Dr. Paul McCutcheon Expert Report (plaintiff)

8/10/2019 Dr. Paul McCutcheon Expert Report (plaintiff)

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antibody levels (titer testing). Over 99%

of

our patients

hava

a lifetime

immunity

without revaccination. If necessary, we will boost the

immunity with

the

appropriate single vaccine. TI1is info:rma-tion and

references

are

illustrated in

my

book,

"The

New Holistic W iY for

Dogs

w.1d

Cats."

Hepatitis:

Th


4/35


5/35

Soft, nonpainful

Oral/Dental

Normal dentition, no gingivitis, no masses or

lesions,

no discomfort

on

palpation, can

open and

close

mouth

easily.

Normal

systems:

General Appearance, Integumentary, Respiratory,

Genitourinary,

Eyes,

Ears, Neural System, Lymph Noqes, Mucous Membranes,

Other Abnormality; Pain

The abnormalities listed

all

appeared normal The normal systems is a covering

sta tement , but curiously notes "pain" with no explanation. The eyes, previously reported as

sclerotic, are now reported normal. There is no indication of recommendation for further lab

tests or radiology which, with the symptoms discussed on March 22 d, 2oll, would seem

appropriate. The ongoing digestive problem was "treated" with probiotics, bu t no reference to

other major concerns. With all the previous signs and Guardian's concerns, the normality

expressed

in

this consultation seems questionable.

No

diagnosis was indicated and

no

therapy.

March

29

1

h,

2011

Guardian

is

concerned

about

the ongoing lethargy,

but

recorded as "doing

well"-

a

confusing contradiction. Considering checking thyroid and radiology.

April 4th, 2011

Guardian reports leg weakness, stiffness, and lethargy.

April

5th, 2011

Pica:

abnormal appetite nd the consumption of inappropriate items

is

a common

finding with s tressed individuals. This is deariy an indication of a patient in considerable

distress.

April 6'h, 2011

Sasha's Blend is dispensed. This is an appropriate proprietary l?roduct for joint care, but

hardly therapeutic for Colombo who, at the March 26"', 2011 appointment, shows no signs of

arthritic problems: "no pain, swelling, or decreased r nge o motion.

April7",

2011

l"elephone Communication

Colombo not able to walk or see very we l-concerned about qiabetes.

April 8th, 2011

Telephone Communication . ,d

Colombo's eyesight is going fast. Discussed nuclear scleros1s- noted only on March

3 ,

2011, but not clarified as

to

degree. No indication

of whether

the retina was examined.

Guardian is concerned about diminished y sight; missing steps.

Aprilll'", 2011

Transfer records to Danforth Veterinary Clinic


6/35

April12 ', 2011

Examination indicates panting, loss of vision, h o ~ s e s o i l i n g , appetite o ~ a y

Excessive

nd

inappropriate urination with good appetite, are indications of stress

(hyperadrenal activity). The panting and loss of vision are o v i o ~ s l y very dlst4'bing nd

debilitating signs.

April13' , 2011

Referral to Dr Gray

April29ri', 2011

lethargy, heavy drooling, blind

May

2nd,

2011

Retinal degeneration was reported (permanent blindness). No beneficial tre tment was

offered.

June

11 ', 2011

lethargic, anorexic, labored breathing.

June 13 , 2011

t

Veterinary Emergency Clinic, chest radiology showed indications of pnet1monia

June 14' , 2011

Dr

Alan Norris report and summary:

Dr.

Au,

I

believe

the clinical

signs

for

which Colombo was a d m i t t e ~ to

the

VEC

were

secondary to pneumonia and respiratory distress.

At

the time of presentation

Colombo was weak,

pyrexic, with increased

panting and

coughing. [n the hours following presentation he became

duller

and

his respiratory signs worsened; he

was started

on nasal oxygen therapy. His

oxygen

requirements were

high

5

Urn

in)

and

he

was

treated

with intravenous fluids, broad spectrum

antibiotic coverage (ampicillin, enrotloxacill), nebulization

and

coupage.

J,lis clinical s i ~ ; n s

improved

initially

but

worsened after 2

days in hospiial.

Initially bronchoalveolar lavage had

been

discussed to

help determine

the nature of Colombo's

pulmonary disease, but due to

increased anesthetic

risk (given

the

level of

respiratory

difficulty);

we eleated

not to pursue

this.

There

was

no prelvous history

of

vomiting/possible aspiration and the

u n d f ; ~ r l y i n g

cause of

Colombo's pneumonia remains

unknown.

Colombo displayed

weakness

in

all

limbs

and neurologic

deficits

in th< > pelvic limbs.

At

this time it

is

not clear

whether these changes were secondary to profound systemic disease, or

the result

of

a true

underlying neuropathy. Given

Colombo's severe

respiratory signs

our

neurolo ;ist,

Dr.

Kilburn, recommended that he be re-examined after resolution

oc

further

treatment of the pneumonia, and that an

MRI

ofthe spine be

perfonned

to

help determine the

etiology of Colombo's neurolo ,>ic

signs.

Given the

historical findings

of

polyuria, polydypsia

and

polyphagia,

aud

the

elevated

resting cortisol underlying

hyperadrenocorticism was suspected.

