Canine adenovirus type-1 and type-2 cause infectious hepatitis and respiratory infection, respectively. Hepatitis caused by adenovirus type-1 may cause severe kidney damage or death. Common signs of this disease include listlessness, fever, loss of appetite, vomiting, excessive thirst, and discharges from the eyes and nose. Adenovirus type-2 is an important factor in kennel cough.
Canine bordetella may contribute to kennel cough. This bacterial infection can occur alone or in combination with distemper, adenovirus type-2 infection, parainfluenza, and other respiratory changes.
Canine leptospirosis is a bacterial infection which may lead to permanent kidney damage. The disease is easily spread to other pets and to humans. Depression, fever, and loss of appetite appear suddenly, and jaundice, vomiting, dehydration, excessive thirst, and excessive urination may indicate liver and kidney damage.
Canine parainfluenza is another cause of kennel cough. Although parainfluenza is often a mild respiratory infection in otherwise healthy dogs, it can be severe in puppies or debilitated dogs.
Canine parvovirus is a disease of widespread distribution which may cause severe dehydrating diarrhea in dogs of varying ages. Parvovirus infection is especially dangerous for puppies and very old dogs. In some instances, this disease leads to secondary heart disorders.
Canine coronavirus infection is highly contagious intestinal disease causing vomiting and diarrhea in dogs of all ages. Especially in young puppies, dehydration from coronavirus infection can be life-threatening.
Lyme disease, a bacterial disease caused by Borrelia Burgdorferi, may be spread by insects such as flies, fleas and ticks. Arthritic-like symptoms may occur.
Rabies, a disease which has reached epidemic proportions throughout the United States, is almost always fatal. Rabies virus attacks the brain and central nervous system, and is transmitted to humans chiefly through the bite of an infected animal.
Kennel Cough - There is no vaccine for complete protection against infectious canine cough. Thirteen different viruses and bacteria are implicated as its cause. Currently vaccines are available for 3 of the 13 known components of the disease complex. These three include Parainfluenza, Adenovirus Type 2, and Bordetella. By vaccinating for these 3 diseases, 90% of the cases of kennel cough can be eliminated. Canine cough is usually a mild, self-limiting disease, but it can develop into a severe bronchopneumonia, especially in younger dogs. The most common sign of this disease is a harsh unproductive cough that leads to gagging or even vomiting.
In addition to the antigen, vaccine suspensions also contain other ingredients which may include other antigens, protein from tissue culture or egg yolk, preservatives like antibiotics, and carrier proteins such as aluminum for enhanced immunogenicity. Therefore, adverse reactions may result as a response to the antigen or to anyone of these additional components. Over the years, improvements in techniques for antigen development and better purification procedures for the production of vaccines has resulted in fewer hazards associated with immunization. However, adverse reactions may still occur in certain individuals. The following are some potential hazards associated with vaccination:
Canine vaccines immunizing against several infectious diseases are routinely manufactured as pre-mixed for administration as all-in-one-vaccines; that is, one inoculant contains many different antigens that are administered as a single "shot". Such vaccines are termed polyvalent vaccines as opposed to monovalent vaccines, which would contain only antigen directed at immunizing against a single infectious agent.
Concerns have often arisen regarding the widespread use of polyvalent vaccines because they are believed to cause a significant decrease in immune function known as immunosuppression. Immunosuppression may result when the amount of antigen introduced into the dog exceeds the ability of the immune system to respond. Such a condition is termed antigen-overload. Immunosuppression may also occur as a result of one antigen component of the vaccine preventing the immune system from responding to another antigen component of the polyvalent vaccine. This latter form of immunosuppression is termed vaccine interference.
Clinical studies exploring different polyvalent vaccines have demonstrated a significant degree of immunosuppression associated with inoculation with polyvalent vaccines; however, duration of immunosuppression was only 7-10 days. Therefore, from a clinical standpoint, such a brief period of immunosuppression in an otherwise healthy dog is not considered cause for concern. However, if a nutritional deficiency or hereditary immune disorder already compromises a dog's immune system, the added immunsuppression may result in clinical illness if the dog is exposed to an infectious disease within the 7-10 day margin. Alternatively, if the dog has already been exposed to an infectious disease and is in the process of defending against a mild infection which is asymptomatic, the increase in immunosuppression caused by administration of the polyvalent vaccine may also result in clinical illness. In the latter situation, clinical symptoms of infection will present within 24-48 hours following vaccination. In these situations, it is common for many dog owners to blame the vaccine for causing the disease, when in actuality, the vaccine only made the underlying condition apparent. In light of this, in dogs suspected of harboring mild infections or who may be immunosuppressed due to other factors (immune disorders, seasonal allergies, certain medications), vaccination with polyvalent vaccines should be postponed until the underlying condition has resolved, or if risk for contracting infectious disease is high, use of monovalent vaccines or killed vaccines might be an alternative option.
