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Gila Monster: Unraveling the Mystique of the Desert's Enigmatic Lizard

Written by Benjamin German, MD

A rare occurrence recently unfolded as a Colorado man succumbed to a bite from a captive Gila monster (Heloderma suspectum). These venomous lizards, native to the southwestern United States and northwestern Mexico, are renowned as one of the few medically significant venomous lizards globally, alongside the Mexican beaded lizard (Heloderma horridum). While past reports of fatalities from Gila monster bites are scant and poorly documented, this recent incident offers a glimpse into the potentially life-threatening effects of their venom on humans.

Gila monsters, the largest native lizards in the United States, can stretch nearly two feet in length. With their robust bodies and bony-scaled skin, sporting vibrant patterns of orange and black, they epitomize the rugged charm of desert landscapes. Preferring rocky desert terrains, these elusive creatures primarily feed on bird eggs and small mammals, spending much of their time hidden in underground burrows or rock crevices, only emerging to bask or forage under cover of darkness during hot weather.

In the realm of venomous reptiles, snakes often steal the limelight with their hollow fangs, well-evolved for delivering potent venom. However, Gila monsters boast a unique arsenal with large grooved teeth designed to inflict deep wounds through which venom, produced by glands in their lower jaw, flows into their prey or adversaries. While this venom primarily serves as a defensive mechanism against predators like coyotes, it can induce severe pain and adverse effects in humans if bitten.

Victims of Gila monster bites commonly report excruciating pain lasting hours to days, accompanied by symptoms such as vomiting, diarrhea, sweating, and even loss of consciousness. Despite the absence of specific antivenom due to the rarity of such incidents, prompt medical attention is crucial, involving tetanus vaccination, pain management, and supportive care.

Encounters with Gila monsters in the wild need not evoke panic, as these creatures typically avoid confrontation, preferring retreat over confrontation. However, handling them recklessly, particularly in captivity, can lead to unpredictable bites, underscoring the importance of cautious interaction.

Having had the privilege of observing these captivating creatures in Arizona’s wilderness, I’ve marveled at their resilience and adaptability to harsh environments. While habitat loss, road mortality, and human interference threaten their survival, Gila monsters offer invaluable insights into venom chemistry, contributing to medical advancements. For example, Gila monster venom contains a protein called exendin-4 that was used to develop treatments for type II diabetes. Further study of these proteins led to the development of drugs like semaglutide, which is widely used for weight loss and treating diabetes.

Despite their formidable reputation, fatalities from Gila monster bites are exceedingly rare, and appreciation for these majestic creatures should not be overshadowed by fear. If blessed with a sighting in the wild, it’s best to admire them from a safe distance, refraining from any attempts at capture or handling. After all, in the enchanting tapestry of the desert southwest, Gila monsters reign as resilient icons worthy of admiration and respect.

If you found this article informative, please consider donating to ASF today. Every donation is 100% tax deductible and goes directly to patient care in Africa.

Exploring Viper Venoms

Venomous snakes, particularly vipers, have long captured the imagination of humanity. From ancient myths to modern scientific study, these creatures have intrigued and sometimes terrified us. Central to their fearsome reputation is their venom – a complex cocktail of bioactive molecules designed for subduing prey and defending against threats. Here, we delve into the fascinating world of venom components in vipers, exploring their diversity, functions, and potential applications.

ASF herpetologists at work! Dr. Cara Smith extracts venom from a black mamba (Dendroaspis polylepis) held by Dr. Alpha Baldé.

Vipers comprise a diverse family of snakes found across the globe, from the jungles of South America to the deserts of Africa and Asia. Despite this diversity, they share common traits in their venom composition. Viper venoms typically contain a mixture of proteins, peptides, enzymes, and other molecules, each serving specific purposes in predation and defense.

Proteinaceous Components

Proteins are major constituents of viper venoms and play crucial roles in envenomation. Among the most notable are:

Metalloproteinases: These enzymes contribute to tissue damage and prey digestion by breaking down proteins in the victim's body.

Phospholipases: Another group of enzymes that disrupt cell membranes, leading to cell death and tissue destruction.

