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Adverse events diagnosed within three days of vaccine administration in dogs


Abstract and Figures

To determine incidence rates and potential risk factors for vaccine-associated adverse events (VAAEs) diagnosed within 3 days of administration in dogs. Retrospective cohort study. 1,226,159 dogs vaccinated at 360 veterinary hospitals. Electronic records from January 1, 2002, through December 31, 2003, were searched for possible VAAEs (nonspecific vaccine reaction, allergic reaction, urticaria, or anaphylaxis) diagnosed within 3 days of vaccine administration. Information included age, weight, sex, neuter status, and breed. Specific clinical signs and treatments were reviewed in a random sample of 400 affected dogs. The association between potential risk factors and a VAAE was estimated by use of multivariate logistic regression. 4,678 adverse events (38.2/10,000 dogs vaccinated) were associated with administration of 3,439,576 doses of vaccine to 1,226,159 dogs. The VAAE rate decreased significantly as body weight increased. Risk was 27% to 38% greater for neutered versus sexually intact dogs and 35% to 64% greater for dogs approximately 1 to 3 years old versus 2 to 9 months old. The risk of a VAAE significantly increased as the number of vaccine doses administered per office visit increased; each additional vaccine significantly increased risk of an adverse event by 27% in dogs < or = 10 kg (22 lb) and 12% in dogs > 10 kg. Young adult small-breed neutered dogs that received multiple vaccines per office visit were at greatest risk of a VAAE within 72 hours after vaccination. These factors should be considered in risk assessment and risk communication with clients regarding vaccination.
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1102 Scientific Reports: Original Study JAVMA, Vol 227, No. 7, October 1, 2005
accines are developed to be immunogens and are
required to have potency, safety, and efficacy before
licensing; however, no vaccine is absolutely reaction free
or completely effective. Although manufacturers’ pre-
marketing safety trials help ensure that vaccine-associ-
ated adverse events (VAAEs) occur infrequently, VAAEs
have evoked public and professional concern regarding
the possible overvaccination of humans and animals.
Traditional postmarketing surveillance of veteri-
nary vaccines relies on veterinarians and owners to
voluntarily submit reports of suspected reactions to
manufacturers or the USDA. Limitations to passive sur-
veillance include variability in report quality, selective
reporting, underreporting, and the inability to deter-
mine whether a vaccine caused the adverse event
described in any report.
The information submitted
in voluntarily generated reports is not necessarily com-
plete and often lacks important details about the ani-
mal, observed event, or concurrent medications
received by the affected animal. Incidence rates and
relative risks for specific VAAEs cannot be calculated
because of the lack of information about the overall
vaccinated population (denominator data or the popu-
lation at risk of a VAAE).
Large, population-based medical record databases
have been used in recent years to conduct epidemio-
logic investigations of human vaccine safety.
these databases are usually generated during the rou-
tine administration of medical care and do not require
the completion of a separate VAAE form, the problem
of underreporting of events is reduced. Large popula-
tions can be examined for infrequent adverse events,
and denominator data on doses given and the avail-
ability of appropriate comparison groups make these
databases ideal for studying vaccine safety.
Banfield, The Pet Hospital, is a small animal gen-
eral practice that uses the same computerized medical
record system in more than 400 hospital locations
throughout the United States. Electronic medical
records are stored in a central data warehouse and can
be easily retrieved for administrative or medical review
and analysis. Proprietary software
containing stan-
dardized codes for physical examinations, laboratory
tests, diagnoses, and treatments is used by all veteri-
narians in the practice. The codes, when combined
with dates, allow determination of temporal relation-
ships between vaccination and potential VAAEs, a fac-
tor that is important for assessing causality.
Abnormalities noticed within a few days of vaccination
may be attributable to an adverse response to the vac-
cine immunogens, but the risk factors and incidence of
these events in companion animals have not been char-
acterized. The purpose of the study reported here was
to use the Banfield database to estimate the incidence
rate and potential risk factors for VAAEs that occurred
within 3 days of vaccine administration in dogs.
Adverse events diagnosed within three days
of vaccine administration in dogs
George E. Moore, DVM, MS, PhD, DACVPM, DACVIM; Lynn F. Guptill, DVM, PhD, DACVIM;
Michael P. Ward,
BVSc, MS, MPVM, PhD; Nita W. Glickman, MPH, PhD; Karen K. Faunt, DVM, DACVIM;
Hugh B. Lewis,
BVMS, DACVP; Lawrence T. Glickman, VMD, DrPH
Objective—To determine incidence rates and poten-
tial risk factors for vaccine-associated adverse events
(VAAEs) diagnosed within 3 days of administration in
Design—Retrospective cohort study.
Animals—1,226,159 dogs vaccinated at 360 veteri-
nary hospitals.
Procedure—Electronic records from January 1, 2002,
through December 31, 2003, were searched for pos-
sible VAAEs (nonspecific vaccine reaction, allergic
reaction, urticaria, or anaphylaxis) diagnosed within 3
days of vaccine administration. Information included
age, weight, sex, neuter status, and breed. Specific
clinical signs and treatments were reviewed in a ran-
dom sample of 400 affected dogs. The association
between potential risk factors and a VAAE was esti-
mated by use of multivariate logistic regression.
Results—4,678 adverse events (38.2/10,000 dogs
vaccinated) were associated with administration of
3,439,576 doses of vaccine to 1,226,159 dogs. The
VAAE rate decreased significantly as body weight
increased. Risk was 27% to 38% greater for neutered
versus sexually intact dogs and 35% to 64% greater
for dogs approximately 1 to 3 years old versus 2 to 9
months old. The risk of a VAAE significantly increased
as the number of vaccine doses administered per
office visit increased; each additional vaccine signifi-
cantly increased risk of an adverse event by 27% in
dogs 10 kg (22 lb) and 12% in dogs > 10 kg.
Conclusions and Clinical Relevance—Young adult
small-breed neutered dogs that received multiple vac-
cines per office visit were at greatest risk of a VAAE
within 72 hours after vaccination. These factors
should be considered in risk assessment and risk
communication with clients regarding vaccination.
J Am Vet Med Assoc
From the Departments of Veterinary Pathobiology (Moore, Ward,
Glickman, Glickman) and Veterinary Clinical Sciences (Guptill),
School of Veterinary Medicine, Purdue University, West Lafayette,
IN 47907-2027; and Banfield, The Pet Hospital, 11815 NE Glenn
Widing Dr, Portland, OR 97220 (Faunt, Lewis). Dr. Ward’s present
address is the Department of Veterinary Integrative Biosciences,
College of Veterinary Medicine and Biomedical Sciences, Texas
A&M University, College Station, TX 77843-4458.
Supported by the CDC National Center for Infectious Diseases
(grant No. R01 CI000093).
Address correspondence to Dr. Moore.
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JAVMA, Vol 227, No. 7, October 1, 2005 Scientific Reports: Original Study 1103
Materials and Methods
Electronic medical records of all dogs at 360 Banfield vet-
erinary hospitals from January 1, 2002 through December 31,
2003 were extracted from the Banfield practice database.
