More from Dr Dodds
Vaccine Protocols
for Dogs
Predisposed to
Vaccine Reactions
W Jean Dodds DVM
DrJean Dodds is the woman who first told the truth
about vaccines to dog lovers. A member of the scientific
community, Dr Dodds clearly felt that dog owners had a right
to know the truth so that they could make informed and wise
decisions. We all owe Dr Dodds a huge, enormous, debt of
gratitude. The following paper was published in the Journal
of the American Animal Hospital Association (37: 1-4, 2001).
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 (1-6). 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
overvaccinating; and using caution in vaccinating ill, geriatric,
debilitated or febrile individuals, and animals from breeds or
families known to be at increased risk for immunologica!
reactions (3,5-
. __________________
Adverse Effects of Vaccines
As the most commonly recognised 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 emphasised 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
immunologica) 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
anaemia (AIHA) resulting in icterus, or
immune-mediated thrombocytopenia
(ITP) resulting in petechiae and
ecchymotic haemorrhage (1-4,9,10,
12,15). Hepatic enzymes may be
m a r k e d l y elevated, and liver or kidney failure may occur by itself or
accompany bone-marrow suppression
(3). Furthermore, MLV vaccination
associated with the
development of transient seizures in
puppies and adult dogs of breeds or
crossbreeds susceptible to immunediseases,
especially those
involving haematological or endocrine
tissues (e.g., AIHA, ITP, autoimmune
thyroiditis) (1-3). Postvaccinal
polyneuropathy is a recognised 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 litter mates and relatives
that are at increased risk for similar adverse vaccine
reactions (1-5).
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
casually to the ill-advised but all-too-common practice of
vaccinating pregnant animals. The potential for side
effects such as promotion of chronic disease sites 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
overvaccinating, 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
immunocompromised 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 (1-3,9,13). 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 pre-existing 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 haematological disease (i.e., AIHA,
ITP, or both) (12). Among the more commonly
recognised 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, Long-Haired
Dachshund, Old English Sheepdog, Scottish Terrier,
Shetland Sheepdog, Shih Tzu, Vizsia, and Weimaraner,
as well as breeds of white or predominantly white coat
colour or with coat colour dilution (e.g., blue and fawn
Doberman Pinschers, the merle Collie, Australian
Shepherd, Shetland Sheepdog, and harlequin Great
Dane) (1-3). 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 30-45 day 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 ostedystrophy (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 reaction (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
summarised below._____________________
Vaccine-Associated Disease in Old English
Sheepdogs.
Old English Sheepdogs appear to be predisposed to
a variety of autoimmune diseases (1-3,13). 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
haematological 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
1 1 5 cases (2). Thyroid disease was recognised as either
aprimary 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 both -
an example of the polyglandular autoimmune (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 are also subject to a variety of immun-mediated
disorders, including Vogt-Koyanagi-Harada 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 anaemia,
neutrophilic leukocytosis, and occasional thrombocytopenia.
Joint aspiration and radiography indicated nonseptic,
nonerosive 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
amyloiosis and wide spread evidence of vasculitis. The
history, signs and close association with immunisation
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 (5.6% that died, and one that became ill but survived
(3).
A genetic basis for immune-mediated disease and
immunodeficiencies states is well known
(1,2,12,13,15,17,1
. 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 non-specific 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 dysregulation (17).
Since the modem 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 (1-3,
10,11). Although litter mates from affected families typically
end up in different locales, all undergo relatively
standardised immunisation 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 recognised 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 2-year period (1986-198
, Couto (3) evaluated
170 related Weimaraners, including affected puppies and
their relatives. 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, diarrhoea, pyderma, 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 the 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) - a group of signs identical to those of the affected
young Akitas described previously. Most affected puppies
also showed leukocytosis (with neutrophilia or neutropenia),
diarrhoea, 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, deizures or 'spaced out' behaviour, 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
antibiotics may be given prophylactically, and vitamin C (500
to 1000 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 CDVand
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).
4 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 to 2- to 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 jeopardise 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
overvaccinating; 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 (3,5-
. 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 behaviour and overall health after the
second or subsequent boosters; and avoiding
revaccination of individuals already experiencing a
significant adverse event. Litter mates 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 above 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 age-old physician's
adage, forwarded by Hippocrates, of 'to help, or at least
do no harm'.
References
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Med1983;27; 163-196.
2. Dodds WJ. Estimating disease prevalence with health surveys and
genetic screening. Adv Vet Sci Comp Med 1995,39:29-96.
3. Dodds WJ. More bumps on the vaccine road. Adv Vet Med
1999;41:715-732.
4. 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.
5. Schultz R. Current and future canine and feline vaccination programs. Vet
Med 1998:93:233-254.
6. Tizard 1. Risks associated with use of live vaccines. J Am Vet Med Assoc
1990;196:1851-1858.
7. Twark L, Dodds WJ. Clinical use of serum parvovirus and distemper virus
antibody liters for determining revaccinatton strategies in healthy dogs. J Am Vet Med
Assoc 2000;217:1021-1024.
8. Tizard I, Ni Y. Use of serologic testing to assess immune status of
companion animals. J Am Vet Med Assoc 1998:213:54-60.
9. Phillips TR. Jensen JL. Rubino MJ, Yang WC. Schultz RD. Effects of
vaccines on the canine immune system. Can J Vet Res 1989.53:154-160.
10. Duvai D, Giger U. Vaccine-associated immune-mediated hemolytic
anaemia in the dog. J Vet Intern Med 1996,10:290-295.