Pedsap 1 Immunology

PEDIATRIC
SELF-ASSESSMENT PROGRAM
P e d S A P 2 0 1 6 B O OK 1
IMMUNOLOGY
Series Editors
Marcia L. Buck, Pharm.D., FCCP, FPPAG
Kalen B. Manasco, Pharm.D., BCPS, AE-C
AMERICAN COLLEGE OF CLINICAL PHARMACY

IMPORTANT INFORMATION ON THE RELEASE OF
PedSAP 2016 BOOK 1 IMMUNOLOGY
TESTING
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ISBN-13: 978-1-939862-32-7 (PedSAP 2016 BOOK 1, Immunology)
Copyright 2016 by the American College of Clinical Pharmacy. All rights reserved. This book is protected by copyright. No part
of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic or
mechanical, including photocopy, without prior written permission of the American College of Clinical Pharmacy.
To cite PedSAP properly:
Authors. Chapter name. In: Buck ML, Manasco KB, eds. Pediatric Self-Assessment Program, 2016 Book 1. Immunology. Lenexa, KS:
American College of Clinical Pharmacy, 2016:page range.
PedSAP is a registered trademark of the American College of Clinical Pharmacy.
Pediatric
Self-Assessment
Program
TABLE OF CONTENTS
Immunology...................................................................................... 1 Clinical and Practice Updates.....................................67
Routine Childhood Immunization Series Interactive Case: Immunology in Solid Organ

Transplantation
By Stacie J. Lampkin, Pharm.D., BCPPS, BCACP, AE-C; and Amy
Wojciechowski, Pharm.D., BCPS By Barrett Crowther, Pharm.D., FAST, BCPS; and Leslie Stach, Pharm.D.,
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 BCPS
Vaccination Schedules Interactive Case . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
and Adherence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Patient Education on Vaccine Concerns . . . . . . . . . . . . . . . . . . . 10
Interpretation of Vaccine Schedules and Administration Translating Evidence into Practice: Human
Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 Papillomavirus Vaccination
Considerations Pertaining to All Vaccinations . . . . . . . . . . . . . . 12
Individual Vaccine Information . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 By Nathan Painter, Pharm.D., CDE; and Stephanie Mayne, MHS
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 Translating Evidence into Practice . . . . . . . . . . . . . . . . . . . . . . . . 79
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
Vaccine Development and Future Targets Translating Evidence into Practice:

By April Yarbrough, Pharm.D., BCPS; and Scott James, M.D.
Vancomycin-Associated Nephrotoxicity
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 By Jennifer Le, Pharm.D., MAS, BCPS-AQ ID, FCCP, FASHP; and Kristen
Importance of Vaccine Development . . . . . . . . . . . . . . . . . . . . . . 33
Nichols, Pharm.D., BCPS-AQ ID, BCPPS
Novel Vaccines in Development . . . . . . . . . . . . . . . . . . . . . . . . . . 35
Translating Evidence into Practice . . . . . . . . . . . . . . . . . . . . . . . . 83
Maternal Vaccination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
Advances in Established Vaccines . . . . . . . . . . . . . . . . . . . . . . . . 41
Advances in Vaccine Delivery . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
Passive Immunization
By Ann M. Philbrick, Pharm.D., BCPS, BCACP
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
Palivizumab . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
Immunoglobulins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
Hyperimmune Globulins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
Pharmacist Role . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
PedSAP 2016 Book 1 Immunology iii Table of Contents

A MESSAGE FROM THE EDITORS
Welcome to the Pediatric Self-Assessment Program (PedSAP), from ACCPs other self-assessment programs, PedSAP mod-
a new recertification component for the Board Certified Pedi- ules come in two formats: (1) the traditional review chapters;
atric Pharmacy Specialist (BCPPS). ACCP has a long tradition and (2) Clinical and Practice Update modules that incorpo-
of offering the best products for continuing pharmacy educa- rate new learning formats such as recorded webinars and
tion and pharmacotherapy specialist certification. PedSAP HTML pages. These new learning formats are hoped to speed
continues that tradition by providing the latest in evidence- the dissemination of new clinical information and satisfy the
based information for the practitioner or clinician working learning preferences of a wider audience.
with this special population.
Some things have not changed: inside this PedSAP book
In designing this series, the primary goal was to provide you will find user-friendly formatting as well as graphic ele-
updates that would improve clinical pharmacy practice and ments such as patient-care scenarios (demonstrating the
patient outcomes. The process began with a careful review application of concepts), treatment algorithms, descriptions
of the content outline developed by the Board of Pharmacy of pivotal studies that may change practice, and summative
Specialties for the Pediatric Pharmacy Specialty Certification practice points. All releases in this series are available elec-
Examination. The 20162018 PedSAP chapters will therefore tronically, enhancing the portability of this product. Prominent
cover the domains of patient management; practice manage- in each chapter are hyperlinks to reference sources, assess-
ment; information management and education; and public ment tools, guidelines and resources, data compilers such as
health and patient advocacy. Specific content for individual PubMed, and even informational videos. Our hope is that this
releases in this series was organized on the basis of the sys- depth of information, ease of access, and emphasis on clinical
tems and patient-care problems that might be expected of the application will have an immediate and positive impact on the
BCPPS. Finally, calls went out to recruit faculty panel chairs, care of pediatric patients.
authors, and reviewers committed to this new specialty and to
the board certification process. We very much appreciate the efforts of all the faculty panel
chairs, authors, and reviewers who lent their time, energy, and
The presentation of information, and its incorporation into expertise to this new series.
practice, was also given careful consideration. In a departure
Marcia L. Buck and Kalen B. Manasco, series editors
Immunology
Immunology Panel
Series Editors: Reviewers

Marcia L. Buck, Pharm.D., FCCP, FPPAG Lindsay C. Trout, Pharm.D., BCPPS
Clinical Coordinator Clinical Pharmacy Specialist
University of Virginia Childrens Hospital Pediatric Critical Care and General Pediatrics
Associate Professor Penn State Milton S. Hershey Medical Center (PSHMC)
Department of Pediatrics Hershey, Pennsylvania
University of Virginia School of Medicine
Clarissa F. Havel, Pharm.D., BCPS
Clinical Professor
Clinical Pharmacist
Virginia Commonwealth University School of Pharmacy
RPh-On-the-Go
Department of Pharmacy Services
Skokie, Illinois
University of Virginia Health System
Charlottesville, Virginia Bernard R. Lee, Pharm.D., BCPS, BCPPS
Kalen B. Manasco, Pharm.D., BCPS Clinical Pharmacist-General Pediatrics
Clinical Associate Professor Department of Pharmacy
Department of Clinical and Administrative Pharmacy Johns Hopkins Medicine-All Childrens Hospital
University of Georgia College of Pharmacy St. Petersburg, Florida
Augusta, Georgia Hazar Alnifaidy, Pharm.D., BCPS
Clinical Pharmacist
Faculty Panel Chair:
Department of Pharmacy
Jennifer Le, Pharm.D., MAS, BCPS, AQ-ID, FCCP, FCSHP Sidra Medical and Research Center
Professor of Clinical Pharmacy Doha, Qatar, Middle East
University of California, San Diego
Skaggs School of Pharmacy and Pharmaceutical Sciences
La Jolla, California VACCINE DEVELOPMENT AND
Faculty-in-Residence FUTURE TARGETS
Long Beach Memorial and Miller Childrens Hospital
Long Beach, California Authors
April H. Yarbrough, Pharm.D., BCPS
ROUTINE CHILDHOOD IMMUNIZATIONS Pediatric Infectious Disease Pharmacist
Pharmacokinetic Specialist
Authors Department of Pharmacy
Stacie J. Lampkin, Pharm.D., BCACP, BCPPS, AE-C Childrens of Alabama
Birmingham, Alabama
Clinical Assistant Professor
Pharmacy Practice Scott James, M.D.
DYouville College School of Pharmacy Assistant Professor
Buffalo, New York Department of Pediatrics, Division of Infectious Diseases
Amy Lynn Wojciechowski, Pharm.D., BCPS, AQ-ID University of Alabama at Birmingham
Birmingham, Alabama
Clinical Assistant Professor
Department of Pharmacy Practice
Reviewers
DYouville College School of Pharmacy
Buffalo, New York Jessica Cottreau, Pharm.D., BCPS
Infectious Diseases Clinical Pharmacist Associate Professor
Department of Pharmacy Rosalind Franklin University of Medicine and Science
Niagara Falls Memorial Medical Center Chicago, Illinois
Niagara Falls, New York
Ashli Rasmussen, Pharm.D., BCPS Elias B. Chahine, Pharm.D., BCPS-AQ ID
Clinical Research Pharmacist Associate Professor of Pharmacy Practice
Celerion, Inc. Pharmacy Practice
Phoenix, Arizona Palm Beach Atlantic University, Lloyd
L. Gregory School of Pharmacy
West Palm Beach, Florida
PASSIVE IMMUNIZATION Clinical Pharmacy Specialist
Pharmacy Services
Author Wellington Regional Medical Center
Ann M. Philbrick, Pharm.D., BCPS, BCACP Wellington, Florida
Associate Professor
Pharmaceutical Care & Health Systems The American College of Clinical Pharmacy and the authors
University of Minnesota College of Pharmacy thank the following individuals for their careful review
Family Medicine & Community Health of the Immunology I chapters:
University of Minnesota Medical School Marisel Segarra-Newnham, Pharm.D., MPH, FCCP, BCPS
Minneapolis, Minnesota Clinical Pharmacy Specialist, Infectious Diseases/HIV
Antimicrobial Stewardship Program Pharmacy Director
Reviewers
Veterans Affairs Medical Center
Jenna Halilovic Maker, Pharm.D., BCPS West Palm Beach, Florida
Associate Professor Clinical Assistant Professor of Pharmacy Practice
Department of Pharmacy Practice University of Florida College of Pharmacy
University of the Pacific Thomas J Long Gainesville, Florida
School of Pharmacy & Health Sciences Ralph H. Raasch, Pharm.D., BCPS
Stockton, California
Associate Professor of Pharmacy (retired)
Clinical Pharmacist
Division of Practice Advancement and Clinical Education
Pediatric and Young Adult Infectious Diseases
Eshelman School of Pharmacy
University of California Davis Medical Center
The University of North Carolina at Chapel Hill
Sacramento, California
Chapel Hill, North Carolina
Ewha Bridget Kim, Pharm.D., BCPS, BCOP
Clinical Pharmacist, Ambulatory Oncology
Massachusetts General Hospital
Boston, Massachusetts
DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST
Consultancies: Stacie J. Lampkin (American Lung Association, Inside Patient Care); Jenana Maker (Actavis Pharma, Inc.)
Stock Ownership:
Royalties:
Grants: Elias B. Chahine (Cubist); Scott James (NIH/NIAID)
Honoraria: Elias B. Chahine (Merck and Co, The Medicines Company, Cubist); Stacie J. Lampkin (Western New York Society of
Health-System Pharmacists)
Other:
Nothing to disclose: Hazar Alnifaidy; Jessica Cottreau; Clarissa F. Havel; Bridget Kim; Bernard R. Lee; Ann M. Philbrick; Ashli
Rasmussen; Lindsay C. Trout; Amy Lynn Wojciechowski; April H. Yarbrough
ROLE OF BPS: The Board of Pharmacy Specialties (BPS) is an autonomous division of the American Pharmacists Association
(APhA). BPS is totally separate and distinct from ACCP. The Board, through its specialty councils, is responsible for specialty
examination content, administration, scoring, and all other aspects of its certification programs. PedSAP has been approved by
BPS for use in BCPPS recertification. Information about the BPS recertification process is available online.
Other questions regarding recertification should be directed to:
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CONTINUING PHARMACY EDUCATION
AND RECERTIFICATION INSTRUCTIONS
ontinuing Pharmacy Education Credit: The American College of Clinical Pharmacy is accredited by the Accreditation
C
Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education (CPE).
PedSAP: Target Audience: The target audience for PedSAP 2016 Book 1 (Immunology) is pediatric pharmacotherapy spe-
cialists and advanced-level clinical pharmacists caring for pediatric patients with several immunologic and antimicrobial
considerations.
Available CPE credits: Purchasers who successfully complete all posttests for PedSAP 2016 Book 1 (Immunology) can earn
9.0 contact hours of continuing pharmacy education credit. The universal activity numbers are as follows: Immunology
0217-0000-16-019-H01-P, 5.0 contact hours; and Clinical and Practice Updates 0217-0000-16-020-H01-P, 4.0 contact hours.
You may complete one or all available modules for credit. Tests may not be submitted more than once.
BCPPS test deadline: 11:59 p.m. (Central) on May 16, 2016.

ACPE test deadline: 11:59 p.m. (Central) on January 14, 2019.
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Recertification Dashboard is a free online tool that can track recertification credits as they are earned through ACCP and schedule
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for the module you waived. Answers will be available starting 1 week after the BCPPS test deadline.
Routine Childhood Immunization Series
By Stacie J. Lampkin, Pharm.D., BCPPS, BCACP, AE-C; and
Amy Wojciechowski, Pharm.D., BCPS, AQ-ID
Reviewed by Lindsay C. Trout, Pharm.D., BCPPS; Clarissa F. Havel, Pharm.D., BCPS; Bernard R. Lee, Pharm.D., BCPS, BCPPS; and Hazar
Alnifaidy, Pharm.D., BCPS
LEARNING OBJECTIVES
1. Distinguish the considerations for administering live versus inactivated vaccines.

2. Assess the role of a pharmacist in promoting the vaccination of pediatric patients to reduce the global burden of vaccine-
preventable infections.
3. Evaluate the current evidence to educate patients and caregivers about vaccination considerations, including safety,
efficacy, and common misconceptions.
4. Justify the role of combination vaccines for the pediatric population.
5. Given a pediatric case, develop a vaccine administration plan using current vaccination recommendations.
6. Distinguish the similarities and differences in childhood vaccine availability, administration, efficacy in disease preven-
tion, adverse effects, contraindications, and warnings.
INTRODUCTION
ABBREVIATIONS IN THIS CHAPTER
Vaccines advance health care by dramatically reducing the morbidity
ACIP Advisory Committee on
Immunization Practices and mortality associated with infectious diseases. Vaccines provide
DTaP Diphtheria, tetanus, and pertussis protection from infectious agents by promoting an immune response
(vaccine) within the body. The first published attempt to induce immunity by
HepA Hepatitis A (vaccine) inoculation with an infectious agent was by made Edward Jenner in
HepB Hepatitis B (vaccine) 1798. He found that by introducing small amounts of fluid from cow-
Hib Haemophilus influenzae type B pox lesions into susceptible people, immunity was developed that
HPV Human papillomavirus (2-valent, could prevent the deadly disease smallpox. Since then, the global
4-valent, 9-valent vaccine) burden of many infectious diseases has been dramatically reduced
IIV Inactivated influenza vaccine through the development of other effective vaccines. Smallpox has
(3-trivalent, 4-quadrivalent) been eradicated globally, and significant reductions in many other
IPV Inactivated poliovirus vaccine various diseases have occurred, including polio, diphtheria, mea-
LAIV Live attenuated influenza vaccine sles, mumps, rubella, pertussis, tetanus, and Haemophilus influenzae
MenACWY Meningococcal quadrivalent type B (Hib) (CDC 2011a). Routine immunizations in children are cru-
(vaccine) cial to reduce the risk of an epidemic and prevent the significant
MMR Measles, mumps, and rubella morbidity and mortality from vaccine-preventable disease (VPD).
vaccine
MMRV Measles, mumps, rubella, and vari-
cella (vaccine) How Vaccines Work
PCV Pneumococcal conjugate vaccine Immunization is the process of generating humoral immunity or pro-
(7-valent, 13-valent) viding protection from disease. The immunity conferred can be either
PPSV23 Pneumococcal polysaccharide active or passive. Active immunization involves provoking the immune
vaccine system to mount a sustained immune response; passive immuniza-
RIV3 Recombinant influenza vaccine tion involves introducing exogenous antibodies to provide temporary,
trivalent
transient protection. Vaccines are an example of active immunization,
RV Rotavirus vaccine stimulating the immune system to produce antibodies, cell-mediated
PedSAP 2016 Book 1 Immunology 7 Routine Childhood Immunization Series

protection in subsequent exposures to the same or a biologi-
Td Tetanus and diphtheria (vaccine) cally similar antigen.
Tdap Tetanus, diphtheria, and acellular
pertussis (vaccine)
Live vs. Inactivated vs. Toxoid Vaccines
VAERS Vaccine Adverse Event Reporting System
Most vaccines contain a live attenuated organism or killed
VPD Vaccine-preventable disease
microorganisms, or a modified bacterial toxin. Live attenuated
vaccines consist of a viable microorganism that undergoes
Table of other common abbreviations.
limited replication in an individual after administration. The
attenuation process decreases the microorganisms viru-
lence while retaining immunogenicity. Because live vaccines
immunity, or both. When a suspension or fraction of microor- more closely mimic natural infection, they often confer life-
ganism (the antigen) is administered into the body, it activates long immunity. A potential drawback, however, is that a true
antigen-presenting cells; these, in turn, secrete proinflamma- infection can occasionally develop and lead to morbidity and
tory cytokines and chemokines, which recruit other leukocytes mortality in immunocompromised hosts. In contrast, inacti-
in response to the inoculation. T and B lymphocytes are then vated vaccines cannot infect the host because they contain
replicated, differentiated, and stored in large pools of mem- no viable organisms. They tend to be less immunogenic than
ory cells, which can be quickly stimulated to provide immune live vaccines and often must be given in multiple doses to pro-
duce lasting immune response. Inactivated vaccines consist
of antigens from the organism that can be recognized by the
immune system to stimulate an antibody response. Booster
BASELINE KNOWLEDGE STATEMENTS doses can further stimulate B cells and antibody response,
producing long-lasting immunity.
Readers of this chapter are presumed to be familiar
Inactivated vaccines differ in composition in the resulting
with the following:
immune response. In contrast to protein-containing vaccines,
Concepts on taking a patient history in preparation
for assessing appropriateness of vaccines pure polysaccharide vaccines do not generate a T-lymphocyte
immune response; they stimulate B lymphocytes directly
General knowledge on interpreting the routine
vaccination schedule for healthy children to produce a solely humoral immune response. In infants
Availability, interchangeability and FDA approved and children younger than 2 years, polysaccharide vac-
indications and ages for vaccines available in the cines have poor immunogenicity and are not recommended.
United States. Linking or conjugating the polysaccharide to a protein carrier
Techniques and how to administer vaccines in converts it to a T lymphocytedependent antigen. Protein-
pediatric patients conjugated polysaccharide vaccines can produce a better
Familiarity with the pathophysiology of vaccine- immune response in infants and young children because of
preventable diseases T-lymphocyte involvement (Offit 2002).
Benefits and risks of assessing data from the Toxoid vaccine contain bacterial toxins that have been
Vaccine Adverse Event Reporting System inactivated by either chemical or heat treatment. The immu-
nogenicity remains after the inactivation process and
ADDITIONAL READINGS stimulates an immune response to the toxin that causes the
disease, rather than to the bacteria itself. Examples of toxoid
The following free resources have additional back- vaccines include tetanus and diphtheria.
ground information on this topic:
CDC. Vaccines & Immunization Topics Pharmacist Role
Epidemiology and Prevention of Vaccine-Preventable Pharmacists should play a role in immunization advocacy
Diseases. The Pink Book: Course Textbook, 13th
by administering vaccines, if permitted; assessing vaccine
Edition (2015)
status for referral; and providing education to families and
Advisory Committee for Immunization Practices.
children. All 50 states, the District of Columbia, and Puerto
Vaccine Recommendations.
Rico permit pharmacists to vaccinate in some capacity, with
Infectious Disease Society of America. 2013
Clinical Practice Guideline for Vaccination of the state-specific variances in degrees of scope, type, and auton-
Immunocompromised Host omy. However, seven states/territories (Connecticut, Florida,
American Pharmacist Association. Immunization Massachusetts, New York, Vermont, West Virginia, and Puerto
Resources Rico) still do not allow pharmacists to immunize children. In
addition, 12 states limit the types of vaccinations a pharma-
Table of common pediatric laboratory reference values. cist can administer to children (APhA 2015). Efforts to expand
the pharmacists role as a health care provider should include