Records were included in the study if the species code was
canine and if treatments included a code for Bordetella vac-
coronavirus vaccine,
multivalent distemper-adenovirus-
parainfluenza-parvovirus-leptospirosis (serovars canicola,
icterohaemorrhagiae, grippotyphosa, and pomona) vaccine,
Giardia vaccine,
Borrelia vaccine,
parvovirus vaccine,
rabies vaccine.
Records for dogs that received both an
injectable heartworm preventive and a vaccine during the
same office visit were not included in analyses.
The date of birth, breed, sex, neuter status, weight, and
date of vaccination were recorded for each dog. Medical
records of dogs that received vaccinations were searched for
possible VAAEs by use of diagnostic codes (vaccine reaction,
allergic reaction, urticaria, anaphylaxis, cardiac arrest, cardio-
vascular shock, and sudden death). Diagnoses
were only included in analyses if the diagnosis
date was within 3 days after vaccine administra-
tion. Date of death, if recorded, was used to
determine if death occurred within 3 days of vac-
cination. The free-text medical note field was
reviewed in a random sample of 400 affected
dogs to determine clinical signs and treatments
associated with a VAAE.
Statistical analyses—All calculations were
performed with statistical software.
Sex and
neuter status were analyzed as categoric vari-
ables. Continuous variables of age and weight
were converted to categoric variables because
nonlinear trends were detected in the model-fit-
ting process. Dogs were grouped on the basis of
age at date of vaccination as follows: 2 to 9
months, > 9 months to 1.5 years, > 1.5 to 2.5
years, > 2.5 to 3.5 years, > 3.5 to 5.5 years, > 5.5
to 8.5 years, and > 8.5 years. Weight was con-
verted from a continuous to a categoric variable
of 5-kg (11-lb) weight groups up to 45 kg
(99 lb). Incidence rates with 95% confidence
limits were calculated via assumption of a bino-
mial distribution for proportions. Tests for trend
were performed across ordered groups by use of
the Cuzick nonparametric test. All VAAE rates
are reported as the number of adverse
events/10,000 dogs vaccinated. For categoric
variables, rates for affected dogs were compared
with rates for nonaffected dogs by use of the χ
test for independence.
Potential risk factors for VAAEs were
evaluated by use of bivariate and multivariate
unconditional logistic regression, and multi-
variate logistic regression included dog ran-
dom effects. Estimates of the odds ratio (OR)
and 95% confidence intervals (CIs) for each
risk factor were obtained by use of exponen-
tials of the regression coefficients. Interactions
between independent variables in the final
multivariate model were assessed for an asso-
ciation with an adverse event. Interactions
between vaccines were not included in multi-
variate analysis because of the large number of
vaccine combinations (n = 58). Maximum
likelihood estimates of the logistic parameters
and final model were assessed for significance
by use of the Hosmer-Lemeshow χ
of-fit test. A value of P < 0.05 was considered
Population—In the 2-year study period, 4,531,837
vaccine doses were administered to 1,537,534 dogs at
360 veterinary hospitals. Excluding from analysis
311,375 dogs that concurrently received injectable
heartworm preventive and vaccinations, 3,439,576 vac-
cine doses were administered to 1,226,159 dogs. Mean
number of vaccine doses administered per dog per
office visit was 2.8 (range, 1 to 6), and 4,678 dogs had
a diagnosis of a VAAE within 3 days of vaccine admin-
istration (38.2 VAAEs/10,000 dogs vaccinated; 95% CI,
37.1 to 39.3). The percentage of VAAEs diagnosed on
days 0 (same day), 1, 2, and 3 postvaccination was
72.8%, 18.9%, 5.5%, and 2.8%, respectively. Of 4,678
VAAEs, 3,080 (65.8%) were coded as vaccine reactions,
1,481 (31.7%) as allergic reactions, 80 (1.7%) as ana-
Figure 1—Mean ± SEM vaccine-associated adverse event (VAAE) rates (No. of
adverse events/10,000 dogs vaccinated) by 5-kg (11-lb) weight groups in 1,226,159
dogs vaccinated at 360 veterinary hospitals from January 1, 2002, to December 31,
2003. The VAAEs were diagnosed within 3 days of vaccine administration.To convert
kilograms to pounds, multiply by 2.2.
Figure 2—Mean ± SEM VAAE rates for all vaccines (n = 1,226,159) and for rabies
vaccine administered alone (118,765) to dogs of various body weights (BWs).
Figure 1 for remainder of key.
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1104 Scientific Reports: Original Study JAVMA, Vol 227, No. 7, October 1, 2005
Figure 3—Mean ± SEM VAAE rates by age in dogs administered 1 or more vaccines
at 360 veterinary hospitals from January 1, 2002, to December 31, 2003.
1 for remainder of key.
Breed Dogs vaccinated (n) VAAE (n) VAAE rate/10,000 dogs 95% CL
Dachshund 41,323 503 121.7 (111.4, 132.8)
Pug 20,214 188 93.0 (80.2, 107.2)
Boston Terrier 9,541 80 83.8 (66.5, 104.3)
Miniature Pinscher 15,310 117 76.4 (63.2, 91.5)
Chihuahua 68,839 524 76.1 (69.8, 82.9)
Maltese 20,663 138 66.8 (56.1, 78.9)
Miniature Schnauzer 15,296 99 64.7 (52.6, 78.7)
Jack Russell Terrier 23,717 129 54.4 (45.4, 64.6)
Toy Poodle 12,311 61 49.5 (37.9, 63.6)
Yorkshire Terrier 33,563 159 47.3 (40.3, 55.3)
Boxer 31,141 142 45.6 (38.4, 53.7)
Pomeranian 27,543 125 45.4 (37.8, 54.0)
Pekingese 9,516 40 42.0 (30.0, 57.2)
Shih Tzu 47,964 199 41.5 (35.9, 47.6)
English Bulldog 5,470 22 40.2 (25.2, 60.8)
Lhasa Apso 15,386 59 38.3 (29.2, 49.4)
Weimaraner 5,393 20 37.1 (22.7, 57.2)
Beagle 34,872 126 36.1 (30.1, 43.0)
Bichon Frise 13,444 46 34.2 (25.1, 45.6)
American Eskimo Dog 5,829 22 33.7 (23.7, 57.1)
American Cocker Spaniel 20,795 70 33.6 (26.3, 42.5)
Shetland Sheepdog 9,891 33 33.4 (23.0, 46.8)
Shar Pei 7,337 24 32.7 (21.0, 48.6)
Miniature Poodle 7,207 23 31.9 (20.2, 47.8)
Golden Retriever 41,779 126 30.2 (25.1, 35.9)
Basset Hound 7,828 23 29.4 (18.6, 44.1)
Welsh Corgi 5,511 16 29.0 (16.6, 47.1)
Siberian Husky 6,362 17 26.7 (15.6, 42.7)
Great Dane 5,211 13 24.9 (13.3, 42.6)
West Highland White Terrier 6,742 16 23.7 (13.6, 38.5)
Labrador Retriever 132,222 312 23.6 (21.1, 26.4)
Doberman Pinscher 6,520 15 23.0 (12.9, 37.9)
American Pit Bull Terrier 6,718 15 22.3 (12.5, 36.8)
Akita 6,161 13 21.1 (11.2, 36.1)
Mixed 44,188 89 20.1 (16.2, 24.8)
Australian Shepherd 16,221 30 18.5 (12.5, 26.4)
Dalmatian 7,234 13 18.0 (9.6, 30.7)
Australian Cattle Dog 5,702 10 17.5 (8.4, 32.2)
Border Collie 13,524 22 16.3 (10.2, 24.6)
Collie 5,708 9 15.8 (7.2, 29.9)
Chow Chow 23,387 32 13.4 (9.4, 19.3)
German Shepherd Dog 60,017 78 13.0 (10.3, 16.2)
Rottweiler 38,538 50 13.0 (9.6, 17.1)
Table 1—Incidence rate per 10,000 dogs and 95% confidence limits (CL) by breed for vaccine-associated
adverse events (VAAEs) diagnosed within 3 days of vaccine administration at 360 veterinary hospitals
from January 1, 2002, to December 31, 2003. Breeds listed if represented by 5,000 vaccinated dogs.
