| W. Jean Dodds, DVM
Journal of the American Animal Hospital Association
May 1, 2001
W. Jean Dodds, DVM Keywords: Canine; Vaccination Protocols
for Dogs; Vaccine Reactions
GUEST Editorial
There is increasing evidence in veterinary medicine that vaccines
can trigger immune mediated and other chronic disorders (i.
e., vaccinosis), especially in certain apparently predisposed
breeds. 16 Accordingly, clinicians need to be aware of this
potential and offer alternative approaches for preventing
infectious diseases in these animals. Such alternatives to
current vaccine practices include: measuring serum antibody
titers; avoidance of unnecessary vaccines or over vaccinating;
and using caution in vaccinating ill, geriatric, debilitated,
or febrile individuals, and animals from breeds or families
known to be at increased risk for immunological reactions.
3,58 Fortunately, the most common effect of vaccine administration
is the stimulation of an immune response that conveys protection
for that disease. This outcome has resulted in the widespread
reduction in morbidity and mortality from the many infectious
diseases that have plagued both animals and humans. An excellent
example of this benefit is the global eradication of smallpox
as the result of a comprehensive immunization program. Despite
these intended benefits, however, vaccination does carry with
it attendant risks.
Adverse Effects of Vaccines
As the most commonly recognized adverse effect of vaccination
is an immediate hypersensitivity or anaphylactic reaction,
practitioners are less familiar with the more rare but equally
serious acute or chronic immune mediated syndromes that can
occur. The veterinary profession and vaccine industry have
traditionally emphasized the importance of giving a series
of vaccinations to young animals to prevent infectious diseases,
to the extent that this practice is considered routine and
is generally safe for the majority of animals. Few clinicians
are prepared, therefore, for encountering an adverse event
and may overlook or even deny the possibility.
Beyond the immediate hypersensitivity reactions, other acute
events tend to occur 24 to 72 hours afterward, or 7 to 45
days later in a delayed type immunological response. 1,6,9,10
Even more delayed adverse effects include mortality from hightitered
measles vaccine in infants, canine distemper antibodies in
joint diseases of dogs, and feline injection site
fibrosarcomas. 3,11 The increasing antigenic load presented
to the host individual by modified live virus (MLV) vaccines
is presumed to be responsible for the immunological challenge
that can result in a delayed hypersensitivity reaction. 6,9
The clinical signs associated with nonanaphylactic vaccine
reactions typically include fever, stiffness, sore joints
and abdominal tenderness, susceptibility to infections, neurological
disorders and encephalitis, autoimmune hemolytic anemia (AIHA)
resulting in icterus, or immune mediated thrombocytopenia
(ITP) resulting in petechiae and ecchymotic hemorrhage. 14,9,10,1215
Hepatic enzymes may be markedly elevated, and liver or kidney
failure may occur by itself or accompany bone marrow suppression.
3 Furthermore, MLV vaccination has been associated with the
development of transient seizures in puppies and adult dogs
of breeds or crossbreeds susceptible to immune mediated diseases,
especially those involving hematological or endocrine tissues
(e. g., AIHA, ITP, autoimmune thyroiditis). 13 Postvaccinal
polyneuropathy is a recognized entity associated occasionally
with the use of distemper, parvovirus, rabies, and possibly
other vaccines. 3,6,9 This can result in various clinical
signs, including muscular atrophy, inhibition or interruption
of neuronal control of tissue and organ function, incoordination,
and weakness. 3 Therefore, we have the responsibility to advise
companion animal breeders and caregivers of the potential
for genetically susceptible littermates and relatives that
are at increased risk for similar adverse vaccine reactions.
