13-561 - CTP - Module - 3FINAL 022514

2014 APhA Pharmacy-Based
IMMUNIZATION DELIVERY
APhA Pharmacy-Based
A National Certificate Training Program
Module 3. Vaccine-Preventable Diseases
13-561
2014, American Pharmacists Association. All rights reserved.
Learning Objectives
At the completion of this activity, participants will be able to:
1. D
escribe the epidemiology, clinical features, and
potential complications of diseases that can be
prevented with vaccines.
2. Identify vaccines available in the U.S. market for
each vaccine-preventable disease and describe their
features.
3. IIdentify the contraindications and precautions for the
use of vaccines available in the United States.
4. IUse recommendations from the Advisory Committee
on Immunization Practices to identify target groups
for receipt of each vaccine.
Introduction
To prepare pharmacists for vaccine delivery, this module

reviews the most common vaccine-preventable diseases and
the vaccines used to prevent them. The discussion includes the
epidemiology, clinical features, and potential complications
of each disease, vaccine indications and contraindications,
vaccine dosage and administration information, and important
vaccine-related adverse effects. The vaccine-preventable
diseases are presented here in the order in which they
appear in the 2013 adult immunization schedule, followed by
vaccines that appear only on the childhood and adolescent
immunization schedule. This module concludes with a brief
discussion of vaccines that do not appear on these schedules,
including vaccines for rabies, international travel, and acts of
bioterrorism, and a look at the development of future vaccines.
Influenza
Influenza is a highly infectious respiratory illness caused by

a virus of the orthomyxovirus family.1 The influenza virus is
primarily spread by aerosolized respiratory droplets from a
cough or sneeze (Figure 3.1). The virus also can be spread
when a person has direct contact with infected droplets from
nasal secretions or saliva from an infected person.
Clinical Features and Potential Complications
The incubation period for influenza can range from 1 to 4

days.1,2 The onset of symptoms is usually abrupt with a high
fever over 38C (101F), nonproductive cough, sore throat,
and muscle aches. Patients also may complain of fatigue,
headache, or a runny nose. People infected with influenza
virus may be contagious beginning 1 day before their
symptoms develop and up to 5 to 7 days after becoming
sick.3
Uncomplicated influenza usually resolves after 3 to 7 days
for the majority of patients. However, in some patients,
influenza is associated with complications that result
in significant morbidity and mortality.4-6 Influenza can
exacerbate underlying medical conditions (e.g., chronic
pulmonary disease, cardiac disease, diabetes). Influenza also
can be associated with secondary bacterial infections (e.g.,
pneumococcal pneumonia, sinusitis, otitis media). The risk
for complications, hospitalization, or death from influenza is
usually higher in patients with underlying medical conditions,
pregnant women, young children, and elderly adults.
Influenza is also an important cause of illness among young,
otherwise healthy adults. In one analysis, it was estimated that
Figure 3.1. Spray of Respiratory Droplets During a Sneeze
Immunization schedules are available online at www.cdc.gov/

vaccines/schedules. Additional information about applying
information in these schedules to practice will be discussed in
Module 4 and the live training seminar.
The material provided in this self-study module is based on the
most up-to-date information available at the time of publication
of the certificate training program. However, the practice of
immunizations changes frequently and it is vital that pharmacists
always check for updates and refer to the current recommendations from the Advisory Committee on Immunization Practices
(ACIP) at the time of providing patient care.
Photo courtesy of CDC Public Health Image Library: Image ID 11161.
the annual burden of influenza among adults 18 to 49 years

of age without high-risk conditions included 5 million illnesses,
2.4 million outpatient visits, 32,000 hospitalizations, and 680
deaths.7 Furthermore, during the 200910 H1N1 pandemic,
adults younger than 65 years of age were at higher risk
for influenza-related complications than during other recent
influenza seasons.7
The rates of influenza-related hospitalizations and deaths
can vary substantially from one influenza season to the next,
depending on the characteristics of the circulating strain of
influenza, as well as factors such as immunization rates and
how well matched the vaccine is to the circulating strains. The
Centers for Disease Control and Prevention (CDC) released
a report that included estimates of deaths associated with
seasonal influenza in the United States from 1976 to 2007.
During these three decades, the estimated number of annual
influenza-related deaths from respiratory and circulatory
causes ranged from a low of 3,349 to a high of 48,614.6
These trends demonstrate how unpredictable influenza can be
and serve as a reminder of why annual influenza vaccination
is crucial.
Influenza Viruses
There are three major types of influenzaA, B, and Cwhich

are differentiated by their surface proteins. Influenza A is the
main cause of epidemic and pandemic human disease.1,2
Influenza A causes a moderate to severe illness that can affect
people of all ages, while influenza B is typically milder and
primarily affects children. Influenza C is rarely reported as a
cause of illness in humans and has not been associated with
epidemic disease.1
Influenza A viruses are categorized into subtypes based
on the two major surface antigens: hemagglutinin (H) and
neuraminidase (N). The hemagglutinin surface antigens
(numbered 1 through 9) help the influenza virus attach to
cells in the body, while the neuraminidase surface antigens
(numbered 1 through 9) help the virus leave the cell and
spread to other cells.1 Most influenza viruses occur in birds.
Fewer combinations of H and N have been identified in
humans than in birds. Influenza viruses are named based
on the type, subtype, geographic origin, strain, and year of
isolation (Figure 3.2).
The surface antigens on influenza viruses change periodically due to evolution within immune or partially immune
populations. Two major types of antigenic change are known:
antigenic drift and antigenic shift. Antigenic drift occurs
continuously and results in minor changes in the antigenic
Figure 3.2. Structure of the Influenza Virus
Type of nuclear
material
Neuraminidase
Hemagglutinin
A/Fujian/411/2002 (H3N2)
Virus
type
Geographic
origin
Strain
number
Year of
isolation
Virus
subtype
Source: Reference 1.
structure of the virus, but the H and N numbers do not change.

When the new version of the virus is different enough from the
previous version, the virus can cause an epidemic because
protection that remains from previous exposures to similar
influenza viruses is incomplete.1
An antigenic shift involves major changes of one or both
of the surface antigens, creating a new strain of the virus.
Antigenic shifts are probably due to genetic recombination
(an exchange of a gene segment called genetic reassortment)
between influenza A viruses, usually those that affect humans,
pigs, and birds. When the new strain of the influenza virus
differs significantly from past strains, a global pandemic may
occur. During a pandemic, serious disease spreads quickly
because the population has little or no antibody protection
from the new strain. Mortality associated with a pandemic is
usually higher than during interpandemic periods.
Influenza Epidemics and Pandemics
An epidemic occurs when an infectious disease spreads

rapidly and affects more people than would be expected
during a typical influenza season. During an annual influenza
epidemic, approximately 5% to 20% of the U.S. population
becomes infected with the influenza virus.8 Annual epidemics
of influenza typically occur in the United States in autumn and
last through the spring, but the exact timing and duration of flu
seasons vary. While influenza outbreaks can happen as early
as October, they typically peak in February. Figure 3.3 shows
peak activity for the United States by month for the 198283
through 201112 influenza seasons. The peak month of
influenza activity is the month with the highest percentage
3
Number of Times as Peak Month
Figure 3.3. Peak Month of Influenza Activity During 198283

Through 201112 Seasons
16
14
12
10
8
6
4
2
0
Oct
Nov
Dec
Jan
Feb
Mar
Apr
May
Month
of respiratory specimens testing positive for influenza virus

infection. During this 30-year period, influenza activity most
often peaked in February (14 seasons, or 47% of the time),
followed by January and March (5 seasons each, or 17% of
the time), and December (4 seasons, or 13% of the time).
A pandemic is a global disease outbreak. Several influenza
pandemics have occurred over the past hundred years,
resulting in significant morbidity and mortality1,2,9:
191819 Spanish flu
Caused by subtype A/H1N1
R
esponsible for at least 30 million to 50 million deaths
worldwide including at least 675,000 deaths in the
United States
195758 Asian flu
R
esponsible for approximately 70,000 deaths in the
United States
196869 Hong Kong flu
R
esponsible for approximately 34,000 deaths in the
United States
200910 H1N1
C
DC estimates 43 million to 89 million people in the
United States were infected
R
esponsible for 8,870 to 18,300 deaths in the United
States
A few trends were observed during the 200910 influenza

pandemic that are not usually seen in annual influenza
epidemics.10 During annual influenza epidemics, rates of
influenza are usually highest in infants and young children
and influenza is a common cause of office visits and visits to
the emergency department in this patient population.2 Adults
aged 65 years and older are typically at highest risk for
complications, hospitalizations, and deaths from influenza.5,6
Pregnant women are also at increased risk of complications.2
The 2009 H1N1 influenza still had a significant impact on
young children and caused a high number of hospitalizations
and deaths in pregnant women. However, complications
during this influenza season occurred more frequently among
adults aged 19 to 64 years. According to one analysis, the
mean age of individuals who died from 2009 H1N1 influenza
was 37 years.10 The estimated number of hospitalizations and
deaths among adults aged 65 years or older was below those
normally seen during an annual influenza epidemic.
While the burden of disease from 2009 H1N1 influenza was
significant, it had the potential to be much more devastating
than what ultimately occurred. A coordinated public health
response and the availability of a pandemic influenza
vaccine helped prevent the spread of influenza and minimize
the potential devastation that could have been caused by
the pandemic. Pharmacists played a significant role in the
public health response to 2009 H1N1 by serving as vaccine
advocates and immunizers.
It is difficult to predict when the next influenza pandemic will
occur or how severe it will be when it does occur. Pharmacists
should be knowledgeable about preventive measures and be
prepared to act. When the next influenza pandemic strikes,
pharmacists will be called on to help educate and immunize
the people in their community.
Influenza Vaccines
The most effective strategy for preventing influenza is annual

vaccination.2 Annual vaccination against influenza is needed
for two reasons. First, protective levels of vaccine-induced
antibody to influenza wane over time (although they do
extend throughout one influenza seasontypically 6 to 8
months depending upon the strain).7 Second, gradual drifts
in influenza surface antigens change the circulating influenza
viruses. Therefore, changes are made to the influenza vaccine
formulation each year to maximize the protection it offers
against influenza.
Using egg-based technology, it takes approximately 6 to

8 months to manufacture an adequate supply of influenza
vaccine. Therefore, early each year, influenza experts must
choose the influenza strains that will be included in the
influenza vaccines to allow enough time to manufacture the
vaccine for the upcoming influenza season. Surveillance
information is used to predict which strains will likely circulate
in the upcoming season. For several decades (since the
197879 influenza season when A/H1N1 was added),
influenza vaccines have contained three strains: type A/
H1N1, type A/H3N2, and type B antigens. Beginning in
2013, quadrivalent influenza vaccine became available,
which contains two type B antigens. The addition of a second
type B antigen was added to protect against the two major
circulating lineages (called Yamagata and Victoria), but it is
expected to produce only a modest reduction in disease.11
This change precipitated the development of a new set of
abbreviations related to influenza vaccine7:
IIV (inactivated influenza vaccine) replaces the
previously used abbreviation TIV (trivalent influenza
vaccine). The abbreviation IIV is followed by a numeric
suffix that specifies the number of antigens in the
vaccine. For 201314, IIVs as a class include:
E
gg-based and cell culturebased trivalent inactivated
influenza vaccines (IIV3)
Egg-based quadrivalent inactivated influenza vaccine
(IIV4)
RIV refers to recombinant hemagglutinin influenza
vaccine, available as a trivalent formulation (RIV3) for
201314.
LAIV refers to live attenuated influenza vaccine,
available as a quadrivalent formulation (LAIV4) for
201314.
Where necessary to refer specifically to cell culture
based vaccine, the prefix cc is used (e.g., ccIIV3).
The available influenza vaccines are shown in Table 3.1.7,12-22
Due to the large number of vaccines available to prevent
influenza and regular changes to products, pharmacists should
anticipate that changes will occur from year to year. Each
year, pharmacists should carefully evaluate package labeling,
storage requirements, product preparation, and administration
instructions for each vaccine that they order.
ACIP does not express a preference for use of any one
influenza vaccine product over another in patients for whom
more than one type of influenza vaccine is appropriate
and available. Three quadrivalent influenza vaccines were

available for the 201314 influenza season, but only one
was approved for children younger than 2 years of age. It
is anticipated that in future seasons, more manufacturers
will transition their products from trivalent to quadrivalent
formulations.
Inactivated Influenza Vaccine
Influenza viruses are inactivated during the manufacturing

process and then broken into subunits to make inactivated
influenza vaccines. Because the influenza viruses have been
inactivated, these vaccines cannot cause influenza. Studies
with IIV3 have found it to be effective in protecting 70% to
90% of healthy people younger than 65 years of age when
the circulating virus strains are closely matched to the strains
in the vaccine.1,2 However, in people older than 65 years
of age, it may be only 30% to 40% effective in preventing
clinical illness. Even though IIV3 is not as effective in
preventing clinical illness in elderly adults, it has been shown
to be effective in preventing complications, hospitalizations,
and death in this patient population.1,2,21
In December 2009, the U.S. Food and Drug Administration
(FDA) approved a new IIV3 called Fluzone High-Dose (Sanofi
Pasteur).22 Fluzone High-Dose contains four times the amount
of each antigen found in the other IIV3 vaccines on the market.
The goal with this high-dose IIV3 is to prompt a stronger
immune response in adults aged 65 years and older. Fluzone
High-Dose induces higher antibody titers than the standard-dose
IIVs; however, at the time this certificate training program was
developed, there were no published studies demonstrating that
the higher titers resulted in greater protection against influenza
illness.2,23 One unpublished study concluded that high-dose IIV3
was more effective than standard dose IIV3 in those aged 65
years and older, but the CDC has not changed its recommendations as of December 2013.24
In May 2011, the FDA approved a new IIV3 called Fluzone
Intradermal (Sanofi Pasteur).25 A specially designed microneedle
and injector system is used to deliver a unique formulation
of vaccine into the intradermal tissue of the deltoid. Fluzone
Intradermal is approved for adults 18 to 64 years of age.
Additionally, in November 2013, the FDA approved a
monovalent inactivated influenza vaccine (Q-Pan H5N1
influenza vaccineGlaxoSmithKline) that provides protection
against the H5N1 influenza virus. The vaccine is approved for
use in adults 18 years of age and older who are at increased
risk of exposure to the H5N1 influenza virus. However, the
vaccine is not commercially available; it is being added to the
5
Table 3.1. Influenza Vaccines Available in the U.S. Market, 201314 Influenza Season
Vaccinea
Trade Name
Manufacturer
Presentation
Mercury
Content (g
Hg/0.5 mL)
Age
Indications
Route
Inactivated influenza vaccine,

trivalent (IIV3), standard dose
Afluria
CSL Limited
0.5 mL single-dose
prefilled syringe
0.0
9 yearsc
IM
5.0 mL multidose vial
24.5
Agriflu
Novartis
0.5 mL single-dose
prefilled syringe
0.0
18 years
IM
Fluarix
GlaxoSmithKline
0.5 mL single-dose
prefilled syringe
0.0
3 years
IM
Flucelvax
Novartis
0.5 mL single-dose
prefilled syringe
0.0
18 years
IM
FluLaval
GlaxoSmithKline
<25.0
3 years
IM
Fluvirin
Novartis
0.5 mL single-dose
prefilled syringe
4 years
IM
25.0
0.25 mL single-dose
prefilled syringe
0.0
635 months
IM
0.5 mL single-dose
prefilled syringe
0.0
36 months
IM
0.5 mL single-dose vial
0.0
36 months
IM
Fluzone
Sanofi Pasteur
25.0
6 months
IM
Fluzone
Intradermal
Sanofi Pasteur
0.1 mL prefilled
microinjection system
0.0
1864 years
ID

trivalent (IIV3), high dose
Fluzone High-Dose
Sanofi Pasteur
0.5 mL single-dose
prefilled syringe
0.0
65 years
IM

quadrivalent (IIV4), standard dose
Fluarix
Quadrivalent
GlaxoSmithKline
0.5 mL single-dose
prefilled syringe
0.0
3 years
IM
Fluzone
Quadrivalent
Sanofi Pasteur
0.25 mL single-dose
prefilled syringe
0.0
635 months
IM
0.5 mL single-dose
prefilled syringe
0.0
36 months
IM
0.0
36 months
IM
Recombinant influenza vaccine,

trivalent (RIV3)
Live attenuated influenza vaccine,
quadrivalent (LAIV4)
Flublok
Protein Sciences
0.0
1849 years
IM
FluMist
MedImmune
0.2 mL prefilled
intranasal sprayer
0.0 (per 0.2

mL)
249 years
IN
Quadrivalentb
a Immunization providers should check Food and Drug Administrationapproved prescribing information for 201314 influenza vaccines for the most complete and
updated information, including (but not limited to) indications, contraindications, and precautions. Package inserts for U.S.-licensed vaccines are available at www.fda.gov/
BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm093833.htm.
bTo identify children who might be at greater risk for asthma and possibly at increased risk for wheezing after receiving LAIV, parents or caregivers of children aged 2 to 4 years
should be asked: In the past 12 months, has a health-care provider ever told you that your child had wheezing or asthma? Children whose parents or caregivers answer yes to
this question and children who have asthma or who had a wheezing episode noted in the medical record within the past 12 months should not receive FluMist.
c Age indication per package insert is 5 years; however, ACIP recommends Afluria not be used in children aged 6 months to 8 years because of increased risk of febrile reactions
noted in this age group with CSLs 2010 Southern Hemisphere IIV3. If no other age-appropriate, licensed inactivated seasonal influenza vaccine is available for a child aged
5 to 8 years who has a medical condition that increases the childs risk for influenza complications, Afluria can be used; however, providers should discuss with the parents or
caregivers the benefits and risks of influenza vaccination with Afluria before administering this vaccine. Afluria may be used in persons aged 9 years.
ACIP = Advisory Committee on Immunization Practices; ID = intradermal; IIV = inactivated influenza vaccine; IIV3 = inactivated influenza vaccine, trivalent; IIV4 = inactivated
influenza vaccine, quadrivalent; LAIV = live attenuated influenza vaccine; IM = intramuscular; IN = intranasal; RIV = recombinant influenza vaccine.
Source: References 7 and 1222.
National Pharmaceutical Stockpile and will be released only if

directed by the Department of Health and Human Services.
NonEgg-Based Influenza Vaccines
In November 2012, the FDA approved the first U.S.-licensed

influenza vaccine manufactured using nonegg-based cell
culture technology (ccIIV3; FlucelvaxNovartis) for the
prevention of influenza in patients 18 years of age and
older.26
In January 2013, the FDA approved another nonegg-based
influenza vaccine (RIV; FlublokProtein Sciences), made with
recombinant hemagglutinin, for the prevention of seasonal
influenza in adults 18 to 49 years of age.
These two new vaccines require less time to manufacture
mainly because the process is not dependent on an egg
supply or limited by the selection of strains that are adapted
for growth in eggs. The shorter manufacturing time could
be useful in the event of a pandemic or vaccine supply
shortage.27
RIV does not use eggs in its manufacturing process. Therefore,
it is approved as an influenza vaccine for patients with egg
allergy. If supplies of RIV run out, ccIIV3 may be considered
as an option for these patients because it contains only a trace
amount of egg protein. However, FDA has not licensed ccIIV3
for use in people who have egg allergies, because the initial
seed virus was grown in eggs.28
Live Attenuated Influenza Vaccine
LAIV (FluMistMedImmune) contains live attenuated influenza

viruses. LAIV was previously available as a trivalent vaccine
but, starting in the 201314 influenza season, is now available
only as quadrivalent vaccine. It contains the same strains
of influenza found in IIV4. Because LAIV is a live virus
vaccine, the viruses in the vaccine must replicate to stimulate
an immune response, similar to that produced by natural
infection. However, the attenuated viruses in LAIV are cold
adapted, which means the viruses can replicate in the cooler
upper airways (e.g., mucosa of the nasopharynx) but not the
warmer lower airways and lungs.12,20 Because the viruses are
attenuated, they cannot replicate in the lower airways and are
not known to cause influenza. LAIV is effective in reducing
influenza illness in children older than 2 years of age and
has been shown to reduce cases of otitis media in some initial
trials. In adults, use of LAIV has been shown to reduce severe
illness, absenteeism, and the number of health care visits.2
Target Groups for Vaccination
ACIP recommends that all persons aged 6 months and older

should be vaccinated against influenza each year.2 This
recommendation, which was effective starting in the 201011
influenza season, is supported by evidence that annual
influenza vaccination is a safe and effective preventive health
measure with potential benefit for all people in this broad age
range. Vaccination should be offered throughout the entire
influenza season.
Historically, ACIP recommended focusing vaccination efforts
on individuals at higher risk for influenza-related complications. While vaccination of high-risk individuals should still
be a target, vaccinating younger healthier people has the
potential not only to protect the individual, but promote herd
immunity through reduced community transmission. When
vaccine supply is limited, vaccination efforts should focus on
immunizing people who29:
Are aged 6 months to 4 years (59 months).
Are aged 50 years and older.
Have chronic pulmonary (including asthma),
cardiovascular (except hypertension), renal, hepatic,
neurologic, hematologic, or metabolic disorders
(including diabetes).
Have altered immunocompetence (including immunosuppression caused by medications or by human
immunodeficiency virus [HIV]).
Are or will be pregnant during the influenza season.
Are aged 6 months to 18 years and receiving long-term
aspirin therapy and who therefore might be at risk for
experiencing Reyes syndrome after influenza virus
infection.
Are residents of nursing homes and other chronic-care
facilities.
Are American Indians/Alaska natives.
Are morbidly obese (body mass index is 40 or greater).
Are health care personnel.
Are household contacts and caregivers of children aged
younger than 5 years and adults aged 50 years and
older, with particular emphasis on vaccinating contacts
of children aged younger than 6 months.
Are household contacts and caregivers of people with
medical conditions that put them at higher risk for severe
complications from influenza.
ACIP recommends that all women who will be pregnant

during the influenza season be vaccinated against influenza.
Unfortunately, pregnant women have one of the lowest
vaccination rates of all adults recommended to receive
seasonal influenza vaccination.2,30 A recent study suggests
that infants born to women vaccinated against influenza
during pregnancy experience fewer influenza-related hospitalizations.30 In addition to decreasing the risk of influenzarelated complications in the pregnant woman, influenza
vaccination appears to provide benefit to the infant after birth,
emphasizing the importance of vaccinating pregnant women
against influenza.
During a vaccine shortage, public health may require a tiered
structure for prioritizing the distribution and administration of
vaccine. Pharmacists must abide by this priority structure to
ensure the most vulnerable people are protected.
Table 3.2. Inactivated Influenza Vaccine Dosing for

