Abstracts
When a Snake Strikes and You're in the Middle of Nowhere!
Keyler, Daniel E.
Department of Experimental & Clinical Pharmacology
University of Minnesota
Minneapolis, Minnesota USA
Professional and amateur herpetologists frequently find their way to the favorable habitats of venomous snakes in the southwestern USA, where they are remote to a medical facility. Consequently, out of the blue, a cascade of confounding events may follow that “unexpected” crotaline bite. What you do if bitten must be linked with a rational approach to avoid confusion and provide an unwinding path to timely medical care. Where are you now that you’ve sustained a venomous bite? Should you institute immediate first aid measures? Who are you going to call for assistance and consultation? How will you be transported for rescue pickup and what is your timeline for getting to a medical facility? Stabilization and rapid transport to a medical facility with antivenom administration capabilities are crucial factors, and the interval prior to arrival at a medical facility (including interhospital transport) is a critical period for patient management. Could antivenom be administered during transport? After arrival at a medical facility are the medical staff experienced with treating venomous snakebite patients and antivenom administration (antivenom availability)? If receiving facility staff is inexperienced will they be amenable to toxicology consultation? Ideally, these considerations and steps should transition smoothly as a functional process. However, all too often, the course of actions following envenoming in remote locations is incongruous despite the involvement of experienced medical personnel. Thus, a key factor for improving the medical outcome for envenomed patients is reliable communication at all levels (passing the torch) and minimizing the number of individuals involved in the communication chain.
Clinically Significant Reptiles of the American Southwest
Cardwell, Michael D.
Arizona Poison and Drug Information Center
College of Pharmacy
University of Arizona
Tucson, Arizona USA
Department of Biology
San Diego State University
San Diego, California USA
The venomous reptile fauna of the American Southwest is abundant and diverse, and no location better exemplifies this richness than southeastern Arizona and southwestern New Mexico. Scientists and hobbyists alike flock here to see, photograph, and study these fascinating creatures. But the area also attracts lots of other visitors who enjoy the weather, scenery, birds, and other wildlife. One thing that all of us share here is the potential for suffering a venomous reptile bite far from the nearest hospital. This presentation will summarize the southwestern reptiles capable of producing medically significant injuries, with an emphasis on those in the region around Rodeo and Portal. You will get a unique look at human encounters from the animals’ viewpoint. How, when, and under what circumstances do rattlesnakes and Gila monsters bite people? Are rattlesnakes evolving to rattle less or produce more toxic venom? Just how deadly are they? There are many myths about venomous reptiles that are widely accepted as fact, including by clinicians and even biologists who study other organisms. This program will bust these myths and provide a better understanding of this group of animals that so many people unreasonably fear. Back to Top
Pitviper Venoms: Composition, Variation and Its Influence on the Symptoms of Envenomation
Mackessy, Stephen P.
School of Biological Sciences
University of Northern Colorado
Greeley, Colorado USA
With the broad utilization of proteomic techniques, highly sensitive dissection of venom compositions is now routinely possible, and with it, an appreciation of the fact that venoms can vary significantly in overall makeup at the species, population and even individual levels. In spite of this, a more conservative observation is that venoms of a particular taxon, such as Crotalus in the United States, are dominated by only a few major protein families, hypothetically making treatment of snakebite more straightforward. However, hidden within this conservative use of protein families by snakes is a diversification of subtypes via gene duplication and neofunctionalization, which may result in different specificities/binding sites/activities of members of the same protein family, even among venoms of closely related species. In addition, some species, subspecies or populations have toxins not as broadly distributed among viper venoms, such as crotoxin homologs and myotoxin a, which in some populations can be exceptionally abundant components of the venoms. How this translates into differential symptoms upon human envenomations is poorly understood but potentially quite important to the mitigation of dominant symptoms. Treatment of viper envenomations in the United States is via the use of one of two available antivenoms, so identification of offending species is somewhat irrelevant in the clinic, as the choices of treatment are more or less identical. However, it is strongly encouraged that offending species be recorded in clinical records, because only then will we be able to dissect out nuances of toxin composition and its effects on symptoms. Back to Top
The Kiss of Death: How Snakes Use Their Venom
Hayes, William K.