a focus on authorization to administer all types of vaccines to
Box 1-1. Available Vaccination Products
all ages of children.
Pharmacists practicing in states where pediatric immu- Individual Vaccines
DTaP (Daptacel, Infanrix)
nizations are not allowed can still provide assessment and
Tdap (Adacel, Boostrix)
referral of children for vaccination. With respect to providing DT (generic)
education to families, pharmacists should be able to dis- Td (Decavac, Tenivac)
cuss information about vaccine efficacy and safety, school TT (generic)
requirements, risks associated with not vaccinating children, HPV2 (Cervarix)
and common misconceptions surrounding vaccines. HPV4 (Gardasil)
HPV9 (Gardasil 9)
MenACWY-CRM (Menveo)
VACCINATION SCHEDULES MecACWY-D (Menactra)
AND ADHERENCE Meningococcal polysaccharide (Menomune)
Meningococcal group B (Bexsero, Trumenba)
Publication of Childhood Immunization PCV13 (Prevnar)
Schedules PPSV23 (Pneumovax)
MMR (M-M-R II)
The CDC annually publishes routine and catch-up vaccine
V (Varivax)
schedules for children ages 018 years; these schedules are IIV3 or IIV4 (Afluria, Agriflu, Fluarix, Flucelvax,
based on recommendations from the Advisory Committee FluLaval, Fluvirin, Fluzone)
on Immunization Practices (ACIP) and approval from the IIV4 (Fluarix, FluLaval, Fluzone)
American Academy of Pediatrics, the American Academy of LAIV4 (FluMist)
Family Physicians, and the American College of Obstetricians HepA (Havrix, Vaqta)
HepB (Engerix-B, Recombivax HB)
and Gynecologists (CDC 2016). Box 1-1 lists available vac-
Hib (PedvaxHIB, ActHIB, and Hiberix)
cines and brand names. IPV (IPOL)
Rotavirus (RotaTeq and Rotarix)
Pediatric Vaccination Coverage Combination Vaccines
Failure to routinely vaccinate children increases the risk of DTaP-IPV/Hib (Pentacel)
an epidemic from VPDs. In 1974, when almost 80% of children DTaP-IPV/HepB (Pediarix)
in Japan were vaccinated for pertussis, there were 393 cases DTaP-IPV (Kinrix, Quadracel)
Hib and meningococcal (MenHibrix)
of pertussis reported and no deaths. By 1976, following rumors
Hib and HepB (Comvax)
that the vaccine was unsafe and not needed, only 10% of HepA and HepB (Twinrix)
infants were vaccinated. In 1979, Japan had a pertussis MMRV (ProQuad)
epidemic, with more than 13,000 cases of pertussis and 41
deaths. In 1981, the number of pertussis cases decreased Information from: Hamborsky J, Kroger A, Wolfe C, eds.
Epidemiology and Prevention of Vaccine-Preventable Diseases
again after the government reinitiated pertussis vaccination (Appendix B-3 and B-4). The Pink Book, 13th ed. Washington,
(Gangarosa 1998). DC: Public Health Foundation, 2015.
Vaccination rates in U.S. children are monitored and
reported in the Morbidity and Mortality Weekly Report. For
children aged 1935 months, coverage was stable from 2013
to 2014. Less than 1% of children received no vaccinations; Among adolescents (ages 1317 years), recommended
however, other children did not receive the recommended vaccination coverage increased in 20132014. In teenagers,
number of injections for each vaccination. Receiving two or the 2014 reported rates were 87.6% for tetanus, diphtheria,
more doses of hepatitis A vaccine (HepA) had the worst per- and acellular pertussis vaccine (Tdap) and 79.3% for first
centage rate at 57.5%, and receiving three or more doses of meningococcal quadrivalent vaccine (MenACWY). Ranges
inactivated poliovirus vaccine (IPV) had the best percentage varied by state; for example, the rate for the first MenACWY
rate at 93.3%. Healthy People 2020 coverage targets were was 46% in Mississippi and 95.2% in Pennsylvania. Moreover,
reached for four vaccination series (i.e., three or more doses of the overall rate for second dose of MenACWY for 17-year-olds
IPV; one or more dose of measles, mumps, and rubella vaccine was only 28.5%. For the human papillomavirus (HPV) vaccine,
[MMR]; three or more doses of hepatitis B vaccine [HepB]; and only 39.75% of girls and 21.6% of boys completed the three-
one or more dose of varicella vaccine). However seven targets dose HPV vaccine series (Reagan-Steiner 2015).
did not (i.e., four or more doses of diphtheria, tetanus, and per- Children enrolled in kindergarten in 20132014 had vacci-
tussis vaccine [DTaP]; the full series of Hib vaccine; HepB birth nation coverage rates of 94.7% for two doses of MMR, 95.0%
dose; four or more doses of pneumococcal conjugate vaccine for the varying local requirements for DTaP, and 93.3% for
[PCV]; two or more doses of HepA; the full series of rotavirus two doses of varicella vaccine among states with a two-
vaccine [RV]; and the combined vaccine series) (Hill 2015). dose requirement. The median total exemption rate was

1.8%, with a range of less than 0.1% for Mississippi to 7.1% able to recognize the signs and symptoms of the VPD and be
in Oregon. Eleven states had an exemption rate of 4% or cognizant that some diseases can be spread by those who
greater (Seither 2014). are asymptomatic (CDC 2015b).
Among children ages 1935 months, coverage rates for
many vaccines were lower for those living below the fed-
PATIENT EDUCATION ON VACCINE
eral poverty level than for those at or above the poverty level
CONCERNS
(Hill 2015). Across all age ranges, vaccination coverage rates
Among the many reasons why parents refuse to have their
varied across states and by vaccine, but there was no con-
children vaccinated are unfounded misconceptions. To effec-
sistency across any region (Hill 2015; Reagan-Steiner 2015;
tively communicate with families refusing to vaccinate, it is
Seither 2014).
important to understand their concerns. Common miscon-
Reasons for under-vaccination and refusal range from vac-
ceptions surround four themes: (1) fear that vaccines or their
cination access to negative patient perceptions; therefore,
additives are harmful, (2) fear that the vaccine will cause the
improving adherence and decreasing exemption requires a
infection, (3) belief that too many vaccines will overwhelm
multifaceted approach. When data are available, initiatives to
the childs immune system, and (4) belief that getting the
improve adherence should be tailored toward local or county
natural VPD is healthier (CDC 2015b; Healy 2011).
vaccination or exemption rate concerns. The CDC Community
Because vaccines have reduced the incidence and mor-
Guide lists the recommended methods to increase appro-
tality of disease, firsthand experience of the devastating
priate vaccination. The programs fall under three themes:
consequences of VPD is rare today. A lack of familiarity with
(1) enhancing access to vaccination services, (2) increasing
these consequences had increased the misconception that
community demand for vaccinations, and (3) ensuring pro-
getting the natural disease is healthier than receiving the
vider or system-based interventions.
vaccine (Healy 2011).
Public Policy and Risks
Individual states require vaccinations for entry into school Misconceptions of Autism Linkage
and even day care facilities. Each state passes its own reg- The most common misconception about vaccines is that
ulations, and there is great variance in what qualifies as an MMR or its additive, thimerosal, can cause autism (AAP 2016;
exemption. All states allow for medical exemptions, many CDC 2015b). The concern with the MMR vaccine and autism
allow for religious exemptions, and some even permit exemp- began in 1998 with Andrew Wakefields study published in
tions because of philosophical beliefs. States also vary in Lancet. His article claimed that the MMR vaccine caused
required documentation and enforcement of regulations. inflammatory bowel disease, which allowed harmful proteins
During an epidemic, many states forego exemptions and to damage the brain. In 2010, Lancet retracted his article for
exclude students without the required vaccinations from ethical misconduct, and 10 of the 13 authors retracted the
school (CDC 2015b). findings (AAP 2016; IAC 2013).
In July 2016, California State Bill 277, one of the strictest Other concerns regarding autism may be caused by the
school vaccine laws, will go into effect. Allowing only med- timing of MMR administration; the vaccine is given at age
ically necessary exemptions, the bill requires parents who 1215 months, and the first symptoms of autism usually
choose not to vaccinate for other reasons to homeschool develop at 15 months (Roberts 2002). However, to date, more
their children because they will not be allowed to attend than 20 articles have found no association between the MMR
school with other students. vaccine and autism (healthychildren.org 2015; IAC 2013).
Currently, the CDCs Public Health Law Program is com- Thimerosal, a preservative that contains mercury, was
piling summaries of school exemption information by each never used in MMR (CDC 2015b). In the 1990s, it was found
state. However, pharmacists should know the pertinent local in other vaccines but was removed in 1999 as a precaution-
law so that they can educate parents about the potential ary safety measure; however, it can still be found in multidose
impact of vaccination refusal. flu vaccines today. To date, studies have found no relation-
Beyond access to school, the risks and consequences of ship between early exposure to thimerosal and autism (CDC
vaccine refusal may affect the health of children and those 2015b; healthychildren.org 2015).
around them. Pharmacists should educate parents to inform
medical staff of their childs vaccination status when they Other Vaccine Substances
call 911, ride in an ambulance, visit a hospital ED, or visit a Further vaccine safety concerns surround adjuvants, preser-
physicians office. This information will greatly affect the dif- vatives, or trace substances such as formaldehyde from the
ferential diagnoses because the child could have a VPD. If the manufacturing process (CDC 2015b). The adjuvant aluminum
child has a VPD, additional precautions (e.g., isolation) must continues to raise safety concerns because of its potential
be taken to protect others who have immunocompromise or for negative health consequences. Vaccines in the United
who may not be vaccinated. In an outbreak, parents must be States that contain aluminum are HepA, HepB, DTaP, Tdap,

Hib, HPV, and PCV13 (CDC 2015b). The amount of aluminum The only major deficiency in the immune system of children
in each ranges from 0.125 mg to 0.625 mg, which is about 1% younger than 2 years is a decreased B-cell response rela-
of the estimated average daily aluminum intake (3050 mg) tive to older children and adults. T celldependent immunity,
from foods, drinking water, and medicines (CDC 2015b). however, is robust even before birth. Pure polysaccharide
Because aluminum has been in vaccines for 70 years and is vaccines invoke immune response solely by B-cell stimu-
only associated with minor injection-site reactions, there is no lation and are thus less effective in children younger than
current recommendation to remove aluminum adjuvants 2 years. To ensure that polysaccharide vaccines are effective
from vaccines. However, further research is evaluating the in this age group, they are conjugated to a protein so that the
toxicology and pharmacokinetics of aluminum adjuvants in child can respond through T celldependent mechanisms
infants and children (Eickhoff 2002). (Offit 2002).
Vaccines as a Disease Cause Alternative Schedules

Some families may believe that their child will contract the Concerned parents may request an alternative vaccine
disease from the vaccine (Healy 2011). As discussed earlier, schedule. Currently, The Vaccine Book: Making the Right
inactivated vaccines cannot cause the illness, and live Decision for Your Child by Dr. William Sears offers alterna-
vaccines only rarely cause disease in healthy children. tive vaccine schedules for concerned parents (Offit 2009).
Occasionally, live vaccines can cause a mild form of the dis- These alternative schedules are not recommended; they lack
ease that is not harmful (CDC 2015b). For example, less than evidence of efficacy and do not decrease adverse events
5% of children will develop a localized or generalized varicella- (Fisher 2009; Offit 2009). In fact, there are risks of following
like rash 526 days after vaccination. Usually, the rash has an alternative schedule that spreads out vaccine adminis-
two to five lesions (IAC 2016). An exception is the patient with tration. Children may be unprotected when they are most
immunocompromise, who may develop a more severe form vulnerable to a VPD. Moreover, there would be a decrease in
of illness (Kroger 2011). Another exception was the live oral the benefits of herd immunity and an increase in the number
polio vaccine, which was known to rarely cause severe illness of physician visits for an immunization (Fisher 2009).
even in healthy children. However, the oral polio vaccine is no
longer used in the United States (CDC 2015b). Patient Education Resources
Parents and families may have additional concerns about
Overwhelming the Immune System vaccinations. Patient-friendly information specific to each
In a national survey, 25% of parents reported believing that too vaccine and vaccines in general can be found on the CDC
many immunizations can weaken a childs immune system website. These materials include vaccine basics and bene-
(Gellin 2000). This concern leads to the belief that giving the fits, frequently asked questions, and true stories of families
recommended number of vaccines at pertinent clinic visits negatively affected by VPD. Other patient resources are found
is unsafe because too many vaccines are given too soon in Box 1-2.
(Oft 2009). Children currently receive 1426 injections by the
time they are 2 years old. INTERPRETATION OF VACCINE
Advocates argue that the high antigen exposure from vac- SCHEDULES AND ADMINISTRATION
cines will weaken the immune system. In reality, children are CONSIDERATIONS
exposed to around 130 antigens in currently recommended
In addition to patient education materials and the vaccine
vaccines, compared with the 200 antigens that were in the
schedules, the CDC website provides great resources to aid
only vaccine, smallpox, administered in the 1900s (Offit 2002).
providers in assessing vaccination status and staying up
It has been estimated that, based on the number of circulat-
to date with evolving research and recommendations. It is
ing B cells in the body, their capacity to respond to antigens,
essential to review the website regularly because the most
and the number of antigenic epitopes contained in each vac-
up-to-date recommendations may change in between annual
cine, infants have the capacity to respond to 10,000 vaccines
publication of the standard schedules. For example, in March
at any given time. Thus, giving 11 vaccines concurrently to
2015, the recommendation for HPV vaccination changed to
an infant would use only about 0.1% of the immune system
capacity (Offit 2002). The CDC maintains that the immune
system will not be overwhelmed by multiple vaccinations,
and the recommended immunization schedule provides the Box 1-2. Patient-Friendly Immunization
best protection from infection (CDC 2015b). Education Resources
Parents may also believe the infants immune system is Parents Guide to Childhood Immunizations
too immature. This belief is not medically justified, because American Academy of Pediatrics
neonates can generate both humoral and cellular immune
Vaccine Education Center at the Childrens Hospital of
Philadelphia
responses from the time of birth, regardless of gestational age.

include the addition of HPV9; this recommendation was not asplenia; these patients should not have PCV13 and Menactra-
incorporated into the official schedule until the 2016 publica- brand meningococcal conjugate vaccine administered at the
tion. In addition, when each new vaccine schedule appears, it same visit. Rather, these vaccines should be separated by at
should be reviewed for updates. least 4 weeks because Menactra is thought to interfere with
Interpreting the schedule for routine vaccine administra- the antibody response to PCV13 (CDC 2015a).
tion in healthy children is straightforward. The footnotes Although not recommended or necessary, there may
associated with the schedule provide additional details such realistically be situations in which a parent or provider
as minimal and maximal administration age and intervals is uncomfortable administering the quantity of vaccines
between vaccinations. Of note, the minimal administrations required at one visit. At this time, a clinical decision will need
interval between live vaccines not given simultaneously to be made in order to determine which vaccines are most
is always 28 days. Administering a vaccine before the min- important. Factors to consider may include, but are not lim-
imum age or recommended interval will likely result in a ited to, current outbreaks in the area, prevalence of disease
suboptimal immune response (Kroger 2011). Factors that for the recommended vaccines, and common age for severe
lead to a suboptimal immune response if a child is too young negative effects if the child contracts the VPD.
include immaturity of the immune system and interference
from maternal antibodies (IAC 2016; Chung Wai Ng 2014). If Combination Vaccines
a multi-series dose of a vaccine is given too early, protec- Administering vaccines with combination products can help
tion to that dose may be reduced because of interference in reduce the number of injections at a visit. Currently, in the
antibody response between the two doses (CDC 2015a; IAC United States, the only four vaccines that are not available
2016). However, vaccines administered 4 days or less before in any combination form for pediatric patients are influenza,
the minimal interval or age are still considered valid, though PCV13, pneumococcal polysaccharide vaccine (PPSV23),
the mandate at the local or state level to count the vaccine and HepA. Although it is ideal to use combination products
as valid may be different. If a dose is administered before the in most situations, there are special considerations with cer-
minimal interval, the repeat dose should be spaced appro- tain products, such as ProQuad and febrile seizure risk (as
priately after the invalid vaccine. If a vaccine is given before discussed later). Another consideration for combination vac-
the minimal age, the dose should be repeated when the child cines is the potential for confusion about the components
reaches the age limit (Kroger 2011). and which vaccines should be administered for subsequent
doses (Kroger 2011).
Assessing the Need for Vaccines
Assessing vaccine status and appropriateness becomes more
CONSIDERATIONS PERTAINING TO
challenging in patients who require catch-up vaccines or who
ALL VACCINATIONS
have additional considerations (e.g., immunocompromise).
The Pink Book Appendix A-15, Summary of Recommendations Contraindications and Precautions
for Child/Teen Immunization, is an essential resource for To prevent the risk of an adverse outcome, contraindications
assessing the need for vaccination in more complex situa- and precautions should be assessed before administering
tions or patients (Hamborsky 2015). However, for full details a vaccine. For specific contraindications and precautions
of all considerations for a specific vaccine, the Morbidity and to each vaccine, see Pink Book Appendix A-15, Summary of
Mortality Weekly Report with ACIP recommendations should Recommendations for Child/Teen Immunization (Hamborsky
be consulted. 2015). Across all vaccines, the only truly universal contrain-
dication is history of severe anaphylaxis to a component in
Administering Multiple Vaccines the vaccine, and the only universal precaution is moderate or
When patients require several vaccines to catch up, a com- severe acute illness with or without fever (CDC 2015a; Kroger
mon question is, Which vaccines are most important to give 2011). There is no concise definition of moderate or severe
at that visit? The American Academy of Pediatrics and ACIP acute illness; rather, it is based on subjectivity of the sever-
recommend to give all needed vaccines at the visit and not ity of symptoms and the cause of illness. Of note, the use of
to delay vaccines. Currently, the number of injections that antibiotics or antivirals does not automatically indicate mod-
can be administered at one time is without limit. If possible, erate or severe illness. Mainly, this precaution is meant to
intramuscular vaccines should be spaced by at least 1 inch prevent confusion between diagnosing the underlying illness
to potentially reduce the risk of overlapping local reactions and confounding it with a vaccination adverse effect (Kroger
(IAC 2016). 2011). Therefore, it will be up to the provider to determine the
In addition, simultaneous administration of most vaccines appropriateness of withholding vaccines because of illness.
has not been shown to increase the incidence of adverse However, many misconceptions cause health care profes-
effects or decrease the efficacy of vaccines (Kroger 2011). sionals to withhold vaccines unnecessarily (Box 1-3). A full
An exception to this is in children with functional or anatomic list of common perceived contraindications/precautions by