Intramuscular Administration
Age of Patient
No. of Doses
Volume
635 months
1 or 2a
0.25 mL
38 years
1 or 2a
0.5 mL
9 years
0.5 mL
Two doses separated by 4 weeks are needed to provide adequate protection for
children receiving influenza vaccine for the first time.
a
Figure 3.4. ACIP Influenza Vaccine Dosing Algorithm for

Children Aged 6 Months to 8 Years
Has the child ever received

influenza vaccine?
2 dosesa
Yes
Vaccine Recommendations
All people aged 6 months and older should receive 1 dose of

the influenza vaccine each year during the influenza season.
The single exception to this recommendation is for all children
aged 6 months to 8 years receiving influenza vaccination for
the first time: these children should receive 2 doses, administered at least 4 weeks apart in the same season.2 These 2
doses are needed to provide adequate protection for the
child, in particular against the A/H1N1 pandemic virus, which
has been included in seasonal influenza vaccines since the
201011 influenza season. If a child less than 9 years old
has received a total of 2 or more doses of seasonal influenza
vaccine since July 1, 2010, then only 1 dose is required during
the current season. If the child has not received a total of 2 or
more doses of seasonal influenza vaccine since July 1, 2010,
or the health care provider cannot verify how many doses the
child has received, then 2 doses should be administered in the
current influenza season. For a child who is not given 2 doses
the first time he or she receives the vaccine, and returns the
following year for vaccination while still younger than 9 years
of age, the child should receive 2 doses during that season.7
Once a child has completed the priming series of 2 doses,
the child will need only 1 dose of vaccine in each subsequent
year. (See Table 3.2 for dosing information and Figure 3.4 for
the childhood administration algorithm.2,7)
No/Dont know
Did the child receive a total

of 2 or more doses of
seasonal influenza vaccine
since July 1, 2010?
No/Dont know
2 dosesa
Yes
1 dose
a
Doses should be administered at least 4 weeks apart.
ACIP = Advisory Committee on Immunization Practices.

When to Offer Influenza Vaccinations
Influenza disease generally occurs in the United States from

December to March each year.1 Influenza vaccination
programs should be started as soon as vaccine is available (if
possible, by October) and should be continued until vaccine is
no longer available or has expired. In recent years, influenza
vaccine has become available as early as July, raising concerns
that effectiveness may wane before the end of the influenza
season. ACIP is continuing to evaluate data surrounding this
issue. In the meantime, ACIP recommends against deferring
vaccination because it could result in missed opportunities to
vaccinate, and may leave individuals vulnerable to illness if
influenza begins circulating early in the season.7 (After a person
is vaccinated, it typically takes approximately 2 weeks before
the vaccine provides protection.)
To maximize protection and avoid missed opportunities,

pharmacists should consider recommending or offering
vaccination any time they provide patient care during the
influenza season.
Strategies for Implementing Influenza Vaccination

Recommendations
According to ACIP recommendations, successful influenza
vaccine clinics typically employ a number of important
strategies to reach those at highest risk during influenza
season2:
Educate and immunize all health care providers and
staff of health care facilitiesincluding pharmacies.
The CDC recommends that convenient access to
influenza vaccine should be provided, free of charge,
by the employer to this group. All health care
providersincluding pharmacistsshould act as role
models and receive their influenza vaccination each
year.
Recommend or offer vaccination any time a patient
is encountered during the influenza season. A
clear, unequivocal recommendation from a health
care provider is one of the strongest predictors of
vaccination.
Provide education to potential vaccine recipients about
the risks of influenza and the potential health benefits of
vaccination.
Implement standing orders, as allowed or required
by state law, to facilitate the provision of vaccine to
patients.
Use a reminder/recall system for patients who were
immunized in previous years, as well as for situations in
which there is a vaccine shortage and patients need to
be recalled when vaccine becomes available.
Choosing an Influenza Vaccine
IIV is preferred for children younger than 2 years of age,

adults 50 years of age and older, and any patient with a
chronic medical condition.2 While Fluzone High-Dose is
approved for adults aged 65 years and older, ACIP has not
expressed a preference for any licensed influenza vaccine in
this patient population at this time. Both IIV3 and IIV4 were
available for the 201314 influenza season; the CDC has no
preference. It is important to remember that the quadrivalent
vaccine will provide additional protection only if the fourth
strain of influenza actually circulates. Because supplies of the
newer vaccines may be limited, pharmacists should immunize

their patients with any appropriate influenza vaccine that is
available.
LAIV is indicated for healthy people 2 to 49 years of age.
The use of LAIV is not indicated for patients with underlying
medical conditions, in patients with a history of wheezing or
asthma, or in pregnant women.
IIV is preferred over LAIV for vaccinating household members,
health care workers, and others who have close contact with
severely immunosuppressed patients during periods when
these patients require care in a protected environment (e.g.,
after a bone marrow transplant). If health care personnel
receive LAIV, they should refrain from contact with severely
immunosuppressed patients for 7 days after vaccine receipt.
ACIP recommends that people with immunosuppression should
receive influenza vaccine annually. However, only IIV should
be administered to a person immunosuppressed for any
reason (either from the underlying illness or treatment of an
illness).
IIV is preferred over LAIV in children and adolescents receiving
long-term aspirin therapy because of the potential association
between Reyes syndrome and wild-type influenza infection.
Contraindications and Precautions
As with all other vaccines, a previous severe allergic reaction

to a vaccine or a vaccine component is a contraindication to
receiving the vaccine.2,31 With the exception of RIV and ccIIV,
influenza vaccines are produced in fertilized chicken eggs.
Severe allergic reactions to eggs are a contraindication to all
other currently available influenza vaccines.1,2,31 ACIP has
published an algorithm for influenza vaccination of people
with egg allergy (Figure 3.5).7 Generally, patients who can
tolerate eating lightly cooked eggs or products containing
eggs (e.g., scrambled eggs) can be vaccinated with any
influenza vaccine.7
Prior history of Guillain-Barr syndrome is not an absolute
contraindication to vaccination with influenza vaccine,
but it is a precaution when it occurred within 42 days of
vaccination.2,31 Any patient with a history of Guillain-Barr
syndrome should be referred to a physician for assessment
to evaluate the risks versus the benefits of receiving influenza
vaccine.
Figure 3.5. ACIP Recommendations Regarding Influenza

Vaccination of People Who Report Allergy to Eggs
Can the person eat lightly cooked

egg (e.g., scrambled egg) without
reaction?a
Yes
No
After eating eggs or egg-containing

foods, does the person experience
ONLY hives?
Administer RIV3,
if patient aged
1849 years
Yes
OR
Administer IIV
No
After eating eggs or

egg-containing foods, does the
individual experience other
symptoms such as:
Cardiovascular changes
(e.g., hypotension)
Respiratory distress
(e.g., wheezing)
Gastrointestinal symptoms
(e.g., nausea/vomiting)
Reaction requiring epinephrine
Reaction requiring emergency
medical attention
Administer vaccine
per usual protocol
Observe for reaction for

at least 30 minutes
following vaccination
Administer RIV3,
if patient aged
1849 years
Yes
OR
Refer to a physician
with expertise in
management of allergic
conditions for
further evaluation
People with egg allergy might tolerate egg in baked products (e.g., bread,
cake). Tolerance to egg-containing foods does not exclude the possibility of egg
allergy. For patients who have no known history of exposure to egg but who
are suspected of being egg-allergic on the basis of previously performed allergy
testing, consultation with a physician with expertise in the management of allergic
conditions should be obtained prior to vaccination. Alternatively, RIV3 may be
administered if the recipient is aged 18 to 49 years.
a
ACIP = Advisory Committee on Immunization Practices; IIV = inactivated influenza

vaccine; RIV3 = recombinant influenza vaccine, trivalent.
If the patient has a valid contraindication or precaution to

receiving influenza vaccine, vaccination should be deferred
or the patient should be referred to his or her primary care
provider.
Potential Adverse Reactions
The most commonly reported adverse reactions with IIV

include local reactions at the injection site. Rarely, patients
may report fever, malaise, or myalgias after receiving IIV.
These effects are more common if the patient has had no prior
exposure to influenza vaccine (e.g., young children).
The adverse reactions reported after administration of LAIV are

usually mild and self-limiting. Runny nose or nasal congestion
is the most common adverse effect. Other possible adverse
effects include headache, fever, vomiting, myalgias, and
abdominal pain, but these appear to be more common after
the first dose than subsequent doses.
Storage and Administration of Influenza Vaccines
All influenza vaccines should be stored in the refrigerator at

2C to 8C (35F to 46F). These vaccines should not be
frozen.
Multiple IIVs are licensed for use and each IIV has specific
age indications (Table 3.1). Be careful to choose a vaccine
that is licensed for use in the patient being vaccinated. Shake
the vial or prefilled syringe before use. The dosing for IIVs is
shown in Table 3.2.2 Most IIVs are administered by intramuscular injection.
Fluzone is the only IIV approved for children younger than 36
months of age. Fluzone Intradermal is approved for adults 18
to 64 years of age and only the manufacturers microneedle
injector should be used to administer this vaccine.
LAIV is administered intranasally using a sprayer device; it

should never be administered orally or by injection. The sprayer
device contains a total dose of 0.2 mL. Half of the contents
(0.1 mL) is administered into one nostril, then the dose-divider clip
is removed and the remaining half (0.1 mL) is administered into
the other nostril. The appropriate technique for administration of
LAIV is discussed in more detail in Module 4.
Special consideration for administration of LAIV.
Influenza antiviral medications reduce the replication of
influenza virus and could potentially interfere with LAIV,
because it must replicate to stimulate an immune response.
If a patient is being treated for influenza with antiviral
medications, LAIV should not be administered until 48 hours
after cessation of the antiviral therapy.2 If the patient must
be treated with antiviral medications within 2 weeks after
receiving LAIV, the vaccine dose should be repeated 48 hours
or more after the final dose of antiviral medication.
10
Tetanus, Diphtheria, and Pertussis
Several vaccines have been formulated to provide protection

against tetanus, diphtheria, and pertussis, although some
contain only a subset of these antigens. Because these
antigens are often combined, they will be discussed together
in this section.
Figure 3.6. Patient With Generalized Tetanus
Tetanus
Tetanus is caused by a toxin produced by Clostridium tetani, a

gram-positive, spore-forming bacterium.1 Tetanus spores are
widespread in the environment and they thrive in anaerobic
conditions. C. tetani can enter the body through any major
or minor wound. Exposure to C. tetani can occur when there
is acute trauma resulting in tissue injury, puncture wounds,
lacerations, abrasions, chronic wounds, or injection drug
use. Many people think that tetanus is solely associated with
outdoor injuries (e.g., stepping on a rusty nail). However,
approximately 45% of the reported acute injuries resulting in
tetanus infection occurred indoors or at home.1
Once C. tetani enters the body through a wound, the spores
begin to germinate and the bacteria replicate. During this
process, the bacteria produce a toxin called tetanospasmin,
which causes the clinical features and complications of the
disease. The toxin is released into the bloodstream and acts
in the central nervous system. The toxin blocks the release of
neurotransmitters, ultimately preventing muscle relaxation and
results in severe muscle spasms. The incubation period can
vary from 3 to 21 days. In general, the shorter the incubation
period, the higher the chance of death.1
Four forms of clinical illness are recognized: local tetanus,
cephalic tetanus, neonatal tetanus, and generalized tetanus.
Local and cephalic tetanus are rare forms of the disease.
In cases of local tetanus, patients experience persistent
contraction of the muscles in the specific area where the
injury occurred. It is possible for local tetanus to precede the
development of generalized tetanus (Figure 3.6). Cephalic
tetanus is a form of the disease that can affect the cranial
nerves. Neonatal tetanus is also extremely rare in the United
States.1,32 Neonatal tetanus occurs primarily in infants of
mothers who were not immune to tetanus, resulting in no
protective passive immunity of the infant (Figure 3.7); neonatal
tetanus typically occurs when the umbilicus is cut with an
unsterile instrument, resulting in an infection of the umbilicus.
Over 80% of tetanus cases are generalized tetanus.1
Generalized tetanus often presents with descending symptoms,
usually starting with trismus (i.e., lockjaw), followed by stiffness
in the neck, difficulty swallowing, muscle rigidity, and severe

muscle spasms. The symptoms associated with generalized
tetanus can persist for 3 to 4 weeks and complete recovery
may take many months. Tetanus can be complicated by
respiratory insufficiency, bone fractures, and infections (e.g.,
pneumonia). Tetanus can be fatal, resulting in death in
approximately 10% of reported cases.1
Rates of tetanus in the United States began to decline from
1900 to the 1940s, when approximately 500 to 600 cases
were reported each year. Tetanus vaccine was introduced in
the late 1940s and the rate of this disease has declined since
that time. During 2001 through 2008, the last years for which
data have been compiled, a total of 233 tetanus cases in the
United States was reported, an average of 29 cases per year.
Almost all reported cases of tetanus are in people who either
have never been vaccinated or those who completed a primary
series but have not had a booster in the preceding 10 years.1
Figure 3.7. Infant With Muscle Rigidity From Neonatal
Tetanus
11
Diphtheria
than 157,000 cases of disease and 5,000 deaths.1,33 Many of

these cases were attributable to a lack of routine immunization
against diphtheria. This experience is a reminder that it is not
sufficient to give patients periodic booster doses of tetanus
toxoid alone. Instead, booster doses of diphtheria are needed
to boost immunity after completing a primary immunizing series
with diphtheria-containing vaccines.34,35
Infection with C. diphtheria can occur at any mucous membrane

in the body. The most common sites of infection include the
tonsils, pharynx, larynx, and nasal mucosa. Other mucous
tissues that can be affected include the skin, ocular tissue eye,
or genital area. The infection can cause tissue destruction and
usually results in the formation of a pseudomembrane, which is
a characteristic sign of diphtheria infection.
Pertussis
Diphtheria is caused by Corynebacterium diphtheriae, an

aerobic, gram-positive bacterium.1 C. diphtheriae can enter
the body through the respiratory tract. The bacterium is
capable of producing a toxin, which can be absorbed into the
bloodstream and distributed through the body. This toxin is
responsible for producing the clinical features and complications of the disease.
Most commonly, diphtheria infection affects the pharynx and

tonsils. Early symptoms are similar to pharyngitis: malaise,
sore throat, low-grade fever, and anorexia. However, within
2 to 3 days, a bluish-white membrane develops on the tonsils
and pharynx. The color of the membrane can change as the
disease progresses. This membrane may extend into the airway
and ultimately cause respiratory obstruction. Attempts to
remove the membrane will result in significant bleeding because
the membrane is firmly attached to surrounding tissue.
Laryngeal diphtheria often follows the same course as
pharyngeal diphtheria, only the larynx is involved. When
patients experience laryngeal diphtheria, they may complain
of symptoms such as a fever, hoarseness, and a barking
cough. Adherence of the membrane to the larynx can lead to
airway obstruction, coma, and death.
Diphtheria infection can lead to serious complications such
as myocarditis (inflammation of the heart) and neuritis
(inflammation of the motor nerves). These serious complications
are due to absorption of the bacterias toxin. Recovery from
the disease depends on the amount of toxin absorbed and the
extent of the complications caused by the toxin. The overall
death rate from diphtheria infection is 10% and mortality is
higher among children and adults over the age of 40 years.1
Diphtheria was a common cause of death among children in
the early 1900s. Because of efforts to vaccinate people against
diphtheria, the disease no longer occurs in the United States
only 5 cases have been reported since 2000.1,8 The disease is
still common in other parts of the world. For example, a large
diphtheria outbreak occurred in Russia, the Ukraine, and nearby
countries throughout the 1990s. This epidemic resulted in more
Pertussis, also called whooping cough, is caused by

Bordetella pertussis, a gram-negative bacterium.1 This disease
is extremely contagious. B. pertussis is most commonly
transmitted by respiratory droplets that are released in the air
when an infected person coughs or sneezes. The bacteria
infect the respiratory tract and produce toxins that interfere
with the function of the respiratory tract, ultimately causing the
characteristic symptoms of pertussis.
Pertussis begins with a catarrhal stage that lasts approximately
1 to 2 weeks. The symptoms of this stage are similar to those
of the common cold: mild cough, runny nose, sneezing, and
fever. This stage is followed by a paroxysmal cough stage,
which can last from 1 to 6 weeks. During this stage, the
patient will experience paroxysms, which are coughing attacks
characterized by numerous, rapid coughs (Figure 3.8). During
the coughing attacks, a high-pitched whooping sound often
can be heard. The whooping sound results when the patient
tries to take a deep breath against a closed glottis. The
paroxysmal coughing can cause vomiting and exhaustion.
The last stage is convalescence. Complete recovery from
pertussis is gradual and can take months.
Figure 3.8. Infant With Pertussis
12
Following the introduction of whole-cell pertussis vaccines in

the 1940s when the reported incidence of pertussis frequently
exceeded 100,000 cases per year, reports of pertussis
declined dramatically to fewer than 10,000 by 1965, and
1,300 cases were reported in 1981. During the late 1980s
pertussis reports began increasing gradually, and by 2012
more than 48,000 cases were reported nationwide.
In 2005, two new vaccines containing tetanus and
diphtheria toxoids and acellular pertussis (Tdap) became
available for use in adolescents and adults. At that time,
ACIP released recommendations to provide a one-time
dose of Tdap to adolescents and adults to boost immunity
to pertussis with the goal of preventing the transmission
of pertussis to young children.34-36 Initially, there was a
decline with 10,007 cases of pertussis being reported in
2008. However, the number of pertussis cases rose again
with 21,291 cases being reported nationally in 2009, and
48,277 in 2012 (Figure 3.9).33,37,38 Substantial regional
increases in the number of pertussis cases also have been
reported.39 The highest incidence of reported pertussis cases
has occurred in infants younger than 1 year of age.
Although the increase in the reported number of cases may
be due in part to increased awareness of pertussis disease,
there is concern that the tetanus and diphtheria toxoids and
acellular pertussis vaccines (i.e., DTaP; currently used for
children) are less potent than the tetanus and diphtheria
toxoids and whole-cell pertussis vaccines (i.e., DTwP) that
had been used previously. Data indicate that children who
have received only DTaP have waning protection, even after
60,000
50,000
40,000
30,000
20,000
10,000
0
19
8
19 0
8
19 2
8
19 4
8
19 6
8
19 8
9
19 0
9
19 2
9
19 4
9
19 6
9
20 8
0
20 0
0
20 2
0
20 4
0
20 6
0
20 8
1
20 0
12
Adolescents and adults are a reservoir of pertussis in the

community, serving as the source of infections in children.
Even though adolescents and adults often experience a mild
form of pertussis, they can still transmit the disease to young
children because the disease is highly contagious. It has
become apparent that adolescents and adults have waning
immunity to pertussis as well as both tetanus and diphtheria.
Figure 3.9. Annual Incidence of Pertussis in the United States

