Richard B. Ford, DVM, MS, DACVIM, DACVPM (Hon)
Since the 1980's veterinarians have seen the introduction of several new companion animal vaccines. Given the outstanding safety and efficacy record of routine vaccination programs for dogs and cats, introduction of new vaccines was readily accepted and implemented. Today, veterinarians practicing in the US have about 80 canine vaccines and 69 feline vaccines (proprietary) to choose from. While common sense dictates that every dog and every cat should not receive every type of vaccine available on the market every year, it is done. Today, there is no data that specifically documents an increase in the occurrence of adverse events that correlates with the increase in the number of licensed vaccines used in companion animal medicine. Unfortunately, published vaccine-associated adverse event data is lacking, despite the increase in the number and use of canine and feline vaccines.
Although veterinarians are encouraged to report known or suspected adverse events to the manufacturer (the recommended first line of reporting) then to the Center for Veterinary Biologics (CVB) of the USDA, it is generally assumed that vaccine-adverse events are under-reported. Furthermore, neither the manufacturer nor the CVB are required to release information regarding adverse event report received. Any effort on the part of a veterinarian to report a vaccine adverse event, therefore, is uni-directional. Data pertaining to vaccine-associated injury is not released by either the USDA or the manufacturer. Unless the type of injury or frequency is so egregious (e.g., vaccine-associated sarcoma) that reports appear in the veterinary literature, vaccine adverse event data is generally not available to veterinarians practicing in the US.
Vaccination is, in fact, a medical procedure. Despite a relatively good safety record, there is always some degree of risk in administering biological agents to a dog or cat. In the absence of a national database through which veterinarians can obtain information regarding field safety of vaccines, information on vaccine adverse events is generally limited to personal experience and observation. This paper is not intended to provide a comprehensive review of all known and potential vaccine adverse events. However, it is intended to increase practitioners' awareness of potential vaccine-associated injury as well as provide information on adverse events associated with inappropriate administration of vaccine.
Vaccine Adverse Event
Taken from the USDA website, "the mission of the USDA is to ensure that animal immunobiologics are in compliance with the Virus-Serum-Toxin Act. Reports are assessed for the possibility of a product deficiency. When necessary, testing is performed or additional information sought. The USDA is, however, unable to make diagnoses or recommendations specific to individual cases. Some of the manufacturers do provide such services. Receipt of a report by the USDA does not necessarily imply that the product caused an adverse event, or even that a particular event actually occurred."
Furthermore, the USDA defines an adverse event as any undesirable occurrence after the use of an immunobiological product (e.g., vaccine), including illness or reaction, whether or not the event was caused by the product. From the standpoint of reporting an adverse event, a veterinarian is not required to establish a cause-and-effect relationship between vaccine administration and the observed "illness or reaction" in order to submit a report. Known, as well as suspect, reactions may be reported.
Adverse events may be reported to any or all of the following:
Manufacturer--Many biologics manufacturers maintain veterinary services departments to handle such reports and may also offer diagnostic advice, treatment recommendations, and guidance on product use. Note: manufacturers are not required to provide financial support for diagnostics or care on behalf of a patient that is reportedly injured following administration of a vaccine.
Center for Veterinary Biologics--Once an adverse event has been reported to the manufacturer, the CVB may be contacted:
On-line: Adverse Event Electronic Form: http://www.aphis.usda.gov/animal_health/vet_biologics/vb_adverse_event.shtml
By fax or mail: Download the 2-page pdf form (17kb) and FAX to (515) 232-7120 or by mail to the CVB.
By telephone: Adverse events may also be reported by calling the CVB at (800) 752-6255.
Types of Adverse Events
In the absence of a defined classification scheme for reporting adverse events, this author finds it useful to discuss vaccine adverse events as acute onset (those that occur within minutes to hours following administration) or late onset (those that occur days or weeks following administration). Acute onset illnesses/reactions may tend to be short lived and resolve relatively quickly; they may also culminate in death of the patient. Late onset illnesses/reactions tend to develop slowly and require longer periods to achieve resolution, if they do. Both acute and late onset events may occur locally (e.g., vaccination-site) or systemically. Both acute and late onset adverse events may culminate in death of the patient. Because of the elapsed time between vaccine administration and development of the illness/reaction, late onset adverse events are less likely to be recognized as vaccine-associated and, therefore, less likely to be reported.
