Vaccine Adverse Events Separating Myth From Reality
Vaccine Adverse Events Separating Myth From Reality
from Reality
JEANNE P. SPENCER, MD; RUTH H. TRONDSEN PAWLOWSKI, MD; and STEPHANIE THOMAS, PharmD
Conemaugh Family Medicine Residency Program, Johnstown, Pennsylvania
Vaccines are one of the most successful medical advances in modern times. Most vaccine-preventable illnesses are
unfamiliar to modern parents. Because of this, parents are increasingly questioning the necessity of immunizing
their children, especially because no vaccine is completely free of adverse effects or the risk of complications. Family
physicians should be aware of the risks and benefits of recommended immunizations. Thimerosal is currently used
only in multidose vials of influenza vaccine, and exposure through vaccines is not associated with adverse neurologic
outcomes. The measles, mumps, and rubella vaccine is not associated with autism. Vaccines are associated with local
reactions, such as pain and erythema. The rotavirus vaccine minimally increases the rate of intussusception, whereas
other vaccines minimally increase the risk of syncope. Although immunization with the human papillomavirus vac-
cine is recommended for all boys and girls, vaccination rates remain low. Physicians should guide parents to credible
resources if they are considering vaccine refusal. If a recommended vaccine is refused, proper documentation is essen-
tial. The Vaccine Adverse Event Reporting System and National Vaccine Injury Compensation Program track adverse
events and allow compensation for documented harms from vaccinations. (Am Fam Physician. 2017;95(12):786-794.
Copyright © 2017 American Academy of Family Physicians.)
W
See related editorial ith the success of vacci- fever and injection site reactions compared
▲
at http://www.aafp.org/ nations, many parents no with the first dose (one in four children).2
afp/2016/0715/p94.html.
longer have contact with One out of 30 children reports up to seven
CME This clinical content
children who have vaccine- days of swelling of the entire thigh or upper
conforms to AAFP criteria
preventable illnesses. Because of this, par- arm after the fourth or fifth dose.2 Syncope
for continuing medical
education (CME). See ents have difficulty balancing the potential may occur—especially in adolescents—after
CME Quiz on page 764. harms and benefits of vaccines. Some parents administration of the human papillomavirus
Author disclosure: No rel- express concern that physicians are not well (HPV) vaccine; quadrivalent meningococcal
evant financial affiliations.
educated on the adverse effects of vaccines or conjugate vaccine (MCV4); or tetanus toxoid,
Patient information: that physicians purposefully withhold infor- reduced diphtheria toxoid, and acellular per-
▲
A handout on this topic, mation on adverse effects.1 Parents may seek tussis (Tdap) vaccine.4 Because of this, ado-
written by the authors of
this article, is available out additional information from websites lescents should be observed for 15 minutes
at http://www.aafp.org/ containing inaccurate information. Family after receiving these vaccines.2,5 Administra-
afp/2017/0615/p786-s1. physicians should gather accurate informa- tion of acetaminophen at the time of vaccina-
html.
tion about the harms and benefits of vaccines tion or shortly afterward may alleviate some
to advocate for vaccination and decrease the adverse effects, but there may be a decreased
incidence of vaccine-preventable diseases. antibody response to some vaccine antigens
in children who receive antipyretics.6 For
Vaccine Adverse Events this reason and because antipyretics do not
Common local reactions to vaccines include prevent febrile seizures, the Centers for Dis-
pain, swelling, and erythema at the injection ease Control and Prevention (CDC) no lon-
site. Systemic reactions, including fever, irrita- ger recommends routine prophylaxis before
bility, drowsiness, and rash, may also occur.2 vaccination.7
Use of a longer needle (25 mm vs. 16 mm)
decreases injection site reactions.3 The fourth Potential Allergens in Vaccines
dose of the diphtheria and tetanus toxoids Trace amounts of antibiotics, such as neo-
and acellular pertussis (DTaP) vaccine is mycin, are present in varicella; measles,
associated with an increased incidence of mumps, and rubella (MMR); and inactivated
786 American
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Vaccine Adverse Events
Diphtheria and tetanus toxoids and Serious allergic reaction12-14 1 per 1,000,000 doses13 Infanrix syringe contains latex11
acellular pertussis (DTaP)
Measles, mumps, and rubella Immune thrombocytopenic 1 per 20,000 doses19,20 Contains neomycin and gelatin8
purpura14-18
Serious allergic reaction14-19,21 < 1 per 1,000,000 doses19,22,23
Measles, mumps, rubella, and varicella Febrile seizure14,15,17-21,24 8.5 per 10,000 doses20 Contains neomycin and gelatin8
June 15, 2017 ◆ Volume 95, Number 12 www.aafp.org/afp American Family Physician 787
Vaccine Adverse Events
Table 2. Statistics on Measles, Mumps, Rubella, and the MMR Vaccine
Highest number of 894,134 cases (1941)39 152,209 cases 12 million cases (1964 to 1965); —
U.S. cases (1968) 40 57,686 cases (1969) 41
Congenital rubella: 20,000
cases (1964 to 1965) 41
Number of recent 189 cases (2015) 42 1,057 cases 6 cases (2015) 44 None in vaccinated
U.S. cases (2015) 43 Congenital rubella: 4 cases persons 46
(2005 to 2011) 45
Mortality risk 2 deaths per 1,000 None reported22 0% to 50%16 397 cases (according to
measles cases19 Congenital rubella: 0%41 the Vaccine Adverse
Event Reporting System;
unknown number of
vaccinations) 21
Encephalitis risk 1 case per 1,000 1 case per 300 to 1 case per 6,000 rubella cases16 1 case per 3 million
measles cases 19 6,000 mumps vaccinations18
cases 22
Subacute sclerosing 8.5 cases per — Rare16 0 to 0.7 cases per 1 million
panencephalitis risk 1 million measles vaccinations39,49
cases 39
the benefits of immunization and the potential harm of after the recommended age of 12 to 15 months.37,38 The
vaccine refusal. Febrile seizures that occur seven to 10 risk of immune thrombocytopenic purpura is increased
days after the first dose of the MMR vaccine are uncom- after both natural measles infection and for up to six
mon, but the risk is increased when the first dose is given weeks after MMR vaccination (Table 2).16,18,19,21-24,39-51
788 American Family Physician www.aafp.org/afp Volume 95, Number 12 ◆ June 15, 2017
Vaccine Adverse Events
Infection with measles, mumps, or rubella causes more meningococcal vaccines that the FDA approved in 2015.
