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Content uploaded by Pedro L Moro
Author content
All content in this area was uploaded by Pedro L Moro on Jun 12, 2019
Content may be subject to copyright.
Vaccine
33
(2015)
3288–3292
Contents
lists
available
at
ScienceDirect
Vaccine
j
o
ur
na
l
ho
me
page:
www.elsevier.com/locate/vaccine
Review
Deaths
following
vaccination:
What
does
the
evidence
show?
Elaine
R.
Miller∗,
Pedro
L.
Moro,
Maria
Cano,
Tom
T.
Shimabukuro
Immunization
Safety
Office
(ISO),
Centers
for
Disease
Control
and
Prevention
(CDC),
Atlanta,
GA,
United
States
a
r
t
i
c
l
e
i
n
f
o
Article
history:
Received
9
March
2015
Received
in
revised
form
5
May
2015
Accepted
11
May
2015
Available
online
23
May
2015
Keywords:
Vaccination
Immunization
Adverse
events
Death
Vaccine
safety
a
b
s
t
r
a
c
t
Vaccines
are
rigorously
tested
and
monitored
and
are
among
the
safest
medical
products
we
use.
Millions
of
vaccinations
are
given
to
children
and
adults
in
the
United
States
each
year.
Serious
adverse
reactions
are
rare.
However,
because
of
the
high
volume
of
use,
coincidental
adverse
events
including
deaths,
that
are
temporally
associated
with
vaccination,
do
occur.
When
death
occurs
shortly
following
vaccination,
loved
ones
and
others
might
naturally
question
whether
it
was
related
to
vaccination.
A
large
body
of
evidence
supports
the
safety
of
vaccines,
and
multiple
studies
and
scientific
reviews
have
found
no
asso-
ciation
between
vaccination
and
deaths
except
in
rare
cases.
During
the
US
multi-state
measles
outbreak
of
2014–2015,
unsubstantiated
claims
of
deaths
caused
by
measles,
mumps,
and
rubella
(MMR)
vaccine
began
circulating
on
the
Internet,
prompting
responses
by
public
health
officials
to
address
common
mis-
interpretations
and
misuses
of
vaccine
safety
surveillance
data,
particularly
around
spontaneous
reports
submitted
to
the
US
Vaccine
Adverse
Event
Reporting
System
(VAERS).
We
summarize
epidemiologic
data
on
deaths
following
vaccination,
including
examples
where
reasonable
scientific
evidence
exists
to
support
that
vaccination
caused
or
contributed
to
deaths.
Rare
cases
where
a
known
or
plausible
theo-
retical
risk
of
death
following
vaccination
exists
include
anaphylaxis,
vaccine-strain
systemic
infection
after
administration
of
live
vaccines
to
severely
immunocompromised
persons,
intussusception
after
rotavirus
vaccine,
Guillain–Barré
syndrome
after
inactivated
influenza
vaccine,
fall-related
injuries
asso-
ciated
with
syncope
after
vaccination,
yellow
fever
vaccine-associated
viscerotropic
disease
or
associated
neurologic
disease,
serious
complications
from
smallpox
vaccine
including
eczema
vaccinatum,
progres-
sive
vaccinia,
postvaccinal
encephalitis,
myocarditis,
and
dilated
cardiomyopathy,
and
vaccine-associated
paralytic
poliomyelitis
from
oral
poliovirus
vaccine.
However,
making
general
assumptions
and
draw-
ing
conclusions
about
vaccinations
causing
deaths
based
on
spontaneous
reports
to
VAERS
–
some
of
which
might
be
anecdotal
or
second-hand
–
or
from
case
reports
in
the
media,
is
not
a
scientifically
valid
practice.
Published
by
Elsevier
Ltd.
1.
Background
Modern
vaccines
are
among
the
greatest
public
health
achieve-
ments
in
history,
preventing
thousands
of
illnesses
and
deaths
each
year
in
the
United
States
alone
[1].