Serine proteases: Involved in the disruption of blood clotting mechanisms, causing hemorrhage and preventing prey from coagulating their blood.

Peptide Toxins: Peptides in viper venoms often possess potent bioactivities and are key players in prey immobilization. Examples include:

  • Disintegrins: Small peptides that interfere with platelet aggregation, leading to impaired blood clotting and increased bleeding.

  • Natriuretic peptides: These molecules induce changes in blood pressure and electrolyte balance, aiding in prey incapacitation.

  • Cytotoxins: Peptides that directly attack cells, causing necrosis and tissue damage.

Neurotoxic Components

While neurotoxicity is more commonly associated with elapid snakes like cobras and mambas, some vipers also produce neurotoxic components in their venom. These substances target the nervous system, leading to paralysis and respiratory failure in prey.

Potential Applications

The study of venom components in vipers isn't merely academic; it holds promise for various practical applications:

Medicine: Venom components have inspired the development of drugs for treating hypertension, thrombosis, and even cancer.

Biotechnology: Enzymes and peptides from viper venoms are being explored for their potential in biotechnological processes, such as drug delivery and industrial enzymology.

Toxicology: Understanding viper venom composition aids in the development of antivenoms and enhances our ability to treat snakebite victims effectively.

Liquid gold. Novel molecules in snake venom hold valuable potential for drug development, biotechnology research, and more.

The venom of vipers represents a treasure trove of bioactive molecules, each finely tuned by evolution for specific purposes. By unraveling the complexities of viper venom components, scientists continue to unlock valuable insights into both fundamental biology and practical applications in medicine, biotechnology, and beyond. As we delve deeper into this fascinating realm, we not only gain a greater understanding of these enigmatic snakes but also harness their secrets for the betterment of human health and technology.

If you found this article informative, please consider donating to ASF today. Every donation is 100% tax deductible and goes directly to patient care in Africa.

Demystifying Snake Antivenoms: Understanding Key Terms

Snakebite is a global health concern, and antivenoms are crucial in mitigating their impact. In this post, we'll unravel the complexities of snakebite antivenoms, breaking down key terms like monovalent, polyvalent, specific, paraspecific, and lyophilized to provide a clearer understanding.

Antivenoms come in two primary types: monovalent and polyvalent. Monovalent antivenoms target a specific snake species, offering a focused defense against its venom. Picture them as specialists tailored for a particular snake, providing precise protection. Conversely, polyvalent antivenoms are designed to cover a broader spectrum, acting as versatile defenders against multiple snake species. They are like comprehensive safety nets, ready to counter various venomous threats. There are also bivalent antivenoms, which provide coverage for only two specific snake species.

In the realm of antivenom, the terms "specific" and "paraspecific" delineate critical distinctions in the manufacturing process and subsequent efficacy against venomous species. When an antivenom is labeled as specific, the venom from the exact species it aims to counteract is utilized during its production. This targeted approach ensures a tailored defense against the venom of a particular snake species, contributing to its precision in treating envenomations.

On the other hand, paraspecific antivenoms operate on a broader yet often equally effective spectrum. In cases like the Thai Red Cross Hematopolyvalent (TRC HPAV), although the antivenom is produced using venom from specific species, Russell’s Viper, Green Pit Viper, and Malayan Pit Viper, it demonstrates effectiveness against additional species from the region. The antivenom's coverage extends beyond the species whose venom was directly involved in its production. For example, it effectively counteracts envenomations from many vipers in the region, even though the venoms from these species weren't used in the manufacturing process. This phenomenon showcases the remarkable adaptability of certain antivenoms, providing a broader shield against a range of venomous threats beyond their initially targeted species.

Manufacturers, in some cases, explicitly include paraspecific coverage in their indications, highlighting the effectiveness of the antivenom against certain related species, even though their venoms were not directly used in the production process. This intentional recognition from the manufacturer provides valuable information to healthcare professionals and snakebite responders, aiding them in making informed decisions about the antivenom's applicability in different scenarios.

However, it's equally crucial to recognize the concept of off-label uses in antivenom treatment. In certain situations, medical professionals may choose to employ an antivenom for treating envenomations from snake species not explicitly mentioned on the label.