Department of Earth and Biological Sciences
Loma Linda University
Loma Linda, California USA
Venomous animals usually rely on their venom to secure food and/or defend themselves, though other functions of venom exist. As a limited commodity and a costly investment, venom should be deployed judiciously. Insufficient venom expenditure will fail to achieve the desired outcome, and excessive use can result in unnecessary metabolic costs of venom regeneration and ecological costs of venom depletion. Thus, natural selection should favor strategies whereby animals modulate, or meter, the quantities of venom expended. This talk will review the assumptions, mechanisms, evidence, and clinical and evolutionary importance of venom-metering by snakes. Ample studies clearly indicate that the amount of venom a snake injects into a target varies with snake size, bite context (predatory or defensive), target identity (species and size), and a host of other factors. Causes for variable quantities of venom expenditure vary, but a number of studies support the interpretation that snakes possess the cognitive (decision-making) capacity to meter venom expenditure during both predatory and defensive contexts. When considered in a larger context, selection should act on multiple features of the venom apparatus, including venom production and storage (venom yield), venom composition, delivery structures, and venom deployment. Although venom composition is often viewed as the critical factor for efficacious venom use, especially in light of shifting prey bases and coevolutionary counter-adaptations of prey, the behavioral capacity of snakes to meter their venom should give them opportunities to “experiment” with venom composition. Nevertheless, the quantity of venom injected is the most important factor influencing pitviper bite severity. Back to Top
The Natural Toxins Research Center: A Resource to Support Snake and Snake Venom Related Research
Sánchez, Elda E. National Natural Toxins Research Centre
Texas A&M University-Kingsville
Kingsville, TX USA
The National Natural Toxins Research Center (NNTRC), a component of Texas A&M University–Kingsville (TAMUK), is a unique animal and biological material resource center organized to support basic and translational research on venomous snakes and their venoms. The NNTRC has served as the only federally funded viper resource center in the U.S., playing a critical role as a provider of high-quality single-source venoms and snake-related research materials to national and international biomedical and biological research programs. The NNTRC aims to provide native venom and purified venom components, recombinant venom proteins, and specialized venom research services of the highest quality to support snake venom–related research in the U.S. and abroad. The NNTRC has assembled a team of experienced scientists and research staff with specialized expertise in the management of venomous snakes and the collection and characterization of snake venoms and anti-venoms. It has also assembled a comprehensive collection of North American venomous snakes, more than 450 animals representing 32 different species consisting of 14 subspecies, maintained under IACUC-approved conditions in a state-of-the-art research serpentarium. The NNTRC is recognized as a reputable and reliable source for venom-related products and specialized services used by academic and commercial research programs to support the development of new drugs and anti-venom therapeutics. The resources of the NNTRC have been applied to research in a wide range of disciplines ranging from genomic and proteomic studies on venom evolution to translational research on nociception and anti-venom therapeutics, research that has been supported by multiple NIH I/C’s, the NSF, Dept of Defense, and national and international research agencies. Back to Top
Treatment of Rattlesnake Envenomation in Small Animals: Lessons from a Lifetime
Carotenuto, Sarah E.
College of Veterinary Medicine
University of Arizona
1580 E Hanley Blvd
Oro Valley, Arizona USA
It’s the sound you DO NOT want to hear. You’re on an evening walk in the wash and you let your dog off leash. He sticks his nose in a bush, yelps, and as he runs back, you hear that characteristic, gut-wrenching rattle and note two punctures on his muzzle, which start bleeding. What veterinary emergency care can you provide immediately in the field? Locally? Is antivenom helpful? Worth the trip into town? What do we know about the rattlesnake vaccine? Join us as we explore the world of snakebites in cats and dogs. Back to Top
100 YEARS OR SO TREATING SNAKEBITES WITH ANTIVENOM
McNally, Jude
Arizona Poison and Drug Information Center (Retired)
College of Pharmacy, University of Arizona
Tucson, Arizona USA
Rare Disease Therapeutics, Inc. (Retired)
2550 Meridian Blvd, Suite 150
Franklin, Tennessee USA
Boesen, Keith
Rare Disease Therapeutics, Inc.