A

o o ~

connect

x s ~ s between

development

of sudden acquired retinal

degeneration

(SARDs) and h y p e r a d r e _ n o c o ~ I o . t s ~ . A_ low

dose

dexamethasone

suppression

test

was

initially recommended

after resolution of cbmcal

s1gns.

Due

to worsening of

clinical signs and financial

concerns, o w n ~ r s elected to h\lmanely

euthanize Colombo overnight

on June 14, 2011. We

are

sorry for

the loss

of

a

beloved

companion.

:ca


7/35

My Summary

On March 3rd, 2011, Colombo was a generally healthy middle aged dog under some stress from

digestive abnormalities.

In

spite of

the

unwellness, he was inoculated with mult\ple vaccines without

consent. The need for

these

vaccines (other than Rabies)

is

in my opinion, negli(iible.

It

was clearly a

mistake

to

give any of those vaccines to an unwell dog.

Colombo continued

to

have some debilitating signs over the next few weeks. The examination

on March 26"', 2011, was poorly documented and definitely did not reflect the seriousness and concerns

of the Guardian. No diagnostics or therapeutics.

Over the next two weeks continuing decline in Colombo's health leading to total irreversible

blindness diagnosed as SARDs. This l

in

reaH:y not a diagnosis, but rather an ~ J x p r e s s i o n of the

unexplained severe degeneration of rs


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Summary

Vaccination Adverse Eve14ts

ROTH, J.A., "Mechanistic Bases for Adverse Vaccine Reactions

and

Vaccine Failures," Advances

in Veterinary

Medicine,

Vol. 41,

pp.

681-700

p.682

"This

article provides

an

overview of some of he reasons why vaccines occasionally produce adverse

reactions

p.684

1

"When

animals deve lop adverse clinical signs within a few days

to

weel\g after vaccination it is important

to determine whether those clinical signs

were

vaccine induced

or were

not due

to

vaccination and only

j

coincidentally occurred after the vaccine

was

administered.

p.686

Modified live vaccine organisms

haw

been attenuated to have reduced virulence ..However, the

attenuated vaccine strains

may

be capable ofproducing disease in immwosuppressed animals. Induction

of disease by vaccine organism has

occasionally

been reported when modified live virus (MLV) vaccines

have been administered

to

healthy animals However.

i t

has

occurred much more frequently when ML

V

vaccines are administered to unhealthvanimals ...

An

example of vaccine-induced disease re,-ulting

from

administration of vaccine to unhealthy animals is

the

induction

of

encephalitis

by MLV canine

distemper virus vaccine

in

dogs infected with canine

parvovirus (Krakowka

et

al., 1982).

Vr/Cv >fl p 687- ADVERSE VACClNE REACTIONS Dl..i E TO VACC Nb-INPUCED IMMUNE

SUPPRESSION

An

ML

V bovine viral diarrhea BVD) virus vaccine

has

been shown

to

suppress nutrophil function and

lymphocyte blastogenensis in cattle (Roth and Kaeberle, 1983). This coFi elates with the observation that

cattle tend to be somewhat more susceptible to bacterial pneumonia after administration ofMLV

BVD

vaccines, especially i he animals

are

stressed at the time of administration. Several connnercially

available canine vaccines have been shown to be capable of inducing lymphopenia and suppressing

blastogenesis of peripheral blood lymphocytes (Phillips et al.,1989; Mll&tro et al., 1986; Kesel and Neil,

1983).

p. 687- ADVERSE VACClNE

REACTIONS

DUE TO

EXCESSIVE :q.IDUCTION OF CYTOKlNE

RELEASE

Interlukin 1 (IL-l), IL-6, and a tomor necrosis factor a (TNF-a)

are

potrnt proinflannnatory cytokines

that are released by macrophages and other cells in response to infectioq, endotoxin and bacterial

components, and some vaccine adjuvants. These proinflannnatory cytokines can induce a wide range of

clinical signs. They may induce acute inflannnation

at

the local site ofproduction, they may also induce


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CARMICHAEL, L.E., Canine Viral Vaccines

at

a Turning

Point

A

~ r s o n a l

Perspective,

Veterinary Medicine, Vol, 41.

Pp.

289-307

p.291

3

It has been estimated that more than 50% of office visits to veterinarians are associated with vaccination.

Several vaccines for dogs (and cats) have been licensed that have poor or qu


12/35

p.297

Efficacious modified-live

CPV

2 vaccines have

been

highly successful

in r ~ v n t i n g

parvovirus

infections

when

administered to seronegative pups, or to dogs with very

low

antibody titers. They

normally

engender

rapid and

enduring immunity,

and

it is probable

that

immunity persists for several

years.

p.304

The reality that all vaccines carry some risks is not fully perceived by

many

owners

and

veterinarians

..

There is a need for better appreciation of

the

risk of adverse ryactions (Duval

and

Giger,

1996).

MOORE, G.E., et

al,

A Space-time Cluster of

Adverse Events s s o c i a t ~ d with Canine Rabies

Vaccine,

Vaccine

23 (2005) 5557-5562

p. 5557

4

Clustering ofadverse events or disease can serve as

an

indicator

of

potenti'll association between adverse

event and

vaccine administration ..

p.5558

... ncreased risk was associated with ..surgically neutered [dogs]. Dogs repeiving multiple vaccines at

one

encounter

were also

at increased risk

ofVAEs

[vaccine-associated eveqts] .

