2014 APhA Pharmacy-Based

IMMUNIZATION DELIVERY

APhA Pharmacy-Based
IMMUNIZATION DELIVERY

A National Certificate Training Program

Module 3. Vaccine-Preventable Diseases

13-561 © 2014, American Pharmacists Association. All rights reserved.

 2014 APhA Pharmacy-Based
IMMUNIZATION DELIVERY

Influenza
Learning Objectives Influenza is a highly infectious respiratory illness caused by
a virus of the orthomyxovirus family.1 The influenza virus is
At the completion of this activity, participants will be able to: primarily spread by aerosolized respiratory droplets from a
cough or sneeze (Figure 3.1). The virus also can be spread
1. D
 escribe the epidemiology, clinical features, and when a person has direct contact with infected droplets from
potential complications of diseases that can be nasal secretions or saliva from an infected person.
prevented with vaccines.

2. Identify vaccines available in the U.S. market for Clinical Features and Potential Complications
each vaccine-preventable disease and describe their The incubation period for influenza can range from 1 to 4
features. days.1,2 The onset of symptoms is usually abrupt with a high
fever over 38°C (101°F), nonproductive cough, sore throat,
3. IIdentify the contraindications and precautions for the and muscle aches. Patients also may complain of fatigue,
use of vaccines available in the United States. headache, or a runny nose. People infected with influenza
virus may be contagious beginning 1 day before their
4. IUse recommendations from the Advisory Committee symptoms develop and up to 5 to 7 days after becoming
on Immunization Practices to identify target groups sick.3
for receipt of each vaccine.
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
Introduction in significant morbidity and mortality.4-6 Influenza can
To prepare pharmacists for vaccine delivery, this module exacerbate underlying medical conditions (e.g., chronic
reviews the most common vaccine-preventable diseases and pulmonary disease, cardiac disease, diabetes). Influenza also
the vaccines used to prevent them. The discussion includes the can be associated with secondary bacterial infections (e.g.,
epidemiology, clinical features, and potential complications pneumococcal pneumonia, sinusitis, otitis media). The risk
of each disease, vaccine indications and contraindications, for complications, hospitalization, or death from influenza is
vaccine dosage and administration information, and important usually higher in patients with underlying medical conditions,
vaccine-related adverse effects. The vaccine-preventable pregnant women, young children, and elderly adults.
diseases are presented here in the order in which they
appear in the 2013 adult immunization schedule, followed by Influenza is also an important cause of illness among young,
vaccines that appear only on the childhood and adolescent otherwise healthy adults. In one analysis, it was estimated that
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 Figure 3.1. Spray of Respiratory Droplets During a Sneeze
bioterrorism, and a look at the development of future vaccines.

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 recommenda-
tions from the Advisory Committee on Immunization Practices
Photo courtesy of CDC Public Health Image Library: Image ID 11161.
(ACIP) at the time of providing patient care.

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the annual burden of influenza among adults 18 to 49 years

of age without high-risk conditions included 5 million illnesses, Figure 3.2. Structure of the Influenza Virus
2.4 million outpatient visits, 32,000 hospitalizations, and 680
deaths.7 Furthermore, during the 2009–10 H1N1 pandemic,
adults younger than 65 years of age were at higher risk
for influenza-related complications than during other recent
influenza seasons.7
Type of nuclear
The rates of influenza-related hospitalizations and deaths material
can vary substantially from one influenza season to the next, Neuraminidase
Hemagglutinin
depending on the characteristics of the circulating strain of
influenza, as well as factors such as immunization rates and A/Fujian/411/2002 (H3N2)
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 Virus Geographic Strain Year of Virus
type origin number isolation subtype
seasonal influenza in the United States from 1976 to 2007.
During these three decades, the estimated number of annual Source: Reference 1.
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 structure of the virus, but the H and N numbers do not change.
and serve as a reminder of why annual influenza vaccination When the new version of the virus is different enough from the
is crucial. previous version, the virus can cause an epidemic because
protection that remains from previous exposures to similar
Influenza Viruses influenza viruses is incomplete.1
There are three major types of influenza—A, B, and C—which
are differentiated by their surface proteins. Influenza A is the An antigenic shift involves major changes of one or both
main cause of epidemic and pandemic human disease.1,2 of the surface antigens, creating a new strain of the virus.
Influenza A causes a moderate to severe illness that can affect Antigenic shifts are probably due to genetic recombination
people of all ages, while influenza B is typically milder and (an exchange of a gene segment called genetic reassortment)
primarily affects children. Influenza C is rarely reported as a between influenza A viruses, usually those that affect humans,
cause of illness in humans and has not been associated with pigs, and birds. When the new strain of the influenza virus
epidemic disease.1 differs significantly from past strains, a global pandemic may
occur. During a pandemic, serious disease spreads quickly
Influenza A viruses are categorized into subtypes based because the population has little or no antibody protection
on the two major surface antigens: hemagglutinin (H) and from the new strain. Mortality associated with a pandemic is
neuraminidase (N). The hemagglutinin surface antigens usually higher than during interpandemic periods.
(numbered 1 through 9) help the influenza virus attach to
cells in the body, while the neuraminidase surface antigens Influenza Epidemics and Pandemics
(numbered 1 through 9) help the virus leave the cell and An epidemic occurs when an infectious disease spreads
spread to other cells.1 Most influenza viruses occur in birds. rapidly and affects more people than would be expected
Fewer combinations of H and N have been identified in during a typical influenza season. During an annual influenza
humans than in birds. Influenza viruses are named based epidemic, approximately 5% to 20% of the U.S. population
on the type, subtype, geographic origin, strain, and year of becomes infected with the influenza virus.8 Annual epidemics
isolation (Figure 3.2). of influenza typically occur in the United States in autumn and
last through the spring, but the exact timing and duration of flu
The surface antigens on influenza viruses change periodi- seasons vary. While influenza outbreaks can happen as early
cally due to evolution within immune or partially immune as October, they typically peak in February. Figure 3.3 shows
populations. Two major types of antigenic change are known: peak activity for the United States by month for the 1982–83
antigenic drift and antigenic shift. Antigenic drift occurs through 2011–12 influenza seasons. The “peak month of
continuously and results in minor changes in the antigenic influenza activity” is the month with the highest percentage

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Figure 3.3. Peak Month of Influenza Activity During 1982–83 A few trends were observed during the 2009–10 influenza
Through 2011–12 Seasons pandemic that are not usually seen in annual influenza
epidemics.10 During annual influenza epidemics, rates of
16
Number of Times as Peak Month

influenza are usually highest in infants and young children

14
and influenza is a common cause of office visits and visits to
12
the emergency department in this patient population.2 Adults
10 aged 65 years and older are typically at highest risk for
8 complications, hospitalizations, and deaths from influenza.5,6
6 Pregnant women are also at increased risk of complications.2
4
2 The 2009 H1N1 influenza still had a significant impact on
0 young children and caused a high number of hospitalizations
Oct Nov Dec Jan Feb Mar Apr May and deaths in pregnant women. However, complications
Month during this influenza season occurred more frequently among
Source: Reference 3.
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
of respiratory specimens testing positive for influenza virus deaths among adults aged 65 years or older was below those
infection. During this 30-year period, influenza activity most normally seen during an annual influenza epidemic.
often peaked in February (14 seasons, or 47% of the time),
followed by January and March (5 seasons each, or 17% of While the burden of disease from 2009 H1N1 influenza was
the time), and December (4 seasons, or 13% of the time). significant, it had the potential to be much more devastating
than what ultimately occurred. A coordinated public health
A pandemic is a global disease outbreak. Several influenza response and the availability of a pandemic influenza
pandemics have occurred over the past hundred years, vaccine helped prevent the spread of influenza and minimize
resulting in significant morbidity and mortality1,2,9: the potential devastation that could have been caused by
• 1918–19 “Spanish flu” the pandemic. Pharmacists played a significant role in the
public health response to 2009 H1N1 by serving as vaccine
– Caused by subtype A/H1N1 advocates and immunizers.
–R
 esponsible for at least 30 million to 50 million deaths
worldwide including at least 675,000 deaths in the It is difficult to predict when the next influenza pandemic will
United States occur or how severe it will be when it does occur. Pharmacists
• 1957–58 “Asian flu” should be knowledgeable about preventive measures and be
prepared to act. When the next influenza pandemic strikes,
– Caused by subtype A/H2N2 pharmacists will be called on to help educate and immunize
–R
 esponsible for approximately 70,000 deaths in the the people in their community.
United States
• 1968–69 “Hong Kong flu”
Influenza Vaccines
– Caused by subtype A/H3N2
The most effective strategy for preventing influenza is annual
–R
 esponsible for approximately 34,000 deaths in the vaccination.2 Annual vaccination against influenza is needed
United States for two reasons. First, protective levels of vaccine-induced
• 2009–10 H1N1 antibody to influenza wane over time (although they do
extend throughout one influenza season—typically 6 to 8
– Caused by subtype A/H1N1
months depending upon the strain).7 Second, gradual drifts
–C
 DC estimates 43 million to 89 million people in the in influenza surface antigens change the circulating influenza
United States were infected viruses. Therefore, changes are made to the influenza vaccine
–R
 esponsible for 8,870 to 18,300 deaths in the United formulation each year to maximize the protection it offers
States against influenza.

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Using egg-based technology, it takes approximately 6 to and available. Three quadrivalent influenza vaccines were
8 months to manufacture an adequate supply of influenza available for the 2013–14 influenza season, but only one
vaccine. Therefore, early each year, influenza experts must was approved for children younger than 2 years of age. It
choose the influenza strains that will be included in the is anticipated that in future seasons, more manufacturers
influenza vaccines to allow enough time to manufacture the will transition their products from trivalent to quadrivalent
vaccine for the upcoming influenza season. Surveillance formulations.
information is used to predict which strains will likely circulate
in the upcoming season. For several decades (since the Inactivated Influenza Vaccine
1978–79 influenza season when A/H1N1 was added), Influenza viruses are inactivated during the manufacturing
influenza vaccines have contained three strains: type A/ process and then broken into subunits to make inactivated
H1N1, type A/H3N2, and type B antigens. Beginning in influenza vaccines. Because the influenza viruses have been
2013, quadrivalent influenza vaccine became available, inactivated, these vaccines cannot cause influenza. Studies
which contains two type B antigens. The addition of a second with IIV3 have found it to be effective in protecting 70% to
type B antigen was added to protect against the two major 90% of healthy people younger than 65 years of age when
circulating lineages (called Yamagata and Victoria), but it is the circulating virus strains are closely matched to the strains
expected to produce only a modest reduction in disease.11 in the vaccine.1,2 However, in people older than 65 years
This change precipitated the development of a new set of of age, it may be only 30% to 40% effective in preventing
abbreviations related to influenza vaccine7: clinical illness. Even though IIV3 is not as effective in
preventing clinical illness in elderly adults, it has been shown
• IIV (inactivated influenza vaccine) replaces the
to be effective in preventing complications, hospitalizations,
previously used abbreviation TIV (trivalent influenza
and death in this patient population.1,2,21
vaccine). The abbreviation IIV is followed by a numeric
suffix that specifies the number of antigens in the
In December 2009, the U.S. Food and Drug Administration
vaccine. For 2013–14, IIVs as a class include:
(FDA) approved a new IIV3 called Fluzone High-Dose (Sanofi
–E
 gg-based and cell culture–based trivalent inactivated Pasteur).22 Fluzone High-Dose contains four times the amount
influenza vaccines (IIV3) of each antigen found in the other IIV3 vaccines on the market.
The goal with this high-dose IIV3 is to prompt a stronger
–Egg-based quadrivalent inactivated influenza vaccine
immune response in adults aged 65 years and older. Fluzone
(IIV4)
High-Dose induces higher antibody titers than the standard-dose
• RIV refers to recombinant hemagglutinin influenza IIVs; however, at the time this certificate training program was
vaccine, available as a trivalent formulation (RIV3) for developed, there were no published studies demonstrating that
2013–14. the higher titers resulted in greater protection against influenza
illness.2,23 One unpublished study concluded that high-dose IIV3
• LAIV refers to live attenuated influenza vaccine,
was more effective than standard dose IIV3 in those aged 65
available as a quadrivalent formulation (LAIV4) for
years and older, but the CDC has not changed its recommenda-
2013–14.
tions as of December 2013.24
• Where necessary to refer specifically to cell culture–
based vaccine, the prefix “cc” is used (e.g., “ccIIV3”). In May 2011, the FDA approved a new IIV3 called Fluzone
Intradermal (Sanofi Pasteur).25 A specially designed microneedle
The available influenza vaccines are shown in Table 3.1.7,12-22 and injector system is used to deliver a unique formulation
Due to the large number of vaccines available to prevent of vaccine into the intradermal tissue of the deltoid. Fluzone
influenza and regular changes to products, pharmacists should Intradermal is approved for adults 18 to 64 years of age.
anticipate that changes will occur from year to year. Each
year, pharmacists should carefully evaluate package labeling, Additionally, in November 2013, the FDA approved a
storage requirements, product preparation, and administration monovalent inactivated influenza vaccine (Q-Pan H5N1
instructions for each vaccine that they order. influenza vaccine—GlaxoSmithKline) that provides protection
against the H5N1 influenza virus. The vaccine is approved for
ACIP does not express a preference for use of any one use in adults 18 years of age and older who are at increased
influenza vaccine product over another in patients for whom risk of exposure to the H5N1 influenza virus. However, the
more than one type of influenza vaccine is appropriate vaccine is not commercially available; it is being added to the

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Table 3.1. Influenza Vaccines Available in the U.S. Market, 2013–14 Influenza Season
Vaccinea Trade Name Manufacturer Presentation Mercury Age Route
Content (μg Indications
Hg/0.5 mL)
Inactivated influenza vaccine, Afluria CSL Limited 0.5 mL single-dose 0.0 ≥9 yearsc IM
trivalent (IIV3), standard dose prefilled syringe
5.0 mL multidose vial 24.5
Agriflu Novartis 0.5 mL single-dose 0.0 ≥18 years IM
prefilled syringe
Fluarix GlaxoSmithKline 0.5 mL single-dose 0.0 ≥3 years IM
prefilled syringe
Flucelvax Novartis 0.5 mL single-dose 0.0 ≥18 years IM
prefilled syringe
FluLaval GlaxoSmithKline 5.0 mL multidose vial <25.0 ≥3 years IM
Fluvirin Novartis 0.5 mL single-dose ≤1 ≥4 years IM
prefilled syringe
5.0 mL multidose vial 25.0
Fluzone Sanofi Pasteur 0.25 mL single-dose 0.0 6–35 months IM
prefilled syringe
0.5 mL single-dose 0.0 ≥36 months IM
prefilled syringe
0.5 mL single-dose vial 0.0 ≥36 months IM
5.0 mL multidose vial 25.0 ≥6 months IM
Fluzone Sanofi Pasteur 0.1 mL prefilled 0.0 18–64 years ID
Intradermal microinjection system
Inactivated influenza vaccine, Fluzone High-Dose Sanofi Pasteur 0.5 mL single-dose 0.0 ≥65 years IM
trivalent (IIV3), high dose prefilled syringe
Inactivated influenza vaccine, Fluarix GlaxoSmithKline 0.5 mL single-dose 0.0 ≥3 years IM
quadrivalent (IIV4), standard dose Quadrivalent prefilled syringe
Fluzone Sanofi Pasteur 0.25 mL single-dose 0.0 6–35 months IM
Quadrivalent prefilled syringe
0.5 mL single-dose 0.0 ≥36 months IM
prefilled syringe
0.5 mL single-dose vial 0.0 ≥36 months IM
Recombinant influenza vaccine, Flublok Protein Sciences 0.5 mL single-dose vial 0.0 18–49 years IM
trivalent (RIV3)
Live attenuated influenza vaccine, FluMist MedImmune 0.2 mL prefilled 0.0 (per 0.2 2–49 years IN
quadrivalent (LAIV4) Quadrivalentb intranasal sprayer mL)
a Immunization providers should check Food and Drug Administration–approved prescribing information for 2013–14 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 CSL’s 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 child’s 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 12–22.

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National Pharmaceutical Stockpile and will be released only if Target Groups for Vaccination
directed by the Department of Health and Human Services. ACIP recommends that all persons aged 6 months and older
should be vaccinated against influenza each year.2 This
Non–Egg-Based Influenza Vaccines recommendation, which was effective starting in the 2010–11
In November 2012, the FDA approved the first U.S.-licensed influenza season, is supported by evidence that annual
influenza vaccine manufactured using non–egg-based cell influenza vaccination is a safe and effective preventive health
culture technology (ccIIV3; Flucelvax—Novartis) for the measure with potential benefit for all people in this broad age
prevention of influenza in patients 18 years of age and range. Vaccination should be offered throughout the entire
older.26 influenza season.

In January 2013, the FDA approved another non–egg-based Historically, ACIP recommended focusing vaccination efforts
influenza vaccine (RIV; Flublok—Protein Sciences), made with on individuals at higher risk for influenza-related complica-
recombinant hemagglutinin, for the prevention of seasonal tions. While vaccination of high-risk individuals should still
influenza in adults 18 to 49 years of age. be a target, vaccinating younger healthier people has the
potential not only to protect the individual, but promote herd
These two new vaccines require less time to manufacture immunity through reduced community transmission. When
mainly because the process is not dependent on an egg vaccine supply is limited, vaccination efforts should focus on
supply or limited by the selection of strains that are adapted immunizing people who29:
for growth in eggs. The shorter manufacturing time could
• Are aged 6 months to 4 years (59 months).
be useful in the event of a pandemic or vaccine supply
shortage.27 • Are aged 50 years and older.
• Have chronic pulmonary (including asthma),
RIV does not use eggs in its manufacturing process. Therefore, cardiovascular (except hypertension), renal, hepatic,
it is approved as an influenza vaccine for patients with egg neurologic, hematologic, or metabolic disorders
allergy. If supplies of RIV run out, ccIIV3 may be considered (including diabetes).
as an option for these patients because it contains only a trace
amount of egg protein. However, FDA has not licensed ccIIV3 • Have altered immunocompetence (including immuno-
for use in people who have egg allergies, because the initial suppression caused by medications or by human
seed virus was grown in eggs.28 immunodeficiency virus [HIV]).
• Are or will be pregnant during the influenza season.
Live Attenuated Influenza Vaccine • Are aged 6 months to 18 years and receiving long-term
LAIV (FluMist—MedImmune) contains live attenuated influenza
aspirin therapy and who therefore might be at risk for
viruses. LAIV was previously available as a trivalent vaccine
experiencing Reye’s syndrome after influenza virus
but, starting in the 2013–14 influenza season, is now available
infection.
only as quadrivalent vaccine. It contains the same strains
of influenza found in IIV4. Because LAIV is a live virus • Are residents of nursing homes and other chronic-care
vaccine, the viruses in the vaccine must replicate to stimulate facilities.
an immune response, similar to that produced by natural • Are American Indians/Alaska natives.
infection. However, the attenuated viruses in LAIV are cold
adapted, which means the viruses can replicate in the cooler • Are morbidly obese (body mass index is 40 or greater).
upper airways (e.g., mucosa of the nasopharynx) but not the • Are health care personnel.
warmer lower airways and lungs.12,20 Because the viruses are
• Are household contacts and caregivers of children aged
attenuated, they cannot replicate in the lower airways and are
younger than 5 years and adults aged 50 years and
not known to cause influenza. LAIV is effective in reducing
older, with particular emphasis on vaccinating contacts
influenza illness in children older than 2 years of age and
of children aged younger than 6 months.
has been shown to reduce cases of otitis media in some initial
trials. In adults, use of LAIV has been shown to reduce severe • Are household contacts and caregivers of people with
illness, absenteeism, and the number of health care visits.2 medical conditions that put them at higher risk for severe
complications from influenza.