The distinction between lyophilized and non-lyophilized antivenoms lies in their formulation and storage characteristics. Lyophilized antivenoms, also known as freeze-dried, undergo a process where water is removed to create a stable powder form. This dehydration process contributes to increased stability, allowing for a longer shelf life and easier transportation and storage. Storage requirements depend on the manufacturer, however most lyophilized antivenoms can be stored at room temperature. Upon reconstitution with a diluent, lyophilized antivenoms regain their potency, ready to be administered.

On the other hand, non-lyophilized antivenoms are in liquid form and do not undergo the dehydration process. While this form may be more straightforward to administer, it can be more susceptible to degradation over time, requiring careful storage conditions and a shorter shelf life. Most manufacturers have switched to producing lyophilized antivenoms. 

Antivenoms continue to be the mainstay of treatment for snake envenomations worldwide. Understanding the nuances in terms used in the production and clinical uses is essential for scientists and clinicians to communicate key concepts.

If you found this article informative, please consider donating to ASF today. Every donation is 100% tax deductible and goes directly to patient care in Africa.

The Push For Exotic Antivenom in the United States

In the United States, a variety of institutions, including zoos, laboratories, and private facilities, house venomous snakes from around the world for various purposes. While stringent safety measures are in place to prevent bites, the potential for human error is omnipresent. Native antivenom, such as Anavip and Crofab, is typically stocked in hospitals, yet the same cannot be said for non-native antivenom. For instance, a king cobra bite necessitates antivenom from the Thai Red Cross in Thailand.

Historically, the responsibility of stocking antivenom for exotic snake bites has fallen on the shoulders of local zoos. When a keeper is bitten, the zoo would generously donate antivenom to the patient. However, this approach not only strains the zoos, requiring time to replace antivenom and putting keepers at risk, but it also poses a danger to the patient due to the time-consuming logistics of organizing and executing antivenom transportation. In cases of envenomation, every minute is crucial.

In a positive shift, many responsible private facilities have taken it upon themselves to stock species-specific antivenom. Nevertheless, this undertaking is no small feat, involving navigating bureaucratic obstacles. Non-native antivenom is categorized as an experimental drug, lacking FDA approval. To stock these experimental drugs, a BB-IND# from the FDA is mandatory, involving complex paperwork and a physician's signature to affirm the antivenom's use. Beyond FDA approval, the non-native antivenom is not available for purchase in the U.S., requiring involvement from the USDA to import the drugs. Obtaining a separate permit from the USDA involves additional paperwork, and the process can be further prolonged by the potential months it takes to ship antivenom.

Most physicians in the U.S. rarely treat native envenomations, let alone exotic envenomations with exotic antivenom. In contrast, the physicians at the Asclepius Snakebite Foundation possess a unique expertise, not only in treating native snakebites but also in managing envenomations from species all over the world.

A significant development has been the founding of the Antivenom Support Group (ASG). Collaborating with the FDA and USDA, the ASG has produced comprehensive guides outlining step-by-step procedures for obtaining the necessary permits and contacting manufacturers overseas. This initiative has spurred a notable increase in private facilities independently stocking their own antivenom. The Asclepius Snakebite Foundation has played a crucial role in this process, with physicians offering valuable assistance. This includes Emergency Action Plan recommendations, or antivenom manufacturer and quantity recommendations customized to each situation, as well as facilitating the acquisition of life-saving medications, and providing essential consultation services during emergency situations across the country.

Through a large network of collaborators including ASF, ASG, FDA, USDA, zoos, private keepers, and others, we strive to improve access to quality antivenoms not only in areas such as West Africa, but also here in the United States as well.

If you found this article informative, please consider donating to ASF today. Every donation is 100% tax deductible and goes directly to patient care in Africa.

