I’m apparently still on this immunology kick, because I seem to be finding it everywhere. Heck, I recently learned that we’ve cured the allergic response to peanuts and eggs in lab mice. Check out the link, the author is hilarious and the material is interesting.

These two articles offer a great look at the overall prevalence and risk factors associated with vaccine-associated adverse events. The components within the vaccine that cause these events are the antigen itself, adjuvants, preservatives, stabilizers, and residues from the tissue culture used to grow the vaccine (Moore, 2005). Vaccine reactions are similar to any acute allergic reaction, and can present with a variety of mild to severe symptoms. The mild being lethargy, anorexia, fever, edema (generalized or local to the injection site), pruitis, uticaria (hives or wheals), and pain at the injection site; the severe being vomiting, dyspnea (labored or shortness of breath), and anaphylaxis. There’s a lot of information about when certain symptoms tended to occur at intervals after the vaccines were given, but any reaction that isn’t within the first 3 days is pretty much never going to be life threatening. If anaphylaxis is going to occur, it’s going to be immediately following vaccination.

The really useful information was the breakdown of risk factors that can be used for client communication. I’ve decided to discuss them here, broken down into cat and dog categories.

Image from meow-cats.com

First, let’s start with cats. I almost like these numbers more because you don’t have to take into account bias based on animal or breed size, as most cats fall into the <20 lbs category. Nonetheless you still have to remember that a 4 pound kitten does way only a fraction of that 5 year old chubby (BCS >5 on a 9 point scale) longhair it will grow to be.

So the first two risk factors require a little bit of thinking in context to explain the numbers. It seems that cats weighing 2-4 Kg (4.4-8.8 lbs) and approximately one year of age are most at risk compared to other weights and ages. The high numbers for these groups can be explained by the number of first encounter events that occur. If you’re recording vaccine reactions, you will record less in older age groups and higher weights (low weight under 10 lbs is going to be suggestive of a young age rather than a smaller cat), because if an adverse event occurred at a young age, either the animal is no longer vaccinated or steps are taken to reduce its risk (medication, strict scheduling, vaccine selection). That being said, just because the numbers are higher by circumstance, this information is very relevant in a clinical setting. Knowing the epidemiology of these events can help technicians at clinics determine when the discussion of vaccine reactions is “routine” or “protocol”, or when it really needs to be a time to educate the client. Vaccine reactions may need to be just a bullet point when Schrodinger is there for his 4th rabies booster and a discussion when he’s receiving his kitten series.

Sex and neuter status have a large impact on reaction risk as well. Intact males actually have a lower risk of adverse events than neutered males and spayed and intact females. Apparently, estrogen has an immune boosting effect, while testosterone has an immune suppressing effect. This benefits intact males when it comes to all allergic reactions (and possibly auto-immune disorders).

Here’s the big one, and the one clinics have the most control over. With each additional vaccine given in a single visit, the risk of an adverse event increases by 28% in cats. That’s huge. Any cases of severe anaphylaxis or death recorded in the study were preceded by the animals receiving 3 or more vaccines in one visit. So clearly the biggest thing any clinic can do to prevent adverse events (or at least severe ones) is to adopt a vaccination schedule that prevents multiple vaccinations from occurring within the same visit. This can be difficult as clients will not want to end up paying for multiple exams throughout the year, but with boosters outside of rabies, exams shouldn’t be necessary unless an annual or other scheduled exam is due. As far as specific vaccines being more prone to adverse events, the only suggestive evidence was when both FVRCP and FeLV were given within the same visit. This is explained by both having two concurrent vaccinations given, and also the theory that vaccines containing multiple antigens or covering multiple serovars (multivalent) are more likely to illicit reactions. Interestingly, while clients are often scared by the potential for vaccine caused neoplasia from the rabies vaccine, it was among the lowest reaction rates observed with the administration of a single vaccine.

Image from peteducation.com

Dogs had much more biased data within the age and breed groups because there is an obvious relationship between body mass and the potential for reaction. When looking at the dog population, a chihuahua can be as little as 6% of the weight of a bullmastiff, yet they receive the same 1ml dose of vaccine. This means that an 8 lb Chihuahua is going to receive proportionally 15 times more vaccine than a 120 lb bullmastiff. Not surprisingly, this causes a bit of inflation in the number of reactions in groups that are smaller in size, such as toy breeds and puppies. The highest risk group in size was 0-10Kg (0-22lbs) and the highest risk age was approximately 2 years of age (with higher rates for <2 than the rates of >2).

Just like I mentioned before when talking about cats, the greatest risk factor for reactions in dogs was the amount of vaccines given in one visit. The difference though, is how the large weight distribution in dogs makes this even more important. Small dogs (<10Kg) are similar to cats in that their risk increases by 24% with every additional vaccine administered that visit, while large  dogs (10-45Kg) increase their risk by 12 percent. All 3 dogs in the study that suffered fatal reactions received 4 or more vaccines at once.

Breed dispositions were difficult to pinpoint, as the suspected breeds are all small breeds which suffer a higher rate of reaction already due to their size. There is suspicion that dachshunds may be predisposed to allergic reactions in general, but so far the evidence is inconclusive concerning vaccines. Only the Lyme vaccine appeared to carry a higher risk than any other, showing again that, with the exception of neoplasia concerns, rabies does not carry with it any additional risk. Spayed and neutered animals, as in cats, are more susceptible to reactions; however the difference between intact and spayed females is much larger in dogs than in cats (where they are nearly identical). Dogs do seem to display an interesting trend where vaccine reactions are more likely to occur on the 3rd booster in a series, likely catching clinicians and clients off guard as they have received the first two without incident. This just states again that the puppy and kitten periods (and new patients) are of much more relevance when discussing vaccine reactions with clients.

The articles are both great, and contain an excellent statistical analysis of millions of animals. They provide a great overall picture of the epidemiology of vaccine-associated adverse events, and are definitely worth a read for both veterinary doctors and staff. Knowing a couple of the more important statistics can reassure the client and lend credibility to technicians that are responsible for discussing these issues.

ResearchBlogging.orgMoore, G., DeSantis-Kerr, A., Guptill, L., Glickman, N., Lewis, H., & Glickman, L. (2007). Adverse events after vaccine administration in cats: 2,560 cases (2002–2005) Journal of the American Veterinary Medical Association, 231 (1), 94-100 DOI: 10.2460/javma.231.1.94

Moore GE, Guptill LF, Ward MP, Glickman NW, Faunt KK, Lewis HB, & Glickman LT (2005). Adverse events diagnosed within three days of vaccine administration in dogs. Journal of the American Veterinary Medical Association, 227 (7), 1102-8 PMID: 16220670