Materials and Methods

The

electronic

medical

records

of

Banfield,

the Pet

Hospital,

were

searched

to

identifY all dogs that

received rabies vaccine alone

in

combination

with

bordatella vaccine, coronavirus vaccine, multivalent

distemper-adrenovirus-parainfluenza-parovirus-leptospirosis vaccine, giardia vaccine, or borrelia vaccine

between January

2002

and

December

2003.

p. 5559

Results

During

the

24-month study period, rabies vaccination (alone or

with

other concurrent vaccinations) was

given to 257,564 dogs; there were 1146 V

AEs

diagnosed (0.445%; 95% CI:0.420-0.471%).

GROGNET,

J.

G.,

Rethinking Traditional

Vaccination Protocol,

A "\iC

Gazette;

Dec. 2011; 127,

12.

p.30

As Dodds points out, the clinical signs associated with vaccine reactions are varied.

They

can begin with

fever, stiffuess, sore joints,

and

abdominal tenderness.

Both

liver

or

kidney damage can be a consequence ofvaccines.


13/35

Neurological disorders, including encephalitis have been reported. A condition called post-vaccinal

polyneuropathy has been associated with the administration of vaccines containing distemper, parovirns,

and rabies, producing incoordination and weakness, as well as seizures.

p.31

Vaccinosis is a diagnosis of exclusion. A dog suffers from symptoms, yet nothing can

be

found on

testing

to

detennine

the

cause ..

Dodds suggests that MLV are so antigenic that they can overwhelm the immune system of

immunocompromised dogs, and even healthy ones.

To current vaccine practices

Measure antibody titers

Don't overvaccinate, and avoid unnecessary vaccines

Don't vaccinate sick dogs or those with fevers.

5

...

Dodds concurs that

you

should avoid vaccinating animals who are already protected.

Despite the evidence Dodds presents, some veterinarians still believe that vaccinations is harmless

and

not linked

to

adverse effects or serious illness. At the extreme opposite end, people adamantly against

vaccinstion fuel hysteria by providing misinformation on negative effects ofvllccines. Dodds suggests

that

neither

of

hese polarized views are helpful.

MIYAJI,

K

Large-scale Survey

o

Adverse Reactions to Canine non-rabies Combined Vaccines in

Japan, Veterinary Immunology and Immunopathology 145(2012) 447-452

p.447

"We

performed a large-scale survey

to

investigate vaccine-associated adverse events VAAEs), including

anaphylaxis,

in

Japan by distributing questionnaires on V AAEs

to

veterinary hospitals from April , 2006

through May 31, 2007. Valid responses were obtained for 57,300 vaccinated at 573

animal

hospitals; we obtained V AAEs information for last 100 vaccinated dogs

in

each veterinary hospital. We

fuund that

of

he 57,300,359 dogs showed V AAEs.

Of he

359 dogs, death was observed in 1,

anaphylaxis

in

41, dermatological signs

in

244, gastrointestinal signs in 160, and other signs in 106.

"No

vaccine . .is completely effective or without adverse reactions, and vaccine-associated adverse events

(V

AAEs) do occur, albeit infrequently, after vaccinations.

p.448

Practicing veterinarians diagnosed adverse reactions and classified them in o 5 groups according to

clinical signs: death, anaphylaxis, dermatological signs .. gastro-intestinal signs (vomiting and diarrhea),

and other signs (including hypodynamia and anorexia).


14/35


15/35


16/35

/

J

Reaction to Adjuvants

Many inactivated vaccines contain adjuvants that potentiate the immune response by creating a depot

effect in the tissues to provide a prolonged antigenic stimulus and by activating macrophages (Roitt

1984)."

Systemic Reactions

"Systemic reactions can include fever, lethargy, anorexia, oedema, urticaria, vomiting, diarrhea, corneal

opacity, dyspnoea, excitement, collapse, convulsions and, on rare occasions death."

MEYER,

E,

K., Vaccine Associated Adverse Events,

Vaccine and

~ c c i n a t i o n s Volume 31,

Number

3,

May

2001, p. 493-514

p. 500

''Unlike human medicine, there is no regulation analogous to the

NCVIA

[National Childhood Vaccine

Injury Act]

that

mandates veterinary reporting

of

vaccine-associated adverse events.

As

regulations

currently exist, vaccine manufa.."tllrers are

not

required t report adverse event reports that they receive

from veterinarians and consumers. F nrthermore, vaccine manufacturers are not currently required to

routinely submit adverse reports to

the

USDA, although USDA personneijilay request adverse event

records for review during manuf-cClllrer site inspections."

p.501

ADVERSE EVR'TS ASSOCL"-TED WTIH VACCINATIONS

8

"Adverse events associated v.ith vac.cination have been well described and are categorized I various ways.