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ACIP recommends that all women who will be pregnant Table 3.2. Inactivated Influenza Vaccine Dosing for
during the influenza season be vaccinated against influenza. Intramuscular Administration
Unfortunately, pregnant women have one of the lowest Age of Patient No. of Doses Volume
vaccination rates of all adults recommended to receive 6–35 months 1 or 2a 0.25 mL
seasonal influenza vaccination.2,30 A recent study suggests
3–8 years 1 or 2a 0.5 mL
that infants born to women vaccinated against influenza
during pregnancy experience fewer influenza-related hospital- ≥9 years 1 0.5 mL
izations.30 In addition to decreasing the risk of influenza-
aTwo doses separated by 4 weeks are needed to provide adequate protection for
related complications in the pregnant woman, influenza children receiving influenza vaccine for the first time.
vaccination appears to provide benefit to the infant after birth,
Source: Reference 2.
emphasizing the importance of vaccinating pregnant women
against influenza.
Figure 3.4. ACIP Influenza Vaccine Dosing Algorithm for
During a vaccine shortage, public health may require a tiered Children Aged 6 Months to 8 Years
structure for prioritizing the distribution and administration of
vaccine. Pharmacists must abide by this priority structure to Has the child ever received No/Don’t know
2 dosesa
ensure the most vulnerable people are protected. influenza vaccine?

Yes
Vaccine Recommendations
All people aged 6 months and older should receive 1 dose of Did the child receive a total
of 2 or more doses of No/Don’t know
the influenza vaccine each year during the influenza season. 2 dosesa
seasonal influenza vaccine
The single exception to this recommendation is for all children since July 1, 2010?
aged 6 months to 8 years receiving influenza vaccination for
the first time: these children should receive 2 doses, adminis- Yes
tered at least 4 weeks apart in the same season.2 These 2
doses are needed to provide adequate protection for the 1 dose
child, in particular against the A/H1N1 pandemic virus, which
has been included in seasonal influenza vaccines since the a Doses should be administered at least 4 weeks apart.
2010–11 influenza season. If a child less than 9 years old ACIP = Advisory Committee on Immunization Practices.
has received a total of 2 or more doses of seasonal influenza Source: Reference 7.
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 When to Offer Influenza Vaccinations
child has received, then 2 doses should be administered in the Influenza disease generally occurs in the United States from
current influenza season. For a child who is not given 2 doses December to March each year.1 Influenza vaccination
the first time he or she receives the vaccine, and returns the programs should be started as soon as vaccine is available (if
following year for vaccination while still younger than 9 years possible, by October) and should be continued until vaccine is
of age, the child should receive 2 doses during that season.7 no longer available or has expired. In recent years, influenza
Once a child has completed the priming series of 2 doses, vaccine has become available as early as July, raising concerns
the child will need only 1 dose of vaccine in each subsequent that effectiveness may wane before the end of the influenza
year. (See Table 3.2 for dosing information and Figure 3.4 for season. ACIP is continuing to evaluate data surrounding this
the childhood administration algorithm.2,7) 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.)

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To maximize protection and avoid missed opportunities, newer vaccines may be limited, pharmacists should immunize
pharmacists should consider recommending or offering their patients with any appropriate influenza vaccine that is
vaccination any time they provide patient care during the available.
influenza season.
LAIV is indicated for healthy people 2 to 49 years of age.
The use of LAIV is not indicated for patients with underlying
Strategies for Implementing Influenza Vaccination medical conditions, in patients with a history of wheezing or
Recommendations asthma, or in pregnant women.
According to ACIP recommendations, successful influenza
vaccine clinics typically employ a number of important IIV is preferred over LAIV for vaccinating household members,
strategies to reach those at highest risk during influenza health care workers, and others who have close contact with
season2: severely immunosuppressed patients during periods when
these patients require care in a protected environment (e.g.,
• Educate and immunize all health care providers and
after a bone marrow transplant). If health care personnel
staff of health care facilities—including pharmacies.
receive LAIV, they should refrain from contact with severely
The CDC recommends that convenient access to
immunosuppressed patients for 7 days after vaccine receipt.
influenza vaccine should be provided, free of charge,
by the employer to this group. All health care
ACIP recommends that people with immunosuppression should
providers—including pharmacists—should act as role
receive influenza vaccine annually. However, only IIV should
models and receive their influenza vaccination each
be administered to a person immunosuppressed for any
year.
reason (either from the underlying illness or treatment of an
• Recommend or offer vaccination any time a patient illness).
is encountered during the influenza season. A
clear, unequivocal recommendation from a health IIV is preferred over LAIV in children and adolescents receiving
care provider is one of the strongest predictors of long-term aspirin therapy because of the potential association
vaccination. between Reye’s syndrome and wild-type influenza infection.
• Provide education to potential vaccine recipients about
the risks of influenza and the potential health benefits of
vaccination.
Contraindications and Precautions
As with all other vaccines, a previous severe allergic reaction
• Implement standing orders, as allowed or required to a vaccine or a vaccine component is a contraindication to
by state law, to facilitate the provision of vaccine to receiving the vaccine.2,31 With the exception of RIV and ccIIV,
patients. influenza vaccines are produced in fertilized chicken eggs.
Severe allergic reactions to eggs are a contraindication to all
• Use a reminder/recall system for patients who were
other currently available influenza vaccines.1,2,31 ACIP has
immunized in previous years, as well as for situations in
published an algorithm for influenza vaccination of people
which there is a vaccine shortage and patients need to
with egg allergy (Figure 3.5).7 Generally, patients who can
be recalled when vaccine becomes available.
tolerate eating lightly cooked eggs or products containing
Choosing an Influenza Vaccine eggs (e.g., scrambled eggs) can be vaccinated with any
IIV is preferred for children younger than 2 years of age, influenza vaccine.7
adults 50 years of age and older, and any patient with a
chronic medical condition.2 While Fluzone High-Dose is Prior history of Guillain-Barré syndrome is not an absolute
approved for adults aged 65 years and older, ACIP has not contraindication to vaccination with influenza vaccine,
expressed a preference for any licensed influenza vaccine in but it is a precaution when it occurred within 42 days of
this patient population at this time. Both IIV3 and IIV4 were vaccination.2,31 Any patient with a history of Guillain-Barré
available for the 2013–14 influenza season; the CDC has no syndrome should be referred to a physician for assessment
preference. It is important to remember that the quadrivalent to evaluate the risks versus the benefits of receiving influenza
vaccine will provide additional protection only if the fourth vaccine.
strain of influenza actually circulates. Because supplies of the

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Figure 3.5. ACIP Recommendations Regarding Influenza These effects are more common if the patient has had no prior
Vaccination of People Who Report Allergy to Eggs exposure to influenza vaccine (e.g., young children).

Can the person eat lightly cooked

egg (e.g., scrambled egg) without
Yes Administer vaccine
per usual protocol
Live Attenuated Influenza Vaccine
reaction?a The adverse reactions reported after administration of LAIV are
usually mild and self-limiting. Runny nose or nasal congestion
No
Administer RIV3, is the most common adverse effect. Other possible adverse
if patient aged effects include headache, fever, vomiting, myalgias, and
18–49 years abdominal pain, but these appear to be more common after
After eating eggs or egg-containing the first dose than subsequent doses.
Yes OR
foods, does the person experience
ONLY hives?
Administer IIV
No
Storage and Administration of Influenza Vaccines
Observe for reaction for All influenza vaccines should be stored in the refrigerator at
at least 30 minutes
following vaccination 2°C to 8°C (35°F to 46°F). These vaccines should not be
frozen.
After eating eggs or
egg-containing foods, does the
individual experience other Administer RIV3,
Inactivated Influenza Vaccine
symptoms such as: if patient aged Multiple IIVs are licensed for use and each IIV has specific
• Cardiovascular changes 18–49 years age indications (Table 3.1). Be careful to choose a vaccine
(e.g., hypotension) that is licensed for use in the patient being vaccinated. Shake
• Respiratory distress Yes
OR the vial or prefilled syringe before use. The dosing for IIVs is
(e.g., wheezing)
• Gastrointestinal symptoms Refer to a physician shown in Table 3.2.2 Most IIVs are administered by intramus-
(e.g., nausea/vomiting) with expertise in cular injection.
• Reaction requiring epinephrine management of allergic
• Reaction requiring emergency conditions for
medical attention
Fluzone is the only IIV approved for children younger than 36
further evaluation
months of age. Fluzone Intradermal is approved for adults 18
a People with egg allergy might tolerate egg in baked products (e.g., bread,
to 64 years of age and only the manufacturer’s microneedle
cake). Tolerance to egg-containing foods does not exclude the possibility of egg injector should be used to administer this vaccine.
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
Live Attenuated Influenza Vaccine
conditions should be obtained prior to vaccination. Alternatively, RIV3 may be
LAIV is administered intranasally using a sprayer device; it
administered if the recipient is aged 18 to 49 years. should never be administered orally or by injection. The sprayer
ACIP = Advisory Committee on Immunization Practices; IIV = inactivated influenza
device contains a total dose of 0.2 mL. Half of the contents
vaccine; RIV3 = recombinant influenza vaccine, trivalent. (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
Source: Reference 7.
the other nostril. The appropriate technique for administration of
LAIV is discussed in more detail in Module 4.
If the patient has a valid contraindication or precaution to
receiving influenza vaccine, vaccination should be deferred Special consideration for administration of LAIV.
or the patient should be referred to his or her primary care Influenza antiviral medications reduce the replication of
provider. 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
Potential Adverse Reactions medications, LAIV should not be administered until 48 hours
after cessation of the antiviral therapy.2 If the patient must
Inactivated Influenza Vaccine be treated with antiviral medications within 2 weeks after
The most commonly reported adverse reactions with IIV receiving LAIV, the vaccine dose should be repeated 48 hours
include local reactions at the injection site. Rarely, patients or more after the final dose of antiviral medication.
may report fever, malaise, or myalgias after receiving IIV.

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Tetanus, Diphtheria, and Pertussis Figure 3.6. Patient With Generalized Tetanus
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.

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, Photo courtesy of CDC Public Health Image Library: Image ID 6373.

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, in the neck, difficulty swallowing, muscle rigidity, and severe
approximately 45% of the reported acute injuries resulting in muscle spasms. The symptoms associated with generalized
tetanus infection occurred indoors or at home.1 tetanus can persist for 3 to 4 weeks and complete recovery
may take many months. Tetanus can be complicated by
Once C. tetani enters the body through a wound, the spores respiratory insufficiency, bone fractures, and infections (e.g.,
begin to germinate and the bacteria replicate. During this pneumonia). Tetanus can be fatal, resulting in death in
process, the bacteria produce a toxin called tetanospasmin, approximately 10% of reported cases.1
which causes the clinical features and complications of the
disease. The toxin is released into the bloodstream and acts Rates of tetanus in the United States began to decline from
in the central nervous system. The toxin blocks the release of 1900 to the 1940s, when approximately 500 to 600 cases
neurotransmitters, ultimately preventing muscle relaxation and were reported each year. Tetanus vaccine was introduced in
results in severe muscle spasms. The incubation period can the late 1940s and the rate of this disease has declined since
vary from 3 to 21 days. In general, the shorter the incubation that time. During 2001 through 2008, the last years for which
period, the higher the chance of death.1 data have been compiled, a total of 233 tetanus cases in the
United States was reported, an average of 29 cases per year.
Four forms of clinical illness are recognized: local tetanus, Almost all reported cases of tetanus are in people who either
cephalic tetanus, neonatal tetanus, and generalized tetanus. have never been vaccinated or those who completed a primary
Local and cephalic tetanus are rare forms of the disease. series but have not had a booster in the preceding 10 years.1
In cases of local tetanus, patients experience persistent
contraction of the muscles in the specific area where the
Figure 3.7. Infant With Muscle Rigidity From Neonatal
injury occurred. It is possible for local tetanus to precede the
Tetanus
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, Photo courtesy of CDC Public Health Image Library: Image ID 6374.
usually starting with trismus (i.e., lockjaw), followed by stiffness

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Diphtheria than 157,000 cases of disease and 5,000 deaths.1,33 Many of

Diphtheria is caused by Corynebacterium diphtheriae, an these cases were attributable to a lack of routine immunization
aerobic, gram-positive bacterium.1 C. diphtheriae can enter against diphtheria. This experience is a reminder that it is not
the body through the respiratory tract. The bacterium is sufficient to give patients periodic booster doses of tetanus
capable of producing a toxin, which can be absorbed into the toxoid alone. Instead, booster doses of diphtheria are needed
bloodstream and distributed through the body. This toxin is to boost immunity after completing a primary immunizing series
responsible for producing the clinical features and complica- with diphtheria-containing vaccines.34,35
tions of the disease.

Infection with C. diphtheria can occur at any mucous membrane Pertussis

in the body. The most common sites of infection include the Pertussis, also called whooping cough, is caused by
tonsils, pharynx, larynx, and nasal mucosa. Other mucous Bordetella pertussis, a gram-negative bacterium.1 This disease
tissues that can be affected include the skin, ocular tissue eye, is extremely contagious. B. pertussis is most commonly
or genital area. The infection can cause tissue destruction and transmitted by respiratory droplets that are released in the air
usually results in the formation of a pseudomembrane, which is when an infected person coughs or sneezes. The bacteria
a characteristic sign of diphtheria infection. infect the respiratory tract and produce toxins that interfere
with the function of the respiratory tract, ultimately causing the
Most commonly, diphtheria infection affects the pharynx and characteristic symptoms of pertussis.
tonsils. Early symptoms are similar to pharyngitis: malaise,
sore throat, low-grade fever, and anorexia. However, within Pertussis begins with a catarrhal stage that lasts approximately
2 to 3 days, a bluish-white membrane develops on the tonsils 1 to 2 weeks. The symptoms of this stage are similar to those
and pharynx. The color of the membrane can change as the of the common cold: mild cough, runny nose, sneezing, and
disease progresses. This membrane may extend into the airway fever. This stage is followed by a paroxysmal cough stage,
and ultimately cause respiratory obstruction. Attempts to which can last from 1 to 6 weeks. During this stage, the
remove the membrane will result in significant bleeding because patient will experience paroxysms, which are coughing attacks
the membrane is firmly attached to surrounding tissue. characterized by numerous, rapid coughs (Figure 3.8). During
the coughing attacks, a high-pitched “whooping” sound often
Laryngeal diphtheria often follows the same course as can be heard. The whooping sound results when the patient
pharyngeal diphtheria, only the larynx is involved. When tries to take a deep breath against a closed glottis. The
patients experience laryngeal diphtheria, they may complain paroxysmal coughing can cause vomiting and exhaustion.
of symptoms such as a fever, hoarseness, and a barking The last stage is convalescence. Complete recovery from
cough. Adherence of the membrane to the larynx can lead to pertussis is gradual and can take months.
airway obstruction, coma, and death.
Figure 3.8. Infant With Pertussis
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 bacteria’s 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 Photo courtesy of CDC Public Health Image Library: Image ID 6379.
countries throughout the 1990s. This epidemic resulted in more

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Pertussis can affect children, adolescents, and adults.

Figure 3.9. Annual Incidence of Pertussis in the United States
Complications from pertussis occur most often among young 1980–2012
children. The most common complication is pneumonia.
Other complications that can occur include seizures and
60,000
encephalopathy, which can be caused by extended periods
of low oxygen supply during the coughing attacks. People 50,000
infected with pertussis may require hospitalization and

Number of Cases
pertussis infection can result in death. Adolescents and adults 40,000
infected with pertussis usually experience a more mild form of
30,000
the disease and are less likely to develop complications.
20,000
Adolescents and adults are a reservoir of pertussis in the
community, serving as the source of infections in children. 10,000
Even though adolescents and adults often experience a mild
form of pertussis, they can still transmit the disease to young 0

20 0
20 2
20 4
20 6
20 8
20 0
12
19 0
19 2
19 4
19 6
19 8
19 0
19 2
19 4
19 6
20 8
children because the disease is highly contagious. It has

0
0
0
0
0
1
8
8
8
8
8
9
9
9
9
9
19
become apparent that adolescents and adults have waning Year
immunity to pertussis as well as both tetanus and diphtheria. Source: Reference 33.

