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Q&A about Rattlesnake Vaccine

Questions and answers about Rattlesnake Vaccine
(May, 2005)


What is Rattlesnake Vaccine?

Crotalus Atrox Toxoid (CAT) is a new vaccine that has had one year of clinical use in California dogs.  It is intended as an aid, both in buying time for an owner to get their dog to a veterinarian and in limiting the ultimate destruction caused by envenomation.  Mortality consequent to envenomation is a significant concern; as is permanent injury such as tissue loss, scarring, and loss of limbs.  Vaccination of dogs with CAT elicits production of IgG antibody capable of binding to the major protein fractions of Crotalus atrox (western diamondback) venom.  Antibody thus formed has been shown to neutralize this venom's effects in vivo and in vitro.  Canine antibodies generated by this vaccine also recognize and bind several major proteins in many other North American rattlesnake venoms.  For at least a few of these other venoms, the vaccine-generated immunity has also been shown to be neutralizing.  The advent of a vaccine capable of generating venom-neutralizing antibodies in situ before envenomation occurs offers veterinarians a means of improving snakebite treatment outcomes over existing protocols.  Vaccine-induced antibodies are immediately available to decrease the effective dose of venom that circulates and has activity in the bitten animal, thus decreasing tissue injury and reducing likelihood of serious systemic effects.  In contrast, unvaccinated dogs may continue to suffer progression of swelling and ecchymosis for 1-2 days.


How is Rattlesnake Vaccine given?

Vaccination recommendations for dogs under 100 pounds are two doses spaced four weeks apart as an initial sequence.  Over 100 pounds, dogs develop more consistent and higher titers if they are given three doses at monthly intervals initially.  Booster recommendations are under development, but depend in part upon the length of time each year that a dog may be exposed to rattlesnakes.  Titers increase after each dose, reaching a peak at about four to six weeks after the last dose, then decline over time.  Preliminary data show titers persisting for about six months.  In dogs which are exposed to rattlesnakes for more than six months in the year, single dose boosters are recommended twice yearly. For dogs with exposures of less than six months, a single dose booster should be given about one month before anticipated exposure each year.


How is Rattlesnake Vaccine different from Antivenin?

Using the example of similar products we are already familiar with, Tetanus Toxoid vaccination is used to protect against tetanus infection, while Tetanus Antitoxin is used after an injury to give immediate passive protection and prevent the damage from Tetanus toxins.  Crotalus Atrox Toxoid (CAT) is a vaccine, whereas antivenin is the specific antidote to venom.  CAT must be given in prior to exposure to rattlesnake venom, while antivenin is used therapeutically following a snakebite.  However, envenomation is an intoxication, not an infectious process.  With an infection, it takes time from the exposure until the actual disease occurs, which gives the body time to make antibodies to fight the infection; whereas snakebite is an injury where the maximum amount of venom is in the body immediately, giving the body no time to make new antibodies.  The amount of actual protection a dog has from CAT vaccination depends on multiple variables, including the antibody titer already present in the circulation at the moment of the snakebite, the
size of the dog, the location of the bite, the number of bites, the amount of venom injected by the bite, the species of the snake, etc.


Is Rattlesnake Vaccination safe?

Safety of the vaccine has been good.  It has been used without ill effects in pregnant animals, in dogs as small as 2 pounds and as large as 175 pounds, and in animals as young as six months and as old as eleven years.  Side effects are infrequent and have been predominantly site reactions (71 cases were reported in an estimated 24,975 doses administered commercially).  Systemic reactions in this group have been extremely rare, and are limited to vomiting (3 cases), diarrhea (2 cases), lethargy (1 case), or localized pain (type I (local) hypersensitivity-1case).  No anaphylactic reactions have been seen in preclinical work, and none have been reported in commercial usage to date.  When site reactions occur, they are generally mild and self-limiting, healing without treatment in a few weeks.


Does that mean my vaccinated dog won't need Veterinary care?

Snakebite remains a Veterinary emergency even for vaccinated dogs. Vaccinated dogs can die form rattlesnake bites.  Clinical evaluation and treatment of the snake bitten vaccinate is the same as for an unvaccinated animal, but there are important differences in prognosis and outcome for some bites.  The severity of venom effects is highly dose-dependant; i.e., the amount and rate at which venom reaches systemic circulation dictates the severity of subsequent symptoms. Intravenous envenomation is often fatal, and body strikes are more dangerous than extremity strikes for equivalent amounts venom deposited.  In mild envenomations, vaccinated dogs with circulating antibody titers begin to reverse the injected venom immediately after the bite.  It is not uncommon to have swelling already receding and bruising absent in the bitten extremity upon presentation at the veterinary clinic (less than two hours after the bite).  Vaccine-induced immunity can be overwhelmed by venom in excess of the dog's current titer, and owners must be strongly encouraged to seek veterinary care in the event of a bite.  Dogs receiving dry bites require the same treatment (observation) regardless of whether they were vaccinated or not.  Only the veterinarian is equipped to adequately evaluate whether the amount of immunity present is handling the dose of venom received, or whether additional interventions (including antivenin) may be appropriate in any given case.  Additionally, vaccine induced immunity does not address the potential for infection consequent to snakebite, and only the veterinarian is positioned to provide appropriate treatment in that event.  Of the three snakebite cases reported to date in which fully vaccinated dogs died, one was clearly an intravenous envenomation (the dog collapsed within eight seconds, was comatose within twenty seconds and died within 10 minutes following a witnessed bite), and two were substantially delayed in seeking treatment.


Can my vaccinated dog have antivenin?

Antivenin is NOT contraindicated in vaccinated animals.  The vaccine antigen is produced from venom (snake protein).  There is no potential for antigenic cross-reactivity with antivenin (horse or sheep protein), thus no potential for increased adverse reactions to antivenin if antivenin is to treat an envenomation injury.  Morbidity and mortality subsequent to envenomation injury is minimized by antivenin's ability to neutralize venom.  Prompt therapy (within four hours) using antivenin and crystalloid fluids will reverse many of the systemic effects of envenomation but has limited effect on local tissue injuries. Irreversible tissue destruction can occur within twenty minutes of a bite; and, while antivenin can prevent further destruction, it cannot reverse necrosis that has occurred prior to its administration. Although elimination of a need for antivenin use in CAT vaccinated dogs may be a likely outcome in many cases, a more appropriate view is that vaccination affords an owner more time to get to veterinary care, and affords practitioner more time to evaluate the patient for optimum treatment protocol.  Antivenin may still be indicated depending upon the severity of the bite.  However, because the dog's antibodies have been available to neutralize venom components from shortly after the bite, far less tissue destruction should occur than in an unvaccinated animal, lower morbidity should be seen, and better outcomes are expected.  In clinical practice there is an unavoidable delay between the snakebite and administration of antivenin.  No such delay occurs in vaccinated dogs because their vaccine-generated antibodies are already circulating at the time of the bite.  Immediate availability of venom neutralizing antibody reduces the "effective dose" of venom and thus the potential for local necrotic and systemic injury following envenomation.