For

the purposes of this discussion, adverse events associated with vaccines are classified as systemic or

local reactions."

p. 502

Systemic Reactions

"Clinical signs such as anorexia, leihargy, fever, and soreness beginning a few hours after vaccination and

persisting fur 24

to

36 hours are reported in association with vaccination. The causes of hese nonspecific

reactions may include vaccine organism replication ofmodified live vaccines, exposure to endotoxins,

adjuvant toxicity, or immune system responsiveness. Most reactions are q rild but

in

some cases the

animals are so severely affected that supportive care may

be

required. Because vaccinations are designed

to

stimulate the immune response, these kinds

of

reactions are

to

be

expected and have been referred

to

as

'normal

toxicity' associated withvaccination.

In

a clinical study involving 2288 routinely vaccinated cats

and kittens, nonspecific systemic signs were reported at a rate

of

1.2%. TJVs study also showed that

reactions were more likely to occur >Vilen multiple vaccines were administji red and that cats older than 1

year

of

age

were

more likely to experience reactions than younger animals."

p.504

"Type l l hypersensitivity involves cel l destruction mediated by antibodies."


17/35

-

I f

a vaccine contains normal cell antigens such as erythrocyte antigens, it may induce antierythrocyte

antibodies, which

can

lead to immune-mediated hemolytic anemia.

Type

i l l

hypersensitivity involves the formation

of

antigen-anttbody il:mpune complexes. This initiates a

number ofbiologic processes, ofwhich the most significant is the component cascade.

p.

505

AUTOIMMUNE DISEASE

There is some concern that vaccination may trigger autoimmune disease. n a controlled retrospective

clinical study, a temporal association was made between vaccine administration in dogs and the clinical

onset of immune-mediated anemia.

IMMUNOSUPPRESSION

One experimental study showed a decrease in lymphocyte numbers anlf response to mitogens in dogs

vaccinated concomitantly with Rockbom strain

of

canine distemper and adrenovirus-1

or

adrenovirus-2.

p.

506

VACCINE

VIRULENCE

Residual vimlence

of

modified-live vaccine can cause adverse events

4

vaccinated animals.

X Reactions occurring 7 to 21 days after vaccination in cats, characterized by fever, anorexia, and lethargy

and occasionally accompanied by joint, spinal, or generalized pain, have been associated with vaccines

containing modified live C. psitacci.

Immunocompromised dogs vaccinated with modified-live canine distemper vaccines have been reported

to develop post-vaccinal encephalititis.

p.510

Postrnarketing surveillance plays a vital role in identifying and monitoring potential risks associated with

vaccine administration

as well

as

1\ith

product efficacy.

The

depth

of

he surveillance system's database,

however, is dependent on active reporting by practicing veterinarians.

p.512

Although vaccination plays a vital role in maintaining animal health, iJlere are risks associated with this

medicinal procedure.

NAVC 2007 Conference, Orlando,

Florida,

Proceeding of

the NJ\

VC

North

American Veterinary

Conference

Jan.

13-27, 2007, Orlando, Flor ida, p. 573-575

p.573

'Predicting the unpredictable vaccine reactions'


18/35


19/35

I

i

f

information that was unavailable for this study; thus, the variation VAAE rllfes among single-antigen

vaccine may not be solely attributable

to

the primary vaccine antigen. The nearly linear response

relationship between number ofvaccines simultaneously administered and the V AAE rate suggests that

vaccine components other than primary antigen may contribute

to

adverse eents.

Neutering appeared to increase risk

ofV

AAE

more than sex.

MACY, D.W., Are We Vaccinating Too Much?

JA

VMA, Vol. 27, No, 4, August

15th,

1995

The

incidence of anaphylaxis and other adverse reactions appear to

be n c r ~ a s i n g .

p.421

One disadvantage to over-vaccinate is the cost,' Dr. Schultz said. 'The client is paying for something

with no effect or i t h the potential of adverse reaction. I believe that d v e r s ~ effects are increasing,

because we are putting more and more components into these animals.

p.422

11

There is a real concern

that

vaccines may predispose susceptible individmds to immune-mediated

disease,' Dr. Schultz said.

'The

more antigens we administer, the higher the potential for hypersensitivity.

Type IV, cellular-mediated. All these types of hypersensitivities are natural parts of the immune response,

but

they cause a

cer.ain

amount of tissue damage. That damage may occur in the kidney, liver, or as was

the case with the adrenovirus Type 1, in the eye.

p.423

...we must evaluate the

ris lc

-benefit ratio ofevery vaccine. In the case canine parovirus, for instance, the

risk

of

death from disease

is e:-.:tremely

high compared with minimal

yet

unproven risk

of

immune

mediated disease from the

a c c i n e ~

The more components we combine into a single dose ofvaccine, the more likely they are to interfere \/

with each other,' Dr. Schultz said. 'Wnen multiple vaccines are given, there is competition at the n t i g e ~

presenting cell level. That

i l l

prevenr the animal from responding normally to each antigen.

p.425

Experts urge balancing

risks

and benefits, and tailoring vaccination schedules to the individual patient.

'We should

not

allow politics, tradition, or greed to enter the decision,' Dr. Macy said. 'Changing

vaccination protocols does not need

to

mean less profit...Veterinarians and tp.e industry need to be honest

with ourselves and assess risk, and

not

be trapped in tradition.