19802012
Number of Cases
Pertussis can affect children, adolescents, and adults.

Complications from pertussis occur most often among young
children. The most common complication is pneumonia.
Other complications that can occur include seizures and
encephalopathy, which can be caused by extended periods
of low oxygen supply during the coughing attacks. People
infected with pertussis may require hospitalization and
pertussis infection can result in death. Adolescents and adults
infected with pertussis usually experience a more mild form of
the disease and are less likely to develop complications.
Year
5 doses of DTaP.40,41 Clusters of parents who refuse to

vaccinate their children also may be contributing to regional
pertussis outbreaks.42
Vaccines
Multiple vaccines are available to provide protection against

tetanus, diphtheria, and/or pertussis and have various abbreviations based on their components.1,12 Capital letters indicate that
there is more antigen in the vaccine; lower-case letters indicate
a lower dosage of antigen. Available vaccines include:
Diphtheria and tetanus toxoids and acellular pertussis
adsorbed (DTaP):
Daptacel (Sanofi Pasteur)
Infanrix (GlaxoSmithKline)
Diphtheria and tetanus toxoids adsorbed (DT):
No trade name (Sanofi Pasteur)
Tetanus and diphtheria toxoids adsorbed, adult (Td):
Decavac (Sanofi Pasteur)
No trade name (Massachusetts Biological
Laboratories)
Tetanus toxoid, reduced diphtheria toxoid, and acellular
pertussis adsorbed (Tdap):
Adacel (Sanofi Pasteur)
Boostrix (GlaxoSmithKline)
Tetanus toxoid (TT) adsorbed:
No trade name (Sanofi Pasteur)
13
DTaP is available in combination with other vaccines often

used in childhood, including polio vaccine (DTaP-IPV;
KinrixGlaxoSmithKline), hepatitis B and polio vaccines
(DTaP-HepB-IPV; PediarixGlaxoSmithKline), and polio
and Haemophilus influenzae type b vaccines (DTaP-IPV-Hib;
PentacelSanofi Pasteur).
All of these inactivated vaccines contain tetanus toxoid (TT),
which is made by inactivating the toxin with formaldehyde.
Although tetanus toxoid is available as a single antigen,
it is not recommended for administration alone, except in
the rare circumstance when the patient has a contraindication to receiving diphtheria toxoid. Patients who should
be vaccinated against tetanus also need protection from
diphtheria and pertussis.
Diphtheria toxoid is the next component of these inactivated
vaccines (D or d). The diphtheria toxoid is also made by
inactivating the toxin with formaldehyde. Td and Tdap
vaccines contain one-third the dose of diphtheria toxoid
compared with the pediatric-strength diphtheria and tetanus
toxoids (DT) or diphtheria and tetanus toxoids and acellular
pertussis adsorbed (DTaP). The lower concentration (hence the
small d in Td and Tdap) helps avoid injection-site reactions
in adults but will still provide protection in these patients as
long as they have received a primary immunizing series.
Diphtheria toxoid is not available as a single antigen.
Whole-cell pertussis vaccines were developed in the 1930s.
To produce this vaccine, whole bacteria were inactivated
with formaldehyde and then combined with diphtheria and
tetanus toxoids (a combination known as DTP or DTwP).

Routine immunization with DTwP vaccine became common
in the United States in the late 1940s and was effective in
preventing disease. However, local adverse events occurred
after nearly half the doses of the vaccine. In addition,
systemic events reported after receipt of the whole-cell
pertussis vaccine included fever higher than 40.5C (105F),
transient hypotonic/hyporesponsive episodes, and transient
convulsions. Because of the concerns about safety and to
avoid adverse events associated with whole-cell pertussis
vaccines, new acellular pertussis (aP or ap) vaccines were
developed that contain only certain components of the
bacteria. DTaP vaccines have replaced whole-cell pertussis
vaccines, which are no longer available in the U.S. market.
Acellular pertussis vaccine is available in combination with
diphtheria and tetanus toxoids as DTaP and Tdap. There is no
commercially available single-antigen pertussis vaccine.
All infants, adolescents, and adults should be immunized

against tetanus, diphtheria, and pertussis unless there is a
valid contraindication or precaution to receiving the vaccine.32
Recommendations for vaccination with tetanus-, diphtheria-,
and pertussis-containing vaccines are summarized in Table
3.3.32,34,35
DTaP Vaccine
Children 6 weeks to 6 years of age should receive diphtheria

and tetanus toxoids combined with pertussis vaccine (DTaP).32
If a specific contraindication to pertussis vaccine is present,
Table 3.3. Recommendations for Vaccination With Tetanus-, Diphtheria-, and Pertussis-Containing Vaccines
Age of Patient
Recommendation
6 weeks6 years
Use DTaP to complete the primary 5-dose series at ages 2, 4, 6, 1518 months and 46 years.
Use DT only if patient has a specific contraindication to the pertussis component of DTaP
710 years (for patients who are not fully

vaccinated against pertussis)
Give a single dose of Tdap

If additional doses of tetanus- and diphtheria-containing vaccines are needed, refer to the catch-up
schedule to complete the primary series
11 years
If there is no record of a Tdap dose, give a single dose of Tdap; follow with 1 dose of Td every 10 years
Pregnant women
1 dose of Tdap during each pregnancy, preferably during the third trimester
Individuals who have close contact with

infants <12 months of age
If there is no record of a Tdap dose, give a single dose of Tdap; follow with 1 dose of Td every 10 years
DT = diphtheria and tetanus toxoids adsorbed; DTaP = diphtheria and tetanus toxoids and acellular pertussis adsorbed; Td = tetanus and diphtheria toxoids adsorbed, adult; Tdap =
tetanus and diphtheria toxoids and acellular pertussis vaccine.
Source: References 32, 34, and 35.
14
then pediatric DT should be used to provide protection against

tetanus. The primary immunizing series in children should
include doses of DTaP given at 2 months, 4 months, 6 months,
15 to 18 months, and 4 to 6 years of age.32
All adolescents and adults should have written documentation of a primary series of tetanus and diphtheria toxoids
containing vaccines.32,34,35 If these records do not exist, a
primary series of 3 doses is needed to provide protection.
This series should consist of 1 dose of Tdap and 2 doses of Td;
Tdap is preferred as the first dose.34,35 The first 2 doses must
be separated by at least 4 weeks and the third dose should be
given at least 6 months after the first dose.
Tdap Vaccine
In 2005, ACIP recommended vaccination with Tdap

for adolescents and adults to improve immunity against
pertussis.34,35 Tdap coverage appears to be increasing among
adolescents; the reported rate of at least 1 Tdap dose within
the past 10 years among 13 to 17 year olds was 68.7% in
2010 and 78.2% in 2011. Rates were higher when Td was
included.43 Only 8.2% of adults 19 to 64 years of age had
received at least 1 dose of Tdap in 2010. However, 64% had
received a dose of any tetanus-containing vaccine in the past
10 years.44 Because pertussis remains poorly controlled in the
United States and vaccination rates in adolescents and adults
are low, ACIP expanded its recommendations in October
2010 to include the following35:
All patients aged 11 to 64 years old should receive a
one-time dose of Tdap.
P
referably, all adolescents would receive a dose of
Tdap at 11 or 12 years of age.
A
ny person 11 to 64 years of age without documentation of a Tdap dose should receive a one-time dose.
All adults aged 65 years and older who have or who
anticipate having close contact with an infant less than
12 months of age and who previously have not received
Tdap should receive a single dose of Tdap.
For other adults aged 65 years and older who have not
previously received Tdap, a single dose of Tdap vaccine
may be given in place of 1 dose of Td vaccine.
Children aged 7 to 10 years who are not fully
vaccinated against pertussis and for whom no contraindication to pertussis vaccine exists should receive a
single dose of Tdap.
All women of childbearing age should be vaccinated with

Tdap during every pregnancy.45 Tdap given to pregnant
women will stimulate the production of pertussis antibodies
that will be transferred through the placenta and help protect
the infant; it also will protect the mother from developing
pertussis.45 Vaccination may be administered any time
during pregnancy but is preferred during the third trimester
(between 27 and 36 weeks gestation) to transfer the highest
concentration of antibodies through the placenta. Women
who have just given birth should receive a single dose of
Tdap immediately postpartum if they have not received a
dose previously. For women who have multiple closely
spaced pregnancies, there is a theoretical risk for severe
local reactions (e.g., Arthus reactions, whole limb swelling);
however, available data have not found an increased
incidence of these reactions.45
ACIP currently recommends only one lifetime dose of Tdap
except for pregnant women who should receive a dose
during each pregnancy. ACIP is considering a revaccination
recommendation for certain high-risk groups, such as health
care providers.
Td Vaccine
Any person who does not have a valid contraindication to

receiving tetanus and diphtheria toxoidscontaining vaccines
should receive booster doses of Td every 10 years once a
primary series has been completed and the person has a
record of receiving 1 dose of Tdap.32
Timing of Tdap Following Td
If a person is a candidate for pertussis vaccination and has

recently received a Td booster dose, ACIP recommends that
Tdap vaccination should not be delayed. Tdap vaccine should
be administered regardless of the interval since the last tetanus
or diphtheria toxoidcontaining vaccine. ACIP reviewed the
available evidence and concluded that while longer intervals
between Td and Tdap vaccination could decrease the potential
occurrence of local reactions, the benefits of protection against
pertussis outweigh the potential risk for adverse events.
Cocooning
Because the risk of complications from pertussis is so great

in babies, people (e.g., grandparents, child care providers,
health care providers) who have close contact with young
children (younger than 12 months of age) should be targeted
to receive Tdap if they have not previously received a dose.35
As described in Module 2, the strategy of surrounding young
children with protection by vaccinating close contacts is known
as cocooning.
15
Special Consideration: Wound Management
Any patient presenting with an acute wound should be

questioned regarding the injury and vaccination history for
tetanus-containing vaccines. If there is no record of a tetanuscontaining vaccine in the past 10 years, patients may require
both tetanus-containing vaccine and tetanus immune globulin
to provide full protection against the disease. Pharmacists
should refer to the current recommendations to determine
appropriate treatment strategies for patients with potential
exposure to tetanus. Recommendations were last published
in 2011 and can be found in the CDCs Manual for the
Surveillance of Vaccine-Preventable Diseases at www.cdc.
gov/vaccines/pubs/surv-manual/chpt16-tetanus.pdf.
Tetanus and diphtheria toxoids and acellular pertussis

containing vaccines should be administered when appropriate
to a patient unless there is a valid contraindication or
precaution to receiving the vaccines. Contraindications
include severe allergic reactions (e.g., anaphylaxis) to a
previous vaccine dose or to a vaccine component.
Precautions include a history of Guillain-Barr syndrome within
6 weeks following a previous dose of tetanus-containing
vaccine, as well of a history of Arthus-type hypersensitivity
reactions after a previous dose of tetanus-containing vaccine.
Patients who have an a history of an Arthus-type reaction
following a previous dose should defer vaccine until at least
10 years have elapsed since the last tetanus toxoidcontaining
vaccine. As for all vaccines, moderate or severe acute illness
with or without fever is also a precaution.
Special Contraindication Concerning DTaP
DTaP vaccine is contraindicated in children who have had a

serious allergic reaction to it or who developed encephalopathy
within 7 days of a previous dose.31,32,34,35 ACIP and the
American Academy of Pediatrics (AAP) cite several precautions
for the use of pertussis vaccine. The precautions regard adverse
events after a previous dose of DTaP, including:
Fever of 40.5C (105F) or greater within 48 hours
following the vaccine dose.
Collapse or shock-like state (i.e., hypotonic/hyporesponsive episode) within 48 hours following the
vaccine dose.
Persistent inconsolable crying for 3 hours or more within
48 hours following the vaccine dose.
Convulsions or seizure with or without fever occurring

within 3 days of the vaccine dose.
These adverse events were more common after receipt of
DTwP but can occur after DTaP. Under usual circumstances,
a child should not be given additional doses of DTaP if a
precautionary adverse event listed above occurred following
a prior dose. However, if the risk of pertussis is high (e.g.,
during a community outbreak of pertussis), the benefit of
pertussis immunity may outweigh the risk of an adverse
event, and the childs primary care provider may decide
to administer the vaccine. An adult who has a history of a
reaction to DTP as a child (except a severe allergic reaction)
may receive Tdap vaccine.
Experts at ACIP and AAP consider it inappropriate to deny the
benefits of pertussis immunization to children with underlying
neurologic conditions (e.g., seizure disorders, epilepsy,
cerebral palsy). However, vaccination should be deferred until
after an evolving neurologic condition resolves or stabilizes.
The most common adverse reactions associated with tetanus

and diphtheria toxoidscontaining vaccines are local injectionsite reactions. These injection-site reactions are usually mild
and self-limiting. However, Arthus reactions have been
reported after administration of these vaccines. Arthus
reactions are the development of exaggerated symptoms such
as severe pain, swelling, edema, and possibly necrosis near
the site of injection.1,34,35 An Arthus reaction after vaccination
with tetanus and diphtheria toxoids is not an allergic reaction
and is not common. However, these reactions may occur if
a patient is immunized with tetanus or diphtheria toxoids too
frequently. Patients with a history of Arthus reactions after
vaccination should not receive doses of Td or Tdap any sooner
than every 10 years.34,35
Acellular pertussis vaccines (i.e., DTaP and Tdap) may produce
local reactions including redness and swelling at the site of the
injection. Local reactions have been reported more frequently
in children after the fourth and/or fifth doses of DTaP.1 Lowgrade fever also has been reported after vaccination with
DTaP and Tdap. Severe adverse events (e.g., fever greater
than 40.5C [105F]), febrile seizures, persistent crying lasting
3 hours or longer, hypotonic/hyporesponsive episodes) have
been reported after DTaP vaccination but occur less frequently
than after vaccination with the whole-cell vaccines. None
of these conditions has been associated with permanent
brain injury. No increased risk of encephalopathy has been
observed with DTaP administration. The CDC continues to
16
monitor long-term surveillance data on the safety of DTaP

relative to the more severe and rare adverse events that were
seen after vaccination with DTwP.
Figure 3.10. Varicella Lesions on a Childs Face
Storage and Administration of Tetanus, Diphtheria,

and Pertussis Vaccines
All vaccines containing tetanus, diphtheria, and pertussis
should be stored in the refrigerator at 2C to 8C (35F
to 46F); these vaccines should not be frozen.12,46 When
administering the vaccine, pharmacists should shake the vial
or prefilled syringe before use and administer the 0.5 mL dose
intramuscularly (for all vaccines containing tetanus, diphtheria,
and pertussis). These vaccines should never be administered
subcutaneously.
Photo courtesy CDC Public Health Image Library: Image ID 10486.
Varicella
Varicella zoster virus is a herpes virus that causes two kinds of

disease.1 Primary infection causes varicella (i.e., chickenpox).
After an acute infection with varicella, the virus lies dormant
in nerve root ganglia. If the virus is reactivated, usually many
years later, a painful condition called herpes zoster (i.e.,
shingles) occurs (see Herpes Zoster section).
complications may include cerebellar ataxia, encephalitis, and

pneumonia. Complications from varicella are more frequent in
adults, children less than 1 year of age, immunocompromised
patients, and newborns of mothers infected with varicella.
Before the varicella vaccine was licensed in the United States,

infection with varicella zoster virus was nearly universal by
age 15 years and an estimated 4 million people developed
varicella each year.1,33 This very contagious virus is communicable from 1 to 2 days before onset through 4 to 5 days after
onset of the characteristic rash. Infection with varicella zoster
virus can be spread to a susceptible person by respiratory
transmission through airborne droplets or by direct contact
with varicella or herpes zoster lesions.
Varicella vaccine (VarivaxMerck) is a live attenuated virus

vaccine.47,48 Because this is a live vaccine, it must replicate
to stimulate an immune response. The vaccine produces
an immune response similar to that produced by natural
infection.1 The varicella vaccine has been shown to reduce the
risk of varicella infection by up to 90% and reduces the risk of
moderate to severe disease by up to 95%.1,12 Since varicella
vaccine was first introduced in the United States in 1995, it
has significantly reduced morbidity and mortality related to
varicella.49,50
Natural varicella is characterized by a generalized rash,

consisting of several hundred to more than a thousand pruritic
vesicles. The highest concentration of vesicles is usually on the
trunk. Lesions also can appear on the face, scalp, extremities,
and mucous membranes of the body. The vesicles contain
a clear fluid and often rupture or drain before they dry and
develop a crust (Figure 3.10).
Complications of varicella most commonly involve secondary
bacterial infections of the lesions with group A streptococci
or staphylococci. These secondary infections can be serious,
leading to clinic visits, hospitalizations, and even death. Other
Vaccine
Breakthrough infections have been reported in people

who have been immunized with 1 dose of vaccine. These
people are more likely to have only mild disease with few
lesions. Data from a 10-year surveillance period revealed
that increases in the severity and incidence of breakthrough
infection were associated with the length of time since
vaccination, suggesting that the protection provided by a
single dose of varicella vaccine wanes over time. Therefore,
a second dose of varicella vaccine was added to the
immunization schedule in 2006.49,51
17
All children greater than 12 months of age should be

vaccinated against varicella. Susceptible adolescents and
adults should be vaccinated if they do not have evidence of
immunity. According to ACIP recommendations, patients who
can demonstrate evidence of immunity to varicella do not
need to be vaccinated. Evidence of immunity can include any
of the following52:
Documentation of age-appropriate vaccination.
Laboratory evidence of immunity or laboratory
confirmation of disease.
Birth in the United States before 1980. (However, for
health care providers, women of childbearing age,
and immunocompromised patients, birth before 1980
should not be considered evidence of immunity because
certainty regarding immunity is desirable in these
populations.)
Diagnosis or verification of history of varicella disease
or herpes zoster by a health care provider. (Verification
of history of disease or diagnosis should be provided by
a health care provider rather than relying on parental or
self-reporting.)
Children should receive a total of 2 doses of varicella vaccine

to provide immunity. The recommended schedule for varicella
vaccine in children is as follows50:
First dose at 12 to 15 months of age.
Second dose at 4 to 6 years of age.
The first dose of varicella vaccine should not be given
before the childs first birthday because circulating maternal
antibodies can interfere with the live vaccine. Any dose of
varicella vaccine administered before the first birthday should
not be counted as valid.
All susceptible adolescents and adults should receive 2 doses
of the varicella vaccine if they cannot demonstrate immunity
to varicella. For children younger than 13 years of age, the
second dose should be given at least 3 months after the first
dose. If the second dose is given sooner than 3 months (e.g.,
to provide protection during an outbreak), the dose can be
considered a valid dose as long as the second dose was given
at least 28 days after the first dose. For patients older than
13 years of age, the 2 doses should be separated by at least
4 weeks.
Susceptible women of childbearing age should be vaccinated

before pregnancy because of a theoretical risk that varicella
is a teratogen at vulnerable stages of fetal development.
Although it is unknown if varicella vaccine is teratogenic,
more than a decade of monitoring inadvertent administration
during or just before pregnancy suggests it is unlikely. After
immunization, women should wait at least 4 weeks before
becoming pregnant. For unvaccinated women who become
pregnant, varicella vaccine should not be administered during
pregnancy.52 Rather, the first dose of varicella vaccine should
be administered immediately after childbirth (before the
woman is discharged from the hospital). The second dose
can be administered 4 to 8 weeks following delivery during a
postpartum health care visit.
For children receiving varicella vaccine, there are two
options: varicella vaccine as a single-antigen vaccine or
varicella in combination with the measles, mumps, rubella
vaccine (MMRV). Postlicensure studies indicated that among
children 12 to 23 months of age, 1 additional febrile seizure
occurred 5 to 12 days after vaccination for every 2,300 to
2,600 children who received the first dose of MMRV vaccine,
compared with children who had received the first dose of
MMR vaccine and varicella vaccine administered as separate
injections at the same visit.53
In June 2009, ACIP released a recommendation on the use
of MMRV.53 For the first dose of measles, mumps, rubella,
and varicella vaccines at age 12 to 47 months, either
MMR vaccine and varicella vaccine or MMRV vaccine
may be used. Providers who are considering administering
MMRV vaccine should discuss the benefits and risks of both
vaccination options with the parents or caregivers. Unless
the parent or caregiver expresses a preference for MMRV
vaccine, CDC recommends that MMR vaccine and varicella
vaccine should be administered separately for the first dose
in this age group. For the second dose of measles, mumps,
rubella, and varicella vaccines at any age (15 months to 12
years) and for the first dose at age 48 months or older, use of
MMRV vaccine generally is preferred over separate injections
of its equivalent component vaccines (i.e., MMR vaccine
and varicella vaccine). This recommendation is consistent
with ACIPs general recommendations regarding use of
combination vaccines, which state that use of a combination
vaccine generally is preferred over its equivalent component
vaccines.31
18
Storage and Administration of Varicella Vaccine
Because varicella vaccine is a live vaccine, it has some additional