15 Commercial vaccines, on rare occasion, can also be contaminated
with other adventitious viral agents, 6,16 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 16 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. 3 Recently, a vaccine manufacturer
had to recall all biological products containing a distemper
component, because they were associated with a higher than
expected rate of central nervous system postvaccinal reactions
1 to 2 weeks following administration. 3
If, as a profession, we conclude that we are over vaccinating,
other issues come to bare, such as the needless client dollars
spent on vaccines, despite the well intentioned solicitation
of clients to encourage annual booster vaccinations so that
pets also can receive a wellness examination. 5 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. 5,6,9 However,
this can overwhelm the immune compromised or even healthy
host that has ongoing exposure to other environmental stimuli
as well as a genetic predisposition that promotes adverse
response to viral challenge. 13,9,13 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 to 3 weeks apart, some veterinarians have
advocated vaccination once a week in stressful situations.
This practice makes little sense, scientifically or medically.
5 An augmented immune response to vaccination is seen in dogs
with preexisting inhalant allergies (i. e., atopy) to pollens.
3 Furthermore, the increasing current problems with allergic
and immunological diseases have been linked to the introduction
of MLV vaccines more than 20 years ago. 6 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.
Predisposed Breeds
Twenty years ago, this author began studying families of dogs
with an apparent increased frequency of immune mediated hematological
disease (i. e., AIHA, ITP, or both). 1,2
Among the more commonly recognized predisposed breeds were
the Akita, American cocker spaniel, German shepherd dog, golden
retriever, Irish setter, Great Dane, Kerry blue terrier, and
all dachshund and poodle varieties; but predisposition was
found especially in the standard poodle, longhaired dachshund,
Old English sheepdog, Scottish terrier, Shetland sheepdog,
shih tzu, vizsla, and Weimaraner, as well as breeds of white
or predominantly white coat color or with coat color dilution
(e. g., blue and fawn Doberman pinschers, the merle collie,
Australian shepherd, Shetland sheepdog, and harlequin Great
Dane). 13 Recently, other investigators have noted the relatively
high frequency of AIHA, ITP, or both in American cocker spaniels
10 and Old English sheepdogs. 13 A significant proportion
of these animals had been vaccinated with monovalent or polyvalent
vaccines within the 30 to 45day period prior to the onset
of their autoimmune disease. 1,2,10 Furthermore, the same
breeds listed above appear to be more susceptible to other
adverse vaccine reactions, particularly postvaccinal seizures,
high fevers, and painful episodes of hypertrophic osteodystrophy
(HOD). 3 For animals that have experienced an adverse vaccine
reaction, the recommendation is often to refrain from vaccinating
these animals until at least after puberty, and instead to
measure serological antibody titers against the various diseases
for which vaccination has been given. This recommendation
raises an issue with the legal requirement for rabies vaccination.
As rabies vaccines are strongly immunogenic and are known
to elicit adverse neurological reactions, 3,5 it would be
advisable to postpone rabies vaccination for such cases. A
letter from the primary care veterinarian stating the reason
for requesting a waiver of rabies vaccination for puppies
or adults with documented serious adverse vaccine reactions
should suffice.
As further examples, findings from the author’s large,
accumulated database of three susceptible breeds are summarized
below.
Vaccine Associated Disease in Old English Sheepdogs
Old English sheepdogs appear to be predisposed to a variety
of autoimmune diseases. 13,13 Of these, the most commonly
seen are AIHA, ITP, thyroiditis, and Addison’s disease.
2,17
Between 1980 and 1990, this author studied 162 cases of
immune mediated hematological diseases in this breed. One
hundred twenty nine of these cases had AIHA, ITP, or both
as a feature of their disease. Vaccination within the previous
30 days was the only identified triggering event in seven
cases and was an apparent contributing factor in another 115
cases. 2 Thyroid disease was recognized as either a primary
or secondary problem in 71 cases, which is likely an underestimate
of the true incidence, as thyroid function tests were not
run or were inconclusive in most of the other cases.
Experience with a particular Old English sheepdog family
supported a genetic predisposition to autoimmune thyroiditis,
Addison’s disease, and AIHA or ITP or bothÑ an
example of the polyglandular autoimmune syndrome. 2,17 Pedigrees
were available from 108 of the 162 Old English sheepdog cases
of autoimmune disease; a close relationship was found among
all but seven of the affected dogs. 2 Two of three pedigrees
available from the studies of Day and Penhale 13 were also
related to this large North American study group.