When a circulating antibody encounters the specific antigen it is directed against in the body, it binds to that antigen in order to destroy it. This binding creates an immune-complex. In some instances, when there is extensive formation of immune complexes, these large molecules may be deposited in certain organs of the body and result in inflammation of local tissue resulting in immune complex disease. An example of this in relation to vaccination occurred with the use of early Canine Adenovirus-1 (CAV-1) vaccine in which, shortly after being administered the vaccine, dogs developed a bluish cast to the cornea of the eyes. This abnormal condition was determined to be caused by fluid retention and inflammation of the corneal tissue resulting from the deposit of antibody-antigen complexes. Though dogs usually regained full vision, CAV-1 vaccines soon became overlooked in favor of the CAV-2 vaccines which protected against both adenovirus type-1 and type-2 but which did not cause the bluish cast. To this day, CAV-1 vaccines are still available, however, they are regarded unfavorably for widespread vaccination despite the fact that the immune-complex disease was later found to be an effect not of the CAV-1 antigen, but rather the high concentration of the carrier protein, bovine serum albumin (BSA), used in the early CAV-1 vaccines. The modern CAV-1 vaccines available today no longer cause "blue eye."
- Vaccine-Induced Vasculitis (An Immune Complex Disease)
Vaccine-induced vasculitis is an adverse reaction that occurs very rarely in dogs, but it has been most often associated with administration of the rabies vaccine (although other vaccines may also be involved). This condition may present as many as 3-6 months following immunization. Additionally, there are causes other than vaccine reactions that may produce vasculitis in canines such as food allergy, drug reactions (i.e. ivermectin and itraconazole), lymphosarcoma, or unknown causes (idiopathic vasculitis). The vaccine-induced form of vasculitis, however, has a distinct, consistent histologic inflammatory (mononuclear/nonleukocytoclastic) pattern that may be helpful for differentiating this reaction from other underlying causes for vasculitis. In general, though cutaneous forms of vaccine-induced vasculitis may be identified by areas of hair loss and large red or purple spots ("purpura.") on the skin that may look like large bruises, the lesions may also appear as hives, a rash, or painful or tender lumps. In more severe cases, loss of blood flow to the skin may produce necrosis (death) of the skin, which will appear as ulcers or small black spots at the tips of the ears or toes.
Symptoms of systemic vasculitis are vague and appear similar to symptoms of many other disorders: fever, lethargy, muscle and joint pain, poor appetite, weight loss, and fatigue. More specific symptoms of vasculitis will be dependent upon the organ or organ systems involved which may include the brain and nervous system (behavioral disturbances, tremors, muscle weakness, seizures), gastrointestinal system (abdominal bloating, pain, bloody stools), the heart and lungs (difficulty breathing, coughing, exercise intolerance, heart enlargment), and the eyes (loss of vision).
In general, vasculitis associated with immunization is another form of "immune complex disease" and is believed to occur in dogs that have abnormal T-cell function. That is, T-cell unresponsiveness to circulating antigens (vaccine components) results in these antigens circulating in the blood for prolonged periods of time and thus providing time for the antigens to be deposited in tissues of the body, primarily the blood vessel walls. When this occurs, white blood cells (macrophages) will recognize the antigen as foreign and commence an attack on the vaccine component. Unfortunately, the inflammatory responses that accompany destruction of the antigen can injure the blood vessel, which will produce the condition of vasculitis. Damage to minor blood vessels may only result in mild symptoms of red patches on the skin where immune-complexes have been deposited. When larger blood vessels are involved or in cases of major systemic involvement, symptoms may be severe. Dependent upon the extent of the organ involvement and damage, many dogs will respond favorably to prompt administration of glucocorticoids (anti-inflammatory steroids). As with other immune-related hematologic disorders, however, dogs with vaccine-induced vasculitis are at high risk to developing and succumbing to the secondary complication of pulmonary emboli (when blood clots formed during vascular damage break free and are deposited in the lungs).
T-cell unresponsiveness that occurs primary to this type of adverse reaction may occur as an inherited defect, but more commonly it occurs as age-related compromise of the immune system. As dogs and humans get older, it is more common to encounter immune-system dysfunction. This presents a dilemma for veterinarians in regard to administration of vaccines because an aged immune system does not only increase risk for the older dog to contract and be more susceptible to infectious diseases, but also increases risk for adverse reactions to immunization. Therefore, not vaccinating places an older dog at considerable risk for acquiring and dying from infection, while vaccinating may cause auto-immune complications (most commonly immune-mediated hemolytic anemia) in some of these older dogs. Because, on average, risks of disease still outweigh immune reactions in older dogs and in absence of any previous indication that a dog may harbor immune dysfunction (currently there are no standard tests that could differentiate those dogs that will have an immune reaction from those who will not), veterinarians will typically recommend vaccination for older dogs. The use of antihistamines in conjunction with vaccinations, however, may be indicated to reduce some components of the inflammatory response associated with immune-complex formation for which these older dogs may be at higher risk (since histamine has been found to play a role in platelet aggregation associated with allergic vasculitis).
The strategy employed to create modified-live vaccines is to diminish the disease-producing effects of the microorganism while retaining their ability to replicate and produce strong immunity in the immunized host. The method for attenuating an infectious virus is to grow it for long periods of time under unfavorable conditions, usually in cells from a species other than its usual host. To survive under these undesirable conditions, the virus will undergo changes which will help it adapt to the new host environment. These changes usually come about as random mutations in the genetic material of the virus. However, not all viruses will adapt through the same type or number of mutations. Prior to recombinant DNA technology which now allows for site-directed mutations, the number and types of mutations in attenuated viruses used in modified-live vaccines were unknown. As a result, some viruses used for immunization had mutations that reverted back to the disease-producing or "wild-type" form when inoculated back into the original host. In this situation, immunization was actually responsible for causing the disease which it was originally designed to protect against. This occurred with some early modified-live rabies vaccines and in human medicine, the type 1 and type 2 polio vaccines.