Following the introduction of whole-cell pertussis vaccines in

the 1940s when the reported incidence of pertussis frequently 5 doses of DTaP.40,41 Clusters of parents who refuse to
exceeded 100,000 cases per year, reports of pertussis vaccinate their children also may be contributing to regional
declined dramatically to fewer than 10,000 by 1965, and pertussis outbreaks.42
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. Vaccines
Multiple vaccines are available to provide protection against
In 2005, two new vaccines containing tetanus and tetanus, diphtheria, and/or pertussis and have various abbrevia-
diphtheria toxoids and acellular pertussis (Tdap) became tions based on their components.1,12 Capital letters indicate that
available for use in adolescents and adults. At that time, there is more antigen in the vaccine; lower-case letters indicate
ACIP released recommendations to provide a one-time a lower dosage of antigen. Available vaccines include:
dose of Tdap to adolescents and adults to boost immunity
• Diphtheria and tetanus toxoids and acellular pertussis
to pertussis with the goal of preventing the transmission
adsorbed (DTaP):
of pertussis to young children.34-36 Initially, there was a
decline with 10,007 cases of pertussis being reported in – Daptacel (Sanofi Pasteur)
2008. However, the number of pertussis cases rose again – Infanrix (GlaxoSmithKline)
with 21,291 cases being reported nationally in 2009, and • Diphtheria and tetanus toxoids adsorbed (DT):
48,277 in 2012 (Figure 3.9).33,37,38 Substantial regional – No trade name (Sanofi Pasteur)
increases in the number of pertussis cases also have been • Tetanus and diphtheria toxoids adsorbed, adult (Td):
reported.39 The highest incidence of reported pertussis cases
– Decavac (Sanofi Pasteur)
has occurred in infants younger than 1 year of age.
– No trade name (Massachusetts Biological
Laboratories)
Although the increase in the reported number of cases may
be due in part to increased awareness of pertussis disease, • Tetanus toxoid, reduced diphtheria toxoid, and acellular
there is concern that the tetanus and diphtheria toxoids and pertussis adsorbed (Tdap):
acellular pertussis vaccines (i.e., DTaP; currently used for – Adacel (Sanofi Pasteur)
children) are less potent than the tetanus and diphtheria – Boostrix (GlaxoSmithKline)
toxoids and whole-cell pertussis vaccines (i.e., DTwP) that • Tetanus toxoid (TT) adsorbed:
had been used previously. Data indicate that children who – No trade name (Sanofi Pasteur)
have received only DTaP have waning protection, even after

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DTaP is available in combination with other vaccines often tetanus toxoids (a combination known as DTP or DTwP).
used in childhood, including polio vaccine (DTaP-IPV; Routine immunization with DTwP vaccine became common
Kinrix—GlaxoSmithKline), hepatitis B and polio vaccines in the United States in the late 1940s and was effective in
(DTaP-HepB-IPV; Pediarix—GlaxoSmithKline), and polio preventing disease. However, local adverse events occurred
and Haemophilus influenzae type b vaccines (DTaP-IPV-Hib; after nearly half the doses of the vaccine. In addition,
Pentacel—Sanofi Pasteur). systemic events reported after receipt of the whole-cell
pertussis vaccine included fever higher than 40.5°C (105°F),
All of these inactivated vaccines contain tetanus toxoid (TT), transient hypotonic/hyporesponsive episodes, and transient
which is made by inactivating the toxin with formaldehyde. convulsions. Because of the concerns about safety and to
Although tetanus toxoid is available as a single antigen, avoid adverse events associated with whole-cell pertussis
it is not recommended for administration alone, except in vaccines, new acellular pertussis (aP or ap) vaccines were
the rare circumstance when the patient has a contraindi- developed that contain only certain components of the
cation to receiving diphtheria toxoid. Patients who should bacteria. DTaP vaccines have replaced whole-cell pertussis
be vaccinated against tetanus also need protection from vaccines, which are no longer available in the U.S. market.
diphtheria and pertussis. Acellular pertussis vaccine is available in combination with
diphtheria and tetanus toxoids as DTaP and Tdap. There is no
Diphtheria toxoid is the next component of these inactivated commercially available single-antigen pertussis vaccine.
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 Target Groups for Vaccination
compared with the pediatric-strength diphtheria and tetanus All infants, adolescents, and adults should be immunized
toxoids (DT) or diphtheria and tetanus toxoids and acellular against tetanus, diphtheria, and pertussis unless there is a
pertussis adsorbed (DTaP). The lower concentration (hence the valid contraindication or precaution to receiving the vaccine.32
small “d” in Td and Tdap) helps avoid injection-site reactions Recommendations for vaccination with tetanus-, diphtheria-,
in adults but will still provide protection in these patients as and pertussis-containing vaccines are summarized in Table
long as they have received a primary immunizing series. 3.3.32,34,35
Diphtheria toxoid is not available as a single antigen.
DTaP Vaccine
Whole-cell pertussis vaccines were developed in the 1930s. Children 6 weeks to 6 years of age should receive diphtheria
To produce this vaccine, whole bacteria were inactivated and tetanus toxoids combined with pertussis vaccine (DTaP).32
with formaldehyde and then combined with diphtheria and 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 weeks–6 years Use DTaP to complete the primary 5-dose series at ages 2, 4, 6, 15–18 months and 4–6 years.

Use DT only if patient has a specific contraindication to the pertussis component of DTaP

7–10 years (for patients who are not fully Give a single dose of Tdap
vaccinated against pertussis)
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 If there is no record of a Tdap dose, give a single dose of Tdap; follow with 1 dose of Td every 10 years
infants <12 months of age

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.

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then pediatric DT should be used to provide protection against All women of childbearing age should be vaccinated with
tetanus. The primary immunizing series in children should Tdap during every pregnancy.45 Tdap given to pregnant
include doses of DTaP given at 2 months, 4 months, 6 months, women will stimulate the production of pertussis antibodies
15 to 18 months, and 4 to 6 years of age.32 that will be transferred through the placenta and help protect
the infant; it also will protect the mother from developing
All adolescents and adults should have written documen- pertussis.45 Vaccination may be administered any time
tation of a primary series of tetanus and diphtheria toxoids– during pregnancy but is preferred during the third trimester
containing vaccines.32,34,35 If these records do not exist, a (between 27 and 36 weeks gestation) to transfer the highest
primary series of 3 doses is needed to provide protection. concentration of antibodies through the placenta. Women
This series should consist of 1 dose of Tdap and 2 doses of Td; who have just given birth should receive a single dose of
Tdap is preferred as the first dose.34,35 The first 2 doses must Tdap immediately postpartum if they have not received a
be separated by at least 4 weeks and the third dose should be dose previously. For women who have multiple closely
given at least 6 months after the first dose. spaced pregnancies, there is a theoretical risk for severe
local reactions (e.g., Arthus reactions, whole limb swelling);
Tdap Vaccine however, available data have not found an increased
In 2005, ACIP recommended vaccination with Tdap incidence of these reactions.45
for adolescents and adults to improve immunity against
pertussis.34,35 Tdap coverage appears to be increasing among ACIP currently recommends only one lifetime dose of Tdap
adolescents; the reported rate of at least 1 Tdap dose within except for pregnant women who should receive a dose
the past 10 years among 13 to 17 year olds was 68.7% in during each pregnancy. ACIP is considering a revaccination
2010 and 78.2% in 2011. Rates were higher when Td was recommendation for certain high-risk groups, such as health
included.43 Only 8.2% of adults 19 to 64 years of age had care providers.
received at least 1 dose of Tdap in 2010. However, 64% had
received a dose of any tetanus-containing vaccine in the past Td Vaccine
10 years.44 Because pertussis remains poorly controlled in the Any person who does not have a valid contraindication to
United States and vaccination rates in adolescents and adults receiving tetanus and diphtheria toxoids–containing vaccines
are low, ACIP expanded its recommendations in October should receive booster doses of Td every 10 years once a
2010 to include the following35: primary series has been completed and the person has a
record of receiving 1 dose of Tdap.32
• All patients aged 11 to 64 years old should receive a
one-time dose of Tdap.
Timing of Tdap Following Td
–P
 referably, all adolescents would receive a dose of If a person is a candidate for pertussis vaccination and has
Tdap at 11 or 12 years of age. recently received a Td booster dose, ACIP recommends that
–A
 ny person 11 to 64 years of age without documen- Tdap vaccination should not be delayed. Tdap vaccine should
tation of a Tdap dose should receive a one-time dose. be administered regardless of the interval since the last tetanus
or diphtheria toxoid–containing vaccine. ACIP reviewed the
• All adults aged 65 years and older who have or who available evidence and concluded that while longer intervals
anticipate having close contact with an infant less than between Td and Tdap vaccination could decrease the potential
12 months of age and who previously have not received occurrence of local reactions, the benefits of protection against
Tdap should receive a single dose of Tdap. pertussis outweigh the potential risk for adverse events.
• For other adults aged 65 years and older who have not
previously received Tdap, a single dose of Tdap vaccine Cocooning
may be given in place of 1 dose of Td vaccine. Because the risk of complications from pertussis is so great
in babies, people (e.g., grandparents, child care providers,
• Children aged 7 to 10 years who are not fully health care providers) who have close contact with young
vaccinated against pertussis and for whom no contra- children (younger than 12 months of age) should be targeted
indication to pertussis vaccine exists should receive a to receive Tdap if they have not previously received a dose.35
single dose of Tdap. As described in Module 2, the strategy of surrounding young
children with protection by vaccinating close contacts is known
as cocooning.

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• Convulsions or seizure with or without fever occurring

Special Consideration: Wound Management within 3 days of the vaccine dose.
Any patient presenting with an acute wound should be
questioned regarding the injury and vaccination history for These adverse events were more common after receipt of
tetanus-containing vaccines. If there is no record of a tetanus- DTwP but can occur after DTaP. Under usual circumstances,
containing vaccine in the past 10 years, patients may require a child should not be given additional doses of DTaP if a
both tetanus-containing vaccine and tetanus immune globulin precautionary adverse event listed above occurred following
to provide full protection against the disease. Pharmacists a prior dose. However, if the risk of pertussis is high (e.g.,
should refer to the current recommendations to determine during a community outbreak of pertussis), the benefit of
appropriate treatment strategies for patients with potential pertussis immunity may outweigh the risk of an adverse
exposure to tetanus. Recommendations were last published event, and the child’s primary care provider may decide
in 2011 and can be found in the CDC’s Manual for the to administer the vaccine. An adult who has a history of a
Surveillance of Vaccine-Preventable Diseases at www.cdc. reaction to DTP as a child (except a severe allergic reaction)
gov/vaccines/pubs/surv-manual/chpt16-tetanus.pdf. may receive Tdap vaccine.

Experts at ACIP and AAP consider it inappropriate to deny the

Contraindications and Precautions benefits of pertussis immunization to children with underlying
Tetanus and diphtheria toxoids and acellular pertussis– neurologic conditions (e.g., seizure disorders, epilepsy,
containing vaccines should be administered when appropriate cerebral palsy). However, vaccination should be deferred until
to a patient unless there is a valid contraindication or after an evolving neurologic condition resolves or stabilizes.
precaution to receiving the vaccines. Contraindications
include severe allergic reactions (e.g., anaphylaxis) to a
previous vaccine dose or to a vaccine component. Potential Adverse Reactions
The most common adverse reactions associated with tetanus
Precautions include a history of Guillain-Barré syndrome within and diphtheria toxoids–containing vaccines are local injection-
6 weeks following a previous dose of tetanus-containing site reactions. These injection-site reactions are usually mild
vaccine, as well of a history of Arthus-type hypersensitivity and self-limiting. However, Arthus reactions have been
reactions after a previous dose of tetanus-containing vaccine. reported after administration of these vaccines. Arthus
Patients who have an a history of an Arthus-type reaction reactions are the development of exaggerated symptoms such
following a previous dose should defer vaccine until at least as severe pain, swelling, edema, and possibly necrosis near
10 years have elapsed since the last tetanus toxoid–containing the site of injection.1,34,35 An Arthus reaction after vaccination
vaccine. As for all vaccines, moderate or severe acute illness with tetanus and diphtheria toxoids is not an allergic reaction
with or without fever is also a precaution. and is not common. However, these reactions may occur if
a patient is immunized with tetanus or diphtheria toxoids too
Special Contraindication Concerning DTaP frequently. Patients with a history of Arthus reactions after
DTaP vaccine is contraindicated in children who have had a vaccination should not receive doses of Td or Tdap any sooner
serious allergic reaction to it or who developed encephalopathy than every 10 years.34,35
within 7 days of a previous dose.31,32,34,35 ACIP and the
American Academy of Pediatrics (AAP) cite several precautions Acellular pertussis vaccines (i.e., DTaP and Tdap) may produce
for the use of pertussis vaccine. The precautions regard adverse local reactions including redness and swelling at the site of the
events after a previous dose of DTaP, including: injection. Local reactions have been reported more frequently
in children after the fourth and/or fifth doses of DTaP.1 Low-
• Fever of 40.5°C (105°F) or greater within 48 hours grade fever also has been reported after vaccination with
following the vaccine dose. DTaP and Tdap. Severe adverse events (e.g., fever greater
• Collapse or shock-like state (i.e., hypotonic/hypo­- than 40.5°C [105°F]), febrile seizures, persistent crying lasting
responsive episode) within 48 hours following the 3 hours or longer, hypotonic/hyporesponsive episodes) have
vaccine dose. been reported after DTaP vaccination but occur less frequently
than after vaccination with the whole-cell vaccines. None
• Persistent inconsolable crying for 3 hours or more within of these conditions has been associated with permanent
48 hours following the vaccine dose. brain injury. No increased risk of encephalopathy has been
observed with DTaP administration. The CDC continues to

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monitor long-term surveillance data on the safety of DTaP

relative to the more severe and rare adverse events that were Figure 3.10. Varicella Lesions on a Child’s Face
seen after vaccination with DTwP.

Storage and Administration of Tetanus, Diphtheria,

and Pertussis Vaccines
All vaccines containing tetanus, diphtheria, and pertussis
should be stored in the refrigerator at 2°C to 8°C (35°F
to 46°F); 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 complications may include cerebellar ataxia, encephalitis, and
disease.1 Primary infection causes varicella (i.e., chickenpox). pneumonia. Complications from varicella are more frequent in
After an acute infection with varicella, the virus lies dormant adults, children less than 1 year of age, immunocompromised
in nerve root ganglia. If the virus is reactivated, usually many patients, and newborns of mothers infected with varicella.
years later, a painful condition called herpes zoster (i.e.,
shingles) occurs (see Herpes Zoster section).
Vaccine
Before the varicella vaccine was licensed in the United States, Varicella vaccine (Varivax—Merck) is a live attenuated virus
infection with varicella zoster virus was nearly universal by vaccine.47,48 Because this is a live vaccine, it must replicate
age 15 years and an estimated 4 million people developed to stimulate an immune response. The vaccine produces
varicella each year.1,33 This very contagious virus is communi- an immune response similar to that produced by natural
cable from 1 to 2 days before onset through 4 to 5 days after infection.1 The varicella vaccine has been shown to reduce the
onset of the characteristic rash. Infection with varicella zoster risk of varicella infection by up to 90% and reduces the risk of
virus can be spread to a susceptible person by respiratory moderate to severe disease by up to 95%.1,12 Since varicella
transmission through airborne droplets or by direct contact vaccine was first introduced in the United States in 1995, it
with varicella or herpes zoster lesions. has significantly reduced morbidity and mortality related to
varicella.49,50

Clinical Features and Potential Complications Breakthrough infections have been reported in people
Natural varicella is characterized by a generalized rash, who have been immunized with 1 dose of vaccine. These
consisting of several hundred to more than a thousand pruritic people are more likely to have only mild disease with few
vesicles. The highest concentration of vesicles is usually on the lesions. Data from a 10-year surveillance period revealed
trunk. Lesions also can appear on the face, scalp, extremities, that increases in the severity and incidence of breakthrough
and mucous membranes of the body. The vesicles contain infection were associated with the length of time since
a clear fluid and often rupture or drain before they dry and vaccination, suggesting that the protection provided by a
develop a crust (Figure 3.10). single dose of varicella vaccine wanes over time. Therefore,
a second dose of varicella vaccine was added to the
Complications of varicella most commonly involve secondary immunization schedule in 2006.49,51
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

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Target Groups for Vaccination Susceptible women of childbearing age should be vaccinated
All children greater than 12 months of age should be before pregnancy because of a theoretical risk that varicella
vaccinated against varicella. Susceptible adolescents and is a teratogen at vulnerable stages of fetal development.
adults should be vaccinated if they do not have evidence of Although it is unknown if varicella vaccine is teratogenic,
immunity. According to ACIP recommendations, patients who more than a decade of monitoring inadvertent administration
can demonstrate evidence of immunity to varicella do not during or just before pregnancy suggests it is unlikely. After
need to be vaccinated. Evidence of immunity can include any immunization, women should wait at least 4 weeks before
of the following52: becoming pregnant. For unvaccinated women who become
pregnant, varicella vaccine should not be administered during
• Documentation of age-appropriate vaccination.
pregnancy.52 Rather, the first dose of varicella vaccine should
• Laboratory evidence of immunity or laboratory be administered immediately after childbirth (before the
confirmation of disease. woman is discharged from the hospital). The second dose
can be administered 4 to 8 weeks following delivery during a
• Birth in the United States before 1980. (However, for
postpartum health care visit.
health care providers, women of childbearing age,
and immunocompromised patients, birth before 1980
For children receiving varicella vaccine, there are two
should not be considered evidence of immunity because
options: varicella vaccine as a single-antigen vaccine or
certainty regarding immunity is desirable in these
varicella in combination with the measles, mumps, rubella
populations.)
vaccine (MMRV). Postlicensure studies indicated that among
• Diagnosis or verification of history of varicella disease children 12 to 23 months of age, 1 additional febrile seizure
or herpes zoster by a health care provider. (Verification occurred 5 to 12 days after vaccination for every 2,300 to
of history of disease or diagnosis should be provided by 2,600 children who received the first dose of MMRV vaccine,
a health care provider rather than relying on parental or compared with children who had received the first dose of
self-reporting.) MMR vaccine and varicella vaccine administered as separate
injections at the same visit.53

Vaccine Recommendations In June 2009, ACIP released a recommendation on the use

Children should receive a total of 2 doses of varicella vaccine of MMRV.53 For the first dose of measles, mumps, rubella,
to provide immunity. The recommended schedule for varicella and varicella vaccines at age 12 to 47 months, either
vaccine in children is as follows50: MMR vaccine and varicella vaccine or MMRV vaccine
may be used. Providers who are considering administering
• First dose at 12 to 15 months of age.
MMRV vaccine should discuss the benefits and risks of both
• Second dose at 4 to 6 years of age. vaccination options with the parents or caregivers. Unless
the parent or caregiver expresses a preference for MMRV
The first dose of varicella vaccine should not be given vaccine, CDC recommends that MMR vaccine and varicella
before the child’s first birthday because circulating maternal vaccine should be administered separately for the first dose
antibodies can interfere with the live vaccine. Any dose of in this age group. For the second dose of measles, mumps,
varicella vaccine administered before the first birthday should rubella, and varicella vaccines at any age (15 months to 12
not be counted as valid. years) and for the first dose at age 48 months or older, use of
MMRV vaccine generally is preferred over separate injections
All susceptible adolescents and adults should receive 2 doses of its equivalent component vaccines (i.e., MMR vaccine
of the varicella vaccine if they cannot demonstrate immunity and varicella vaccine). This recommendation is consistent
to varicella. For children younger than 13 years of age, the with ACIP’s general recommendations regarding use of
second dose should be given at least 3 months after the first combination vaccines, which state that use of a combination
dose. If the second dose is given sooner than 3 months (e.g., vaccine generally is preferred over its equivalent component
to provide protection during an outbreak), the dose can be vaccines.31
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.