severe adverse effects than the MMR vaccine, and vac- Previous vaccines against serogroup B meningitis caused
cine refusal has been linked to recent outbreaks of these adverse effects from cross allergenicity with antigens in
infections.45 the human central nervous system.61 The CDC’s Advisory
Committee on Immunization Practices recommends
HPV Vaccine routine use of these vaccines only in high-risk persons
HPV is a sexually transmitted infection that can cause and during outbreaks because of the low prevalence of the
genital warts and anogenital and oropharyngeal can- disease.62 These two meningococcal serogroup B vaccines
cers.52,53 The HPV vaccine has been recommended for are not interchangeable.62
all adolescents since 2011.53 However, as of 2013 only
57.3% of girls and 34.6% of boys had received at least Influenza Vaccine and Guillain-Barré Syndrome
one dose.53 HPV immunization rates are suboptimal The 1976 swine influenza vaccine was associated with a
partly because of unfounded concerns that it encourages four- to eightfold increased risk of Guillain-Barré syn-
sexual activity at a younger age and reduces other pro- drome, or an attributable risk of one case per 100,000
tective behaviors.52,54,55 Although hepatitis B can also be persons vaccinated.57,63 A study of the 2009 influenza
sexually transmitted, this vaccine has had near univer- vaccine did not show a similar association.64 Although
sal uptake. Despite concerns about the safety of the vac- the literature is conflicting, the influenza vaccine may
cine, the most common adverse effects are transient and at worst slightly increase the risk of Guillain-Barré
similar to those of other vaccines, such as mild pain and syndrome: one hospital admission per 1 million vacci-
bruising at the injection site, headache, lightheadedness, nations, or one additional case per 1.25 million vaccina-
and syncope.53,56,57 tions.57,63,65 Studies suggest that influenza infection has a
stronger association with Guillain-Barré syndrome than
Rotavirus Vaccine does the vaccine, so vaccination may actually decrease
The first rotavirus vaccine licensed in the United States the overall incidence.57,63
was withdrawn because of an increased incidence of
intussusception. Children who have received the newer Varicella and Zoster Vaccines
vaccines have only a slightly increased risk of intus- Before routine vaccination, wild-type varicella caused
susception compared with unvaccinated infants and a approximately 10,000 hospitalizations and 100 deaths
lower risk compared to those with rotavirus infection. annually.66 All 50 states mandate vaccination of school-
Intussusception occurs during the time of maximum aged children with the varicella vaccine.67 Adverse effects
viral replication after vaccination: three to five days after are generally mild and include erythema and pain at
immunization with the pentavalent vaccine (Rotateq) the injection site (Table 3 14,66,68-76). Local reactions occur
and four to six days after immunization with the mon- in 19% of vaccinated children and 24% of vaccinated
ovalent vaccine (Rotarix).58 The risk of intussusception adolescents and adults (slightly more after the second
is about one event per 100,000 vaccine doses.58 Immu- dose).66 Both the varicella and the zoster vaccines con-
nizing a birth cohort of 4 million children would avert tain the same attenuated Oka varicella strain. A recent
255,000 physician visits, 137,000 visits to the emergency Institute of Medicine report supports a causal relation-
department, and 44,000 hospitalizations, and would ship between varicella vaccination and disseminated
prevent 13 deaths.59 Oka strain varicella-zoster infections such as pneumo-
nia, meningitis, or hepatitis, especially in persons with
Meningococcal Vaccine demonstrated immunodeficiencies.27 Adverse events such
Universal immunization with MCV4 has been recom- as anaphylaxis may be related to sensitivity to vaccine
mended for adolescents since 2005. The initial dose is components (e.g., gelatin) rather than to the attenuated
recommended at 11 to 12 years of age, with a booster at vaccine virus itself. Nearly one in three unvaccinated per-
16 years of age. This vaccine protects against serogroups sons in the United States will develop herpes zoster, and
A, C, W135, and Y. Previous concerns about an increased this risk increases with age.77 In general, zoster vaccine is
risk of Guillain-Barré syndrome associated with the vac- well tolerated. The most common adverse effects are ery-
cine were unfounded.60 The most common adverse effects thema (36%), pain or tenderness (35%), swelling (26%),
are fever, headache, injection site erythema, and dizzi- and itchiness (7%) at the injection site.76 The benefits of
ness. Immunity wanes over time, even after the booster vaccination and rates of adverse events are greater in per-
dose.60 There are now two well-tolerated serogroup B sons 60 to 69 years of age compared with older adults.77
June 15, 2017 ◆ Volume 95, Number 12 www.aafp.org/afp American Family Physician 789
Vaccine Adverse Events
Table 3. Statistics on Varicella and the Varicella Vaccine