Snakebite Treatment: Past, Present, and Future

The Antivenin Nearctic Crotalidae treated bites by crotalids such as cottonmouths (picture by Meg Jerrard on Unsplash)

The Antivenin Nearctic Crotalidae treated bites by crotalids such as cottonmouths (picture by Meg Jerrard on Unsplash)

Snakebites have challenged humans for centuries. Without a proper understanding of how snake venoms worked, physicians used the same ineffective treatments through much of history. These practices included manually sucking the venom out of a wound or serving Theriac, a concoction made of herbs, spices, opium, ground-up snakes, and even powdered mummies, to the victim. These remedies remained popular in western medicine into the seventeenth century.1

Antivenom, or antivenin, was developed in the 1890s as a new treatment for envenomation. Though who first created antivenom is heavily debated, most credit a French immunologist named Albert Calmette (1863-1933) who sought a treatment for cobra envenomations in Vietnam. Having witnessed a large number of monocle cobra bites after a heavy rainy season, he decided he had to act. He developed a new serum by injecting small, non-lethal doses of cobra venom into various animals; these animals went on to develop antibodies capable of neutralizing the venom. Calmette would then extract some blood from the animals and isolate the antibodies to purify into antivenom.2 This technique is still used in animals such as horses and goats to create antivenom today.3

Calmette’s discovery eventually led to commercial production of antivenoms. Three decades later, the HK Mulford Company of Philadelphia, overseen by the Antivenin Institute of America, began producing the first commercial antivenom in the United States. Their antivenom, called the Antivenin Nearctic Crotalidae, could treat the bites of various North American crotalids (copperheads, cottonmouths, and rattlesnakes). This versatility was possible because of the antivenom’s polyvalence–it contained antibodies effective against the venoms of numerous species.4

Antivenoms are now manufactured all over the world to treat all kinds of snakebites. However, the technology is far from perfect. Polyvalent antivenoms continue to be a work in progress today, and one of the main difficulties in creating a versatile and effective antivenom stems from the variation in venom across species. Elapids like cobras and taipans, for example, usually possess neurotoxic venom, while crotalids such as rattlesnakes and adders possess a completely different hemotoxic venom.

Due to significant diversity in venoms, drug companies must develop antivenoms specific to each snake species. Existing polyvalent antivenoms are limited and can only treat a few of the species most responsible for envenomations. For example, the main polyvalent antivenom produced in India only covers the “Big 4” snake species out of the 60 capable of envenoming humans. As a result, there is no antivenom treatment for people who have been bitten by many snakes not included in the “Big 4.” Without any other available treatment, doctors are forced to use this same antivenom on these patients, often leading to treatment failure. Furthermore, all Indian antivenom manufacturers source their venoms from one geographical population of each species, and because of variations within different populations of the same species, these antivenoms may not be very effective for patients of different locations.5 Similar issues exist with antivenoms produced around the world.

Current antivenom technology is limited due to the complexities of venom across and within species. However, scientists are creating new potential therapies with the goal of more effectively treating all snakebites. For example, the drug manufacturer Ophirex is conducting clinical trials for a PLA2 inhibitor, varespladib, which could treat snakebites from more species than any current treatment. Unlike traditional antivenom technology, the drug works by blocking PLA2 enzymes that play a major role in bleeding, tissue destruction, and paralysis. This class of enzymes are found in 95% of all snake venoms and may be the key to developing treatments that cover snakebites more broadly. Other small molecule therapeutics such as metalloproteinase inhibitors, aptamers, and chelators, among many others, are also currently being studied. As companies experiment with new therapies, antivenom technology will continue to grow and improve, hopefully resulting in better health outcomes for snakebite patients around the world.6

If you found this article informative, please consider donating to ASF today. Every donation is 100% tax deductible and goes directly to patient care in Africa.

What to Expect When You're Expecting... And Snakebitten

Pregnancy is a unique and life-changing journey, but it can also bring unexpected challenges and risks. One such risk, though rare, is the possibility of a snakebite. Snakebites during pregnancy require careful and prompt attention due to potential risks for both the mother and the unborn child. It is important for patients and their healthcare providers to understand the essential aspects of snakebite treatment in pregnancy, emphasizing safety measures for both the mother and her developing baby.

Understanding the Risks

Snakebites during pregnancy can be particularly concerning due to the potential complications they may cause. The severity of the snakebite and its subsequent effects on the mother and fetus depends on various factors, such as the snake species, the amount of venom injected, and the gestational stage of the pregnancy.