contraindications and precautions to consider. Patients with
immunosuppression should be referred to their primary care
provider for vaccine decisions. If a patient has recently received
a blood product, live vaccines can be inactivated by antibodies
that may be present in the blood products, such as immune
globulin, whole blood, or plasma. For patients in need of
varicella vaccine who have received a blood product in the
previous year, the pharmacist should refer to updated references
(e.g., Epidemiology and Prevention of Vaccine-Preventable
Diseases also known as The Pink Book, ACIP general
recommendations on immunization) to determine the appropriate
interval before the vaccine can be administered.1,31
If the unreconstituted vaccine powder is inadvertently stored

in the refrigerator, it can remain viable for up to 72 hours at
this temperature, but it must be discarded if unused within
72 hours. The vaccine, which requires reconstitution before
injection, should be reconstituted with the diluent provided with
the vaccine. The diluent can be stored in the refrigerator or at
room temperature before use. Once reconstituted, varicella
vaccine should be administered immediately to avoid loss of
potency. Vaccine that is not administered within 30 minutes of
reconstitution must be discarded.
Varicella vaccine is contraindicated in patients with a history

of hypersensitivity to a prior dose or to any component of the
vaccine.31 The varicella vaccine contains very small amounts
of neomycin and gelatin.12 Patients having a history of
anaphylaxis to either of these components should be referred
to an allergy specialist for vaccine decisions. Women who
are pregnant should not receive varicella-containing vaccine
during pregnancy.
A personal or family (i.e., sibling or parent) history of seizure is

a precaution for use of MMRV vaccine.53
Varicella vaccine must replicate to evoke an immune response

and thus adverse reactions that are similar to symptoms of the
natural disease can occur. For example, patients may develop
a varicella-like rash after vaccination. These rashes are usually
minor, with few lesions, and usually are maculopapular rather
than vesicular. Additionally, this live vaccine can result in a
latent infection that can later present as herpes zoster. Herpes
zoster has occurred among patients who have received
varicella vaccine although at a lower rate than after natural
infection. As with other vaccines, local injection site reactions
can be expected after vaccination. Systemic symptoms (e.g.,
fever) after varicella vaccination are not commonly reported.
Transmission of the attenuated virus in varicella vaccine is rare,
although it has been reported.1,52 From the reported cases, it
appears that this occurs only in patients who develop a rash after
vaccination. If a rash develops, patients should avoid contact
with people who do not have evidence of immunity
(e.g., infants) or those at high risk for complications from varicella
(e.g., immunocompromised individuals) until the rash resolves.52
Varicella vaccine is a live vaccine that is sensitive to

temperature.48 Proper storage conditions are essential to
ensure vaccine potency. Varicella-containing vaccines should
be protected from light and kept frozen at a temperature
of 15C (5F) or colder before use. Varicella-containing
vaccine must be stored in refrigerator/freezer units that have
a separate sealed freezer compartment or preferably in a
separate freezer unit.
The dose of varicella vaccine is 0.5 mL. This vaccine should

be administered subcutaneously.
Herpes Zoster
Following an acute varicella infection (i.e., chickenpox), the

varicella zoster virus can lie dormant in the neural dorsal
root ganglia. When the virus is reactivated, it causes herpes
zoster (i.e., shingles).54 Since herpes zoster is a reactivation
of the varicella zoster virus, it can only occur in patients who
previously had chickenpox or, more rarely, in a patient who
has received the live varicella vaccine. Approximately 1 of
every 3 people will develop herpes zoster during his or her
lifetime.1,55 Risk factors associated with the development of
herpes zoster include advanced age, immunosuppression,
intrauterine exposure, or contracting varicella when younger
than 18 months of age.1
Once the virus is reactivated, it travels along the sensory

nerves to the skins surface and results in a painful condition
known as herpes zoster or shingles. Acute pain is the most
common symptom of shingles and usually precedes the
appearance of the rash. The rash from herpes zoster usually
appears as discrete patches of erythema that progress to
grouped vesicles over a period of 7 to 10 days.55 The rash
usually appears on one side of the body and is typically
19
distributed along one of the dermatomes (Figure 3.11). (A

dermatome is a localized area of the skin that is innervated
by one spinal nerve.) Patients with active zoster lesions can
transmit varicella zoster virus to susceptible people from the
time the rash develops until the lesions crust over.55 If the virus
is transmitted to a susceptible person, it can cause primary
varicella infection (i.e., chickenpox) in this person rather than
causing herpes zoster. In addition to the rash, patients with
herpes zoster may experience itching, paresthesia, fever,
headache, chills, upset stomach, and malaise. Very rarely,
herpes zoster can result in pneumonia, hearing problems,
blindness, encephalitis, or death.55
Figure 3.11. Patient With Herpes Zoster Rash
Oka/Merck strain as Varivax.12 The potency of the HZV to

prevent herpes zoster is at least 14 times greater than that of
the varicella vaccine to prevent chickenpox.48,58 Thus, the two
vaccines are not interchangeable. The added potency in HZV
is needed to elicit an appropriate immune response in older
adults who are immune to varicella because of having had
chickenpox earlier in life.
HZV has been shown to be effective in reducing the risk of
developing herpes zoster. This vaccine is indicated for the
prevention of herpes zoster; it is not indicated for the treatment
of an active case of herpes zoster.58 HZV also has been
shown to be effective in reducing the complications associated
with herpes zoster, particularly PHN.1,12 Vaccine efficacy
appears to be highest for younger patients (50 to 59 years
of age). Among older recipients, vaccine efficacy against
herpes zoster is somewhat reduced, but HZV will still provide
protection and should be administered.
Target Group for Vaccination
Postherpetic neuralgia (PHN), a chronic neuropathic pain

condition, is the most common sequela of herpes zoster.55
PHN is defined as pain that lasts 90 days or more after
the onset of the rash, and may persist for months or years.
The impact of PHN on quality of life has been found to be
comparable to that of congestive heart failure, myocardial
infarction, type 2 diabetes, and major depression.56 PHN
develops in 10% to 50% of patients with herpes zoster, and
increases with age and in immunocompromised individuals.57
Herpes zoster is also associated with the development of other
neurologic conditions including ophthalmologic complications,
Bells palsy, transient ischemic attacks, and stroke.57
Vaccine
A vaccine that protects against herpes zoster (Zostavax

Merck) was licensed by the FDA in 2006.58 The herpes zoster
vaccine (HZV) is a live attenuated vaccine containing the same
ACIP recommends routine vaccination of all individuals 60

years of age and older who have no valid contraindications
or precautions to receiving the vaccine. The ACIP recommendation to vaccinate people 60 years of age and older is
based on concerns about waning immunity if given to younger
people. The FDA has approved HZV for all individuals 50
years of age and older who do not have contraindications to
the vaccine. As of December 2013, ACIP has not endorsed
the lower end of the FDA-approved age range because of the
issue of waning immunity and higher risk of herpes zoster in
patients 60 years of age and older.
A single dose of HZV is recommended for adults 60 years

and older, regardless of whether they have had a prior
episode of herpes zoster or report a history of chickenpox.55
Those with chronic medical conditions may be vaccinated
unless a contraindication or precaution exists because of their
condition.
In 2011, FDA expanded the age indication for zoster vaccine
to include adults 50 to 59 years old for preventing herpes
zoster. This decision was based on a large study showing that
the vaccine reduced the risk of herpes zoster by approximately
70% in this population. Because the risk of getting shingles and
developing PHN is much lower for adults aged 50 to 59 years
than for those aged 60 years and older, ACIP recommends
zoster vaccine only for adults at least 60 years of age.
20
Nonetheless, individuals 50 to 59 years of age may be

vaccinated. Health care providers may consider whether
the patient would have poor tolerance to herpes zoster PHN
symptoms when making a recommendation. For example, the
provider may recommend HZV for a patient with preexisting
chronic pain, severe depression, other comorbidities,
intolerance to treatment medications due to hypersensitivity
or interactions with other medications, or occupational
considerations.59
In a randomized clinical study, a reduced immune response
to HZV was observed in individuals who received concurrent
administration of 23-valent pneumococcal polysaccharide
vaccine (PPSV23) and HZV compared with individuals who
received these vaccines 4 weeks apart. Based on these
data, the package insert for HZV vaccine advises that
health care providers consider administration of the two
vaccines separated by at least 4 weeks.56 However, the
clinical relevance of the observed reduction in antibody titers
is unknown because there is no correlate of protection for
antibody titers against varicella zoster virus as a measure of
protection against herpes zoster. It is likely that cell-mediated
immunity plays a larger role, but T-cell function was not
assessed in this study. The results were additionally confounded
by unexplained differences across comparison groups in
the baseline varicella zoster virus antibody titers. Antibody
levels to PPSV23 serotypes 3, 14, 19A, and 22F also were
assessed during this study and were unaffected by simultaneous
administration; the significance of this observation is unknown.
Finally, study results indicated that the safety profile of HZV is
unaffected by simultaneous administration of PPSV23.
Consequently, to avoid introducing barriers to patients and
providers who are interested in administration of these two
vaccines, ACIP has not changed its recommendation for
simultaneous vaccination. ACIP continues to recommend
that HZV and PPSV23 be administered at the same visit if the
patient is eligible for both vaccines. Practitioners should use
their professional judgment based on the available data and
the policies of their practice.
The vaccine for herpes zoster is contraindicated in individuals

with a history of anaphylaxis to a previous dose of the
vaccine or to gelatin, neomycin, or any other component of
the vaccine.1 However, a neomycin allergy that manifests
as contact dermatitis should not be considered a contraindication. The vaccine is also contraindicated in patients with the
following conditions:
Immunosuppression due to leukemia, lymphoma,

generalized malignancy, immune deficiency disease, or
immunosuppressive therapy
Active untreated tuberculosis
Pregnancy
Moderate or severe acute illness with or without fever is a
precaution for receipt of HZV. If there is no valid contraindication or precaution to receipt of HZV, the vaccine should be
administered.
The most common adverse events reported with HZV include

redness, pain or tenderness, swelling, and pruritus at the site
of the injection. Patients also have reported headache after
receiving the vaccine.
Following receipt of HZV, transmission of the virus from a
vaccinated person to a susceptible person has not been
documented.54 According to the current recommendations,
vaccinated people do not need to take any precautions
around young children, pregnant women, and immunocompromised patients following receipt of the vaccine unless a
varicella-like rash develops after vaccination. Rates of this
type of rash occurring after administration of HZV are rare,
but if a rash develops, susceptible people should avoid contact
with the infected lesions.
Storage and Administration of Herpes Zoster

Vaccine
The herpes zoster vaccine is supplied in vials of lyophilized
vaccine and a separate package of diluent and must be
reconstituted prior to injection. All varicella-containing
vaccines are live vaccines that should be protected from light
and stored in the freezer at temperatures of 50C to 15C
(58F to 5F).12,46 The vaccine may be kept at refrigerator
temperatures of 2C to 8C (35F to 46F) for up to 72 hours
prior to reconstitution.58,60 If this vaccine is not used within
72 hours after removal from the freezer or is not used within
30 minutes of reconstitution, it should be discarded.
The diluent should be stored separately from the vaccine and
can be stored in the refrigerator or at room temperature. The
vaccine should be reconstituted with the diluent immediately
upon removal from the freezer and administered within
30 minutes of reconstitution. If the reconstituted vaccine
is not administered within 30 minutes, the vaccine should
21
be discarded. Reconstituted or unreconstituted refrigerated

vaccine should never be refrozen.
The dose of the HZV is a single 0.65 mL subcutaneous
injection, preferably in the posterior upper arm.
Human Papillomavirus
Human papillomavirus (HPV) infection is the most common

sexually transmitted infection in the United States.1,33 More
than 20 million U.S. women and men are infected with HPV
and an estimated 6.2 million new infections occur each
year.1,33 Infection is most common among individuals in their
late teens and early 20s. Important risk factors for acquiring
HPV infection include sexual activity at an early age and
with multiple partners; however, infection can occur following
a single sexual encounter. At least 50% of sexually active
people will get HPV at some point in their lifetime.1
HPV is a double-stranded DNA virus that preferentially infects
epithelial cells. It has been identified as the etiologic agent for
cervical and other cancers, genital warts, and other diseases.
Of the nearly 100 HPV types that have been identified,
approximately 40 can infect the genital mucosa and 16 are
considered high-risk carcinogens. The high-risk HPV types
include 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68,
69, 73, and 82.
High-risk HPV types are detected in 99% of cervical cancers.1
Together, HPV types 16 and 18 account for approximately
70% of all cervical cancers.33 In 2010, almost 12,000
new cases of cervical cancer were diagnosed in the United
States and nearly 4,000 women died from cervical cancer
in 2010.61,62 In addition to cervical cancer, high-risk HPV
has been associated with vulvar, vaginal, anal, penile, oral,
and pharyngeal cancers.1 Low-risk HPV types (e.g., 6, 11)
cause the majority of cases of genital warts. Genital warts,
or condylomata acuminata, are growths of the cervicovaginal, vulvar, and external genitalia. While these growths
rarely progress to cancer, they are responsible for numerous
physician visits each year and considerable concern among
patients with the disorder.
The initial infection with HPV typically causes no signs or

symptoms and consequently many people unknowingly
spread the virus to others.63 In some individuals, the infection
resolves spontaneously without adverse health consequences;
in others the infection persists. Older age, infection with

multiple HPV types, and infection with a high-risk HPV type
are risk factors for persistent infection. Persistent infection is a
key risk factor for the development of moderate- or high-grade
cervical dysplasia and cancer. Although there is no cure
for persistent HPV infection, there are treatments for the
pathologic conditions caused by the infection, most notably
cervical cancer and genital warts. Because cervical and
other HPV-related cancers occur after many years of persistent
infection, cases and deaths from these cancers will continue to
occur owing to the large number of people currently infected
with HPV.
Vaccines
The first HPV vaccine, HPV4 (GardasilMerck), was licensed

by the FDA in 2006.12,63 It is an inactivated, recombinant,
quadrivalent vaccine prepared from highly purified virus-like
particles from HPV types 6, 11, 16, and 18. HPV4 is supplied
as a sterile suspension for injection in a single-dose vial or a
prefilled syringe. After completing the 3-dose series of HPV4,
more than 99.5% of recipients develop an antibody response
to all four HPV types in the vaccine.1 In women naive to
these HPV types, the vaccine has been shown to reduce the
incidence of precancerous cervical lesions, precancerous
vaginal and vulvar lesions, and genital warts at baseline by
nearly 100%.1 HPV4 is also licensed to prevent precancerous
anal lesions and anal cancer in women and men.
A second HPV vaccine, HPV2 (CervarixGlaxoSmithKline),
was licensed for use in women by the FDA in 2009.64,65 It
is an inactivated, recombinant, bivalent vaccine that contains
virus-like particles from HPV types 16 and 18. HPV2 is
available in a single-dose vial or a prefilled syringe. Within
1 month after completing the 3-dose series, 99% of vaccine
recipients develop an antibody response to HPV types 16 and
18.66 Vaccination with HPV2 has been shown to reduce the
incidence of precancerous cervical lesions caused by HPV
types 16 and 18. HPV2 is not approved for use in men.
HPV2 and HPV4 vaccines are indicated for administration

to girls and women 9 to 26 years of age.67 HPV4 is also
licensed for use in boys and men 9 to 26 years of age.63
Male patients may choose to be vaccinated with HPV4
to reduce their likelihood of acquiring genital warts or
developing anal cancer, but HPV2 is not indicated.64
22
Ideally, HPV vaccine should be given prior to the onset of

sexual activity to provide protection before potential exposure
to HPV occurs through sexual contact. Vaccination before
exposure to any type of HPV will allow the individual to
receive full benefit from the vaccine. However, patients who
are already sexually active should be vaccinated, because
they still may receive benefit from vaccination.
The HPV vaccines are not indicated for the treatment of HPV
infection. These vaccines are for prophylaxis only. They
cannot prevent disease due to preexisting HPV infection and
will not prevent HPV due to HPV types not included in the
respective vaccines.
ACIP recommends routine vaccination of boys and girls aged

11 to 12 years with a 3-dose series of HPV vaccine.67 Boys
should receive only HPV4. Girls may receive either HPV4
or HPV2. HPV4 will provide protection against diseases
caused by HPV types 6, 11, 16, and 18 (i.e., genital warts,
precancerous lesions, and cancers). HPV2 will provide
protection against diseases caused by HPV types 16 and 18
(i.e., precancerous lesions and cancers but not genital warts).
Health care providers should advise their patients of the
differences in coverage between the two available vaccines.
Vaccination can be given as early as 9 years of age at the
discretion of the health care provider. All 3 doses should be
completed to provide protective immunity. The second dose
should be administered 1 to 2 months after the first dose and
the third dose should be administered 6 months after the first
dose.65-67
Catch-up vaccination is recommended for girls and women
aged 13 to 26 years who have not been vaccinated or
those who have not completed the full 3-dose series. If the
series has been interrupted, it does not need to be restarted.
Catch-up vaccination with HPV4 is recommended for boys
and men aged 13 to 21 years who have not been vaccinated
previously or who have not completed the 3-dose series. Men
aged 22 to 26 years may be vaccinated. For immunocompromised male patients, ACIP recommends routine vaccination
with HPV4 as for all male recipients, and vaccination through
age 26 years for those who have not been vaccinated
previously or who have not completed the 3-dose series.
Men who have sex with men are at higher risk for infection
with HPV types 6, 11, 16, and 18 and associated conditions,
including genital warts and anal cancer. For men who have
sex with men, ACIP recommends routine vaccination with
HPV4 as for all male patients, and vaccination through age 26

years for those who have not been vaccinated previously or
who have not completed the 3-dose series.68
The HPV vaccine may be given concurrently with other
age-appropriate vaccines. If given simultaneously, each
vaccine should be administered using a separate syringe at a
different anatomic site.31
The HPV vaccine should be administered to a patient when

appropriate unless there is a valid contraindication or
precaution to receiving the vaccine. Contraindications include
a severe allergic reaction to a previous vaccine dose or to a
vaccine component.
Precautions include moderate or severe illness with or without
fever. Pregnant women should not be vaccinated because
it is not known whether the vaccine can cause fetal harm. If
pregnancy is identified after the vaccine series has begun,
the remaining doses should be delayed until pregnancy is
completed.
Pain at the injection site is the most common adverse event

reported. Other adverse events include redness, swelling,
fever, and pruritus. Syncope (i.e., fainting) after vaccination
with HPV also has been reported. This may be attributable
to vaccinating adolescents; syncope following vaccination
appears to be more common in this age group. Immunizing
pharmacists should be prepared to protect the patient from
injury from falling during fainting. According to ACIP,
clinicians should observe vaccinated patients for at least
15 minutes after vaccination to monitor for syncope adverse
events.31
Important Patient Counseling Information
Vaccination against HPV does not replace the need for

routine cervical cancer screening.67 Women who have been
vaccinated should maintain the same recommended schedule
of screening with annual examinations including Papanicolaou
(Pap) tests. In addition, sexually active patients should
be educated to use barrier protection to prevent sexually
transmitted infections.
23
Storage and Administration of Human

Papillomavirus Vaccines
HPV vaccines should be stored in the refrigerator at 2C to
8C (35F to 46F).12,47 They must be protected from light
and should not be frozen. When administering the vaccine,
providers should shake the vial or prefilled syringe before
use. The 0.5 mL dose should be administered intramuscularly,
preferably in the deltoid muscle.
(Figure 3.13). This can occur in 30% to 40% of infected

people. Mumps can cause significant complications such as
aseptic meningitis, orchitis (inflammation of the testicles) in
postpubertal males, and permanent deafness. Death from
mumps can occur but it is rare.
Figure 3.13. Child With the Mumps
Measles, Mumps, and Rubella