Average annual U.S. 4 million cases per year from 1980 to 199014,66 Prevents an estimated 3.5 million cases per year 68
cases
Transmission rate to 90% in susceptible household contacts14,69 Varicella zoster virus was transmitted from vaccine
susceptible contacts 10% to 35% of persons with limited exposure14 recipients with postvaccination rash to 3 household
contacts from 1995 to 200570
Mortality Prevaccine era: 105 deaths per year from 1970 to 2 deaths ever reported from Oka strain of varicella
199469 zoster virus in immunocompromised or likely
Postvaccine era: 17 deaths per year from 2008 to immunocompromised individuals72
201171
Generalized varicella- 100% of persons with varicella14 37 reports of rash from 1995 to 2005, some in
like rash incidence immunocompromised patients 70
Herpes zoster risk (in 230 cases per 100,000 varicella cases in 200874 48 cases per 100,000 vaccinations (2008)74
children younger than
18 years)
Cerebellar ataxia risk 1 case per 4,000 varicella cases in children younger Weak evidence 14
than 15 years14
Encephalitis risk 1.8 cases per 10,000 varicella cases66 12 cases from 1995 to 200570
Pneumonia risk 1 case per 400 varicella cases in adults 75 5 cases ever reported (4 in immunocompromised
children)14
Congenital varicella < 2% risk from primary maternal varicella infection66 0 cases in 87 women vaccinated before or during
syndrome risk 2% of infants 13 to 20 weeks of gestational age pregnancy 76
who have varicella14
Vaccine Refusal
The rate of parental refusal of all or selective Table 4. Credible Immunization Resources for Parents
immunizations is increasing.78 The Ameri-
can Academy of Family Physicians (AAFP) American Academy of Pediatrics
does not support immunization exemption https://www.healthychildren.org/english/safety-prevention/immunizations/
policies except in cases of allergic or medi- pages/default.aspx
cal contraindication.79 Physicians should Centers for Disease Control and Prevention
http://www.cdc.gov/vaccines/vac-gen/default.htm
provide vaccine information statements
Children’s Hospital of Philadelphia
to parents who are considering vaccine
http://www.chop.edu/centers-programs/parents-pack#.VsIAQLQrJmo
refusal or delay and direct them to cred-
Every Child by Two Initiative, Vaccinate Your Family Program
ible sources of information (Table 4).80,81 If http://www.vaccinateyourfamily.org
parents decide against a recommended vac- Immunization Action Coalition
cine, they should sign a refusal to vaccinate http://www.vaccineinformation.org
form, and this declination should be docu-
mented with provision of the vaccine infor- Information from references 80 and 81.
mation statement.82 The American Academy
790 American Family Physician www.aafp.org/afp Volume 95, Number 12 ◆ June 15, 2017
Vaccine Adverse Events
downloads/not-vacc-risks-color-office.pdf).
SORT: KEY RECOMMENDATIONS FOR PRACTICE Physicians should continue to discuss the
benefits of immunizations at subsequent vis-
Evidence
Clinical recommendation rating References its because some parents may reconsider the
decision not to vaccinate, and some simply
A 25-mm needle should be used instead of a A 3 postpone certain vaccinations.
16-mm needle to reduce the risk of adverse
reactions to vaccinations.
Consequences of Failure to Vaccinate
Antipyretics are not recommended for routine A 6, 7
prophylaxis before immunizations. In 2014, there were 667 cases of measles in
The measles, mumps, and rubella vaccine does C 35, 36 the United States, mainly within an unvac-
not increase the risk of autism and should be cinated Amish community.20 In 2012, the
routinely used.
largest U.S. pertussis outbreak since 1955
Parents who refuse a recommended vaccine should C 7, 79, 82
sign a refusal to vaccinate form.
occurred, including 48,277 cases and 20
pertussis-related deaths.86 Pertussis cases
A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited- have been linked to multiple causes, includ-
quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual ing waning immunity to the vaccine and
practice, expert opinion, or case series. For information about the SORT evidence
rating system, go to http://www.aafp.org/afpsort.
children who are unvaccinated under non-
medical exemption.87-89 The choice of some
parents not to immunize increases the infec-
tion risk for all children, including those
who are immunized. Sustained community-
level transmission can occur in the pres-
ence of imperfect vaccine effectiveness and
waning immunity, putting those who are
susceptible—especially young infants and
persons with medical contraindications—at
increased risk.87 In the absence of a direct
threat from disease, it is clear that some
patients and parents will not participate in
vaccination programs unless absolute safety
can be assured. Full vaccination of students
enhances the safety of all, but states vary
in regard to acceptable reasons for parental
Medical and religious exemptions vaccination refusal (Figure 1).90
Medical exemptions only
Medical and personal belief exemptions Vaccine Adverse Event Reporting
System
Figure 1. School vaccine exemption laws.