Patient Care Scenario
A 12-month-old boy with no significant medical history HepB 0 months, 2 months
comes to your clinic for a well visit in October. He started
RV 2 months, 4 months
his routine vaccinations appropriately but fell out of care
DTaP 2 months, 4 months
because of a lack of health insurance and has received no
vaccines since he was 4 months old. His vaccine history Hib (ActHIB) 2 months, 4 months
is as follows: PCV13 2 months, 4 months
IPV 2 months, 4 months
What vaccinations are best to administer to this patient

today?
ANSWER
First, look at figure 1 of the Recommended Immunization Recommended Immunization Schedule for Persons Aged
Schedule for Persons Aged 0 Through 18 Years to evalu- 0 Through 18 Years to determine how to approach the vac-
ate which vaccines he is behind schedule on, as well as cines he has fallen behind on.
which ones would normally be due at 12 months of age. The following table describes an evaluation for each
Then, consult the catch-up schedule in figure 2 of the vaccine:
Vaccine Vaccine Indicated? Notes

HepB Yes Administer third dose on schedule now
RV No Contraindicated in those > 8 mo
DTaP Yes Catch up for third dose now; in 6 mo, give fourth dose
Tdap No Not indicated for those < 7 yr
Hib Yes Catch up for third dose now; no longer will need fourth dose
PCV13 Yes Catch up for third dose now; no longer will need fourth dose
PPSV23 No Not indicated for those < 2 yr
IPV Yes Administer third dose on schedule now
IIV Yes Administer first dose now; in 4 wk, give second dose
LAIV No Contraindicated in those < 2 yr
MMR Yes Administer first dose on schedule now
Varicella Yes Administer first dose on schedule now
HepA Yes Administer first dose on schedule now
HPV No Not indicated for those < 9 yr
Meningococcal No Only indicated in patients < 11 yr if high risk
This patient currently needs HepB, DTaP, Hib, PCV13, ProQuad, it is recommended to counsel the family on the
IPV, IIV, MMR, varicella, and HepA. Although it may seem small increased risk of febrile seizures compared with
like nine vaccines is a large number to administer in a sin- administering the vaccine as MMR and varicella as two
gle visit, ACIP and the AAP recommend giving all needed separate injections. If several intramuscular injections
vaccines at the visit and not to delay vaccines. It is safe are given into the same muscle, they should be adminis-
to give multiple vaccines at the same visit, whereas defer- tered at least 1 inch apart. Because DTaP and PCV13 are
ring some until a later date may expose the child to an the most likely to cause local injection-site reactions, it
unnecessary risk of delayed immunity. The number of may be prudent to give the injections containing these
injections required may be reduced by offering com- vaccines in separate limbs, if possible.
bination vaccines. Several different combinations of
1. Immunization Action Coalition. Ask The Experts:
formulations can provide the necessary vaccines in as
Topics [homepage on the Internet].
few as six injections. One example is ProQuad (MMRV)
plus IIV plus PCV13 plus Pentacel (DTaP/Hib/IPV) plus 2. Robinson CL. Advisory Committee on Immunization
HepA plus HepB. Twinrix (HepA/HepB) is not approved in Practices recommended immunization schedules
pediatric patients and should be given as a separate HepA for persons aged 0 through 18 years United States,
and HepB vaccine in this population. If administering 2016. MMWR 2016; 65:86-7.
vaccine can be found in Table 7 of the Morbidity and Mortality the risk of adverse reactions or overburden the immune sys-
Weekly Report General Recommendations on Immunization. tem. However, the rates of antibody response and vaccine
Special considerations do exist. Some parents may worry adverse reactions in children with mild illness are similar to
that vaccinating a child with mild acute illnesses will increase those in healthy children (Offit 2002). Regardless, it would

Box 1-3. Conditions Generally Not Box 1-4. Specific Immunodeficiencies
Considered Contraindications to Primary
Vaccination Severe antibody deficiencies (e.g., X-linked, agamma-
Minor acute illness such as diarrhea and minor upper globulinemia and common variable immunodeficiency)
respiratory tract illnesses (including otitis media) with Less severe antibody deficiencies (e.g., selective IgA
or without low-grade fever deficiency and IgG subclass deficiency)
Mild to moderate local reactions and/or low-grade or Complete T-lymphocyte defects (e.g., severe combined
moderate fever after a prior dose of the vaccine immunodeficiency [SCID] disease, complete DiGeorge
Current antimicrobial therapy syndrome)
Recent exposure to infectious disease Partial T-lymphocyte defects (e.g., most patients with
Convalescent phase of illness DiGeorge syndrome, Wiskott-Aldrich syndrome, ataxia
Pregnant or immunosuppressed person in the household telangiectasia)
Preterm birth Persistent complement, properdin, or factor B defi-
Breastfeeding ciency chronic granulomatous disease, leukocyte
Allergies to products presumed to be in vaccine, but are adhesion defect, and myeloperoxidase deficiency
not in vaccine Secondary
HIV/AIDS
Information from: Kroger AT, Sumaya CV, Pickering LK, et al. Malignant neoplasm (leukemia, lymphoma, or general-
Centers for Disease Control and Prevention. General rec- ized malignancy)
ommendations on immunization: recommendations of the
Advisory Committee on Immunization Practices (ACIP). Transplantation
MMWR 2011;60:1-61; Hamborsky J, Kroger A, Wolfe C, eds. Immunosuppressive or radiation therapy
Epidemiology and Prevention of Vaccine-Preventable Diseases. Asplenia
The Pink Book, 13th ed. Washington, DC: Public Health Chronic renal disease
Foundation, 2015.
IgA = immunoglobulin A; IgG = immunoglobulin G.
Information from: Hamborsky J, Kroger A, Wolfe C, eds.
Appendix A-26; Epidemiology and Prevention of Vaccine-
Preventable Diseases. The Pink Book, 13th ed. Washington, DC:
Public Health Foundation, 2015.
be important in this situation to appropriately educate and
empower parents to decide whether they still want to with-
hold vaccines until after illness has improved. Prematurity
is generally not a contraindication to vaccinations; however,
one exception is RV, which should be deferred until discharge Immunosuppression
for any child who has been in the hospital since birth (Kroger Another controversy in vaccine administration is determining
2011). Waiting to administer RV until a premature infant is the safety and efficacy of administering vaccines in chil-
clinically stable and no longer in the hospital will outweigh dren with altered immunocompetence. Immunodeficiencies
the theoretical risk of an adverse reaction as the result of a are classified into primary and secondary (Box 1-4).
lower level of rotavirus maternal antibody in very preterm Immunodeficiencies make patients more susceptible to
infants (Cortese 2009). infection, so additional vaccines are often warranted; how-
All children should receive all routine vaccines, including ever, they also increase the risk of complications with live
MMR, varicella, and RV, even if there are household or close vaccines, so some immunizations may be contraindicated.
contacts with immunocompromise. The only exception to this Even after classification, it is difficult to assess the degree
is the smallpox vaccine, which should not be administered to which a drug or disease causes immunosuppression and
if household members have immunocompromise; however, whether a vaccine is indicated or should be withheld until
smallpox vaccination is no longer routinely recommended in later (Kroger 2011). The Pink book appendix Vaccination of
the United States since the eradication of the naturally occur- Persons with Primary and Secondary Immune Deficiencies
ring disease (Kroger 2011). Inactivated influenza vaccine summarizes vaccine efficacy, contraindications, and rec-
(IIV) is recommended over live attenuated influenza vaccine ommendations by type of immunodeficiency. For example,
(LAIV) for individuals in close contact with a severely immu- asplenia makes patients particularly susceptible to infection
nocompromised person. Because of theoretical transmission with encapsulated bacteria, so recommended vaccines are
of the virus, if LAIV is received, contact should be avoided for targeted toward these organisms.
7 days after administration (Grohskopf 2015). Viruses from Timing of vaccination is important to ensure adequate
the MMR vaccine are not transmitted to contacts, and it is immunity as well. For planned splenectomies, vaccination
rare for varicella to be transmitted (Kroger 2011). To reduce at least 14 days before surgery is optimal. For emergency
the transmission of rotavirus that is shed during the first splenectomies when preoperative vaccination is not pos-
weeks after vaccine administration, everyone should wash sible, waiting until at least 14 days after surgery produces
hands after changing the childs diaper (Cortese 2009). the best immune response (Shatz 1998). In some situations,

consultation with an infectious disease or immunology spe-
cialist is indicated (Kroger 2011). Table 1-1. Intervals Between Administration of MMR
From a safety standpoint, risk and benefit must be consid- or Varicella and Immune Globulin Preparations
ered when deciding to administer a vaccine. All inactivated
Interval
vaccines can safely be administered to children with immu- (months) Products
nosuppression, who are already at an increased risk of the
3 RBCs, adenine-saline added blood
disease and its complications. Live vaccines may increase
transfusion
the risk of severe complications because of uninhibited rep-
Hepatitis A IG
lication (Kroger 2011). However, depending on the type of Hepatitis B IG
immunodeficiency and degree of immunosuppression, certain Tetanus IG
live vaccines may be recommended. This includes varicella in
4 Rabies IG
patients with HIV infection who are not severely immunocom-
promised (defined as a CD4+ T-lymphocyte count greater than 5 Varicella IG
200 cells/mm3 for adolescents and a percentage greater than 6 Blood transfusion with packed RBCs
15 for infants and children (CDC 2015a; Rubin 2014). Blood transfusion with whole blood
Another consideration with altered immunocompetence Botulinum immune globulin intravenous
is vaccine effectiveness. This also depends on the degree (human)
of immunosuppression and the type of immunodeficiency. CMV (cytomegalovirus) IG
Because they are safe to give, inactivated vaccines are rec- Measles IG
ommended to be given as scheduled, even though there may 7 Blood transfusion with plasma/platelet
be a suboptimal immune response. However, patients receiv- products
ing chemotherapy or radiation will likely have a suboptimal 8 IGIV dose 400 mg/kg/dose IV
immune response, and inactivated vaccines should be with-
10 IGIV dose 1000 mg/kg/dose IV
held, if possible. If vaccines are administered, both live and
inactivated vaccines may potentially require readministra-
tion after immune function has improved to ensure adequate IG = immunoglobulin; IGIV = intravenous immunoglobulin;
IV = intravenously.
immunity, though no specific criteria for revaccination have
Information from: Hamborsky J, Kroger A, Wolfe C, eds.
been established (Kroger 2011)
Appendix A-24. In Epidemiology and Prevention of Vaccine-
Preventable Diseases. The Pink Book, 13th ed. Washington,
Drugs Affecting Immune Status DC: Public Health Foundation, 2015.
Corticosteroids and certain drugs can cause some level of
immunosuppression, although to what degree is not clearly
established. Because of safety concerns, the consensus is Administration of antibody-containing products are
that live vaccines should be delayed if a patient is receiv- thought to interfere with live vaccine replication of the MMR
ing high-dose steroids (defined as either 2 mg/kg or more or and varicella vaccines (CDC 2015a). Therefore, it is recom-
20 mg/day or more of prednisone or equivalent) for 14 days or mended to give the vaccines at least 2 weeks before the
more. Live vaccines can safely be administered 1 month after antibody product. However, the intervals for administration
discontinuing high-dose therapy. Patients receiving chronic vary by product (Table 1-1).
maintenance physiologic replacement corticosteroids should Because of the many exceptions and considerations to
not have vaccines deferred. However, doses higher than these recommendations, the guidelines from the Infectious
physiologic maintenance may reduce the immune response Diseases Society of America and CDC should also be con-
(Kroger 2011). sulted when administering vaccines in children with altered
In general, children who are going to receive chemother- immunocompetence. For example, children may retain
apy, other immunosuppressive drugs, or radiation should immune memory and not require repeat vaccination if they are
optimally have all types of vaccines administered at least receiving chemotherapy or radiation for certain malignancies.
14 days before starting therapy. When vaccines are admin- Inactivated vaccines may also be recommended in patients
istered less than 14 days before or during therapy, they receiving low-dose intermittent or maintenance therapy of
should be readministered at least 3 months after therapy is immunosuppressive agents. Moreover, if the benefit of vacci-
discontinued, if immunosuppression has resolved. This rec- nation outweighs the risk, a live vaccine might be indicated in
ommendation stems from a possible suboptimal response the patient with immunocompromise (Kroger 2011).
to vaccines and potential safety concerns for live vaccines
during this time. One exception is IIV; it should be adminis- General Adverse Effects
tered even during immunosuppression and does not need to Common vaccine-specific adverse effects are discussed
be repeated (Kroger 2011). in the following. Some adverse effects encompass most

vaccines: these include pain, injection-site reactions, fever true risk, antipyretics should be reserved for postvaccination
or flu-like illness, syncope, and anaphylaxis. Clinically sig- treatment of an adverse event (Das 2014).
nificant adverse effects after vaccine administration should Syncope after vaccinations is common, especially in those
be reported to the Vaccine Adverse Event Reporting System 1118 years of age. A VAERS report found that 62% of reported
(VAERS), a national surveillance reporting system (CDC 2015a). fainting episodes occurred in this age range (CDC 2015b). It is
The pain associated with childhood vaccines can lead to recommended to observe patients while they sit or lie down
long-term negative effects, such as conditioned fear of nee- for 15 minutes after vaccinating. In addition, giving patients
dles and avoidance of associated procedures. Even though a beverage or snack may reduce the chance of fainting (CDC
the perception of pain varies from patient to patient, there 2015b; Kroger 2011).
are methods to reduce the pain associated with vaccination. Anaphylaxis occurs in about 1 of 1.5 million doses of vac-
These measures include breastfeeding, giving sweetened cines administered to children and adolescents. If an allergic
solutions for infants younger than 12 months, injecting the reaction occurs, the person administering the vaccine should
most painful vaccine last, using tactile stimulation in chil- be prepared to care for the patient and have an emergency
dren 4 years and older, using distraction, and applying topical plan in place. It is also recommended that all individuals
anesthetics (CDC 2015a). administering vaccines be certified in cardiopulmonary resus-
Injection-site reactions usually present as soreness, red- citation (CDC 2015a).
ness, itching, or swelling at the injection site. If a reaction
occurs, the symptoms usually resolve within a few days but INDIVIDUAL VACCINE INFORMATION
may last up to a week. Treatment consists of cold compresses
Diphtheria, Tetanus, and Pertussis
and, depending on the severity of the reaction, analgesics or
antipyretics (Rosenblatt 2015; Schmitt 2015). Injection-site Overview of Infection Disease
reactions can occur with any vaccine and are not associated Diphtheria is caused by the bacterium Corynebacterium diph-
with specific vaccine components. If a skin reaction (e.g., theriae, a gram-positive bacillus, and manifests as an upper
rash) varies from the typical presentation of an injection-site respiratory tract infection. C. diphtheriae produces a toxin
reaction, the patient should be referred for a follow-up. Many that is responsible for producing the clinical features and
vaccines can cause rare skin reactions that are specific to the complications of the disease. The infection affects mucous
vaccine or its components (Rosenblatt 2015). membranes, primarily in the tonsils, pharynx, larynx, and
Fever or flu-like illness is also a common adverse effect. nasal mucosa, and can lead to formation of the diseases hall-
Usually, the fever begins within 24 hours of vaccine admin- mark, a pseudomembrane. As the pseudomembrane grows
istration and resolves in 12 days. For live vaccines such in size, it can extend into the airway space and cause respira-
as MMR and varicella, fever may be delayed for 14 weeks tory obstruction and subsequently death from asphyxiation.
(Schmitt 2015). A fever from vaccines should be approached Additional complications of the toxin include myocarditis,
similarly to any other fever. Children who develop fever from neuropathy, paralysis, and pneumonia. Without treatment,
vaccinations have no higher risk of febrile seizures. The about 50% of patients with diphtheria will die; even with
only exception is the slight increase risk of febrile seizures proper treatment, the mortality rate remains about 10%.
within 512 days after the first dose of the MMR vaccine or Vaccination is extremely effective in preventing diphthe-
the measles, mumps, rubella, and varicella vaccine (MMRV) ria. Because of high vaccination rates, fewer than five U.S.
(CDC 2015b). When MMR and varicella are administered cases were reported in the past decade. However, diphtheria
separately to children 1247 months of age, about 4 of remains a significant threat in other areas of the world such
10,000 children will have a febrile seizure compared with 8 as India and Nepal (CDC 2015a; WHO 2015).
of every 10,000 children who receive MMRV. It is therefore Tetanus is disease caused by Clostridium tetani; this
recommended to discuss this risk with all families before gram-positive anaerobic bacterium produces a neurotoxin
administering MMRV so that they can decide whether the that causes muscles to contract. C. tetani enters the body
combination MMRV vaccine or separate injections of MMR through a wound or cut in the skin and travels through-
and varicella are most appropriate, especially if there is a out the body to manifest its effects on various sites of the
personal or family history of febrile seizures or epilepsy CNS. The resulting unopposed muscular contraction can
(CDC 2015b). lead to spasms, seizures, and autonomic nervous system
For all of the previously mentioned vaccines, prophylactic dysfunction. The associated death rate, even with appropri-
acetaminophen or ibuprofen are not recommended because ate treatment, is 10%20%. Vaccination has made tetanus
of insufficient evidence that they reduce discomfort, fever uncommon in the United States, with an average of around
associated with vaccines, or risk of febrile seizures (Kroger 30 cases per year, primarily in those who are unvaccinated or
2011; Sullivan 2011). In addition, pretreatment with antipy- not up to date with booster shots (CDC 2015a).
retics may decrease immune response to the vaccines (Das Pertussis (whooping cough) is a respiratory disease
2014). Although more studies are needed to determine the caused by Bordetella pertussis, a gram-negative aerobic

