W. Novak

Banfield, The Pet Hospital, Portland, OR, USA.

Vaccines are essential tools for disease prevention and the control of disease spread. They work best when administered to a high percentage of pets in any large population. Because they are administered to healthy pets and are intended as a disease-preventive measure, vaccines are quite reasonably expected to be safe as well as effective. Both vaccine safety and effectiveness depend to a variable extent on how individual pets react to the immune stimulus of the vaccine, as well as to its intrinsic qualities. The latter of these-the vaccines’ intrinsic qualities-is one reason that vaccines are never entirely free of reactions, some of which may be severe, eg, anaphylactic shock. Nevertheless, the incidence of significant adverse effects such as anaphylaxis are generally quite low (1/10,000 to 10/10,000 pets vaccinated) and the risk/benefit ratio is extremely favorable.

Any discussion relating to adverse vaccine reactions should start by defining what constitutes an adverse reaction versus expected side effects. Vaccines, by design, are supposed to stimulate an immune response. Local injection site pain, or small injection site swellings that resolve within two weeks, are expected side effects. Low-grade fever and mild to moderate lethargy are not uncommon side effects as well. More severe localized reactions (such as the necrotizing vasculitis sometimes associated with rabies vaccines) or systemic allergic reactions (anaphylaxis) are true adverse reactions.

Post-vaccination adverse reactions can be classified into the following degrees of severity:

• Class I - Not related to vaccine
• Class II - Lump/swelling at vaccination site
• Class III - Facial swelling; generalized urticaria
• Class IV - Systemic signs; fever, vomiting, diarrhea
• Class V - Anaphylaxis, shock, collapse, death

The risk of adverse effects should be carefully explained to each client prior to vaccination, as clients generally have a low tolerance for unexpected events.

Equally, they have a low tolerance for the development of any condition that could have been prevented.

INCIDENCE OF VACCINE-ASSOCIATED ADVERSE REACTIONS

The incidence of post-vaccination adverse reactions in dogs remains relatively low. According to data from our practice’s reporting system, only 16 dogs out of every 10,000 vaccinated showed any kind of adverse reaction, as detailed in Table 1. The rate of anaphylaxis was much lower, at 2/10,000 vaccinated dogs. Most recorded reactions were in reaction Classes II and III.

Comparison of Vaccines (Single Vaccine Administered During Visit)

In a study of canine vaccination administration in Florida between April 2001 and September 2002, the number of adverse reactions was compared following administration of different vaccines. (Table 2) Coronavirus vaccines were associated with more adverse reactions (mostly type II, lump/swelling at injection site) than the other vaccines. However, incidence numbers were small and of little clinical significance.

Comparison of Vaccines (Single vs. Multivalent)

Within the same patient pool in Florida, the canine patients who received single-dose vaccines were compared with canine patients who received multivalent vaccines during the same time span. Almost a fourfold increase in the total number of reactions is seen with the multivalent vaccine as opposed to single-dose vaccines. However, the incidence is still very small and most reactions are transitory and not clinically significant.

While it is not surprising that more reactions are seen as more antigens are given, it is important to note that the number of reactions seen following a multivalent vaccination is of the same order as the number of reactions seen when multiple monovalent vaccines are given as separate injections. However, the data in this study do not address the cumulative reaction rate for cases in which multiple vaccines are divided out into separate patient visits. If a vaccine reaction is indeed a response to a single antigen, rather than to the presence of multiple antigens, then it can be hypothesized that cumulative reaction rates would be similar between patients receiving multivalent vaccines and those receiving multiple monovalent vaccines spread out over different visits.

Incidence of Adverse Reactions in Canines: Breed Comparison

Data from our practice’s national database examining the incidence of post-vaccination adverse reactions in small breeds versus large breeds shows a clear increase in incidence in smaller breeds This finding reinforces the importance of conducting field safety studies to augment laboratory-based safety studies using isolated dogs of a single breed (usually beagles). Results from Florida case records between April 2001 and September 2002 are highly similar, and confirm the data obtained through the Banfield adverse reaction reporting system indicating a relationship between breed size/weight and incidence of adverse reactions.

This phenomenon (more reactions seen in smaller breeds) has been noted by others, and the breed and family susceptibility suggest a genetic predisposition to adverse reactions [1]. A vaccine specially developed for smaller breeds may be warranted. Should this be accomplished and prove safer, a small-breed vaccine may allay general concern about vaccine safety, as well as aid in the development of additional evidence-based vaccination strategies to reduce the occurrence of vaccination-associated adverse reactions.

PRE-TREATMENT OF PETS WITH HISTORY OF ADVERSE VACCINE REACTIONS

When a patient has a history of previous vaccine reactions, further vaccination of this pet requires serious consideration. Issues to be considered include:

• The severity of the previous reaction (that is, a local reaction vs. a systemic reaction)
• The vaccine to which the reaction was previously attributed
• The pet’s long-term history with regard to vaccinations
• What is best for the pet
• Public health concerns
• Local ordinances regarding vaccination

It is also important to remember that the factors involved in causing an adverse reaction are not completely understood, and are quite often not repeated, even when re-vaccinating the same pet with the same vaccine. A previous reaction may have been the result of:

• Vaccine storage
• Administration technique
• Concurrent medications
• Concurrent underlying pathophysiology when the pet receives the vaccinations (that is, the pet is not healthy at vaccination)

There may be situations where it is appropriate to decide against administering a specific vaccine to a pet. Conversely, there may be situations where it is inappropriate to decide against vaccination of a pet. In cases where vaccination is deemed appropriate and agreed upon by the client (who should be educated regarding the benefits, risks, and potential financial costs), a preventive protocol for patients with a previous history of acute systemic reactions to vaccination is as follows:

• The pet should be premedicated with diphenhydramine 2.2 mg/kg IM 15 to 20 minutes prior to vaccinating (oral dosing should not be considered appropriate for guaranteeing adequate drug delivery)
• The pet should have an IV catheter placed to allow immediate treatment with shock fluids, steroids, and epinephrine if a reaction should occur
• The pet should be vaccinated early in the day
• The pet should be hospitalized throughout the day for observation

When the pet is sent home at the end of the day:

• The client should leave with the phone number of their local emergency hospital.
• The client should be shown what to watch for overnight.
• The pet should receive a second dose of diphenhydramine IM prior to discharge.

It is important to phone the client in the morning to make certain the pet is healthy and the client happy with the extra care their pet received.

VACCINE SAFETY ANALYSIS

All vaccines may be associated with several different types of reactions, but the overall incidence rate is very low. This is particularly true for severe reactions that warrant concern and treatment. Reactions of concern include aggressive sarcomas in cats and generalized hypersensitivity reactions including anaphylaxis in both species. The latter are mostly associated with small dog breeds. The risk/benefit analysis for the patients typically treated in small mammal practice (urban/suburban, indoor/outdoor pet) in all regions clearly favors vaccination over non-vaccination. As expressed in third-party surveys, clients have a low tolerance for pets succumbing to diseases that could have been prevented, and the low incidence of adverse events supports an aggressive, broad approach to disease prevention. This is true especially because vaccination must be effective on a population basis to provide reliable protection for individual pets.

The development of ever-safer vaccines should be encouraged, including a potential separate vaccine for smaller-breed dogs, but in our opinion there is little convincing evidence supporting a less aggressive approach to vaccination. Pending solid evidence that vaccines offer longer-term protection than has been demonstrated so far, we believe in exercising caution before relaxing vaccination protocols, so that patients can be assured of protection from preventable disease.