Adverse reactions to vaccines and other medications range from mild to life threatening

by Kenneth L. Marcella, D.V.M.

THE SIGHT of a horse the day after vaccination with a stiff, swollen neck that makes it difficult for him to lower his head to eat grass or with large welts all over his itchy skin may make some horsemen reconsider the merits of vaccinating. In truth, most adverse reactions to vaccines are minor, and the benefits of vaccinating greatly outweigh the risk of not protecting the horse against disease.

Vaccination to stimulate the immune system to produce protection against a disease is a complex process. So, too, is the production of a vaccine. The more complex the process, the more potential for problems.

Abnormalities and adverse or negative reactions can occur in numerous ways, and intricacies in the process of vaccine production and use sometimes can cause these responses.

Immunological reactions in the horse fall into one of four main categories. All these responses can be either acute, occurring immediately (zero to eight hours), or delayed, occurring many hours to days after initial exposure.

•Type I is an anaphylactic reaction, the typical shock-like response or exaggerated immune reaction to an injected, ingested, inhaled, or otherwise contacted antigen. (An antigen is a protein source that is foreign to the body and recognized by the immune system as an invader. Inhaled pollen, injected proteins in vaccines and other drugs, proteins on the surface of parasites, and the venom in an insect sting are all examples of antigens.) Type I reactions are almost always immediate and usually involve the entire body of the horse, so they are called systemic;

•Type II are cytotoxic reactions that occur in the body as a response to an antigen. This type of response activates a host of molecules in the body that contribute to tissue damage. This mechanism is called a complement cascade and is the cause for much of the swelling, soreness, and pain associated with some adverse reactions;

•Type III reactions are immune-complex reactions, a response that occurs only in individuals that have had prior exposure to an antigen. If such an individual encounters that same antigen at a later point in time (such as occasionally happens in older horses that receive vaccinations over a long period), the potential for a type III reaction exists.

Injection of antigens into the muscle or under the skin are such a common cause of type III reactions that they have been given a special name, Arthrus reactions. Such reactions result in edema or significant swelling, an itchy rash, fever, swollen joints and associated lameness, hemorrhage or bleeding in various tissues, and occasionally kidney failure; and

•Type IV reactions are cell-mediated responses, more delayed reactions involving localized swelling and tissue response.

Many specific molecules are involved in this complex immunological response, and each molecule functions in a specific way. Antibodies, such as immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin E (IgE), are produced by the horse in response to exposure to an antigen. When antigens bind to these antibodies, they activate molecules in the immune system that attack other cells to cause the release of still more molecules. Types of molecules released by these immune complexes include histamine, leukotrienes, prostaglandins, and many others.

Histamines cause an increase in mucous secretions in the nose, mouth, throat, trachea (windpipe), and lungs. Histamines cause swelling or edema, and along with leukotrienes and prostaglandins, they cause significant smooth-muscle contraction. These molecules usually contribute to a response that ultimately destroys the antigen, but the process can be damaging to the horse in unusual situations, such as adverse vaccine responses.

These molecules are part of the complement cascade. Depending on the severity of the reaction, the smooth-muscle contraction in the lungs, along with the increased mucous secretion, can cause respiratory distress and death.

Sensitivity to adjuvants

Reactions to vaccinations in the horse rarely involve type I to IV immune responses. They have been reported but are uncommon. Severe and serious reactions to vaccines are uncommon, in general.

Most vaccine reactions in horses are thought to occur in response to adjuvants and not to the disease antigen. Adjuvants are components added to vaccines that are designed to enhance the body's response and to help the body achieve better disease protection. They act in many different ways to prolong the exposure of the antigen's proteins to the immunological cells of the body.

Because these adjuvants are response enhancers or aggravators, they can cause reactions by themselves. The swelling, tenderness, and stiffness in the neck of most horses that react to a vaccination are caused by a response to an adjuvant contained in the vaccine and not by an allergic reaction. Knowing the true cause of most equine vaccine reactions is a tremendous help in preventing adverse responses.

Vaccine producers constantly work to improve the protection offered by vaccines while reducing adverse responses. Kevin Hankins, D.V.M., technical veterinary consultant for Fort Dodge Animal Health, deals with adverse vaccine reactions in horses, and he feels that simply handling and using vaccines correctly significantly can reduce adverse reactions.