bacterium. Pertussis is known for its paroxysmal coughing reaction after previous vaccination is not a contraindication
spells, which lead to the characteristic high-pitched whoop to further receipt of the Td or Tdap vaccines; however, it is
sound on inspiration. Pertussis was a common childhood ill- generally recommended to wait at least 10 years between
ness and a major cause of child mortality. From 1922 to 1940, boosters because the severity of the reaction is correlated
the incidence averaged 150 reported cases per 100,000; this with the frequency of toxoid exposure.
was significantly reduced after introduction of the vaccine
in the 1940s, and the incidence was 0.5 cases per 100,000 Human Papillomavirus
in 1976 (Faulkner 2015). However, pertussis incidence in the Overview of Infection Disease
United States has increased during the past 3 decades. The Human papillomavirus is a DNA virus that can cause infec-
annual number of cases in 2012 was 48,000, up from a low of tion in the skin or mucous membranes; spread primarily
1300 in 1981. This can be attributed to more vaccine refus- through contact with infected skin, mucous membranes, or
als as well as to the switch to acellular vaccine from whole body fluids, it is the most common sexually transmitted infec-
cell vaccine, which was more immunogenic. In response, the tion, affecting most sexually active individuals. An estimated
ACIP has expanded its recommendations regarding pertussis 79 million people in the United States are infected with HPV,
vaccination several times since 2010 to combat the growing with 14 million new infections annually, half of which are in
threat of disease (CDC 2015a). individuals 1524 years of age (Satterwhite 2013). There
are more than 150 serotypes of HPV, many of which cause
Recommended Administration Schedule
subclinical infection and go unnoticed. Of primary clinical
The DTaP vaccine is given as a five-dose series to children concern, however, are the infections that can lead to cancer
younger than 7 years. Minimal intervals after the first two or warts. Human papillomavirus is strongly associated with
doses are 4 weeks, with a 6-month interval before each of the cancers of the cervix, penis, anus, and oropharynx, with sero-
last two doses. The Tdap vaccine is recommended for adoles- types 16 and 18 being the most common culprits, followed
cents as a single dose. For children and adolescents 7 years by serotypes 31, 33, 45, 52, and 58. Anogenital warts are also
and older who have not completed the primary DTaP series, a caused by HPV, with more than 90% associated with sero-
three-dose series should be given: one dose of Tdap, followed types 6 and 11 (Markowitz 2014).
at least 4 weeks later with a dose of tetanus and diphtheria
vaccine (Td) and a second dose of Td at least 6 months after Recommended Administration Schedule
the first. For pediatric patients, the formulations including As recommended by ACIP, boys and girls should have routine
pertussis should always be used unless there is a contraindi- HPV vaccination with a three-dose series beginning at age 11
cation (Robinson 2016). or 12, with a minimal starting age of 9 years. Female patients
In 2011, ACIP expanded its pertussis vaccine recommen- 926 years of age should be vaccinated with HPV vaccine,
dations to include all individuals 11 years and older who have with no preference given by ACIP between HPV2, HPV4, and
not received a dose of Tdap, emphasizing the need for this HPV9. Male patients 921 years of age, as well as up to age 26
vaccine in adults who will be in contact with infants younger for high-risk patients (i.e., men who have sex with men, those
than 12 months. The intent is to protect infants, who are most with immunocompromise), should be vaccinated with HPV4
at risk of pertussis complications, by preventing carrier trans- or HPV9. If the formulation of previous doses is unknown, or
mission before they develop adequate immunity from their unavailable, any of the available HPV vaccine formulations
primary vaccination series (CDC 2011b). In addition, since may be used to complete the series for female patients; HPV4
2012, Tdap has been recommended for pregnant women dur- or HPV9 is preferred for male patients.
ing each pregnancy (regardless of the timing of previous Approved in 2014, HPV9 is a new formulation with
vaccinations), preferably between 27 and 36 weeks gesta- expanded serotypes that offers protection against an addi-
tion to maximize antibody transfer through the placenta for tional 10%15% of HPV-associated cancers (Petrosky 2015).
protection of the infant after birth (CDC 2013b). However, ACIP has made no recommendations about revac-
cinating (or restarting the vaccine series) for those who
Vaccine-Specific Considerations previously received HPV vaccine doses and who desire the
Arthus reactions have been described for patients receiv- additional serotype coverage offered by HPV9. Clinical and
ing vaccines that contain tetanus or diphtheria toxoid. This pharmacoeconomic evidence is currently insufficient to sup-
immune-mediated type III hypersensitivity reaction causes port revaccination of those who have already completed the
a localized vasculitis at the injection site, leading to severe vaccine series; however, some data suggest that revacci-
pain, swelling, induration, and hemorrhage within 412 hours nation with HPV9 after completing a series of HPV4 is safe
after the injection. Arthus reactions are generally self-limiting (Petrosky 2015).
and resolve without treatment in 12 days; however, symp- Several studies showing the noninferiority of two-dose or
tomatic management with analgesics or anti-inflammatory even one-dose regimens compared with the full three-dose
drugs can be considered (Butler 1976). A history of Arthus HPV vaccine series have prompted some organizations to

alter their recommendations (Kriemer 2015; Dobson 2013). Recommended Administration Schedule
For example, WHO now recommends only a two-dose sched- Vaccination with a quadrivalent meningococcal vaccine
ule for adolescents who initiate the vaccine series before (MenACWY) is routinely recommended for adolescents as
14 years of age (WHO 2014). However, ACIP has not altered its well as younger children who are at high risk of disease,
recommendations and continues to support completion of a including patients with functional or anatomical asplenia,
three-dose series. with complement deficiency, or living in an area of high menin-
gococcal disease prevalence or in outbreak settings (Cohn
Vaccine-Specific Considerations 2013). The prevalence of meningococcal disease caused by
Adherence to recommended vaccination schedules for HPV serogroup B has prompted the development and recent U.S.
vaccine has lagged behind that of many other vaccines, with approval of new recombinant vaccines. Additional adminis-
completion of the recommended three-dose series in only tration of a vaccine covering serogroup B is recommended
around one-half of adolescent girls by age 17 and less than in patients at high risk of disease because of the conditions
one-fourth of boys by age 17 (Reagan-Steiner 2015). Reasons listed earlier or in the setting of an outbreak (Folaranmi 2015).
for the low vaccine uptake include lack of knowledge about The serogroup B meningococcal vaccine was incorporated
the risks of HPV-associated cancer, general concerns about into the 2016 vaccination schedule for high-risk groups and
vaccine efficacy and safety, high cost of the vaccine, and nonhigh-risk groups that may receive the vaccine based on
unfounded concerns about the vaccines promoting sexual individual clinical decision making.
promiscuity (Fernndez 2014). Several studies have shown
that HPV vaccination does not increase sexual activity Vaccine-Specific Considerations
among teens and is not associated with an increase in over- One particularly dangerous drug-related risk factor for menin-
all sexually transmitted infection rates (Jena 2015; Liddon gococcal disease is the monoclonal antibody eculizumab.
2012). Pharmacists can significantly affect the prevention of Eculizumab is used in the treatment of paroxysmal nocturnal
HPV and related cancers by educating patients and screen- hemoglobinuria and atypical hemolytic uremic syndrome; it
ing for vaccination status. In addition, because most states works by interfering with complement-mediated hemolysis.
now allow pharmacists to administer the HPV vaccine, immu- The complement deficiency induced by eculizumab has been
nization can be performed at the time of assessment in the associated with cases of severe and deadly meningitis from
pharmacy to reduce the risk of lack of patient follow-through N. meningitidis and has prompted the FDA to require a boxed
on recommendations. warning and a Risk Evaluation and Mitigation Strategies
(REMS) program for this drug. According to the package
Meningococcus insert, a main component of the REMS program is adminis-
Overview of Infection Disease
tration of the quadrivalent meningococcal vaccine at least
14 days before initiating eculizumab. Although the prescribing
Meningococcal disease is caused by the bacterium Neisseria
information and REMS program do not specifically mention
meningitidis, an aerobic gram-negative diplococcus that can
vaccination with the newer serogroup B meningococcal vac-
cause severe infections including meningitis and bactere-
cine, it would be prudent to consider adding this vaccine in
mia. N. meningitidis strains are classified according to the
patients undergoing eculizumab therapy who are at risk of
antigenic structure of their polysaccharide capsule, with
all serotypes of meningococcal infection. In addition, eculi-
serotypes A, B, C, W135, X, and Y causing the most clinically
zumab increases the risk of infection with other encapsulated
important infections. Disease is spread by transmission of
bacteria, including H. influenzae and Streptococcus pneumo-
the bacteria from droplets and close contact with an infected
niae, so the need for vaccines against those agents should
or colonized individual. Patients most at risk of the invasive
also be assessed.
disease are those without a functional spleen, with comple-
ment deficiency, or living in crowded housing situations.
Pneumococcus
The disease generally has a rapid onset of fever, headache,
and stiff neck, and patients may also have nausea, vomiting, Overview of Infection Disease
photophobia, and confusion. Overall rates of meningococcal S. pneumoniae is a gram-positive aerobic bacterium that
disease are highest in children younger than 1 year, with a causes many types of illnesses, with the most severe mor-
second peak in adolescence associated with close contact bidity and mortality associated with pneumonia, bacteremia,
with classmates in school and dormitories on college cam- and meningitis. In the United States, an estimated 900,000
puses. Most clinical disease in the United States is caused people acquire pneumococcal pneumonia each year, with
by serogroup B (about 60%), followed by serogroups C and almost 50% of these patients requiring hospitalization and
Y (CDC 2015a). Periodic outbreaks have gained public atten- a mortality rate of 5%7%. An additional 3700 deaths annu-
tion in recent years, including several on college campuses ally are attributable to bacteremia or meningitis caused by
(Soeters 2015) and in urban populations of men who have sex S. pneumoniae. Since the introduction of the pneumococcal
with men (MDH 2015; CDC 2013a). vaccines, rates of infection and death from S. pneumoniae

have decreased substantially, both among the specific sero- order in which it appears, beginning at the head and ending
types covered by the vaccine and overall. For example, before in the extremities. Measles is generally self-limiting but can
PCV7, the incidence of PCV7-type invasive pneumococcal occasionally be severe, leading to complications including
disease was 80 cases per 100,000 in children younger than pneumonia, encephalopathy, and even death in a small pro-
5 years; this decreased to less than 1 case per 100,000 by portion of patients.
2007 (CDC.gov 2015a). The burden of measles has decreased significantly in the
United States since the vaccine was introduced in 1963, with
Recommended Administration Schedule the incidence decreasing by more than 95% from its peak.
Vaccination with a four-dose series of PCV13 is univer- However, several recent outbreaks have brought about a
sally recommended for all children beginning at 2 months resurgence of measles; in 2014 there were 668 cases across
of age. The PPSV is recommended for children 2 years and 27 states. Most of the outbreaks were associated with virus
older with high-risk conditions (e.g., sickle cell disease, ana- that was imported from an endemic area of the world, or by
tomic or functional asplenia, chronic cardiac, pulmonary or people who traveled to one of those areas. Because measles
renal disease, diabetes, CSF leaks, HIV infection, immuno- is highly contagious, a single source can quickly spread dis-
suppression, diseases associated with immunosuppressive ease throughout a community, particularly through patients
and/or radiation therapy, solid organ transplantation, those who are unvaccinated or under-vaccinated (CDC 2015a).
who have or will have a cochlear implant). In addition, chil- The outbreak that garnered the most attention was in
dren 618 years of age at high risk of pneumococcal disease Orange County, California, because it was associated with
should receive doses of both PCV13 (unless they have com- exposure to the virus at a Disney theme park. A total of 125
pleted the PCV13 series) and PPSV23, separated by at least confirmed measles cases were associated with this out-
8 weeks. break (Zipprich 2015).
In older children with high-risk conditions, extra attention Mumps is a virus in the Paramyxoviridae family that is
should be paid to the primary PCV series because these chil- spread by the respiratory route. The virus replicates in the
dren may or may not have received PCV13, given that until nasopharynx and surrounding lymph nodes, then spreads
2010, the routine vaccination consisted of PCV7. See Pink throughout the body in the bloodstream. After an initial pro-
Book Appendix A-15, Summary of Recommendations for drome, consisting of nonspecific symptoms of fever, malaise,
Child/Teen Immunization, for details of recommended timing myalgia, anorexia, and headache, mumps most commonly
of vaccine administration. manifests as parotitis. The inflammation can affect several
salivary glands and can be unilateral or bilateral. Orchitis
Vaccine-Specific Considerations can also occur in up to 50% of postpubescent males infected
In addition to the invasive infections that pneumococcal with mumps, which can lead to further complications includ-
vaccine was designed to prevent, including meningitis and ing testicular atrophy. Other serious complications, though
bacteremia, PCV has a benefit in reducing otitis media caused rare, can also occur, including meningitis, deafness, myocar-
by S. pneumoniae (Fortanier 2014). From a public health ditis, and death (CDC 2015a). After the introduction of routine
standpoint, this is an important benefit, given the frequency vaccination the incidence of mumps declined sharply to less
of otitis media in young children. However, data cannot be than 1% of previous rates. However, outbreaks have occurred
extrapolated to a patient-specific level because many organ- in the past few years, primarily attributed to communities
isms can cause otitis media. with low vaccination rates or to close contact in crowded set-
tings. Public interest in mumps spiked during a 2014 outbreak
Measles, Mumps, and Rubella
that occurred among players and staff in the National Hockey
Overview of Infection League (Ruderfer 2015).
Measles virus, a species in the genus Morbillivirus, caused Rubella virus, also known as German measles, is a viral
disease in almost all children in the pre-vaccine era. Measles, illness spread by the respiratory route. It manifests pri-
also known as rubeola, spreads by the respiratory route and marily as a mild illness with a primary feature of rash that
manifests systemically as the virus spreads throughout begins on the face and spreads down through the trunk and
the body. Typical early clinical features include a prodrome to the feet and hands, similar to measles. Systemic symp-
phase, which begins with a fever followed by the three Cs toms of rubella are generally mild and can include low-grade
(i.e., cough, coryza, and conjunctivitis). Koplik spots, which fever, malaise, lymphadenopathy, upper respiratory symp-
are punctate bluish white spots on mucous membranes, are toms, and arthralgias. The biggest concern with rubella, and
considered pathognomonic for measles. The generalized the primary motivation for vaccination against the virus, is
rash that occurs with measles typically begins at the hair- congenital rubella syndrome (CRS). Rubella infection early
line of the face and upper neck and then continues downward during a womans pregnancy can cause severe problems
and outward across the body until it reaches the hands and with the fetus and may lead to fetal death, spontaneous abor-
feet. The rash usually resolves after several days in the same tion, or preterm delivery. If the child survives the infection

and is born alive, CRS can affect all organ systems, with Recommended Administration Schedule
severity and location depending on the stage of gestation The recommended immunization regimen for varicella virus
when the infection occurred. The most common complica- is a two-dose series that is initiated at 12 months of age.
tion of CRS is permanent deafness, which can often be the Varivax should not be confused with Zostavax. Zostavax is
sole manifestation of the disease in an infant. Other compli- the zoster vaccine used in adults for shingles prevention and
cations of CRS include eye defects, cardiac defects, bone is about 14 times more potent.
alterations, liver damage, spleen damage, and mental retar-
Vaccine-Specific Considerations
dation (CDC 2015a).
Because varicella vaccine is a live-attenuated virus, all the
Recommended Administration Schedule considerations pertaining to immunosuppression and blood
The MMR vaccine is universally recommended for all chil- products for live vaccines apply. Of note, the vaccine con-
dren as a two-dose series beginning at 12 months of age, or tains gelatin and neomycin, so patients who are allergic to
for any child who has not yet completed the primary immuni- these components should not be vaccinated with varicella,
zation series. In addition, the MMR vaccine may be given to MMRV, or shingles (CDC 2015b). Occasionally, a child will
children as young as 6 months if they will be traveling outside develop a mild, localized rash resembling chickenpox after
the United States. These children should still subsequently varicella vaccination. When this occurs, concern for trans-
receive the full two-dose series according to the immuniza- mission exists because the virus, though attenuated, is
tion schedule (McLean 2013). actively replicating in vivo. In general, if the rash is limited
to maculopapular lesions, there is no risk of transmission.
Vaccine-Specific Considerations If the lesions become open vesicles, it is theoretically pos-
Because MMR is a live-attenuated virus vaccine, all the con- sible to transmit disease until they all crust over, although it
siderations pertaining to immunosuppression and blood is still quite rare. However, if vesicles develop after varicella
products for live vaccines apply. Of note, the vaccine con- vaccination, a noncontagious vaccine-induced rash cannot
tains gelatin and neomycin, so patients who are allergic be differentiated from a true varicella infection. Therefore,
to these components should not be vaccinated with MMR if a rash develops 721 days after vaccine administration,
(CDC 2015b). contact should be avoided with susceptible individuals or
Public concerns about the MMR vaccine causing autism immunocompromised patients who are at risk of severe com-
have been shown to be unfounded and based on fraudulent plications of disease until the rash resolves (IAC 2016).
work, as discussed previously (Retraction 2010). Some antiviral agents may interfere with the efficacy
of the varicella vaccine because, as a live vaccine, it
Varicella requires active replication to stimulate the immune system;
Overview of Infection Disease this can be impaired in the presence of antiviral medica-
tions active against varicella zoster virus (e.g., acyclovir,
Varicella (chickenpox) is caused by the varicella zoster virus.
ganciclovir). See Pink Book Appendix A-15, Summary of
This herpesvirus causes a pruritic rash that appears first on
Recommendations for Child/Teen Immunization, for more
the head and trunk and then spreads to the rest of the body.
specific recommendations on timing of antivirals around the
It progresses from macules to papules to vesicles before
vaccine (Hamborsky 2015).
finally crusting over and healing. It is highly infectious and
easily spreads person-to-person through aerosolized virus
Influenza
particles. Among household members and close contacts,
an estimated 90% of susceptible individuals will contract the Overview of Infection Disease
virus after exposure to an infected person. Influenza is a respiratory illness spread by respiratory drop-
Initial infection is generally mild, and symptoms resolve lets after an infected person coughs or sneezes. Generally a
without specific treatment, although occasionally, bacterial seasonal disease that peaks in the winter months, the exact
superinfection can cause severe complications. After initial timing and the length of influenza season vary with location
varicella zoster virus infection, the virus remains dormant and climate. Influenza is characterized by an abrupt onset
in the dorsal root ganglia of the nervous system and can of severe systemic and respiratory symptoms including, but
be reactivated later in life to cause herpes zoster (shingles) not limited to, fever, chills, myalgia, headache, malaise, non-
during periods of stress or decreased immunity. Before the productive cough, sore throat, and rhinitis. Uncomplicated
varicella vaccine was introduced in 1995, around 150,000 influenza generally resolves within 7 days; however, chil-
200,000 cases of varicella disease occurred annually, leading dren with comorbid conditions may have more severe or
to 100150 deaths each year. Significant declines of more prolonged disease or secondary bacterial infections. These
than 80%90% in both incidence and mortality from varicella complications and secondary infections can lead to signifi-
have occurred since widespread vaccination was initiated in cant morbidity and mortality, particularly from post-influenza
the United States in the 1990s (CDC 2015a). pneumonia or respiratory failure. In addition, febrile seizures

have been reported in up to 20% of children hospitalized with if the initial vaccine the child received contained exactly the
influenza (CDC 2015a). same influenza strains as the current season; then, a single
The influenza vaccine varies in efficacy each year because dose would be adequate. However, it is often difficult to deter-
of the variability in influenza strains circulating. Efficacy is mine this with certainty, so it is recommended to err on the
generally in the 50%60% range; however, in some recent side of caution and give the two-dose series to optimize effi-
years, it has been as low as 23% (CDC 2015a). Although this cacy (Grohskopf 2015).
is much lower than what we have come to expect from many
other types of vaccines, influenza vaccination can still play Vaccine-Specific Considerations
an important role in reducing the burden of influenza morbid- Influenza vaccines have traditionally been grown in chicken
ity and mortality. A recent Cochrane review found a number eggs; there is therefore a potential risk to patients with severe
needed to vaccinate of 3971 to prevent one case of influ- egg allergy. However, several studies have shown that even
enza or influenza-like illness, whereas adverse effects were patients with documented egg allergies have an extremely
similar to placebo (Demicheli 2014). In addition, prevention low chance of a severe allergic reaction, and even mild aller-
of influenza can reduce complications of the disease, includ- gic reactions to the influenza vaccine are uncommon (Des
ing pneumonia and associated hospitalizations (Grijalva Roches 2012). Current ACIP recommendations state that
2015). However, still less than one-half of eligible patients children with a history of egg allergy that includes only hives
in the United States receive the influenza vaccine each year, (but not anaphylaxis or angioedema) can be given IIV3 or IIV4
which further limits the vaccines potential to reduce influ- as long as they are monitored for at least 30 minutes after
enza illness and related complications. Pharmacists can vaccination by an appropriate health care provider. In addi-
help improve vaccination rates by educating patients and tion, patients who can tolerate eating lightly cooked eggs are
administering vaccinations throughout the influenza season unlikely to have a true allergy and can be administered IIV
(CDC 2015a). using the same general precautions. The LAIV formulation
has not been extensively studied in egg allergy and should
Recommended Administration Schedule be avoided until further information is available. Alternatively,
Annual vaccination against influenza at the beginning of there is a completely egg-free recombinant vaccine for-
each influenza season is universally recommended for all mulation, recombinant influenza vaccine trivalent (RIV3),
patients 6 months and older. The vaccine should be adminis- which can be administered to patients with any severity of
tered before the onset of influenza activity in the community. egg allergy. However, RIV3 is currently not approved for use
Vaccination should continue to be offered as long as influ- in pediatric patients, so any use in children younger than
enza viruses are circulating. No preference is given for 18 years would be off-label (Grohskopf 2015). Several clinical
quadrivalent or trivalent vaccine, and the 20152016 guide- trials assessing safety and immunogenicity in children have
lines removed the previous preference for LAIV over IIV in been completed, although the full results are not yet available
healthy children 28 years of age. The guidance now suggests at the time of writing this chapter (NIH 2015a, 2015b).
that any product that is available and for which the patient is A prevalent misconception about the influenza vaccine,
eligible should be administered. The rationale for this recom- and a common reason given for declining to be vaccinated, is
mendation is to decrease the chance of missed opportunity the concern that the vaccine can cause influenza illness. The
for vaccination because of waiting for the availability of a pre- inactivated injectable vaccine is a completely nonviable form
ferred product. In addition, evidence is conflicting regarding of the virus that cannot replicate, so it cannot cause illness.
the previously reported superiority of LAIV that had led ACIP However, the vaccine can cause adverse effects includ-
to give it a preferential recommendation in younger children ing low-grade fever, headaches, and muscle aches, which
(Grohskopf 2015). A recently published study reports that patients may falsely attribute to the influenza virus. Some
rates of influenza during the 20132014 season were actually patients may coincidentally contract influenza after vacci-
higher amongst children who received the LAIV compared to nation, but not from the vaccine itself. It takes 1014 days
those that received IIV (Chung 2016). to develop an adequate antibody response to the vaccine to
Children 6 months to 8 years of age require a second dose provide protection, so if patients are exposed to the virus dur-
of influenza vaccine at least 4 weeks after the first dose in ing this time, they may develop disease despite receiving the
the first season they are vaccinated to optimize response. vaccine. Other non-influenza viruses can also present with
Response rate after a single dose improves with age and similar symptoms, which could be mistaken by patients to be
varies by influenza serotype, but it improves with a second influenza disease.
dose for all serotypes in children younger than 9 years (Neuzil Although LAIV is an attenuated form that theoretically
2006). If a child in this age group previously received only a could cause illness, it is a weakened form of the virus and has
single dose in an influenza season, it is still recommended been adapted to replicate only in the colder temperatures of
that the child be given two doses in the current season to the nasal passages, so it cannot cause infection in the lungs.
ensure optimal response. The only exception to this would be Because of the small theoretical risk of causing disease,