Measles
Measles is a very contagious infection caused by a virus from

the paramyxovirus group.1 The virus is spread by respiratory
transmission and is communicable from 4 days before until 4
days after the characteristic rash
appears. The classic symptoms
Figure 3.12. Child With
of measles include fever, cough,
Measles Rash
coryza (runny nose), conjunctivitis, Koplik spots (a bluish-white
rash on mucous membranes,
especially the mouth), followed
by the development of a
maculopapular rash approximately 14 days after exposure.
The rash usually appears first
on the face and neck and then
progresses downward to the
trunk, arms, and legs (Figure
3.12). Complications of measles
can include diarrhea, otitis
media, pneumonia, encephalitis,
and death. Young children and
Photo courtesy of CDC Public
Health Image Library:
adults over 20 years of age are
Image ID 132.
at higher risk of complications
from the disease.
Mumps
Mumps infection is also caused by a paramyxovirus.1 Mumps

is contagious but not to the same extent as measles. Mumps
is spread by the respiratory route and the virus is communicable from 3 days before until 4 days after the onset of
symptoms. Some patients may not experience symptoms from
mumps infection while others have nonspecific symptoms (e.g.,
headache, fever, myalgia, malaise). When symptoms are
present, the most common symptom characteristic of mumps
infection is parotitis (inflammation of the parotid glands)
Rubella
Rubella virus is a member of the togavirus family.1 The

rubella virus is transmitted through the respiratory route and
is communicable from 7 days before until 5 to 7 days after
the rash appears.
Rubella itself is
Figure 3.14. Child With Rubella
generally a mild
disease, causing
few complications. Rubella is
characterized by
a maculopapular
rash that occurs
approximately 2
weeks after exposure
(Figure 3.14). Other
symptoms, most
commonly reported in
adult women infected
with rubella, include
Photo courtesy of CDC Public Health Image
Library: Image ID 10145.
arthralgia and
arthritis.
24
Even though rubella is generally a mild disease, there is great

public health concern about congenital rubella syndrome
(CRS).69 If a pregnant woman is infected with rubella, the
fetus can become infected and fetal harm can occur. Fetal
infection with rubella virus can lead to spontaneous abortion,
fetal death, or premature delivery. Complications of CRS
include deafness, cataracts, heart defects, and mental
retardation. A worldwide pandemic of rubella occurred in
196465 and at least 20,000 infants were affected by CRS in
the United States.1,33 Over 6,250 spontaneous abortions and
over 2,100 excess neonatal deaths were reported. Among
the infants who survived, 11,600 were deaf, 3,580 blind, and
1,800 mentally handicapped.
Sustaining Vaccination Efforts to Eliminate

Outbreaks
Vaccination efforts have been successful in significantly

decreasing the number of cases of measles, mumps, and
rubella in the United States.1,33 Before measles vaccine was
introduced in this country, measles virus infected nearly
everyone by 15 years of age and accounted for an estimated
3 million to 4 million cases of measles each year (i.e., the
entire annual birth cohort).1,33 After implementation of routine
vaccination, the number of measles cases dropped significantly in the United States, reaching a record low of 37 cases
reported in 2004.1 Most cases of measles that now occur
in the United States are linked to infections acquired outside
this country. The number of mumps cases reached a record
low of 231 cases in 2003. However, as discussed in Module
1, outbreaks of measles and mumps have occurred in recent
years, demonstrating that people are still susceptible to these
diseases.70-72 Many of the reported cases in the outbreaks
occurred in people who were not vaccinated or inadequately
vaccinated. Furthermore, many of the cases reported during
the outbreak were imported from other countries.
In addition to concerns about outbreaks of measles and
mumps, CRS must be kept under control. The devastation that
can be caused by CRS, as witnessed during the last rubella
pandemic, should be reason enough to vaccinate patients
against this disease. Vaccination efforts must continue across
the county to minimize or eliminate outbreaks and provide
protection from these diseases.
Vaccines
The measles, mumps, and rubella vaccine (M-M-R IIMerck)

is a live virus vaccine.73 Although the measles, mumps, and
rubella (MMR) vaccine protects 95% of recipients after a
single dose, 5% of patients who receive the vaccine will not

respond. While this number may seem low, the unprotected
5% of recipients is enough to sustain viral transmission and
outbreaks of disease, particularly in crowded environments
such as schools and college dormitories. The recommendation
to provide a second dose of MMR vaccine provides protection
in close to 99% of recipients.
All individuals 12 months of age or older who do not have a

contraindication should be vaccinated.
Children should receive a 2-dose series with the first dose

between 12 and 15 months of age and the second dose at 4
to 6 years of age.74 As discussed in the section on varicella,
children may be vaccinated with either MMR vaccine or
MMRV vaccine.
The first dose should not be given before the childs first
birthday because circulating maternal antibodies can interfere
with the vaccine. All children and adolescents up through 18
years of age should have documentation of 2 doses of MMR
vaccine. If no reliable documentation is available, administer
2 doses of MMR vaccine separated by at least 4 weeks.
Certain adults should receive MMR vaccine.75 In general,
adults born before 1957 are considered immune to measles
and mumps. However, health care providers born before
1957 must be able to demonstrate evidence of measles,
mumps, and rubella immunity or laboratory confirmation
of the three diseases. Health care providers born before
1957 who cannot demonstrate adequate proof of immunity
should consider receiving MMR vaccine (2 doses separated
by at least 28 days if the provider does not have immunity
to measles or mumps; 1 dose if the provider does not have
immunity to rubella).
Adults born in 1957 or later should have documentation of at
least 1 dose of MMR vaccine (unless it is contraindicated), or
laboratory evidence of immunity to each of the three diseases,
or documentation of provider-diagnosed measles or mumps
disease. A second dose of MMR should be recommended
for adults born in 1957 or later who (1) recently have been
exposed to the diseases (e.g., outbreak setting); (2) are
students in postsecondary educational institutions; (3) work in
a health care facility; or (4) plan to travel internationally.
25
Women of childbearing age who do not have acceptable

documentation of prior vaccination or serologic evidence of
rubella immunity should be vaccinated prior to pregnancy.74
A physicians diagnosis or a personal history of rubella is not
considered acceptable evidence of immunity. Women should
receive the MMR vaccine at least 4 weeks before becoming
pregnant. MMR vaccine should not be given to a pregnant
patient or to a patient who plans to become pregnant within 4
weeks. Pregnant women who do not have evidence of rubella
immunity should receive the MMR vaccine upon completion of
the pregnancy.
MMR vaccine should be administered when appropriate to a

patient unless there is a valid contraindication or precaution
to receiving the vaccine. MMR vaccine is contraindicated in
patients with a history of hypersensitivity to a prior dose or to
any component of the vaccine.31 The vaccine contains very
small amounts of neomycin and gelatin.73 A patient with a
history of an anaphylactic reaction to one of these components
should be referred to the physician for vaccine decisions.
Women who are pregnant should not receive MMR vaccine.
Measles and mumps vaccine viruses are grown in chick
embryo fibroblast tissue culture. However, MMR does not
contain a significant amount of egg protein so patients with
severe egg allergy may be vaccinated with extreme caution.
Because MMR is a live vaccine, there are some additional
contraindications and precautions to consider. Patients
with immunosuppression should not receive MMR vaccine
and should be referred to their primary care provider for
vaccination decisions. If a patient has received a blood
product in the previous year, live MMR vaccine viruses
can be inactivated by antibodies that may be present in
the product; for such patients in need of MMR vaccine,
the pharmacist should refer to updated references (e.g.,
Epidemiology and Prevention of Vaccine-Preventable
Diseases, ACIP general recommendations on immunization) to
determine the appropriate interval before the vaccine can be
administered.1,31
Mild injection-site reactions can be expected after vaccination

with MMR vaccine. Other adverse events that have been
reported include fever, rash, arthralgia, and arthritis. Parotitis
and deafness rarely occur after vaccination. Rarely, encephalopathy may be temporally associated with a dose of the
vaccine, but this event has not been proven to be caused
by the vaccine.1,12 Most adverse effects observed after

vaccination with MMR are transient and occur among people
susceptible to infection. As a result, adverse events after
the second dose are uncommon, because most recipients of
second doses are already immune to the diseases.
Rarely, MMR vaccine may cause thrombocytopenia within 2
months after vaccination. Estimates of the frequency of clinically
apparent thrombocytopenia from Europe are 1 case per 30,000
to 40,000 vaccinated susceptible persons, with a temporal
clustering of cases occurring 2 to 3 weeks after vaccination. The
clinical course of these cases was usually transient and benign,
although hemorrhage occurred rarely. The risk for thrombocytopenia during rubella or measles infection is much greater than
the risk after vaccination. Based on case reports, the risk for
MMR-associated thrombocytopenia may be higher for patients
who have previously had immune thrombocytopenic purpura,
particularly for those who had thrombocytopenic purpura after
an earlier dose of MMR vaccine.
Storage and Administration of Measles, Mumps,

and Rubella Vaccines
MMR vaccine is provided as lyophilized vaccine and diluent.
The vaccine should be protected from light at all times and
should be stored in the refrigerator at 2C to 8C (35F to
46F) or freezer at temperatures as cold as 50C (58F).1,46
Diluent should not be frozen. The lyophilized vaccine should
be stored in the refrigerator before reconstitution, and reconstituted according to the manufacturers instructions just before
use. The 0.5 mL dose should be administered subcutaneously immediately after reconstitution. MMR vaccine must
be administered within 8 hours of reconstitution or it must
be discarded. MMRV must be used within 30 minutes of
reconstitution.
Pneumococcal Disease
Pneumococcal disease is caused by Streptococcus

pneumoniae, a gram-positive coccobacillus bacteria. Some
pneumococci are encapsulated, with surfaces composed
of complex polysaccharides. These capsules allow the
bacteria to evade some immune cells (e.g., phagocytes)
and interfere with the activation of an immune response.1
A persons immune system must be able to recognize the
polysaccharide capsule and create antibodies directed
against the polysaccharide capsule to provide protection
against this infection.
26
S. pneumoniae is a human pathogen that colonizes the

nasopharynx of up to 70% of children and adults.1 Over
90 serotypes of S. pneumoniae have been known to cause
serious disease. In the years prior to widespread use of
pneumococcal conjugate vaccine, the 10 most common
serotypes accounted for approximately 62% of invasive
pneumococcal disease.1 Although carriers of S. pneumoniae
may be asymptomatic, they can transmit the bacteria to others.
S. pneumoniae can be transmitted by airborne respiratory
droplets or by direct contact with infected respiratory
secretions and it is a significant cause of illness in adults and
children, causing an estimated 4,000 deaths annually in the
United States.76 Infections associated with S. pneumoniae
include pneumonia, bacteremia, meningitis, sinusitis, and otitis
media.1,33
Pneumococcal pneumonia is the most common infection due
to S. pneumoniae, accounting for approximately one-third
of community-acquired pneumonias and one-half of all
hospital-acquired pneumonias.1 Nearly 175,000 adults are
hospitalized with pneumococcal pneumonia each year in
the Unites States.1,33 Pneumococcal pneumonia can occur as
the primary infection or as a secondary complication from
influenza infection. Pneumococcal pneumonia has a short
incubation period of only 1 to 3 days and typically has an
abrupt onset with symptoms of fever, shaking chills, productive
cough, pleuritic chest pain, malaise, weakness, difficulty
breathing, and rapid, shallow breathing.1,33
Pneumococcal bacteremia is a serious infection of the
bloodstream caused by S. pneumoniae. Bacteremia occurs in
approximately one-third of patients who have pneumococcal
pneumonia. While the symptoms of pneumococcal bacteremia
are usually nonspecific (e.g., fever, chills, difficulty breathing),
this is a serious infection that can lead to septicemia and
cause death in 20% of patients (up to 60% of elderly
patients).1,33
S. pneumoniae can cause pneumococcal meningitis, which
is inflammation of the membranes surrounding the brain and
spinal cord. One-fourth of all people with pneumococcal
meningitis also have pneumonia.1 Signs and symptoms of
pneumococcal meningitis are similar to other bacterial causes
of meningitis and may include headache, lethargy, irritability,
seizures, vomiting, cranial nerve involvement, and coma.
Neurologic sequelae are common in patients who survive a
case of pneumococcal meningitis. Death can occur in 30% of
patients (up to 80% of elderly patients).1,33
Before the availability of a pneumococcal conjugate vaccine

for infants and toddlers, invasive pneumococcal disease
caused significant morbidity and mortality in this age group.1
Each year in the United States, an estimated 17,000 cases of
invasive pneumococcal disease occurred in children
and an estimated 200 children died from these infections.
S. pneumoniae also caused up to 5 million cases of acute
otitis media each year.1,33,77 While the burden of otitis media
is not significant in terms of mortality data, it is a significant
cause of lost time from work for parents and caregivers. It
also contributes to the health care dollars spent on visits to
physicians and medication therapies.77
Drug-Resistant Streptococcus pneumoniae
Before 1990, S. pneumoniae was usually susceptible to

penicillin, allowing most infections to be treated with penicillin
alone.33 However, resistance to penicillin and to multiple other
classes of antimicrobial medications has increased significantly over time. The CDC reports cases of drug-resistant
S. pneumoniae across the country, accounting for up to 40%
of pneumococcal isolates in some areas.1
The treatment of pneumococcal disease is difficult owing to the
emergence of drug-resistant S. pneumoniae. As drug-resistant
strains have become more common, empiric treatment with
broad-spectrum agents has been used to treat pneumococcal
infections. However, inappropriate antibiotic use contributes
to the development of drug-resistant S. pneumoniae,
complicating the situation further.33 As antibiotics become
less effective in treating pneumococcal disease, prevention by
vaccination becomes even more important to protect people
from this disease and its complications.
Vaccines
The 7-valent pneumococcal conjugate vaccine (PCV7;

PrevnarWyeth) was the first pneumococcal conjugate
vaccine available in the United States. The most recent
data available indicate that the overall rates of invasive
pneumococcal disease in people of all ages decreased by
45% since the PCV7 vaccine was introduced in 2000.76 This
decrease in invasive pneumococcal disease is an example
of herd immunity because PCV7 was given only to children
younger than 7 years of age. Vaccination with PCV7 resulted
in reduced transmission of pneumococcal infection caused
by the serotypes contained in the vaccine and ultimately
decreased the overall rate of invasive pneumococcal disease.
Even though there is generally less invasive pneumococcal
disease, other strains of S. pneumoniae that are not in the
27
PCV7 vaccine have become more common. PCV7 has been

replaced by the 13-valent pneumococcal vaccine, which
added 6 more serotypes to those in PCV7, and the current
PCV13 provides more comprehensive coverage against
pneumococcal disease.
13-Valent Pneumococcal Conjugate Vaccine
The pneumococcal conjugate vaccine PCV13 (Prevnar 13

Pfizer) was approved in 2010.78 PCV13 targets 13 serotypes
of S. pneumoniae (i.e., 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14,
18C, 19A, 19F, and 23F). PCV13 also is indicated for the
prevention of otitis media caused by S. pneumoniae serotypes
4, 6B, 9V, 14, 18C, 19F, and 23F.
PCV13 is a conjugate vaccine, meaning that polysaccharides
are linked to a protein (a diphtheria protein in this case) during
the manufacturing process. As discussed in Module 2, the
process of conjugation is necessary because children younger
than 2 years of age do not consistently mount an effective
immune response to pure polysaccharide vaccines.
23-Valent Pneumococcal Polysaccharide Vaccine
The pneumococcal polysaccharide vaccine (PPSV23;

Pneumovax 23Merck) contains polysaccharides from 23
strains of S. pneumoniae that were most prevalent at the time
when the vaccine was licensed.1,12
Over 80% of healthy adults who receive PPSV23 will respond
by developing antibodies against the serotypes contained
in the vaccine within 2 to 3 weeks after vaccination.1,79
Vaccine efficacy declines with advancing age and may be
less effective in patients with underlying illness. However, the
vaccine can still provide protection for these high-risk patients
and should be administered. Because this is a pure polysaccharide vaccine, it is not adequately effective in children
younger than 2 years of age.
PPSV23 has been shown to reduce the risk of invasive
disease (e.g., bacteremia, meningitis) by 60% to 70%.1,79
To date, study results have not demonstrated consistent
evidence that PPSV23 reduces the incidence of pneumococcal
pneumonia.1,12,79,80 However, studies do suggest that even
if PPSV23 does not prevent pneumococcal pneumonia,
vaccination with PPSV23 can improve outcomes in patients
with pneumococcal pneumonia. In these studies, patients
with pneumococcal pneumonia who had been vaccinated
experienced fewer complications, decreased length of hospital
stay, decreased need for admission to the intensive care unit,
and a lower rate of death.81-83
Despite the decreases in invasive pneumococcal disease since

the introduction of PCV7, invasive pneumococcal disease
remains an important cause of illness and death in the United
States. PCV13 and PPSV23 have both routine uses and
recommended uses for high-risk individuals. High-risk children
and adults are listed in Table 3.4.76,77
Children and Adolescents
All children aged 2 months to 59 months should be routinely

vaccinated with PCV13. The recommended routine
vaccination schedule for the 4-dose series is administration at
2, 4, 6, and 12 to 15 months of age.84
Unvaccinated children 7 months of age and older do not
require a full series of 4 doses. The number of doses a child
needs to complete the series depends on the childs current
age. Unvaccinated children aged 7 to 11 months should
receive 2 doses of vaccine at least 4 weeks apart, followed
by a booster dose at age 12 to 15 months. Unvaccinated
children aged 12 to 23 months should receive 2 doses of
vaccine, at least 8 weeks apart. Previously unvaccinated
healthy children 24 to 59 months of age should receive a
single dose of PCV13.
Unvaccinated children 24 to 71 months of age with certain
chronic medical conditions should receive 2 doses of PCV13
separated by at least 8 weeks. These conditions include
chronic heart and lung disease, diabetes, cerebrospinal fluid
leak, cochlear implant, sickle cell disease and other hemoglobinopathies, functional or anatomic asplenia, HIV infection,
or immunocompromising conditions resulting from disease or
treatment of a disease.
For children aged 14 to 59 months who have previously
received an age-appropriate PCV7 series, a single
supplemental dose of PCV13 should be administered to
provide protection against the 6 additional serotypes
contained in PCV13. For children who have an underlying
medical condition, a single supplemental PCV13 dose is
recommended through 71 months of age. This includes
children who have received PPSV23 previously. PCV13 should
be administered at least 8 weeks after the most recent dose of
PCV7 or PPSV23.84
28
Table 3.4. High-Risk Indications and Recommendations for Administration of PCV13 and PPSV23
Risk Group
Underlying Medical Condition
PCV13a
Recommended
Immunocompetent patients
Patients with functional or anatomic asplenia
Immunocompromised patients
PPSV23
Recommended
Chronic heart diseaseb
Chronic lung diseasec
Diabetes mellitus
Cerebrospinal fluid leaks
Cochlear implants
Alcoholism
Chronic liver disease
Cigarette smoking
Revaccination
5 Years After
First Dose
Sickle cell disease/other

hemoglobinopathies
Congenital or acquired asplenia
Congenital or acquired
immunodeficienciesd
HIV infection
Chronic renal failure
Nephrotic syndrome
Leukemia
Lymphoma
Hodgkin disease
Generalized malignancy
Iatrogenic immunosuppressione
Solid organ transplant
Multiple myeloma
Children aged 2 to 5 years with chronic conditions (e.g., heart disease, diabetes), immunocompromising conditions (e.g., HIV), functional or anatomic asplenia (including sickle
cell disease), cerebrospinal fluid leaks, or cochlear implants, and who have not previously received PCV13, have been recommended to receive PCV13 since 2010.
a
b
c
Including congestive heart failure and cardiomyopathies.
Including chronic obstructive pulmonary disease, emphysema, and asthma.
Includes B-(humoral) or T-lymphocyte deficiency, complement deficiencies (particularly C1, C2, C3, and C4 deficiencies), and phagocytic disorders (excluding chronic
granulomatous disease).
d
Diseases requiring treatment with immunosuppressive drugs, including long-term systemic corticosteroids and radiation therapy.
HIV = human immunodeficiency virus; PCV13 = 13-valent pneumococcal conjugate vaccine; PPSV23 = 23-valent pneumococcal polysaccharide vaccine.
Source: References 76 and 77.
High-risk children 6 to 18 years of age who have received

a 3-dose series of PCV7 should receive the a supplemental
single dose of PCV13 up to the age of 18 years regardless
of whether they have previously received PCV7 or PPSV23.
Children younger than 71 months should receive 2 doses of
PCV13 if fewer than 2 doses of PCV 7 were administered.
Multiple doses should be given at least 8 weeks apart.
PPSV23 is recommended only for children who have high-risk

conditions. For these children, PPSV23 should be administered
at least 8 weeks after the last dose of PCV to children aged
2 years or older. A second PPSV23 dose should administered
after 5 years to children with anatomic or functional asplenia
(including sickle cell disease) or an immunocompromising
condition.84
29
Adults
Routine vaccination with PPSV23 should be provided for

all adults aged 65 years and older, as well as residents of
nursing homes or long-term care facilities, and adults who
smoke cigarettes.75 Typically, a single dose of PPSV23 is
sufficient for most patients and routine revaccination is not
recommended.
Adults with immunocompromising conditions are
recommended to receive both PCV13 and PPSV23 vaccines.
The PCV13 dose should be administered first, followed by
PPSV23 at least 8 weeks later. If PPSV23 has been administered but PCV13 has not, the PCV13 should be administered
at least 1 year after PPSV23. See Figure 3.15 for an algorithm
of when to administer pneumococcal vaccine to adults with
selected conditions.76
One-time PPSV23 revaccination 5 years after the first dose is
recommended for adults 19 to 64 years of age with certain
immunocompromising conditions. Those who have received
1 or 2 doses of PPSV23 before 65 years of age should
receive an additional dose at age 65 years (resulting in a
maximum of 3 lifetime doses of PPSV23).75
The pneumococcal vaccine should be administered unless

there is a valid contraindication or precaution to receiving the
vaccine. PCV13 and PPSV23 are contraindicated for patients
who have had a severe allergic reaction (e.g., anaphylaxis) to
a previous vaccine dose or to a vaccine component (including
a diphtheria toxoidcontaining vaccine for the PCV13
vaccine). Precautions include moderate or severe acute illness
with or without fever.
Pneumococcal Conjugate Vaccine
Local injection-site reactions are the most commonly reported

adverse reactions after administration of PCV. Fever also has
been reported. Less frequent adverse events that can occur
include irritability, drowsiness, restless sleep, and decreased
appetite.76,77
Pneumococcal Polysaccharide Vaccine
Up to half of the patients who receive PPSV23 will develop

a mild, local reaction that may include mild pain, swelling,
and redness at the injection site.1,80 Fever and myalgias after
PPSV23 administration occur in fewer than 1% of recipients.
Storage and Administration of Pneumococcal