05-02-0089.qxp 9/13/2005 10:38 AM Page 1104
JAVMA, Vol 227, No. 7, October 1, 2005 Scientific Reports: Original Study 1105
phylaxis, 32 (0.7%) as urticaria, and 5 (0.1%) as cardiac
arrest. Death was reported in association with vaccina-
tion in 3 dogs (0.024 deaths/10,000 dogs vaccinated
[2.4 deaths/1,000,000]; 95% CI, 0.005 to 0.072).
Bivariate analyses—The population included
252,434 (20.6%) sexually intact males, 191,601
(15.6%) sexually intact females, 378,224 (30.8%)
neutered males, and 403,900 (32.9%) spayed females.
Among those groups, unadjusted VAAE rates/10,000
dogs were 32.9 (95% CI, 30.7 to 35.2), 35.7 (95% CI,
33.1 to 38.5), 39.1 (95% CI, 37.1 to 41.1), and 41.2
(95% CI, 39.8 to 43.8), respectively. Among all dogs,
the VAAE rates in 2002 (1,942/515,447 [37.7/10,000])
and 2003 (2,736/710,712 [38.5/10,000]) were not sig-
nificantly different (P = 0.47).
The VAAE rates decreased significantly as body
weight increased (P for trend < 0.001; Figure 1). For
all vaccines or for rabies vaccine alone, the VAAE rate
for 10.1- to 45.0-kg (22.2- to 99.0-lb) dogs was
approximately half the rate for dogs that weighed 0 to
10.0 kg (0 to 22.0 lb; P < 0.001; Figure 2). For rabies
vaccine administered alone, VAAE rates/10,000 dogs
that weighed 0 to 10.0 kg, 10.1 to 45.0 kg, and > 45 kg
were 32.1 (222/69,178), 15.3 (69/45,088), and 0.0
(0/1,966), respectively. In 586,817 dogs 9 months
old, the VAAE rate was 38.6/10,000 dogs vaccinated
(95% CI, 37.1 to 40.3), and the VAAE rate significant-
ly increased with age until 1.5 to 2.5 years of age
(VAAE rate, 53.8; 95% CI, 49.5 to 58.4; Figure 3). The
VAAE rates decreased progressively thereafter in older
age categories. Among breeds with 5,000 or more dogs
vaccinated, Dachshund, Pug, Boston Terrier, Miniature
Pinscher, and Chihuahua breeds had the highest rates
of VAAEs with 121.7, 93.0, 83.8, 76.4, and 76.1
adverse events/10,000 dogs vaccinated, respectively
(Table 1). The VAAE rate for mixed-breed dogs was in
the bottom quintile of all rates.
The risk of a VAAE significantly increased as the
number of vaccines administered per office visit
increased (P for trend < 0.001). Unadjusted
VAAE rates increased from 25.2 for a single
vaccine to 56.3/10,000 dogs when 6 vac-
cines were simultaneously administered
(705/279,330 and 397/70,554, respective-
ly). A strong linear dose-response relation-
ship (r
= 0.985) was detected between
adjusted VAAE rates and the number of
vaccines administered. In all dogs, each
additional vaccine administered per office
visit increased the rate of a VAAE by 24.2%;
the rate increase was significantly (P <
0.001) greater in dogs that weighed 0 to
10.0 kg, compared with dogs that weighed
10.1 to 45.0 kg (27.3% vs 11.5%, respec-
tively; Figure 4). The 3 dogs with recorded
deaths each had received 4 vaccines at
their last office visit.
The VAAE rates associated with admin-
istration of a single dose of different vaccines
differed significantly (P < 0.001). The lowest
rate was observed with parenteral adminis-
tration of Bordetella vaccine (15.4/10,000; 82
VAAEs/53,238 doses), and the highest rate was observed
with Borrelia (Lyme disease) vaccine (43.7/10,000; 132
VAAEs/30,201 doses). The VAAE rates for Giardia vac-
cine (23.4/10,000; 97 VAAEs/41,447 doses), rabies vac-
cine (24.7/10,000; 293 VAAEs/118,765 doses), coron-
avirus vaccine (26.2/10,000; 15 VAAEs/5,735 doses), and
tospirosis vaccine (28.8/10,000; 86 VAAEs/29,852 doses)
were not significantly different (P = 0.526). There were
< 100 doses of parvovirus vaccine administered alone,
and no adverse events were recorded. There were 8
paired combinations of vaccines administered to at least
5,000 dogs. The VAAE rates for those combinations
ranged from 15.5/10,000 for Bordetella and Giardia vac-
cines (13 VAAEs/8,405 dogs) to 54.1/10,000 for concur-
rent administration of Borrelia and rabies vaccine (33
VAAEs/6,097 dogs). Concurrent administration of a
rabies and multivalent distemper vaccine to 25,171 dogs
resulted in 99 VAAEs or a VAAE rate of 39.3/10,000 dogs.
Multivariate analysis—A multivariate logistic
regression model including sex, neuter status, age,
weight, and number of vaccines received satisfied
requirements for goodness of fit (P = 0.72). In the final
model, the OR of a VAAE increased significantly (P <
0.001) as weight decreased and as the number of vac-
cines increased (Table 2). Risk for dogs that weighed 5
kg was more than 4 times the risk for dogs that weighed
> 45 kg (OR, 4.46; 95% CI, 2.67 to 7.46; P < 0.001).