however, LAIV is contraindicated in immunocompromised has declined since the vaccine was introduced. At its peak in
individuals, as are other live virus vaccines (CDC 2015a). the 1980s, the annual number of reported cases in the United
States was greater than 25,000, compared with around 3000
Hepatitis A cases in recent years. True incidence is estimated to be
Overview of Infection Disease 10-fold higher than these reported numbers because many
Hepatitis A is an RNA virus in the Picornaviridae family that people asymptomatically have the infection chronically
is transmitted by the fecal-oral route and causes an inflam- (CDC 2015a).
matory disease of the liver. Unlike some other hepatitis
Recommended Administration Schedule
viruses, hepatitis A virus is generally self-limiting and does
Vaccination with HepB is universally recommended for all
not progress to a chronic long-term infection. Symptoms
children as a three-dose series beginning at birth. Of note,
of the disease include nausea, anorexia, fever, malaise, and
this is the only vaccine that is routinely recommended in neo-
abdominal pain. Patients may also present with jaundice,
nates. All doses administered before 6 weeks of age should
scleral icterus, and elevated transaminases. Primary sources
be the monovalent HepB rather than combination products
of infection are close contact with an infected household
with any other vaccines. For catch-up vaccination in children
member or sex partner. In addition, outbreaks can occur in
who did not receive the initial vaccination series, the adult
the food industry when a food handler has the infection and
formulation with a higher amount of HepB antigen than the
spreads the virus through raw or undercooked foods.
pediatric vaccine may be used in children 11 years or older
Vaccination has significantly reduced the burden of hep-
(CDC 2015a).
atitis A disease, with an annual incidence of 25,00035,000
cases before universal vaccination, decreasing to less than Vaccine-Specific Considerations
2000 cases annually in recent years (CDC 2015a).
For infants born to hepatitis B virus antigen-positive moth-
Recommended Administration Schedule ers, hepatitis B immune globulin should also be administered
within 12 hours of birth plus the original required vaccine. In
The HepA vaccine is universally recommended for all children
these patients, postvaccination testing should be performed
beginning at 12 months of age, followed by a second dose at
12 months after the completion of at least three doses of
least 6 months later. Older children who have not yet been
HepB to ensure immunity (CDC 2015a).
vaccinated should follow the catch-up schedule to receive
The HepB vaccine can also be used for postexposure pro-
adequate protection against the virus (CDC 2015a).
phylaxis in children who have potentially been exposed to the
Vaccine-Specific Considerations virus and lack documented immunity. The vaccine can be
The HepA vaccine is preferred for postexposure prophylaxis given with or without immune globulin, depending on the hep-
in healthy patients 140 years of age who have been exposed atitis B status of the source and the vaccination status of the
to the virus in the previous 2 weeks. Immunocompromised patient (Mast 2006).
patients, those with preexisting liver disease, or those who
have contraindications to the vaccine must still use immune H. influenzae Type B
globulin rather than vaccination for postexposure prophy- Overview of Infection Disease
laxis because of decreased response to the vaccine. Children H. influenzae is a gram-negative coccobacillus that com-
who have previously received immune globulin should monly colonizes the respiratory tract and can cause invasive
still receive the routine HepA vaccine as recommended infections including pneumonia, bacteremia, meningitis,
(CDC 2015a). and epiglottitis, as well as relatively superficial infections
including otitis media and cellulitis. There are six strains of
Hepatitis B
H. influenzae with a polysaccharide capsule (types af), as
Overview of Infection Disease well as nonencapsulated (non-typeable) strains. Historically,
Hepatitis B virus causes an inflammatory disease of the liver. Hib has been associated with the most invasive infections
It is a double-stranded DNA virus in the Hepadnaviridae fam- and the greatest morbidity and mortality. Invasive Hib is
ily that is transmitted by blood or body fluids, most often associated with a mortality rate of 3%6%, and Hib menin-
through sexual contact or sharing needles with infected gitis can cause long-term sequelae, including hearing loss
individuals. Some people clear hepatitis B virus after initial and neurologic deficits in up to 20% of survivors. Before the
infection, but some will develop a long-term, chronic infec- introduction of the Hib vaccine, the annual incidence of Hib
tion. The frequency of developing a chronic infection declines disease was around 20,000 cases. The vaccine has dramat-
with age and occurs in about 90% of infants infected with ically decreased the incidence by more than 99% since its
hepatitis B virus compared with 2%6% of adults. Chronic introduction in the late 1980s. Most H. influenzae infections in
hepatitis B can cause significant morbidity, including cirrho- the United States are now from non-typeable strains that are
sis or hepatocellular carcinoma. The incidence of hepatitis B not covered by the vaccine (CDC 2015a).

Recommended Administration Schedule concentrated in Pakistan and Afghanistan, with sporadic
The Hib vaccine is universally recommended for all chil- cases still occurring in other parts of the Middle East and
dren beginning at age 2 months, with catch-up vaccination Africa (Global Polio 2015).
routinely recommended for unimmunized children up to
age 5 years. The number of total doses and schedule varies Recommended Administration Schedule
depending on the specific vaccine formulation used. ActHIB, The IPV is universally recommended as a four-dose series
MenHibrix, and Pentacel require a three-dose primary series beginning at age 2 months and as a catch-up vaccine for any-
followed by a booster dose of any Hib-containing vaccine. one younger than 18 years who has not completed the series
PedvaxHIB and COMVAX require a two-dose series followed (CDC 2015b). The IPV is the only polio vaccine product that
by a booster dose of any Hib-containing vaccine. The dif- has been available in the United States since 2000. However,
ferent number of doses required is because of the varying the oral polio vaccine is used in areas of the world where
levels of immunogenicity to the vaccines with different car- endemic polio is still circulating (CDC 2015a).
rier proteins in their formulation (Kelly 2004). Select high-risk
children older than 5 years should also be given the Hib vac- Vaccine-Specific Considerations
cine if they are not already immune, including patients with Of note, although IPV protects the recipient from developing
asplenia or HIV (Briere 2014). polio disease, if a child immunized with IPV travels to an area
of the world where polio is endemic and is exposed, the virus
Vaccine-Specific Considerations may still be able to actively replicate in the intestinal tract
Although is it generally recommended to complete a vac- and be passed on to others. General precautions, including
cination series with the same vaccine formulation, if the good hand hygiene, should be taken on return from travel to
same formulation is not available for subsequent doses, polio-endemic areas (CDC 2015a).
any other Hib-containing vaccine may be administered
and still be considered valid. An exception is the Hiberix Rotavirus
vaccine, which is only indicated for use as a booster dose
Overview of Infection Disease
in children 12 months to 4 years of age who have already
Rotavirus commonly causes intestinal disease in pediatric
received at least one prior dose of Hib-containing vaccine
patients, particularly infants and young children. Infection
(CDC 2015a).
with rotavirus manifests as severe watery diarrhea, often
with vomiting, fever, and abdominal pain. Complications
Polio
from rotavirus are primarily because of dehydration from
Overview of Infection Disease excessive diarrhea and vomiting. Rotavirus is spread by the
Polio is a potentially fatal infection that has historically fecal-oral route and is most prevalent during the winter and
caused significant morbidity and mortality throughout the spring months (CDC 2015a).
world. Polio is an RNA enterovirus in the Picornaviridae fam-
ily that is spread by the fecal-oral route. Most infections Recommended Administration Schedule
are asymptomatic or subclinical; however, in around 5% of The RV is universally recommended for all children beginning
infections, manifestations such as fever, pharyngitis, gas- at 2 months of age. If using RotaTeq, three doses are neces-
troenteritis, and flu-like symptoms occur. In addition, in a sary, whereas Rotarix requires only two doses. No preference
smaller percentage of patients (0.5%), polio can invade the for one formulation or the other is given by ACIP, and both
CNS, resulting in irreversible paralysis by damage to dorsal are effective at preventing disease. It is acceptable to use a
root ganglia and motor and autonomic neurons of the spinal different formulation on subsequent administrations, but if a
cord and gray matter of the brain. The neuronal damage can RotaTeq product is used for any of the doses, a total of three
manifest as flaccid paralysis of the extremities, respiratory doses of RV should be given. Of note, the RV series should not
failure, and neurogenic bladder (CDC 2015a). be initiated after age 15 weeks. The maximal age for the final
Before the introduction of polio vaccine, the virus was dose of the series is 8 months, after which no further doses
responsible for more than 15,000 cases of paralysis annu- should be given even if the series has not been completed
ally in the United States. Because of diligent vaccination (Cortese 2009).
efforts, endogenous polio was eradicated from the United
States in 1979. Vaccination continues to be recommended Vaccine-Specific Considerations
because of the existence of polio disease in other parts of The RV is generally well tolerated, with GI upset being most
the world that can potentially be brought into the country prevalent adverse effect. A rare but serious complication of
through travelers. The overall incidence of polio disease has RV is intussusception. This complication occurred more com-
declined by more than 99% since the launch of global polio monly with a previous formulation of RV, RotaShield, which
eradication efforts in 1988 (CDC 2015a). Several hundred was removed from the market in 1999. Current vaccines pose
cases still occur annually throughout the world, primarily a much lower risk (CDC 1999).

CONCLUSION REFERENCES
Infections with VPDs remain a significant cause of morbid- American Academy of Pediatrics (AAP). Immunization.
ity and mortality in the United States and throughout the [homepage on the Internet]. 2016.
world. Improvement in vaccine coverage will continue to American Pharmacists Association (APhA). Guidelines for
reduce the burden of, and in some cases eliminate, VPDs. Pharmacy-Based Immunization Advocacy.
Pharmacists impact on routine pediatric immunizations
American Pharmacists Association (APhA); NASPA
will continue to evolve as authorization to vaccinate chil-
Foundation. 2015. Pharmacist-Administered Vaccines:
dren expands across state laws and regulations. With this
Based upon APhA/NASPA Survey of State IZ Laws/Rules.
increasing role comes the added responsibility of assessing
the appropriateness of vaccines according to recommended Briere EC, Rubin L, Moro PL, et al. CDC. Prevention and
CDC schedules and determining risks and benefits among all control of Haemophilus influenzae type b disease: recom-
mendation of the Advisory Committee on Immunization
vaccines regardless of patient complexity. In states that do
Practices (ACIP) recommendations and reports. MMWR
not permit them to vaccinate children, pharmacists should 2014; 63:1-14.
still assess and refer all patients for appropriate vaccines.
Sustaining proper adherence to vaccine schedules is a con- Butler K, Lewis GP. The effect of anti-inflammatory com-
pound on the biochemical changes in the Arthus reaction.
tinuous public health problem; pharmacists should educate
J Pathol 1976; 119:175-82.
families about the importance of vaccination and be able to
address concerns and dispel misconceptions that may lead CDC. Birth-18 Years and Catch-up Immunization Schedules.
to vaccine refusal. 2016.
CDC. Parents Guide to Childhood Immunizations. 2015a.
CDC. Withdrawal of rotavirus vaccine recommendation.

MMWR 1999; 48:1007.
Practice Points
Infectious diseases have been a source of great mor- CDC. Recommended adult immunization schedule United
bidity and mortality throughout history. The introduction States, 2011. MMWR 2011a; 60:49-57.
of vaccines to prevent infections has proven to be one of
the greatest medical achievements to date. Pharmacists CDC. Notes from the field: serogroup C invasive meningo-
should be familiar with the scientific, social, and politi- coccal disease among men who have sex with men New
cal issues related to vaccines and public health: York City, 2010-2012. MMWR 2013a; 61:1048.
Vaccines induce protection from disease by provoking an CDC. Updated recommendations for use of tetanus toxoid,
immune response by administration of microorganisms, or
reduced diphtheria toxoid, and acellular pertussis vac-
fractions of microorganisms, into the body.
cine (Tdap) in pregnant women Advisory Committee
Vaccines can be classified in various ways, including live on Immunization Practices (ACIP), 2012. MMWR 2013b;
versus inactivated versus toxoid and polysaccharide versus
62:131-5.
protein conjugated. Each type differs in its consider-
ations regarding the mechanism of provoking an immune CDC. Updated recommendations for use of tetanus toxoid,
response, number of doses required, duration of immunity, reduced diphtheria toxoid, and acellular pertussis vaccine
and patient eligibility criteria. (Tdap) in pregnant women and persons who have or antic-
Pharmacists play several important roles related to pedi- ipate having close contact with an infant aged <12 months
atric immunization, including administering vaccines, as- Advisory Committee on Immunization Practices (ACIP),
sessing vaccine eligibility, and providing patient education, 2011. MMWR 2011b; 60:1424-6.
provider guidance, and legislative advocacy.
Recommended pediatric immunization schedules are pub- CDC. CDC A-Z index.
lished annually by the CDC according to the best available
evidence regarding the efficacy and safety of available CDC. Vaccines & Immunizations. 2016.
vaccines.
Adherence to these recommended schedules is the best Chung JR, Flannery B, Thompson MG, et al. Seasonal effec-
way to reduce the burden of VPDs. tiveness of live attenuated and inactivated influenza
Pharmacists play a critical role in educating the public vaccine. Pediatrics 2016; 137:1-10.
about vaccinations and clarifying myths and misconcep-
Cohn AC, MacNeil JR, Clark TA, et al. Prevention and con-
tions that patients may have.
trol of meningococcal disease: recommendations of the
Pharmacists should be able to interpret immunization
schedules and recommend appropriate vaccines according
Advisory Committee on Immunization Practices (ACIP).
to patient-specific factors. MMWR 2013; 62:1-22.
In addition to general considerations that pertain to all vac- Cortese MM, Parashar UD. Centers for Disease Control and
cines, each individual vaccine has specific considerations
Prevention. Prevention of rotavirus gastroenteritis among
related to efficacy, safety, formulation, immunization
infants and children: recommendations of the ACIP.
timing, and technique.
MMWR 2009; 58:1-25.

Das RR, Panigrahi I, Naik SS. The effect of prophylactic Healthychildren.org. Vaccine Studies: Examine the Evidence.
antipyretic administration on post-vaccination adverse
reactions and antibody response in children: a systematic Healy CM, Pickering LK. How to communicate with vaccine-
review. PLoS One 2014; 9:e10662. hesitant parents. Pediatrics 2011; 127:S127133.
Des Roches A, Paradis L, Gagnon R, et al. Egg-allergic Hill HA, Elam-Evans LD, Yankey D, et al. National, state, and
patients can be safely vaccinated against influenza. selected Local area vaccination coverage among children
J Allergy Clinical Immunol 2012; 130:1213-6. aged 1935 months United States, 2014. MMWR 2015;
63:889-96.
Dobson SR, McNeil S, Dionne M, et al., Immunogenicity of 2
doses of HPV vaccine in younger adolescents vs 3 doses Immunization Action Coalition (IAC). MMR Vaccine Does Not
in young women. JAMA 2013; 309:1793-802. Cause Autism: Examine the evidence! 2013.
Eickhoff TC, Myers M. Workshop summary: aluminum in Immunization Action Coalition (IAC). Ask the Experts:
vaccines. Vaccine 2002; 20:S1-4. Topics. 2016.
Faulkner A, Skoff T, Martin S, et al. Pertussis. MPH Manual Jefferson T, Di Pietrantonj C, Rivetti A, et al. Vaccines for pre-
for the Surveillance of Vaccine-Preventable Diseases. venting influenza in healthy adults. Cochrane Database
Atlanta: CDC, 2015:10.1-12. Syst Rev 2014; 3:CD001269.
Fernndez ME, Le YL, Fernndez-Espada N, et al. Knowledge, Jena AB, Goldman DP, Seabury SA. Incidence of sexually
attitudes, and beliefs about human papillomavirus (HPV) transmitted infections after human papillomavirus
vaccination among Puerto Rican mothers and daughters, vaccination among adolescent females. JAMA Intern Med
2010: a qualitative study. Prev Chronic Dis 2014; 11:1-8. 2015;175:617-23.
Fisher MC, Bocchini JA. Adhering to vaccine schedule is Kelly DF, Moxon ER, Pollard AJ. Haemophilus influenzae type
best way to protect children from disease. AAP News b conjugate vaccines. Immunology 2004;113:163-74.
2009; 30:1-2. Kriemer AR, Struyf F, Del Rosario-Raymundo MR, et al.
Folaranmi T, Rubin L, Martin SW, et al. Use of Serogroup B Efficacy of fewer than three doses of an HPV-16/18 AS04-
Meningococcal Vaccines in Persons Aged 10 Years at adjuvanted vaccine: combined analysis of data from the
Increased Risk for Serogroup B Meningococcal Disease: Costa Rica Vaccine and PATRICIA trials. Lancet Oncol
Recommendations of the Advisory Committee on 2015; 16:776-86.
Immunization Practices, 2015. MMWR 2015; 64:608-12. Kroger AT, Sumaya CV, Pickering LK, et al. Centers for
Fortanier AC, Venekamp RP, Boonacker CWB, et al. Disease Control and Prevention. General recommenda-
Pneumococcal conjugate vaccines for preventing otitis tions on immunization: recommendations of the Advisory
media. Cochrane Database Syst Rev 2014; 4:CD001480. Committee on Immunization Practices (ACIP). MMWR
2011; 60:1-61.
Gangarosa EJ, Galazka AM, Wolfe CR, et al. Impact of
anti-vaccine movements on pertussis control: the untold Liddon NC, Leichliter JS, Markowitz LE. Human papilloma-
story. Lancet 1998; 351:356-61. virus vaccine and sexual behavior among adolescent and
young women. Am Journal Prev Med 2012; 42:44-52.
Gellin BG, Maiback EW, Marcuse EK. Do parents understand
immunizations? A national telephone survey. Pediatrics Markowitz LE, Dunne EF, Saraiya M, et al. Centers for
2000; 106:1097-102. Disease Control and Prevention. Human papillomavirus
vaccination: recommendations of the Advisory Committee
Global Polio Eradication Initiative. Data and Monitoring: on Immunization Practices (ACIP). MMWR 2014; 63:1-30.
Polio This Week.
Mast EE, Margolis HS, Fiore AE, et al. A comprehensive
Grijalva CG, Zhu Y, Williams DJ, et al. Association between immunization strategy to eliminate transmission of
hospitalization with community-acquired laboratory-con- hepatitis B virus infection in the United States: recom-
firmed influenza pneumonia and prior receipt of influenza mendations of the Advisory Committee on Immunization
vaccination. JAMA 2015; 314:1488-97. Practices (ACIP) part 1: immunization of infants, children,
and adolescents. MMWR 2006; 55:30-3.
Grohskopf LA, Sokolow LZ, Olsen SJ, et al. Prevention and
control of influenza with vaccines: recommendations McLean HQ, Fiebelkorn AP, Temte JL, Centers for Disease
of the Advisory Committee on Immunization Practices, Control and Prevention, et al. Prevention of measles,
United States, 201516 influenza season. MMWR 2015; rubella, congenital rubella syndrome, and mumps, 2013
64:818-25. summary: recommendations of the ACIP. MMWR 2013;
62:1-34.
Guide to Community Preventive Services. Increasing appro-
priate vaccination. 2016. Minnesota Department of Health (MDH). Meningococcal
Meningitis: 2015
Hamborsky J, Kroger A, Wolfe C, eds. Epidemiology and
Prevention of Vaccine-Preventable Diseases. The Pink Book, Neuzil KM, Jackson LA, Nelson J, et al. Immunogenicity and
13th ed. Washington, DC: Public Health Foundation, 2015. reactogenicity of 1 versus 2 doses of trivalent inactivated