However,
as
illness,
disability
and
death
from
vaccine-preventable
diseases
have
decreased,
con-
cerns
over
vaccine
safety
have
increased
[2].
Despite
the
reality
that
a
person
is
far
more
likely
to
be
seriously
or
fatally
injured
by
a
dis-
ease
prevented
by
vaccines
than
by
a
vaccine
itself,
there
appears
Abbreviations:
ACIP,
Advisory
Committee
on
Immunization
Practices;
CDC,
Centers
for
Disease
Control
and
Prevention;
FDA,
Food
and
Drug
Administration;
IOM,
Institute
of
Medicine;
MMR,
measles,
mumps,
&
rubella
combination
vaccine;
OPV,
oral
poliovirus
vaccine;
SIDS,
sudden
infant
death
syndrome;
VAERS,
Vaccine
Adverse
Event
Reporting
System;
VAPP,
vaccine-associated
paralytic
polio.
∗Corresponding
author
at:
1600
Clifton
Rd
NE,
Mailstop
D-26,
Atlanta,
GA
30333,
United
States.
Tel.:
+1
404
639
8268;
fax:
+1
404
639
8834.
E-mail
address:
Erm4@cdc.gov
(E.R.
Miller).
to
be
a
trend
toward
increased
refusal
or
delay
of
recommended
vaccinations
due
to
perceived
safety
concerns
[3].
During
the
US
multi-state
measles
outbreak
of
2014–2015,
most
infected
persons
were
not
vaccinated
against
measles
or
had
unknown
vaccination
status
[4].
Early
on,
unsubstantiated
claims
of
deaths
caused
by
the
measles,
mumps,
and
rubella
(MMR)
vac-
cine
began
circulating
on
the
Internet
[5–7].
The
original
claim
was
based
on
data
from
the
US
Vaccine
Adverse
Event
Reporting
System
(VAERS).
It
is
important
to
realize,
however,
that
VAERS
is
a
volun-
tary
reporting
system
which
accepts
any
submitted
report
of
an
adverse
event
without
judging
its
clinical
significance
or
whether
it
was
caused
by
a
vaccination
[8].
VAERS
is
a
signal
detection
and
hypothesis
generating
passive
surveillance
system
and
therefore
any
broad
claim
of
cause
and
effect
with
respect
to
deaths
follow-
ing
vaccination
based
on
VAERS
reports
should
not
be
interpreted
as
proof
of
causality.
We
summarize
historical
information
and
published
epidemio-
logic
data
on
deaths
following
vaccination,
including
events
where
http://dx.doi.org/10.1016/j.vaccine.2015.05.023
0264-410X/Published
by
Elsevier
Ltd.
E.R.
Miller
et
al.
/
Vaccine
33
(2015)
3288–3292
3289
reasonable
scientific
evidence
exists
to
conclude
that
vaccination
caused
or
contributed
to
deaths.
There
are
instances
where
medical
errors
or
other
human
factors,
not
the
vaccine
as
it
was
meant
to
be
used,
have
caused
deaths
following
vaccination
[9,10].
However,
our
summary
is
restricted
to
deaths
possibly
related
to
the
vaccine
itself.
2.
Historical
events
In
the
era
of
modern
medicine,
some
of
the
first
concerns
about
vaccines
causing
death
date
to
isolated,
but
high
profile
past
vac-
cine
safety
incidents.
The
“Cutter
Incident”
in
1955
involved
a
flaw
in
the
Salk
polio
vaccine
manufacturing
process
at
Cutter
Labora-
tories
that
led
to
production
of
substantial
amounts
of
what
was
thought
to
be
inactivated
vaccine
that
contained
live
poliovirus.
The
result
has
been
called
“.
.