Compared with the risk of a VAAE associated with a sin-
gle vaccination, simultaneous administration of 3 vac-
cines increased the risk approximately 50% (OR, 1.51;
95% CI, 1.37 to 1.67; P < 0.001), and with 5 simultane-
ous vaccinations, risk doubled (OR, 2.06; 95% CI, 1.82
to 2.33; P < 0.001). Risk of a VAAE was significantly
increased for neutered dogs, compared with sexually
intact dogs. The VAAE risk was greatest for dogs approx-
imately 1 to 3 years old and least for dogs 6 years of age.
Description of VAAEs—In a random sample of
400 dogs with a VAAE diagnosed within 3 days of vac-
Figure 4—Mean ± SEM VAAE rates by number of vaccines administered per
office visit at 360 veterinary hospitals in dogs of various BWs from January 1,
2002 to December 31, 2003.
Figure 1 for remainder of key.
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1106 Scientific Reports: Original Study JAVMA, Vol 227, No. 7, October 1, 2005
cine administration, the predominant clinical signs
were facial or periorbital edema (30.8% [123/400]),
wheals or urticaria (20.8% [83/400]), generalized pru-
ritus (15.3% [61/400]), and vomiting (10.3%
[41/400]). Localized vaccination-site reactions (eg,
swelling, inflammation, or soreness) represented 8.0%
(32/400) of VAAEs, and systemic nonspecific signs (eg,
fever, lethargy, or anorexia) represented 5.5% (22/400)
of VAAEs. Collapse was the only clinical sign recorded
in 4 (1.0%) dogs. Most dogs in this sample were treat-
ed with an antihistamine and glucocorticoid (34.5%
[138/400]), an antihistamine alone (22.5% [90/400]),
or glucocorticoid alone (11.5% [46/400]). Less com-
monly used treatments included fluids, oxygen, diuret-
ics, or nonsteroidal anti-inflammatory drugs; epineph-
rine was administered to 3.2% (13/400) of dogs. For 69
of 400 (17.0%) dogs, no treatment was prescribed.
By use of this large population of dogs that
received primary care, it was possible to accurately
estimate the incidence rate of practitioner-diagnosed
VAAEs that occurred within 3 days of vaccine adminis-
tration. Although most VAAEs were recorded the same
day as vaccination, the 3-day period was selected as a
reasonable time for owners to report events or return
their dog to a veterinarian for examination. This peri-
od increased the likelihood that the observed event was
the result of a vaccination but excluded sequelae with
a longer latency period. The use of a primary care prac-
tice database permitted inclusion of VAAEs that may
not have been reported to industry or a federal agency
via a separate passive system. Rates for VAAEs were
determined by use of the actual number of vaccine
doses administered; therefore, a practice database pro-
vided more comprehensive event (numerator) data
while also providing population (denominator) data.
Traditional passive surveillance systems that receive
and summarize adverse event reports alone are not
useful for determination of incidence rates or potential
risk factors and are often characterized by under-
reporting of events.
National vaccine sales data have been used as the
denominator in some calculations of VAAE rates, but
such calculations result in estimates per dose of vaccine
sold rather than per dog, cannot determine the effect of
concurrently administered multiple vaccines, and are
also influenced by underreporting of adverse events.
Such estimates have reported
VAAE rates ranging
from 0.13 to 0.40/10,000 vaccine doses, whereas preli-
censure clinical studies reported postvaccination reac-
tions in excess of 1% or > 100 reactions/10,000 vaccine
In the present study, a VAAE rate of 0.38%
(approx 38 adverse events/10,000 vaccinated dogs or
13/10,000 doses administered) was found.
The risk of a VAAE in this study population was
inversely related to a dog’s weight. This weight-
response relationship was previously suggested by
results of a study
in which dogs of toy breeds had sig-
nificantly more suspected VAAEs than other dogs,
although body weight was not evaluated. The manufac-
turers’ recommended dose for all vaccines administered
in our study was 1 mL regardless of body weight, and
all vaccines were from single-dose vials. Vaccines, in
contrast to virtually all veterinary pharmaceuticals, are
prescribed on a 1-dose-fits-all basis, rather than by body
weight. Prelicensing clinical trials investigate the safety
of vaccines with doses in excess of label directions but
only in a limited number of dogs. The results of this
study suggest that trials in dogs that weigh > 10 kg
underestimate the expected VAAE rate in smaller dogs.
Prelicensing clinical trials also investigate the safe-
ty of vaccines in several hundred dogs at multiple hos-
pital locations, but specific breeds may be under- or
overrepresented. Mature weights of dogs of different
breeds may vary by 5 to 10 times and occasionally by
> 50 times. Therefore, a 1-mL vaccine dose results in a
ratio of vaccine volume received per kilogram of body
weight that can vary widely. When multiple vaccines
are simultaneously administered to a dog, the ratio of
volume received per kilogram of body weight per
patient also varies. The importance of this volume-to-
weight ratio in relation to adverse event risk was evi-
dent in this study by the increase in VAAE rates as the
number of simultaneously administered vaccine doses
increased, even when adjusted for weight.
Factors known to cause vaccine reactions include
the primary vaccine agent or antigen, adjuvants,
preservatives, stabilizers, and residues from tissue cul-
tures used in vaccine production.
The overall for-
Risk factor Odds ratio 95% CL
Sex and neuter
Male, sexually 1.00 NA NA
Female, sexually 1.06 (0.95, 1.18) 0.287
Male, neutered 1.27 (1.16, 1.38) 0.001
Female, spayed 1.38 (1.27, 1.51) 0.001
No. of vaccines per
1 1.00 NA NA
2 1.36 (1.23, 1.51) 0.001
3 1.51 (1.37, 1.67) 0.001
4 1.91 (1.73, 2.11) 0.001
5 2.06 (1.82, 2.33) 0.001
6 2.31 (2.03, 2.62) 0.001
0 to 5 kg 4.46 (2.67, 7.46) 0.001
5 to 10 kg 4.21 (2.51, 7.05) 0.001
10 to 15 kg 3.00 (1.77, 5.06) 0.001
15 to 20 kg 2.52 (1.48, 4.29) 0.001
20 to 25 kg 1.93 (1.13, 3.32) 0.017
25 to 30 kg 1.93 (1.12, 3.33) 0.018
30 to 35 kg 1.91 (1.10, 3.32) 0.022
35 to 40 kg 1.68 (0.94, 3.00) 0.081
40 to 45 kg 1.54 (0.81, 2.92) 0.183
45 kg 1.00 NA NA
2 to 9 mo 1.00 NA NA
1 y 1.51 (1.37, 1.67) 0.001
2 y 1.64 (1.49, 1.81) 0.001
3 y 1.35 (1.20, 1.52) 0.001
4 to 5 y 1.06 (0.95, 1.19) 0.282
6 to 8 y 0.79 (0.70, 0.90) 0.001
8 y 0.50 (0.43, 0.59) 0.001
NA = Not applicable.
To convert kilograms to pounds, multiply by 2.2.
Table 2—Adjusted odds ratios and 95% CLs (multivariate logistic
regression) for potential risk factors for VAAEs in 1,226,159 dogs.