The FDA and the CDC maintain the Vaccine
Reprinted with permission from Johns Hopkins Bloomberg School of Public Health. School
exemption laws by state. http://www.vaccinesafety.edu/cc-exem.htm. Accessed January 24,
Adverse Event Reporting System (VAERS) as
2017. a postmarketing safety surveillance program
for adverse events that occur after immuni-
of Pediatrics (AAP) has developed a form that can be zation. Vaccine manufacturers and health care profes-
used to document vaccine refusal (http://www.aap.org/ sionals are required to submit potential adverse events.91
en-us/Documents/immunization_ refusaltovaccinate. VAERS receives approximately 30,000 reports each year.
pdf). The CDC recommends against dismissing the The effectiveness of VAERS as an early warning system
patient or family from the practice if they refuse vac- was demonstrated by reports of an increased incidence
cination.83 However, the AAP now accepts this practice of intussusception after immunization with rotavirus
if done in a conscientious way.84,85 vaccine.91 In 1990, the Vaccine Safety Datalink, a col-
The AAFP has collaborated with the CDC and the AAP laboration between the CDC and nine health care orga-
to develop a handout for parents who choose not to vacci- nizations, was developed to investigate rare and serious
nate (http://www.cdc.gov/vaccines/hcp/conversations/ adverse effects reported in the medical literature and to
June 15, 2017 ◆ Volume 95, Number 12 www.aafp.org/afp American Family Physician 791
Vaccine Adverse Events
VAERS. The program monitors vaccine safety when a 4. Slade BA, Leidel L, Vellozzi C, et al. Postlicensure safety surveillance for
quadrivalent human papillomavirus recombinant vaccine. JAMA. 2009;
new vaccine is approved or when there are new vaccine 302(7):750-757.
recommendations.92 5. Centers for Disease Control and Prevention. Fainting (syncope). http:/ /cdc.
gov/vaccinesafety/concerns/fainting.html. Accessed December 21, 2015.
National Vaccine Injury Compensation Program 6. Prymula R, Siegrist CA, Chlibek R, et al. Effect of prophylactic
The National Childhood Vaccine Injury Act of 1986 paracetamol administration at time of vaccination on febrile reactions
and antibody responses in children:two open-label, randomised con-
established the no-fault National Vaccine Injury Com- trolled trials. Lancet. 2009;374(9698):1339-1350.
pensation Program to compensate patients and families 7. National Center for Immunization and Respiratory Diseases. General
injured by recommended vaccines. This law requires recommendations on immunization:recommendations of the Advisory
Committee on Immunization Practices (ACIP) [published correction
physicians who administer vaccines to document the
appears in MMWR Recomm Rep. 2011;60(29):993]. MMWR Recomm
provision of current vaccine information statements Rep. 2011;60(2):1-64.
along with the vaccine manufacturer and lot number. 8. Centers for Disease Control and Prevention. Vaccine excipient and media
The program’s website includes a table of covered vaccine summary. http: / /www.cdc.gov/vaccines/pubs/pinkbook/downloads/
appendices/B/excipient-table-2.pdf. Accessed February 1, 2016.
injuries.93 Injuries outside those listed and suspected to
9. Centers for Disease Control and Prevention. Epidemiology and prevention
be vaccine related can also be compensated but require of vaccine-preventable diseases:general recommendations on immu-
additional evidence. The program is funded by an excise nization. http: / /www.cdc.gov/vaccines/pubs/pinkbook/genrec.html.
tax on vaccines. Accessed February 24, 2016.
10. Immunization Action Coalition. Influenza vaccination of people with
This article updates a previous article on this topic by Kimmel.94 a history of egg allergy. http: / /www.immunize.org/catg.d/p3094.pdf.
Accessed February 24, 2016.
Data Sources: Essential Evidence Plus was searched using the key word
11. Centers for Disease Control and Prevention. Latex in vaccine packaging.
vaccine. PubMed was also searched using the key words vaccine adverse
http:/ /www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/B/
effects and thimerosal. Searches were also performed for individual
latex-table.pdf. Accessed May 18, 2016.
vaccines, and the websites of the Centers for Disease Control and Pre-
vention, the American Academy of Pediatrics, the American Academy of 12. Kelso JM, Greenhawt MJ, Li JT, et al. Adverse reactions to vaccines prac-
tice parameter 2012 update. J Allergy Clin Immunol. 2012;130(1):25-43.