Acute Onset Adverse Events
Among the most commonly observed acute-onset vaccine adverse events recognized in dogs include angioneurotic edema (head and facial edema), particularly in puppies and small dogs (are dachshunds over-represented?), wheals, pruritus, and local swelling. Vomiting is a common acute onset reaction observed in cats. These reactions likely represent true acute hypersensitivity. In dogs, acute onset reactions are frequently, but not exclusively, attributed to administration of leptospirosis vaccine. Generally, smaller dogs are reported to have the highest rate of vaccine adverse events. Malaise, generalized pain, and pain at the injection site within 24-hours post-vaccination are observed by owners of both dogs and cats. Such reactions frequently resolve spontaneously within 72 hours. Use of non-steroid anti-inflammatory is commonly practiced either as treatment of pain/lethargy or as pre-vaccination treatment to prevent the development of pain/lethargy. Severe, life threatening reactions occur in both dogs and cats. The clinical events are not well documented but generally target the respiratory tract. Pulmonary edema, respiratory distress and hypotension may predominate. An association between acute onset adverse events and the number of vaccines administered has been suggested.
Prevention of acute onset vaccine reactions is empirical. Administration of oral diphenhydramine appears to be commonly practiced in an attempt to prevent reactions in dogs that have previously been observed to develop acute-onset angioneurotic edema post-vaccination. Efficacy of such treatment is undocumented. Corticosteroids are commonly used in the treatment of patients that develop acute onset post-vaccinal reactions. Interestingly, animals that have been spayed/neutered appear to have an increase in adverse reactions.
Late Onset Adverse Events
Because of the time between vaccine administration and development of clinical signs, recognition and documentation of late onset adverse events is significantly more difficult than documenting acute onset reactions. Feline vaccine-associated sarcoma (VAS) is perhaps the best documented, and arguably the most significant, vaccine adverse event reported among companion animals. Untreated, feline VAS is likely to be fatal. Most authors agree that inflammation at the injection-site, often attributed to vaccine adjuvant, is responsible. The AAFP Feline Vaccine Advisory Panel has recommended that, when feasible, veterinarians avoid the use of vaccines in cats that are associated with (local) inflammation.
Vaccine-induced disease is rare but does still occur subsequent to administration of modified-live virus (e.g., canine distemper and parvovirus vaccines) and avirulent live bacterial vaccines (intranasally administered Bordetella bronchiseptica vaccine). Documentation of the cause-and-effect relationship between vaccine-induced diseases is difficult to establish. Recent reports have suggested a relationship between administration of modified-live canine distemper vaccine and osteodystrophy (e.g., hypertrophic osteodystrophy and cranio-mandibular osteodystrophy).
Vaccine-associated ischemic vasculitis has been described as both a focal (vaccination-site) and generalized dermatopathy in dogs; similar reactions in cats are rarely observed (or reported). Reactions may cause loss of hair and discoloration of skin and hair at the injection site within 3 to 4 weeks post vaccination. More severe reactions may occur 1 to 3 months post-vaccination. Lesions may develop on the ear tips resulting in ischemic necrosis and loss of tissue. Occasionally, multi-focal and generalized ischemic skin reactions are observed. Rabies vaccine (killed-adjuvanted) may be over-represented.
Frequency of Vaccine Adverse Events
Reliable estimates of the rates of vaccine adverse events in veterinary medicine are not readily available. Information available to the USDA is based on voluntary (passive) reports submitted to the vaccine manufacturer and the USDA. While it may be possible to calculate a reporting rate, the relationship between a reporting rate and an incidence rate is not clear. This relationship may vary by type and severity of event, species, manufacturer, and even from one month to the next. Under appropriate conditions, a reporting rate may sometimes be used to estimate minimum incidence, which may be used for certain comparisons. Reports involving a large number of dogs and cats indicated the occurrence of vaccine adverse events was 38.2 per 10,000 dogs and 51.6 per 10,000 cats. Adverse events reports were limited to those occurring within 3 days post vaccination
Failure to Immunize
Although difficult to confirm, failure of a vaccine to immunize is also regarded as an adverse vaccine event. The most common reason that vaccine fails to immunize a dog or cat is inference by maternal immunity. Furthermore, individual animals may mount an inadequate immune response to one or more vaccines administered. Such individuals are deemed "non-responders". However it is particularly difficult to establish vaccine failure to immunize versus patient failure to respond to vaccination.
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3. Greene and Schultz, Chapt 111 in Infectious Diseases of the Dog and Cat, 3rd ed. p 2006.
4. USDA Adverse Event Reporting: http://www.aphis.usda.gov/animal_health/vet_biologics/vb_adverse_event.shtml