influenza vaccine in vaccine-nave 5-8 year old children. Shatz DV, Schinsky MF, Pais LB, et al. Immune responses of
J Infect Dis 2006; 194:1302-9. splenectomized trauma patients to the 23-valent pneumo-
coccal polysaccharide vaccine at 1 versus 7 versus
Ng M, How C. Childhood immunisation. Singapore Med J 14 days after splenectomy. J Trauma 1998; 44:760-5.
2014; 55:12-7.
Soeters HM, McNamara LA, Whaley M, et al. Serogroup B
NIH. Immunogenicity and safety of FluBlok trivalent recom- meningococcal disease outbreak and carriage evaluation
binant hemagglutinin influenza vaccine in healthy at a college Rhode Island, 2015. MMWR 2015; 64:606-7.
pediatrics. ClinicalTrials.gov Bethesda, MD: National
Library of Medicine (US), 2000a. Sullivan JE, Farrar HC. Section on Clinical Pharmacology and
Therapeutics; Committee on Drugs. Fever and Antipyretic
NIH. Safety, reactogenicity and immunogenicity of Flublok Use in Children. Pediatrics 2011; 127:580-7.
quadrivalent (recombinant influenza vaccine, seasonal
formulation). (NCT01959945). ClinicalTrials.gov, Bethesda, World Health Organization. Diphtheria Reported Cases. 2015.
MD: National Library of Medicine (US), 2000b.
World Health Organization. Human papillomavirus vaccines:
Offit PA, Moser CA. The problem with Dr Bobs alternative WHO position paper, October 2014. Wkly Epidemiol Rec
vaccine schedule. Pediatrics 2009; 123:e164-9. 2014; 43:465-92.
Offit PA, Quarles J, Gerber MA, et al. Addressing parents Zipprich J, Winter K, Hacker J, et al. Measles outbreak
concerns: do multiple vaccines overwhelm or weaken the California, December 2014-February 2015. MMWR 2015;
infants immune system? Pediatrics 2002;109:124-9. 64:153-4.
Petrosky E, Bocchini JA, Hariri S, et al. Use of 9-valent
human papillomavirus (HPV) vaccine: updated HPV vac-
cination recommendations of the Advisory Committee on
Immunization Practices. MMWR 2015; 64:300-4.
Reagan-Steiner S, Yankey D, Jeyarajah J, et al. National,

regional, state, and selected local area vaccination cover-
age among adolescents aged 1317 years United States,
2014. MMWR 2015; 64:784-92.
Retraction ileal-lymphoid nodular hyperplasia, non-

specific colitis, and pervasive developmental disorder in
children. Lancet 2010; 375:445.
Roberts W, Harford M. Immunization and children at risk for

autism. Paediatr Child Health 2002; 7:623-32.
Robinson CL. Advisory Committee on Immunization

Practices recommended immunization schedules for
persons aged 0 through 18 years United States, 2016.
MMWR 2016; 65:86-7.
Rosenblatt AE, Stein SL. Cutaneous reactions to vaccina-

tions. Clin Dermatol 2015; 33:327-32.
Rubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA clinical

practice guideline for vaccination of the immunocompro-
mised host. Clin Infect Dis 2014; 58:309-18.
Ruderfer D, Krilov LR. Vaccine-preventable outbreaks: still

with use after all these years. Pediatr Ann 2015; 44:e76-81.
Satterwhite CL, Torrone E, Meites E, et al. Sexually trans-

mitted infections among US women and men: prevalence
and incidence estimates; 2008. Sex Transm Dis 2013;
40:187-93.
Schmitt BD; for Seattle Childrens Hospital Research

Foundation. Should Your Child See a Doctor: Immunization
Reactions. 2015.
Seither R, Masalovich S, Knighton CL, et al. Vaccination cov-

erage among children in kindergarten United States,
2013-14 school year. MMWR 2014; 63:913-20.

Self-Assessment Questions
1. A 12-year-old boy with no significant medical history 4. A 4-year-old girl (weight 15 kg) with asthma presents to
comes to your clinic for a routine checkup. After review- your clinic for a checkup. She is on day 4 of her second
ing his medical chart and immunization history, you 5-day course of prednisolone solution (30 mg/day) for an
recommend that he be given tetanus, diphtheria, and asthma exacerbation. The pediatrician plans to admin-
acellular pertussis vaccine (Tdap), human papillomavi- ister the vaccines recommended for 4-year-olds but has
rus 9 vaccine (HPV9), and meningococcal quadrivalent concerns about possible contraindications to live vac-
vaccine (MenACWY-D) today. His mother states that he cines, including the measles, mumps, and rubella (MMR)
needs the Tdap and MenACWY-D vaccines but not the and varicella vaccines. Which one of the following is best
HPV9 vaccine because he is not yet sexually active. to recommend for this patient?
Which one of the following is the best response to give
A. Wait 1 month after completion of prednisone, then
this patients mother?
administer MMR and V vaccines separately.
A. Recommend vaccination with HPV2 today and B. Wait 1 month after completion of prednisone, then
recommend returning for HPV9 when he is sexually administer MMRV combination vaccine.
active. C. Administer MMR and varicella vaccines separately
B. Emphasize the importance of giving MenACWY-D today.
at the same time as the HPV vaccine for optimal D. Administer MMRV combination vaccine today.
efficacy.
C. Recommend that the HPV9 vaccine be given today Questions 5 and 6 pertain to the following case.
because of the importance of developing immunity J.K. is a 34-year-old woman who is 30 weeks pregnant with
to HPV early. her second child. She has gestational diabetes but no other
D. Emphasize that all recommended vaccines should significant medical history. Her husband, R.K., and 3-year-old
be given today because that is what the vaccine son, A.L., accompany her to her clinic visit in October. R.K. is
schedule recommends. a 37-year-old man with a medical history of hypertension and
hypercholesterolemia. A.L. is up to date with his vaccinations
Questions 2 and 3 pertain to the following case. and has a history of egg allergy, but he can eat scrambled
M.M. is 10-year-old boy who is up to date on all of his routine eggs. J.K. and R.K currently live alone with their son, but R.K.s
childhood vaccinations, including pneumococcal conju- mother (G.M.) will be moving in with them to help care for the
gate vaccine 7 (PCV7). He is brought to the ED after being in child when it is born. G.M is a 74-year-old woman with osteo-
a motor vehicle crash. The physician determines that there arthritis, hypertension, heart failure, and chronic obstructive
is internal organ damage and decides M.M. needs an emer- pulmonary disease.
gency splenectomy.
5. The most recent tetanus-containing vaccine received
2. Which one of the following vaccines and timing of vacci- by each of the family members is as follows: J.K. Tdap
nation is best to recommend for M.M.? 9 years ago and 3 years ago; R.K. tetanus and diphtheria
(Td) 4 years ago; G.M. Td 10 years ago; and A.L. diphthe-
A. Meningococcal, pneumococcal, and Haemophilus
ria, tetanus, and pertussis (DTaP) 2 years ago. Which one
influenzae type B (Hib) as soon as possible
of the following is best to recommend regarding who in
B. Meningococcal and pneumococcal as soon as
this family should receive Tdap at this time?
possible
C. Meningococcal, pneumococcal, and Hib at least A. J.K., R.K., and G.M.
14 days after surgery B. J.K. and G.M.
D. Meningococcal and pneumococcal at least 14 days C. R.K. and G.M.
after surgery D. G.M. only.
3. Which one of the following is best to recommend for 6. Which one of the following is the most appropriate influ-
pneumococcal vaccination administration in M.M.? enza vaccine for A.L. today, assuming all are readily
available in the clinic?
A. PCV13 only
B. PCV13 first, followed by PPSV23 8 weeks later A. Inactivated influenza vaccine trivalent (IIV3)
C. PPSV13 first, followed by PCV23 12 weeks later B. Inactivated influenza vaccine quadrivalent (IIV4)
D. PPSV23 only C. Live attenuated influenza vaccine (LAIV4)
D. Recombinant influenza vaccine trivalent (RIV3)

7. For which one of the following patients would it be best C. Give immunoglobulin for hepatitis A only.
to withhold varicella vaccine? D. Give HepA vaccine only.
A. A 2-year-old girl with asthma who received the MMR
vaccine 14 days ago Questions 11 and 12 pertain to the following case.
B. A 4-year-old girl currently receiving amoxicillin/ B.B. is in the clinic for his 4-month-old checkup. The boys
clavulanate for otitis media medical history includes prematurity (born at 28 weeks) and
C. A 6-year-old boy with chronic kidney disease and a a complex neonatal ICU (NICU) stay. Currently, B.B. is sta-
glomerular filtration rate of 30 mL/minute/1.73 m2 ble and has diagnoses of bronchopulmonary dysplasia (BPD)
D. A 12-year-old boy with HIV and a CD4+ count of 600 (on budesonide), gastroesophageal reflux disease (on lanso-
cells/mL (25%) prazole), and developmental delay. B.B. received HepB at
birth, but his mother refused 2-month vaccines during the
8. For community pharmacists in states that do not permit
NICU stay. The mother again refuses vaccines at this visit
pharmacists to vaccinate pediatric patients, which one
because she is concerned that receiving all the vaccines at
of the following strategies would have the most imme-
once will overwhelm B.B.s immune system and he will end
diate effect on increasing vaccination coverage among
up in the hospital.
their patients?
11. Which one of the following approaches would best
A. Organize a petition to lobby the state legislature to
ensure B.B. receives all the recommended vaccines?
expand the age group of patients that pharmacists
are allowed to vaccinate. A. Provide his mother with educational materials and
B. Evaluate each childs profile to evaluate which honor her vaccine refusal.
vaccines should be administered and communicate B. Recommend an alternative vaccine schedule so that
this information to the parent and pediatrician. he can receive vaccines over an extended period
C. Place informational brochures about vaccine- rather than all at once.
preventable illnesses in every prescription bag that C. Administer DTaP and PCV13 because he is less likely
is dispensed from the pharmacy. to be protected from these diseases through herd
D. Play informational videos in the waiting area of immunity.
the pharmacy with guidance on recommended D. Educate the mother about her misconceptions and
immunization schedules. reinforce that it is safe and effective to give all the
recommended vaccines at this visit.
9. An 18-month-old girl is brought to the clinic by her mother
for a routine checkup in late September. You determine 12. If B.B.s mother agrees to receive all vaccines today and
that the child is due for vaccination with hepatitis B vac- future vaccines on schedule, which one of the following
cine (HepB), DTaP, inactivated polio vaccine (IPV), IIV, would be the best recommendation for when B.B. should
and hepatitis A vaccine (HepA). Which one of the follow- return for catch-up vaccines and which vaccines should
ing is best to administer to this patient today? be given?
A. Pediarix (DTaP-IPV-HepB), IIV, and HepA vaccines A. 8 weeks to receive DTaP, IPV, Hib, HepB, rotavirus
B. Kinrix (DTaP-IPV), IIV, and Twinrix (HepA-HepB) vaccine (RV), and Prevnar
vaccines B. 4 weeks to receive DTaP, IPV, Hib, RV, and Prevnar
C. Pediarix (DTaP-IPV-HepB) and HepA vaccines; and 8 weeks to receive HepB
advise the mother to return after November 1 for IIV C. 4 weeks to receive DTaP, IPV, Hib, HepB, and Prevnar
D. DTaP, IPV, HepB, IIV, and HepA vaccines D. 4 weeks to receive DTaP, IPV, Hib, and Prevnar and
8 weeks to receive HepB
10. An outbreak of hepatitis A is reported in a local pizza
shop related to a cook who was infected with the virus. 13. An infant girl was born at 24 weeks gestation; she is
A 7-year-old boy attended a birthday party and ate now aged 7 weeks and 5 days and is stable in the NICU.
lunch at the restaurant 5 days ago. He is brought in by Her current diagnoses include BPD. She receives budes-
his mother, who requests postexposure prophylaxis. onide, chlorothiazide, and potassium chloride. Which
The boy has never received the HepA vaccine. Which one of the following is best to recommend regarding this
one of the following recommendations is best for this patients vaccines?
patient? A. Hold all vaccines until she is corrected to full term.
A. Do not give postexposure prophylaxis. B. Hold all vaccines until she is 2 months old.
B. Give immunoglobulin for hepatitis A and HepA C. Give DTaP, IPV, Hib, HepB, RV, and Prevnar.
vaccine. D. Give DTaP, IPV, Hib, HepB, and Prevnar.

14. A 48-month-old boy with a history of febrile seizures is PCV13 2 months, 4 months, 6 months, 15 months
to receive DTaP-IPV, MMR, and varicella today. Which IPV 2 months, 4 months, 15 months
one of the following is best to recommend for this MMRV 15 months
patient? HepA 15 months, 24 months
A. Give prophylactic acetaminophen, and give MMRV Which one of the following vaccines is best to recom-
combination. mend for this patient to receive today?
B. Give prophylactic acetaminophen, and give MMR
A. DTaP, IPV, MMRV, PPSV23
and varicella as separate vaccinations.
B. DTaP, IPV, MMRV
C. Do not give prophylactic acetaminophen, and give
C. DTaP, IPV, PPSV23
MMRV combination.
D. DTaP, IPV
D. Do not give prophylactic acetaminophen, and give
MMR and varicella as separate vaccinations. 17. You wish to advocate for expansion of pharmacist autho-
rization to administer vaccines in pediatric patients. In
15. A 15-month-old girl received the MMRV vaccine 10 days which one of the following age ranges would pharma-
ago. Two days ago, she developed a rash on her trunk cists be most likely to demonstrate the greatest effect
that consists of five or six vesicular lesions. Her mother on vaccination adherence rates?
calls the clinic and asks if she should be concerned
A. 018 months
about infection and if they should take any precautions.
B. 1935 months
Which one of the following is the best response to this
C. 46 years
inquiry?
D. 1317 years
A. MMRV cannot cause infection, so the rash is likely
18. A 4-year-old girl (DOB August 3, 2011) is about to start
an allergy. Give your daughter diphenhydramine,
kindergarten. Her parents come to the office on Septem-
apply 1% hydrocortisone cream, and the infection
ber 8, 2015, because the school called to say that the
should improve.
girls cant attend until she receives her 4-year-old vac-
B. The rash is likely a low-level infection caused by the
cines. The mother is irate and states that the girl already
weakened measles virus in the vaccine. No cases of
received them. The state law does not count vaccines
disease transmission from a rash like this have been
valid if they are administered any earlier than the recom-
reported, so no extra precautions are needed.
mended minimum age or interval by the CDC schedule. A
C. The rash is likely a low-level infection caused by the
review of the patients record shows the following:
weakened varicella virus in the vaccine. No cases of
disease transmission from a rash like this have been
10/4/11 Pediarix, Comvax, Prevnar, RV
reported, so no extra precautions are needed.
12/8/11 Pediarix, Comvax, Prevnar, RV
D. It is impossible to distinguish a non-contagious 2/6/12 Pediarix, Prevnar, RV
vaccine-induced rash from a true varicella infection. 8/20/12 Prevnar, HepA, MMR, varicella
Keep her isolated from susceptible individuals until 12/5/12 Hib, DTaP
the vesicular lesions crust over. 8/8/13 HepA
8/1/15 Varicella, Kinrix
16. A 4-year-old boy is in your clinic in late July for a rou-
8/28/15 MMR
tine checkup. His medical history is significant for
asthma, which is controlled with montelukast and Which one of the following would best resolve this issue?
as-needed albuterol. He received rabies immune glob-
A. Tell the parents that you will call the school and
ulin and vaccine in early May after being exposed to a
inform them the vaccines she received are still
raccoon at the family cabin in the woods. His mother
efficacious and she can return to school.
asks which vaccines he should receive today to pre-
B. Apologize to the parents and administer the Kinrix
pare him for attending prekindergarten this fall. She
today, and follow school policy for filling out a
states that he has kept on schedule with all of his rou-
temporary medical exemption for MMR.
tine vaccinations to date. His vaccine history shows
C. Apologize to the parents and administer the Kinrix
the following:
today, and follow school policy for filling out a
temporary medical exemption for Varicella.
HepB 0 months, 2 months, 6 months
RV 2 months, 4 months D. Apologize to the parents and administer the
DTaP 2 months, 4 months, 6 months, 15 months Kinrix today, and follow school policy for filling
Hib 2 months, 4 months, 6 months, 15 months out a temporary medical exemption for MMR and
varicella.

19. A 13-year-old boy who has no significant medical his-
tory and is not sexually active is in the clinic for an initial
checkup. On questioning, the parents report that the
child is up to date and was vaccinated by the previous
pediatrician, but the office permanently closed, and the
vaccination record is unavailable. The parents do not
want to repeat vaccines and only consent to six vaccines
being given at one time. Which one of the following vac-
cines would be best to administer to this patient today?
A. Give Tdap, HPV, Menactra, HepB, MMR, and varicella.
B. Give Tdap, Menactra, HepB, HepA, IPV, and MMR.
C. Give Tdap, IPV, Menactra, HPV, Twinrix, and MMRV.
D. Give no vaccines and rely on the parents history
that he is up to date.
20. A 12-month-old boy is brought to the pharmacy by his
parents. Eight hours earlier, the boy received his routine
vaccines (Prevnar, HepA, MMR, and varicella). Now, his
parents report that the childs temperature is 101F and
that he is sleeping more than usual. The parents also
state that they think his arms hurt, because he whines
when they touch his arms. Which one of the following is
the best action to take for this patient?
A. Report these adverse effects to VAERS and send the
child to his physician for workup.
B. Report these adverse effects to VAERS and
recommend ibuprofen or acetaminophen.
C. Do not report to VAERS and recommend ibuprofen
or acetaminophen.
D. Do not report to VAERS and send the child to his
physician for further workup.

