Vaccine Safety: Medical Contraindications, Myths,
and Risk Communication
AUTHOR DISCLOSURE Dr Smith has
disclosed that he has received grants from
Sanofi Pasteur and Novartis. This commentary
does not contain a discussion of an
unapproved/investigative use of
a commercial product/device.
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Michael Smith, MD, MSCE*
*Division of Pediatric Infectious Diseases, University of Louisville School of Medicine, Louisville, KY.
Educational Gap
Some parents are more concerned about the safety of vaccines than the
diseases they are designed to prevent. To maintain high levels of
immunization, pediatricians must be familiar with vaccine safety and
vaccine risk communication. Formal training in these areas is lacking
(Williams SE, Swain R. Formal training in vaccine safety to address parental
concerns not routinely conducted in US pediatric residency program.
Vaccine. 2014;32(26):3175–3178).
Objectives After completing this article, readers should be able to:
1. Recognize adverse reactions to various vaccine constituents and
manage them appropriately.
2. Plan an immunization regimen for a patient with egg allergy.
3. Plan an immunization regimen for a patient with an immune deficiency,
including an immune deficiency that results from chemotherapy.
4. Understand the basic mechanisms for assessing vaccine safety in the
United States.
5. Plan an appropriate approach to addressing the needs of the vaccine-
hesitant family.
INTRODUCTION
Vaccines are one of the most successful public health interventions of all time.
Diseases that once caused significant morbidity and mortality in children are at
all-time lows in the United States. Although many parents and physicians no
longer have personal experiences with vaccine-preventable diseases, they remain
a short plane flight away. The largest measles outbreak in the United States in
more than 20 years occurred in 2014, and most cases occurred in unvaccinated
individuals.* Some were unvaccinated because they were not eligible for
*As of February 13, 2015, the Centers for Disease Control and Prevention reported 141 measles cases for
2015. – Editor-in-Chief
Vol. 36 No. 6 JUNE 2015 227
 vaccination, either due to age or an underlying medical
condition. However, many of these individuals remained
unvaccinated by personal choice.
The first section of this article reviews medical contra-
indications and precautions for childhood immunizations.
This is followed by a discussion of current processes to
ensure vaccine safety in the United States. The final section
summarizes some of the more common myths about vac-
cine safety and discusses strategies to communicate vaccine
safety to families.
The Advisory Committee on Immunization Practices
(ACIP) lists contraindications and precautions for each
vaccine. (1) ACIP defines a contraindication as “a condition
in a recipient that increases the risk for a serious adverse
reaction.” Vaccines should not be administered to individ-
uals with a contraindication for that vaccine. In contrast,
a precaution is “a condition in a recipient that might
increase the risk for a serious adverse reaction or that
might compromise the ability of the vaccine to produce
immunity.” In general, vaccination should be deferred
when a precaution is present. However, in certain circum-
stances, such as an outbreak of a vaccine-preventable
disease to which an individual has a precaution but not
a contraindication, the benefits of vaccination may out-
weigh the risks.
Contraindications are relatively uncommon. We review
two general contraindications in detail:
1) For all vaccines, a severe anaphylactic reaction to a prior
dose of a vaccine or vaccine component.
2) For live viral vaccines, administration to individuals with
a known severe immunodeficiency.
ANAPHYLAXIS
The risk of anaphylaxis after vaccine receipt is very low. A
review of 7.5 million administered vaccine doses from 1991
to 1997 identified only five cases of anaphylaxis for an es-
timated 0.65 cases/1 million doses. More recently, only nine
cases of anaphylaxis were filed with the National Vaccine
Injury Compensation Program between 2000 and 2009.
Even though the absolute risk of anaphylaxis is low, several
individuals each year may have an anaphylactic response to
vaccination because millions of Americans are vaccinated
annually. For this reason, the ACIP recommends that all
vaccines be administered in a facility with the appropriate
equipment and personnel trained to recognize and treat
anaphylaxis.
Many different components of a vaccine can be associ-
ated with an allergic reaction. These include the antigens
themselves, stabilizers, and preservatives. Some of the more
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commonly encountered allergens in vaccines are egg pro-
teins, gelatin, yeast, and latex.
Egg Allergies
Egg proteins are present in vaccines against yellow fever,
influenza, measles-mumps-rubella (MMR), and rabies. Of
these, only yellow fever vaccines have sufficient quantities to
cause clinically significant reactions in most children with
egg allergies. For that reason, children with egg allergy who
require pre-travel vaccination against yellow fever should be
referred to an allergist.