2550 Meridian Blvd, Suite 150
Franklin, Tennessee USA
Without antivenom therapy, pitviper envenomation was, and still is, considered a potentially life-threatening event. In the early 1900s, simply surviving pitviper envenomation was considered an acceptable if not favorable outcome. Treatment prior to antivenoms may have included alcohol (both orally and by injection), strychnine, quinine, bromine compounds (also known as Bibron's antidote) and carbolic acid, enemas, cauterization, and many others. Sadly, reports from the period suggest that some patients, particularly children, died as a result of their enormous alcohol ingestion rather than the envenomation. A French scientist, Albert Calmette developed the first antivenom against cobra venom in 1895. Based on this work the HK Mulford Co licensed the first US species antivenom in 1927. Wyeth whole IgG antivenom, licensed in 1953, dominated the U.S. antivenom market for almost 50 years until a much safer F(ab) was introduced in 2001. Eighteen years later an F(ab’)2 antivenom entered the U.S. market with a similar safety profile and longer lasting effects. We will explore how the sausage gets made as the search continues for the next best tools to treat snakebite by reviewing the laborious and often tedious journey of AV development in the U.S. There are at least 12 important milestones when navigating through the FDA approval process: Animal testing, IND application, Phase 1-3 clinical trials, Review meeting, BLA application, Application review, Drug labeling, Facility inspection, BLA approval. In this talk we cover obstacles inherit in each step of the process. Then we may finally tackle the age old question, why are antivenoms so expensive? Back to Top
National Snakebite Support: A Social Media Platform for Improving Snakebite Education and Treatment
Wyatt, Kimberly M.
Good Samaritan College
Cincinnati, Ohio USA
kimberly.wyatt@email.gscollege.edu
Despite the existence of well-established protocols for the treatment of snake envenomations, many healthcare professionals in the United States still fail to properly manage snakebites. Factors such as lack of exposure during medical training, outdated practices, and misinformation about snakes can lead to inappropriate care and poor patient outcomes. Although social media is a frequent source of misinformation, it can also be a valuable educational resource. In 2016, National Snakebite Support was established to improve knowledge of snakebite prevention and treatment among healthcare providers and the public. Staffed by a volunteer team of medical toxicologists and veterinarians with expertise in the clinical management of snakebites, NSS serves as a repository of current, evidence-based information about envenomations. Using Facebook as a forum for real-time communication with healthcare professionals or individuals actively dealing with snakebites, NSS provides resources to advocate for and guide proper treatment. This talk will highlight some of the challenges and successes of using social media as a tool for snakebite education and outreach. Utilizing Facebook has enabled National Snakebite Support to reach a larger audience than would be achieved through other platforms and has led to proper care for many individuals who did not initially receive appropriate treatment. Back to Top
Evaluation of Pitviper Envenomation: Pre-hospitalization Protocols
Brandehoff, Nicklaus P.
Rocky Mountain Poison and Drug Center Denver, Colorado USA
Department of Emergency Medicine University of Colorado School of Medicine Aurora, Colorado USA
nick.brandehoff@me.com
Venomous snakebites are a medical emergency that need to have prompt evaluation and intervention to minimize the chance of long term disability and/or death. Pre-hospital care is the vital initial process in snakebite care. Developing and implementing pre-hospital protocols that are evidence-based and consistently executed is a necessary step and should be available to EMS systems around the country. Unfortunately, many non-evidence based and occasionally harmful practices continue to occur. In order to ensure the best possible medical care for patients in the United States, EMS systems should meticulously evaluate their protocols and update them on a regular basis. Back to Top
Mojave Rattlesnake (Crotalus scutulatus) Venoms and Envenomings
Greene, Spencer
Department of Emergency Medicine
HCA Houston Healthcare - Kingwood
Kingwood, Texas, USA
The geographic variation of Mojave Rattlesnake (Crotalus scutulatus) venom is well established. Venom containing the Mojave toxin, a pre-synaptically-acting phospholipase A2, causes neurologic effects but has minimal proteolytic and hemorrhagic activity. Venom lacking Mojave toxin primarily causes tissue injury and hematologic toxicity. Additionally, the presence of a separate myotoxin can contribute to rhabdomyolysis independent of local tissue injury. A review of patients with Mojave rattlesnake bites reported to the American College of Medical Toxicology (ACMT) North American Snakebite Registry (NASBR), supplemented by a review of the snakebite literature, found that patients develop variable clinical features following envenomation. In subjects bitten in Arizona, envenomated patients typically develop local swelling, while neurological toxicity is rare. Hypotension is common. In California, swelling and neurological effects are observed with similar frequency; patients have both or one without the other. Rhabdomyolysis in the absence of significant tissue swelling is also reported. Hematologic toxicity, including thrombocytopenia, hypofibrinogenemia, and elevated prothrombin time, is seen in a minority of patients irrespective of geographic location. Both antivenoms with FDA approval to treat North American crotalid envenomations have been used successfully to treat Mojave rattlesnake envenomations. Back to Top
Regional Case Study: A Bite from a Juvenile Tamaulipan Rock Rattlesnake (Crotalus morulus)
Keyler, Daniel E
Department of Experimental and Clinical Pharmacology
University of Minnesota
Minneapolis, Minnesota USA
Grossart, Elizabeth A.