Learner Chapter Evaluation: Routine Childhood Immunizations.
As you take the posttest for this chapter, also evaluate the Use the 5-point scale to indicate whether this chapter pre-
materials quality and usefulness, as well as the achievement pared you to accomplish the following learning objectives:
of learning objectives. Rate each item using this 5-point scale:
12. Distinguish the considerations for administering live ver-
Strongly agree sus inactivated vaccines.
Agree 13. Assess the role of a pharmacist in promoting the vacci-
Neutral nation of pediatric patients to reduce the global burden
Disagree of vaccine-preventable infections.
Strongly disagree 14. Evaluate the current evidence to educate patients and
caregivers about vaccination considerations, including
1. The content of the chapter met my educational needs. safety, efficacy, and common misconceptions.
2. The content of the chapter satisfied my expectations. 15. Justify the role of combination vaccines for the pediatric
population.
3. The author presented the chapter content effectively.
16. Given a pediatric case, develop a vaccine administration
4. The content of the chapter was relevant to my practice plan using current vaccination recommendations.
and presented at the appropriate depth and scope.
17. Distinguish the similarities and differences in childhood
5. The content of the chapter was objective and balanced. vaccine availability, administration, efficacy in disease
6. The content of the chapter is free of bias, promotion, or prevention, adverse effects, contraindications, and
advertisement of commercial products. warnings.
7. The content of the chapter was useful to me. 18. Please provide any specific comments related to any
8. The teaching and learning methods used in the chapter perceptions of bias, promotion, or advertisement of
were effective. commercial products.
9. The active learning methods used in the chapter were 19. Please expand on any of your above responses, and/or
effective. provide any additional comments regarding this chapter:
10. The learning assessment activities used in the chapter

were effective.
11. The chapter was effective overall.

Vaccine Development and
Future Targets
By April Yarbrough, Pharm.D., BCPS; and Scott James, M.D.
Reviewed by Jessica Cottreau, Pharm.D., BCPS; and Ashli Rasmussen, Pharm.D., BCPS
LEARNING OBJECTIVES
1. Design an effective strategy for developing a new vaccine.

2. Develop an appropriate strategy to determine which of the newer vaccines can be considered for frontline health care
employees and/or patients.
3. Evaluate current evidence to determine the appropriateness of maternal vaccinations.
4. Devise a guideline for alternative vaccine administration to pediatric and adult patients.
INTRODUCTION
The story of vaccines to prevent infectious diseases in humans pre-
CMV Cytomegalovirus
dates Edward Jenners use of material from cowpox pustules to
EBOV Ebola virus
provide protection against smallpox; evidence suggests that the
GBS Group B streptococcus
Chinese used the first smallpox inoculation as early as 1000 CE
HSV Herpes simplex virus
(Common Era). Successful vaccines for diseases such as smallpox
RSV Respiratory syncytial virus
and rabies were developed and used in patients starting in 1796 and
Table of other common abbreviations. 1885, respectively. During the next 150 years, vaccine development
changed not just to target endemic or pandemic infections but also
to provide research focused on innovative technologies and tech-
niques to combat childhood diseases such as polio and measles.
Today, vaccine development is looking to remedy noninfectious ill-
nesses such as allergies and cancer.
IMPORTANCE OF VACCINE
DEVELOPMENT
Almost 300 vaccines are reported to be in current development.
According to the CDC, 10 infectious diseases have been at least 90%
eradicated in the United States as the result of vaccines. These pub-
lic health triumphs show the contributions that vaccines have made
in protecting millions of children and families from vaccine-pre-
ventable illnesses. In 2013, biopharmaceutical research companies
reported 271 vaccines in development for a variety of illness includ-
ing infectious diseases, cancer, neurologic disorders, allergies, and
type 1 diabetes (PhRMA 2013). Vaccine development is a complex
process that includes input from researchers, manufacturers, reg-
ulators, the public health community, and potential purchasers.
Because vaccine development is time- and resource-intensive,
PedSAP 2016 Book 1 Immunology 33 Vaccine Development and Future Targets

establishing and understanding the priorities for develop- to evade the hosts immune system. A vaccines success is
ing and fostering partnerships and collaboration among all based on its ability to induce antibodies that block or neutral-
stakeholders is essential to address the challenges of devel- ize an infectious agent or its products. Antibody-mediated
oping new and improved vaccines (NVAC 2015). protection is not sufficient in all infectious diseases. The pri-
Development of human vaccines remains challenging mary killers of today, for which there are not yet vaccines,
because pathogens have highly sophisticated mechanisms are restrained to some extent not only by antibodies but also
by cell-mediated immunity. These infections include HIV,
respiratory syncytial virus (RSV), and malaria, which are dis-
cussed later. Several candidates are entering clinical trials
BASELINE KNOWLEDGE STATEMENTS for infectious diseases as the result of evidence for protec-
tive efficacy in a human challenge model. The ultimate goal
Readers of this chapter are presumed to be familiar of a vaccine is to develop long-lived immunologic protection,
with the following: in which the first encounter with a pathogen is remem-
Baseline knowledge of currently available vaccines bered, leading to enhanced memory responses that either
and routine schedules completely prevent reinfection or greatly reduce the severity
Understanding of the drug development process of disease (Kaech 2002).
as it pertains to preclinical discovery and phase
transitioning
NIH Department of Health and Human Services; Controversies in Vaccine Advances
Basic Policies for Protection of Human Research All stages of vaccine research and development carry chal-
Subjects, specifically Subpart B Protections for lenges. These include shortening the time of discovery of
Pregnant Women, Human Fetuses and Neonates vaccine candidates, producing and clinically developing vac-
Involved in Research
cines, and ensuring that vaccines generate an appropriate
The most common congenital/perinatally trans- immune response (generation of neutralizing antibodies)
mitted infections in pregnancy and the standard of
that is of adequate strength to provide effective protection
care for diagnosis and treatment
(Kaufmann 2014). As with all drug, vaccines in development
Risk factors for acquisition of RSV in healthy
must go through many years of clinical testing. However,
neonates/infants
advances in scientific fields such as genomics and manu-
Risks associated with current vaccine therapies
facturing technologies are becoming increasingly useful in
Current vaccine administration techniques
vaccine development.
Knowledge of common pediatric infections (CMV,
Maternal immunization has emerged in the past decade
HSV, influenza, RSV, malaria, TB)
as a promising public health strategy to prevent and
combat maternal, fetal, and neonatal infections. Several
ADDITIONAL READINGS recommended maternal vaccines are already available;
however, lack of widespread acceptance by all involved
The following free resources have additional back-
stakeholders (medical providers and mothers) has limited
massive vaccination initiatives like those with childhood
The National Academies Press. Public Health and
Prevention [homepage on the Internet]. immunizations.
CDC. Vaccines and Preventable Diseases [home-
page on the Internet]. SMART Vaccine Tool
Gilbert GL. Infections in pregnant women. Med J A priority of the 2010 National Vaccine Plan (DHHS 2014a,
Aust 2002;176:229-36.
2014b) was to develop a catalogue of priority vaccine tar-
U.S. Department of Health and Human Resources.
gets of domestic and global health importance to aid
Protection of Human Research Subjects [home-
decision-makers and stakeholders in prioritizing the develop-
page on the Internet].
ment of vaccines and targets. With this in mind, the Institute
American Academy of Pediatrics. Chapters:
Immunization in Special Clinical Circumstances; of Medicine, with support of the National Vaccine Program
Cytomegalovirus Infection; Herpes Simplex; Office, developed a new vaccine decision-support tool called
Influenza; Respiratory Syncytial Virus; Malaria; the Strategic Multi-Attribute Ranking Tool for Vaccines,
Group B Streptococcal Infections; Tuberculosis. or SMART tool. The tool, which is moving through several
Red Book: 2015 Report of the Committee on phases of development (currently at phase 3), ranks vaccines
Infectious Diseases. according to many attributes (Table 2-1). As described by its
developers, the SMART tool is intended to help with decision
Table of common pediatric laboratory reference values.
support, not to be the decision-maker.

Table 2-1. Choices of Attributes in SMART Vaccines 1.1
Health considerations Premature deaths averted per year

Incident cases prevented per year
QALYs gained or DALYs averted
Economic considerations Net direct costs (savings) of vaccine use per year
Workforce productivity gained per year
One-time costs
Cost-effectiveness ($/QALY or $/DALY)
Demographic considerations Benefits infants and children
Benefits women
Benefits socioeconomically disadvantaged
Benefits military personnel
Benefits other priority population
Public concerns Availability of alternative public health measures
Potential complications caused by vaccines
Disease raises fear and stigma in the public
Serious pandemic potential
Scientific and business Likelihood of financial profitability for the manufacturer
considerations Demonstrates new production platforms
Existing or adaptable manufacturing techniques
Potential litigation barriers beyond usual
Interests from NGOs and philanthropic organizations
Programmatic considerations Potential to improve delivery methods
Fits into existing immunization schedules
Reduces challenges relating to cold-chain requirements
Intangible values Eradication or elimination of the disease
Vaccine raises public health awareness
Policy considerations Interest for national security, preparedness, and response
Advances nations foreign policy goals
User-defined attributes Up to seven attributes
DALYs = disability-adjusted life-years; NGOs = nongovernmental organizations; QALYs = quality-adjusted life-years.

Information from: Institute of Medicine and National Research Council. Ranking Vaccines: Applications of a Prioritization Software
Tool: Phase III: Use Case Studies and Data Framework. Washington, DC: National Academies Press, 2015.
NOVEL VACCINES IN DEVELOPMENT In more endemic areas, the WHO reports that one child dies
Researchers are using promising new scientific approaches every 30 seconds from malaria. Economic disadvantaged
to build on the successful history of vaccination against individuals are most afflicted, resulting in further deterio-
infectious diseases. Recent developments have focused on ration of economic status. Currently, a staggering statistic
minimizing risks in prominent outbreaks (e.g., Ebola virus reported by the WHO is that one-half of the worlds popula-
[EBOV]) and highlighted the need for accelerated develop- tion is at risk of malaria infection, with infants and pregnant
ment and testing of vaccines for communicable diseases. women being most vulnerable to severe morbidity and mortal-
ity (Lorenz 2014). In 2008, the WHO reported that the malaria
Malaria Vaccine burden constituted almost 250 million cases of disease and
The burden of malaria has declined in many endemic settings almost 1 million deaths.
in Africa and elsewhere (WHO 2015b). Some areas consider There is currently no available vaccine for malaria. Further
the local elimination of malaria achievable with current con- complicating this epidemic, the parasite that causes malaria
trol approaches, but this is thought to be effective only where has developed advanced drug resistance to the most read-
transmission intensity is low and reintroduction is unlikely. ily available treatments. During the past decade, several

antimalarials have been subsequently removed from the mar- The most clinically advanced candidate, RTS,S, specifi-
ket after they were deemed completely ineffective because cally targets the preerythrocytic stage; in initial clinical trials,
of widespread drug resistance. Currently, Cambodia and it conferred about 50% protection from clinical malaria in
Thailand have the highest cases of drug resistance to malaria children 517 months of age and about 30% protection in
(WHO 2015b). children 612 weeks of age (Agnandji 2012). However, vac-
Malaria is usually caused when Plasmodium falciparum is cine efficacy was undetectable 3 years after vaccination. In
transmitted by the Anopheles mosquito. The Plasmodium par- phase III studies, subjects received four doses of RTS,S. The
asite has a complex life cycle, forming sporozoites that the overall incidence of malaria was reduced by 39% over 4 years
mosquito inoculates into its host. Once sporozoites enter the in children and by 27% over 3 years in infants. This level of
host, a replication cycle begins within 214 days. Sporozoites protection, although not optimal and possibly too low to
enter the plasma and red blood cells, undergo morphologic achieve malaria eradication, has cleared the way for its spon-
changes, and release malarial toxin and a variety of antigens, sors to apply for prequalification with the WHO, specifically
causing increasing symptoms and later sequelae (Chia 2014). for immunization in specific sub-Saharan African countries
The life cycle of P. falciparum in humans consists of the pre- (Tinto 2015).
erythrocytic, asexual, and gametocyte stages. Each stage Further advances are clearly still needed in malaria vaccine
can be characterized by the expression of stage-specific development. Further development of a newer generation of
proteins that are targets of host immune responses. The var- malaria vaccines largely depends on a better understanding
ious stages of the life cycle are the current target for vaccine of the parasites life cycle and how different adjuvants affect
development (Arama 2014). host responses, as well as discovery of ways to identify and
The purpose of vaccination strategies is to induce protec- target potentially new antigens.
tive memory immune responses that will provide protection
if the disease-causing agent (sporozoites) are encountered HIV Vaccine
(Arama 2014). Protective immunity against malaria requires More than 2 million AIDS-related deaths occurred globally
a timely and coordinated interplay between innate and adap- in 2008, and more than 33 million people are living with HIV/
tive immunity and further involves dendritic cells, NK cells, AIDS. Despite promising advances in prevention, an estimated
B cells, and CD4+ and CD8+ T cells (Chia 2014). The parasites life 2.7 million new HIV infections occurred that same year, with
cycle inside the host enables it to evade the normal protective the CDC predicting that number to double by 2015 census
immune responses. Research on the genome of Plasmodium statistics. This pandemic poses an ever-growing challenge
shows that the parasite is composed of about 5400 differ- to the overall development and progress of global society
ent protein-encoding genes, some expressed at only specific more than 30 years after HIV was first recognized (OConnell
stages in the life cycle. Most current vaccine development 2012). Development of a safe, globally effective, and afford-
efforts are focused on only four antigens (WHO 2015b). able HIV vaccine offers the best hope for future control of this
The ideal malaria vaccine requires three essential fea- pandemic.
tures: (1) components that will induce an effective immune Prophylactic vaccines against HIV-1 prevent the estab-
response to the different stages of the malaria infection lishment of infection through the generation of neutralizing
(sporozoites and reproduction); (2) components that will over- antibodies, or generation of T-cell responses that result in
come the parasites complex antigenic variation and genetic attenuation of pathogenesis once infection occurs (Douek
variation; and (3) induction of more than one type of immune 2006). The latter approach has been called T-cell vaccination.
response in the host, including cell-mediated and humoral Whole inactivated HIV-1 vaccines have not been considered
components. Such a multi-compartmental vaccine would serious candidates for human immunization, largely because
likely increase the probability of a sustainable and effective of concerns that inactivation would be incomplete, thus allow-
host immune response (Beeson 2014; Chia 2014). ing for the replication of active virus. Together with complex
Despite decades of effort to develop vaccines against host responses, developing an effective HIV vaccine faces
malaria, no strong candidate has yet emerged. Vaccines for other formidable scientific challenges such as high genetic
other types of infection have a high rate of efficacy (90% or variability of the virus, lack of immune correlates of protec-
greater) (Lorenz 2014); many experts agree that a potential tion, limitations within existing animal models, and logistical
malaria vaccine is unlikely to meet these high standards. problems associated with the conduct of many clinical trials
Three types of vaccine candidates target different stages (Girard 2006).
in the life cycle of the parasite: (1) transmission-block- More than 35 vaccine candidates have been tested in
ing vaccines, helpful in preventing the spread of disease; phase I/II clinical trials, involving more than 10,000 volun-
(2) preerythrocytic vaccines, aimed at preventing disease teers, and two phase III trials have been completed, involving
progression in the infected host; and (3) blood-stage vac- more than 7500 volunteers. In total, more than 187 sepa-
cines, designed at eliciting anti-invasion and anti-disease rate trials have been conducted since 1987 (OConnell 2012).
responses (Arama 2014). Many vaccine concepts and vaccination strategies have been

tested, including DNA vaccines, subunit vaccines, live-vector various limitations (efficacy, safety, recurrent outbreaks) have
recombinant vaccines, and various prime-boost vaccine hindered each candidates realization into FDA trials (Cooper
combinations. However, only five vaccine candidates have 2015). Most existing vaccines focus on the EBOV glycopro-
been advanced to efficacy testing. tein as the target immunogen because of its predominant
The recombinant glycoprotein (rgp) 120-subunit vaccines surface expression, essential role in viral entry, and primary
AIDSVAX B/B and AIDSVAX B/E and the Merck Adenovirus role in development of neutralizing antibodies.
serotype (Ad) viral-vector expressing vaccine failed to show One of the most promising vaccines for EBOV to date is a
a reduction in infection rate or lowering of postinfection viral recombinant vesicular stomatitis virus platform (VSV-EBOV),
set point. In 2009, a phase III trial tested a combination of two which consists of a live-attenuated vaccine vector that has
vaccine types. The ALVAC-HIV (vCP1452) given with a biva- shown an acceptable preclinical safety profile and marked
lent rgp 120 (AIDSVAX B/E) booster showed only 31% efficacy efficacy in pre- and postexposure vaccination in rodent and
in protection compared with placebo from infection among monkey models. In recent phase I clinical trials, VSV-EBOV
community-risk participants in Thailand and was deemed was reported to cause arthritis in about 20% of volunteers
ineffective for overall protection (OConnell 2012). Building who were given the highest available dose. Overall, however,
on the results of this study when combining antibody neu- the vaccine was safe and immunogenic, warranting further
tralization with vector priming agents, a fifth efficacy trial evaluation in phase II and III trials (Marzi 2015). These further
was begun in 2009. The HVTN 505 study tested a DNA/ trials failed to achieve long-term immunogenicity.
recombinant adenovirus prime-boost combination but was Currently, the vaccine has been remodeled as rVSV-
terminated in 2013 because of lack of efficacy compared with ZEBOV and is studied using a strategy deemed ring
placebo after 4 years of more than 2500 participants (Rubens vaccination, in which contacts, and contacts of contacts, of
2015; Hammer 2013). Table 2-2 reviews the five most reported an infected patient are vaccinated. This vaccine consists of
phase II and III HIV clinical vaccine trials by vaccine type and a live-attenuated virus, but it is now a recombinant vesicular
their results (Brown 2015). stomatitis virus (rVSV) expressing Zaire Ebola virus (ZEBOV)
glycoproteins. This vaccine was highly successful in prevent-
EBOV Vaccine
ing infection in a recent study that enrolled of two groups
The largest documented outbreak of Ebola hemorrhagic fever determined at random: the immediate group, which received
caused by EBOV started in rural Guinea in 2013. It quickly the vaccine shortly after coming in contact with a patient
spread regionally, predominantly to Sierra Leone and Liberia. with EBOV (4123 patients randomized, 2014 vaccinated);
This global health crisis to date accounts for almost 27,200 and the delayed group, which were vaccinated 3 weeks after
cases, with a mortality rate of greater than 50% (Marzi 2015). contact with patients with EBOV (3528 patients randomized,
Ebola is a member of the Filoviridae family of enveloped, 1498 vaccinated). Ten days after randomization, none of the
single-stranded, negative-sense RNA viruses. Although sev- patients in the immediate group developed EBOV, whereas
eral promising EBOV vaccines have recently been described, 16 patients from the delayed group developed the disease.
Table 2-2. Pertinent Phase II and II Human HIV-1 Vaccine Trials
Candidate Phase Volunteers Location Year Result

Published
ALVAC-HIV (vCP1521)/AIDSVAX III 16,403 Thailand 2009 31% efficacy, deemed no

MN-CM244 rgp120 efficacy
AIDSVAX B/E III 2500 Thailand 2006 No efficacy
AIDSVAX B/B III 5400 United States 2005 No efficacy
MRKAd5 HIV-1 gag/pol/nef trivalent IIb 3000 United States, 2008 No efficacy (HVTN 502/
(Step Trial) Peru, RSA Merck 023)
DNA (VRC-HIVDNA016-00-VP)/rAd5 IIb 2504 US 2013 Terminated in 2013 because of
(VRC-HIVADV014-00-VP) lack of efficacy (HVTN 505)
RSA = Republic of South Africa.

