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Vaccination Protocols for Dogs
Predisposed to Vaccine Reactions
by
W. Jean Dodds, DVM
Journal of the American Animal Hospital Association
May 1, 2001
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 high titered
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 (19861988), 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
Weimarane 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 at risk 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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References
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