HORZINEK, M.C., ''Vaccine Use and Disease Prevalence in Dogs and ;::ats,

Veterinary

Microbiology, 117 (2006) 2-8

Why

has veterinary medicine adopted a practice that causes raised eyebrows in the biomedical

enviromnent, e.g., when talking to immunologists? The reason is largely i s ~ o r i c : in the first years of


20/35

..

C--- -------

----=------- -' --

vaccine development, the objective of maximum protection

was

thought

to

be achieved

by

maximum

antigenic stimulation."

p.4

The

scientific arguments in favour

ofless

frequent revaccinations are traditionally based

on

antibody

titers. Protection against most viral diseases is indeed antibody-mediated, and antibodies are easily

mediated.

n dogs these have been found to persist for more than 7years, the study did not look later."

12

"Finally, duration of immunity (DOI) experiments in dogs have

now

proven beyond a reasonable doubt

that 3 years protection is achieved against challenge with distemper, adrenovirus-1 and parovirus (Gore et

a ., 2005)."

p. 5

A year ly vaccination interview, sensibly part of a yearly health check, but not necessarily followed by an

injection, should become standard."

p.

"Whereas the 'one siz 'fits all shot has been practiced as a routine in the past, 'vaccination to measure'

will

have to come in its place in

the

future."

OBJECTIVE ASSESSMEN1

OF

JMMUNISATION

"Post-vaccinal serology

..

s

not

new

to

companion animal medicine: evidejlce of antibodies to rabies

virus decides whether a dog

may travel. _A fl assessment of he animal's immune status would provide the

vet with information about

the

success rate of

her

measures, and reassure tl .e client."

p. 7

"Interpretation

of

he serology datav.ill be an element of he vaccinal interyiew."

Most animals in an

area,

a prodnce, a country should

be vaccinated-

rather

than

revaccinating the same

dog

or

cat time and time again, which neither improves its own immune Stl\tuS

nor

contributes to herd

immunity.

HORZINEK. M.C., ''Vaccination Protocols for Companion

Animals:

The Veterinarian's

Perspective,"

J.

Comp. Path. 2010.

VoL

142.8129-8132.

p.l29

"Although geriatric medicine for

these

species has received some recent attention; there is little study

of

the

vaccination requirements

of

such n i m a l s ~

Ageing populations

of

companion dogs, cats and horses are animals that require specific veterinary

attention when it comes it comes to the prevention of infectious diseases."


21/35

13

p. 130

Non-core vaccines are defined according to geography and risk of exposure

..

The recent surge in pet vaccination guideline groups

was

initiated

in

2000 .. and followed in 2003 by the

American Animals Hospita l Association (AAHA) for the dog (Paul et al, 2()06).

Guidelines result from a consensus process, are non-compulsory and are based on available, qualified

evidence; they are intended to complement the official information found

in

the package insert and should

fill in the gap between regulations.

Acceptance

of

his change has been slow, both by manufacturers and veterinarians, mainly because of

the misconception that the availability

of

vaccines with an extended duratiqn

of

immunity (DO ) would

mean that fewer vaccines would be sold and applied.

A

clinical examination is a standard

part of the

visit: only healthy pets are vaccinated, unless there are

reasons (e.g. chronic conditions

in

elderly animals) to

do

otherwise.

.l31

In fact the new adage is to vaccinate more animals with core components, but the individtL l.) dog and cat

less frequently (Day et al., 2007).

There are scientific and societal reasons for the change in immunization protocols. Scientific arguments

include the long persistence of protective antibody titers (in

dogs>

7 years for CDV and CPV; in cats> 4

years for FPV, FCV and FHV), the longevity

of

memory

B-

and T -cel l populations (life-long for some

antigens),

but

also by industry

in

preparation

of

heir product registration (which only establishes a

minimum DOl).

...

an

elderly

dog

needs a vaccination protocol different from that

ofan

adplescent (immunology).

The vaccination topics to

be

covered

in the

first

year may

serve as

an

example: the owner is informed

about preventable diseases,

the

advantages

of

vaccination versus treatment (risk-benefit considerations

including cost), potent ial side-effects

and

complications, a possible lack ofprotection

..

ad onset of

duration

of

protection.

p.132

There are also age-related diseases in the dog and cat: a higher stLSceptibility for infections and immune

senescence have been inferred and demonstrated.

Old dogs show lower lymphocyte proliferative responses and lower CD4:CD8 T-cell ratios, but have

protective titres against CDV, CPV and rabies before revaccination.


22/35


23/35

15

vaccinated with the vaccine in question in a given time period is unknown, it is not possible to calculate a

troe adverse reaction incidence or risk rate."

p.705

Most surveillance efforts are designed to relate specific adverse reactions

to

recently administered

vaccines, that is, to vaccination in the previous hours, days, or even months. However, in the past few

years, there appears to be considerable increase

in

the number of dogs and

catS

recognized

to

have

immune-mediated diseases with onset

of

middle or older ages. While a variety qf causes or predisposing

factors are known

or

thought

to

precipitate immune-mediated diseases,

it

has been suggested that some of

these can be triggered

by

frequent e:>..-posure

to

modified live vaccines (Dodds, 1985)."

p.706

The present system of post-marketing surveillance for veterinary vaccines can be improved considerably

if industry-wide standards are adopted for characterizing and counting adverse reactions and if individual

manufacturers consider the following:

p.707

"Increase ascertainment of adverse reactions by encouraging more complete reporting by veterinarians."