Egg allergy was a contraindication for influenza vaccine
for many years, but this is no longer true. Since 2011, the
ACIP has relaxed recommendations for influenza vaccina-
tion among individuals with egg allergies. (2) The current
guidelines are summarized below and are based on severity
of the allergic response to eggs:
1) Children who can eat lightly cooked (ie, scrambled) eggs
may be vaccinated without any additional precautions.
Note that consumption of baked egg products does not
rule out an egg protein allergy because the heating may
denature proteins.
2) Children who develop hives only (and not cardiovascular,
respiratory, or gastrointestinal symptoms) may be vacci-
nated with inactivated influenza vaccine if they are
observed for at least 30 minutes after vaccination.
3) Children who experience cardiovascular (hypotension),
respiratory (wheezing), or gastrointestinal (nausea/vom-
iting) symptoms or any reaction requiring epinephrine or
emergency medical attention should be referred to an
allergy specialist before vaccination.
Gelatin
Gelatin is used as a stabilizer in several vaccines, including
influenza (Fluzone
[Sanofi Pasteur, Swiftwater, PA] and
FluMist
[MedImmune, Gaithersburg, MD]), MMR, measles-
mumps-rubella-varicella (MMRV), rabies (RabAvert
[Novartis
Vaccines, Cambridge, MA]), typhoid (Vivotif
, Crucell Vac-
cines, Miami Lakes, FL), varicella, and zoster vaccines. Gelatin
is believed to be responsible for most of the reported anaphy-
lactic responses to MMR vaccine. ACIP recommends exer-
cising extreme caution when administering any of these
vaccines to children with a history of anaphylaxis to gelatin
or a gelatin-containing product.
Yeast
Hepatitis B and quadrivalent (but not bivalent) human
papillomavirus (HPV) vaccines include antigens that are
cultured in recombinant Saccharomyces cerevisiae (baker’s
yeast). Although anaphylaxis after receipt of these vaccines
is uncommon, documented allergy to baker’s yeast is a con-
traindication for these two vaccines.
Latex
Some vaccines use latex in vials or syringes. A recent list of
these vaccines is available at http://www.cdc.gov/vaccines/
pubs/pinkbook/downloads/appendices/b/latex-table.pdf
and in each vaccine-specific package insert. In general,
children with severe (anaphylactic) allergy to latex should
not receive vaccines supplied in vials or syringes that contain
natural rubber unless the benefit of vaccination outweighs
the risk. Children with nonanaphylactic reactions may receive
these vaccines.
CONTRAINDICATIONS FOR LIVE VACCINES
Immunocompromised Patients
Data regarding the safety and immunogenicity of vaccines
for children with immune deficiencies are limited. How-
ever, the Infectious Diseases Society of America (IDSA)
guidelines for vaccination of immunocompromised pa-
tients (3) and The American Academy of Pediatrics (AAP)
Red Book offer excellent summaries of the available evi-
dence. (4) Generally, children with immune deficiencies
may safely receive inactivated vaccines. Children with cer-
tain primary immune deficiencies require additional pneu-
mococcal and meningococcal vaccines above and beyond
the routine childhood immunization schedule. Although
live viral vaccines are contraindicated in certain immune
deficiencies, this is not true for every vaccine and every
immune deficiency state. The following section summarizes
general indications for live vaccines. Specific recommenda-
tions for individual patients should be made in conjunction
with a specialist in immunology or infectious diseases.
Primary Immune Deficiencies
Live viral vaccines should be avoided in children with
antibody deficiencies. Safety data are limited in this popula-
tion and live vaccines are unlikely to be immunogenic due to
passive receipt of immune globulin intravenous (IGIV). An
exception is children with isolated immunoglobulin A defi-
ciency, who may receive live vaccines. In general, live vaccines
should also be avoided in children with T-cell deficiencies.
However, children with incomplete DiGeorge syndrome may
receive vaccines if they have adequate immune function. The
IDSA guidelines suggest that live viral vaccines may be
administered to children with DiGeorge syndrome with
CD3 counts of at least 500, CD8 counts of at least 200,
and a normal mitogen response. (3)
Children with phagocyte cell deficiencies (eg, chronic
granulomatous disease, leukocyte adhesion deficiency) may
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receive live viral vaccines, but they should not receive live
bacterial vaccines such as oral typhoid or Bacille Calmette
Guérin. Children with complement deficiencies may receive
live vaccines.
Acquired Conditions
Infants with human immunodeficiency virus (HIV) infec-
tion or perinatal HIV exposure may receive rotavirus vac-
cine. (3) MMR and varicella vaccines may be administered to
children aged 1 through 13 years with CD4þ T-lymphocyte
percentages of 15% or greater and to children at least 14 years
old with absolute CD4 counts of at least 200. However,
children with HIV should not receive live attenuated influ-
enza vaccine (LAIV) or MMRV.