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Contraindications and Precautions Storage and Administration of Varicella Vaccine

Varicella vaccine is contraindicated in patients with a history Varicella vaccine is a live vaccine that is sensitive to
of hypersensitivity to a prior dose or to any component of the temperature.48 Proper storage conditions are essential to
vaccine.31 The varicella vaccine contains very small amounts ensure vaccine potency. Varicella-containing vaccines should
of neomycin and gelatin.12 Patients having a history of be protected from light and kept frozen at a temperature
anaphylaxis to either of these components should be referred of –15°C (5°F) or colder before use. Varicella-containing
to an allergy specialist for vaccine decisions. Women who vaccine must be stored in refrigerator/freezer units that have
are pregnant should not receive varicella-containing vaccine a separate sealed freezer compartment or preferably in a
during pregnancy. separate freezer unit.

Because varicella vaccine is a live vaccine, it has some additional If the unreconstituted vaccine powder is inadvertently stored
contraindications and precautions to consider. Patients with in the refrigerator, it can remain viable for up to 72 hours at
immunosuppression should be referred to their primary care this temperature, but it must be discarded if unused within
provider for vaccine decisions. If a patient has recently received 72 hours. The vaccine, which requires reconstitution before
a blood product, live vaccines can be inactivated by antibodies injection, should be reconstituted with the diluent provided with
that may be present in the blood products, such as immune the vaccine. The diluent can be stored in the refrigerator or at
globulin, whole blood, or plasma. For patients in need of room temperature before use. Once reconstituted, varicella
varicella vaccine who have received a blood product in the vaccine should be administered immediately to avoid loss of
previous year, the pharmacist should refer to updated references potency. Vaccine that is not administered within 30 minutes of
(e.g., Epidemiology and Prevention of Vaccine-Preventable reconstitution must be discarded.
Diseases also known as “The Pink Book,” ACIP general
recommendations on immunization) to determine the appropriate The dose of varicella vaccine is 0.5 mL. This vaccine should
interval before the vaccine can be administered.1,31 be administered subcutaneously.

A personal or family (i.e., sibling or parent) history of seizure is

a precaution for use of MMRV vaccine.53
Herpes Zoster
Following an acute varicella infection (i.e., chickenpox), the
Potential Adverse Reactions varicella zoster virus can lie dormant in the neural dorsal
Varicella vaccine must replicate to evoke an immune response root ganglia. When the virus is reactivated, it causes herpes
and thus adverse reactions that are similar to symptoms of the zoster (i.e., shingles).54 Since herpes zoster is a reactivation
natural disease can occur. For example, patients may develop of the varicella zoster virus, it can only occur in patients who
a varicella-like rash after vaccination. These rashes are usually previously had chickenpox or, more rarely, in a patient who
minor, with few lesions, and usually are maculopapular rather has received the live varicella vaccine. Approximately 1 of
than vesicular. Additionally, this live vaccine can result in a every 3 people will develop herpes zoster during his or her
latent infection that can later present as herpes zoster. Herpes lifetime.1,55 Risk factors associated with the development of
zoster has occurred among patients who have received herpes zoster include advanced age, immunosuppression,
varicella vaccine although at a lower rate than after natural intrauterine exposure, or contracting varicella when younger
infection. As with other vaccines, local injection site reactions than 18 months of age.1
can be expected after vaccination. Systemic symptoms (e.g.,
fever) after varicella vaccination are not commonly reported.
Clinical Features and Potential Complications
Transmission of the attenuated virus in varicella vaccine is rare, Once the virus is reactivated, it travels along the sensory
although it has been reported.1,52 From the reported cases, it nerves to the skin’s surface and results in a painful condition
appears that this occurs only in patients who develop a rash after known as herpes zoster or shingles. Acute pain is the most
vaccination. If a rash develops, patients should avoid contact common symptom of shingles and usually precedes the
with people who do not have evidence of immunity appearance of the rash. The rash from herpes zoster usually
(e.g., infants) or those at high risk for complications from varicella appears as discrete patches of erythema that progress to
(e.g., immunocompromised individuals) until the rash resolves.52 grouped vesicles over a period of 7 to 10 days.55 The rash
usually appears on one side of the body and is typically

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distributed along one of the dermatomes (Figure 3.11). (A Oka/Merck strain as Varivax.12 The potency of the HZV to
dermatome is a localized area of the skin that is innervated prevent herpes zoster is at least 14 times greater than that of
by one spinal nerve.) Patients with active zoster lesions can the varicella vaccine to prevent chickenpox.48,58 Thus, the two
transmit varicella zoster virus to susceptible people from the vaccines are not interchangeable. The added potency in HZV
time the rash develops until the lesions crust over.55 If the virus is needed to elicit an appropriate immune response in older
is transmitted to a susceptible person, it can cause primary adults who are immune to varicella because of having had
varicella infection (i.e., chickenpox) in this person rather than chickenpox earlier in life.
causing herpes zoster. In addition to the rash, patients with
herpes zoster may experience itching, paresthesia, fever, HZV has been shown to be effective in reducing the risk of
headache, chills, upset stomach, and malaise. Very rarely, developing herpes zoster. This vaccine is indicated for the
herpes zoster can result in pneumonia, hearing problems, prevention of herpes zoster; it is not indicated for the treatment
blindness, encephalitis, or death.55 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
Figure 3.11. Patient With Herpes Zoster Rash 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

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 recommen-
dation 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
Photo courtesy of CDC Public Health Image Library: Image ID 6886.
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.
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 Vaccine Recommendations
the onset of the rash, and may persist for months or years. A single dose of HZV is recommended for adults 60 years
The impact of PHN on quality of life has been found to be and older, regardless of whether they have had a prior
comparable to that of congestive heart failure, myocardial episode of herpes zoster or report a history of chickenpox.55
infarction, type 2 diabetes, and major depression.56 PHN Those with chronic medical conditions may be vaccinated
develops in 10% to 50% of patients with herpes zoster, and unless a contraindication or precaution exists because of their
increases with age and in immunocompromised individuals.57 condition.
Herpes zoster is also associated with the development of other
neurologic conditions including ophthalmologic complications, In 2011, FDA expanded the age indication for zoster vaccine
Bell’s palsy, transient ischemic attacks, and stroke.57 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
Vaccine 70% in this population. Because the risk of getting shingles and
A vaccine that protects against herpes zoster (Zostavax— developing PHN is much lower for adults aged 50 to 59 years
Merck) was licensed by the FDA in 2006.58 The herpes zoster than for those aged 60 years and older, ACIP recommends
vaccine (HZV) is a live attenuated vaccine containing the same zoster vaccine only for adults at least 60 years of age.

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Nonetheless, individuals 50 to 59 years of age may be • Immunosuppression due to leukemia, lymphoma,

vaccinated. Health care providers may consider whether generalized malignancy, immune deficiency disease, or
the patient would have poor tolerance to herpes zoster PHN immunosuppressive therapy
symptoms when making a recommendation. For example, the
• Active untreated tuberculosis
provider may recommend HZV for a patient with preexisting
chronic pain, severe depression, other comorbidities, • Pregnancy
intolerance to treatment medications due to hypersensitivity
or interactions with other medications, or occupational Moderate or severe acute illness with or without fever is a
considerations.59 precaution for receipt of HZV. If there is no valid contraindi-
cation or precaution to receipt of HZV, the vaccine should be
In a randomized clinical study, a reduced immune response administered.
to HZV was observed in individuals who received concurrent
administration of 23-valent pneumococcal polysaccharide
vaccine (PPSV23) and HZV compared with individuals who Potential Adverse Reactions
received these vaccines 4 weeks apart. Based on these The most common adverse events reported with HZV include
data, the package insert for HZV vaccine advises that redness, pain or tenderness, swelling, and pruritus at the site
health care providers “consider administration of the two of the injection. Patients also have reported headache after
vaccines separated by at least 4 weeks.”56 However, the receiving the vaccine.
clinical relevance of the observed reduction in antibody titers
is unknown because there is no correlate of protection for Following receipt of HZV, transmission of the virus from a
antibody titers against varicella zoster virus as a measure of vaccinated person to a susceptible person has not been
protection against herpes zoster. It is likely that cell-mediated documented.54 According to the current recommendations,
immunity plays a larger role, but T-cell function was not vaccinated people do not need to take any precautions
assessed in this study. The results were additionally confounded around young children, pregnant women, and immunocom-
by unexplained differences across comparison groups in promised patients following receipt of the vaccine unless a
the baseline varicella zoster virus antibody titers. Antibody varicella-like rash develops after vaccination. Rates of this
levels to PPSV23 serotypes 3, 14, 19A, and 22F also were type of rash occurring after administration of HZV are rare,
assessed during this study and were unaffected by simultaneous but if a rash develops, susceptible people should avoid contact
administration; the significance of this observation is unknown. with the infected lesions.
Finally, study results indicated that the safety profile of HZV is
unaffected by simultaneous administration of PPSV23.
Storage and Administration of Herpes Zoster
Consequently, to avoid introducing barriers to patients and Vaccine
providers who are interested in administration of these two The herpes zoster vaccine is supplied in vials of lyophilized
vaccines, ACIP has not changed its recommendation for vaccine and a separate package of diluent and must be
simultaneous vaccination. ACIP continues to recommend reconstituted prior to injection. All varicella-containing
that HZV and PPSV23 be administered at the same visit if the vaccines are live vaccines that should be protected from light
patient is eligible for both vaccines. Practitioners should use and stored in the freezer at temperatures of –50°C to –15°C
their professional judgment based on the available data and (–58°F to 5°F).12,46 The vaccine may be kept at refrigerator
the policies of their practice. temperatures of 2°C to 8°C (35°F to 46°F) 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
Contraindications and Precautions 30 minutes of reconstitution, it should be discarded.
The vaccine for herpes zoster is contraindicated in individuals
with a history of anaphylaxis to a previous dose of the The diluent should be stored separately from the vaccine and
vaccine or to gelatin, neomycin, or any other component of can be stored in the refrigerator or at room temperature. The
the vaccine.1 However, a neomycin allergy that manifests vaccine should be reconstituted with the diluent immediately
as contact dermatitis should not be considered a contraindi- upon removal from the freezer and administered within
cation. The vaccine is also contraindicated in patients with the 30 minutes of reconstitution. If the reconstituted vaccine
following conditions: is not administered within 30 minutes, the vaccine should

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be discarded. Reconstituted or unreconstituted refrigerated in others the infection persists. Older age, infection with
vaccine should never be refrozen. multiple HPV types, and infection with a high-risk HPV type
are risk factors for persistent infection. Persistent infection is a
The dose of the HZV is a single 0.65 mL subcutaneous key risk factor for the development of moderate- or high-grade
injection, preferably in the posterior upper arm. 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
Human Papillomavirus other HPV-related cancers occur after many years of persistent
Human papillomavirus (HPV) infection is the most common infection, cases and deaths from these cancers will continue to
sexually transmitted infection in the United States.1,33 More occur owing to the large number of people currently infected
than 20 million U.S. women and men are infected with HPV 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 Vaccines
HPV infection include sexual activity at an early age and The first HPV vaccine, HPV4 (Gardasil—Merck), was licensed
with multiple partners; however, infection can occur following by the FDA in 2006.12,63 It is an inactivated, recombinant,
a single sexual encounter. At least 50% of sexually active quadrivalent vaccine prepared from highly purified virus-like
people will get HPV at some point in their lifetime.1 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
HPV is a double-stranded DNA virus that preferentially infects prefilled syringe. After completing the 3-dose series of HPV4,
epithelial cells. It has been identified as the etiologic agent for more than 99.5% of recipients develop an antibody response
cervical and other cancers, genital warts, and other diseases. to all four HPV types in the vaccine.1 In women naive to
Of the nearly 100 HPV types that have been identified, these HPV types, the vaccine has been shown to reduce the
approximately 40 can infect the genital mucosa and 16 are incidence of precancerous cervical lesions, precancerous
considered high-risk carcinogens. The high-risk HPV types vaginal and vulvar lesions, and genital warts at baseline by
include 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, nearly 100%.1 HPV4 is also licensed to prevent precancerous
69, 73, and 82. anal lesions and anal cancer in women and men.

High-risk HPV types are detected in 99% of cervical cancers.1 A second HPV vaccine, HPV2 (Cervarix—GlaxoSmithKline),
Together, HPV types 16 and 18 account for approximately was licensed for use in women by the FDA in 2009.64,65 It
70% of all cervical cancers.33 In 2010, almost 12,000 is an inactivated, recombinant, bivalent vaccine that contains
new cases of cervical cancer were diagnosed in the United virus-like particles from HPV types 16 and 18. HPV2 is
States and nearly 4,000 women died from cervical cancer available in a single-dose vial or a prefilled syringe. Within
in 2010.61,62 In addition to cervical cancer, high-risk HPV 1 month after completing the 3-dose series, 99% of vaccine
has been associated with vulvar, vaginal, anal, penile, oral, recipients develop an antibody response to HPV types 16 and
and pharyngeal cancers.1 Low-risk HPV types (e.g., 6, 11) 18.66 Vaccination with HPV2 has been shown to reduce the
cause the majority of cases of genital warts. Genital warts, incidence of precancerous cervical lesions caused by HPV
or condylomata acuminata, are growths of the cervico- types 16 and 18. HPV2 is not approved for use in men.
vaginal, vulvar, and external genitalia. While these growths
rarely progress to cancer, they are responsible for numerous
physician visits each year and considerable concern among Target Groups for Vaccination
patients with the disorder. 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
Clinical Features and Potential Complications Male patients may choose to be vaccinated with HPV4
The initial infection with HPV typically causes no signs or to reduce their likelihood of acquiring genital warts or
symptoms and consequently many people unknowingly developing anal cancer, but HPV2 is not indicated.64
spread the virus to others.63 In some individuals, the infection
resolves spontaneously without adverse health consequences;

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Ideally, HPV vaccine should be given prior to the onset of HPV4 as for all male patients, and vaccination through age 26
sexual activity to provide protection before potential exposure years for those who have not been vaccinated previously or
to HPV occurs through sexual contact. Vaccination before who have not completed the 3-dose series.68
exposure to any type of HPV will allow the individual to
receive full benefit from the vaccine. However, patients who The HPV vaccine may be given concurrently with other
are already sexually active should be vaccinated, because age-appropriate vaccines. If given simultaneously, each
they still may receive benefit from vaccination. vaccine should be administered using a separate syringe at a
different anatomic site.31
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 Contraindications and Precautions
will not prevent HPV due to HPV types not included in the The HPV vaccine should be administered to a patient when
respective vaccines. 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 Recommendations vaccine component.
ACIP recommends routine vaccination of boys and girls aged
11 to 12 years with a 3-dose series of HPV vaccine.67 Boys Precautions include moderate or severe illness with or without
should receive only HPV4. Girls may receive either HPV4 fever. Pregnant women should not be vaccinated because
or HPV2. HPV4 will provide protection against diseases it is not known whether the vaccine can cause fetal harm. If
caused by HPV types 6, 11, 16, and 18 (i.e., genital warts, pregnancy is identified after the vaccine series has begun,
precancerous lesions, and cancers). HPV2 will provide the remaining doses should be delayed until pregnancy is
protection against diseases caused by HPV types 16 and 18 completed.
(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. Potential Adverse Reactions
Pain at the injection site is the most common adverse event
Vaccination can be given as early as 9 years of age at the reported. Other adverse events include redness, swelling,
discretion of the health care provider. All 3 doses should be fever, and pruritus. Syncope (i.e., fainting) after vaccination
completed to provide protective immunity. The second dose with HPV also has been reported. This may be attributable
should be administered 1 to 2 months after the first dose and to vaccinating adolescents; syncope following vaccination
the third dose should be administered 6 months after the first appears to be more common in this age group. Immunizing
dose.65-67 pharmacists should be prepared to protect the patient from
injury from falling during fainting. According to ACIP,
Catch-up vaccination is recommended for girls and women clinicians should observe vaccinated patients for at least
aged 13 to 26 years who have not been vaccinated or 15 minutes after vaccination to monitor for syncope adverse
those who have not completed the full 3-dose series. If the events.31
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 Important Patient Counseling Information
previously or who have not completed the 3-dose series. Men Vaccination against HPV does not replace the need for
aged 22 to 26 years may be vaccinated. For immunocom- routine cervical cancer screening.67 Women who have been
promised male patients, ACIP recommends routine vaccination vaccinated should maintain the same recommended schedule
with HPV4 as for all male recipients, and vaccination through of screening with annual examinations including Papanicolaou
age 26 years for those who have not been vaccinated (Pap) tests. In addition, sexually active patients should
previously or who have not completed the 3-dose series. be educated to use barrier protection to prevent sexually
Men who have sex with men are at higher risk for infection transmitted infections.
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

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Storage and Administration of Human (Figure 3.13). This can occur in 30% to 40% of infected
Papillomavirus Vaccines people. Mumps can cause significant complications such as
HPV vaccines should be stored in the refrigerator at 2°C to aseptic meningitis, orchitis (inflammation of the testicles) in
8°C (35°F to 46°F).12,47 They must be protected from light postpubertal males, and permanent deafness. Death from
and should not be frozen. When administering the vaccine, mumps can occur but it is rare.
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. 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
Figure 3.12. Child With appears. The classic symptoms
Measles Rash of measles include fever, cough,
coryza (runny nose), conjuncti-
vitis, Koplik spots (a bluish-white
rash on mucous membranes,
especially the mouth), followed
by the development of a Photo courtesy of CDC Public Health Image Library: Image ID 130.
maculopapular rash approxi-
mately 14 days after exposure.
The rash usually appears first
on the face and neck and then Rubella
progresses downward to the Rubella virus is a member of the togavirus family.1 The
trunk, arms, and legs (Figure rubella virus is transmitted through the respiratory route and
3.12). Complications of measles is communicable from 7 days before until 5 to 7 days after
can include diarrhea, otitis the rash appears.
media, pneumonia, encephalitis, Rubella itself is
and death. Young children and Figure 3.14. Child With Rubella generally a mild
Photo courtesy of CDC Public
Health Image Library: adults over 20 years of age are disease, causing
Image ID 132.
at higher risk of complications few complica-
from the disease. tions. Rubella is
characterized by
a maculopapular
Mumps rash that occurs
Mumps infection is also caused by a paramyxovirus.1 Mumps approximately 2
is contagious but not to the same extent as measles. Mumps weeks after exposure
is spread by the respiratory route and the virus is communi- (Figure 3.14). Other
cable from 3 days before until 4 days after the onset of symptoms, most
symptoms. Some patients may not experience symptoms from commonly reported in
mumps infection while others have nonspecific symptoms (e.g., adult women infected
headache, fever, myalgia, malaise). When symptoms are Photo courtesy of CDC Public Health Image with rubella, include
present, the most common symptom characteristic of mumps Library: Image ID 10145. arthralgia and
infection is parotitis (inflammation of the parotid glands) arthritis.