While snakebites can lead to serious consequences regardless of the victim's age or health, pregnant women face additional challenges due to the potential harm that venomous toxins can inflict on fetal development. It is crucial to address snakebite treatment promptly and efficiently to minimize risks.

Immediate Actions to Take

1. Seek Medical Attention: If a pregnant woman is bitten by a potentially venomous snake, immediate medical attention is crucial. She should call for emergency medical services or head to the nearest healthcare facility as soon as possible. It is essential to share her pregnancy status with healthcare providers so that they can make informed decisions about her treatment.

2. Immobilization: To slow down the spread of venom through the body, limit movement of the affected limb.

3. Stay Calm: Panic can accelerate the heart rate and spread venom more quickly throughout the body. It is essential for the pregnant woman, her partner, or any accompanying person to stay as calm as possible and reassure the mother.

Treatment Considerations

Snakebite treatment in pregnancy requires a careful balancing act between addressing the mother's health and ensuring the safety of the developing fetus. Here are some key considerations:

1. Antivenom Administration: The decision to administer antivenom should be made by healthcare professionals experienced in snakebite management. They will consider factors such as the snake species, the severity of the bite, and the mother's overall health, including her pregnancy status. Antivenom can be life-saving for both the mother and baby, but careful considerations need to be made.

2. Monitoring: Pregnant women who receive antivenom or other treatments for snakebites may require closer monitoring. Vital signs, fetal heart rate, and the progression of symptoms should be carefully observed.

3. Imaging and Laboratory Tests: Healthcare providers may use ultrasound or other imaging techniques to assess the fetus's well-being and development following a snakebite. Laboratory tests, such as complete blood count and coagulation profile, should be done to monitor for any abnormalities.

4. Preterm Labor Considerations: In severe snakebite cases, there may be a risk of inducing preterm labor. Healthcare providers will closely monitor the pregnancy and take necessary actions to prevent preterm delivery if possible.

Snakebites during pregnancy require immediate medical attention and careful consideration of treatment options. The health and safety of both the mother and the unborn child should be the top priority. Pregnant women, especially those in snake-prone areas, should take precautions, such as wearing protective clothing and being cautious when walking in tall grass or wooded areas.

In the unfortunate event of a snakebite, it is crucial to remember that prompt medical attention, appropriate antivenom use, and close monitoring are essential to improve the chances of a positive outcome for both the mother and her developing baby. Expert physicians are equipped to make informed decisions to ensure the best possible care and safety during this challenging time.

Breastfeeding

Breastfeeding is an intimate and often unique bonding time between mother and child.  Though rare, snakebites can occur to lactating mothers, and the question often arises whether breastfeeding should continue. While no good data exist on whether breastfeeding is safe, anecdotal evidence in areas where alternatives to breastfeeding are not readily available suggests it is safe to breastfeed both after a snakebite and after receiving antivenom.

If you found this article helpful, please consider donating to ASF today. Every donation is 100% tax deductible and goes directly to patient care in Africa.

How is Antivenom Made?

Snakebites are a global health crisis, affecting millions of people every year. Venomous snakes can deliver a lethal dose of venom with a single bite, making immediate treatment a matter of life or death. Thankfully, immunology pioneers in the 1890’s were the first to develop snake antivenom…and we still use the same process today!

Snake venom is a complex cocktail of various proteins, enzymes, and other substances, each with its unique effects on the human body. These venom components can cause severe tissue damage, interfere with blood clotting, can cause paralysis, and even lead to organ failure. Snake antivenom, on the other hand, is a specialized serum that contains antibodies capable of neutralizing the venom's toxic effects.

The steps for antivenom production.

Step 1: Venom Collection: To produce snake antivenom, venomous snakes are carefully selected and milked for their venom. This process involves stimulating the snake's venom glands while safely collecting the venom drops. Expert herpetologists or trained professionals perform this task, ensuring minimal harm to the snake and themselves.

Step 2: Venom Dilution: Once collected, the venom is carefully diluted. This step is crucial to reduce its toxicity and make it safe for subsequent use in the production of antivenom. Dilution also helps in standardizing the venom concentration for consistent batch production.