.one
of
the
worst
pharmaceutical
disasters
in
US
history”[11],
with
40,000
cases
of
polio
resulting
in
51
cases
of
permanent
paralysis
and
five
deaths
among
vaccinated
individ-
uals,
and
113
cases
of
paralysis
and
five
deaths
among
contacts
of
vaccinated
individuals
[11,12].
As
a
result
of
the
Cutter
Incident,
the
US
government
implemented
much
more
vigilant
monitoring
and
regulation
of
the
vaccine
industry
[13].
The
Food
and
Drug
Administration
(FDA)
now
requires
extensive
testing
to
evaluate
the
safety
and
efficacy
of
vaccines
prior
to
licensure.
After
licensure,
FDA
requires
ongoing
lot-release
testing
and
manufacturing
facility
inspections.
Additionally,
manufacturers
are
required
to
conduct
post-licensure
safety
monitoring
for
their
products
and
report
to
the
FDA
[14,15].
In
1976,
concerns
in
the
United
States
about
a
possible
influenza
pandemic
involving
a
virus
similar
to
the
deadly
1918
pandemic
strain
resulted
in
a
large-scale
vaccination
program
for
the
entire
country.
Approximately
45
million
people
were
vaccinated
in
10
weeks
with
what
became
known
as
the
“swine
flu
vaccine”
[16].
The
US
government
abruptly
stopped
the
vaccination
program
when
no
swine
flu
cases
were
detected
outside
the
military
base
where
the
disease
originated
and
when
an
unexpectedly
high
number
of
cases
of
Guillain–Barré
syndrome
were
reported
in
vaccinated
indi-
viduals.
The
vaccine
was
estimated
to
have
caused
approximately
one
Guillain–Barré
syndrome
case
per
100,000
persons
vaccinated
[17],
resulting
in
53
deaths
[18].
As
a
result
of
the
association
between
the
1976
swine
flu
vaccine
and
Guillain–Barré
syndrome,
this
condition
is
closely
monitored
every
influenza
season
as
part
of
influenza
vaccine
safety
monitoring
in
the
United
States.
3.
Current
epidemiologic
data
on
death
associated
with
vaccination
Multiple
large
reviews
and
studies
have
been
conducted
to
eval-
uate
the
association
between
vaccination
and
death.
The
results
have
consistently
been
reassuring.
The
Institute
of
Medicine
(IOM)
reviewed
deaths
reported
to
VAERS
after
childhood
vaccines
in
the
early
1990s
[19].
Some
of
the
reports
did
not
have
enough
informa-
tion
to
make
a
determination
about
causality,
but
among
reports
with
adequate
follow-up,
the
IOM
concluded
that
the
vast
major-
ity
of
reported
deaths
were
coincidental
and
not
causally
related
to
vaccination.
There
was
one
death
due
to
a
vaccine
strain
viral
infec-
tion:
a
3-month-old
infant
died
from
myocarditis
after
oral
polio
vaccine
(which
is
no
longer
licensed
for
use
in
the
United
States)
and
DTP
vaccine;
vaccine
strain
poliovirus
was
isolated
from
the
child’s
myocardium.
In
another
review
of
1266
deaths
reported
to
VAERS
from
1990
to
1997,
nearly
half
of
the
deaths
were
due
to
sud-
den
infant
death
syndrome
(SIDS)
with
a
peak
in
1992–1993
and
a
decline
after
the
“Back
to
Sleep”
campaign
was
implemented
[20].
The
study
also
found
that
death
reports
to
VAERS
from
causes
other
than
SIDS
also
declined
from
1993
to
1996
as
the
population
and
the
number
of
vaccines
administered
increased,
which
was
reas-
suring.
In
addition
to
SIDS,
there
were
multiple
causes
of
death
which
were
not
vaccine
related,
including
infectious,
congenital,
neoplastic,
cardiac,
and
cases
with
unknown
causes
due
to
incom-
plete
information.
