Viral disease and recent vaccination with single or combination modified live-virus (MLV) vaccines, especially those containing distemper virus, adenovirus 1 or 2, and parvovirus are increasingly recognized contributors to immune-mediated blood disease, bone marrow failure, and organ dysfunction. 1-11 Potent adjuvanted killed vaccines like those for rabies virus also can trigger immediate and delayed (vaccinosis) adverse vaccine reactions.7-10 Genetic predisposition to these disorders in humans has been linked to the leucocyte antigen D-related gene locus of the major histocompatibility complex, and is likely to have parallel associations in domestic animals. 5, 7
Beyond immediate hypersensitivity reactions, other acute events tend to occur 24-72 hours afterwards, or 7-45 days later in a delayed type immunological response. 1-4, 6-10 Even more delayed adverse effects include mortality from high-titered measles vaccine in infants, canine distemper antibodies in joint diseases of dogs, and feline injection-site fibrosarcomas. 5,7 The increasing antigenic load presented to the host individual by modified-live virus (MLV) vaccines during the period of viremia is presumed to be responsible for the immunological challenge that can result in a delayed hypersensitivity reaction. 2, 3, 6, 7
The clinical signs associated with vaccine reactions typically include fever, stiffness, sore joints and abdominal tenderness, susceptibility to infections, neurological disorders and encephalitis, collapse with autoagglutinated red blood cells and icterus (autoimmune hemolytic anemia) (AIHA), or generalized petechiae and ecchymotic hemorrhages (immune-mediated thrombocytopenia)(ITP).1, 2, 4, 7, 8, 12, 13 Hepatic enzymes may be markedly elevated, and liver or kidney failure may occur by itself or accompany bone marrow suppression. Furthermore, MLV vaccination has been associated with the development of transient seizures in puppies and adult dogs of breeds or cross-breeds susceptible to immune-mediated diseases especially those involving hematologic or endocrine tissues (e.g. AIHA, ITP, autoimmune thyroiditis). 1,7,10 Post-vaccinal polyneuropathy is a recognized entity associated occasionally with the use of distemper, parvovirus, rabies and presumably other vaccines. 2, 3, 7 This can result in various clinical signs including muscular atrophy, inhibition or interruption of neuronal control of tissue and organ function, muscular excitation, incoordination and weakness, as well as seizures. 7 Certain breeds or families of dogs appear to be more susceptible to adverse vaccine reactions, particularly post-vaccinal seizures, high fevers, and painful episodes of hypertrophic osteodystrophy (HOD).7, 9 Therefore, we have the responsibility to advise companion animal breeders and caregivers of the potential for genetically susceptible littermates and relatives to be at increased risk for similar adverse vaccine reactions.1, 4, 6-9, 14-17 In popular (or rare) inbred and linebred animals, the breed in general can be at increased risk as illustrated in the examples below.
Commercial vaccines can on rare occasion be contaminated with other adventitious viral agents, 3, 15 which can produce significant untoward effects such as occurred when a commercial canine parvovirus vaccine was contaminated by blue tongue virus. It produced abortion and death when given to pregnant dogs,15 and was linked causally to the ill-advised but all too common practice of vaccinating pregnant animals. The potential for side-effects such as promotion of chronic disease states in male and non-pregnant female dogs receiving this lot of vaccine remains in question, although there have been anecdotal reports of reduced stamina and renal dysfunction in performance sled dogs. 17 Recently, a vaccine manufacturer had to recall all biologic products containing a distemper component, because they were associated with a higher than expected rate of central nervous system postvaccinal reactions 1-2 weeks following administration. 17 Vaccination of pet and research dogs with polyvalent vaccines containing rabies virus or rabies vaccine alone was recently shown to induce production of antithyroglobulin autoantibodies, a provocative and important finding with implications for the subsequent development of hypothyroidism. 10 Furthermore, injection site fibrosarcomas have recently been documented in dogs as well as cats. 18
Other issues arise from overvaccination, as the increased cost in time
and dollars spent needs to be considered, despite the well-intentioned
solicitation of clients to encourage annual booster vaccinations so that
pets also can receive a wellness examination.6 Giving annual boosters when
they are not necessary has the client paying for a service which is likely
to be of little benefit to the pet’s existing level of protection
against these infectious diseases. It also increases the risk of adverse
reactions from the repeated exposure to foreign substances.
Polyvalent MLV vaccines which multiply in the host elicit a stronger antigenic challenge to the animal and should mount a more effective and sustained immune response. 2, 3, 6 However, this can overwhelm the immunocompromised or even a healthy host that has ongoing exposure to other environmental stimuli as well as a genetic predisposition that promotes adverse response to viral challenge. 1, 2, 7, 14, 16, 17 The recently weaned young puppy or kitten being placed in a new environment may be at particular risk. Furthermore, while the frequency of vaccinations is usually spaced 2-3 weeks apart, some veterinarians have advocated vaccination once a week in stressful situations, a practice makes little sense scientifically or medically.6
An augmented immune response to vaccination is seen in dogs with pre-existing
inhalant allergies (atopy) to pollens. 7 Furthermore, the increasing current
problems with allergic and immunological diseases has been linked to the
introduction of MLV vaccines more than 20 years ago. 3 While other environmental
factors no doubt have a contributing role, the introduction of these vaccine
antigens and their environmental shedding may provide the final insult that
exceeds the immunological tolerance threshold of some individuals in the
pet population. The accumulated evidence indicates that vaccination protocols
should no longer be considered as a “one size fits all” program.
