were collected over 3 years from five hospitals in the Mandalay region. These included 3803 snakebite cases reported from Mandalay region. Of these, 355 were listed as bites by a witnessed green-coloured snake. In 22 cases, the snakes responsible were retained and preserved, then expertly identified; 21 were medically important white-lipped pit vipers (Trimeresurus albolabris), and one as an Asian vine snake, Ahaetulla prasina (Colubridae, Ahaetuliinae) which is not of medical importance. Among confirmed Trimeresurus albolabris bites, 15/21 developed swelling of the bitten limb, and 3/21 coagulopathy, defined as a positive 20-min whole blood clotting test (20WBCT). None developed necrosis, blistering, thrombocytopenia or acute kidney injury (AKI). Of the remaining 333 patients bitten by green snakes that were not specifically identified, 241 (72%) developed swelling of the bitten limb, and 62 (19%) coagulopathy. AKI occurred in 21/333 patients, but only one required dialysis. At least 10/21 of the cases with AKI in this study were more likely to represent bites from Trimeresurus spp. than D. siamensis because the snake responsible was brought into the hospital, examined and described by the treating physician as "green-coloured". This study describes a previously unpublished case of AKI from envenoming by T. erythrurus in Yangon, and reviews cases of AKI following bites by this species and T. albolabris in Myanmar. This confirms that, at least on rare occasions, Trimeresurus spp. envenoming can cause AKI. This has important implications for snakebite management in Myanmar as the finding of local swelling, coagulopathy and AKI is generally considered pathognomonic of D. siamensis envenoming. Further collection of confirmed Trimeresurus spp. bites is required in Myanmar in order better to define the syndrome of envenoming and to assess the possible need for antivenom against Trimeresurus spp. in this country.

Two cases of bites by a South African psammophiid snake, Psammophylax rhombeatus, are described and analyzed. These are the first detailed reports of local envenoming by a Psammophylax spp. While handling a wild-collected 1 m P. rhombeatus, the snake inflicted a protracted bite proximal to the metacarpophalangeal joint of digit #5, left hand of a 24-year-old male amateur herpetologist. Local edema persisted for three days, but no pain or other signs or symptoms including non-specific autonomic effects (e.g. headache, nausea) occurred. In a second case, a 28-year-old male herpetologist-photographer was repositioning a 0.58 m female P. rhombeatus in order to photograph the snake and her egg clutch, when the snake bit the metacarpophalangeal joint of digit #5, left hand, and briefly advanced its jaws. The bite caused mild local pain, progressive edema of the left hand, and arthralgia; resolution required almost 1 week. Bites from non-front-fanged snakes such as these by P. rhombeatus are uncommonly reported in comparison with those described for front-fanged snakes (e.g. Viperidae, Elapidae). Therefore, documentation of bites even with minimal effects provides information essential for the construction of an accurate medical risk profile for these less-known species.

True venom systems evolved at least twice in extant reptiles – first, early in helodermatid lizards and second, much later in advanced snakes (non-front-fanged colubroids and front-fanged colubroids – viperids, elapids and the lamprophiid genus Atractaspis). In helodermatids, the venom gland lies along the lower jaw and empties near grooved, multiple teeth within the mouth. As these slow-moving lizards feed largely on eggs and nestlings, this venom system probably comprises part of a defensive strategy. Within venomous snakes, the venom gland lies in the temporal region. In viperids and elapids, it generally consists of a main venom gland, pressurized by the contraction of directly attached striated muscles and thereby facilitating the forceful ejection of a pre-stored venom bolus during a delivered strike, and an accessory gland with connecting ducts eventually emptying into a hollow fang. Gland morphology is variable, and some smaller fossorial (burrowing) species have less luminal storage space for pre-synthesized venom. The burrowing asps or mole vipers (Atractaspis spp., Lamprophiidae, Atractaspidinae) possess only a main venom gland, although it too is pressurized by striated muscles. Several genera of front-fanged fossorial or semi-fossorial species, including some species of Atractaspis spp., some night adders (Causus spp., 7 species; Viperidae, Viperinae) and long-glanded coral snakes (Calliophis spp., 11 species; Elapidae), as well as Buerger's forest snake (Toxicocalamus buergersi, Elapidae), have unusually elongated venom glands. As mentioned, most front-fanged venom systems are closed systems producing a sudden, high-pressure discharge of the venom bolus drawn from a reservoir within the gland. The pressure generated in some studied crotaline viperid venom glands may exceed 30 psi, comparable to automobile tire pressure. In contrast, many non-front-fanged colubroid snakes possess a low-pressure system based on a gland lacking a large reservoir, which releases secretion (venom) more slowly into oral epithelium adjacent to teeth that are sometimes deeply grooved and may be partly enclosed, e.g., have a partially formed lumen but are never fully enclosed or hollow. Consequently, prey acquisition/subjugation systems based on a "Duvernoy's" or "low-pressure venom gland" system may employ an adaptive strategy different from that of front-fanged venomous snakes. In viperids, elapids and Atractaspis, the venom system 100discharges a bolus of venom quickly, in many cases (but not all) dispatching the prey (or perhaps thwarting a predator). Such differences in deployment of these oral glands, in an adaptive context, account for variation in gland structure and in the composition of their products. Although extensive research has focused on the toxic properties of these oral secretions, it is now clear that venom components perform multiple biological functions. However, assigned biological roles must be based on either experimental or carefully obtained observational evidence, not conjecture or assumption, whereby it is shown that the oral secretions in fact are injected at levels capable of producing favorable prey capture/subjugation results. However, some prey-specific toxins may compensate for minimal venom volumes that are ultimately delivered to vertebrate and invertebrate species that account for a large proportion of ingested prey items. Elucidating the intricacies of reptile venom, as well as other oral products, and their delivery will significantly improve our understanding of the evolution of the complexity of composition and function of these secretions and their delivery to prey and/or possibly predators.

Weinstein, Scott A. MSc, PhD, MBBS, MD, FAAFP; Sanders, Kate L. PhD; White, Julian MBBS, MD Author Information