This
review
also
found
that
among
the
death
reports,
a
higher
percent
of
the
infants
had
low
birth
weight
than
in
the
general
US
population
(16.8%
vs.
7.2%);
lower
birth
weight
infants
are
known
to
have
higher
mortality
rates
during
the
first
two
years
of
life
[20].
Multiple
other
published
reviews
of
VAERS
data
for
specific
vaccines
and
vaccine
types
have
found
no
con-
cerning
patterns
that
would
suggest
a
causal
relationship
between
vaccination
and
deaths
[21–26].
In
2003,
the
IOM
examined
the
relationship
between
vaccina-
tions
and
SIDS.
The
IOM
rejected
a
causal
association
between
the
whole
cell
pertussis-containing
vaccine
(which
is
no
longer
in
use
in
the
United
States)
and
SIDS
and
between
exposure
to
multiple
vaccines
and
SIDS.
The
IOM
concluded
that
inadequate
evidence
existed
to
accept
or
reject
a
causal
relationship
between
several
other
vaccines
and
SIDS.
Additionally,
the
IOM
did
“.
.
.
not
recom-
mend
a
policy
review
of
the
recommended
childhood
vaccination
schedule
by
any
of
the
national
or
federal
vaccine
advisory
bodies
on
the
basis
of
concerns
about
sudden
unexpected
death
in
infancy”
[27].
A
study
published
in
2013
using
electronic
health
record
databases
reviewed
health
information
on
over
13
million
vac-
cinated
persons
and
compared
causes
of
death
in
the
vaccinated
study
population
to
the
general
US
population.
The
death
rate
one
or
two
months
following
vaccination
was
lower
than
that
in
the
general
US
population,
and
the
causes
of
death
were
similar
[28].
This
study
provides
convincing
evidence
that
vaccinations
are
not
associated
with
an
increased
risk
of
death
at
the
population
level.
4.
Evidence
in
favor
of
causal
associations
between
vaccination
and
death
Although
the
evidence
supports
the
safety
of
vaccines,
there
are
rare
instances
where
causal
relationships
between
vaccination
and
death
have
been
established
or
a
plausible
theoretical
risk
exists.
4.1.
Anaphylaxis
following
vaccination
Many
vaccines
have
been
determined
to
rarely
cause
ana-
phylaxis.
The
risk
of
anaphylaxis
is
less
than
two
cases
per
million
doses
of
vaccines
administered
to
children
and
adoles-
cents
[29].
While
anaphylaxis
is
serious
and
can
be
fatal,
death
and
other
complications
can
be
prevented
with
rapid
treatment
using
effective
medications
including
epinephrine,
corticosteroids
and
beta-agonists.
A
10-year
review
of
claims
to
the
US
National
Vaccine
Injury
Compensation
Program
noted
five
cases
of
death
from
anaphylaxis
after
vaccinations
[30].
Another
study
published
in
2003
using
electronic
health
record
databases
found
that
after
7,644,049
doses
of
vaccination
in
children
and
adolescents,
there
were
five
possible
cases
of
vaccine
associated
anaphylaxis
and
none
resulted
in
death
[29].
The
Centers
for
Disease
Control
and
Preven-
tion
(CDC)
Advisory
Committee
on
Immunization
Practices
(ACIP)
recommends
screening
patients
for
contraindications
and
precau-
tions,
including
allergy
history,
prior
to
vaccination
[31].
However,
since
anaphylaxis
following
vaccination
is
not
always
predictable
or
preventable,
ACIP
also
recommends
that
healthcare
providers
be
prepared
to
treat
medical
emergencies
including
anaphylaxis
if
they
occur
[31].
4.2.
Severely
immunocompromised
persons
receiving
live
vaccines
Live
vaccine
viruses
are
attenuated
so
they
do
not
cause
infec-
tion
in
individuals
with
intact
immune
systems.
Live
vaccines,
3290
E.R.
Miller
et
al.