"Lack of adherence to proper vaccine-temperature maintenance may result in a lack of vaccine effectiveness and in an increase in local reactions post-vaccination," Hankins said.

Vaccines are labeled with warnings to store them in the dark, shake well before use, and keep them between 35¡ and 45¡. Because of the way vaccines are produced, failure to follow those label warnings most likely will increase the incidence of adverse reactions and decrease the vaccine's efficacy.

"Most vaccine reactions are, in part, due to mishandling of the vaccine by owners who give the injections themselves," said Hankins, though he was quick to add that sometimes veterinarians become lax about storage and use of vaccines, as well.

"Antigens and adjuvants are closely combined during the production of a vaccine," Hankins explained.

Freezing physically breaks apart this complex, and subsequent use of that vaccine may allow a higher amount of only adjuvant to be injected, which can greatly increase the reactivity. "Stiffness and localized swelling can be increased up to ten times in such situations," he said.

Allowing the vaccine to become too warm reduces efficacy but does not increase reactivity. Failure to shake the vial well before use can allow more adjuvant than antigen to be injected in a concentrated area and can potentiate reactions.

Anaphylactic shock

True anaphylactic reactions are rare, but even in the best of situations, when they occur, these abnormal responses often are fatal. In such cases, the body perceives a minimally harmful, foreign protein--from a bee sting, a snakebite, a drug, or even a peanut--as a serious threat, and it launches a massive overreaction. These reactions occur very quickly, usually within minutes, and they progress extremely rapidly. Many veterinarians can relate information about reactions that took place so quickly they could not get from their truck to the struggling horses in time to offer treatment.

Horses experiencing anaphylactic reactions will have hives and itchiness, wheezing, difficulty breathing and an elevated heart rate, dizziness or vague neurological signs, paleness, and excessive sweating. These signs can progress to disorientation, collapse, shock, and possibly death.

Many molecules come into play during these anaphylactic reactions. Histamine is released causing increased secretions from the respiratory track. Edema or significant swelling occurs along with smooth-muscle contraction. Leukotrienes are released, which causes smooth-muscle contraction and prolongs the body's exaggerated reaction. Prostaglandin has similar effects.

A full-blown, anaphylactic reaction will cause specific cells, called mast cells, to be released throughout the body. These mast cells cause massive dilation of blood vessels throughout the body, which results in a drop in blood pressure that leads to full collapse and shock.

Treatment for anaphylactic shock is aimed at supporting the body at all times and trying to reverse the histamine effects. It usually requires administration of epinephrine, which is available in single-dose vials for such a situation. Administration of this potent antihistamine should be tried in an emergency situation, even with the knowledge that anaphylactic shock progresses so rapidly that often nothing can be done.

Epinephrine is meant to be given intravenously, and because it also can cause adverse responses, it should be given by a veterinarian, if possible.

Supportive fluid therapy often is crucial to these reaction cases, and the horse should be given flunixin meglumine (Banamine) to protect cell membranes and to lessen the signs of colic caused by smooth-muscle contraction. Steroids are helpful in reducing tissue damage during shock and in stabilizing other body systems, so they frequently are used in large doses, as well.

Because anaphylactic reactions usually occur rapidly, having emergency supplies close at hand and ready to be used may allow you to avert disaster.

Strategies to reduce reactions

The increased use of multiple or combination vaccines also has increased the percentage of reactions seen in horses, because these vaccines use multiple antigens and adjuvants. A horse is far more likely to respond adversely to such injections, so many veterinarians recommend stretching out vaccine schedules for those horses prone to respond poorly. Vaccinating these animals with a single vaccine and then administering another single-disease vaccine ten to 14 days later seems to decrease reactions.

If horse owners purchase and give their own vaccines, they should be aware of some important handling tips. Keep vaccines cold but not frozen. Hankins advised that when transporting vaccines from the store or home to the barn, do not place them in contact with ice. Syringes are thin plastic, and localized freezing can occur in areas that contact an ice pack or the freezer door or shelf. It is best to wrap the vaccines to maintain a consistently cool temperature without freezing.

The sight of your horse with a stiff, swollen neck or with itchy skin and welts following vaccination can be disheartening, but remember that almost all such reactions respond to anti-inflammatory administration, cold compresses, and compassionate care. These reactions usually are localized responses and not allergic reactions.

Kenneth L. Marcella, D.V.M., is a practicing veterinarian in Canton, Georgia.