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JAVMA, Vol 227, No. 7, October 1, 2005 Scientific Reports: Original Study 1107
mulation of various vaccine components (eg, antigen,
adjuvants, and diluent) is proprietary information that
was unavailable for analysis in our study; thus, the
variation in VAAE rates among single-antigen vaccines
may not be solely attributable to the primary vaccine
antigen. The nearly linear dose-response relationship
between number of vaccines simultaneously adminis-
tered and the VAAE rate suggests that vaccine compo-
nents other than the primary antigen may contribute to
adverse events. In a recent study
of 8 dogs that devel-
oped immediate-type allergic reactions and had high
concentrations of specific serum IgE against the vac-
cines, 7 had specific IgE against fetal calf serum.
The increased risk of VAAEs in smaller breeds in
this study was consistent with the weight-related find-
ings; however, a genetic predisposition of some breeds to
VAAEs is also possible. Although Dachshunds have been
considered at increased risk for VAAEs,
some studies
have not found a difference in hypersensitivity reactions
for this breed, compared with all other breeds. Genetic
susceptibility to allergy occurs in humans,
and both
family and breed genetics may play a similar role in dogs
with respect to VAAEs. Likewise, because of genetic het-
erogeneity, the relatively low VAAE rate observed in
mixed-breed dogs suggests that laboratory safety trials
that use such dogs may underestimate the VAAE rates
that would occur in purebred dogs. This is important
because purebred dogs comprise at least two thirds of
the US dog population.
The risk of allergic reaction has been reported
increase after the third or fourth injection of a vaccine
(ie, a booster response). In our study, VAAE risk
increased for dogs up to 2 years of age and then
declined thereafter. In a controlled study,
IgE concen-
trations were found to be greatest after vaccination at 2
and 3 years of age, corresponding to a dog’s third and
fourth doses of vaccine, but were not as increased after
vaccination at 4 years of age. Because of variations in
canine vaccination protocols, the third injection of vac-
cine may constitute the last puppy vaccination or a
booster at 1 year of age. The decline in the VAAE rate
observed after 2 years of age in this study may have
been attributable to allergen desensitization, initiation
of alternative vaccination protocols in predisposed
dogs, or owner refusal to revaccinate dogs that previ-
ously had a VAAE.
Neutering appeared to increase risk of a VAAE
more than sex. Females mount stronger immune
responses after vaccination or infection than males
because of a dimorphic enhancing effect of estrogens
and a protective effect of androgens.
reduces serum estrogen and testosterone concentra-
tions and also removes their negative feedback on the
pituitary gland, resulting in significant increases in fol-
licle-stimulating hormone and luteinizing hormone
concentrations in female and male dogs.
These pitu-
itary hormones may independently, or through interac-
tion with primary sex hormones, influence the
immune response to vaccination.
In this study, rates for adverse events associated
with the administration of single vaccines were not sig-
nificantly different for multivalent distemper (with 4
Leptospira serovars), Giardia, rabies, and coronavirus
vaccines. Vaccines containing inactivated Leptospira
bacterins have been considered to be more allergenic
than tissue culture lines of virus vaccines, but newer
subunit vaccines have been developed to reduce this
The multivalent vaccine used by the veteri-
nary hospitals in our study was a purified Leptospira
product that contained the immunogenic envelope,
and increased allergenicity of vaccines containing
Leptospira was not clearly detected in this large popu-
lation of dogs. The risk of hypersensitivity reactions
after administration of Borrelia vaccine has been con-
sidered moderate.
These reactions can be attributable
to an immunologic response to proinflammatory sur-
face antigens,
which is a possible cause for the
increased VAAE rates associated with administration of
the vaccine in this study. Event rates for specific vac-
cines in this study may or may not be representative of
other vaccines, but data pertaining to other products
are lacking for comparison.
Clinical signs of VAAEs and the predominance of
same-day events in this study were generally indica-
tive of immediate-type hypersensitivity reactions.
Signs associated with immediate hypersensitivity vary
by species and are related to the location of mast cells
that degranulate in the presence of an allergen.
Cutaneous or dermatologic events were most com-
monly reported by veterinarians within 3 days of vac-
cine administration, consistent with most reports of
suspected canine VAAEs submitted to the US
Adverse events documented in the
patient medical notes reviewed in this study were not
generally described as life-threatening, even when the
diagnosis code was anaphylaxis.
The size of large practice databases can make full
validation of diagnoses or a complete record review of
all patient information exorbitantly time-consuming.
Validation of a subset of records within large databases
has been recommended
to overcome this problem,
and medical notes were reviewed for a subset of the
population in our study. In an assessment of the impact
of validating only 1% to 2% of a study population
against paper-based medical records, errors of misclas-
sified diagnoses only modestly bias outcome rate ratios
toward the null hypothesis.
The use of practice data-
bases also presents new but surmountable challenges
in processing and analyzing extremely large data sets,
sometimes exceeding 500 MB in storage size.
Adverse events in this study, as in all postmarketing
surveillance systems, were based on diagnoses made by
different practitioners. Although diagnoses consistent
with vaccine reactions were selected by practitioners
from the available codes in the software, computerized
databases are dependent on coded outcomes and some
codes may be nonspecific.
Standardized case defini-
tions for VAAEs are not available in veterinary medicine
and are only currently being addressed in human med-
Bias may therefore be introduced into a study if
adverse events are not captured by the existing data-
base, either because they do not result in an office con-
sultation or because appropriate coding is not chosen.
Biases that potentially affect studies with large data-
bases are not unlike those of nonautomated data
sources that require case definitions, manual abstrac-
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1108 Scientific Reports: Original Study JAVMA, Vol 227, No. 7, October 1, 2005
tion, coding, and computerization. In a large practice,
reporting biases or misdiagnoses that may potentially
be introduced by a few individuals are reduced because
of the large number of hospitals contributing data. The
random effects variation related to individual veterinar-
ians was not evaluated in the multivariate model, but
incorporation of dog random effects into analysis
resulted in minimal change in ORs because of the large
number of dogs (data not shown).
The population size in large databases produces
statistical power such that calculated P values are often
small and within traditional significance levels. Study
results must therefore not be interpreted solely on sig-
nificance but rather on clinical importance. Although
VAAE rates in this study were higher than estimated
rates reported from passive surveillance systems, these
events are relatively infrequent or uncommon in a hos-
pital population. Dog characteristics that increase
VAAE risk should be highlighted in risk communica-
tion with clients, but risk aversion of adverse events
must be tempered with the risk of sickness and death
from infectious diseases.
Research will be required to characterize the pri-
mary allergenic components of different licensed vet-
erinary vaccines, and then it will need to be deter-
mined whether vaccine allergenicity and volume can
be reduced while immunologic protection is main-
tained, particularly for smaller dogs. Until such time,
practitioners may choose to reduce the number of vac-
cines simultaneously administered to small dogs (but
not reduce the volume of an individual vaccine) and
alert owners to risk factors for VAAEs.