/
Vaccine
33
(2015)
3288–3292
however,
are
contraindicated
for
people
who
are
severely
immuno-
compromised
[31]
since
their
weakened
immune
systems
may
result
in
the
live
vaccine
causing
illness.
Two
published
case
reports
describe
immunocompromised
children
who
received
varicella
vaccine,
and
where
vaccine
strain
varicella
zoster
virus
infection
contributed
to
their
deaths
[32,33].
In
one
case,
a
4-year-old
child
who
had
been
in
complete
remission
from
acute
lymphoblas-
tic
leukemia
for
five
months
received
varicella
vaccine
during
a
2-week
break
from
chemotherapy
[32];
in
the
other
case,
a
15-
month-old
did
not
have
a
diagnosis
of
being
immunocompromised,
but
had
failure
to
thrive
and
several
hospitalizations
beginning
at
five
months
of
age
for
infections
and
respiratory
problems
requiring
steroid
treatment
[33],
indicating
a
possible
undiagnosed
immu-
nodeficiency.
There
are
at
least
six
case
reports
of
death
among
severely
immunocompromised
persons
that
have
been
linked
to
vaccine
strain
measles
virus
infection
[34],
including
a
case
of
vac-
cine
associated
pneumonitis
in
an
immunocompromised
person
with
HIV
[35]
and
a
case
of
measles
inclusion-body
encephali-
tis
in
a
21-month-old
child
with
primary
immunodeficiency
[36].
CDC
recommends
screening
prior
to
vaccination
so
that
contraindi-
cations
and
precautions,
including
previously
diagnosed
immune
system
problems
are
identified
[31].
4.3.
Intussusception
after
rotavirus
vaccine
Intussusception
is
a
rare
medical
condition
in
which
the
bowel
folds
in,
or
telescopes,
on
itself.
It
can
resolve
on
its
own,
but
might
also
require
medical
treatment
or
in
some
cases
surgery.
In
very
rare
instances,
it
can
result
in
death
(less
than
1%
of
cases
in
developed
countries)
[37].
RotaShield®,
the
first
licensed
rotavirus
vaccine,
was
withdrawn
from
use
in
1999
after
a
greater
than
expected
number
of
reports
of
intussusception
were
detected
in
post-marketing
surveillance
[38].
The
attributable
risk
of
intussus-
ception
was
estimated
to
be
one
case
for
every
4670–9474
infants
vaccinated
[39]
and
one
intussusception
death
after
RotaShield®
was
reported
in
the
literature
[40].
There
is
a
small
increased
risk
of
intussusception
associated
with
the
rotavirus
vaccines
that
are
cur-
rently
licensed
and
in
use
(RotaTeq®and
Rotarix®),
but
the
risk
is
substantially
lower
than
for
RotaShield®at
approximately
one
case
in
20,000–100,000
doses
[41–43].
One
study
estimated
that
among
a
hypothetical
4.3
million
US
birth
cohort
followed
to
age
five
years,
currently
licensed
rotavirus
vaccines
prevent
14
deaths,
more
than
53,000
hospitalizations
and
more
than
169,000
emergency
room
visits;
by
comparison
the
vaccines
are
estimated
to
result
in
an
excess
of
0.2
deaths,
45
hospitalizations,
and
13
short
stay
visits
from
vaccine
associated
intussusception
[44].
A
published
review
of
VAERS
reports
for
2006–2012
for
the
two
currently
licensed
rotavirus
vaccines
indicated
two
death
reports
from
intussuscep-
tion;
however,
definitive
causal
associations
with
vaccination
were
not
established
in
either
case
[45].
4.4.
Guillain–Barré
syndrome
after
seasonal
and
2009
H1N1
(pandemic)
inactivated
influenza
vaccines
Guillain–Barré
syndrome
is
a
rare
disorder
in
which
a
per-
son’s
own
immune
system
damages
peripheral
nerve
cells,
causing
muscle
weakness
and
sometimes
paralysis
[46].