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Even though rubella is generally a mild disease, there is great single dose, 5% of patients who receive the vaccine will not
public health concern about congenital rubella syndrome respond. While this number may seem low, the unprotected
(CRS).69 If a pregnant woman is infected with rubella, the 5% of recipients is enough to sustain viral transmission and
fetus can become infected and fetal harm can occur. Fetal outbreaks of disease, particularly in crowded environments
infection with rubella virus can lead to spontaneous abortion, such as schools and college dormitories. The recommendation
fetal death, or premature delivery. Complications of CRS to provide a second dose of MMR vaccine provides protection
include deafness, cataracts, heart defects, and mental in close to 99% of recipients.
retardation. A worldwide pandemic of rubella occurred in
1964–65 and at least 20,000 infants were affected by CRS in
the United States.1,33 Over 6,250 spontaneous abortions and Target Groups for Vaccination
over 2,100 excess neonatal deaths were reported. Among All individuals 12 months of age or older who do not have a
the infants who survived, 11,600 were deaf, 3,580 blind, and contraindication should be vaccinated.
1,800 mentally handicapped.

Vaccine Recommendations
Sustaining Vaccination Efforts to Eliminate Children should receive a 2-dose series with the first dose
Outbreaks between 12 and 15 months of age and the second dose at 4
Vaccination efforts have been successful in significantly to 6 years of age.74 As discussed in the section on varicella,
decreasing the number of cases of measles, mumps, and children may be vaccinated with either MMR vaccine or
rubella in the United States.1,33 Before measles vaccine was MMRV vaccine.
introduced in this country, measles virus infected nearly
everyone by 15 years of age and accounted for an estimated The first dose should not be given before the child’s first
3 million to 4 million cases of measles each year (i.e., the birthday because circulating maternal antibodies can interfere
entire annual birth cohort).1,33 After implementation of routine with the vaccine. All children and adolescents up through 18
vaccination, the number of measles cases dropped signifi- years of age should have documentation of 2 doses of MMR
cantly in the United States, reaching a record low of 37 cases vaccine. If no reliable documentation is available, administer
reported in 2004.1 Most cases of measles that now occur 2 doses of MMR vaccine separated by at least 4 weeks.
in the United States are linked to infections acquired outside
this country. The number of mumps cases reached a record Certain adults should receive MMR vaccine.75 In general,
low of 231 cases in 2003. However, as discussed in Module adults born before 1957 are considered immune to measles
1, outbreaks of measles and mumps have occurred in recent and mumps. However, health care providers born before
years, demonstrating that people are still susceptible to these 1957 must be able to demonstrate evidence of measles,
diseases.70-72 Many of the reported cases in the outbreaks mumps, and rubella immunity or laboratory confirmation
occurred in people who were not vaccinated or inadequately of the three diseases. Health care providers born before
vaccinated. Furthermore, many of the cases reported during 1957 who cannot demonstrate adequate proof of immunity
the outbreak were imported from other countries. should consider receiving MMR vaccine (2 doses separated
by at least 28 days if the provider does not have immunity
In addition to concerns about outbreaks of measles and to measles or mumps; 1 dose if the provider does not have
mumps, CRS must be kept under control. The devastation that immunity to rubella).
can be caused by CRS, as witnessed during the last rubella
pandemic, should be reason enough to vaccinate patients Adults born in 1957 or later should have documentation of at
against this disease. Vaccination efforts must continue across least 1 dose of MMR vaccine (unless it is contraindicated), or
the county to minimize or eliminate outbreaks and provide laboratory evidence of immunity to each of the three diseases,
protection from these 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
Vaccines exposed to the diseases (e.g., outbreak setting); (2) are
The measles, mumps, and rubella vaccine (M-M-R II—Merck) students in postsecondary educational institutions; (3) work in
is a live virus vaccine.73 Although the measles, mumps, and a health care facility; or (4) plan to travel internationally.
rubella (MMR) vaccine protects 95% of recipients after a

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Women of childbearing age who do not have acceptable by the vaccine.1,12 Most adverse effects observed after
documentation of prior vaccination or serologic evidence of vaccination with MMR are transient and occur among people
rubella immunity should be vaccinated prior to pregnancy.74 susceptible to infection. As a result, adverse events after
A physician’s diagnosis or a personal history of rubella is not the second dose are uncommon, because most recipients of
considered acceptable evidence of immunity. Women should second doses are already immune to the diseases.
receive the MMR vaccine at least 4 weeks before becoming
pregnant. MMR vaccine should not be given to a pregnant Rarely, MMR vaccine may cause thrombocytopenia within 2
patient or to a patient who plans to become pregnant within 4 months after vaccination. Estimates of the frequency of clinically
weeks. Pregnant women who do not have evidence of rubella apparent thrombocytopenia from Europe are 1 case per 30,000
immunity should receive the MMR vaccine upon completion of to 40,000 vaccinated susceptible persons, with a temporal
the pregnancy. 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 thrombocy-
Contraindications and Precautions topenia during rubella or measles infection is much greater than
MMR vaccine should be administered when appropriate to a the risk after vaccination. Based on case reports, the risk for
patient unless there is a valid contraindication or precaution MMR-associated thrombocytopenia may be higher for patients
to receiving the vaccine. MMR vaccine is contraindicated in who have previously had immune thrombocytopenic purpura,
patients with a history of hypersensitivity to a prior dose or to particularly for those who had thrombocytopenic purpura after
any component of the vaccine.31 The vaccine contains very an earlier dose of MMR vaccine.
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.
Storage and Administration of Measles, Mumps,
Women who are pregnant should not receive MMR vaccine. and Rubella Vaccines
Measles and mumps vaccine viruses are grown in chick MMR vaccine is provided as lyophilized vaccine and diluent.
embryo fibroblast tissue culture. However, MMR does not The vaccine should be protected from light at all times and
contain a significant amount of egg protein so patients with should be stored in the refrigerator at 2°C to 8°C (35°F to
severe egg allergy may be vaccinated with extreme caution. 46°F) or freezer at temperatures as cold as –50°C (–58°F).1,46
Diluent should not be frozen. The lyophilized vaccine should
Because MMR is a live vaccine, there are some additional be stored in the refrigerator before reconstitution, and reconsti-
contraindications and precautions to consider. Patients tuted according to the manufacturer’s instructions just before
with immunosuppression should not receive MMR vaccine use. The 0.5 mL dose should be administered subcutane-
and should be referred to their primary care provider for ously immediately after reconstitution. MMR vaccine must
vaccination decisions. If a patient has received a blood be administered within 8 hours of reconstitution or it must
product in the previous year, live MMR vaccine viruses be discarded. MMRV must be used within 30 minutes of
can be inactivated by antibodies that may be present in reconstitution.
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 Pneumococcal Disease
determine the appropriate interval before the vaccine can be Pneumococcal disease is caused by Streptococcus
administered.1,31 pneumoniae, a gram-positive coccobacillus bacteria. Some
pneumococci are encapsulated, with surfaces composed
of complex polysaccharides. These capsules allow the
Potential Adverse Reactions bacteria to evade some immune cells (e.g., phagocytes)
Mild injection-site reactions can be expected after vaccination and interfere with the activation of an immune response.1
with MMR vaccine. Other adverse events that have been A person’s immune system must be able to recognize the
reported include fever, rash, arthralgia, and arthritis. Parotitis polysaccharide capsule and create antibodies directed
and deafness rarely occur after vaccination. Rarely, encepha- against the polysaccharide capsule to provide protection
lopathy may be temporally associated with a dose of the against this infection.
vaccine, but this event has not been proven to be caused

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Clinical Features and Potential Complications Before the availability of a pneumococcal conjugate vaccine
S. pneumoniae is a human pathogen that colonizes the for infants and toddlers, invasive pneumococcal disease
nasopharynx of up to 70% of children and adults.1 Over caused significant morbidity and mortality in this age group.1
90 serotypes of S. pneumoniae have been known to cause Each year in the United States, an estimated 17,000 cases of
serious disease. In the years prior to widespread use of invasive pneumococcal disease occurred in children
pneumococcal conjugate vaccine, the 10 most common and an estimated 200 children died from these infections.
serotypes accounted for approximately 62% of invasive S. pneumoniae also caused up to 5 million cases of acute
pneumococcal disease.1 Although carriers of S. pneumoniae otitis media each year.1,33,77 While the burden of otitis media
may be asymptomatic, they can transmit the bacteria to others. is not significant in terms of mortality data, it is a significant
cause of lost time from work for parents and caregivers. It
S. pneumoniae can be transmitted by airborne respiratory also contributes to the health care dollars spent on visits to
droplets or by direct contact with infected respiratory physicians and medication therapies.77
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 Drug-Resistant Streptococcus pneumoniae
include pneumonia, bacteremia, meningitis, sinusitis, and otitis Before 1990, S. pneumoniae was usually susceptible to
media.1,33 penicillin, allowing most infections to be treated with penicillin
alone.33 However, resistance to penicillin and to multiple other
Pneumococcal pneumonia is the most common infection due classes of antimicrobial medications has increased signif-
to S. pneumoniae, accounting for approximately one-third icantly over time. The CDC reports cases of drug-resistant
of community-acquired pneumonias and one-half of all S. pneumoniae across the country, accounting for up to 40%
hospital-acquired pneumonias.1 Nearly 175,000 adults are of pneumococcal isolates in some areas.1
hospitalized with pneumococcal pneumonia each year in
the Unites States.1,33 Pneumococcal pneumonia can occur as The treatment of pneumococcal disease is difficult owing to the
the primary infection or as a secondary complication from emergence of drug-resistant S. pneumoniae. As drug-resistant
influenza infection. Pneumococcal pneumonia has a short strains have become more common, empiric treatment with
incubation period of only 1 to 3 days and typically has an broad-spectrum agents has been used to treat pneumococcal
abrupt onset with symptoms of fever, shaking chills, productive infections. However, inappropriate antibiotic use contributes
cough, pleuritic chest pain, malaise, weakness, difficulty to the development of drug-resistant S. pneumoniae,
breathing, and rapid, shallow breathing.1,33 complicating the situation further.33 As antibiotics become
less effective in treating pneumococcal disease, prevention by
Pneumococcal bacteremia is a serious infection of the vaccination becomes even more important to protect people
bloodstream caused by S. pneumoniae. Bacteremia occurs in from this disease and its complications.
approximately one-third of patients who have pneumococcal
pneumonia. While the symptoms of pneumococcal bacteremia
are usually nonspecific (e.g., fever, chills, difficulty breathing), Vaccines
this is a serious infection that can lead to septicemia and The 7-valent pneumococcal conjugate vaccine (PCV7;
cause death in 20% of patients (up to 60% of elderly Prevnar—Wyeth) was the first pneumococcal conjugate
patients).1,33 vaccine available in the United States. The most recent
data available indicate that the overall rates of invasive
S. pneumoniae can cause pneumococcal meningitis, which pneumococcal disease in people of all ages decreased by
is inflammation of the membranes surrounding the brain and 45% since the PCV7 vaccine was introduced in 2000.76 This
spinal cord. One-fourth of all people with pneumococcal decrease in invasive pneumococcal disease is an example
meningitis also have pneumonia.1 Signs and symptoms of of herd immunity because PCV7 was given only to children
pneumococcal meningitis are similar to other bacterial causes younger than 7 years of age. Vaccination with PCV7 resulted
of meningitis and may include headache, lethargy, irritability, in reduced transmission of pneumococcal infection caused
seizures, vomiting, cranial nerve involvement, and coma. by the serotypes contained in the vaccine and ultimately
Neurologic sequelae are common in patients who survive a decreased the overall rate of invasive pneumococcal disease.
case of pneumococcal meningitis. Death can occur in 30% of Even though there is generally less invasive pneumococcal
patients (up to 80% of elderly patients).1,33 disease, other strains of S. pneumoniae that are not in the

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PCV7 vaccine have become more common. PCV7 has been Target Groups for Vaccination
replaced by the 13-valent pneumococcal vaccine, which Despite the decreases in invasive pneumococcal disease since
added 6 more serotypes to those in PCV7, and the current the introduction of PCV7, invasive pneumococcal disease
PCV13 provides more comprehensive coverage against remains an important cause of illness and death in the United
pneumococcal disease. States. PCV13 and PPSV23 have both routine uses and
recommended uses for high-risk individuals. High-risk children
13-Valent Pneumococcal Conjugate Vaccine and adults are listed in Table 3.4.76,77
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, Vaccine Recommendations
18C, 19A, 19F, and 23F). PCV13 also is indicated for the
prevention of otitis media caused by S. pneumoniae serotypes Children and Adolescents
4, 6B, 9V, 14, 18C, 19F, and 23F. All children aged 2 months to 59 months should be routinely
vaccinated with PCV13. The recommended routine
PCV13 is a conjugate vaccine, meaning that polysaccharides vaccination schedule for the 4-dose series is administration at
are linked to a protein (a diphtheria protein in this case) during 2, 4, 6, and 12 to 15 months of age.84
the manufacturing process. As discussed in Module 2, the
process of conjugation is necessary because children younger Unvaccinated children 7 months of age and older do not
than 2 years of age do not consistently mount an effective require a full series of 4 doses. The number of doses a child
immune response to pure polysaccharide vaccines. needs to complete the series depends on the child’s current
age. Unvaccinated children aged 7 to 11 months should
23-Valent Pneumococcal Polysaccharide Vaccine receive 2 doses of vaccine at least 4 weeks apart, followed
The pneumococcal polysaccharide vaccine (PPSV23; by a booster dose at age 12 to 15 months. Unvaccinated
Pneumovax 23—Merck) contains polysaccharides from 23 children aged 12 to 23 months should receive 2 doses of
strains of S. pneumoniae that were most prevalent at the time vaccine, at least 8 weeks apart. Previously unvaccinated
when the vaccine was licensed.1,12 healthy children 24 to 59 months of age should receive a
single dose of PCV13.
Over 80% of healthy adults who receive PPSV23 will respond
by developing antibodies against the serotypes contained Unvaccinated children 24 to 71 months of age with certain
in the vaccine within 2 to 3 weeks after vaccination.1,79 chronic medical conditions should receive 2 doses of PCV13
Vaccine efficacy declines with advancing age and may be separated by at least 8 weeks. These conditions include
less effective in patients with underlying illness. However, the chronic heart and lung disease, diabetes, cerebrospinal fluid
vaccine can still provide protection for these high-risk patients leak, cochlear implant, sickle cell disease and other hemoglo-
and should be administered. Because this is a pure poly- binopathies, functional or anatomic asplenia, HIV infection,
saccharide vaccine, it is not adequately effective in children or immunocompromising conditions resulting from disease or
younger than 2 years of age. treatment of a disease.