Although VAAE rates were higher for certain risk
factors or some vaccines, compared with other factors
or vaccines, the rates for VAAEs were low in the overall
population. Evidence of VAAEs does not indicate that
vaccines are not safe but rather that there is a small risk
of adverse events associated with certain dog factors or
vaccines. Premarketing safety studies, when fiscally or
logistically limited in size, will remain limited in power
to detect rare adverse events that may be more common
among animals with particular risk factors.
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... A retrospective observational study of over 1 million dogs demonstrated that the incidence of acute adverse events in dogs within 3 days was highest for those receiving a B. burgdorferi bacterin vaccine (i.e., LymeVax R ; 43.7/10,000 doses) compared with all other vaccines examined (22). Studies evaluating the field safety of canine B. burgdorferi vaccines documenting minimal adverse events have limited generalizability, as only acute adverse events up to 10 days post-vaccination were evaluated (19,22,23). ...
... A retrospective observational study of over 1 million dogs demonstrated that the incidence of acute adverse events in dogs within 3 days was highest for those receiving a B. burgdorferi bacterin vaccine (i.e., LymeVax R ; 43.7/10,000 doses) compared with all other vaccines examined (22). Studies evaluating the field safety of canine B. burgdorferi vaccines documenting minimal adverse events have limited generalizability, as only acute adverse events up to 10 days post-vaccination were evaluated (19,22,23). ...
... Consequentially, this perception may have led to increased owner/veterinarian awareness of this disease in these particular breed groups and consequently an increased recommendation and uptake of prevention strategies such as vaccination and diagnostic testing in these breed groups. Additionally, the reduced odds of leptospirosis vaccine administration in the Toy breed group (in the KC breed group model, S1) and certain brachycephalic breeds might reflect concerns over increased risk of adverse vaccine reactions reported in Toy breeds and some brachycephalic breeds [32][33][34]. ...
Full-text available
Background Leptospirosis is a zoonotic disease that is found globally and affects most mammalian species. Vaccination of dogs against leptospirosis is an important approach to preventing clinical disease, or reducing disease severity, as well as reducing transmission of the infection to humans. Although it is generally considered to be a ‘core’ vaccine, there is limited information on the level of leptospirosis vaccine usage and factors associated with its usage in dogs in the UK. The study aimed to report the uptake of leptospirosis vaccination and factors associated with its usage in a cohort of dogs under primary veterinary care during a 12-month period. Results From a population of 905,543 dogs, 49% (95%CI 48.9–49.1%) had at least one leptospirosis vaccine administered during the 12 months of study. Adult dogs had reduced odds of receiving a leptospirosis vaccine when compared to dogs < 1 year old, with dogs > 8 years old having a greater than ten-fold reduction in odds (OR = 0.08, 95%CI 0.07–0.09). Odds of receiving a leptospirosis vaccine was increased in insured dogs when compared to uninsured dogs (OR = 1.22, 95%CI = 1.17–1.28). Neutered dogs had reduced odds of receiving a leptospirosis vaccine (OR = 0.87, 95%CI 0.83–0.91). Breed associations with receiving a leptospirosis vaccine varied. Several breeds were associated with increased odds of receiving a leptospirosis vaccine when compared to crossbreed dogs, including Border Terriers (OR = 1.49, 95%CI 1.42–1.57), Golden Retrievers (OR = 1.30, 95%CI = 1.24–1.37), Cocker Spaniels (OR = 1.27, 95%CI 1.23–1.31) and West Highland White Terriers (OR = 1.27, 95%CI 1.22–1.31). French Bulldogs (OR = 0.64, 95%CI = 0.62–0.67), Staffordshire Bull Terriers (OR = 0.79, 95%CI 0.78–0.82) and Pugs (OR = 0.91, 95%CI =0.88–0.95) had significantly reduced odds of receiving a leptospirosis vaccination during the study. Conclusion This work identified that almost half of the UK primary care attending population received a leptospirosis vaccine during the year. Several demographic variables were associated with leptospirosis vaccine administration, with age being particularly important. Both the proportion of uptake and factors associated with leptospirosis vaccine usage can be used as a benchmark for comparisons in the future. Additionally, an understanding of which populations have reduced odds of receiving a leptospirosis vaccine can potentially be used for initiatives to encourage owner vaccination uptake in these groups.
... One of the reasons for this result is that the Leisguard ® dose administration is linked to body weight so large dogs need a high daily dose and therefore a higher expenditure than when being used for small dogs [16]. Another explanation is the fact that small size dogs are more prone to adverse effects after vaccination [30,31]. ...
Full-text available
Background: There are several screening tools for detecting Leishmania infantum infection in dogs and various preventive measures to protect against it. Some studies have investigated them, but not many have described their current use. The aim of this study was to investigate which preventive measures and serological screening tools for L. infantum infection were employed from 2012 to 2018 in dogs from different endemic European countries. Methods: A set of electronic datasheets was completed for each dog from several veterinary centres. Classification of preventive measures included: (1) repellents, (2) vaccines and (3) immunomodulators. Classification of serological tests included the: (1) direct agglutination test (DAT), (2) enzyme-linked immunosorbent assay (ELISA), (3) indirect immunofluorescence (IFI), (4) rapid tests and (5) other assays. Dogs were also classified depending on their risk of exposure and living area. Results: Information from 3762 dogs was gathered. Preventive measures were applied in 91.5% of dogs and the most frequently used were repellents (86.2%) followed by vaccines (39.8%) and Leisguard® (15.3%). The different types of repellents (collar and spot-on) were used similarly. A combination of a vaccine and repellents was preferred in the high-risk group while the low-risk preferred a combination of Leisguard® and a repellent (Chi-square test: X2 = 88.41, df = 10, P < 0.001). Furthermore, all preventive measures were similarly used through the years except for repellents, which were predicted to have a small increase of use each year. Regarding serological screening tools, the most used were rapid and ELISA tests. Rapid tests, ELISA tests and DAT were used similarly through the years, but a significant change was found in the use of IFI and other assays whose use decreased a little each year. Conclusions: Repellents were the preferred measure, while vaccines and Leisguard® were second-line options. Some dogs were not treated by any measures, which highlights the need for dog owner education. Moreover, there seems to be a preference for rapid tests in the clinical setting to detect specific L. infantum antibodies while ELISA or IFI are less often employed. This underlines an increasing problem, as qualitative rapid tests have a variable diagnostic performance limiting the adequate diagnosis of seropositive dogs in endemic areas.
... In all those cases, the dilution difference was 1.5 or less. Thus, in those animals, the clinicians may suggest to repeat the test or to perform VN, especially in those breeds in which vaccine-associated adverse events (VAAEs) are reported with a higher frequency (i.e., small or toy breeds) [21]. This may have interfered with the calculation of sensitivity, specificity, and accuracy as well, especially in those few cases in which a one-dilution difference would discriminate a protective from an unprotective immunity. ...