Most
people
recover
fully
from
Guillain–Barré
syndrome,
but
some
may
have
permanent
nerve
damage.
Known
risk
factors
for
GBS
include
bac-
terial
or
viral
infections,
especially
Campylobacter
jejuni
[47]
and
other
infections
causing
diarrhea
or
respiratory
illnesses
[46].
Stud-
ies
assessing
the
risk
of
Guillain–Barré
syndrome
after
seasonal
inactivated
influenza
vaccine
since
1976
have
shown
either
no
risk
or
a
small
increased
risk
on
the
order
of
one
to
two
cases
per
mil-
lion
doses
administered
[48],
which
is
similar
to
the
risk
observed
with
the
2009
influenza
A
(H1N1)
monovalent
vaccine
[49].
However,
one
study
found
the
cumulative
risk
of
GBS
over
the
entire
influenza
season
was
lower
in
individuals
that
received
2009
H1N1
(pandemic)
inactivated
influenza
vaccines
compared
to
unvaccinated
individuals,
indicating
that
vaccination
might
pre-
vent
GBS
cases
[50].
Another
study
using
electronic
health
record
data
from
2000
through
2009
found
that
among
38
confirmed
or
probable
GBS
cases
that
occurred
within
six
weeks
of
seasonal
inactivated
influenza
vaccine,
two
deaths
occurred
during
a
median
follow-up
time
of
6½
months;
in
neither
of
the
cases
that
resulted
in
death
was
a
causal
association
established
with
vaccination
[51].
Approximately
5%
of
Guillain–Barré
syndrome
cases
are
fatal
[52],
but
given
the
indeterminate
association
between
influenza
vacci-
nation
and
GBS,
risk
of
death
from
vaccine-associated
GBS
would
have
to
be
considered
theoretical.
4.5.
Syncope
(fainting)
after
vaccination
leading
to
head
trauma
and
death
The
IOM
concluded
that
the
available
evidence
convincingly
supports
a
causal
relationship
between
the
injection
of
a
vaccine
and
syncope
[53],
although
this
relationship
exists
for
any
medical
procedure
involving
a
needle
stick
(e.g.,
blood
draw).
In
a
study
on
quadrivalent
human
papillomavirus
vaccine
among
young
women,
15%
reported
presyncope
or
syncope
after
the
first
dose
[54].
Post-
vaccination
syncope
can
result
in
injuries
including
head
trauma.
A
VAERS
case
report
described
an
incident
of
death
attributed
to
blunt
head
trauma
following
a
fall
secondary
to
vasovagal
syncope
that
occurred
several
minutes
after
vaccination
with
hepatitis
B
vac-
cine
[55].
Syncope
is
an
acute
event
that
typically
occurs
within
15
minutes
of
vaccination
[56],
and
the
Advisory
Committee
on
Immunization
Practices
suggests
a
15-minute
observation
period
after
vaccination,
especially
if
the
patient
is
an
adolescent
[31].
4.6.
Yellow
fever
vaccine-associated
viscerotropic
and
neurologic
disease
A
rare,
serious
reaction
to
yellow
fever
vaccine
called
yellow
fever
vaccine-associated
viscerotropic
disease
has
similar
symp-
toms
to
yellow
fever
illness.
Initial
symptoms,
which
usually
occur
within
one
week
of
vaccination,
are
fever,
along
with
feeling
gener-
ally
unwell,
muscle
pain,
nausea,
vomiting,
and/or
diarrhea.
These
symptoms
can
progress
to
multisystem
organ
failure
and
death.
More
than
60
cases
worldwide
have
been
reported
to
CDC
and
of
those,
63%
resulted
in
death
[57].
The
incidence
of
yellow
fever
vaccine-associated
viscerotropic
disease
in
the
United
States
is
0.4
cases
per
100,000
doses
administered
[57].