"Vaccine manufacrlh-ers should standardize their reporting systems to be consistent with each other in

terms

of

type and severity

of

adverse reactions."

p.709

A decision

to

vaccinate companion animals against a particular disease may involve consideration of the

efficacy of

he

vaccine, me likelihood of the animal being exposed

to the i s < ~ a S e c a u s i n g

agent, the age

and health of he animal,

and

the probability of side effect."

DODDS,

W.J., More Bumps of the

Vaccine

Road, Advances

n

Veterinary Medicine, Vol. 41

p. 715

In veterinary medicine, evidence implicating vaccines in triggering immune-mediated and other chronic

disorders (vaccinosis) is gmwing (Dodds, 1983, 1993, 1995a, 1997; Phillips and Schultz, 1992; Alderink

et

al, 1995; Schultz, 1995a,b; DL-oval

and

Giger, 1996)."

p. 716

"Determining causality for adverse effectS of vaccines can be asked as three f .Uestions: Can it? (potential

causality);

Did

it? (retrodictive causality); and Will it? (predictive causality) (Stratton et al., 1994)."

Other factors to be weighed in considering the implications

of

causality include ..vaccine related issues

such as dosage in relation to body mass and age, advantages and disadvantages of modified live

(attenuated) and killed (inactivated) vaccines, hormonal state during vaccine (Smith eta ., 1990), and

periodicity ofbooster vaccinations in relation to duration of immunity (Dod9s, 1997). Alternatives

to


24/35

16

current vaccine practices include measuring serum antibody titres; avoidance of unnecessary vaccines or

overvaccinating; caution in vaccinating sick, very old, debilitated, or febrile individuals."

OVERVIEW OF ADVERSE EFFECTS OF VACCINES

"The onset of adverse effects ofvaccinations can be expressed as au immediate hypersensitivity or

anaphylactic reaction; an acute event occurring 24-72 hours afterwards, or 10-28 days later

in

a delayed

type immunologic response (Dodds, 1983, 1995a, 1997; Tizard, 1990; Phillips and Schultz, 1992; Duval

and

Giger, 1996)."

"The

increasing antigenic load presented to the individual host by modified live virus (MLV) vaccines

during the

period ofviremia is presumed to

be

responsible for immunologic challenge that can result in a

delayed hypersensitivity reaction (Tizard, 1990; Phillips and Schultz, 1992),"

"These adverse vaccine reactions typically include fever, stiffness, sore joints and abdominal tenderness,

susceptibility to infections, neurologic disorders and encephalitis, collapse 'Yith auto agglutinated red

blood

cells

and

icterus ( amoimmune hemolytic anemia, AlliA).

"Liver enzymes may be markedly elevated,

aud

liver

or

kidney failure may occur

..

"

"Post-vaccinal polyneuropathy is a recognized entity associated occasionally with the use

of

distemper,

parovirus, rabies, and pre5llli1ably other vaccines (Tizard, 1990; Phillips and Schultz, 1992; Dodds, 1993;

Collins, 1994; Gloyd, 1995)."

"This can resuh in various clinical signs including muscular atrophy, inhibition or interruption

of

neuronal control

of

tissue and organ function, muscular excitation, incoordination and weakness, as well

as seizures (Dodds, 1993, 1997)."

p. 718

"Giving

annual boosters when

they

are not necessary has the client paying for a service that is likely to be

of little benefit

to

the

pef

s existing level ofprotection against these infectioj s diseases.

It

also increases

the

risk

of

adverse reactions from repeated exposure

to

foreign substances (Smith, 1995; Alderink eta ;

1995)."

p 719

"Polyvalent MLV vaccines that multiply in the host elicit a stronger

n t i g e ~ c

challimge to the animal and

should mount a more effective and sustained immune response .. However this can overwhelm the

immunocompromised

or

even healthy hos t that has ongoing exposure

to

other enviromnental stimuli as

well as

a genetic predisposit ion

that

promotes adverse response

to

viral challenge."

p 727

"An increasing number

of

experts

...

advocate lengthening the interval between boosters, especially for

geriatric animals (Frick and Brooks, 1981; Tizard, 1990; Alderink eta ; 1995; Schultz, 1995a,b)."


25/35

17

Except where vaccination is required by law, animals that previously e x p ~ r i e n c e d an adverse reaction

to

vaccination or are at genetic or physiological 1isk for such reactions can have serum antibody titres

measured annually instead of revaccination."

p. 728

The overall risk-benefit ratio of usin2: multiple ant igen vaccines

:iven

sin:)j ltaneously and repeatedly

should

be

reexamined

..

"

DOl- Duration of Immunity

SCHULTZ, R.D., Duration of Immunity

for

Canine and Feline Vaccines: A Review, Veterinary

Microbiology,

117

(2006) 75-79

p.

76

The results

of

this

study

showed

that

antibody titres were maintained for years without revaccination.

It

also showed

that

all challenged animals were protected from clinical

i s e a s ~ J .

The results from

this

limited group

of

dogs clearly demonstrated the

Norden

modified live vaccines

provided immunity for

a t

lea,"t years against CDV and CPV-2."

