Adverse vaccination events: Separating fact from fiction (Proceedings)
Vaccines are such a routine part of everyday veterinary practice that we often forget about potential reactions and complications until they occur. Veterinarians tend to be familiar with vaccine reactions such as fever and lethargy. Other adverse events are less common and may be difficult to link to vaccination. The following discusses recognition and management of various types of reactions, and whether there is evidence that vaccines cause autoimmune illnesses or chronic diseases.
Pain or stinging at the time of injection is usually not due to the antigen. Inactivating ingredients or adjuvants are responsible, although temperature (cold from the fridge) may play a role. Hand-warming the syringe before injection may help, but do not leave vaccines at room temperature for extended periods of time.Inflammation (swelling) at the vaccine site appears about one day later and may last up to one week. Unless infection or abscessation occurs, no treatment is needed but this should be documented and reported. Lumps that persist for over a month, or increase in size (greater than 2 cm), should be biopsied, especially in cats.
Vasculitis, most often from subcutaneous rabies vaccines, may lead to alopecia, scaling, and a permanent scar-like circular area. This is reported in toy and small breeds of dogs, and the cause is unknown. Potential medical therapy includes pentoxifylline and vitamin E, while surgical resection of the lesion is curative. Future vaccinations should be avoided or minimized, if possible, and a different brand of vaccine may help avoid the same problem.
Type I hypersensitivity (allergy, acute vaccine reaction, anaphylaxis) can result from the vaccine antigen or other proteins and material found in the product. Antibodies to bovine serum albumin and fibronectin have been detected in dogs, presumably due to residues of fetal calf serum used in vaccine production. These reactions happen within minutes up to 2-3 hours, although owners may not recognize signs until up to 8 hours later. Late-phase responses may persist for 48 hours.
In dogs, the clinical sign is most commonly urticaria and angioedema ("hives" or swelling) involving the face, head, and ears. Vomiting and diarrhea may be seen, and respiratory distress is rare but serious. Cats more often have GI signs (acute onset vomiting and diarrhea), and less commonly respiratory distress or urticaria.
Treatment for both dogs and cats is supportive. As soon as signs appear, injectable drugs such as corticosteroids, antihistamines, and/or epinephrine are given depending on severity. Other therapies such as IV fluids and oxygen are occasionally needed, and facilities for endotracheal intubation and ventilation should be available. A typical approach for mild cases is to give dexamethasone 0.2 mg/kg IV and diphenhydramine 2 mg/kg IM. To treat late-phase reactions, oral corticosteroids and antihistamines are dispensed for 2-3 days. For pets with a history of these kinds of vaccine reactions, at all future vaccine visits they are pretreated with a similar protocol and then monitored in the hospital for at least 8 hours. In cases of life-threatening reactions, future vaccination should be avoided if possible. If absolutely necessary, vaccines should be split into multiple visits (3 or more weeks apart) along with pretreating and careful monitoring.
Immune-mediated diseases have been associated with vaccines in dogs. However, the mechanisms have not been elucidated and cause-and-effect is not proven. A retrospective study published in 1996 concluded that a temporal relationship existed between vaccination and immune-mediated hemolytic anemia (IMHA). 15 of 58 dogs (26%) with idiopathic IMHA were found to have onset of clinical signs within 1 month of vaccination. The remaining cases were presented 2 months to 55 months after vaccination. Different brands of vaccine were used, and all dogs received DHLPP. Eight of the 15 IMHA cases also received rabies and a few dogs had other vaccines. Other studies were undertaken to confirm this association but did not find any evidence that IMHA occurred more frequently after vaccination. In the United Kingdom, a retrospective study of 41 cases of IMHA or immune-mediated thrombocytopenia (ITP) showed that 12% had been vaccinated within the past month.
A case series in a veterinary orthopedic journal described 27 dogs with immune-mediated arthritis, of which 4 (15%) were recently vaccinated (3-15 days, mean 11 days). Clinical signs included stiff gaits, a reluctance to move, and difficulty rising. All received diagnostic workups and were treated with doxycycline and carprofen. Signs resolved quickly (1-2 days after treatment). One dog was revaccinated and developed arthritic signs 12 days later, while another dog was revaccinated with no signs.
Hypothryoidism resulting from autoimmune thyroiditis has been identified in dogs, and antibodies (Ab) produced against canine thyroglobulin are diagnostic of this condition. A study in research Beagles and pet dogs attempted to discover if vaccination could cause this disorder. Results were mixed - Ab were found to canine and bovine thyroglobulin (probably because of bovine protein contaminants in the vaccines) but no cases of hypothyroidism were observed.
Are certain breeds predisposed to vaccine reactions? One author suggests that Old English Sheepdogs, Akitas, and Weimaraners have higher rates of vaccine-associated immune-mediated diseases than other breeds, but evidence is lacking. Hypertrophic osteodystrophy has been linked with modified-live distemper vaccines in Weimaraners, with average age of onset 13.5 weeks and 10.5 days post-vaccination. In a retrospective study of over one million dogs, the reaction rate (all types) was 38.2/10,000. Young adult dogs (1-3 years) and small-breed dogs were at higher risk. The top 5 breeds for reactions were Dachshund, Pug, Boston Terrier, Miniature Pinscher, and Chihuahua. Boxers were the only large breed with more reactions than average. Breed variations in response to rabies vaccination were recently reported. Genetic makeup most likely plays a major role in the risk of vaccine reaction.
Other reactions reported in cats include lethargy (with or without fever), vomiting, facial edema, and generalized pruritus. In one study, the reported rate of vaccine adverse events was 51.6 per 10,000 cats vaccinated.
In the UK, a questionnaire was mailed to 9055 dog owners who had visited a veterinary clinic in the past year, and 4040 were returned. The main question was whether the dog had any signs of ill health after vaccination. The results were that 16.4% of dogs vaccinated within the past 3 months had an illness, while 18.8% of dogs vaccinated >3 months earlier had ill health.
Despite several studies that show no association between vaccination and immune-mediated diseases, it is reasonable that animals with a history of IMHA or ITP or other illnesses should not be vaccinated routinely in the future. Certainly it would be beneficial to customize individual protocols in such cases, and minimize the number and frequency of vaccinations.