Another
rare
reaction
to
yellow
fever
vaccine
is
yellow
fever
vaccine-associated
neurologic
disease.
This
includes
several
con-
ditions,
such
as
meningoencephalitis
(inflammation
of
the
brain
and
its
membranes),
Guillain–Barré
syndrome,
acute
disseminated
encephalomyelitis
(inflammation
of
the
brain
and
spinal
cord),
and
bulbar
palsy
(paralysis
of
the
motor
units
of
the
cranial
nerves).
Less
than
one
case
per
100,000
vaccine
doses
administered
is
reported,
and
it
is
rarely
fatal
[57].
Both
yellow
fever
vaccine-associated
viscerotropic
and
neuro-
logic
disease
are
more
common
in
persons
aged
60
years
or
older
[57],
therefore
age
60
years
or
older
is
a
precaution
to
receiv-
ing
this
vaccine.
In
the
United
States,
yellow
fever
vaccine
is
recommended
only
for
travelers
who
plan
to
visit
areas
where
the
disease
is
present
and
for
laboratory
personnel
who
work
with
yellow
fever
virus
[58].
4.7.
Complications
from
smallpox
vaccine
Serious
adverse
reactions
and
complications
from
smallpox
vac-
cine
can
result
in
death
in
rare
cases
[59].
Based
on
historical
E.R.
Miller
et
al.
/
Vaccine
33
(2015)
3288–3292
3291
data,
the
death
rate
following
smallpox
vaccination
is
approxi-
mately
one
death
per
million
persons
receiving
an
initial
dose
and
one
death
per
four
million
among
persons
receiving
another
dose
after
the
first
dose
[60].
Death
has
also
occurred
among
non-
vaccinated
persons
who
had
accidental
contact
with
vaccination
sites
of
vaccine
recipients
[60].
Reactions
that
can
cause
or
con-
tribute
to
death
include
eczema
vaccinatum,
progressive
vaccinia,
postvaccinal
encephalitis,
myocarditis,
and
dilated
cardiomyopa-
thy.
Additionally,
vaccination
of
pregnant
women
can
cause
fetal
infection
resulting
in
stillbirth
or
infant
death
[59,60].
Patients
should
be
carefully
screened
for
precautions
and
contraindications
prior
to
receipt
of
smallpox
vaccine
[61].
In
2008,
a
new
small-
pox
vaccine,
ACAM2000TM,
replaced
the
previously
used
vaccine,
Dryvax®.
The
data
indicate
that
ACAM2000TM has
a
similar
safety
profile
to
Dryvax®[61,62].
Naturally
occurring
smallpox
disease
has
been
eliminated
worldwide,
and
in
the
United
States,
smallpox
vaccine
is
currently
only
given
to
military
personnel
and
selected
individuals
that
might
be
at
high
risk
of
exposure,
such
as
laboratory
scientists
that
work
with
smallpox
or
similar
viruses
[63].
4.8.
Vaccine-associated
paralytic
poliomyelitis
from
oral
poliovirus
vaccine
Vaccine-associated
paralytic
poliomyelitis
(VAPP)
is
a
rare
adverse
reaction
that
can
occur
in
a
recipient
of
live
oral
poliovirus
vaccine
(OPV)
or
in
a
contact
of
a
recipient
of
OPV
[64].
It
can
occur
in
healthy
persons
and
in
persons
with
immune
system
abnormalities.
OPV
is
no
longer
used
in
the
Unites
States
and
has
been
replaced
with
inactivated
poliovirus
vaccine,
but
OPV
is
still
used
in
many
parts
of
the
world.
A
recent
review
puts
the
risk
of
VAPP
at
around
4.7
cases
per
million
births
with
an
estimated
498
cases
annually
worldwide
[65].
VAPP
can
result
in
death,
but
this
is
rare
[66].