Full-text available
Core vaccinations and specific antibody titer evaluations are strongly recommended worldwide by all the vaccination guidelines. Virus neutralization (VN) is considered the gold standard for measuring antibody titer against canine distemper virus, but it is complex and time consuming, and the use of in-clinics tests would allow to obtain quicker results. The aim of this study was to evaluate the agreement of the commercial in-clinics VacciCheck test compared to VN. A total of 106 canine sera were analyzed using both methods. The best agreement was obtained using a protective threshold of ≥1:32. VacciCheck showed 95.5% sensitivity, 87.2% specificity, and 92.5% accuracy. The Cohen’s kappa coefficient between methods was 0.84 (CI 95% 0.73 to 0.95), revealing an optimal agreement between the two methods (p = 0.0073). The evaluation of discordant results reveal that most samples had less than 1.5 dilution difference, and that usually did not affect the classification as protected or non-protected. Results also suggest that, in dubious cases, especially when a protective result is expected, retesting is advisable. In conclusion, VacciCheck may be considered as a reliable instrument that may help the clinician in identifying the best vaccine protocol, avoiding unnecessary vaccination, and thus reducing the incidence of adverse effects.
... Rather than being required for pet health as are core vaccines, non-core vaccine recommendations may be presented as optional, leaving pet owners to make decisions without fully understanding the risks and benefits. Although vaccineassociated adverse events are known to be uncommon [22], it is also possible that veterinarians and pet owners experience hesitancy surrounding the use of non-core vaccines that are perceived as optional. The addition of a non-core vaccine to a patient's preventive care plan is also often associated with an additional cost to the pet owner, which can serve as an additional barrier to adherence to clinic recommendations. ...
Vaccination guidelines for dogs and cats indicate that core vaccines (for dogs, rabies, distemper, adenovirus, parvovirus; for cats, feline parvovirus, herpes virus-1, calicivirus) are essential to maintain health, and that non-core vaccines be administered according to a clinician’s assessment of a pet’s risk of exposure and susceptibility to infection. A reliance on individual risk assessment introduces the potential for between-practice inconsistencies in non-core vaccine recommendations. A study was initiated to determine non-core vaccination rates of dogs (Leptospira, Borrelia burgdorferi, Bordetella bronchiseptica, canine influenza virus) and cats (feline leukemia virus) in patients current for core vaccines in veterinary practices across the United States. Transactional data for 5,531,866 dogs (1,670 practices) and 1,914,373 cats (1,661 practices) were retrieved from practice management systems for the period November 1, 2016 through January 1, 2020, deidentified and normalized. Non-core vaccination status was evaluated in 2,798,875 dogs and 788,772 cats that were core-vaccine current. Nationally, median clinic vaccination rates for dogs were highest for leptospirosis (70.5%) and B. bronchiseptica (68.7%), and much lower for canine influenza (4.8%). In Lyme-endemic states, the median clinic borreliosis vaccination rate was 51.8%. Feline leukemia median clinic vaccination rates were low for adult cats (34.6%) and for kittens and 1-year old cats (36.8%). Individual clinic vaccination rates ranged from 0 to 100% for leptospirosis, B. bronchiseptica and feline leukemia, 0–96% for canine influenza, and 0–94% for borreliosis. Wide variation in non-core vaccination rates between clinics in similar geographies indicates that factors other than disease risk are driving the use of non-core vaccines in pet dogs and cats, highlighting a need for veterinary practices to address gaps in patient protection. Failure to implement effective non-core vaccination strategies leaves susceptible dogs and cats unprotected against vaccine-preventable diseases.
A 5-year-old female Springer Spaniel dog was submitted for necropsy after sudden death following vaccination against Leptospira spp. Gross examination revealed a diffuse dark red discolouration of skeletal musculature, severe diffuse congestion of all the abdominal organs and a contracted spleen. Severe dilation and reduction in wall width was seen in the right ventricle and histological examination revealed multifocal replacement of the right ventricular myocardium by a large amount of fibrofatty tissue. Pathological changes were consistent with post-vaccinal anaphylactic shock in a dog with arrhythmogenic right ventricular cardiomyopathy (ARVC), a rare condition typical of Boxer dogs but not previously reported in Springer Spaniels. Canine vaccine-associated adverse events are discussed and ARVC is compared with the corresponding human cardiac condition.
Objective To describe the clinical features of dogs treated for suspected anaphylaxis in Perth, Western Australia. Design Single-centre observational case series with retrospective and prospective phases. Methods This was a two-phase study of dogs with clinical suspicion of anaphylaxis presenting to the emergency service of a university teaching hospital. Dogs required evidence of, and appropriate treatment of, a type 1 hypersensitivity reaction as well as two or more organs affected (or cardiovascular signs alone) to be included. Phase 1 includes retrospective case series of 186 dogs (March 2006–December 2018). Phase 2 includes prospective descriptive case series of 46 dogs (October 2017–July 2018) focused on clinical signs. Results In phase 1, 88 (47%) dogs had evidence of insect exposure prior to the acute event. One hundred forty (75%) dogs had dermatological signs, 141 (76%) had gastrointestinal signs and 129 (69%) had cardiovascular signs. Ninety-two (49%) dogs had vasoconstrictive shock (5 with bradycardia), 24 (13%) had vasodilatory shock, 8 (4%) had mixed vasodilatory and vasoconstrictive shock and 5 (3%) had unclassifiable shock. On focused abdominal ultrasound, 42 of 71 (59%) dogs had gallbladder wall oedema and 3 of 71 (4%) dogs had peritoneal free fluid. In phase 2, the distributions of insect exposure, organ dysfunction and sonographic abnormalities were similar to phase 1. Conclusion Dogs presenting with suspected anaphylaxis showed a broad range of presentations. Dermatological signs were absent in a proportion of dogs, vasoconstrictive shock was more frequent than vasodilatory and unique features of shock were identified. This study highlights the challenges of diagnosis based on presenting features alone.
Zusammenfassung Wenngleich Impfstoffe, v. a. die gegen das kanine Parvovirus (CPV), heutzutage als sehr sicher gelten, können in seltenen Fällen dennoch postvakzinale Nebenwirkungen auftreten. Hierzu zählen zum einen milde Symptome, die sich kurz (innerhalb weniger Tage) nach der Impfung entwickeln (z. B. gastrointestinale Symptome, Fieber, reduziertes Allgemeinbefinden, Lymphadenopathie). Sie werden als Folgen der Replikation des Impfvirus gewertet und sind ein Anzeichen für eine gute Immunantwort. Die ebenfalls kurz nach der Impfung vorkommenden anaphylaktischen Reaktionen können lebensbedrohlich sein. Betroffene Hunde zeigen Symptome wie Ödeme, Speicheln, Erbrechen, Durchfall, Hypotension und/oder Schock. Oft ist unklar, welcher Bestandteil des Impfstoffs die anaphylaktische Reaktion ausgelöst hat. Es ist daher wichtig, Hunde mit vorangegangenen anaphylaktischen Reaktionen nur noch mit unbedingt notwendigen Komponenten zu impfen. Sind Wiederholungsimpfungen notwendig, z. B. weil sich keine Antikörper gegen CPV nachweisen lassen, sollte besser eine Monovakzine gegen CPV (und ggf. gegen weitere notwendige Komponenten) verwendet werden. Ein Wechsel des Impfstoffherstellers beugt möglicherweise ebenfalls einer erneuten anaphylaktischen Reaktion vor. Die längere Zeit nach Impfung auftretenden Autoimmunkrankheiten, z. B. die immunmediierte hämolytische Anämie (IMHA), könnten die Folge einer zu häufigen Vakzination von Hunden sein oder durch Impfung getriggert werden. So wurden einige Hunde mit IMHA einige Wochen vor Ausbruch der Erkrankung geimpft. Bei diesen Hunden sollten weitere Impfungen unbedingt vermieden werden.