Family Physicians, the Vaccine Adverse Event Reporting System, and the
Health Resources and Services Administration were also searched. Search 13. Centers for Disease Control and Prevention. Vaccine information state-
dates: October 28, 2015, to January 17, 2017. ment. Diphtheria, tetanus, and pertussis (DTaP) vaccine:what you need to
know. http: / /www.cdc.gov/vaccines/hcp/vis/vis-statements/dtap.pdf.
The authors thank Kaitlyn Thomas for assistance with the preparation of Accessed February 23, 2016.
the manuscript. 14. Stratton KR, et al., eds.;Institute of Medicine. Adverse Effects of Vac-
cines:Evidence and Causality. Washington, DC:National Academies
Press; 2012.
The Authors 15. Klein NP, Lewis E, Fireman B, et al. Safety of measles-containing vaccines
JEANNE P. SPENCER, MD, is program director at Conemaugh Family Medi- in 1-year-old children. Pediatrics. 2015;135(2):e321-e329.
cine Residency Program, Johnstown, Pa., and a clinical assistant professor 16. Centers for Disease Control and Prevention. Epidemiology and preven-
of family and community medicine at Drexel University College of Medi- tion of vaccine-preventable diseases:rubella. http:/ /www.cdc.gov/
cine, Philadelphia, Pa. vaccines/pubs/pinkbook/rubella.html. Accessed May 16, 2016.
17. Feibelkorn AP, Goodson JL;Centers for Disease Control and Preven-
RUTH H. TRONDSEN PAWLOWSKI, MD, is an assistant program director at tion. Chapter 3:infectious diseases related to travel. Measles (rubeola).
Conemaugh Family Medicine Residency Program. https: / /wwwnc.cdc.gov/travel/yellowbook/2016/infectious-diseases-
related-to-travel/measles-rubeola. Accessed May 16, 2016.
STEPHANIE THOMAS, PharmD, is an associate director of the pharmacy
residency program at Conemaugh Family Medicine Residency Program. 18. M-M-R II (measles, mumps, and rubella virus vaccine live) [package insert].
https:/ /www.merck.com/product/usa/pi_circulars/m/mmr_ii/mmr_ii_
Address correspondence to Jeanne P. Spencer, MD, Conemaugh Family pi.pdf. Accessed May 16, 2016.
Medicine Residency Program, 1086 Franklin St., Johnstown, PA 15905 19. Centers for Disease Control and Prevention. Epidemiology and preven-
(e-mail: [email protected]). Reprints are not available from the tion of vaccine-preventable diseases:measles. http:/ /www.cdc.gov/
authors. vaccines/pubs/pinkbook/downloads/meas.pdf. Accessed May 16, 2016.
20. Centers for Disease Control and Prevention. Measles, mumps and rubella
(MMR) vaccine safety. http: / /www.cdc.gov/vaccinesafety/vaccines/
REFERENCES mmr-vaccine.html. Accessed May 16, 2016.
1. Glanz JM, Wagner NM, Narwaney KJ, et al. A mixed methods study of 21. National Vaccine Information Center. Can measles vaccine cause injury
parental vaccine decision making and parent-provider trust. Acad Pedi- and death? http:/ /www.nvic.org/vaccines-and-diseases/measles/measles-
atr. 2013;13(5):4 81-488. vaccine-injury-death.aspx. Accessed May 16, 2016.
2. Centers for Disease Control and Prevention. Possible side-effects from 22. Centers for Disease Control and Prevention. Epidemiology and preven-
vaccines. http: / /www.cdc.gov/vaccines/vac-gen/side-effects.htm. tion of vaccine-preventable diseases:mumps. http:/ /www.cdc.gov/
Accessed December 9, 2015. vaccines/pubs/pinkbook/mumps.html. Accessed May 16, 2016.
3. Beirne PV, Hennessy S, Cadogan SL, Shiely F, Fitzgerald T, MacLeod F. 23. Bohlke K, Davis RL, Marcy SM, et al.;Vaccine Safety Datalink Team. Risk
Needle size for vaccination procedures in children and adolescents. of anaphylaxis after vaccination of children and adolescents. Pediatrics.
Cochrane Database Syst Rev. 2015;( 6):CD010720. 2003;112(4):815-820.
792 American Family Physician www.aafp.org/afp Volume 95, Number 12 ◆ June 15, 2017
Vaccine Adverse Events
24. Centers for Disease Control and Prevention. Vaccine safety:VSD MMRV 43. Centers for Disease Control and Prevention. Mumps cases and outbreaks.
safety study. http: / /www.cdc.gov/vaccinesafety/vaccines/mmrv/vsd- http: / /www.cdc.gov/mumps/outbreaks.html. Accessed May 16, 2016.
mmrv-safety-study.html. Accessed February 23, 2016. 4 4. Centers for Disease Control and Prevention. Notice to readers:final
25. Centers for Disease Control and Prevention. Vaccine information
2013 reports of nationally notifiable infectious diseases. MMWR Morb
statement. Meningococcal ACWY vaccines–MenACWY and MPSV4: Mortal Wkly Rep. 2014;63(32):702.
what you need to know. http: / /www.cdc.gov/vaccines/hcp/vis/ 45. Centers for Disease Control and Prevention. Manual for the surveillance of
vis-statements/mening.pdf. Accessed February 23, 2016. vaccine-preventable diseases:chapter 15:congenital rubella syndrome.