Live viral vaccines should not be administered during
chemotherapy. MMR and varicella vaccines may be admin-
istered 3 months after completion of chemotherapy except
for children who have received anti-B-cell regimens (eg,
rituximab). Vaccinations for these children should be deferred
until 6 months after therapy completion. It is safe to receive
inactivated vaccines during chemotherapy, but these vaccines
generally should not be administered during induction or
consolidation due to concerns about immunogenicity.
Influenza Vaccine
The ACIP publishes recommendations for annual influenza
vaccination each year. For the 2014–2015 season, LAIV is
recommended for healthy children 2 to 8 years of age if
available. (5) Immunocompromised children should not
receive LAIV. In addition, the following groups of children
should not receive LAIV:
1) Children younger than 2 years of age.
2) Children receiving aspirin or aspirin-containing products.
3) Children with egg allergy.
4) Children 2 to 4 years of age with asthma or a documented
episode of wheezing within the previous 12 months.
5) Children receiving influenza-specific antivirals within
48 hours of vaccination.
The presence of asthma in individuals 5 years and older
or any other medical condition that increases the likelihood
of complications after natural influenza infection (eg,
chronic pulmonary, cardiovascular, metabolic, or neurologic
conditions) is a precaution for administering LAIV.
Vaccination of Household Contacts of
Immunocompromised Children
Appropriate vaccination of household contacts is just as
important as vaccine recommendations for the immuno-
compromised children themselves. All household contacts
may receive inactivated vaccines. Household contacts may
also receive age-appropriate MMR, varicella, rotavirus, and
Vol. 36 No. 6 JUNE 2015 229
 zoster vaccines if the contacts are immunocompetent. House-
hold contacts of immunocompromised children may also
receive LAIV with a few exceptions. According to IDSA, LAIV
is contraindicated if:
1) The patient is a stem cell transplant recipient within
2 months after transplant.
2) The patient is a stem cell transplant recipient with graft
versus host disease.
3) The patient has severe combined immune deficiency.
If any of the above criteria are met, inactivated influenza
vaccine should be administered to household contacts. LAIV
may be considered if the vaccine recipient can avoid contact
with the immunocompromised patient for 7 days after
vaccination.
Other Contraindications
In addition to general vaccine contraindication, there are
vaccine- or condition-specific contraindications:
1) No pertussis-containing vaccine should be administered
to a patient who develops encephalopathy with no alter-
native explanation within 7 days of receiving a pertussis-
containing vaccine.
2) No Haemophilus influenzae type b (Hib) vaccine should be
administered to infants younger than 6 weeks of age.
3) No rotavirus vaccine should be administered to children
with severe combined immunodeficiency or a history of
intussusception.
4) No live viral vaccines should be administered during
pregnancy.
PRECAUTIONS FOR CHILDHOOD IMMUNIZATIONS
A full list of precautions is available from the ACIP, (1) but
some of the more common ones are summarized below.
The presence of moderate or severe acute illness with or
without fever is one precaution that applies to all vaccines.
The precaution is not based on a lack of efficacy but because
the expected adverse effects of vaccination might be con-
fused with the natural progression of disease. For example,
if a child with a febrile upper respiratory tract infection is
vaccinated and develops fever the next day, it may be difficult
to differentiate between progression to bacterial otitis, sinus-
itis, or pneumonia and appropriate response to vaccine. On
the one hand, worsening disease progression may be missed.
On the other hand, a clinical change such as a rash may be
falsely attributed to the vaccine when it is, in fact, part of the
natural disease progression. Note that use of antimicrobial
therapy does not preclude vaccination per se. The only time
this is an issue is when a child requires therapy with an agent
that has activity against a specific live vaccine. Thus, children
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receiving an influenza antiviral should not receive LAIV,
children receiving acyclovir should not receive varicella vac-
cine, and children receiving an antibacterial with Gram-
negative activity should not receive oral typhoid vaccine.
The immunogenicity of live viral vaccines may be
affected if they are administered in close succession. LAIV,
MMR, varicella, or zoster vaccines can be administered on
the same day. However, if they are not administered on the
same day, their administration should be separated by at
least 28 days. The immunogenicity of inactivated vaccines is
not affected by concomitant receipt of live viral vaccines.
Another frequently encountered precaution is deferral of
MMR and varicella vaccines in children who have received
antibody-containing products. These include IGIV, disease-
specific antibody, and some blood products. Doses of these
vaccines should be considered invalid if one of the pre-
viously noted antibody-containing products is administered
within 2 weeks after vaccination. The required interval
between antibody-containing products and receipt of live
viral vaccines varies by product and dose (Table 1).