Step 3: Animal Immunization: Next comes the immunization stage. The diluted venom is injected into a host animal, often horses, although other animals like sheep or goats can also be used. Horses have proven to be particularly effective in producing large quantities of antibodies. The injected venom stimulates the animal's immune system to produce a defensive response, generating specific antibodies to combat the venom toxins.

Step 4: Antibody Harvesting: Over a period of several weeks, the host animal's immune system produces a significant quantity of antibodies against the venom. Regular blood samples are collected from the animal, typically from the jugular vein, and processed to separate the serum, which contains the valuable antibodies. The animal's well-being is closely monitored throughout the process, and steps are taken to ensure their comfort and health.

Step 5: Purification and Standardization: The harvested serum is subjected to purification techniques to remove any impurities and concentrate the desired antibodies. Various purification methods, such as chromatography and filtration, are employed to achieve this. The purified antibodies are then analyzed and standardized to ensure consistent quality and potency.

Step 6: Testing and Packaging: The final step involves rigorous testing of the antivenom to assess its effectiveness and safety. The antivenom is tested for its ability to neutralize the venom's toxic effects through in vitro assays and in vivo tests. Once the product meets the required standards, it is packaged into vials or ampoules, ready for distribution to hospitals and healthcare facilities.

The production of snake antivenom is a complex and intricate process that involves careful venom collection, animal immunization, antibody harvesting, purification, standardization, and extensive testing. Thanks to the efforts of scientists, herpetologists, and veterinary professionals, snake antivenom plays a vital role in saving countless lives affected by snakebites. As research and technology continue to advance, the development of more effective and accessible antivenoms holds great promise in reducing the global burden of snakebite fatalities.

If you found this article helpful, please consider donating to ASF today. Every donation is 100% tax deductible and goes directly to patient care in Africa.

Veterinary Experts Do Not Recommend The Rattlesnake Vaccine

Every spring, as the weather warms up, we want to shed our winter coats and get out with the dogs onto trails and into open spaces. Unfortunately, as our pooches explore the environment with their noses, they may encounter snakes coming out of brumation.

This can cause concerns for dog owners. Many will ask their vets, “What can I do?” Unfortunately, some vets will recommend the rattlesnake vaccine. Touted to “buy time” getting to an emergency clinic or even to ward off the envenomation, the rattlesnake vaccine is an often used but poorly supported treatment for dogs.

The rattlesnake vaccine uses inactivated western diamondback rattlesnake (Crotalus atrox) venom. The manufacturers claim it “is intended to help create an immunity to protect your dog against the effects of western diamondback rattlesnake venom.” However, there is no evidence to support the vaccine being effective, and some data suggest it could be harmful by causing an allergic reaction to snake venom.

The American Animal Hospital Association (AAHA) recently released a statement highlighting the lack of evidence of vaccine (toxoid) efficacy. Read It Here.

Key points from the AAHA’s statement:

1.      There is NO published data supporting the efficacy of the vaccine in dogs.

2.      In a study that was performed in mice, where mice were given 50-1,500 TIMES the dose of the toxoid given to dogs during routine vaccination, survival following exposure to snake venom was still not guaranteed, and some vaccinated mice actually died or required euthanasia earlier than unvaccinated mice exposed to the same amount of venom.

3.      Adverse reactions, including anaphylaxis, have been reported in vaccinated dogs.

4.      Though the manufacturers make claims of cross-protection (protection from envenomation by pit viper species other than the western diamondback rattlesnake, the species used in the production of the toxoid), there are no data to support this claim.

From the AAHA: “Veterinarians choosing to use this toxoid should be aware of the lack of peer-reviewed published data. Polyvalent antivenin therapy is an alternative to vaccination in suspect cases of rattlesnake bite.”

The vaccine did not prove effective in a retrospective study looking at 272 cases of rattlesnake envenomations in dogs. Read It Here.

Key findings from the study:

1.      There was no evidence that vaccination lessened morbidity or mortality.

2.      No measurable benefit could be identified associated with rattlesnake vaccination.

From this case series: “Vaccination for protection of the general canine population from rattlesnake envenomation cannot be recommended by these authors.”