26. Centers for Disease Control and Prevention. Vaccine information state- http: / /www.cdc.gov/vaccines /pubs /surv-manual /chpt15-crs.html.
ment. Rotavirus vaccine:what you need to know. http:/ /www.cdc.gov/ Accessed May 16, 2016.
vaccines/hcp/vis/vis-statements/rotavirus.pdf. Accessed February 23, 4 6. McLean HQ, Fiebelkorn AP, Temte JL, Wallace GS;Centers for Disease
2016. Control and Prevention. Prevention of measles, rubella, congenital
27. Institute of Medicine. The Childhood Immunization Schedule and
rubella syndrome, and mumps, 2013:summary recommendations of
Safety:Stakeholder Concerns, Scientific Evidence, and Future Studies. the Advisory Committee on Immunization Practices (ACIP). MMWR
Washington, DC:National Academies Press;2013. Recomm Rep. 2013;62(RR-04):1-34.
28. Centers for Disease Control and Prevention, Advisory Committee on 47. Centers for Disease Control and Prevention. Transmission of measles.
Immunization Practices. Recommended immunization schedules for http: / /www.cdc.gov/measles/about/transmission.html. Accessed May
persons aged 0 through 18 years, United States, 2016. http:/ /www. 17, 2016.
cdc.gov/vaccines/schedules/downloads/child/0-18yrs-child-combined-
4 8. Minnesota Department of Health. Rubella clinical information. http: / /
schedule.pdf. Accessed May 17, 2016.
www.health.state.mn.us/divs/idepc/diseases/rubella/hcp/clinical.html.
29. Grohskopf L;Centers for Disease Control and Prevention, Advisory
Accessed May 17, 2016.
Committee on Immunization Practices. Proposed recommenda-
49. Patja A, Davidkin I, Kurki T, Kallio MJ, Valle M, Peltola H. Serious adverse
tions 2016-17 influenza season. http: / /www.cdc.gov/vaccines/acip/
events after measles-mumps-rubella vaccination during a fourteen-year
meetings/downloads/slides-2016-02/flu-04-grohskopf.pdf. Accessed
prospective follow-up. Pediatr Infect Dis J. 2000;19(12):1127-1134.
May 17, 2016.
50. Centers for Disease Control and Prevention. Measles (rubeola):compli-
30. Ball LK, Ball R, Pratt RD. An assessment of thimerosal use in childhood
cations of measles. http: / /www.cdc.gov/measles/about/complications.
vaccines. Pediatrics. 2001;107(5):1147-1154.
html. Accessed May 17, 2016.
31. Thompson WW, Price C, Goodson B, et al.;Vaccine Safety Datalink
51. Centers for Disease Control and Prevention. Mumps:for healthcare pro-
Team. Early thimerosal exposure and neuropsychological outcomes at
viders. http: / /www.cdc.gov/mumps/hcp.html. Accessed June 22, 2016.
7 to 10 years. N Engl J Med. 2007;357(13):1281-1292.
52. Zimet GD, Rosberger Z, Fisher WA, Perez S, Stupiansky NW. Beliefs,
32. Price CS, Thompson WW, Goodson B, et al. Prenatal and infant expo-
behaviors and HPV vaccine:correcting the myths and the misinforma-
sure to thimerosal from vaccines and immunoglobulins and risk of
tion. Prev Med. 2013;57(5):414-418.
autism. Pediatrics. 2010;126(4):656-664.
53. Stokley S, Jeyarajah J, Yankey D, et al.;Immunization Services Division,
33. U.S. Food and Drug Administration. Vaccines, blood and biologics:thi-
National Center for Immunization and Respiratory Diseases;Centers
merosal in vaccines. http:/ /www.fda.gov/BiologicsBloodVaccines/Safety
for Disease Control and Prevention (CDC). Human papillomavirus vac-
Availability/VaccineSafety/UCM096228. Accessed February 24, 2016.
cination coverage among adolescents, 2007-2013, and postlicensure
34. Mitkus RJ, King DB, Walderhaug MO, Forshee RA. A comparative phar- vaccine safety monitoring, 2006-2014—United States. MMWR Morb
macokinetic estimate of mercury in U.S. infants following yearly expo- Mortal Wkly Rep. 2014;63(29):620-624.
sures to inactivated influenza vaccines containing thimerosal. Risk Anal.
2014;34(4):735-750. 54. Mapes D. It’s not about sex, it’s about cancer. http:/ /www.fredhutch.org/
en/news/center-news/2015/02/HPV-vaccine-not-increase-promiscuity.
35. Godlee F, Smith J, Marcovitch H. Wakefield’s article linking MMR vac-
html. Accessed May 29, 2016.
cine and autism was fraudulent. BMJ. 2011;342:d1678.
55. Muncie HL Jr, LaBato AL. HPV vaccination:overcoming parental and
36. Taylor B, Miller E, Farrington CP, et al. Autism and measles, mumps, and
physician impediments. Am Fam Physician. 2015;92(6):4 49-454.
rubella vaccine:no epidemiological evidence for a causal association.