PARENTAL VACCINE HESITANCY
It is equally important to review how pediatricians should
discuss vaccine safety with parents who are concerned about
vaccines and request delay of vaccination. The remainder of
this review focuses on some of the underlying reasons for
parental vaccine hesitancy and strategies and talking points
that may be used to reassure parents.
Perceived Risks of Vaccines
Perhaps the most challenging aspect of effective vaccine risk
communication in 2015 is related to the fact that vaccines
work. Because vaccine-preventable diseases are no longer
prevalent, many parents are not familiar with them and may
not perceive them as dangerous (Figure). At the same time,
vaccines are unique among pharmaceutical agents in that
they are administered to otherwise healthy children to
prevent future disease. In this context, the perceived risks
of vaccination outweigh the actual risks of disease for
some parents, and some opt to delay or avoid vaccines
completely.
When discussing vaccines with parents, it is important to
emphasize that not vaccinating is truly a risk, as evidenced
by the current measles epidemic. In 2014, there were 644
cases of measles in the United States, mostly among unvac-
cinated individuals. This represents the greatest number of
cases in 2 decades. Measles is one of the most contagious
vaccine-preventable diseases and is often the first sign of
waning immunization rates in a community. (1)
 imply causation. Only individuals who were vaccinated and
TABLE 1. Recommended Intervals Between had the event of interest are included. Second, there is no
Antibody-containing Products and denominator that can be used to calculate the incidence of
Measles or Varicella Vaccine adverse effects. Nevertheless, VAERS can quickly identify
potential vaccine-associated adverse events that may be
DISEASE-SPECIFIC IMMUNOGLOBULIN RECOMMENDED
further evaluated using other epidemiologic methods.
(IG) INTERVAL
The VSD partners with nine large managed care organi-
Tetanus IG, hepatitis A IG, hepatitis B IG 3 mo
zations and prospectively collects data on millions of indi-
Rabies IG 4 mo viduals each year. Vaccinations are entered into the medical
Varicella IG, measles IG prophylaxis in 5 mo record as part of routine medical care, and any subsequent
nonimmunocompromised host medical history, including adverse events, can be detected.
Measles IG prophylaxis in 6 mo Unlike VAERS, VSD includes data from vaccinated children
immunocompromised host who did not have an adverse event, which allows for a true
Immunoglobulin Intravenous (IGIV) denominator to calculate the incidence of adverse reactions
Products
after vaccination. Additionally, VSD includes children who
Cytomegalovirus IGIV 6 mo may not have received a certain vaccine. This means that VSD
IGIV replacement therapy for immune 8 mo can also be used to determine the relative risk of an adverse
deficiencies, treatment of immune event by comparing rates in vaccinated individuals to rates in
thrombocytopenia purpura
(400 mg/kg), or varicella prophylaxis unvaccinated individuals. Several of the studies referred to in
this article are based on VSD data.
Treatment of immune thrombocytopenia 10 mo
purpura (1000 mg/kg) Fortunately, most vaccine adverse effects are transient
Kawasaki disease 11 mo and mild. Fever and injection site redness and pain pre-
dominate. Although serious adverse events after vaccination
Blood Transfusions
are rare, parents should be counseled about these potential
Washed red blood cells (RBCs) None occurrences. In 2011, the Institute of Medicine (IOM)
RBCs with adenine-saline added 3 mo published a consensus report on vaccine safety based on
Packed RBCs or whole blood 6 mo a thorough review of thousands of studies. (7) Of 158
potential vaccine adverse events, the IOM found strong
Plasma or platelets 7 mo
evidence of a causal association between vaccines and
Adapted from ACIP(1) and AAP(6) recommendations. 14 specific outcomes. The body of evidence favored accep-
tance of causal association for an additional four outcomes
and favored rejection for five outcomes (Table 2).
Nonetheless, vaccines are not completely without risk. Pre-
licensure randomized, controlled trials provide the strongest
evidence for the incidence of vaccine adverse events. However,
these studies are primarily designed to assess vaccine efficacy or
immunogenicity and may be underpowered for detecting rare
vaccine adverse effects. Following vaccine licensure, monitoring
continues to identify rare adverse events that may only become
evident after a vaccine is introduced at the population level.
These include the Vaccine Adverse Events Reporting System
(VAERS) and the Vaccine Safety Datalink (VSD).
VAERS is a passive postlicensure reporting system main-
tained jointly by the US Food and Drug Administration
(FDA) and the Centers for Disease Control and Prevention.