Vaccine Associated Disease in Young Akitas
Akitas also are subject to a variety of immune mediated disorders,
including VogtKoyanagiHarada syndrome (VKH), pemphigus, and
heritable juvenile onset immune mediated polyarthritis (IMPA).
3,14 Juvenile onset IMPA occurs in Akitas less than 8 months
of age. Of 11 closely related puppies in the author’s
case series, the mean age of onset was 14 weeks. 3 Initial
signs appeared 3 to 29 days following vaccination with polyvalent
MLV or killed virus or both, with a mean reaction time of
14 days. All had profound joint pain and cyclic febrile illness
lasting 24 to 48 hours. Hemograms revealed mild non regenerative
anemia, neutrophilic leukocytosis, and occasional thrombocytopenia.
Joint aspiration and radiography indicated non septic, non
erosive arthritis. Despite treatment for immune mediated disease
and pyrexia, all eight dogs had relapsing illness and died
or were euthanized by 2 years of age from progressive systemic
amyloidosis and renal failure. Necropsies were performed on
three dogs, two of which had glomerular amyloidosis and widespread
evidence of vasculitis. The history, signs, and close association
with immunization suggested that juvenile onset polyarthritis
and subsequent amyloidosis in these Akitas may have been an
autoimmune response triggered by the viral antigens or other
components of vaccines. 3 The vaccine related history was
reviewed for 129 puppies belonging to the family of Akitas
discussed above. Polyvalent MLV vaccine was given to 104 of
them, with 10 (9.8%) puppies showing adverse reactions and
death. Another six puppies received a polyvalent all killed
vaccine product (no longer commercially available) with no
reactors, and 19 puppies received homeopathic nosodes initially
followed by killed canine parvovirus (CPV) vaccine, with one
reactor that died and one that became ill but survived. 3
A genetic basis for immune mediated diseases and immunodeficiencies
states is well known. 1,2,12,13,15,17,18 The mechanism for
triggering immune mediated disease is poorly understood, but
predisposing factors have been implicated when genetically
susceptible individuals encounter environmental agents that
induce nonspecific inflammation, molecular mimicry, or both.
3,17 The combined effects of these genetic and environmental
factors override normal self tolerance and are usually mediated
by T cell imbalance or dys regulation. 17 Since the modern
Akita arose from a relatively small gene pool, understanding
the potential environmental triggers of juvenile onset IMPA
has immediate importance. Numerous agents have been implicated,
including drugs, vaccines, viruses, bacteria, chemicals, and
other toxins. 13,10,11 Although the littermates from affected
families typically end up in different locales, all undergo
relatively standardized immunization procedures at a similar
age.
Vaccine Associated Disease in Young Weimaraners
The Weimaraner breed appears to be especially prone to both
immune deficiency and autoimmune diseases, which have been
recognized with increasing frequency in related members of
the breed over the past 15 years. 3 Autoimmune thyroiditis
leading to clinically expressed hypothyroidism is probably
the most common of these disorders, along with
vaccine associated HOD of young Weimaraners. 2,3,17 During
a 2year period (), Couto evaluated 170 related Weimaraners,
including affected puppies and their relatives, and the findings
were relayed in a breed newsletter as discussed in an earlier
reference. 3 Clinical signs of the affected dogs included
high fevers, polyarthritis with pain and swelling typical
of HOD, coughing and respiratory distress from pneumonia,
enlarged lymph nodes, diarrhea, pyoderma, and mouth ulcers.