Lancet. 1999;353(9169):2026-2029. 56. Giacomet V, Penagini F, Trabattoni D, et al. Safety and immunogenic-
ity of a quadrivalent human papillomavirus vaccine in HIV-infected and
37. Rowhani-Rahbar A, Fireman B, Lewis E, et al. Effect of age on the risk
HIV-negative adolescents and young adults. Vaccine. 2014;32(43):
of fever and seizures following immunization with measles-containing
5657-5661.
vaccines in children. JAMA Pediatr. 2013;167(12):1111-1117.
57. Miller ER, Moro PL, Cano M, Shimabukuro TT. Deaths following vaccina-
38. Marin M, Broder KR, Temte JL, Snider DE, Seward JF;Centers for Disease
tion:what does the evidence show? Vaccine. 2015;33(29):3288-3292.
Control and Prevention (CDC). Use of combination measles, mumps,
rubella, and varicella vaccine:recommendations of the Advisory Com- 58. Haber P, Patel M, Pan Y, et al. Intussusception after rotavirus vaccines
mittee on Immunization Practices (ACIP). MMWR Recomm Rep. 2010; reported to US VAERS, 2006-2012. Pediatrics. 2013;131(6):1042-1049.
59(RR-3):1-12. 59. Cortese MM, Parashar UD;Centers for Disease Control and Prevention
39. Maldonado Y. Measles. In:Behrman RE, Kliegman RM, Jenson HB, eds. (CDC). Prevention of rotavirus gastroenteritis among infants and chil-
Nelson Textbook of Pediatrics. 16th ed. Philadelphia, Pa.:Saunders;2000: dren:recommendations of the Advisory Committee on Immunization
946-951. Practices (ACIP). MMWR Recomm Rep. 2009;58(RR-2):1-25.
40. Maldonado Y. Mumps. In:Behrman RE, Kliegman RM, Jenson HB, eds. 60. Cohn AC, MacNeil JR, Clark TA, et al.;Centers for Disease Control and
Nelson Textbook of Pediatrics. 16th ed. Philadelphia, Pa.:Saunders;2000: Prevention (CDC). Prevention and control of meningococcal disease:
954-955. recommendations of the Advisory Committee on Immunization Prac-
41. Maldonado Y. Rubella. In:Behrman RE, Kliegman RM, Jenson HB, eds. tices (ACIP). MMWR Recomm Rep. 2013;62(RR-2):1-28.
Nelson Textbook of Pediatrics. 16th ed. Philadelphia, Pa.:Saunders;2000: 61. Leca M, Bornet C, Montana M, Curti C, Vanelle P. Meningococcal vac-
951-954. cines:current state and future outlook. Pathol Biol (Paris). 2015;63(3):
42. Centers for Disease Control and Prevention. Measles cases and out- 144-151.
breaks. http: / /www.cdc.gov/measles/cases-outbreaks.html. Accessed 62. Centers for Disease Control and Prevention. Vaccine information state-
February 24, 2016. ments (VISs):serogroup B meningococcal (MenB) VIS. http:/ /www.cdc.
June 15, 2017 ◆ Volume 95, Number 12 www.aafp.org/afp American Family Physician 793
Vaccine Adverse Events
gov/vaccines/hcp/vis/vis-statements/mening-serogroup.html. Accessed 78. Flanagan-Klygis EA, Sharp L, Frader JE. Dismissing the family who
June 23, 2016. refuses vaccines:a study of pediatrician attitudes. Arch Pediatr Adolesc
63. Kwong JC, Vasa PP, Campitelli MA, et al. Risk of Guillain-Barré syndrome Med. 2005;159(10):929-934.
after seasonal influenza vaccination and influenza health-care encoun- 79. American Academy of Family Physicians. Immunization exemptions.
ters: a self-controlled study. Lancet Infect Dis. 2013;13(9):769-776. http: / /www.aafp.org/about/policies/all/immunizations-exemptions.
6 4. Dieleman J, Romio S, Johansen K, Weibel D, Bonhoeffer J, Sturkenboom M; html. Accessed June 20, 2016.
VAESCO-GBS Case-Control Study Group. Guillain-Barré syndrome and 8 0. Immunization Action Coalition. Reliable sources of immunization informa-
adjuvanted pandemic influenza A (H1N1) 2009 vaccine:multinational tion:where parents can go to find answers! http: / /www.immunize.org/
case-control study in Europe. BMJ. 2011;343:d3908. atg.d/p4012.pdf. Accessed February 23, 2016.
65. Centers for Disease Control and Prevention (CDC). Preliminary results: 81. Centers for Disease Control and Prevention. Provider resources for vac-
surveillance for Guillain-Barré syndrome after receipt of influenza A cine conversations with parents. http: / /www.cdc.gov/vaccines/hcp/
(H1N1) 2009 monovalent vaccine—United States, 2009-2010. MMWR conversations/conv-materials.html. Accessed February 23, 2016.
Morb Mortal Wkly Rep. 2010;59(21):657-661. 82. American Academy of Pediatrics. Documenting refusal to vaccinate. http://
66. Centers for Disease Control and Prevention. Epidemiology and preven- www.aap.org/en-us/Documents/immunization_refusaltovaccinate.pdf.
tion of vaccine-preventable diseases:varicella. http:/ /www.cdc.gov/ Accessed February 25, 2016.
vaccines/pubs/pinkbook/varicella.html. Accessed June 20, 2016.