Vaccines
Both the PCV13 and PPSV23 vaccines should be stored in
the refrigerator at 2C to 8C (35F to 46F); these vaccines
should not be frozen.85,86 When administering the vaccine,
the vial or manufacturer-filled syringe should be shaken before
use. The 0.5 mL dose of PCV13 should be administered
intramuscularly. The dose of PPSV23 is also 0.5 mL, and
this vaccine may be administered either intramuscularly or
subcutaneously.
Meningococcal Disease
Meningococcal disease includes the spectrum of illness caused

by Neisseria meningitidis, including meningitis, bacteremia,
and bacteremic pneumonia. N. meningitidis is an aerobic,
gram-negative bacterium with a polysaccharide capsule that
surrounds the outer membrane of the bacteria and helps it
evade certain cells of the immune system (e.g., phagocytes).1
N. meningitidis is classified into serogroups based on the
structure of the polysaccharide capsule. Although 13 polysaccharide capsules have been identified, 5 specific serogroups
cause almost all invasive disease: A, B, C, Y, and W-135.1,33
In the United States, serogroups C, Y, and W-135 account
for more than 75% of meningococcal disease in people
older than 11 years of age, while serogroup B is the most
common cause of meningococcal disease in infants, but is
not contained in any vaccines licensed for use in the United
States.33 Although serogroup A is common in Africa, it is
rarely reported in the United States.1
N. meningitidis is transmitted by the respiratory route. Once

the bacteria colonize in the nasopharynx, they begin to
replicate. The bacteria are capable of invading the body
through the bloodstream, causing invasive disease. The
number of reported cases of invasive meningococcal disease
has been declining in the last few years. Fewer than 1,000
cases of invasive meningococcal disease have been reported
each year since 2009. The reason for this decline is not
known with certainty but at least partially may be due to
increased use of meningococcal conjugate vaccine.
The most common form of invasive disease caused by
N. meningitidis is meningitis.33 It typically presents with
nonspecific symptoms similar to other types of meningitis.
Symptom onset is usually sudden and can include high fever,
headache, myalgia, stiffness of the neck, and sensitivity to
30
Figure 3.15. ACIP Pneumococcal Vaccine Algorithm for Adults With Selected Conditions
Immunocompromised persons, persons with functional or anatomic asplenia,

persons with CSF leaks or cochlear implants
Is patient
1964 years
old?
NO
YES
Is patient
65 years
old?
NO
Refer to
Pediatric
Schedule.
YES
Has patient
received PPSV23
in the past?
NO
Give PCV13.
Has patient
received PPSV23
since turning
age 65 years?
8 weeks later
Give PPSV23.
YES
5 years later
YES
NO
Give PCV13 if it
has been at least
1 year after
last PPSV23 and
give PPSV23
8 weeks later if
it has been >5 years
since last PPSV23.
Give PPSV23.
How
many
doses?
Give PCV13
1 year
after last
PPSV23.
1
Give PCV13
1 year
after PPSV23.
Give PCV13
1 year
after last
PPSV23.
8 weeks later
Give PPSV23
if 5 years since
previous PPSV23.
After age 65 years, give PPSV23 if it

has beenat least 5 years since last
PPSV23 and 1 year after last PCV13.
The lifetime maximum number of doses
of PPSV23 is 3.
ACIP = Advisory Committee on Immunization Practices;

CSF = cerebrospinal fluid; PCV13 = 13-valent
pneumococcal conjugate vaccine; PPSV23 = 23-valent
pneumococcal polysaccharide vaccine.
31
light. In addition to meningitis, N. meningitidis can cause

sepsis, pneumonia, arthritis, otitis media, and epiglottitis.
Despite appropriate antibiotic therapy, approximately 9% to
12% of patients die from invasive meningococcal disease.1
If the bacteria invade the bloodstream, the death rate can
reach up to 40%. Those who survive meningococcal infection
can have significant complications such as hearing loss,
neurological damage, and limb loss.
Risk factors for meningococcal disease include certain
immunodeficiencies. In addition, antecedent viral infection,
crowded housing, chronic underlying illness, and active
and passive smoking are associated with increased risk for
disease.87 First-year college students living in dormitories have
been found to have higher risk for meningococcal disease
than other students.
The first quadrivalent polysaccharide vaccine for the prevention
of meningococcal disease was licensed in 1981. The first
conjugate vaccine was approved and recommended for use in
2005. The incidence of meningococcal disease has declined
annually since a peak of disease in the late 1990s. Although
the disease incidence is currently at a historically low rate, 10%
to 15% of those who contract the disease continue to die from it,
and an additional 11% to 19% have long-term sequelae.87
Vaccines
Currently, three vaccines are available in the U.S. market

that protect against N. meningitidis serogroups A, C, Y, and
W-135 (MenomuneSanofi Pasteur; MenactraSanofi
Pasteur; and MenveoNovartis).88-90 Additionally, a bivalent
meningococcal vaccine (MenHibrixGlaxoSmithKline)
protects against C and Y in combination with providing
protection against Hib.
These vaccines are not effective against serogroup B.1
Research is ongoing to develop a vaccine to protect against
serogroup B meningococcus.
Menomune (MPSV4) is a quadrivalent pure meningococcal
polysaccharide vaccine. Because this is a polysaccharide
vaccine, it is not generally effective in children younger than 2
years of age. Menactra and Menveo are protein-conjugated
meningococcal vaccines (also referred to as MCV4 or
MenACWY). Menactra is licensed for patients 9 months to
55 years of age; Menveo is licensed for patients 2 months to
55 years of age. MCV4 is preferred over MPSV4 for patients
aged 55 years and younger. MenHibrix (Hib-MenCY) is a
polysaccharide vaccine in combination with Hib approved
only for children 6 weeks to 18 months of age.
Nearly 98% of patients will develop high levels of antibodies

after vaccination.1 Protection will not usually be achieved for
at least 7 to 10 days after vaccination.
ACIP recommends routine vaccination for the following

patients87:
Adolescents aged 11 to 12 years, with a booster dose
at 16 years.
All previously unvaccinated adolescents aged 13 to 15
years, with a booster dose at age 16 to 18 years.
Children aged 2 months to 10 years with high-risk
conditions.
People aged 2 months to 55 years who are at high risk
for meningococcal disease.
People at high risk include:
College freshmen living in dormitories.
Military personnel.
Patients with anatomic or functional asplenia.
Patients with immunodeficiencies (e.g., complement
component deficiency).
People who travel to countries where N. meningitidis is
endemic (e.g., meningitis belt of sub-Saharan Africa).
People who travel to countries where vaccination is
required (e.g., travelers to Saudi Arabia for annual Hajj).
Microbiologists who routinely handle N. meningitidis
isolates.
A single dose of meningococcal conjugate vaccine should

be administered to all patients in any of the target groups
listed in the previous section. ACIP now recommends routine
vaccination with MCV4 for all adolescents 11 to 12 years
of age, followed by a booster dose given at 16 years of
age.87 This recommendation is based on evidence suggesting
that people immunized at age 11 or 12 years may have
decreased protective immunity after 5 years, when their risk
for meningococcal disease is greatest.
All adolescents aged 13 to 18 years who have not received
MCV4 should receive a dose of the meningococcal conjugate
vaccine. Adolescents who receive the first dose of MCV4
at 13 to 15 years of age should receive a booster dose at
32
16 to 18 years of age with a minimum interval of at least 8

weeks between doses. Healthy people who receive their first
routine dose of MCV4 at or after age 16 years do not need
a booster dose. Routine vaccination of healthy people who
are not at increased risk of exposure to N. meningitidis is not
recommended.
Patients with certain medical conditions (i.e., persistent
complement component deficiency, anatomical or functional
asplenia, or HIV infection) should receive 2 doses of MCV4
at least 8 weeks apart.87 A single dose of MCV4 in these
patients will not produce a sufficient immune response to
provide complete protection. Although HIV infection is not an
indication for MCV4 vaccination, an HIV-infected person may
have another indication for vaccination (e.g., international travel). People with HIV infection and an indication
for vaccination should receive a 2-dose primary series.
Children younger than 19 months at increased risk of
exposure or with high-risk medical conditions (e.g., asplenia)
should receive either an infant age-appropriate series of
Hib-MenCY or MCV4; (see the child and adolescent schedule
for detailed recommendations based on high-risk condition).84
MenHibrix should not be administered to a child who travels
to sub-Saharan Africa or the Hajj, or to international travelers
who require meningococcal vaccine because it does not
contain serogroups A or W-135. Only Menveo (for patients
aged 2 months and older) or Menactra (for patients aged
9 months and older) should be administered.
Previously, ACIP recommended only MPSV4 (Menomune) for use
in adults aged 56 years and older. The most recent meningococcal recommendations, published in March 2013, recommend
the use of either MCV4 vaccine (Menactra or Menveo) for adults
age 56 years and older who (1) were vaccinated previously with
MCV4 and now need revaccination or (2) are recommended to
receive multiple doses (e.g., adults with asplenia, microbiologists
working with N. meningitidis). Both MCV4 vaccine products
are licensed for use in people through 55 years of age, which
means that the ACIP-recommended use of these vaccines in
people aged 56 years and older is off-label. MPSV4 should
be used only for previously unvaccinated persons 56 years and
older who are expected to need a single dose of meningococcal
vaccine, such as an international traveler or in response to a
meningococcal outbreak.87
All meningococcal vaccines (i.e., Hib-MenCY, MCV4, and
MPSV4) are recommended for control of disease during
community meningitis outbreaks. Pharmacists should
refer to their local health department for advice regarding
immunization during meningococcal outbreaks.
Revaccination
Children at continued risk for meningococcal disease who

were previously vaccinated with MCV4 or MPSV4 should
receive an additional dose of MCV4 after 3 years if the first
dose was administered at 2 to 6 years of age. Patients who
have completed the 2-dose primary series and remain at
continued risk for meningococcal disease should be revaccinated 5 years after the last dose of the primary series.87
Patients with persistent complement component deficiency
or anatomic or functional asplenia should receive 1 dose of
MCV4 every 5 years after completing the 2-dose primary
series with MCV4.87
Any patient meeting the above criteria and having no valid

contraindications or precautions should receive meningococcal
vaccine.1 Meningococcal vaccines are contraindicated in
individuals who have had a severe allergic reaction (e.g.,
anaphylaxis) to a previous vaccine dose or to a vaccine
component. Moderate or severe acute illness with or without
fever is a precaution.
A history of Guillain-Barr syndrome had previously been
a precaution for Menactra (MCV4). The CDC and FDA, in
partnership with state health departments, have been monitoring
cases of Guillain-Barr syndrome among adolescents who
received MCV4. With more than 2 million doses of Menactra
given since 2005, there has been no evidence of an increased
risk of Guillain-Barr syndrome. Based on this information, ACIP
removed the precaution for use of Menactra in people with a
history of Guillain-Barr syndrome.87
The most common adverse events after administration of

meningococcal vaccine are injection-site reactions. Adverse
effects are generally mild, and may include pain and redness
at the site of injection. Systemic reactions (e.g., headache,
malaise, fever) also have been reported.
Storage and Administration of Meningococcal

Vaccines
Meningococcal vaccines should be stored in the refrigerator

at 2C to 8C (35F to 46F) and protected from light at all
times.12,46 For MCV4, pharmacists should shake the vial or
prefilled syringe before use, and administer the 0.5 mL dose
intramuscularly. Menveo must be prepared for administration
33
by reconstituting the MenA lyophilized conjugate vaccine

component with the MenCYW-135 liquid conjugate vaccine
component according to manufacturers instructions. For
MPSV4, pharmacists should reconstitute the product according
to the manufacturers instructions just before use and administer
the 0.5 mL dose of MPSV4 subcutaneously. (MPSV4 should not
be administered intramuscularly.)
Hepatitis A
Hepatitis A is an acute infection caused by a picornavirus.1

Hepatitis A is spread by the fecal-oral route and by consuming
contaminated food and water. The hepatitis A virus enters
the body through the mouth and can be found in the stool of
infected people. The virus replicates in the liver of infected
people.
Before the availability of the hepatitis A vaccine, approximately 20,000 to 30,000 cases of hepatitis A were reported
in the United States each year.33 With the use of safe and
effective vaccines, the incidence of hepatitis A in this country
has declined significantly. However, hepatitis A infection
remains endemic in other areas of the world. People at risk
for hepatitis A infection include international travelers, men
who have sex with men, and users of illegal drugs.
The incubation period for hepatitis A is 15 to 50 days.

Hepatitis A is characterized by fever, nausea, vomiting,
liver inflammation, jaundice, and dark urine. The disease is
usually more severe among adults than children. Symptoms
of hepatitis A usually last 1 to 2 months but can persist up to
6 months. Complications can include liver failure and, rarely,
death. Hepatitis A does not cause chronic infection or chronic
liver disease.33
Vaccines
Two inactivated vaccines are currently licensed in the United

States (HavrixGlaxoSmithKline; VaqtaMerck).12,91,92 Each
of these vaccines is available in two different formulations: a
pediatric formulation for patients aged 12 months to 18 years
and an adult formulation for patients older than 18 years of
age. Pharmacists should choose the appropriate formulation
based on the age of the patient receiving the vaccine. The
volume of the dose differs depending on the formulation used.
The recommended vaccine schedule is the same for both
brands. Twinrix (GlaxoSmithKline) may be used for individuals
who require both hepatitis A and hepatitis B vaccine.
The first dose of the hepatitis A vaccine provides protective

levels of antibodies in more than 95% of patients and nearly
100% of patients will be fully protected after completing the
2-dose series.1
According to ACIP, hepatitis A vaccine should be routinely

recommended for all children 12 to 23 months of age, any
person at increased risk for infection, or any person wanting
to reduce the risk of hepatitis A infection.93 People traveling
internationallywith the exception of travel to Canada,
Western Europe, Japan, New Zealand, or Australiashould
be vaccinated against hepatitis A. Vaccination should
be routinely recommended for household members and
other close personal contacts of internationally adopted
children arriving from areas of the world where hepatitis A is
endemic.94
Additionally, men who have sex with men, injection drug
users, laboratory workers potentially exposed to this virus,
people with chronic liver disease or clotting factor disorders,
or any other person at increased risk for hepatitis A infection
should be vaccinated. Hepatitis A vaccine is not routinely
recommended for health care workers, day care workers,
sanitation workers, or food handlers, although the vaccine
may be recommended for food handlers in some areas.
Hepatitis A vaccine also plays a role in postexposure
prophylaxis for individuals who have been exposed to
hepatitis A. Pharmacists should refer to up-to-date recommendations in such circumstances.
Children should receive 2 doses of vaccine with the first dose

given at 1 year of age, followed by a booster dose 6 to 12
months later.93 Adults should receive an initial dose followed
by a booster dose 6 to 18 months later. For travelers, it is
preferable to administer the dose of vaccine at least 2 weeks
before travel to allow time for the patient to develop protective
antibodies against hepatitis A virus. However, when less than
2 weeks are available, the vaccine may be administered any
time before departure.
The hepatitis A vaccine should be administered when

appropriate unless the patient has a valid contraindication or
precaution to receiving the vaccine. Hepatitis A vaccines are
contraindicated in individuals who have had a severe allergic
34
reaction (e.g., anaphylaxis) to a previous vaccine dose or to a

vaccine component. Moderate or severe acute illness with or
without fever is a precaution.
The most common adverse events following hepatitis A

vaccination include injection-site reactions. Redness, pain, or
swelling at the site of injection are common. Some patients
report mild systemic symptoms (e.g., low-grade fever). Serious
systemic reactions are uncommon.
Storage and Administration of Hepatitis A Vaccine
Hepatitis A vaccines should be stored in the refrigerator at