Furthermore, the rattlesnake vaccine toxoid may predispose snakebitten dogs to anaphylaxis by providing the necessary sensitizing exposure to snake venom antigens. Read It Here.

Key findings from the study:

1.      There are no peer-reviewed publications providing evidence of clinical efficacy in snakebitten dogs.

2.      Anaphylaxis requires prior sensitization to an antigen; it is proposed that repeated vaccinations with the rattlesnake toxoid vaccine serve as a sensitization event to snake venom.

From the authors: “These dogs had previously been vaccinated with the C. atrox toxoid vaccine on more than one occasion, which may have served as the initial sensitization required for the development of anaphylaxis.”

Snakebites are medical emergencies for pets and humans alike. Effective antivenom is the only thing that can neutralize venom and improve outcomes.

If you would like to learn more about veterinary ativenoms, please see this post by Dr. Cory Woliver (A Primer on Antivenoms Used by Veterinarians).

If you found this article helpful, please consider donating to ASF today. Every donation is 100% tax deductible and goes directly to patient care in Africa.

A Primer on Antivenoms Used by Veterinarians

Many people ask about the antivenoms that are used for envenomations in dogs and cats, so here is your immunology lesson for the week.

We have three veterinary-specific products available to us: Venom Vet, Rattler, and ACP. These are all licensed to be used for ALL North American pit viper bites (rattlesnakes, copperheads, and cottonmouths). It is rare to use CroFab or Anavip (the human pit viper antivenoms) in veterinary medicine due to the cost and the fact that there are labeled products for animals, but either could be used in animals. Coral snake antivenom is a human product that we use on animals and is different from pit viper antivenom.

All veterinary antivenom products are derived from horses. Basically, venom is collected from snakes and injected into horses. This process is repeated a number of times. After enough time has passed for the venom to generate an immune response (antibody production), a sample of the horses’ blood is collected and filtered to harvest the antibodies.

Antivenom is a product derived from those horse antibodies. These antibodies or antibody fragments are what work to neutralize the venom. Antibodies look sort of like a Y. The top part is called the Fab (fragment antigen binding) region.  The bottom part is called the Fc (fragment crystallizable) region. Collectively, the entire antibody is referred to as an IgG molecule.

https://ruo.mbl.co.jp/bio/e/support/method/antibody-structure.html

Antivenom can either be made using the whole antibody or just a region of the antibody. The larger the molecule size, the longer the half-life, meaning the antivenom stays in circulation longer. Full IgG molecules are larger than F(ab)2 pieces (the top of the Y, minus the Fc). The upside of IgG antivenoms is that because they stay in circulation longer, you may end up needing less total antivenom. The downside is that with the Fc fragment still attached, you have a higher risk of hypersensitivity reactions.

The Venom Vet product is an F(ab)2 molecule. This means that the most reactive part of the antibody (the Fc portion) has been removed, so there should be fewer allergic reactions in theory. ACP is a whole IgG molecule, making it theoretically more likely to cause an allergic reaction. Rattler is also whole IgG, but instead of being a small, highly concentrated volume of antibodies, it is 50ml of equine plasma. Due to Rattler being plasma from a different species, there is a larger theoretical chance of allergic reaction. The coral snake antivenom is also an IgG product.

Overall, reactions to these products are rare. Usually, fewer than 10% of cases. If allergic (hypersensitivity) reactions occur, they are treatable, whether it is hives or anaphylaxis. You can treat these reactions with Benadryl and/or epinephrine. The reason allergic reactions happen is because there are foreign (horse) proteins in the antivenom. Studies have shown that all of these products have the same efficacy but varying allergic reaction rates. Lower reaction rates have been noted for F(ab)2 products (2.5-3.5%) compared to IgG (7.2-9.3%). But all are good products; if your pet needs antivenom, any of these is a solid option.

Average costs for these products range from about $300-1,000 per vial. If you live in an area with venomous snakes, you should consider getting pet insurance or putting aside some money in case of a bite to a pet, as total envenomation treatment costs can range from about $800-10,000+ depending on how bad the bite is.