Walter, Frank G.
Department of Emergency Medicine
University of Arizona College of Medicine
Tucson, Arizona USA
Arizona Poison and Drug Information Center
University of Arizona College of Pharmacy
Tucson, Arizona USA
Ashley, Bob
Chiricahua Desert Museum
Rodeo, New Mexico USA
A case of envenoming involving a juvenile Tamaulipan Rock Rattlesnake (Crotalus morulus), a small-bodied montane species from northern Mexico, revealed that a small individual can deliver a bite with significant medical consequences. A 54-year-old male professional herpetologist was bitten on the left thumb by a captive C. morulus. Pain, swelling, bruising, and pressure in the thumb were experienced within minutes. On presentation, he reported 7/10 pain and had firm edema in his thumb and thenar eminence. Laboratory studies showed normal platelet count, PT, PTT, and creatine kinase. He was treated with pain medication and 10 vials of Crotalidae Immune F(ab’)2 (equine) approximately three hours post envenoming. Follow-up lab values remained normal, but he developed lymphangitic streaking and axillary lymphadenopathy followed by progression of edema and emergence of a hemorrhagic bulla prompting treatment with 2 additional 10-vial antivenom doses. His platelet count declined to 125 x 103/µL 24 hours post envenoming and numbness in his thumb developed. Following completion of antivenom therapy the decline in platelets halted and thrombocytopenia improved to 131 x 103/µL prior to discharge 46 hours post-envenoming; fibrinogen, PT, PTT, and CK remained normal. At 5 months follow-up he had no residual signs or symptoms. The venom of C. morulus includes proteolytic venom enzymes that induce local soft tissue destruction, pain, and edema with ecchymosis and blister formation. Although C. morulus venom contains a unique disintegrin (morulustatin) no fibrinogenolytic activity was observed. Back to Top
Veterinary Medicine’s Snakebite Landscape
Woods, Craig W.
The Institute for Future Health
Complex Adaptive Systems
Arizona State University
Tempe, Arizona USA
There are approximately 150 million client-owned dogs and cats in the United States. We have previously estimated over 100,000 canine pit viper envenomings present to veterinary clinics each year in the United States, a figure far exceeding human envenomings. Dogs and humans experience similar pathophysiological consequences and receive similar treatment for pit viper envenoming. Importantly, client-owned dogs represent a comparable population in which to study pitviper envenoming. In this presentation I will review the veterinary medical landscape, comparative pathophysiology and treatment of pitviper envenoming including approved veterinary antivenoms. In addition, I will review perceived gaps and opportunities in veterinary medicine including opportunities for One Health collaborations between researchers, physicians, and veterinarians to advance scientific research and pharmaceutical development. Back to Top
Nuances in the Medical Management of Pitviper Envenoming
Bush, Sean P.
Duke University Health Systems
Duke University
Durham, North Carolina USA
The clinical presentation of pitviper envenoming has been estimated to have a thousand-fold variability. Patients may present with symptoms and signs as trivial as a minor puncture wound or could rapidly progress to multisystem failure and sometimes even death. It is difficult to predict which bites will progress, but “dry” bites have been shown to occur in less than ten percent of rattlesnake bites. Envenomation severity may vary by snake and patient size. Venom is comprised of various toxins in varying concentrations that may vary within an individual snake from season to season and over the course of its lifetime. Snake genus and species may be associated with syndromic presentations, and this may vary geographically. Some components of the envenomation syndrome are neutralized remarkably well by available antivenom(s) but some are not. In this presentation, the presenter will use videography and photography to demonstrate the spectrum of pitviper envenoming and the dynamic response to medical management. Back to Top