It allows any individual, including clinicians and parents, to Figure. In the decade before 1963 when a measles vaccine became
report a believed vaccine-associated adverse effect to the available, nearly all children contracted measles by the time they were
15 years old, according to the U.S. Centers for Disease Control and
system. VAERS includes data from the entire country but Prevention. Some 3 to 4 million people in the U.S. were infected each
year, 400 to 500 people died, 48,000 were hospitalized, and 4,000
has several important limitations. First, temporal associa-
suffered encephalitis from measles. This 9-month-old boy with
tion between vaccination and an adverse effect does not a temperature of 40.5°C (105°F) exhibits a significant measles rash.

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 TABLE 2. Evidence for Vaccine Adverse Events and Strength of Association
VACCINE(S) ADVERSE EVENT

Outcomes for which evidence convincingly supports causality

Varicella 1) Disseminated varicella infection (widespread chickenpox rash shortly after vaccination) without
other organ involvement
2) In individuals with immunodeficiency, disseminated varicella infection with subsequent
infection resulting in pneumonia, meningitis, or hepatitis
3) Vaccine strain viral reactivation (appearance of chickenpox rash months to years after
vaccination) without other organ involvement
4) Vaccine strain viral reactivation with subsequent infection resulting in meningitis or encephalitis
(inflammation of the brain)
5) Anaphylaxis
Measles-mumps-rubella (MMR) 1) In individuals with immunodeficiency, measles inclusion body encephalitis
2) Febrile seizures
3) Anaphylaxis
Influenza Anaphylaxis
Hepatitis B Anaphylaxis
Tetanus toxoid Anaphylaxis
Meningococcal Anaphylaxis
Injection-related events 1) Deltoid bursitis
2) Syncope
Outcomes for which evidence favors causal association
Human papillomavirus Anaphylaxis
MMR Transient arthralgia in women
MMR Transient arthralgia in children
Outcomes for which evidence favors rejection of causal association
MMR Autism
Inactivated influenza 1) Bell’s palsy
2) Exacerbation of asthma or reactive airways disease
MMR Type 1 diabetes
Diphtheria-tetanus Type 1 diabetes
Tetanus toxoid Type 1 diabetes
Acellular pertussis Type 1 diabetes

Adapted from Adverse Effects of Vaccines: Evidence and Causality. (7)

A more recent systematic review included 67 additional
studies not reviewed in the IOM report. (8) These studies
were either published after the IOM report or were inves-
tigations of routine childhood vaccines (hepatitis A, Hib,
inactivated polio vaccine, pneumococcal conjugate vaccine
[PCV13], and rotavirus) that were not considered by the IOM.
This systematic review included five studies of MMR vaccine
that were published after the IOM report. These studies
supported the findings that MMR is associated with febrile
seizures but not with autism. The review also included four
high-quality studies assessing the relationship between vac-
cination and leukemia and found no association. The authors
did find moderate evidence for associations between hepatitis
A vaccine and purpura in children aged 7 to 17 years, mild
gastrointestinal events and febrile seizures after influenza
vaccination, anaphylaxis after meningococcal vaccination in
children allergic to the ingredients, febrile seizures after
PCV13 (especially when coadministered with influenza vac-
cine), intussusception with rotavirus vaccines, and purpura
and varicella vaccine in children aged 11 to 17 years.
Although the clinician should acknowledge these potential
vaccine adverse effects, he or she must put their incidence into
context. The authors noted that the several identified vaccine
adverse events were extremely rare, especially when the

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epidemiology of natural disease is considered. Worldwide, there The report included 12 children, all of whom had inflam-
are 20 million cases of measles and 164,000 deaths each year matory bowel disease and eight of whom had autism. This
and the rate of adverse outcomes after natural infection is high. study had significant flaws, most notably that case reports do
Approximately 1 in 10 children with measles also gets an ear not offer strong proof of causal association. Furthermore,
infection and up to 1 in 20 develops pneumonia. About 1 in history of MMR receipt was based on parental recall.
1,000 contracts encephalitis and 1 or 2 in 1,000 die. By Because these parents believed that MMR was responsible
comparison, the risk of MMR-associated immune thrombocy- for their children’s autism, it is not surprising that they
topenia purpura is approximately 1 in 40,000 doses and is reported a temporal association between MMR vaccination
transient. Thus, when compared to the risks associated with and the development of autistic symptoms. There are also
natural disease, vaccines emerge as the clear choice. ethical concerns about this study based on its funding and
the fact that patients were not randomly enrolled. Because of
Cause or Coincidence
these ethical concerns, Lancet retracted the article in 2010.