Full-text available
The Vaccine Safety Datalink is a collaborative project involving the National Immunization Program of the Centers for Disease Control and Prevention and several large health maintenance organizations in the USA. The project began in 1990 with the primary purpose of rigorously evaluating concerns about the safety of vaccines. Computerized data on vaccination, medical outcome (e.g. outpatient visits, emergency room visits, hospitalizations, and deaths) and covariates (e.g. birth certificates, census data) are prospectively collected and linked under joint protocol at multiple health maintenance organizations for analysis. Approximately 6 million persons (2% of the population of the USA) are now members of health maintenance organizations participating in the Vaccine Safety Datalink, which has proved to be a valuable resource providing important information on a number of vaccine safety issues. The databases and infrastructure created for the Vaccine Safety Datalink have also provided opportunities to address vaccination coverage, cost-effectiveness and other matters connected with immunization as well as matters outside this field.
Full-text available
Mild local and systemic reactions to vaccines are to be expected as a natural consequence of vigorously stimulating the immune system. Dramatic adverse reactions to vaccines are occasionally due to mistakes during the production or handling of vaccines. More often, they are due to not following label instructions, particularly the restriction to only use vaccines in healthy animals. It is important to publish well-documented instances of adverse vaccine reactions so that producers and users of vaccines can all learn from the experience and avoid similar problems. Vaccine failure to protect from disease is usually due to problems with either client education or compliance with good animal management practices. It is important for clients to understand the proper timing and method of vaccine administration, what to realistically expect for vaccine efficacy, and the importance of minimizing immunosuppressive factors and exposure to high doses of infectious agents in vaccinated animals. Veterinary vaccines have produced dramatic benefits in terms of animal health, human health, and efficiency of food production. Advances in research and the accumulating experience with vaccines are leading to safer and more effective vaccines. Proper usage of vaccines and adherence to good management practices will continue to be essential to achieve maximal vaccine safety and efficacy.
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The availability of large, population-based, automated, medical care databases provides unique opportunities for monitoring the safety of childhood vaccines. The authors assessed the quality of automated vaccination databases by comparing them with vaccinations documented in paper-based medical records at three large US West Coast health maintenance organizations (HMOs) participating in the Vaccine Safety DataLink (VSD) study, a Centers for Disease Control and Prevention collaborative study of childhood vaccine safety. The authors randomly selected 1% or 2% samples of VSD study populations (n = 1,224-2,577) for data quality analyses. Agreement between automated and abstracted vaccinations required identical triads of child identification number, vaccination date, and vaccine type. Separate analyses were conducted for each HMO and for each vaccine type administered between 1991 and 1995. Agreement was measured by three matching proportions: 1) the proportion of automated vaccinations present in the abstracted source, 2) the proportion of abstracted vaccinations present in the automated source, and 3) the proportion of vaccinations from either source present in both sources. Overall, for common childhood vaccines, proportion 1 ranged from 83% to 99%, proportion 2 ranged from 82% to 98%, and proportion 3 ranged from 70% to 97%. Lack of automated data was the most frequent type of discrepancy, followed by date mismatches and vaccine type mismatches. Vaccination exposure classification errors in the range reported here were found by mathematical modeling to only modestly bias measured medical outcome rate ratios toward the null hypothesis. The results of the data quality analyses support the usefulness of vaccination exposure data derived from these automated HMO vaccination databases.
Concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured in serum samples obtained from 100 dogs. Groups (n = 25/group) consisted of sexually intact and ovariohysterectomized bitches and sexually intact and castrated male dogs. Mean (+/- SD) concentrations of LH in the serum of sexually intact and ovariohysterectomized bitches were 1.2 (+/- 0.9) and 28.7 (+/- 25.8) ng/ml, respectively. Mean concentrations of FSH in the serum of sexually intact and ovariohysterectomized bitches were 98 (+/- 49) and 1,219 (+/- 763) ng/ml, respectively. Mean concentrations of LH in the serum of sexually intact and castrated male dogs were 6.0 (+/- 5.2) and 17.1 (+/- 9.9) ng/ml, respectively. Mean concentrations of FSH in the serum of sexually intact and castrated male dogs were 89 (+/- 28) and 858 (+/- 674) ng/ml, respectively. In addition to history, physical examination results, and other laboratory values, the measurement of serum gonadotropin concentrations may aid in determining whether dogs have been neutered.
Immunizations against most vaccine-preventable diseases will be needed indefinitely unless the disease is eradicated. Public acceptance of immunizations may be threatened as vaccine coverage increases and disease decreases, however, due to the increase in both causally and coincidentally related vaccine adverse events. The post-marketing surveillance for such events in the USA in response to the mandatory reporting requirements of the National Childhood Injury Act of 1986. While VAERS has many methodological limitations intrinsic to such systems, it can play an important role in helping to monitor vaccine safety and maintain public confidence in immunizations.
The current review summarizes case reports attributing autoimmune diseases and phenomena to various vaccines and suggests potential mechanisms. It has to be emphasized that the demonstration of a temporal relationship does not necessarily attribute autoimmunity to a vaccine. The subject is complicated by the fact that one vaccine may cause more than one autoimmune phenomenon, and a particular immune process may be caused by more than one vaccine. Furthermore, vaccines differ in their pathogenic influence on the immune system. There is no doubt that the new recombinant hepatitis B virus vaccine is different from mumps, measles and rubella vaccines in its ability to trigger autoimmunity, probably by completely different mechanisms. The data summarized here suggest that some vaccines may in rare cases induce autoimmune disorders. The subject of the vaccine-autoimmunity relationship is still obscure; reports have been rare, no laboratory experimentation on this topic has been undertaken, and there are few animal models. For the time being no conclusions can be drawn. Since vaccines are an important prophylactic intervention, the risk-benefit ratio clearly leans towards the advantages of infectious disease prevention. Vaccination routines should not be changed in the healthy population or for patients with known autoimmune disorders. Laborious clinical and laboratory studies should be initiated in order to evaluate the new emerging subject of vaccine-induced autoimmunity.