For these special cases, appropriate alternatives to current vaccine
practices include: measuring serum antibody titers; avoidance of unnecessary
vaccines or overvaccinating; caution in vaccinating sick or febrile individuals;
and tailoring a specific minimal vaccination protocol for dogs of breeds
or families known to be at increased risk for adverse reactions.6,7,19-22
Considerations include starting the vaccination series later, such as
at nine or ten weeks of age when the immune system is more able to handle
antigenic challenge; alerting the caregiver to pay particular attention
to the puppy’s behavior and overall health after the second or
subsequent boosters; and avoiding revaccination of individuals already
experiencing a significant adverse event. Littermates of affected puppies
should be closely monitored after receiving additional vaccines in a
puppy series, as they too are at higher risk.
1. Dodds WJ. Immune-mediated diseases of the blood. Adv Vet Sci Comp Med 1983; 27:163-196.
2. Phillips TR, Jensen JL, Rubino MJ, Yang WC, Schultz RD. Effects on vaccines on the canine immune system. Can J Vet Res 1989; 53: 154-160.
3. Tizard I. Risks associated with use of live vaccines. J Am Vet Med Assoc 1990; 196:1851-1858.
4. Duval D, Giger U. Vaccine-associated immune-mediated hemolytic anemia in the dog. J Vet Int Med 1996;10: 290-295.
5. Cohen AD, Shoenfeld Y. Vaccine-induced autoimmunity. J Autoimmunity 1996; 9: 699-703.
6. Schultz R. Current and future canine and feline vaccination programs. Vet Med 1998; 93:233-254.
7. Dodds WJ. More bumps on the vaccine road. Adv Vet Med 1999; 41: 715-732.
8. HogenEsch H, Azcona-Olivera J, Scott-Moncrieff C, Snyder PW, Glickman LT. Vaccine-induced autoimmunity in the dog. Adv Vet Med 1999; 41:733-744.
9. Dodds WJ. Vaccination protocols for dogs predisposed to vaccine reactions. J Am An Hosp Assoc 2001; 38: 1-4.
10. Scott-Moncrieff JC, Azcona-Olivera J, Glickman NW, Glickman LT, HogenEsch H. Evaluation of antithyroglobulin antibodies after routine vaccination in pet and research dogs. J Am Vet Med Assoc 2002; 221: 515-521.
11. Paul MA (chair) et al. Report of the AAHA Canine Vaccine Task Force: 2003 canine vaccine guidelines, recommendations, and supporting literature. AAHA, April 2003, 28 pp.
12. May C, Hammill J, Bennett, D. Chinese shar pei fever syndrome: A preliminary report. Vet Rec 1992;131: 586-587.
13. Scott-Moncrieff JC, Snyder PW, Glickman LT, Davis EL, Felsburg PJ. Systemic necrotizing vasculitis in nine young beagles. J Am Vet Med Assoc 1992; 201: 1553-1558.
14. Dodds WJ. Estimating disease prevalence with health surveys and genetic screening. Adv Vet Sci Comp Med 1995; 39: 29-96.
15. Wilbur LA, Evermann JF, Levings RL, Stoll LR, Starling DE, Spillers CA, Gustafson GA, McKeirnan AJ. Abortion and death in pregnant bitches associated with a canine vaccine contaminated with blue tongue virus. J Am Vet Med Assoc 1994; 204:1762-1765.
16. Day MJ, Penhale WJ. Immune-mediated disease in the old English sheepdog. Res Vet Sci 1992; 53: 87-92.
17. Dougherty SA, Center SA. Juvenile onset polyarthritis in Akitas. J Am Vet Med Assoc 1991; 198: 849-855.
18. Vascellari M, Melchiotti E, Bozza MA et al. Fibrosarcomas at presumed sites of injection in dogs: characteristics and comparison with non-vaccination site fibrosarcomas and feline post-vaccinal firosarcomas. J Vet Med 50 (6): 286-291, 2003.
19. Twark L, Dodds WJ. Clinical use of serum parvovirus and distemper virus antibody titers for determining revaccination strategies in healthy dogs. J Am Vet Med Assoc 2000; 217:1021-1024.
20. Flemming DD, Scott JF. The informed consent doctrine: what veterinarians should tell their clients. J Am Vet Med Assoc 224: 1436-1439, 2004.
21. Klingborg DJ, Hustead DR, Curry-Galvin E, et al. AVMA Council on Biologic
and Therapeutic Agents’ report on cat and dog vaccines. J Am Vet
Med Assoc 221: 1401-1407, 2002.
22. Schultz RD, Ford RB, Olsen J, Scott F. Titer testing and vaccination: a new look at traditional practices. Vet Med, 97: 1-13, 2002 (insert).