Cory Woliver, DVM

University of Florida

If you found this article helpful, please consider donating to ASF today. Every donation is 100% tax deductible and goes directly to patient care in Africa.

How to Treat Snakebites For First Responders in the United States

Approximately 9,000 snakebite envenomations occur yearly in the United States.  Most of these envenomations are due to pit vipers, including rattlesnakes, cottonmouths, and copperheads.  Fortunately, due to rapid access to medical care, deaths are rare, with only 3 to 5 occurring nationwide each year.  Our emergency medical system is the first link in the chain of treating patients.  In comparison to many areas of the world, the U.S. has an advanced system of highly-trained EMTs and paramedics skilled in the prompt assessment, stabilization, and transport of critically ill patients.

We are often contacted to discuss the best way to treat patients in the prehospital setting.  The short of it is to consider a snakebite envenomation a medical emergency.  The mantra “time is tissue” applies to snakebites just the same as it does to STEMIs or strokes.  Getting to the hospital quickly (and safely) is a key part of EMS treatment for snakebites.  Antivenom is the only medication we have that will stop the progression of an envenomation.

Unfortunately, many outdated or even dangerous protocols persist. So for those looking for more guidance, here is a quick, evidenced-based guide for prehospital management of pit viper envenomations in the United States.

    1. As always, initially assess Airway, Breathing, and Circulation and treat any immediate life threats.

    2. If there are signs of an allergic reaction, treat them according to your local protocols.  Keep in mind that systemic toxicity from venom can look very similar to anaphylaxis.  Don’t worry about which is which in this scenario.  Treat both at the same time and figure out which one was the culprit later.

    3. Assess the affected limb.  Remove any jewelry, watches, rings, or other items that may cause constriction if swelling occurs or worsens.

    4. Establish IV access in an unaffected limb.

    5. Elevation of the extremity prehospital is controversial.  Some experts believe it increases systemic absorption, while others disagree.  Nonetheless, the general consensus is to keep it at least at the level of the heart or above.  Discussing which is better with a local snakebite expert may provide more clarity, as opinions typically vary by region.

    6. Provide pain control per your protocols. IV opioids are usually the first line, but other medications, including IV Tylenol or pain dose ketamine, may be viable options. Some experts use ketorolac or other NSAIDs in copperhead envenomations without adverse events occurring due to their very low rate of hematologic toxicity.

    7. Be judicious with IV fluids. If the patient is hypotensive, obviously treat with volume resuscitation.  But if they are comfortable and have normal or even high blood pressure, IV fluids may potentially worsen local edema and swelling.  This is theoretical but something to consider.  I would not flood them with a bunch of fluids if they look well.

    8. Transport the patient to the appropriate hospital per your local protocol.  Typically this would be your local hospital that stocks antivenom. However, some protocols may direct you to larger tertiary hospitals where a snakebite expert can see the patient at the bedside.

    9. When in doubt about a snakebite, contacting your base hospital or the poison center (1-800-222-1222) for further guidance is always a good option.

There are many misconceptions about snakebite first aid. You may encounter patients that have already done things that are not recommended, or you may have been taught some of these unsupported or potentially harmful practices. We DO NOT recommend the following.

    1.  DO NOT apply a tourniquet or compression bandage.

    2.  DO NOT use a suction device.

    3.  DO NOT cut near the wound or try to suck the venom out with your mouth.

    4.  DO NOT use a taser or other electrical shock devices.

    5.  DO NOT bring the snake to the hospital.  Taking a picture of the snake from a safe distance is ok, but identification isn’t necessary for proper treatment.

    6.  DO NOT apply ice or heat to the envenomation site.

If your protocols differ from the above recommendations, consider having your medical director contact a regional snakebite expert or our staff so your service can offer the best evidence-based care to patients.  We are always willing to help improve patient care locally and globally.

In summary, the best possible treatment is to manage the ABCs, provide good pain control, and get the patient to a hospital quickly so they can receive antivenom if necessary.

Nicklaus Brandehoff, MD

Asclepius Snakebite Foundation

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