" ...approximately

iOOO

dogs have been vaccinated with products from all tjle major US veterinary

biological companies. The DOI for the various products is determined by antibody titres .. "

p. 77

At present it should be understood that the rabies vaccines are the only products for which

the USDA

require minimum DOI studies

for

licensing purposes. Currently

USDA

approval is

not

required for the

recommendation of ell.'tended DOI vaccination programs for any other vaccine."

"Duration

of immunity

following vaccination or natural infection

is

dependent

on

two major mechanisms:

1) the persistence of

memory

B

and

T cells stimulated

at

the time

of

vaccination/infectionand (2) the

persistence

of

long

lived

plasma cells that I have termed "memory effector B cells", which continue

to

produce antibody

for years

after initial immune stimulation."

" ...

DOI

studies in both the cat

and

the dog show memory effector B cells" continue to produce antibody

to core vaccines in

the

absence of overt antigenic stimulation for many years. Thus, revaccination does

not appear necessary

to

maintain these cells."

SCHULTZ,

R.D

et al;

Age

and

Long-term Protective

Immunity in

Dogs

and

Cats,

J.

Comp.

Path.

2010, Vol.142, S103-S108

p. 103

"Vaccination can provide an immune response that is similar in duration to that following a natural

infection. n

general, adoptive immunity to viruses develops earliest and

is

highly effective. Such anti

viral immune responses often result

in

the development

of

sterile immunity and the duration

of

immunity

(DOI) is often l ifelong."


26/35

18

The present study examines the DOI for core viral vaccines in dogs that had not been revaccinated for as

long

as 9 years. These animals had serum antibody to canine distemper vjrus (CDV), canine parolvirus

type 2 (CPV-2) and canine adrenovirns type- (CAV-1) at levels considered protective and when

challenged with these viruses, the dogs resisted infection and/or disease."

The

decline

of

immunity in older animals (immunosenescence)

may

make them more susceptible to

certain infectious diseases. Studies immunosenescence in the dog and cat have suggested a decline in the

immune system with age .. "

p.105

The

longest period

oftime

after initial vaccination that dogs were

sampl


27/35


28/35

20

DODDS W.J., ''Vaccination Protocols for Dogs Predisposed to Vaccine Rfllctions, Journal of the

American Animal Hospital Association, May/June 2001, Vol.

37

p. 2

"There is increasing evidence in veterinary medicine that vaccines can tr igger immune-mediated and

other chronic disorders (i.e., vaccinosis), especially in certain apparently predisposed breeds."

"

...

vaccination does carry

with

it attendant risks."

ADVERSE EFFECTS OF VACCINES

As the most immediate recognized adverse effect ofvaccination is an immediate hypersensitivity or

anaphylactic reaction, practitioners are less familiar with the more rare but eq 1llllY serious acute or

chronic immune mediated syndromes than can occur."

Beyond the immediate hypersensitivity reactions, other than acute events tend to occur 24 to 72 hours

afterwards,

or

even 7

to

45 days later in a delayed-type immunological response."

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.

The

clinical signs of nonanaphylactic vaccine reactions typically include

fev


29/35

21

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.

A

significant portion of hese animals had been vaccinated with monovalent or polyvalent vaccines

within

the

30

to

45 day period prior to

the

onset

of

heir autoinunune disease.

SCHULTZ,

R.D., I

Considerations in

Designing Effective

and

Safe Vaccination

Programs

for

Dogs, Recent

Advances in Canine

Infectious Disease,

CARMICHAEL,

I,.E., (E.d.)

Although a few of he vaccines are available as monovalent products (e.g., rapies, canioe parovirus),

most

are available only

as

multi-component products that contain between 2 tolO components.

Core vaccines which are considered essential, and should

be

given to every dog, are termed are termed

core vaccioes. All other vaccioes are regarded as non-core and should be used io dogs considered high

risk on an as needed basis.

Diseases that pose serious risk to susceptible dogs, or to public health, which are readily preventable by

current vaccines ioclude rabies virus

(RV);

canine parovirus caused by canioe parovirus-2 (CPV

2);

canioe distemper caused by canine distemper virus (CDV); and infectious canine hepeatitis caused by

(ICH) caused by canine adrenovirus

type-1

(CAV

-1)

...controlled by adenoviflls-2 vaccioe (CAV-2).

Table2

Canine Distemper 7yr

Minimum

duration of nunuuity

Canine parovirus 2

Canioe adrenovirus-2

''Why are there significant differences io the number of doses and o m p o n e n ~ of vaccioes routinely given

io the maximum vs. minimum disease prevention programs? Those differences arise primarily from

misperceptions about how vaccioes work, which vaccioes are necessary, and how often vaccioe should be

given duriog the life of he dog to provide protective inununity.

If a dog is at high risk of exposure to an important disease like CPV-2, a monovalent CPV-2 vaccine is

recommended, not a multi-component product. The risk ofadverse reactions has been greater with multi

component vaccioes.

Canine parainfluenza

and B bronchiseptica-

CPI

is

included

as

a componeqt of all current parenteral

vaccines containiog CDV, CPV-2 and CAV; therefore

it

is

given

to

very

dog that receives the core

vaccine.