Fortunately, the number of children who have not received
Before retraction, the study received substantial media
any vaccines has remained below 1% for the past decade,
attention, and rates of MMR vaccination significantly decreased
which is reassuring. On the other hand, any adverse health
in the United Kingdom, where the study was published, and to
outcome that occurs in the first 2 years of a child’s life most
a much lesser extent in the United States. The MMR-autism
likely will occur in a child who is vaccinated. Parents must be
hypothesis has never been confirmed. Many large epidemio-
reminded that temporal association between vaccination
logic studies that included hundreds of thousands of children
and an adverse event does not mean that the association
have failed to identify an association between MMR and autism.
is causal. This is particularly true for chronic diseases of
In 2001, the IOM concluded there was no association between
uncertain cause, such as autism, that are diagnosed at the
MMR and autism and reaffirmed this in 2004 and 2011.
same age as many childhood vaccines are administered.
The mercury-containing vaccine preservative thimerosal
has also been suggested to be linked to autism. This is based
The Internet
on an FDA report from 1999 suggesting that the concen-
Although the media perpetuates vaccine safety myths, the
trations of ethylmercury, a thimerosal metabolite, exceeded
primary source of information for many parents is the
acceptable levels as determined by the Environmental Pro-
Internet. Nearly 90% of United States adults report using
tection Agency (EPA). However, the EPA recommendations
the Internet, with even higher rates among young adults with
are based on data for methylmercury, a common environ-
college degrees. Several studies have demonstrated a growing
mental toxin. In contrast, thimerosal is metabolized to ethyl-
prevalence of vaccine misinformation on the Internet, in
mercury, which is excreted much more quickly and has not
large part due to antivaccine advocacy websites that are often
been associated with neurodevelopmental delay. Nevertheless,
linked to each other. A simple Internet search is more likely to
because of the theoretical concern of thimerosal in childhood
lead to misinformation than reliable evidence-based facts
vaccines, it has been removed from all childhood vaccines,
about vaccines. Social media sites are also filled with personal
except some influenza vaccines, for more than a decade. This
anecdotes of alleged vaccine injuries.
has not had an impact on rates of autism. Since then, multiple
The Internet does contain many excellent evidence-based
large epidemiologic studies have confirmed that thimerosal
resources for both physicians and parents. However, distin-
exposure is not associated with autism. Despite these reassur-
guishing between reliable and unreliable Internet sites can be
ing data, some parents still have concerns about thimerosal in
difficult for parents. Table 3 lists websites that offer accurate,
influenza vaccines. For these parents, LAIV, which is recom-
science-based information about vaccines and vaccine safety.
mended for children as noted previously, or single-use vials
Many of these websites have ready-to-print materials for
that do not contain thimerosal may be used.
families that can be handed out in the office. For parents
who would like to conduct their own searches, the AAP offers
resources for evaluating vaccine websites: http://www2.aap.
Alternative Schedules
org/immunization/families/evaluatingwebinfo.html. A newer parental concern relates to the safety of the immu-
nization schedule. A study published a decade ago found
that nearly 25% of parents were concerned that children
SPECIFIC VACCINE SAFETY CONCERNS
receive too many vaccines and that these vaccines may over-
Vaccines and Autism whelm the developing immune system. Since that time, the
The putative association between MMR and autism was first immunization schedule has become even more crowded,
reported in 1998 in a small case series published in Lancet. with new vaccines against rotavirus, pneumococcal disease,

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 TABLE 3. Organizations Offering Credible Information About Vaccines
and Vaccine Safety
ORGANIZATION URL

Professional
American Academy of Family Physicians (AAFP) http://www.aafp.org
American Academy of Pediatrics (AAP) http://www.cispimmunize.org
Association for Prevention Teaching and Research (APTR) (formerly the Association http://www.atpm.org
of Teachers of Preventive Medicine)
Centers for Disease Control and Prevention http://www.cdc.gov/vaccines
Infectious Diseases Society of America (IDSA) http://www.idsociety.org
Pediatric Infectious Diseases Society (PIDS) http://www.pids.org
Advocacy and Safety Assessment
Allied Vaccine Group http://www.vaccine.org
Children’s Hospital of Philadelphia Vaccine Education Center http://vec.chop.edu/service/vaccine-education-center
Every Child by Two (ECBT) http://www.ecbt.org
Global Alliance for Vaccines and Immunization (GAVI) http://www.gavialliance.org
Immunization Action Coalition (IAC) http://www.immunize.org
Institute for Vaccine Safety, Johns Hopkins Bloomberg School of Public Health http://www.vaccinesafety.edu
National Foundation for Infectious Diseases (NFID) http://www.nfid.org
Sabin Vaccine Institute (SVI) http://www.sabin.org
For Parents
Children’s Hospital of Philadelphia Vaccine Education Center http://vec.chop.edu/service/vaccine-education-center
Immunization Action Coalition (IAC) http://www.vaccineinformation.org
National Network for Immunization Information (NNii) http://www.immunizationinfo.org
Parents of Kids with Infectious Diseases (PKID) http://www.pkids.org
Vaccinate Your Baby http://www.vaccinateyourbaby.com
Voices for Vaccines http://www.voicesforvaccines.org

and hepatitis A for young children and meningococcal, HPV,
and tetanus-diphtheria-pertussis (Tdap) vaccines for adoles-
cents. These new vaccines represent a triumph for public
health but may overwhelm some parents and their clinicians.