In
the
United
States,
from
1980
to
1989
there
were
80
VAPP
cases
reported
and
among
these
reported
cases,
two
patients
(3%)
died
within
60
days
after
onset
of
paralysis
[67].
5.
Conclusion
Vaccines
are
rigorously
tested
and
monitored
and
are
among
the
safest
medical
products
we
use.
Millions
of
vaccinations
are
administered
to
children
and
adults
in
the
United
States
each
year.
Serious
adverse
reactions
are
uncommon
and
deaths
caused
by
vac-
cines
are
very
rare.
Healthcare
providers
can
take
specific
actions
to
help
prevent
adverse
reactions,
including
proper
screening
for
con-
traindications
and
precautions
and
observing
a
15-minute
waiting
period
after
vaccinating
to
prevent
fall-related
injuries
from
syn-
cope.
CDC
and
FDA
continuously
monitor
the
safety
of
US
licensed
vaccines.
All
serious
VAERS
reports,
including
reports
of
death,
are
reviewed.
A
report
is
considered
serious
if
at
least
one
of
the
fol-
lowing
is
reported:
death,
life-threatening
illness,
hospitalization
or
prolongation
of
hospitalization,
or
permanent
disability
[68].
In
addition,
CDC
and
FDA
scientists
use
statistical
techniques
to
check
for
disproportional
reporting
in
the
VAERS
database
for
deaths
and
other
adverse
events
for
individual
types
and
brands
of
vaccines
[69].
If
CDC
or
FDA
were
to
detect
a
potential
new
safety
problem
with
MMR
or
any
other
US
licensed
vaccine,
this
“signal”
would
be
further
assessed
and
regulatory
and/or
public
health
action
would
be
taken,
if
necessary.
With
respect
to
the
recent
claims
of
deaths
caused
by
MMR
vac-
cine
[5–7],
drawing
broad
cause
and
effect
conclusions
between
vaccination
and
deaths
based
on
spontaneous
reports
to
VAERS,
some
of
which
might
be
anecdotal
or
second
hand,
is
not
a
scientif-
ically
valid
practice.
In
fact,
a
review
of
the
VAERS
data
reveals
that
many
of
the
death
reports
for
MMR
vaccine
involved
children
with
serious
preexisting
medical
conditions
or
were
likely
unrelated
to
vaccination
(e.g.,
accidents).
These
complete
VAERS
reports
and
any
accompanying
medical
records,
autopsy
reports
and
death
certifi-
cates
have
been
reviewed
in
depth
by
FDA
and
CDC
physicians
and
no
concerning
patterns
have
emerged
that
would
suggest
a
causal
relationship
with
the
MMR
vaccine
and
death.
The
evidence
for
the
safety
and
effectiveness
of
vaccines
routinely
given
to
children
and
adults
in
the
Unites
States
is
over-
whelmingly
favorable.
In
the
case
of
MMR
vaccine,
this
includes
preventing
hundreds
of
potential
measles-related
deaths
each
year
[34].
Any
discussion
of
the
true
risks
of
vaccination
should
be
balanced
by
acknowledgment
of
the
well-established
benefits
of
vaccines
in
preventing
disease,
disability
and
deaths
from
infec-
tious
diseases.
Funding
The
review
was
conducted
by
the
Centers
for
Disease
Control
and
Prevention
(CDC)
and
no
external
sources
of
funding
were
used.
Acknowledgement
We
gratefully
acknowledge
Dr.
Frank
DeStefano
for
his
input
and
review
of
this
article.
Disclosures:
No
authors
have
a
conflict
of
interest,
including
spe-
cific
financial
interests
and
relationships
and
affiliations
relevant
to
the
subject
matter
or
materials
discussed
in
the
manuscript.
Disclaimer:
The
findings
and
conclusions
in
this
report
are
those
of
the
authors
and
do
not
necessarily
represent
the
official
position
of
the
Centers
for
Disease
Control
and
Prevention.
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