2C to 8C (35F to 46F); these vaccines should not be
frozen.12,46 To administer hepatitis A vaccines, shake the vial
or prefilled syringe before use. For children and adolescents
1 to 18 years of age, administer 0.5 mL intramuscularly. For
adults 19 years and older, administer 1 mL intramuscularly.
fever, malaise, and headache. As the infection progresses,

patients may experience additional symptoms such as nausea,
vomiting, right upper quadrant pain, and myalgias. Acute
illness most often involves jaundice, characterized by yellow
skin, yellow eyes, and dark urine. Many patients will recover
from an acute case of hepatitis B infection. However, others
will develop complications from the disease. Some infected
patients develop acute liver failure, which can lead to hospitalization and high mortality risk.
Younger individuals are more likely to develop chronic
infection; the risk is 90% if infected at birth, 50% if infected
at 1 to 5 years of age, and 5% if infected as an adult.1 (The
increased risk at birth is a primary factor supporting a birth
dose of hepatitis B vaccine for all infants.) Chronic infection
can lead to cirrhosis, hepatocellular carcinoma, and death.
Hepatitis B causes up to 80% of hepatocellular cancers.1
Nearly 25% of people with chronic hepatitis B infection will
die prematurely.
Vaccines
Hepatitis B
The hepatitis B virus is a bloodborne pathogen transmitted by

exposure to infected blood or body fluids.1,95,96 It is a small
DNA virus that specifically infects humans. The virus replicates
in the liver, causing complications such as acute hepatitis,
chronic hepatitis, cirrhosis, liver cancer, and death.
Worldwide, an estimated 2 billion people have been infected
with hepatitis B at some point in their lives, and more than
350 million people worldwide suffer from chronic hepatitis B
infection.1 In the United States, an estimated 1.4 million
people are chronically infected with hepatitis B virus.97
Patients with chronic hepatitis B can infect other people, even
when asymptomatic. According to the CDC, 38,000 new
cases of hepatitis B occurred in 2008.97 More than half of
new infections result from sexual contact with an infected
person.1 Injection drug use, household contact, and health
care exposures are also risk factors for hepatitis B.
Hepatitis B infection develops after an incubation period

of 2 to 5 months, during which individuals are infectious.
Approximately half of the people infected with hepatitis B are
asymptomatic. Those who are symptomatic will be contagious
for 1 to 2 months after the onset of symptoms. Symptoms
start with a prodrome of nonspecific symptoms such as
Hepatitis B vaccines consist of purified hepatitis B surface

antigen (HBsAg), a protein found on the outer viral coat.
The first such vaccine (Heptavax BMerck) was produced
from human serum and available from 1981 to 1991.
Subsequently, recombinant DNA technology made it possible
to harvest HBsAg from genetically engineered brewers yeast
(Saccharomyces cerevisiae). Two vaccines utilizing this newer
technology are currently licensed (Recombivax HBMerck
and Engerix-BGlaxoSmithKline).1,98,99 The two hepatitis B
vaccines currently in the market are inactivated vaccines. Both
of these vaccines reduce the risk of disease by 80% to 100%
after 3 doses.1
A comprehensive strategy has been adopted by ACIP to

eliminate hepatitis B in infants, children, adolescents, and
adults.95,96 Infants should receive their first dose of hepatitis
B vaccine shortly after birth.95 A birth dose is vital to protect
against maternal transmission. Infants born to mothers positive
for HBsAg need both hepatitis B vaccine and hepatitis B
immune globulin (HBIG) promptly at birth.
The comprehensive strategy also calls for immunization of all
susceptible children and adolescents not previously vaccinated.
Adults who should receive hepatitis B vaccination include
those at risk for infection by sexual exposure (e.g., people with
multiple sex partners), those at risk for percutaneous exposure
35
to blood (e.g., health care workers), patients with diabetes,

patients with chronic liver or renal disease, patients infected
with HIV, international travelers, and all unvaccinated adults
who want to be protected against the illness regardless of risk
factors. Having a known risk factor for hepatitis B infection is
not a requirement for vaccination of adults.
In 2011, ACIP recommended that all previously unvaccinated adults aged 19 to 59 years with diabetes type 1 or
type 2 should be vaccinated against hepatitis B as soon as
possible after a diagnosis of diabetes is made.100 Patients
with diabetes aged 60 years and older may be vaccinated at
the discretion of the treating clinician based on the increased
need for assisted blood glucose monitoring in long-term care
facilities, likelihood of acquiring hepatitis B infection, need to
manage its complications or chronic sequelae, and likelihood
of immune response to vaccination.75 Because this is a
relatively new recommendation, many patients with diabetes
have not yet been vaccinated against hepatitis B. Pharmacists
should be proactive in offering hepatitis B vaccination to
patients with diabetes.
The first dose of hepatitis B vaccine should be administered to

all infants at birth.95 The second dose should be administered
at 1 to 2 months of age followed by the third and final dose
at 6 months of age. For infants who do not to receive a birth
dose, the series should be started as soon as possible. If the
infant falls behind the recommended schedule, the second
dose should be administered at least 4 weeks after the first
dose.84 The third dose should be administered at least 2
months after the second dose and at least 4 months after the
first dose. The third dose should not be administered before
24 weeks of age.
All adolescents without documentation of hepatitis B vaccine

should receive a primary series of hepatitis B vaccine.95 This
can be accomplished in one of two ways. A 3-dose series
can be completed with either Engerix-B or Recombivax
HB. The routine schedule for the 3-dose series is 0, 1, and
6 months.84 Another option is to use the adult dose of
Recombivax HB (10 g/1 mL) and administer this vaccine
in a 2-dose series to adolescents aged 11 to 15 years. This
2-dose series has been approved for use only in this age
group and only for Recombivax HB.98 The recommended
schedule for the 2-dose series is to administer the initial dose
to patients at age 11 to 12 years, followed by a second
dose 4 to 6 months after the first dose. This 2-dose series
has been shown to produce the same immunologic response
in this age group as the standard dose (5 g/0.5 mL) given
in the 3-dose series.95
All adults with an indication for the vaccine should receive
a complete 3-dose series of hepatitis B vaccine with either
Recombivax HB or Engerix-B.96 The routine schedule for
vaccination of adults is 0, 1, and 6 months. (If hepatitis A
vaccination is also required, Twinrix may be used.) Dosing
of hepatitis B vaccine in patients on dialysis depends on the
vaccine used; specific dosing information is shown in
Table 3.5.
Testing for Immunity
Routine testing for immunity after vaccination is not generally

recommended. Serological confirmation of the immune
response to vaccination is recommended only for people in
the following risk groups1:
Health care workers at risk of exposure to blood or
body fluids in the workplace.
Infants born to HBsAg-positive mothers.
Table 3.5. Hepatitis B Vaccine Dosing, Intramuscular

Recombivax HB
Dose
Volume
5 g
0.5 mL
10 g
Adults aged 20 years

Individuals on dialysis
Birth to age 19 years

Adolescents aged 1115 years
No. of
Doses
Engerix-B
No. of
Doses
Dose
Volume
10 g
0.5 mL
1 mL
10 g
1 mL
20 g
1 mL
40 g
1 mL
40 g
2 mL
4b
Recombivax HB is licensed by the Food and Drug Administration for dosing of adolescent patients who have not previously been immunized against hepatitis B, consisting of an
expedited 2-dose schedule, administered with the second dose 4 to 6 months after the initial dose. Engerix-B is not licensed for this use.
a
Engerix-B for individuals on dialysis: administer a series of 4 doses (2 mL each) as a single 2-mL dose or use 2 1-mL doses on a 0-, 1-, 2-, 6-month schedule.
Source: References 1, 98, and 99.
36
Immunocompromised individuals (e.g., dialysis patients,

people with HIV).
Sex partners of people with chronic hepatitis B virus
infection.
If a person seroconverts (i.e., develops measurable antibodies
after vaccination defined as hepatitis B surface antibody
[anti-HBs] titer of 10 mIU/mL or higher following 3 properly
spaced doses of vaccine), protection from hepatitis B disease
infection appears to persist indefinitely. However, anti-HBs
antigen antibody levels will gradually decline to undetectable
levels in the blood. For all immunocompetent patients,
protection seems to persist after 3 doses even if circulating
anti-HBs antibodies fall to undetectable levels. This protection
is related to the memory T lymphocytes that develop after
vaccination and persist despite the lack of measurable
antibodies circulating in the bloodstream.
Anti-HBs antigen antibody titers should be measured 1 month
after the third dose of the vaccine series to determine whether
the person has seroconverted. Infants born to HBsAg-positive
mothers should be tested 3 to 12 months after the last dose.
People who initially achieve an anti-HBs antibody titer of
10 mIU/mL after immunization have responded to the
vaccine and are considered protected. For those who do
not seroconvert, refer to the CDC recommendations
regarding repeat vaccination.1
Additional Dosing Information for Hepatitis B Vaccine
Recombivax HB and Engerix-B are essentially interchangeable,

but the dosage in microgram content per dose varies between
the two brands (Table 3.5).1,98,99 Because intermittent changes
in recommended dosing or package concentrations can
occur, pharmacists should not memorize this dosing table.
Pharmacists should always refer to updated references and be
familiar with the vaccine they stock and the appropriate doses
for that product. Pharmacists should verify the volume to be
administered to deliver the appropriate dose in micrograms
based on the specific product being used.
Unless a contraindication or precaution is present, the

vaccine can be administered to all eligible infants, children,
adolescents, and adults. Hepatitis B vaccines are contraindicated in individuals who have had a severe allergic
reaction (e.g., anaphylaxis) to a previous vaccine dose or to
a vaccine component. Moderate or severe acute illness with
or without fever is a precaution.
Transient adverse events that can be expected after administration of hepatitis B vaccine include injection-site pain, fatigue,
headache, or low-grade fever. Serious reactions are rare.
Storage and Administration of Hepatitis B Vaccine
Hepatitis B vaccines should be stored in the refrigerator at

2C to 8C (35F to 46F); these vaccines should not be
frozen.12,46 To administer hepatitis B vaccines, shake the vial
or prefilled syringe before use. Administer the appropriate
dose (Table 3.5) intramuscularly shortly after preparation.
Rotavirus
Rotavirus is a double-stranded RNA virus that, prior to the

availability of a vaccine, infected nearly every child by
5 years of age.1 It is the most common cause of severe
gastroenteritis in infants and children.101 Rotavirus is most
commonly contracted by children between the ages of 6 and
24 months. In the prevaccine era in the United States,
rotavirus gastroenteritis peaked in the cooler months and
typically progressed from the Southwest during November and
December to the Northeast by April and May.
The primary means of transmission is by the fecal-oral route

through person-to-person contact or contact with fomites
(contaminated objects). After an incubation period of 24 to
72 hours, the infected person may develop symptoms that can
range from self-limiting watery diarrhea to severe diarrhea
with fever and vomiting. The symptoms typically last for 3 to
7 days. Rotavirus infection in infants and children can result
in more serious disease such as severe diarrhea, dehydration,
electrolyte imbalances, and in some cases, death.
An initial infection with rotavirus after 3 months of age is
most likely to cause severe gastroenteritis and dehydration.1
Infection with rotavirus can occur several times throughout
a persons lifetime and it appears that initial infection may
protect a child from developing subsequent severe gastroenteritis. After a single natural infection, 38% of children are
protected against subsequent infection with rotavirus, 77% are
protected against subsequent rotavirus-associated diarrhea
of any severity, and 87% are protected against subsequent
moderate-to-severe rotavirus-associated diarrhea.101
Therefore, vaccination, which mimics the immunoprotective
response from a natural infection in an individual, should help
prevent rotavirus infection and its associated complications.
37
Each year during the 1990s and early 2000s, rotavirus

resulted in approximately 410,000 physician visits, 205,000
to 272,000 emergency department visits, and 55,000 to
70,000 hospitalizations among U.S. infants and children,
with total annual direct and indirect costs of approximately
$1 billion.101 Vaccination against rotavirus has been shown
to decrease the morbidity, health care expenditures, and
mortality associated with this disease.33,102
Vaccines
Currently, there are two FDA-licensed rotavirus vaccines

(RotaTeqMerck; RotarixGlaxoSmithKline).103,104 Both
vaccines are live, oral vaccines indicated for the prevention of
rotavirus gastroenteritis in infants and children.
Although RotaTeq and Rotarix are currently marketed in
the United States, they were not the first vaccines against
rotavirus. In 1998, an FDA-licensed rhesus-based tetravalent
vaccine (RotaShieldWyeth) was recommended for routine
vaccination of infants. However, in 1999, this vaccine
was voluntarily removed from the market because of an
apparent association with the development of intussusception.
Intussusception is an uncommon type of bowel obstruction
that occurs when the bowel folds in on itself. Intussusception
occurs most frequently in young children and often there is
no known cause. When identified and treated early, most
individuals will fully recover. Following administration of
RotaShield, the risk for intussusception was most elevated
within 3 to 14 days after receipt of the first dose of the
vaccine; there was also an increased risk within 3 to 14 days
after the second dose. Therefore, RotaShield was removed
from the market.
All infants without a valid contraindication should receive the

rotavirus vaccine. Infants who have had rotavirus gastroenteritis before completing the primary series should still
complete the entire series. Premature infants born before 37
weeks of gestation may receive the vaccine provided they are
at least 6 weeks of age, are being or have been discharged
from the hospital, are clinically stable, and the benefits of
receiving the vaccine outweigh the risks.105
ACIP does not express a preference for RotaTeq or Rotarix, but

does recommend that the same product be used to complete
the series whenever possible.105 RotaTeq is administered
orally in a 3-dose series, with doses administered at ages 2,

4, and 6 months. Rotarix is administered orally in a 2-dose
series, with doses administered at ages 2 and 4 months. If
RotaTeq is administered for any of the doses in the series, a
total of 3 doses must be given to provide adequate protection
for the patient.
The minimum age for the first dose of rotavirus vaccine is 6
weeks and the maximum age for the first dose is 14 weeks 6
days.84 Vaccination should not be initiated for infants ages 15
weeks 0 days or older because there are insufficient data on
the safety of a first dose in older infants. The minimum interval
between doses of rotavirus vaccine is 4 weeks. The maximum
age for the last dose of rotavirus vaccine is 8 months 0 days.
Children with a serious allergic reaction to a prior dose should

not receive the rotavirus vaccine. These vaccines should be
avoided in children with gastrointestinal problems or a history
of intussusception. Because these are live vaccines, they should
not be administered to immunocompromised children or
children with a history of severe combined immunodeficiency
because of the potential risk for vaccine-acquired rotavirus
infection.106
Rotavirus vaccines are contraindicated in patients who
have had a severe allergic reaction (e.g., anaphylaxis) to a
previous vaccine dose or to a vaccine component. The oral
applicator for Rotarix contains latex; patients with a history of
anaphylactic reaction to latex should not receive this brand.
Precautions include moderate or severe acute illness with or
without fever, pre-existing gastrointestinal disease, previous
history of intussusception, altered immunocompetence other
than severe combined immunodeficiency, spina bifida, or
bladder exstrophy.
The most common adverse events associated with rotavirus

vaccines include fever, vomiting, diarrhea, loss of appetite,
and irritability. There is a theoretical risk that the live virus
from the vaccine could be spread to susceptible contacts after
vaccination.105 Infants who have close contact with pregnant
women, immunocompromised individuals, and those on
immunosuppressive therapy may be vaccinated with consideration of the risks and benefits.
38
Large prelicensure clinical trials of both RotaTeq and Rotarix

did not find an increased risk for intussusception among
vaccine recipients. A large postlicensure study of more than
1.2 million rotavirus vaccine recipients found a very small
increased risk of intussusception (1 to 1.5 additional cases
of intussusception per 100,000 vaccinated infants) in the
7 to 21 days following the first dose. No increased risk of
intussusception was found after the second or third doses. The
CDC and FDA continue to believe that the benefits of rotavirus
vaccination outweigh the risks associated with vaccination and
that routine vaccination of infants should continue.107
A study conducted by the CDC Vaccine Safety Datalink from
May 2006 to February 2010 found no increased risk of
intussusception following vaccination with RotaTeq. However,
the study indicated an increased risk of intussusception
following dose 1 and dose 2 of Rotarix. Over 200,000
doses of Rotarix have been given to children monitored in the
Vaccine Safety Datalink. Based on these findings, 1 case of
intussusception would be expected for approximately each
20,000 children who are fully vaccinated.108
Storage and Administration of Rotavirus Vaccines
Rotavirus vaccines should be stored in the refrigerator at 2C

to 8C (35F to 46F) and protected from light at all times.12,46
RotaTeq Administration
RotaTeq is an oral suspension supplied in ready-to-use, 2 mL,

single-dose tubes. After removing the twist-off cap, the dosing
tube should be placed in the infants mouth, pointed toward
the inner cheek, and the tube squeezed gently until empty.
The entire contents of the tube should be administered to the
infant, however the tip of the tube may hold a residual drop.
There are no food or drink restrictions after the vaccine dose.
If the infant regurgitates, vomits, or spits out a small amount
of the vaccine, readministration is not recommended and
the infant should receive future vaccinations as scheduled.
RotaTeq should be administered as a 3-dose series to infants
at 2, 4, and 6 months of age.103
Rotarix Administration
Once removed from the refrigerator, Rotarix must be reconstituted prior to administration. Preferably, the 1 mL dose should
be administered as soon as possible after reconstitution but
it must be administered within 24 hours. The oral applicator
should be placed in the infants mouth, pointed toward the
inner cheek, and the tube squeezed gently until empty. The
entire contents of the applicator should be administered to the
infant. If the infant regurgitates, vomits, or spits out a small
amount of the vaccine, readministration is not recommended
and the infant should receive future vaccinations as scheduled.

Rotarix should be administered as a 2-dose series to infants at
2 and 4 months of age.104
Haemophilus influenzae type b
H. influenzae type b (Hib) is an aerobic gram-negative

coccobacillus.1 Hib is spread by respiratory transmission
from asymptomatic carriers. The polysaccharide capsule on
the bacteria allows it to evade the immune system and cause
disease. While this disease is rarely seen in patients older
than the age of 5 years, invasive Hib disease can cause
significant morbidity and mortality in children younger than
5 years of age.
Before the availability of vaccines, Hib affected 1 of every

200 children in the United States, accounting for more than
20,000 cases each year.1,33 It was the leading cause
of bacterial meningitis in children younger than 5 years
of age. Invasive Hib disease also caused epiglottitis,
pneumonia, osteomyelitis, arthritis, cellulitis, and bacteremia.
Complications of invasive Hib infection were significant,
including deafness and other neurologic sequelae (e.g.,
mental retardation, seizures, developmental delay) in up
to 30% of survivors.33 Hib had been the leading cause of
acquired mental retardation before widespread vaccination.
Mortality rates associated with Hib disease were also high
before vaccine use, with up to 5% of patients dying despite
appropriate antibiotic treatment.1 Hib vaccines have significantly lowered disease incidence from 20,000 cases in 1985
to 17 cases reported in 2010.109,110
Vaccines
The initial Hib vaccines were purified polysaccharide vaccines,

first licensed in 1985. Because polysaccharide vaccines are
not as effective in children younger than 2 years of age
and this disease most commonly affects young children
conjugated vaccines were developed to increase effectiveness
in young children.
The single-antigen Hib vaccines currently available in the U.S.
market include:
ActHIB (Sanofi Pasteur)
PedvaxHIB (Merck)
Hiberix (GlaxoSmithKline)
39
Currently available combination Hib vaccines include:

Comvax (Merck)protects against Hib and hepatitis B
Pentacel (Sanofi Pasteur)protects against Hib,
diphtheria, tetanus, pertussis, and polio
MenHibrix (GlaxoSmithKline)protects against Hib and
meningococcal serogroups C and Y
All infants without a valid contraindication should receive Hib

vaccine.110
The recommended schedule for vaccine use and the number

of doses needed depends on the vaccine product selected.
ActHIB requires a 3-dose primary series followed by a booster
dose and PedvaxHIB requires a 2-dose primary series followed
by a booster dose. The recommended routine vaccine
schedules for ActHIB and PedvaxHIB are shown in Table 3.6.1
Hiberix is approved only as a booster dose for use in children
15 months to 4 years of age who have completed the primary
series of Hib vaccines.110,111 Combination vaccines may be
used in situations where children require protection against
more than one disease. Children who are behind schedule
may not require a full series of 3 or 4 doses of Hib vaccine, and
the health care provider should consult the current childhood
immunization schedule to determine the appropriate dosing
schedule for the series when a child falls behind.
Hib vaccine is not routinely given to children aged 5 years or
older. However, patients with certain conditions (i.e., anatomic
or functional asplenia, sickle-cell disease, immunodeficiency,
immunosuppression, leukemia, or HIV infection) may be at
increased risk for invasive Hib disease. One dose of singleantigen Hib vaccine should be considered for older children,
adolescents, and adults with these high-risk conditions. If
indicated, these patients should receive a single 0.5 mL dose
of Hib conjugate vaccine.1
Hib vaccines are contraindicated for patients who have had

a severe allergic reaction (e.g., anaphylaxis) to a previous
vaccine dose or to a vaccine component. Precautions include
moderate or severe acute illness with or without fever.
Hib vaccines are well tolerated and adverse events after

vaccination are not common. Adverse events that may be
reported after receipt of Hib vaccine include transient injectionsite reactions such as swelling, redness, or pain. Systemic
reactions (e.g., fever) after vaccination are unusual, and
serious reactions are rare.
Storage and Administration of Haemophilus

influenzae type b Vaccines
Hib vaccines should be stored in the refrigerator at 2C to 8C
(35F to 46F); these vaccines should not be frozen.12,33 When
administering Hib vaccines, providers should shake the vial or
prefilled syringe before use and administer the 0.5 mL dose
intramuscularly.
Poliomyelitis
Poliomyelitis is caused by an enterovirus.1 There are three

poliovirus serotypes that cause disease (although type 2 virus
was eradicated worldwide in 1999). Antibodies against one
serotype do not produce significant protection against other
serotypes.
Polio viruses enter the body through the mouth and replicate
in the pharynx and gastrointestinal tract. Approximately 95%
of poliovirus infections are asymptomatic. Approximately
4% to 8% of polio infections consist of a minor, nonspecific
illness that are indistinguishable from other viral illnesses.
In approximately 1% of infections, viruses enter the central
Table 3.6. Haemophilus influenzae type b Routine Vaccine Schedule

Age of Patient
Vaccine
2 Months
4 Months
6 Months
1215 Months
ActHIB
Dose 1
Dose 2
Dose 3
Booster
PedvaxHIB
Dose 1
Dose 2
Booster
40
nervous system from the bloodstream and destroy the anterior

horn cells of the spinal cord. This causes flaccid paralysis of
muscles, but leaves sensory function intact.1 Many individuals
with paralytic poliomyelitis recover completely and, in
most, muscle function returns to some degree. Weakness
or paralysis still present 12 months after onset is usually
permanent.1
Asymptomatic patients can transmit the virus to other people.
Poliomyelitis is communicable beginning 7 to 10 days before
the onset of symptoms. Viruses can be shed in the stool for 3
to 6 weeks in both symptomatic and asymptomatic infected
patients.
Vaccines
An inactivated poliovirus vaccine (IPV) was first licensed in