Several reasons argue against alternative vaccine sched-
ules. First, the current immunization schedule is designed
to protect children against diseases when they are most
susceptible; delay prolongs susceptibility to infection. It is
impossible for parents, pediatricians, or authors of pub-
lished alternative immunization schedules to predict when
a child will come into contact with a vaccine-preventable
disease. Second, the concern that vaccines may overwhelm
the immune system is not science-based. From the moment
of birth, infants are bombarded with microbes from the
maternal genitourinary tract and the environment that
challenge the developing immune system. The additional
antigenic exposure from vaccines pales in comparison. In
fact, the neonatal immune system theoretically could respond
to up to 10,000 vaccines at a time. (9) Furthermore, although
the number of childhood immunizations has increased over
the past 2 decades, the total antigenic burden from vaccines
has decreased, largely due to discontinuation of whole-cell
pertussis vaccines. Finally, several studies have demonstrated
that children who receive their vaccines on time are no more
likely to develop autism or neurodevelopmental delay than
children whose vaccine receipt is delayed.
Human Papillomavirus and Promiscuity
In 2013, 57.3% of girls and 34.6% of boys received at least
one dose of HPV vaccine. Receipt of three vaccines was

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much lower at 37.6% and 13.9%, respectively. Some parents
are concerned that this vaccine leads to sexual promiscuity.
However, a recent review of medical claims of 1,398 adoles-
cent girls found no differences in rates of pregnancy, sexually
transmitted infection testing, diagnosis, or contraceptive
counselling between those who did and did not receive
HPV vaccine. (10) More importantly, thousands of Americans
die each year from HPV-associated cancers. This is nearly
1000 times as many as succumb to meningococcal disease,
yet rates for meningococcal vaccination approach 80%. Once
again, the key point is risk perception; it is critical for
clinicians to frame HPV vaccine as a cancer vaccine and
not just a vaccine against a sexually transmitted disease.
ADDRESSING VACCINE HESITANCY
Recommendations for discussing vaccine safety with con-
cerned parents have been published. (11) The style and
approach needs to be tailored to each individual family.
Some parents may refuse all vaccines, others may have
concerns about specific vaccines, and still others may simply
have a few basic questions. The specific reasons for vaccine
concerns vary widely from parent to parent.
Parents whose primary concern is the number of injec-
tions may be reassured by the use of combination vaccines.
At the 2-month health supervision visit, for example, chil-
dren receive vaccines against seven diseases: diphtheria,
tetanus, pertussis, polio, pneumococcus, Hib, and rotavirus.
One is an oral vaccine, and one is combination vaccine that
includes all of the other components except PCV. Framing
this encounter as “two injections and a drink” may be more
effective than “immunization against seven diseases.”
Other parents may be worried that multiple injections at the
same visit may cause excessive pain, and they wonder
whether this could be reduced by spreading the injections
out across several visits. Spacing out vaccines over two or
three visits may actually lead to more stressful stimuli in
addition to the inconvenience of extra visits to the office.
Clinicians should be familiar with strategies that have been
shown to reduce immunization pain. (12) These include use
of sucrose in children and young infants and age-appropriate
distraction techniques such as storytelling and blowing for
older children.
Some parents may object to vaccines on religious grounds.
For example, cells originally obtained from aborted fetuses
are used in certain vaccines, most notably rubella. It is
important to remind parents that these fetuses were not
aborted for the purpose of creating these vaccines. Indeed,
the Catholic Church has concluded that Catholics may receive
these vaccines because they do not contribute to current rates
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of abortion and are important for the well-being of children
and the greater public health. Individuals of Islamic and
Jewish faith may have concerns about vaccines containing
gelatin as a stabilizer because it is of porcine origin. However,
because gelatin is cooked and not consumed as food, Muslim
and Jewish scholars have determined that gelatin-containing
vaccines are acceptable. (13)
Finally, some parents may have concerns about vaccine
mandates. For these parents, emphasizing the direct benefit
of vaccination to their child, not just to society as a whole,
may be an effective strategy.