In most cases, clinical signs were first detected shortly
after vaccination with a second dose of polyvalent MLV vaccine
when the puppies were between 2 and 5 months of age. This
author has studied more than 60 Weimaraners with vaccine associated
disease. In 24 cases described in a previous article, 3 the
mean age of onset of clinical signs was 13.5 weeks, with a
mean reaction time of 10.5 days post vaccination. Males were
predominantly affected. All affected puppies showed high spiking
fevers, cyclic episodes of pain, and polyarthritis (HOD)Ñ
a group of signs identical to those of the affected young
Akitas described previously. Most affected puppies also showed
leukocytosis (with neutrophilia or neutropenia), diarrhea,
lethargy, anorexia, and enlarged lymph nodes. Some puppies
also had levels of immunoglobulin A, immunoglobulin M, or
both below those expected for their age, and one puppy had
immunoglobulin G (IgG) deficiency as well. Other signs included
coughing, pneumonia, depression, seizures or ”spaced
out” behavior, refusal to stand or move, and hyperesthesia
(“ walking on eggshells”). The outcome for half
of these cases was good (12 of the 24 are healthy adults),
although two died, three were euthanized as puppies, and three
remained chronically ill as adults. Another four cases were
lost to follow up.
Management of this clinical syndrome is best accomplished
with an initial dose of parenteral corticosteroids followed
by a tapering course of corticosteroids over 4 to 6 weeks.
Systemic broad spectrum antibiotic may be given prophylactically,
and vitamin C (500 to 1,000 mg daily) can be included to promote
immune support. Recurring episodes are treated by increasing
the corticosteroid dosage for a few days until the flare up
has subsided. The response to initial corticosteroid treatment
is always dramatic, with fever and joint pain usually subsiding
within a matter of hours.
Serological titers for canine distemper virus (CDV) and CPV
were determined in 19 of the 24 affected Weimaraner puppies,
and all were adequate. Upon reaching adulthood, serum antibody
titers were reevaluated, and detectable CDV and CPV specific
IgG persisted. Several of these dogs have subsequently developed
hypothyroidism and are receiving thyroid replacement. 3,4,17
Thus, to avoid recurrence of adverse effects, which has been
shown to be even more severe if another vaccine booster is
given, serological titers for CDV and CPV are measured. 7
Another approach recommended by Weimaraner breeders and this
author is to modify the vaccination protocol, especially for
puppies from families known to have experienced adverse vaccine
reactions. Examples would be to limit the number of antigens
used in the vaccine series to those infectious agents of most
clinical concern (i. e., CDV, CPV, and rabies virus), separating
these and other antigens by 2to 3 week intervals, and giving
rabies vaccine by itself at 6 months of age. A booster series
is administered at 1 year by separating the CDV, CPV, rabies
virus, and other vaccine components, where possible, and giving
them on separate visits at least 2 weeks apart. Thereafter,
serological antibody titers can be measured (except for those
vaccines required by law, unless a specific exemption is made
on an individual case basis).
Recommendations
Practitioners should be encouraged during the initial visit
with a new puppy owner or breeder to review current information
about the breed’s known congenital and heritable traits.
Several databases, veterinary textbooks, and review articles
contain the relevant information to assist here. 2 For those
breeds at increased risk, the potential for adverse reactions
to routine vaccinations should be discussed as part of this
wellness program. Because breeders of atrisk breeds have likely
alerted the new puppy buyer to this possibility, we should
be mindful and respectful of their viewpoint, which may be
more informed than ours about a specific breed or family issue.
To ignore or dismiss these issues can jeopardize the client
patient relationship and result in the client going elsewhere
for veterinary services or even turning away from seeking
professional care for these preventive health measures. As
a minimum, if we are unaware of the particular concern expressed,
we can research the matter or ask the client for any relevant
scientific or medical documentation. 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 over vaccinating; using
caution in vaccinating sick, very old, debilitated, 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. 3,58 Considerations include starting
the vaccination series later, such as at 9 or 10 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. Altering the puppy vaccination
protocol, as suggested previously for the Weimaraner, is also
advisable.
Following these recommendations may be a prudent way for
our profession to balance the need for individual patient
disease prevention with the ageold physician’s adage,
forwarded by Hippocrates, of “to help, or at least do
no harm.”
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