PPSV23 has been shown to reduce the risk of invasive For children aged 14 to 59 months who have previously
disease (e.g., bacteremia, meningitis) by 60% to 70%.1,79 received an age-appropriate PCV7 series, a single
To date, study results have not demonstrated consistent supplemental dose of PCV13 should be administered to
evidence that PPSV23 reduces the incidence of pneumococcal provide protection against the 6 additional serotypes
pneumonia.1,12,79,80 However, studies do suggest that even contained in PCV13. For children who have an underlying
if PPSV23 does not prevent pneumococcal pneumonia, medical condition, a single supplemental PCV13 dose is
vaccination with PPSV23 can improve outcomes in patients recommended through 71 months of age. This includes
with pneumococcal pneumonia. In these studies, patients children who have received PPSV23 previously. PCV13 should
with pneumococcal pneumonia who had been vaccinated be administered at least 8 weeks after the most recent dose of
experienced fewer complications, decreased length of hospital PCV7 or PPSV23.84
stay, decreased need for admission to the intensive care unit,
and a lower rate of death.81-83

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Table 3.4. High-Risk Indications and Recommendations for Administration of PCV13 and PPSV23
Risk Group Underlying Medical Condition PCV13a PPSV23
Recommended Recommended Revaccination
5 Years After
First Dose
Immunocompetent patients Chronic heart diseaseb ✓

Chronic lung diseasec ✓

Diabetes mellitus ✓

Cerebrospinal fluid leaks ✓ ✓

Cochlear implants ✓ ✓

Alcoholism ✓

Chronic liver disease ✓

Cigarette smoking ✓

Patients with functional or anatomic asplenia Sickle cell disease/other ✓ ✓ ✓

hemoglobinopathies

Congenital or acquired asplenia ✓ ✓ ✓

Immunocompromised patients Congenital or acquired ✓ ✓ ✓

immunodeficienciesd

HIV infection ✓ ✓ ✓

Chronic renal failure ✓ ✓ ✓

Nephrotic syndrome ✓ ✓ ✓

Leukemia ✓ ✓ ✓

Lymphoma ✓ ✓ ✓

Hodgkin disease ✓ ✓ ✓

Generalized malignancy ✓ ✓ ✓

Iatrogenic immunosuppressione ✓ ✓ ✓

Solid organ transplant ✓ ✓ ✓

Multiple myeloma ✓ ✓ ✓
a
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.
b
Including congestive heart failure and cardiomyopathies.
c
Including chronic obstructive pulmonary disease, emphysema, and asthma.
d
Includes B-(humoral) or T-lymphocyte deficiency, complement deficiencies (particularly C1, C2, C3, and C4 deficiencies), and phagocytic disorders (excluding chronic
granulomatous disease).
e
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 PPSV23 is recommended only for children who have high-risk
a 3-dose series of PCV7 should receive the a supplemental conditions. For these children, PPSV23 should be administered
single dose of PCV13 up to the age of 18 years regardless at least 8 weeks after the last dose of PCV to children aged
of whether they have previously received PCV7 or PPSV23. 2 years or older. A second PPSV23 dose should administered
Children younger than 71 months should receive 2 doses of after 5 years to children with anatomic or functional asplenia
PCV13 if fewer than 2 doses of PCV 7 were administered. (including sickle cell disease) or an immunocompromising
Multiple doses should be given at least 8 weeks apart. condition.84

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Adults Storage and Administration of Pneumococcal

Routine vaccination with PPSV23 should be provided for Vaccines
all adults aged 65 years and older, as well as residents of Both the PCV13 and PPSV23 vaccines should be stored in
nursing homes or long-term care facilities, and adults who the refrigerator at 2°C to 8°C (35°F to 46°F); these vaccines
smoke cigarettes.75 Typically, a single dose of PPSV23 is should not be frozen.85,86 When administering the vaccine,
sufficient for most patients and routine revaccination is not the vial or manufacturer-filled syringe should be shaken before
recommended. use. The 0.5 mL dose of PCV13 should be administered
intramuscularly. The dose of PPSV23 is also 0.5 mL, and
Adults with immunocompromising conditions are this vaccine may be administered either intramuscularly or
recommended to receive both PCV13 and PPSV23 vaccines. subcutaneously.
The PCV13 dose should be administered first, followed by
PPSV23 at least 8 weeks later. If PPSV23 has been adminis-
tered but PCV13 has not, the PCV13 should be administered
at least 1 year after PPSV23. See Figure 3.15 for an algorithm Meningococcal Disease
of when to administer pneumococcal vaccine to adults with Meningococcal disease includes the spectrum of illness caused
selected conditions.76 by Neisseria meningitidis, including meningitis, bacteremia,
and bacteremic pneumonia. N. meningitidis is an aerobic,
One-time PPSV23 revaccination 5 years after the first dose is gram-negative bacterium with a polysaccharide capsule that
recommended for adults 19 to 64 years of age with certain surrounds the outer membrane of the bacteria and helps it
immunocompromising conditions. Those who have received evade certain cells of the immune system (e.g., phagocytes).1
1 or 2 doses of PPSV23 before 65 years of age should N. meningitidis is classified into serogroups based on the
receive an additional dose at age 65 years (resulting in a structure of the polysaccharide capsule. Although 13 polysac-
maximum of 3 lifetime doses of PPSV23).75 charide 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
Contraindications and Precautions for more than 75% of meningococcal disease in people
The pneumococcal vaccine should be administered unless older than 11 years of age, while serogroup B is the most
there is a valid contraindication or precaution to receiving the common cause of meningococcal disease in infants, but is
vaccine. PCV13 and PPSV23 are contraindicated for patients not contained in any vaccines licensed for use in the United
who have had a severe allergic reaction (e.g., anaphylaxis) to States.33 Although serogroup A is common in Africa, it is
a previous vaccine dose or to a vaccine component (including rarely reported in the United States.1
a diphtheria toxoid–containing vaccine for the PCV13
vaccine). Precautions include moderate or severe acute illness
with or without fever. Clinical Features and Potential Complications
N. meningitidis is transmitted by the respiratory route. Once
the bacteria colonize in the nasopharynx, they begin to
Potential Adverse Reactions replicate. The bacteria are capable of invading the body
through the bloodstream, causing invasive disease. The
Pneumococcal Conjugate Vaccine number of reported cases of invasive meningococcal disease
Local injection-site reactions are the most commonly reported has been declining in the last few years. Fewer than 1,000
adverse reactions after administration of PCV. Fever also has cases of invasive meningococcal disease have been reported
been reported. Less frequent adverse events that can occur each year since 2009. The reason for this decline is not
include irritability, drowsiness, restless sleep, and decreased known with certainty but at least partially may be due to
appetite.76,77 increased use of meningococcal conjugate vaccine.

Pneumococcal Polysaccharide Vaccine The most common form of invasive disease caused by
Up to half of the patients who receive PPSV23 will develop N. meningitidis is meningitis.33 It typically presents with
a mild, local reaction that may include mild pain, swelling, nonspecific symptoms similar to other types of meningitis.
and redness at the injection site.1,80 Fever and myalgias after Symptom onset is usually sudden and can include high fever,
PPSV23 administration occur in fewer than 1% of recipients. headache, myalgia, stiffness of the neck, and sensitivity to

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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 NO Is patient NO Refer to

19–64 years ≥65 years Pediatric
old? old? Schedule.

YES YES

Has patient
Has patient NO NO Give PCV13 if it
received PPSV23
received PPSV23 has been at least
since turning
in the past? 1 year after
age 65 years?
Give PCV13. last PPSV23 and
give PPSV23
8 weeks later 8 weeks later if
it has been >5 years
Give PPSV23.
since last PPSV23.
YES
5 years later YES

Give PPSV23.

Give PCV13
How 1 1 year
many after last
doses? Give PCV13 PPSV23.
1 year
after PPSV23.

2 8 weeks later

Give PPSV23
Give PCV13 if 5 years since
1 year previous PPSV23.
after last
PPSV23.

ACIP = Advisory Committee on Immunization Practices;

CSF = cerebrospinal fluid; PCV13 = 13-valent
After age 65 years, give PPSV23 if it pneumococcal conjugate vaccine; PPSV23 = 23-valent
has beenat least 5 years since last pneumococcal polysaccharide vaccine.
PPSV23 and 1 year after last PCV13.
The lifetime maximum number of doses Source: Reference 76.
of PPSV23 is 3.

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light. In addition to meningitis, N. meningitidis can cause Nearly 98% of patients will develop high levels of antibodies
sepsis, pneumonia, arthritis, otitis media, and epiglottitis. after vaccination.1 Protection will not usually be achieved for
Despite appropriate antibiotic therapy, approximately 9% to at least 7 to 10 days after vaccination.
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 Target Groups for Vaccination
can have significant complications such as hearing loss, ACIP recommends routine vaccination for the following
neurological damage, and limb loss. patients87:
• Adolescents aged 11 to 12 years, with a booster dose
Risk factors for meningococcal disease include certain
at 16 years.
immunodeficiencies. In addition, antecedent viral infection,
crowded housing, chronic underlying illness, and active • All previously unvaccinated adolescents aged 13 to 15
and passive smoking are associated with increased risk for years, with a booster dose at age 16 to 18 years.
disease.87 First-year college students living in dormitories have
• Children aged 2 months to 10 years with high-risk
been found to have higher risk for meningococcal disease
conditions.
than other students.
• People aged 2 months to 55 years who are at high risk
The first quadrivalent polysaccharide vaccine for the prevention for meningococcal disease.
of meningococcal disease was licensed in 1981. The first
conjugate vaccine was approved and recommended for use in People at high risk include:
2005. The incidence of meningococcal disease has declined
• College freshmen living in dormitories.
annually since a peak of disease in the late 1990s. Although
the disease incidence is currently at a historically low rate, 10% • Military personnel.
to 15% of those who contract the disease continue to die from it,
• Patients with anatomic or functional asplenia.
and an additional 11% to 19% have long-term sequelae.87
• Patients with immunodeficiencies (e.g., complement
component deficiency).
Vaccines • People who travel to countries where N. meningitidis is
Currently, three vaccines are available in the U.S. market endemic (e.g., “meningitis belt” of sub-Saharan Africa).
that protect against N. meningitidis serogroups A, C, Y, and
W-135 (Menomune—Sanofi Pasteur; Menactra—Sanofi • People who travel to countries where vaccination is
Pasteur; and Menveo—Novartis).88-90 Additionally, a bivalent required (e.g., travelers to Saudi Arabia for annual Hajj).
meningococcal vaccine (MenHibrix—GlaxoSmithKline) • Microbiologists who routinely handle N. meningitidis
protects against C and Y in combination with providing isolates.
protection against Hib.

These vaccines are not effective against serogroup B.1 Vaccine Recommendations
Research is ongoing to develop a vaccine to protect against A single dose of meningococcal conjugate vaccine should
serogroup B meningococcus. be administered to all patients in any of the target groups
listed in the previous section. ACIP now recommends routine
Menomune (MPSV4) is a quadrivalent pure meningococcal vaccination with MCV4 for all adolescents 11 to 12 years
polysaccharide vaccine. Because this is a polysaccharide of age, followed by a booster dose given at 16 years of
vaccine, it is not generally effective in children younger than 2 age.87 This recommendation is based on evidence suggesting
years of age. Menactra and Menveo are protein-conjugated that people immunized at age 11 or 12 years may have
meningococcal vaccines (also referred to as MCV4 or decreased protective immunity after 5 years, when their risk
MenACWY). Menactra is licensed for patients 9 months to for meningococcal disease is greatest.
55 years of age; Menveo is licensed for patients 2 months to
55 years of age. MCV4 is preferred over MPSV4 for patients All adolescents aged 13 to 18 years who have not received
aged 55 years and younger. MenHibrix (Hib-MenCY) is a MCV4 should receive a dose of the meningococcal conjugate
polysaccharide vaccine in combination with Hib approved vaccine. Adolescents who receive the first dose of MCV4
only for children 6 weeks to 18 months of age. at 13 to 15 years of age should receive a booster dose at
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16 to 18 years of age with a minimum interval of at least 8 Revaccination

weeks between doses. Healthy people who receive their first Children at continued risk for meningococcal disease who
routine dose of MCV4 at or after age 16 years do not need were previously vaccinated with MCV4 or MPSV4 should
a booster dose. Routine vaccination of healthy people who receive an additional dose of MCV4 after 3 years if the first
are not at increased risk of exposure to N. meningitidis is not dose was administered at 2 to 6 years of age. Patients who
recommended. have completed the 2-dose primary series and remain at
continued risk for meningococcal disease should be revacci-
Patients with certain medical conditions (i.e., persistent nated 5 years after the last dose of the primary series.87
complement component deficiency, anatomical or functional
asplenia, or HIV infection) should receive 2 doses of MCV4 Patients with persistent complement component deficiency
at least 8 weeks apart.87 A single dose of MCV4 in these or anatomic or functional asplenia should receive 1 dose of
patients will not produce a sufficient immune response to MCV4 every 5 years after completing the 2-dose primary
provide complete protection. Although HIV infection is not an series with MCV4.87
indication for MCV4 vaccination, an HIV-infected person may
have another indication for vaccination (e.g., inter-
national travel). People with HIV infection and an indication Contraindications and Precautions
for vaccination should receive a 2-dose primary series. Any patient meeting the above criteria and having no valid
Children younger than 19 months at increased risk of contraindications or precautions should receive meningococcal
exposure or with high-risk medical conditions (e.g., asplenia) vaccine.1 Meningococcal vaccines are contraindicated in
should receive either an infant age-appropriate series of individuals who have had a severe allergic reaction (e.g.,
Hib-MenCY or MCV4; (see the child and adolescent schedule anaphylaxis) to a previous vaccine dose or to a vaccine
for detailed recommendations based on high-risk condition).84 component. Moderate or severe acute illness with or without
MenHibrix should not be administered to a child who travels fever is a precaution.
to sub-Saharan Africa or the Hajj, or to international travelers
who require meningococcal vaccine because it does not A history of Guillain-Barré syndrome had previously been
contain serogroups A or W-135. Only Menveo (for patients a precaution for Menactra (MCV4). The CDC and FDA, in
aged 2 months and older) or Menactra (for patients aged partnership with state health departments, have been monitoring
9 months and older) should be administered. cases of Guillain-Barré syndrome among adolescents who
received MCV4. With more than 2 million doses of Menactra
Previously, ACIP recommended only MPSV4 (Menomune) for use given since 2005, there has been no evidence of an increased
in adults aged 56 years and older. The most recent meningo- risk of Guillain-Barré syndrome. Based on this information, ACIP
coccal recommendations, published in March 2013, recommend removed the precaution for use of Menactra in people with a
the use of either MCV4 vaccine (Menactra or Menveo) for adults history of Guillain-Barré syndrome.87
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 Potential Adverse Reactions
working with N. meningitidis). Both MCV4 vaccine products The most common adverse events after administration of
are licensed for use in people through 55 years of age, which meningococcal vaccine are injection-site reactions. Adverse
means that the ACIP-recommended use of these vaccines in effects are generally mild, and may include pain and redness
people aged 56 years and older is off-label. MPSV4 should at the site of injection. Systemic reactions (e.g., headache,
be used only for previously unvaccinated persons 56 years and malaise, fever) also have been reported.
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 Storage and Administration of Meningococcal
Vaccines
All meningococcal vaccines (i.e., Hib-MenCY, MCV4, and Meningococcal vaccines should be stored in the refrigerator
MPSV4) are recommended for control of disease during at 2°C to 8°C (35°F to 46°F) and protected from light at all
community meningitis outbreaks. Pharmacists should times.12,46 For MCV4, pharmacists should shake the vial or
refer to their local health department for advice regarding prefilled syringe before use, and administer the 0.5 mL dose
immunization during meningococcal outbreaks. intramuscularly. Menveo must be prepared for administration

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by reconstituting the MenA lyophilized conjugate vaccine The first dose of the hepatitis A vaccine provides protective
component with the MenCYW-135 liquid conjugate vaccine levels of antibodies in more than 95% of patients and nearly
component according to manufacturer’s instructions. For 100% of patients will be fully protected after completing the
MPSV4, pharmacists should reconstitute the product according 2-dose series.1
to the manufacturer’s instructions just before use and administer
the 0.5 mL dose of MPSV4 subcutaneously. (MPSV4 should not
be administered intramuscularly.) Target Groups for Vaccination
According to ACIP, hepatitis A vaccine should be routinely
recommended for all children 12 to 23 months of age, any
Hepatitis A person at increased risk for infection, or any person wanting
Hepatitis A is an acute infection caused by a picornavirus.1 to reduce the risk of hepatitis A infection.93 People traveling
Hepatitis A is spread by the fecal-oral route and by consuming internationally—with the exception of travel to Canada,
contaminated food and water. The hepatitis A virus enters Western Europe, Japan, New Zealand, or Australia—should
the body through the mouth and can be found in the stool of be vaccinated against hepatitis A. Vaccination should
infected people. The virus replicates in the liver of infected be routinely recommended for household members and
people. other close personal contacts of internationally adopted
children arriving from areas of the world where hepatitis A is
Before the availability of the hepatitis A vaccine, approxi- endemic.94
mately 20,000 to 30,000 cases of hepatitis A were reported
in the United States each year.33 With the use of safe and Additionally, men who have sex with men, injection drug
effective vaccines, the incidence of hepatitis A in this country users, laboratory workers potentially exposed to this virus,
has declined significantly. However, hepatitis A infection people with chronic liver disease or clotting factor disorders,
remains endemic in other areas of the world. People at risk or any other person at increased risk for hepatitis A infection
for hepatitis A infection include international travelers, men should be vaccinated. Hepatitis A vaccine is not routinely
who have sex with men, and users of illegal drugs. 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.
Clinical Features and Potential Complications Hepatitis A vaccine also plays a role in postexposure
The incubation period for hepatitis A is 15 to 50 days. prophylaxis for individuals who have been exposed to
Hepatitis A is characterized by fever, nausea, vomiting, hepatitis A. Pharmacists should refer to up-to-date recommen-
liver inflammation, jaundice, and dark urine. The disease is dations in such circumstances.
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, Vaccine Recommendations
death. Hepatitis A does not cause chronic infection or chronic Children should receive 2 doses of vaccine with the first dose
liver disease.33 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
Vaccines preferable to administer the dose of vaccine at least 2 weeks
Two inactivated vaccines are currently licensed in the United before travel to allow time for the patient to develop protective
States (Havrix—GlaxoSmithKline; Vaqta—Merck).12,91,92 Each antibodies against hepatitis A virus. However, when less than
of these vaccines is available in two different formulations: a 2 weeks are available, the vaccine may be administered any
pediatric formulation for patients aged 12 months to 18 years time before departure.
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 Contraindications and Precautions
volume of the dose differs depending on the formulation used. The hepatitis A vaccine should be administered when
The recommended vaccine schedule is the same for both appropriate unless the patient has a valid contraindication or
brands. Twinrix (GlaxoSmithKline) may be used for individuals precaution to receiving the vaccine. Hepatitis A vaccines are
who require both hepatitis A and hepatitis B vaccine. contraindicated in individuals who have had a severe allergic

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reaction (e.g., anaphylaxis) to a previous vaccine dose or to a fever, malaise, and headache. As the infection progresses,
vaccine component. Moderate or severe acute illness with or patients may experience additional symptoms such as nausea,
without fever is a precaution. 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
Potential Adverse Reactions from an acute case of hepatitis B infection. However, others
The most common adverse events following hepatitis A will develop complications from the disease. Some infected
vaccination include injection-site reactions. Redness, pain, or patients develop acute liver failure, which can lead to hospital-
swelling at the site of injection are common. Some patients ization and high mortality risk.
report mild systemic symptoms (e.g., low-grade fever). Serious
systemic reactions are uncommon. 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
Storage and Administration of Hepatitis A Vaccine increased risk at birth is a primary factor supporting a birth
Hepatitis A vaccines should be stored in the refrigerator at dose of hepatitis B vaccine for all infants.) Chronic infection
2°C to 8°C (35°F to 46°F); these vaccines should not be can lead to cirrhosis, hepatocellular carcinoma, and death.
frozen.12,46 To administer hepatitis A vaccines, shake the vial Hepatitis B causes up to 80% of hepatocellular cancers.1
or prefilled syringe before use. For children and adolescents Nearly 25% of people with chronic hepatitis B infection will
1 to 18 years of age, administer 0.5 mL intramuscularly. For die prematurely.
adults 19 years and older, administer 1 mL intramuscularly.

