Manuscript: A Case Report of Delayed, Severe, Paroxysmal Muscle Cramping after Chilean Rose Tarantula (Grammostola rosea) Envenomation

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.

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.

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.

Aluminium phosphide (AlP) is a toxic agent associated with a high mortality rate following acute exposure from various routes. The aim of this study was to determine the clinical and laboratory findings useful for predicting the medical outcome of AlP-poisoned patients using established scoring systems. This is a prospective study of AlP-poisoned patients from 2010 to 2015 in Ardabil, Iran. All patients that presented with a confirmed diagnosis of acute AlP poisoning in the study interval were included in the study. Clinical and laboratory data, using Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA) and Simplified Acute Physiology Score II (SAPS II) scoring systems, were compared for their predictive value in determining differences between survived and non-survived patients. Univariate analysis (Mann-Whitney or t-test), multiple logistic regression analysis, receiver operating characteristic (ROC) curve analysis and the Pearson correlation test were performed using STATA/SE 13.0 and the Nomolog Software. A total of 68 AlP-poisoned patients with confirmed acute AlP poisoning were included for evaluation. Of these, 36 were non-survived. Multiple logistic regression analysis was performed using parameters and values derived from patient clinical and laboratory data, and revealed that four factors were significant for predicting mortality: Glasgow coma score (GCS); systolic blood pressure (SBP); urinary output (UOP); and serum HCO3 . A four-variable, risk-prediction nomogram was developed for identifying high-risk patients and predicting the risk of mortality. Study results showed that SBP of <92.5 mmHg (p = 0.006); HCO3- < 12.9 mEq/L (p = 0.01), UOP < 1725 mL/day (p = 0.04); and GCS < 14.5 (p = 0.003) were significant predictors of AlP mortality. Scoring systems analysis showed SAPS II score >24.5, APACHE II score >8.5 and SOFA score >7.5 were predictive of non-survival patients. The results of our study showed that SBP, GCS, UOP and serum HCO3 levels are the best prognostic factors for predicting mortality in AlP-poisoned patients. According to the area under the ROC curve of the APACHE II score, when compared with SOFA and SAPS II scores, the APACHE II score can more effectively discriminate between non-survivors and survived patients.

A great natural diversity exists across animal taxa and species that produce venom, and although venoms are primarily used in the acquisition of prey and secondarily for defense, it is their adverse effects on humans that have driven scientific and medical research. The spectrum of venom-producing organisms and the venom components and toxins across organism species is highly variable. Venom components function in concert and selectively in their actions producing pathophysiological effects for subduing prey. In contrast, when non-prey species such as humans are encountered, the biting or stinging as a result of a defensive or fear response may result in envenomation. Following envenomation a myriad of venom-/toxin-induced adverse and toxicological insults to various physiological systems may result. What creatures are venomous, how they envenomate, their venom composition, how their venom components/toxins work mechanistically, and the pathophysiological effects of venom in envenomated humans led to the quest for remedies and antidotes. Prominently, among therapeutic advancements was the development of passive antisera therapy in the late1800s for cobra envenomation (Calmette 1894). Today’s formulations of snake venom immunotherapies (antivenom) are relatively unchanged with respect to general antibody structure and mechanism of action. However, recent technological advances in antibody preparation, purification, and product formulation and combined venomic and antivenomic technologies are leading to novel, refined toxin-targeted antivenoms (Calvete et al. 2009). Toxinology has been translational over time, across biological systems, across scientific disciplines, and technologically, leading to our improved understanding of venom-producing animals, venoms, and the design and development of more efficacious antivenoms.

INTRODUCTION:Protobothrops mangshanensis, the Mangshan pit viper, is a rare pit viper native to the area surrounding Mount Mang in China's Hunan province. Toxicity from envenomation is not well characterized. CASE DETAILS:A 33-year-old male presented to an emergency department (ED) after being bitten on the forearm by his P. mangshanensis. He complained of mild swelling and pain at the bite site. He was admitted for observation and toxicology consultation. Following initially normal coagulation studies including platelets, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and D-dimer, fibrinogen decreased to 121 mg/dL and D-dimer concurrently rose to 377 ng/mL over 24 h. On hospital day 2 fibrinogen stabilized at 109 mg/dL and he was discharged with outpatient laboratory monitoring. Three days later, he returned with bruising to the contralateral arm. Fibrinogen was undetectable (<40 mg/dL) and PT was 14.6 s. He declined admission but returned 2 d later with bruising to the nose. Bloodwork revealed immeasurably prolonged PT, aPTT, and thrombin time, but he eloped. Late that evening he returned and was treated with three vials of Green pit viper (Trimeresurus albolabris) antivenom. Within 24 h coagulopathy improved markedly; at five days, coagulation abnormalities resolved. DISCUSSION:Mangshan pit viper envenomations may cause isolated hemotoxicity, despite molecular studies suggesting additional neurotoxicity and myotoxicity. T. albolabris antivenom appears effective in treating the resultant coagulopathy. CONCLUSION:We report the natural history of envenomation by the Mangshan pit viper. A delayed coagulopathy, apparently fibrinolytic in nature, is unaccompanied by local tissue destruction and responsive to Green pit viper antivenom.

The environmental toxicologist must be aware of a vast array of potentially toxic substances produced by animals and plants. Venomous lizards have grooved teeth with four venom glands on each side of the mandible that supply the teeth with venom from the dorsal surface. Venomous animals are those creatures which produce a poison in a highly-developed gland or group of cells and inject the substance into another animal or plant by a bite or sting. Only a relatively small number of arthropods are sufficiently venomous to be a health hazard to humans. Only a few species of mammals are venomous. The majority of plant intoxications in the US occur from the ingestion of plants that contain gastroenteric irritants. Several plants in the US contain atropine or atropine-related alkaloids. Nitrates accumulate in the vegetative tissues especially in the stalk of certain plants. In general, dermatotoxic plants cause irritation, blistering, pain, and itching.