ADVERSE REACTIONS

The risks ofadverse reactions from vaccioes are not

well

studied,

nor

are adverse reaction rates well

documented.

Even

where documented, the information is not readily available. The inunuue mediated

hypersensitivities caused by vaccioes are well known and occur io every species.


30/35

22

V ..

he most common vaccine reactions observed in dogs include pain, sqreness, stiffuess and /or lethargy

at variable times

of

vaccination. Swelling, persistent lump

.. Post-vaccin -1

neurologic disease (e.g.,

encephalitis) was rare

...

More recently it has been shown experimentally that dogs develop an

autoimmune response after vaccination, something that was known to ocpur in other species."

/ "Furthermore, a study

of

dogs in veterinary clinics showed a slight

n r e ~ e

in cases

of

autoimmune

V

hemolytic anemia within 30 days following vaccination with multi-comppnent vaccines."

WSAV A- Guidelines for the Vaccination ofDogs and Cats

Compiled by the

vaccination Guideline

Group

M J Day- Chairman,

School

of Veterinary

Science, University

of

Bristol,

UK

M.C. Horzinek-

(Formerly)

Department of Microbiology, Virology :Pivision, University ofUtrecht,

Netherlands

R.D. Schultz,

Department

ofPathobiological Sciences, University

of

wiscons in-Madison, USA

p. 1

We should

aim

to vaccinate everv animal with core vaccines, and to vaPfinate each individual less

frequentlv bv onlv civing non-core vaccines that are necessary for that animaL"

"The VGG has defined non-core vaccines as those that are required by only those animals whose

geographical location, local environment

or

lifestyle places them

at

risk

of

contracting specific

infections."

"Each country that had its own vaccination guidelines was also

asked to

send a copy

of

hese

to

the

VGG."

"Responses were received from 27 countries, both from developed and d iveloping nations."

The

VGG recognizes

the

importance

of

adverse reaction reporting schemes but understands that these

are variably developed in different countries. Wherever possible, veterinapans should

be

actively

encouraged

to

report all possible adverse events

to

the manufacturer and/qr regulatory authority to expand

the

knowledge base

that

drives improvement

of

vaccine safety."

p.4

A second major concept regarding vaccination

of

dogs and cats has been the recognition that we should

aim to reduce the 'vaccine load' on individual animals in order to n m ~ potential for adverse reactions

to

vaccine products."

p. 5

"Dogs that have responded

to

vaccination with MLV core vaccines maintllin a solid immunity

(immunological memory) for many years in the absence

of

any repeat vac\)ination."


31/35

p.6

Antibody tests are useful for monitoring immunity to CDV, CPV 2, CAV 1 and rabies virus.

, Adverse Events

23

.

\

Adverse events are defmed

as

any side effects or unintended consequences (including lack

of

protection)

associated with

the

administration

of

vaccine products. They include any injury, toxicity, or

hypersensitivity reaction associated

with

vaccination, whether or

not

the event

can

be directly attributed

to

the

vaccine.

CPV-2 PAROVIRUS

p l8

DOl

after natural infection/disease is life-long

DOl after vaccination with

ML

V vaccine is

9

years or longer, based on challenge and serological studies

In geographical areas or isolation facilities where CPV-2

is

not endemic in domestic or wild susceptible

species, MLV vaccines should not be used as the virus will be shed and could potentially revert to

virulence a well as infect other individuals or other species

CDV- DISTEMPER

p.20

DOl after vaccination is 9 years or longer

p.

19

CAV-2

ADRENOVIRUS

.

...

here are combination or monovalent products to protect against the canine respiratory disease

complex (CRDC), which includes multiple bacteria (notably bordatella bronchiseptica)

...

SARDS

MONTGOMERY,

K W, et al, Acute blindness in

dogs:

Sudden acquired

retinal

degeneration

syndrome

versus neurological disease (140 cases, 2000-2006), Veterinary Ophthalmology, 2008, 11,

5,314-320

p.314

Objective to evaluate dogs with amaurosis and compare signalment history, 9ptbalmic examination and

neurological abnormalities between dogs diagnosed with sudden acquired retinal degeneration syndrome

(SARDS) versus neurological disease (ND).

Results 120 dogs were diagnosed with SARDS and 20 dogs with ND based on

ERG

results. Mixed-breed

dogs were most commonly diagnosed with SARDS as well as ND.


32/35

"Cushings-like symptoms were reported more frequently in SARDS dogs ..."

p

315

"Besides exhibiting sings ofhyperadrenocorticism that can persist for months possibly due to chronic

stress SARDS dogs are generally considered systemically healthy."

"Neurological deficits reported in SARDS dogs included unilateral pelvic llipb weakness, decreased

conscious proprioception, and bilateral facial nerve paralysis."

p. 317

"Consistent

with

previous reports, dogs affected by SARDS were predomina1}tly middle-aged or older,

and females were more commonly diagnosed."

p.318

24

"

...

weight gain

and

lethargy that were commonly reported are probably relatl(d to the Cushing's like signs

that SARDS dogs exhibit."

"Polyuria, polydipsia, and polyphagia were reported more frequently (P

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Dr. Paul McCutcheon Expert Report (plaintiff)

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