Vaccines
Hepatitis B vaccines consist of purified hepatitis B surface
Hepatitis B antigen (HBsAg), a protein found on the outer viral coat.
The hepatitis B virus is a bloodborne pathogen transmitted by The first such vaccine (Heptavax B—Merck) was produced
exposure to infected blood or body fluids.1,95,96 It is a small from human serum and available from 1981 to 1991.
DNA virus that specifically infects humans. The virus replicates Subsequently, recombinant DNA technology made it possible
in the liver, causing complications such as acute hepatitis, to harvest HBsAg from genetically engineered brewer’s yeast
chronic hepatitis, cirrhosis, liver cancer, and death. (Saccharomyces cerevisiae). Two vaccines utilizing this newer
technology are currently licensed (Recombivax HB—Merck
Worldwide, an estimated 2 billion people have been infected and Engerix-B—GlaxoSmithKline).1,98,99 The two hepatitis B
with hepatitis B at some point in their lives, and more than vaccines currently in the market are inactivated vaccines. Both
350 million people worldwide suffer from chronic hepatitis B of these vaccines reduce the risk of disease by 80% to 100%
infection.1 In the United States, an estimated 1.4 million after 3 doses.1
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 Target Groups for Vaccination
cases of hepatitis B occurred in 2008.97 More than half of A comprehensive strategy has been adopted by ACIP to
new infections result from sexual contact with an infected eliminate hepatitis B in infants, children, adolescents, and
person.1 Injection drug use, household contact, and health adults.95,96 Infants should receive their first dose of hepatitis
care exposures are also risk factors for hepatitis B. 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
Clinical Features and Potential Complications immune globulin (HBIG) promptly at birth.
Hepatitis B infection develops after an incubation period
of 2 to 5 months, during which individuals are infectious. The comprehensive strategy also calls for immunization of all
Approximately half of the people infected with hepatitis B are susceptible children and adolescents not previously vaccinated.
asymptomatic. Those who are symptomatic will be contagious Adults who should receive hepatitis B vaccination include
for 1 to 2 months after the onset of symptoms. Symptoms those at risk for infection by sexual exposure (e.g., people with
start with a prodrome of nonspecific symptoms such as multiple sex partners), those at risk for percutaneous exposure

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to blood (e.g., health care workers), patients with diabetes, All adolescents without documentation of hepatitis B vaccine
patients with chronic liver or renal disease, patients infected should receive a primary series of hepatitis B vaccine.95 This
with HIV, international travelers, and all unvaccinated adults can be accomplished in one of two ways. A 3-dose series
who want to be protected against the illness regardless of risk can be completed with either Engerix-B or Recombivax
factors. Having a known risk factor for hepatitis B infection is HB. The routine schedule for the 3-dose series is 0, 1, and
not a requirement for vaccination of adults. 6 months.84 Another option is to use the adult dose of
Recombivax HB (10 μg/1 mL) and administer this vaccine
In 2011, ACIP recommended that all previously unvacci- in a 2-dose series to adolescents aged 11 to 15 years. This
nated adults aged 19 to 59 years with diabetes type 1 or 2-dose series has been approved for use only in this age
type 2 should be vaccinated against hepatitis B as soon as group and only for Recombivax HB.98 The recommended
possible after a diagnosis of diabetes is made.100 Patients schedule for the 2-dose series is to administer the initial dose
with diabetes aged 60 years and older may be vaccinated at to patients at age 11 to 12 years, followed by a second
the discretion of the treating clinician based on the increased dose 4 to 6 months after the first dose. This 2-dose series
need for assisted blood glucose monitoring in long-term care has been shown to produce the same immunologic response
facilities, likelihood of acquiring hepatitis B infection, need to in this age group as the standard dose (5 µg/0.5 mL) given
manage its complications or chronic sequelae, and likelihood in the 3-dose series.95
of immune response to vaccination.75 Because this is a
relatively new recommendation, many patients with diabetes All adults with an indication for the vaccine should receive
have not yet been vaccinated against hepatitis B. Pharmacists a complete 3-dose series of hepatitis B vaccine with either
should be proactive in offering hepatitis B vaccination to Recombivax HB or Engerix-B.96 The routine schedule for
patients with diabetes. 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 Recommendations vaccine used; specific dosing information is shown in
The first dose of hepatitis B vaccine should be administered to Table 3.5.
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 Testing for Immunity
at 6 months of age. For infants who do not to receive a birth Routine testing for immunity after vaccination is not generally
dose, the series should be started as soon as possible. If the recommended. Serological confirmation of the immune
infant falls behind the recommended schedule, the second response to vaccination is recommended only for people in
dose should be administered at least 4 weeks after the first the following risk groups1:
dose.84 The third dose should be administered at least 2
• Health care workers at risk of exposure to blood or
months after the second dose and at least 4 months after the
body fluids in the workplace.
first dose. The third dose should not be administered before
24 weeks of age. • Infants born to HBsAg-positive mothers.

Table 3.5. Hepatitis B Vaccine Dosing, Intramuscular

Recombivax HB No. of Engerix-B No. of
Doses Doses
Dose Volume Dose Volume

Birth to age 19 years 5 μg 0.5 mL 3 10 μg 0.5 mL 3

Adolescents aged 11–15 years a

10 μg 1 mL 2 — — —

Adults aged ≥20 years 10 μg 1 mL 3 20 μg 1 mL 3

Individuals on dialysis 40 μg 1 mL 3 40 μg 2 mL 4b

a
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.
b
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.

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• Immunocompromised individuals (e.g., dialysis patients, Potential Adverse Reactions

people with HIV). Transient adverse events that can be expected after adminis-
• Sex partners of people with chronic hepatitis B virus tration of hepatitis B vaccine include injection-site pain, fatigue,
headache, or low-grade fever. Serious reactions are rare.
infection.

If a person seroconverts (i.e., develops measurable antibodies Storage and Administration of Hepatitis B Vaccine
after vaccination defined as hepatitis B surface antibody Hepatitis B vaccines should be stored in the refrigerator at
[anti-HBs] titer of 10 mIU/mL or higher following 3 properly 2°C to 8°C (35°F to 46°F); these vaccines should not be
spaced doses of vaccine), protection from hepatitis B disease frozen.12,46 To administer hepatitis B vaccines, shake the vial
infection appears to persist indefinitely. However, anti-HBs or prefilled syringe before use. Administer the appropriate
antigen antibody levels will gradually decline to undetectable dose (Table 3.5) intramuscularly shortly after preparation.
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 Rotavirus
vaccination and persist despite the lack of measurable Rotavirus is a double-stranded RNA virus that, prior to the
antibodies circulating in the bloodstream. availability of a vaccine, infected nearly every child by
5 years of age.1 It is the most common cause of severe
Anti-HBs antigen antibody titers should be measured 1 month gastroenteritis in infants and children.101 Rotavirus is most
after the third dose of the vaccine series to determine whether commonly contracted by children between the ages of 6 and
the person has seroconverted. Infants born to HBsAg-positive 24 months. In the prevaccine era in the United States,
mothers should be tested 3 to 12 months after the last dose. rotavirus gastroenteritis peaked in the cooler months and
People who initially achieve an anti-HBs antibody titer of typically progressed from the Southwest during November and
10 mIU/mL after immunization have responded to the December to the Northeast by April and May.
vaccine and are considered protected. For those who do
not seroconvert, refer to the CDC recommendations
regarding repeat vaccination.1 Clinical Features and Potential Complications
The primary means of transmission is by the fecal-oral route
Additional Dosing Information for Hepatitis B Vaccine through person-to-person contact or contact with fomites
Recombivax HB and Engerix-B are essentially interchangeable, (contaminated objects). After an incubation period of 24 to
but the dosage in microgram content per dose varies between 72 hours, the infected person may develop symptoms that can
the two brands (Table 3.5).1,98,99 Because intermittent changes range from self-limiting watery diarrhea to severe diarrhea
in recommended dosing or package concentrations can with fever and vomiting. The symptoms typically last for 3 to
occur, pharmacists should not memorize this dosing table. 7 days. Rotavirus infection in infants and children can result
Pharmacists should always refer to updated references and be in more serious disease such as severe diarrhea, dehydration,
familiar with the vaccine they stock and the appropriate doses electrolyte imbalances, and in some cases, death.
for that product. Pharmacists should verify the volume to be
administered to deliver the appropriate dose in micrograms An initial infection with rotavirus after 3 months of age is
based on the specific product being used. most likely to cause severe gastroenteritis and dehydration.1
Infection with rotavirus can occur several times throughout
a person’s lifetime and it appears that initial infection may
Contraindications and Precautions protect a child from developing subsequent severe gastro-
Unless a contraindication or precaution is present, the enteritis. After a single natural infection, 38% of children are
vaccine can be administered to all eligible infants, children, protected against subsequent infection with rotavirus, 77% are
adolescents, and adults. Hepatitis B vaccines are contra- protected against subsequent rotavirus-associated diarrhea
indicated in individuals who have had a severe allergic of any severity, and 87% are protected against subsequent
reaction (e.g., anaphylaxis) to a previous vaccine dose or to moderate-to-severe rotavirus-associated diarrhea.101
a vaccine component. Moderate or severe acute illness with Therefore, vaccination, which mimics the immunoprotective
or without fever is a precaution. response from a natural infection in an individual, should help
prevent rotavirus infection and its associated complications.
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Each year during the 1990s and early 2000s, rotavirus orally in a 3-dose series, with doses administered at ages 2,
resulted in approximately 410,000 physician visits, 205,000 4, and 6 months. Rotarix is administered orally in a 2-dose
to 272,000 emergency department visits, and 55,000 to series, with doses administered at ages 2 and 4 months. If
70,000 hospitalizations among U.S. infants and children, RotaTeq is administered for any of the doses in the series, a
with total annual direct and indirect costs of approximately total of 3 doses must be given to provide adequate protection
$1 billion.101 Vaccination against rotavirus has been shown for the patient.
to decrease the morbidity, health care expenditures, and
mortality associated with this disease.33,102 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
Vaccines weeks 0 days or older because there are insufficient data on
Currently, there are two FDA-licensed rotavirus vaccines the safety of a first dose in older infants. The minimum interval
(RotaTeq—Merck; Rotarix—GlaxoSmithKline).103,104 Both between doses of rotavirus vaccine is 4 weeks. The maximum
vaccines are live, oral vaccines indicated for the prevention of age for the last dose of rotavirus vaccine is 8 months 0 days.
rotavirus gastroenteritis in infants and children.
Contraindications and Precautions
Although RotaTeq and Rotarix are currently marketed in Children with a serious allergic reaction to a prior dose should
the United States, they were not the first vaccines against not receive the rotavirus vaccine. These vaccines should be
rotavirus. In 1998, an FDA-licensed rhesus-based tetravalent avoided in children with gastrointestinal problems or a history
vaccine (RotaShield—Wyeth) was recommended for routine of intussusception. Because these are live vaccines, they should
vaccination of infants. However, in 1999, this vaccine not be administered to immunocompromised children or
was voluntarily removed from the market because of an children with a history of severe combined immunodeficiency
apparent association with the development of intussusception. because of the potential risk for vaccine-acquired rotavirus
Intussusception is an uncommon type of bowel obstruction infection.106
that occurs when the bowel folds in on itself. Intussusception
occurs most frequently in young children and often there is Rotavirus vaccines are contraindicated in patients who
no known cause. When identified and treated early, most have had a severe allergic reaction (e.g., anaphylaxis) to a
individuals will fully recover. Following administration of previous vaccine dose or to a vaccine component. The oral
RotaShield, the risk for intussusception was most elevated applicator for Rotarix contains latex; patients with a history of
within 3 to 14 days after receipt of the first dose of the anaphylactic reaction to latex should not receive this brand.
vaccine; there was also an increased risk within 3 to 14 days
after the second dose. Therefore, RotaShield was removed Precautions include moderate or severe acute illness with or
from the market. without fever, pre-existing gastrointestinal disease, previous
history of intussusception, altered immunocompetence other
than severe combined immunodeficiency, spina bifida, or
Target Groups for Vaccination bladder exstrophy.
All infants without a valid contraindication should receive the
rotavirus vaccine. Infants who have had rotavirus gastro-
enteritis before completing the primary series should still Potential Adverse Reactions
complete the entire series. Premature infants born before 37 The most common adverse events associated with rotavirus
weeks of gestation may receive the vaccine provided they are vaccines include fever, vomiting, diarrhea, loss of appetite,
at least 6 weeks of age, are being or have been discharged and irritability. There is a theoretical risk that the live virus
from the hospital, are clinically stable, and the benefits of from the vaccine could be spread to susceptible contacts after
receiving the vaccine outweigh the risks.105 vaccination.105 Infants who have close contact with pregnant
women, immunocompromised individuals, and those on
immunosuppressive therapy may be vaccinated with consider-
Vaccine Recommendations ation of the risks and benefits.
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

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Large prelicensure clinical trials of both RotaTeq and Rotarix and the infant should receive future vaccinations as scheduled.
did not find an increased risk for intussusception among Rotarix should be administered as a 2-dose series to infants at
vaccine recipients. A large postlicensure study of more than 2 and 4 months of age.104
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 Haemophilus influenzae type b
intussusception was found after the second or third doses. The H. influenzae type b (Hib) is an aerobic gram-negative
CDC and FDA continue to believe that the benefits of rotavirus coccobacillus.1 Hib is spread by respiratory transmission
vaccination outweigh the risks associated with vaccination and from asymptomatic carriers. The polysaccharide capsule on
that routine vaccination of infants should continue.107 the bacteria allows it to evade the immune system and cause
disease. While this disease is rarely seen in patients older
A study conducted by the CDC Vaccine Safety Datalink from than the age of 5 years, invasive Hib disease can cause
May 2006 to February 2010 found no increased risk of significant morbidity and mortality in children younger than
intussusception following vaccination with RotaTeq. However, 5 years of age.
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 Clinical Features and Potential Complications
Vaccine Safety Datalink. Based on these findings, 1 case of Before the availability of vaccines, Hib affected 1 of every
intussusception would be expected for approximately each 200 children in the United States, accounting for more than
20,000 children who are fully vaccinated.108 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,
Storage and Administration of Rotavirus Vaccines pneumonia, osteomyelitis, arthritis, cellulitis, and bacteremia.
Rotavirus vaccines should be stored in the refrigerator at 2°C Complications of invasive Hib infection were significant,
to 8°C (35°F to 46°F) and protected from light at all times.12,46 including deafness and other neurologic sequelae (e.g.,
mental retardation, seizures, developmental delay) in up
RotaTeq Administration to 30% of survivors.33 Hib had been the leading cause of
RotaTeq is an oral suspension supplied in ready-to-use, 2 mL, acquired mental retardation before widespread vaccination.
single-dose tubes. After removing the twist-off cap, the dosing
tube should be placed in the infant’s mouth, pointed toward Mortality rates associated with Hib disease were also high
the inner cheek, and the tube squeezed gently until empty. before vaccine use, with up to 5% of patients dying despite
The entire contents of the tube should be administered to the appropriate antibiotic treatment.1 Hib vaccines have signifi-
infant, however the tip of the tube may hold a residual drop. cantly lowered disease incidence from 20,000 cases in 1985
There are no food or drink restrictions after the vaccine dose. to 17 cases reported in 2010.109,110
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. Vaccines
RotaTeq should be administered as a 3-dose series to infants The initial Hib vaccines were purified polysaccharide vaccines,
at 2, 4, and 6 months of age.103 first licensed in 1985. Because polysaccharide vaccines are
not as effective in children younger than 2 years of age—
Rotarix Administration and this disease most commonly affects young children—
Once removed from the refrigerator, Rotarix must be reconsti- conjugated vaccines were developed to increase effectiveness
tuted prior to administration. Preferably, the 1 mL dose should in young children.
be administered as soon as possible after reconstitution but
it must be administered within 24 hours. The oral applicator The single-antigen Hib vaccines currently available in the U.S.
should be placed in the infant’s mouth, pointed toward the market include:
inner cheek, and the tube squeezed gently until empty. The
• ActHIB (Sanofi Pasteur)
entire contents of the applicator should be administered to the
infant. If the infant regurgitates, vomits, or spits out a small • PedvaxHIB (Merck)
amount of the vaccine, readministration is not recommended
• Hiberix (GlaxoSmithKline)
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Currently available combination Hib vaccines include: Contraindications and Precautions

Hib vaccines are contraindicated for patients who have had
• Comvax (Merck)—protects against Hib and hepatitis B
a severe allergic reaction (e.g., anaphylaxis) to a previous
• Pentacel (Sanofi Pasteur)—protects against Hib, vaccine dose or to a vaccine component. Precautions include
diphtheria, tetanus, pertussis, and polio moderate or severe acute illness with or without fever.
• MenHibrix (GlaxoSmithKline)—protects against Hib and
meningococcal serogroups C and Y
Potential Adverse Reactions
Hib vaccines are well tolerated and adverse events after
Target Groups for Vaccination vaccination are not common. Adverse events that may be
All infants without a valid contraindication should receive Hib reported after receipt of Hib vaccine include transient injection-
vaccine.110 site reactions such as swelling, redness, or pain. Systemic
reactions (e.g., fever) after vaccination are unusual, and
serious reactions are rare.
Vaccine Recommendations
The recommended schedule for vaccine use and the number
of doses needed depends on the vaccine product selected.
Storage and Administration of Haemophilus
ActHIB requires a 3-dose primary series followed by a booster influenzae type b Vaccines
dose and PedvaxHIB requires a 2-dose primary series followed Hib vaccines should be stored in the refrigerator at 2°C to 8°C
by a booster dose. The recommended routine vaccine (35°F to 46°F); these vaccines should not be frozen.12,33 When
schedules for ActHIB and PedvaxHIB are shown in Table 3.6.1 administering Hib vaccines, providers should shake the vial or
Hiberix is approved only as a booster dose for use in children prefilled syringe before use and administer the 0.5 mL dose
15 months to 4 years of age who have completed the primary intramuscularly.
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 Poliomyelitis
the health care provider should consult the current childhood Poliomyelitis is caused by an enterovirus.1 There are three
immunization schedule to determine the appropriate dosing poliovirus serotypes that cause disease (although type 2 virus
schedule for the series when a child falls behind. was eradicated worldwide in 1999). Antibodies against one
serotype do not produce significant protection against other
Hib vaccine is not routinely given to children aged 5 years or serotypes.
older. However, patients with certain conditions (i.e., anatomic
or functional asplenia, sickle-cell disease, immunodeficiency,
immunosuppression, leukemia, or HIV infection) may be at Clinical Features and Potential Complications
increased risk for invasive Hib disease. One dose of single- Polio viruses enter the body through the mouth and replicate
antigen Hib vaccine should be considered for older children, in the pharynx and gastrointestinal tract. Approximately 95%
adolescents, and adults with these high-risk conditions. If of poliovirus infections are asymptomatic. Approximately
indicated, these patients should receive a single 0.5 mL dose 4% to 8% of polio infections consist of a minor, nonspecific
of Hib conjugate vaccine.1 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 12–15 Months
ActHIB Dose 1 Dose 2 Dose 3 Booster

PedvaxHIB Dose 1 Dose 2 — Booster

Source: Reference 1.