1955. A trivalent, oral attenuated poliovirus vaccine (OPV)
was licensed in 1963. OPV was the vaccine of choice in the
United States following its approval; this live vaccine was very
effective, conferred long-lasting immunity, and it was easy to
administer. Unfortunately, because the live attenuated viruses
in the vaccine were shed in the stool, it was possible for the
shed virus to spread to susceptible contacts of the vaccinated
person thereby causing vaccine-associated paralytic
poliomyelitis. The overall risk of vaccine-associated paralytic
poliomyelitis was 1 case per 2 million to 3 million OPV doses
distributed, affecting 8 to 10 people per year in the United
States.1
Concerns about the risks associated with OPV prompted the
development of an enhanced potency inactivated poliovirus
vaccine (IPOLSanofi Pasteur), which was licensed in 1987.
Owing to the availability of this safe, effective IPV, distribution
of OPV in the United States ceased in 2001 and IPV became
the vaccine of choice. IPV is highly effective in producing
immunity, with 99% of patients developing protective antibody
levels after 3 doses.1 In addition to protecting people from
the disease, IPV has the advantage of being an inactivated
vaccine and therefore cannot cause paralytic poliomyelitis.
Polio Eradication
Disease rates rapidly fell with widespread use of the polio

vaccines, leading to elimination of polio disease in the
United States and other countries. The Western hemisphere
was certified as polio-free in 1994. Even though there are
no reported cases of polio in the United States, continued
immunization is needed to guard against imported infections.
The World Health Organization (WHO) had hoped to
eradicate poliovirus from the entire planet by 2005, however
disease still exists in a few countries in Africa, Asia, and

the Middle East. More information on global poliovirus
eradication efforts can be found online at
www.polioeradication.org.
Vaccinate all children against poliovirus.112 Routine

vaccination of adults is not recommended unless the adult is
traveling overseas to a poliovirus-endemic area.
The recommended IPV schedule is to vaccinate all children at

ages 2 months, 4 months, 6 to 18 months, and 4 to 6 years.
For an adult requiring vaccination, the recommendations vary
depending on the individuals vaccination history112:
Written documentation of having completed the primary
series: administer 1 booster dose of IPV.
Written documentation of having received 1 but not all
doses of the series: administer the remaining doses of
the series.
No documentation of polio vaccination: administer the
primary series of 3 doses of IPV. The recommended
schedule is 0, 1 to 2 months, and 6 to 12 months.
However, if time is a factor and the patient must
travel before completing the series, refer to the ACIP
guidelines for additional information on how to
appropriately schedule the vaccine series to maximize
protection for the patient.
Any child or adult who needs IPV should receive the vaccine
unless a valid contraindication or precaution is present. IPV
contains trace amounts of streptomycin, polymyxin B, and
neomycin, which can cause hypersensitivity in patients who
are sensitive to these antibiotics.12
Precautions include moderate or severe acute illness with or
without fever, and pregnancy.
The most commonly reported adverse events after IPV administration are local injection-site reactions. No serious adverse
reactions have been reported after vaccination.
41
Storage and Administration of Poliomyelitis Vaccine
IPV should be stored in the refrigerator at 2C to 8C (35F to

46F); the vaccine should not be frozen.12,46 When administering IPV, providers should shake the vial or prefilled syringe
before use and administer the 0.5 mL dose of IPV either
intramuscularly or subcutaneously.
Everyone involved in vaccine delivery must exercise caution

to select the proper combination product to ensure that
the patient receives the appropriate vaccines to provide
protection. Furthermore, it is important to document each
individual antigen administered. For example, if Twinrix is
administered to a patient, the pharmacist should record in the
immunization record that the patient received both hepatitis A
and hepatitis B vaccines.
Combination Vaccines
Vaccine manufacturers have developed a wide variety of

combination vaccines to reduce the number of injections
required to fully vaccinate patients. These combinations tend
to make immunization more acceptable, especially to parents
of children who prefer the reduced number of injections.
Currently licensed combination vaccines (as of December
2013) include:
Comvax (Merck)protects against Hib and hepatitis B
Kinrix (GlaxoSmithKline)protects against diphtheria,
tetanus, pertussis, and polio
MenHibrix (GlaxoSmithKline)protects against Hib and
meningococcal serogroups C and Y
Pediarix (GlaxoSmithKline)protects against diphtheria,
tetanus, pertussis, hepatitis B, and polio
Pentacel (Sanofi Pasteur)protects against diphtheria,
tetanus, pertussis, polio, and Hib
ProQuad (Merck)protects against measles, mumps,
rubella, and varicella
Twinrix (GlaxoSmithKline)protects against hepatitis A
and hepatitis B
As noted earlier, ACIPs general recommendations regarding
use of combination vaccines state that use of a combination
vaccine generally is preferred over its equivalent component
vaccines.31 Licensed combination vaccines can be used
whenever any components of the combination are indicated
and its other components are not contraindicated and if
licensed by the FDA for that dose in the series. Use of
combination vaccines can reduce the number of injections
and alleviate concern associated with the number of
injections. While the combination vaccines may be preferred
to decrease the number of necessary injections, the array
of products can present the opportunity for confusion
due to sound-alike product names or choosing the wrong
combination product.
Non-Routine Vaccines
Pharmacists may be involved in the administration of vaccines

that do not appear on routine immunization schedules.
Non-routine vaccines include those used to prevent rabies,
immunizations for international travelers, and vaccines that
could be used to protect against bioterrorism agents.
Rabies
Rabies is caused by a rhabdovirus, a group of RNA viruses.

Transmission of the virus to humans is from the bite of an
infected animal. While all mammals (e.g., dogs, skunks,
raccoons) may transmit the virus, bat exposures are the most
common source of transmissions in the United States.113 Once
the virus enters the body, it affects the central nervous system,
causing acute encephalitis and neurologic dysfunction.
On average, only 1 or 2 rabies cases are reported in humans
in the United States each year.113 Even though these numbers
are small, concern persists because rabies is almost always
fatal if left untreated. In modern history, only 2 people are
known to have survived rabies infection without receiving
postexposure prophylaxis.114
Each year, approximately 16,000 to 39,000 people receive
rabies postexposure prophylaxis because they have come
in contact with potentially rabid animals.115 Oftentimes, it is
difficult to capture or find the animal that inflicted the wound
to determine the presence of rabies in the animal. If the rabies
status of the animal is unknown, the vaccine is often given to
protect the patient because the benefits of giving the vaccine
(i.e., preventing death) outweigh the risks (i.e., low adverse
effect profile).
Rabies Vaccines
Currently, two formulations of rabies vaccines are available in

the United States: human diploid cell vaccine (ImovaxSanofi
Pasteur) and purified chick embryo cell vaccine (RabAvert
Novartis). Additionally, two formulations of rabies immune
42
globulin, which are used for postexposure management to

provide immediate short-term antibody protection against
rabies virus, are currently marketed in the United States:
Imogam Rabies-HT (Sanofi Pasteur) and HyperRAB S/D
(Talecris).
recreational activities, quality of lodging, season of year,

altitude, mode of travel, and other factors. The proper set of
vaccines needed for an individual depends on that persons
previous vaccinations, age, occupation, activities, health
status, and itinerary.
Although travelers usually focus on the need for protection

against exotic diseases (e.g., yellow fever, typhoid fever), it
is no less important to ensure that travelers have received
all routine vaccinations. Some of these diseases, such as
measles, mumps, and rubella occur far more frequently in
developing countries than in the United States. As mentioned
previously, some vaccines have specific travel indications (e.g.,
hepatitis A, meningococcal, poliovirus).
Rabies vaccine is appropriately used for pre-exposure

prevention in specific populations. For example, people
with possible occupational exposures (e.g., veterinarians,
laboratory workers who have contact with animals) are
candidates for pre-exposure prophylaxis. In addition, travelers
at increased risk for contact with rabid animals in regions
without accessible health care for postexposure prophylaxis
to prevent rabies may be candidates for pre-exposure
prophylaxis.
According to the current recommendations from ACIP,
postexposure prophylaxis to prevent rabies should include
prompt cleansing of the wound, followed by administration
of both rabies vaccine and rabies immune globulin.115
Postexposure prophylaxis is considered a medical urgency, not
a medical emergency. Patients with potential rabies exposures
should be referred to experts in the field of rabies for
appropriate postexposure prophylaxis. Local and state public
health departments may be valuable resources of information
in these cases.
Vaccines for International Travel
Pharmacists who are involved with international travelers

health perform a valuable service by helping people who
may otherwise travel without proper medical advice and
the proper prophylaxis to help avoid preventable infections.
Travel advice is complex and must be comprehensive to fully
protect the patient. This section is not designed to prepare
pharmacists to provide comprehensive international travel
services; rather, it is intended to complete the review of
vaccines available in the U.S. market. Before recommending
the vaccines mentioned in this section, pharmacists should
receive additional training regarding the use of these vaccines,
indications and contraindications, dosing and administration,
and potential adverse effects. Pharmacists interested in
establishing a travel health service may consult the American
Pharmacists Associations advanced competency training
program, Pharmacy-Based Travel Health Services, available in the
Continuing Education section of www.pharmacist.com.
Health risks are not uniform within any country because the
medical threat varies according to destination, business and
Yellow Fever
Yellow fever is a viral infection that can be transmitted to a

human by a bite from an infected mosquito.116,117 The yellow
fever vaccine (YF-VaxSanofi Pasteur) contains live attenuated
viruses and needs to be refrigerated.118 Yellow fever vaccine
must be used or discarded within 60 minutes of reconstitution.
The 0.5 mL dose is administered by subcutaneous injection,
and 10-year booster doses are required for individuals with
continued exposure.
Administration of yellow fever vaccine is limited to provider
sites that have been issued a special permit by their state
health departments to be authorized yellow fever vaccination
centers. In many states, only one or two vaccine provider sites
statewide may have yellow fever certificate approval. ACIP
released revised guidelines on the use of yellow fever vaccine
in 2010.118 Pharmacists involved in providing yellow fever
vaccination must consult updated references for additional
information prior to administering the vaccine.116-118
Typhoid Fever
Typhoid is a food- and water-borne illness caused by the

bacterium Salmonella typhi.119 Options for typhoid prevention
include a 4-dose series of live attenuated oral typhoid vaccine
capsules or a single injection of inactivated typhoid polysaccharide vaccine.
The live attenuated typhoid vaccine (VivotifBerna) is given
orally in the form of capsules. The regimen is 1 capsule every
other day for 4 doses (i.e., over 7 days). Patients should be
directed to swallow the capsules 1 hour before meals, using
water that is cooler than body temperature. The capsules
should be refrigerated between doses. Oral typhoid vaccine
should not be given concurrently with antibiotics, including
several medications used in antimalarial therapy (which may
43
be a barrier for travelers to malaria-endemic areas). This live

vaccine may be administered to individuals aged 6 years and
older. Immunity persists longer than with inactivated typhoid
vaccine; however, if the recipient continues travel or remains
in a typhoid-endemic area, the oral vaccine series should be
administered every 5 years.
One inactivated typhoid vaccine (Typhim ViSanofi Pasteur)
is currently marketed in the United States. It is administered
by intramuscular injection. This vaccine is approved for use
in individuals aged 2 years and older. Waning immunity
requires the vaccine to be readministered every 2 years if risk
of exposure persists.
Japanese Encephalitis
Japanese encephalitis is a mosquito-borne viral illness endemic

in areas of Asia.120 It is the most common cause of encephalitis in Asia. One Japanese encephalitis vaccine is licensed
in the United States (IxiaroNovartis). (In 2006, production
of the previously available JE-Vax was discontinued.) Ixiaro
is an inactivated vaccine that is administered intramuscularly
as a 2-dose series at 0 and 28 days. It is approved for use
in patients 2 months of age and older. Japanese encephalitis vaccine is recommended for travelers who plan to spend
1 month or longer in endemic areas during the Japanese
encephalitis transmission season.
Agents of Bioterrorism
Attacks by terrorists with anthrax spores in autumn 2001

reminded Americans of the lethality of germs used as
weapons. Letters containing anthrax spores were mailed
to several news media offices and 2 U.S. Senators, killing
5 people and infecting 17 others. Communities across the
country re-evaluated their emergency response plans following
this event. In the event of an act of bioterrorism, post-outbreak
efforts are likely to involve the distribution of both antibiotics
and vaccines. Pharmacists can help their communities by
understanding and assisting with local response plans.
Smallpox
Smallpox is a potentially deadly disease caused by the

variola virus and is fatal in approximately 30% of infected
individuals.121 The last naturally acquired case of smallpox
occurred in Somalia in 1977. Smallpox eradication was
certified by the World Health Assembly in 1980.
Although only 2 countries (i.e., the United States and
Russia) are known to have stocks of smallpox virus, there is
concern that other countries or individuals also might have
the virus and could use it as a bioterrorism agent. The

U.S. Government maintains a stockpile of smallpox vaccine
sufficient for the entire population of the country.121
The current licensed vaccine (ACAM2000Sanofi Pasteur)
is a lyophilized, live vaccinia virus vaccine. A single drop
of vaccine is placed on the tip of the bifurcated needle and
then, while holding the skin of the deltoid area taut, 3 or 15
(depending upon primary or revaccination) rapid and tightly
concentric punctures are made to the skin. A small amount of
blood (a petechia) should be seen after vaccination to ensure
the skin has been penetrated and vaccine administered. A
lesion will develop at the site of vaccination. Because vaccinia
virus can spread from the vaccination site to other people
until the scab has fallen away, the lesion must be protected
carefully by bandaging for approximately 2 to 3 weeks while
the lesion progresses from a red papule to a pustule to a scab.
Vaccinated people also can spread vaccinia virus to other
areas of their own body through autoinoculation if the vaccine
site is rubbed and then touched to other areas.
The CDC restricted its initial recommendations for vaccination
to: (1) smallpox response teamsthose responding to
investigate cases and initiate control measures, as well as
those responsible for administering smallpox vaccine in the
pre-event vaccination program and (2) smallpox health
care teamsthose health care personnel from participating
hospitals who will be asked to evaluate, manage, and treat
the initial suspected and diagnosed cases. The CDC does
not recommend routinely vaccinating the general population
against smallpox because of the adverse effect profile of
smallpox vaccination.
Pharmacists interested in learning more about smallpox
vaccine should consult ACIP recommendations as well as the
CDCs website (www.bt.cdc.gov/agent/smallpox/).
Anthrax
Anthrax disease is caused by a gram-positive spore-forming

rod, Bacillus anthracis.122 The bacteria can live in the soil
and may remain dormant for many decades. Animals can
become infected when they eat or inhale the spores. Humans
can become infected if they come in contact with an infected
animal, consume contaminated meat from an infected
animal, or inhale spores from the environment. Anthrax
infection can be cutaneous, gastrointestinal, or inhalational,
with inhalational being the most serious. Left untreated,
inhalational anthrax is usually fatal. Interested pharmacists
should consult an infectious diseases text for more information.
44
The best protection against anthrax is vaccination with anthrax

vaccine adsorbed (BioThraxEmergent BioSolutions). The
vaccine is inactivated and has been licensed by the FDA since
1970. The administration schedule involves a 5-dose series of
0.5 mL intramuscular injections at 0 weeks, 4 weeks, 6 months,
12 months, and 18 months, plus annual booster doses.122
The vaccine is routinely administered to at-risk personnel
working in selected laboratories and in people engaged in
activities at high risk for exposure (e.g., military personnel).
Appropriate identification of an exposure to anthrax is
important because the vaccine is given concurrently with
antibiotic prophylaxis in suspected exposure cases.
Currently, anthrax vaccine is available primarily through
the U.S. Department of Defense and the CDC. Pharmacists
interested in learning more about anthrax and anthrax vaccine
should consult ACIP recommendations or visit the CDCs
website (www.cdc.gov/anthrax/).
A Look to the Future
Despite the overwhelming benefits of available vaccines,

infectious diseases continue to exert an enormous toll both in
the United States and around the world. Effective vaccines
have not yet been developed and marketed for infectious
diseases such as HIV, tuberculosis, and malaria, which together
cause 4 million deaths annually worldwide. Furthermore,
many existing vaccine production technologies do not allow
for a fast response to developing outbreaks. For example,
most influenza vaccines are manufactured through a process
that incubates virus in eggs and requires several months for
vaccine production; this process does not readily provide rapid
production of large quantities of vaccine in the event that a
novel influenza virus emerges and causes a pandemic.123
Recently licensed cell-based influenza vaccines are available
and have the advantage of shorter production timelines.
Research into vaccines to prevent HIV has met numerous
roadblocks. Clinical trials to date for a vaccine to prevent new
HIV infections have been largely disappointing.124 However,
investigations on new potential vaccines are continuing.
Research into a vaccine to prevent malaria has had more
success recently. A trial of a malaria vaccine candidate
(known as RTS,S) reduced cases of clinical malaria by 46%
in young children aged 5 to 17 months in Africa after first
vaccination, compared with children immunized with a control
vaccine. Infants aged 6 to 12 weeks after first vaccination
had 27% fewer cases of clinical malaria. It is expected

that this vaccine candidate may be submitted for regulatory
approval in 2014.125
New administration technologies are an ongoing area of
research, particularly methods that allow for needleless
administration. Technologies under development include
microneedle arrays and nanopatches.126,127
Conclusion
Vaccines have been successful in preventing a broad range

of infectious diseases. Immunizing pharmacists can make
a significant impact on their patients health by becoming
involved in vaccine administration. Identifying patients in
need of vaccinations and making recommendations to protect
these patients are key components of any immunization
program and overall patient care. To make appropriate
recommendations, pharmacists must know which vaccines
are available and the populations served by these vaccines
as well as recognize when contraindications and precautions
exist for specific patients. Standards and recommendations
in immunization practice change regularly because of
the ongoing nature of these developments. Immunizing
pharmacists must make a commitment to staying up to date
as new information emerges about new vaccines and technologies as well as changes to the use of existing vaccines.
Armed with the knowledge of vaccines currently available
in the United States, participants of this certificate training
program are now prepared to advance to the upcoming
modules on essential information on administering vaccines
and establishing a pharmacy-based immunization service.
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2014 APhA Pharmacy-Based

A National Certificate Training Program

Module 3. Vaccine-Preventable Diseases

2014, American Pharmacists Association. All rights reserved.

2014 APhA Pharmacy-Based

To prepare pharmacists for vaccine delivery, this module

Influenza is a highly infectious respiratory illness caused by

Clinical Features and Potential Complications

The incubation period for influenza can range from 1 to 4

Immunization schedules are available online at www.cdc.gov/

Photo courtesy of CDC Public Health Image Library: Image ID 11161.

2014 APhA Pharmacy-Based

the annual burden of influenza among adults 18 to 49 years

There are three major types of influenzaA, B, and Cwhich

Figure 3.2. Structure of the Influenza Virus

structure of the virus, but the H and N numbers do not change.

Influenza Epidemics and Pandemics

An epidemic occurs when an infectious disease spreads

2014 APhA Pharmacy-Based

Number of Times as Peak Month

Figure 3.3. Peak Month of Influenza Activity During 198283

of respiratory specimens testing positive for influenza virus

Module 3. Vaccine-Preventable Diseases

A few trends were observed during the 200910 influenza

The most effective strategy for preventing influenza is annual

2014 APhA Pharmacy-Based

Using egg-based technology, it takes approximately 6 to

and available. Three quadrivalent influenza vaccines were

Inactivated Influenza Vaccine

Influenza viruses are inactivated during the manufacturing

2014 APhA Pharmacy-Based

Inactivated influenza vaccine,

5.0 mL multidose vial

5.0 mL multidose vial

5.0 mL multidose vial

0.5 mL single-dose vial

5.0 mL multidose vial

Inactivated influenza vaccine,

Inactivated influenza vaccine,

0.5 mL single-dose vial

Recombinant influenza vaccine,

0.5 mL single-dose vial

0.0 (per 0.2

Module 3. Vaccine-Preventable Diseases

2014 APhA Pharmacy-Based

National Pharmaceutical Stockpile and will be released only if

NonEgg-Based Influenza Vaccines

In November 2012, the FDA approved the first U.S.-licensed

Live Attenuated Influenza Vaccine

LAIV (FluMistMedImmune) contains live attenuated influenza

Module 3. Vaccine-Preventable Diseases

Target Groups for Vaccination

ACIP recommends that all persons aged 6 months and older

2014 APhA Pharmacy-Based

ACIP recommends that all women who will be pregnant

Table 3.2. Inactivated Influenza Vaccine Dosing for

Figure 3.4. ACIP Influenza Vaccine Dosing Algorithm for

Has the child ever received

Module 3. Vaccine-Preventable Diseases

All people aged 6 months and older should receive 1 dose of

Did the child receive a total

Doses should be administered at least 4 weeks apart.

ACIP = Advisory Committee on Immunization Practices.