How to Deliver the Message?
The best method of communicating with parents who have
concerns about vaccine safety is an area in which further
research is needed. A recent meta-analysis of interventions
to reduce parental vaccine refusal and vaccine hesitancy
only identified 30 studies published between 1990 and
2012. (14) Half of the studies focused on the use of parent-
centered information or education that was primarily
limited to brochures. Easy access to reliable vaccine infor-
mation, such as the websites provided in Table 3, is clearly
important. A promising strategy is to introduce these
materials to parents before the health supervision visit.
This includes venues such as prenatal open houses or
during postpartum visits on the maternity ward. However,
the most critical element in effective vaccine risk com-
munication may be how the message is delivered.
A handful of studies have begun to address this impor-
tant question. Opel and colleagues (15) videotaped interac-
tions between pediatricians and parents, some of whom
were vaccine-hesitant. The authors were particularly inter-
ested in how physicians initiated discussions about vaccines
and how the parents responded. Parental resistance was less
likely when physicians used a presumptive approach; that is,
presuming that the parents would agree with vaccination. In
contrast, when physicians used participatory approaches
that allowed for more parental decision-making, vaccine
resistance was more common. Physician response to paren-
tal vaccine resistance was also documented. Almost 50% of
the initially resistant parents ultimately accepted vaccination
when the physician persisted in recommendations. Of note,
though, only 50% of the physicians followed through with
their initial recommendations when faced with parental
concern.
Numerous studies have shown that a trusting relation-
ship is the single most important element in effective
vaccine risk communication. This is true for all parents
but most especially for those who request exemptions. One
study of parents who were planning on deferring vaccines
Vol. 36 No. 6 JUNE 2015 235
 for their child determined that advice from their pediatri-
cian changed their mind.
What If They Still Say No?
Some physicians may choose to dismiss vaccine-hesitant
families from their practice. The AAP recommends that
clinicians engage in ongoing dialogues with families who
are concerned about vaccine safety. (16) Because dismissing
such patients may result in families seeking care from pro-
viders who do not support routine immunization (who may
not have formal medical training), clinicians should make
their best efforts to engage these families. Furthermore, it is
unethical to dismiss patients actively under one’s care without
a solid transition plan. That said, allowing a child who is not
up-to-date on vaccines to sit in a waiting room clearly places
other patients at risk. During the 2008 measles outbreak in
San Diego, California, four children were exposed to measles
in their pediatrician’s office when an intentionally unvacci-
nated 7-year-old child presented with fever, sore throat, and
a rash. The exposed children included three infants younger
than 1 year of age, one of whom was admitted to the hospital.
If a family refuses one or more vaccines at a given
office visit, consider scheduling a follow-up visit to ad-
minister any remaining vaccines. Clinicians also should
remain up-to-date on the local epidemiology of vaccine-
preventable diseases. For example, the incidence of
pertussis and measles reached historical peaks in the
past 2 years. These outbreaks may convince some vaccine-
hesitant parents to immunize their children. If parents
continue to refuse vaccines, this should be documented
in the medical record. An AAP-approved template is avail-
able online at: http://www.aap.org/en-us/about-the-aap/
Committees-Councils-Sections/Section-on-infectious-
diseases/Documents/RefusaltoVaccinate.pdf.
Summary
• On the basis of first principles, anaphylaxis to a vaccine or
vaccine component is a contraindication to future receipt of that
vaccine. (1)
• On the basis of strong evidence, live viral vaccines should not be
administered to severely immunocompromised children. (1) (3) (4) (7)
• On the basis of some evidence with consensus, children with egg
allergies may receive inactivated influenza vaccine. (2)
• On the basis of strong evidence, neither measles-mumps-rubella
vaccine nor thimerosal causes autism. (7)
• On the basis of some evidence with consensus, alternative
vaccination schedules have no benefit and receipt of human
papillomavirus vaccines does not result in promiscuity. (9) (10)
• On the basis of first principles and consensus, vaccine risk
communication requires a tailored approach to each individual
family. (11) (14) (15) (16)
References for this article are at http://pedsinreview.aappublica-
tions.org/content/36/6/227.full.

Parent Resources from the AAP at HealthyChildren.org

• http://www.healthychildren.org/English/safety-prevention/immunizations/Pages/Vaccine-Safety-The-Facts.aspx
• Spanish: http://www.healthychildren.org/spanish/safety-prevention/immunizations/Paginas/Vaccine-Safety-The-Facts.aspx

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