83. National Center for Immunization and Respiratory Diseases. General
67. Immunization Action Coalition. Varicella mandates for school and child recommendations on immunization:recommendations of the Advisory
care. http: / /www.immunize.org/laws/varicella.asp. Accessed December Committee on Immunization Practices (ACIP) [published correction
9, 2015. appears in MMWR Recomm Rep. 2011;60:993]. MMWR Recomm Rep.
68. Centers for Disease Control and Prevention. Chickenpox (varicella):monitor- 2011;60(2):1-64.
ing the impact of varicella vaccination. http:/ /www.cdc.gov/chickenpox/ 8 4. American Academy of Pediatrics. Reaffirmation:responding to parents
surveillance/monitoring-varicella.html. Accessed May 13, 2016. who refuse immunization for their children. Pediatrics. 2013;131:e1696.
69. Marin M, Güris D, Chaves SS, Schmid S, Seward JF;Advisory Committee 85. Edwards KM, Hackell JM;Committee on Infectious Diseases, Committee
on Immunization Practices, Centers for Disease Control and Prevention on Practice and Ambulatory Medicine. Countering vaccine hesitancy.
(CDC). Prevention of varicella. recommendations of the Advisory Com- Pediatrics. Published online ahead of print August 25, 2016. http://
mittee on Immunization Practices (ACIP). MMWR Recomm Rep. 2007; pediatrics.aappublications.org/content/early/2016/08/25/peds.2016-
56(RR-4):1-40. 2146. Accessed January 24, 2017.
70. Galea SA, Sweet A, Beninger P, et al. The safety profile of varicella vac-
86. Atwell JE, Salmon DA. Pertussis resurgence and vaccine uptake:implica-
cine: a 10-year review. J Infect Dis. 2008;197(suppl 2):S165-S169.
tions for reducing vaccine hesitancy. Pediatrics. 2014;134(3):602-604.
71. Leung J, Bialek SR, Marin M. Trends in varicella mortality in the United
87. Atwell JE, Van Otterloo J, Zipprich J, et al. Nonmedical vaccine exemp-
States:data from vital statistics and the national surveillance system.
tions and pertussis in California, 2010. Pediatrics. 2013;132(4):624-630.
Hum Vaccin Immmunother. 2015;11(3):662-668.
8 8. Davis MM. Toward high-reliability vaccination efforts in the United
72. Leung J, Siegel S, Jones JF, et al. Fatal varicella due to the vaccine-strain
States. JAMA. 2016;315(11):1115-1117.
varicella-zoster virus. Hum Vaccin Immunother. 2014;10(1):146-149.
89. California Legislative Information. Senate bill no. 277:public health:vacci-
73. Chaves SS, Haber P, Walton K, et al. Safety of varicella vaccine after
nations (2015-2016). http:/ /leginfo.legislature.ca.gov/faces/billNavClient.
licensure in the United States:experience from reports to the Vac-
xhtml?bill_id=201520160SB277. Accessed June 7, 2016.
cine Adverse Event Reporting System, 1995-2005. J Infect Dis. 2008;
197(suppl 2):S170-S177. 9 0. Johns Hopkins Bloomberg School of Public Health. School exemption
laws by state. http:/ /www.vaccinesafety.edu/cc-exem.htm. Accessed
74. Weinmann S, Chun C, Schmid DS, et al. Incidence and clinical charac-
January 24, 2017.
teristics of herpes zoster among children in the varicella vaccine era,
2005-2009. J Infect Dis. 2013;208(11):1859-1868. 91. Centers for Disease Control and Prevention. Vaccine safety:vaccine
75. Whitley RJ. Varicella-zoster virus. In:Mandell GL, Douglas RG, Bennett safety datalink (VSD). http:/ /www.cdc.gov/vaccinesafety/ensuring
JE, Dolin R, eds. Mandell, Douglas, and Bennett’s Principles and Practice safety/monitoring/vsd/index.html. Accessed January 11, 2016.
of Infectious Diseases. 5th ed. Philadelphia, Pa.:Churchill Livingstone; 92. Health Resources and Services Administration. National vaccine injury
2000:1580-1586. compensation program. http: / /www.hrsa.gov/vaccinecompensation/
76. Wise RP, Salive ME, Braun MM, et al. Postlicensure safety surveillance vaccinetable.html. Accessed February 23, 2016.
for varicella vaccine [published correction appears in JAMA. 2000; 93. Health Resources and Services Administration. Vaccine injury table.
284(24):3129]. JAMA. 2000;284(10):1271-1279. http: / /www.hrsa.gov/vaccinecompensation/vaccineinjurytable.pdf.
77. Gagliardi AM, Gomes Silva BN, Torloni MR, Soares BG. Vaccines for Accessed February 25, 2016.
preventing herpes zoster in older adults. Cochrane Database Syst Rev. 94. Kimmel SR. Vaccine adverse events:separating myth from reality. Am
2012;(10):CD008858. Fam Physician. 2002;66(11):2113-2121.
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