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nervous system from the bloodstream and destroy the anterior disease still exists in a few countries in Africa, Asia, and
horn cells of the spinal cord. This causes flaccid paralysis of the Middle East. More information on global poliovirus
muscles, but leaves sensory function intact.1 Many individuals eradication efforts can be found online at
with paralytic poliomyelitis recover completely and, in www.polioeradication.org.
most, muscle function returns to some degree. Weakness
or paralysis still present 12 months after onset is usually
permanent.1 Target Groups for Vaccination
Vaccinate all children against poliovirus.112 Routine
Asymptomatic patients can transmit the virus to other people. vaccination of adults is not recommended unless the adult is
Poliomyelitis is communicable beginning 7 to 10 days before traveling overseas to a poliovirus-endemic area.
the onset of symptoms. Viruses can be shed in the stool for 3
to 6 weeks in both symptomatic and asymptomatic infected
patients. Vaccine Recommendations
The recommended IPV schedule is to vaccinate all children at
ages 2 months, 4 months, 6 to 18 months, and 4 to 6 years.
Vaccines
An inactivated poliovirus vaccine (IPV) was first licensed in For an adult requiring vaccination, the recommendations vary
1955. A trivalent, oral attenuated poliovirus vaccine (OPV) depending on the individual’s vaccination history112:
was licensed in 1963. OPV was the vaccine of choice in the
• Written documentation of having completed the primary
United States following its approval; this live vaccine was very
series: administer 1 booster dose of IPV.
effective, conferred long-lasting immunity, and it was easy to
administer. Unfortunately, because the live attenuated viruses • Written documentation of having received 1 but not all
in the vaccine were shed in the stool, it was possible for the doses of the series: administer the remaining doses of
shed virus to spread to susceptible contacts of the vaccinated the series.
person thereby causing vaccine-associated paralytic
• No documentation of polio vaccination: administer the
poliomyelitis. The overall risk of vaccine-associated paralytic
primary series of 3 doses of IPV. The recommended
poliomyelitis was 1 case per 2 million to 3 million OPV doses
schedule is 0, 1 to 2 months, and 6 to 12 months.
distributed, affecting 8 to 10 people per year in the United
However, if time is a factor and the patient must
States.1
travel before completing the series, refer to the ACIP
guidelines for additional information on how to
Concerns about the risks associated with OPV prompted the
appropriately schedule the vaccine series to maximize
development of an enhanced potency inactivated poliovirus
protection for the patient.
vaccine (IPOL—Sanofi 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 Contraindications and Precautions
the vaccine of choice. IPV is highly effective in producing Any child or adult who needs IPV should receive the vaccine
immunity, with 99% of patients developing protective antibody unless a valid contraindication or precaution is present. IPV
levels after 3 doses.1 In addition to protecting people from contains trace amounts of streptomycin, polymyxin B, and
the disease, IPV has the advantage of being an inactivated neomycin, which can cause hypersensitivity in patients who
vaccine and therefore cannot cause paralytic poliomyelitis. are sensitive to these antibiotics.12

Polio Eradication Precautions include moderate or severe acute illness with or

Disease rates rapidly fell with widespread use of the polio without fever, and pregnancy.
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 Potential Adverse Reactions
no reported cases of polio in the United States, continued The most commonly reported adverse events after IPV adminis-
immunization is needed to guard against imported infections. tration are local injection-site reactions. No serious adverse
The World Health Organization (WHO) had hoped to reactions have been reported after vaccination.
eradicate poliovirus from the entire planet by 2005, however

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Storage and Administration of Poliomyelitis Vaccine Everyone involved in vaccine delivery must exercise caution
IPV should be stored in the refrigerator at 2°C to 8°C (35°F to to select the proper combination product to ensure that
46°F); the vaccine should not be frozen.12,46 When adminis- the patient receives the appropriate vaccines to provide
tering IPV, providers should shake the vial or prefilled syringe protection. Furthermore, it is important to document each
before use and administer the 0.5 mL dose of IPV either individual antigen administered. For example, if Twinrix is
intramuscularly or subcutaneously. 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 Non-Routine Vaccines
required to fully vaccinate patients. These combinations tend Pharmacists may be involved in the administration of vaccines
to make immunization more acceptable, especially to parents that do not appear on routine immunization schedules.
of children who prefer the reduced number of injections. Non-routine vaccines include those used to prevent rabies,
immunizations for international travelers, and vaccines that
Currently licensed combination vaccines (as of December could be used to protect against bioterrorism agents.
2013) include:
• Comvax (Merck)—protects against Hib and hepatitis B
Rabies
• Kinrix (GlaxoSmithKline)—protects against diphtheria, Rabies is caused by a rhabdovirus, a group of RNA viruses.
tetanus, pertussis, and polio Transmission of the virus to humans is from the bite of an
infected animal. While all mammals (e.g., dogs, skunks,
• MenHibrix (GlaxoSmithKline)—protects against Hib and
raccoons) may transmit the virus, bat exposures are the most
meningococcal serogroups C and Y
common source of transmissions in the United States.113 Once
• Pediarix (GlaxoSmithKline)—protects against diphtheria, the virus enters the body, it affects the central nervous system,
tetanus, pertussis, hepatitis B, and polio causing acute encephalitis and neurologic dysfunction.
• Pentacel (Sanofi Pasteur)—protects against diphtheria,
On average, only 1 or 2 rabies cases are reported in humans
tetanus, pertussis, polio, and Hib
in the United States each year.113 Even though these numbers
• ProQuad (Merck)—protects against measles, mumps, are small, concern persists because rabies is almost always
rubella, and varicella fatal if left untreated. In modern history, only 2 people are
• Twinrix (GlaxoSmithKline)—protects against hepatitis A known to have survived rabies infection without receiving
and hepatitis B postexposure prophylaxis.114

As noted earlier, ACIP’s general recommendations regarding Each year, approximately 16,000 to 39,000 people receive
use of combination vaccines state that use of a combination rabies postexposure prophylaxis because they have come
vaccine generally is preferred over its equivalent component in contact with potentially rabid animals.115 Oftentimes, it is
vaccines.31 Licensed combination vaccines can be used difficult to capture or find the animal that inflicted the wound
whenever any components of the combination are indicated to determine the presence of rabies in the animal. If the rabies
and its other components are not contraindicated and if status of the animal is unknown, the vaccine is often given to
licensed by the FDA for that dose in the series. Use of protect the patient because the benefits of giving the vaccine
combination vaccines can reduce the number of injections (i.e., preventing death) outweigh the risks (i.e., low adverse
and alleviate concern associated with the number of effect profile).
injections. While the combination vaccines may be preferred
to decrease the number of necessary injections, the array Rabies Vaccines
of products can present the opportunity for confusion Currently, two formulations of rabies vaccines are available in
due to sound-alike product names or choosing the wrong the United States: human diploid cell vaccine (Imovax—Sanofi
combination product. Pasteur) and purified chick embryo cell vaccine (RabAvert—
Novartis). Additionally, two formulations of rabies immune

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globulin, which are used for postexposure management to recreational activities, quality of lodging, season of year,
provide immediate short-term antibody protection against altitude, mode of travel, and other factors. The proper set of
rabies virus, are currently marketed in the United States: vaccines needed for an individual depends on that person’s
Imogam Rabies-HT (Sanofi Pasteur) and HyperRAB S/D previous vaccinations, age, occupation, activities, health
(Talecris). status, and itinerary.

Vaccine Recommendations Although travelers usually focus on the need for protection
Rabies vaccine is appropriately used for pre-exposure against exotic diseases (e.g., yellow fever, typhoid fever), it
prevention in specific populations. For example, people is no less important to ensure that travelers have received
with possible occupational exposures (e.g., veterinarians, all routine vaccinations. Some of these diseases, such as
laboratory workers who have contact with animals) are measles, mumps, and rubella occur far more frequently in
candidates for pre-exposure prophylaxis. In addition, travelers developing countries than in the United States. As mentioned
at increased risk for contact with rabid animals in regions previously, some vaccines have specific travel indications (e.g.,
without accessible health care for postexposure prophylaxis hepatitis A, meningococcal, poliovirus).
to prevent rabies may be candidates for pre-exposure
prophylaxis. Yellow Fever
Yellow fever is a viral infection that can be transmitted to a
According to the current recommendations from ACIP, human by a bite from an infected mosquito.116,117 The yellow
postexposure prophylaxis to prevent rabies should include fever vaccine (YF-Vax—Sanofi Pasteur) contains live attenuated
prompt cleansing of the wound, followed by administration viruses and needs to be refrigerated.118 Yellow fever vaccine
of both rabies vaccine and rabies immune globulin.115 must be used or discarded within 60 minutes of reconstitution.
Postexposure prophylaxis is considered a medical urgency, not The 0.5 mL dose is administered by subcutaneous injection,
a medical emergency. Patients with potential rabies exposures and 10-year booster doses are required for individuals with
should be referred to experts in the field of rabies for continued exposure.
appropriate postexposure prophylaxis. Local and state public
health departments may be valuable resources of information Administration of yellow fever vaccine is limited to provider
in these cases. 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
Vaccines for International Travel statewide may have yellow fever certificate approval. ACIP
Pharmacists who are involved with international travelers’ released revised guidelines on the use of yellow fever vaccine
health perform a valuable service by helping people who in 2010.118 Pharmacists involved in providing yellow fever
may otherwise travel without proper medical advice and vaccination must consult updated references for additional
the proper prophylaxis to help avoid preventable infections. information prior to administering the vaccine.116-118
Travel advice is complex and must be comprehensive to fully
protect the patient. This section is not designed to prepare Typhoid Fever
pharmacists to provide comprehensive international travel Typhoid is a food- and water-borne illness caused by the
services; rather, it is intended to complete the review of bacterium Salmonella typhi.119 Options for typhoid prevention
vaccines available in the U.S. market. Before recommending include a 4-dose series of live attenuated oral typhoid vaccine
the vaccines mentioned in this section, pharmacists should capsules or a single injection of inactivated typhoid polysac-
receive additional training regarding the use of these vaccines, charide vaccine.
indications and contraindications, dosing and administration,
and potential adverse effects. Pharmacists interested in The live attenuated typhoid vaccine (Vivotif—Berna) is given
establishing a travel health service may consult the American orally in the form of capsules. The regimen is 1 capsule every
Pharmacists Association’s advanced competency training other day for 4 doses (i.e., over 7 days). Patients should be
program, Pharmacy-Based Travel Health Services, available in the directed to swallow the capsules 1 hour before meals, using
Continuing Education section of www.pharmacist.com. water that is cooler than body temperature. The capsules
should be refrigerated between doses. Oral typhoid vaccine
Health risks are not uniform within any country because the should not be given concurrently with antibiotics, including
medical threat varies according to destination, business and several medications used in antimalarial therapy (which may

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be a barrier for travelers to malaria-endemic areas). This live the virus and could use it as a bioterrorism agent. The
vaccine may be administered to individuals aged 6 years and U.S. Government maintains a stockpile of smallpox vaccine
older. Immunity persists longer than with inactivated typhoid sufficient for the entire population of the country.121
vaccine; however, if the recipient continues travel or remains
in a typhoid-endemic area, the oral vaccine series should be The current licensed vaccine (ACAM2000—Sanofi Pasteur)
administered every 5 years. is a lyophilized, live vaccinia virus vaccine. A single drop
of vaccine is placed on the tip of the bifurcated needle and
One inactivated typhoid vaccine (Typhim Vi—Sanofi Pasteur) then, while holding the skin of the deltoid area taut, 3 or 15
is currently marketed in the United States. It is administered (depending upon primary or revaccination) rapid and tightly
by intramuscular injection. This vaccine is approved for use concentric punctures are made to the skin. A small amount of
in individuals aged 2 years and older. Waning immunity blood (a petechia) should be seen after vaccination to ensure
requires the vaccine to be readministered every 2 years if risk the skin has been penetrated and vaccine administered. A
of exposure persists. lesion will develop at the site of vaccination. Because vaccinia
virus can spread from the vaccination site to other people
Japanese Encephalitis until the scab has fallen away, the lesion must be protected
Japanese encephalitis is a mosquito-borne viral illness endemic carefully by bandaging for approximately 2 to 3 weeks while
in areas of Asia.120 It is the most common cause of encepha- the lesion progresses from a red papule to a pustule to a scab.
litis in Asia. One Japanese encephalitis vaccine is licensed Vaccinated people also can spread vaccinia virus to other
in the United States (Ixiaro—Novartis). (In 2006, production areas of their own body through autoinoculation if the vaccine
of the previously available JE-Vax was discontinued.) Ixiaro site is rubbed and then touched to other areas.
is an inactivated vaccine that is administered intramuscularly
as a 2-dose series at 0 and 28 days. It is approved for use The CDC restricted its initial recommendations for vaccination
in patients 2 months of age and older. Japanese encepha- to: (1) smallpox response teams—those responding to
litis vaccine is recommended for travelers who plan to spend investigate cases and initiate control measures, as well as
1 month or longer in endemic areas during the Japanese those responsible for administering smallpox vaccine in the
encephalitis transmission season. “pre-event vaccination program” and (2) smallpox health
care teams—those health care personnel from participating
hospitals who will be asked to evaluate, manage, and treat
Agents of Bioterrorism the initial suspected and diagnosed cases. The CDC does
Attacks by terrorists with anthrax spores in autumn 2001 not recommend routinely vaccinating the general population
reminded Americans of the lethality of germs used as against smallpox because of the adverse effect profile of
weapons. Letters containing anthrax spores were mailed smallpox vaccination.
to several news media offices and 2 U.S. Senators, killing
5 people and infecting 17 others. Communities across the Pharmacists interested in learning more about smallpox
country re-evaluated their emergency response plans following vaccine should consult ACIP recommendations as well as the
this event. In the event of an act of bioterrorism, post-outbreak CDC’s website (www.bt.cdc.gov/agent/smallpox/).
efforts are likely to involve the distribution of both antibiotics
and vaccines. Pharmacists can help their communities by Anthrax
understanding and assisting with local response plans. Anthrax disease is caused by a gram-positive spore-forming
rod, Bacillus anthracis.122 The bacteria can live in the soil
Smallpox and may remain dormant for many decades. Animals can
Smallpox is a potentially deadly disease caused by the become infected when they eat or inhale the spores. Humans
variola virus and is fatal in approximately 30% of infected can become infected if they come in contact with an infected
individuals.121 The last naturally acquired case of smallpox animal, consume contaminated meat from an infected
occurred in Somalia in 1977. Smallpox eradication was animal, or inhale spores from the environment. Anthrax
certified by the World Health Assembly in 1980. infection can be cutaneous, gastrointestinal, or inhalational,
with inhalational being the most serious. Left untreated,
Although only 2 countries (i.e., the United States and inhalational anthrax is usually fatal. Interested pharmacists
Russia) are known to have stocks of smallpox virus, there is should consult an infectious diseases text for more information.
concern that other countries or individuals also might have

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The best protection against anthrax is vaccination with anthrax had 27% fewer cases of clinical malaria. It is expected
vaccine adsorbed (BioThrax—Emergent BioSolutions). The that this vaccine candidate may be submitted for regulatory
vaccine is inactivated and has been licensed by the FDA since approval in 2014.125
1970. The administration schedule involves a 5-dose series of
0.5 mL intramuscular injections at 0 weeks, 4 weeks, 6 months, New administration technologies are an ongoing area of
12 months, and 18 months, plus annual booster doses.122 research, particularly methods that allow for needleless
administration. Technologies under development include
The vaccine is routinely administered to at-risk personnel microneedle arrays and nanopatches.126,127
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 Conclusion
antibiotic prophylaxis in suspected exposure cases. Vaccines have been successful in preventing a broad range
of infectious diseases. Immunizing pharmacists can make
Currently, anthrax vaccine is available primarily through a significant impact on their patients’ health by becoming
the U.S. Department of Defense and the CDC. Pharmacists involved in vaccine administration. Identifying patients in
interested in learning more about anthrax and anthrax vaccine need of vaccinations and making recommendations to protect
should consult ACIP recommendations or visit the CDC’s these patients are key components of any immunization
website (www.cdc.gov/anthrax/). 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
A Look to the Future exist for specific patients. Standards and recommendations
Despite the overwhelming benefits of available vaccines, in immunization practice change regularly because of
infectious diseases continue to exert an enormous toll both in the ongoing nature of these developments. Immunizing
the United States and around the world. Effective vaccines pharmacists must make a commitment to staying up to date
have not yet been developed and marketed for infectious as new information emerges about new vaccines and technol-
diseases such as HIV, tuberculosis, and malaria, which together ogies as well as changes to the use of existing vaccines.
cause 4 million deaths annually worldwide. Furthermore,
many existing vaccine production technologies do not allow Armed with the knowledge of vaccines currently available
for a fast response to developing outbreaks. For example, in the United States, participants of this certificate training
most influenza vaccines are manufactured through a process program are now prepared to advance to the upcoming
that incubates virus in eggs and requires several months for modules on essential information on administering vaccines
vaccine production; this process does not readily provide rapid and establishing a pharmacy-based immunization service.
production of large quantities of vaccine in the event that a
novel influenza virus emerges and causes a pandemic.123
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December 2010.

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74. Centers for Disease Control and Prevention. Measles, mumps, 88. Menomune [package insert]. Swiftwater, PA: Sanofi Pasteur;
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2):1–28.

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106. Centers for Disease Control and Prevention. Addition of 117. World Health Organization. International Travel and Health. 2012.
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page/yellowbook-home-2014. Accessed November 19, 2013

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