Information from: OConnell RJ, Kim JH, Corey L, et al. Human immunodeficiency virus vaccine trials. Cold Spring Harb Perspect Med
2012;2:a007351; and Rubens M, Ramamoorthy V, Saxena A, et al. HIV vaccine: recent advances, current roadblocks, and future
directions. J Immunol Res 2015;2015:560347.

The 10-day cutoff was used to account for the normal (e.g., neonates, dialysis patients, postoperative cardiac sur-
accepted incubation time of EBOV and to allow the adap- gery patients) have been unsuccessful to date.
tive immune responses induced by the vaccine to develop Similar to other vaccine developments, attempts to
(Henao-Restrepo 2015). The WHO has called these new data develop S. aureus vaccine have used a variety of mecha-
a landmark in the future of controlling Ebola outbreaks nisms. Taking a cue from the Haemophilus influenzae vaccine,
(Kmietowicz 2015). The WHO has reported that the trial will a polysaccharide-specific vaccine (types 5 and 8) was devel-
continue to collect more conclusive evidence on the vaccines oped and studied in 3600 dialysis patients in California. The
capacity to protect populations through herd immunity. Given vaccine overall was well tolerated. However, at the end of the
the vaccines safety, the extended study will likely include trial, it was deemed insignificant in maintaining any long-term
13- to 17-year olds and possibly children 612 years of age efficacy, with overall infection rates after week 50 (p=0.23)
(Kmietowicz 2015). no different between treated and placebo groups (overall
efficacy no greater than 57% at 40 weeks) (Shinefield 2002).
Staphylococcus aureus Vaccine Current studies focus on protective antigens and protein
S. aureus, the most commonly isolated human bacterial immunogenicity. Several host proteins (primarily protein A)
pathogen, is an important cause of skin and soft tissue have been identified in mice and monkeys causing a spe-
infections, pneumonia, and invasive infections (Daum 2012). cific rise in antibody response when present. This protein A is
An epidemic of S. aureus cases began in the 1990s, and the believed to be protective for S. aureus from antibody attack;
past decade has seen an increase in cases of community- further, it has been theorized to limit the efficacy of current
acquired infections caused by strains with two new genetic vaccine trends against S. aureus. Of particular promise is the
backgrounds (USA400 and USA300). The increase in the potential to select antigens that induce both humoral and
clinical burden of S. aureus disease associated with the T cellmediated immunity in order to generate immune syn-
recent epidemic and the occurrence of many infections ergy against S. aureus infections (Spellberg 2012). In addition,
among previously healthy individuals has prompted dis- although neutralizing antibodies are known to be important
cussions about whether there is a need for a universal or a against toxic shock syndrome, antitoxoid vaccines have yet
niche-based immunization strategy (Daum 2012). Attempts to be fully explored. Table 2-3 summarizes current S. aureus
to target subsets of the population for immunization vaccine research.
Table 2-3. S. aureus Vaccines Receiving Clinical Evaluation as of 2014
Currently enrolling or about to enroll
Manufacturer Vaccine Study Phase Composition of Vaccine

Novartis 4 component I-adult Not disclosed. All proteins
Pfizer 4 component I-adult Conjugated capsular polysaccharides,
5 & 8; clumping factor A, manganese
transporter C
Novodigm Recombinant protein I-adult rA13p-N
GSK 4 component I-adult Not disclosed
Enrollment complete
Merck 1 component II/III efficacy isdBa

Biosynexus Passive monoclonal IIb/III efficacy Anti-lipoteichoic acid antibodyb
antibody
Nabi 2 component III Conjugate 5 & 8, recombinant
exoprotein A
a
Enrollment halted in 2011 by recommendation of the Independent Data Monitoring Committee.
b
No significant decrease in staphylococcal sepsis among very low-birth-weight neonates.
c
Efficacy in reduction of infection at 54 weeks nonsignificant.
Information from: Daum RS, Spellberg B. Progress toward a Staphylococcus aureus vaccine. Clin Infect Dis 2012;54:560-7;
and Fowler VG, Proctor RA. Where does a Staphylococcus aureus vaccine stand? Clin Microbiol Infect 2014;20:66-75.

Given all that we have learned about the organism during that are secreted into the colostrum and milk and ingested
vaccine development, and the wide range of clinical devel- by the newborn during breastfeeding (Gall 2005).
opment programs available, a vaccine against S. aureus
targeting community-acquired infection looks promising. Complications of Maternal Vaccination
Uncovering the true role of host-specific infection biomark- Although many maternal vaccines have been successful, our
ers and the ways in which they may help prevent disease overall knowledge of this strategy is lacking in many areas.
seems to be the most promising area of research for vaccine All current maternal vaccines were initially designed for
development. Researchers are optimistic that a vaccine will and tested in nonpregnant women, but the diverse immune
be ready for human efficacy studies within the next decade changes during pregnancy may cause pregnant women to
(Fowler 2014). respond suboptimally or differently than nonpregnant women
(Faucette 2015). Although the influenza vaccine has been
MATERNAL VACCINATION shown safe and effective in maternal immunization, many
The concept of maternal immunization has been established concerns are still raised over vaccines during pregnancy,
for some time; however, there has been recent renewed including ethical and legal issues and, most importantly, con-
interest and focus in maternal immunization as a means to cern for potential short- and long-term deleterious effects of
protect young infants from vaccine-preventable infections in utero exposure of vaccines on the fetus and newborn.
(Lindsey 2013). Currently, the CDC recommends routine maternal vac-
Maternal immunization continues to exemplify an effec- cination with hepatitis A and B, influenza (annually),
tive vaccination strategy by protecting the mother, her meningococcal (if indicated), and tetanus, diphtheria, and
developing fetus, and her later-born infant against infec- pertussis (Tdap) (with each pregnancy). Other vaccines are
tious disease. Maternal immunization yields this trifecta of not routinely recommended because of the significant knowl-
protection by enhancing antibody levels against particular edge gap in their short- and long-term safety in pregnancy.
infections. These antibodies are transferred to the fetus by Until further research is completed regarding the safety of
the placenta or to the infant through breast milk. Studies have these non-routine vaccines during pregnancy, the CDC
established the benefits of maternal influenza vaccination. In relies heavily on the risk-benefit ratio of specific diseases
a randomized controlled trial in Bangladesh, pregnant women before making recommendations for maternal immunization
vaccinated against influenza were significantly less likely to with these specific vaccines (Faucette 2015).
develop febrile respiratory illness and had fewer clinical visits Another major concern surrounding maternal vaccination
than pregnant women in the control group who received pneu- stems from the long-standing observation that the pres-
mococcal vaccine only. In addition, infants whose mothers ence of maternal antibodies in the infant can interfere with
had been immunized with inactivated influenza vaccine dur- the infants humoral immune response to vaccines both sys-
ing pregnancy had a 63% reduction in laboratory-confirmed temically and at mucosal sites (by breastfeeding), although
influenza and a 29% reduction in respiratory illness with fever cell-mediated immune responses are not affected. The inhib-
compared with infants whose mothers had only received itory effect on infant response to vaccination has been highly
pneumococcal vaccine (Zaman 2008). variable among different vaccines and even different studies
of the same vaccine (Beigi 2014). Thus, although maternal
Importance of Maternal to Fetal Immunization immunization is a potential intervention to prevent many
The main rationale for maternal vaccination is that humoral early childhood infections, many are researching strategies
immunity can be passively transferred to the fetus and new- that allow infant immunization to be deferred until infant
born. Historically, the fetuss susceptibility to infections was immune responses have matured, believing that it is more
believed to be because of the immaturity of the fetal immune cost-effective for the developing world (Healy 2006).
system and its tendency to mount tolerogenic responses Several vaccine prospects are in the pipeline for additional
to antigens. Neonates are at heightened risk because of a maternal immunizations. This review focuses on the most
less intact mucosal barrier and lack of immunologic mem- developed of these, which include RSV, cytomegalovirus
ory, as well as the immaturity of the neonatal immune (CMV), group B Streptococcus (GBS), and herpes simplex virus
system, with its inability to develop adult-like protective (HSV).
immune responses when exposed to certain pathogens
(Faucette 2015). Maternal vaccination generates active, Respiratory Syncytial Virus
innate, humoral, and cell-mediated immune protection in the Respiratory syncytial virus is a ubiquitous cause of acute
mother to increase resistance against infections and reduce respiratory illness in early childhood, infecting most children
the chance of vertical transmission. In addition, maternal by the end of their first year of life. Globally, RSV is the most
vaccination elicits systemic immunoglobulin (Ig)G antibod- common cause of acute lower respiratory tract infection and
ies that are transferred to the fetus through the placenta in is a major contributor to morbidity and mortality, leading to
humans, as well as mucosal IgG, IgA, and IgM antibodies an estimated 3.4 million hospitalizations and at least 66,000

deaths per year in children younger than 5 years (Nair 2010). In utero transmission of CMV occurs in mothers without
Although mortality occurs predominantly in developing preexisting CMV immunity (primary infection) or in women
countries, hospitalization rates remain high in industrialized with preexisting antibody to CMV either by reactivation of
countries: about 1% of all children will be hospitalized for RSV previous maternal infection or acquisition of a different viral
lower respiratory tract infection within 1 year of life. Because strain during pregnancy (Boppana 2001). Primary maternal
of this significant burden of disease and the lack of an effec- CMV infection during pregnancy is associated with a greater
tive treatment beyond supportive care, developing a vaccine risk of in utero transmission than nonprimary infection, but
to prevent RSV-related illness is a high priority. because of the high prevalence of disease in the overall pop-
Although RSV has only one known serotype, many anti- ulation, almost two-thirds of infants with congenital CMV
genically distinct strains circulate in communities, causing infection are born to mothers who are already seropositive
yearly epidemics in the winter and early spring in temperate (Wang 2011).
climates. After primary infection, host immunity wanes rap- Strategies exist for preventing mother-to-child trans-
idly, and subsequent reinfection is common. The fact that mission and for treatment aimed at reducing the long-term
natural immunity affords so little protection also speaks to sequelae of symptomatic congenital CMV infection. These
the challenges in developing an effective RSV vaccine. strategies include antenatal interventions (e.g., CMV hyper-
Accordingly, infants can be provided passive immunity immunoglobulin, counseling on behavioral risk modification)
through monthly injections of palivizumab, a recombinant and postnatal interventions (e.g., antiviral therapy for symp-
monoclonal antibody, during the yearly RSV epidemic season. tomatic neonates) (Manicklal 2013). Even as further studies
Palivizumab is given by intramuscular injection at a dose of advance these interventions, prevention of congenital CMV
15 mg/kg once every 30 days for up to 5 consecutive months infection through vaccination remains an attractive goal.
during RSV season. Palivizumab effectively reduces the risk Because of public health impact and a favorable cost analy-
of severe lower respiratory tract infection caused by RSV in sis, the Institute of Medicine ranked the development of a CMV
certain categories of high-risk infants, including premature vaccine as the highest priority in its 2000 report (IOM 2000).
infants born before 29 weeks gestational age, those with Investigation into CMV vaccines began more than 4 decades
chronic lung disease of prematurity, and those with hemo- ago with live-attenuated virus candidates, but these failed to
dynamically significant congenital heart disease. However, yield adequate protection. More recent efforts with recom-
cost-benefit analyses show that palivizumab prophylaxis binant live-attenuated CMV vaccines with deletion of genes
is unsuitable as the long-term mainstay of RSV prevention responsible for immune evasion have shown promise in ani-
efforts (AAP 2015). mal models (Schleiss 2015). Subunit vaccines are another
In an effort to address the highest burden of RSV dis- class of candidates that have focused on surface glycopro-
ease, the approach to developing an RSV vaccine has largely tein B (gB). A phase II study of a gB/MF59 adjuvant subunit
prioritized young infants as the most appropriate target vaccine in seronegative women showed vaccine efficacy of
population, but investigations into vaccine candidates for 50% for prevention of CMV infection in young mothers (Pass
women of childbearing age have also been under way. Live- 2009). Given the molecular diversity of CMV infections, it
attenuated vaccines are predominantly being developed for is unlikely that a single antigenic component will generate
use in infants, whereas a variety of subunit vaccines are in sufficiently broad immunogenicity. As such, several mul-
preclinical and phase IIII clinical testing in adults (Anderson ticomponent subunit and DNA vaccine candidates aimed
2013). Maternal vaccination as a means of providing passive at achieving broad cross-neutralizing humoral and cellular
immunity to vulnerable infants in the first 6 months of life is immune responses are in the early stages of investigation
increasingly becoming a realistic endeavor, so much so that (Manicklal 2013).
the WHO RSV Vaccine Consultation Expert Group has stated
that a licensed RSV vaccine could be commercially available Group B Streptococcus
within 510 years (Modjarrad 2016). Group B Streptococcus is the most common cause of neo-
natal sepsis in the United States. Implementation of routine
Cytomegalovirus screening for GBS for pregnant women in the third trimester
Cytomegalovirus is the leading cause of congenital infection of gestation and administration of intrapartum antibiotic pro-
worldwide and, although the incidence varies in different pop- phylaxis have resulted in a dramatic drop in the incidence of
ulations, affects 0.5%2% of all live births (Kenneson 2007). early-onset neonatal sepsis associated with GBS, but rates
Infants congenitally infected with CMV are at significant risk are at a plateau at 0.34 cases per 1000 live births (CDC 2010).
of developing permanent sequelae, including sensorineural However, maternal intrapartum antibiotic prophylaxis has no
hearing loss and neurodevelopmental delay. Maternal CMV effect on late-onset GBS infection in the newborn.
seroprevalence can be 45%100%, with higher prevalence Group B Streptococcus is a normal part of human GI flora
and earlier CMV acquisition associated with lower socioeco- and colonizes in the vagina in up to 50% of women. Infant
nomic status and non-white race (Cannon 2010). acquisition of GBS occurs during delivery by the birth canal.

The onset of infection shortly after birth does not allow for improved mortality, it is not entirely effective, and infants can
infant immunization as a method of prevention. Experimental be left with significant long-term morbidity. Vaccine strat-
vaccines for one the most common serotypes, GBS type III, egies aimed at preventing or controlling HSV infections in
have been evaluated in phase III trials of pregnant women. women, and thereby preventing mother-to-child transmission
These vaccines were safe and well tolerated, resulting in a of HSV, are an ongoing need.
substantial antibody response in women and significantly Despite much effort by researchers, an effective HSV vac-
higher antibody levels in infants at the time of birth and in the cine has yet to advance beyond clinical trials. Several factors
first few weeks of life when compared with controls (Munoz make HSV a particularly difficult target for an effective vac-
2013). Vaccines to protect mothers and infants against sev- cine strategy, including a relatively large genome that makes
eral prevalent serotypes have the potential to reduce the it difficult to identify optimal protein targets, gene-encoded
morbidity and mortality caused by GBS in the neonatal period. immune evasion mechanisms, viral latency, and the fact that
Development of a GBS maternal immunization work group host reinfection is not uncommon even with established
has brought to light many opportunities to advance current immunity to a primary infection. In addition, because of the
knowledge of GBS infection and disease. The work group has intricate interaction of HSV with innate and adaptive immune
suggested several areas of research that deserve consider- responses, there is incomplete understanding of the most
ation when evaluating a GBS vaccine and implementing a appropriate correlates of immunity with which to objectively
maternal immunization program. The immunogenicity and discern host protective immunity when evaluating vaccine
efficacy of the vaccine should be well established in clinical candidates (Chung 2012).
trials before implementation. Immunologic correlates of pro- Many vaccine candidates have gone through preclinical
tection should be determined (T-cell function in pregnancy, studies and clinical trials to date. Most strategies have aimed
antibody response in GBS-positive mother vs. GBS-negative). at preventing or controlling genital herpes, which would
Finally, the group suggests that determining the duration of potentially also reduce maternal transmission to newborns.
serum antibodies and of the protection they confer in mothers Subunit vaccines have been the most evaluated platform.
and infants is necessary to assess the need for repeated vac- One candidate, an adjuvant recombinant HSV-2 gD vaccine,
cination of mothers in subsequent pregnancies (Black 2013). progressed to a phase III trial, where it failed to prevent HSV-2
There are many unanswered questions related to GBS genital disease in seronegative women. However, of interest,
vaccine development. Although several vaccine candidates this vaccine was 58% effective at protecting against HSV-1
are in phase I studies, no vaccine has reached beyond genital disease compared with a control (hepatitis A) vaccine
phase II because of the lack of efficacy data. A GBS vaccine (Belshe 2012). The overall failure of this candidate highlights
for pregnant women would likely add to the currently avail- the concern that the single antigenic component vaccine may
able vaccines that can be given during pregnancy to protect be unable to generate broad and effective immunogenicity.
mothers and infants against serious and potentially lethal dis- Although several other vaccine platforms are being evalu-
eases. Successful introduction of the vaccine during routine ated, including live-attenuated viruses, replication-defective
prenatal care and further education to the public and provider viruses, killed viruses, recombinant vector vaccines, and DNA
regarding GBS and importance of vaccination will be critical vaccines, none is beyond preclinical or phase 1 clinical test-
components of a GBS maternal immunization program. ing (Chung 2012).
Herpes Simplex Virus ADVANCES IN ESTABLISHED

Herpes simplex virus infections are common worldwide in VACCINES
adolescents and adults. The two distinct types of HSV are Vaccines are overwhelmingly recognized as one of the great-
type 1 (HSV-1) and type 2 (HSV-2). Primary acquisition of HSV est medical advances of the past 160 years. Scientists are
results in lifelong infection, with periodic episodes of viral discovering not only the evolution of new preventable diseases
reactivation, which can be clinical or subclinical. Although but also the need for continuous research and improvement
less common than primary acquisition, mother-to-child of established vaccines. The growing number and type of
transmission of HSV can cause substantial morbidity and vaccine targets within established vaccines, as well as the
mortality in infants. Neonatal acquisition of HSV infection new vaccine technology allowing for more effective formula-
occurs in about 1 in 3200 live births in the United States and tions, contribute the growing advances of accepted, routine
is most likely to occur during labor and delivery than in utero vaccines.
or postnatally (Brown 2003).
The antiviral treatment of choice for neonatal HSV infec- Influenza
tion is acyclovir, which is given intravenously at a dose of The influenza virus can cause serious respiratory disease,
60 mg/kg/day divided every 8 hours. After completing intrave- leading to hospitalization and sometimes death in some
nous therapy, infants should be transitioned to oral acyclovir patients. An annual, seasonal flu vaccine is recommended
for a 6-month suppressive course. Although this therapy has for all individuals older than 6 months to reduce the risk of

contracting seasonal flu and spreading it to others who may worldwide TB vaccination, together with new drug therapies,
be at high risk of complications. Although the primary strain by 2025 (WHO 2015a).
of influenza each year cannot be predicted with exact cer- Bacillus Calmette-Gurin (BCG) remains the only vaccine
tainty, the CDC evaluates random samples circulating during available for TB. It is routinely administered to newborns in
the flu season to evaluate how closely the vaccine matches countries with endemic TB because of its efficacy in prevent-
the circulating virus. In addition to virus matching, the CDC ing the most severe forms of TB in early childhood. However,
conducts various studies throughout the season to evaluate there is a true consensus that BCG cannot provide significant
how well the vaccine actually protects against mild, moderate, protection against pulmonary TB in adults (Anderson 2005;
and severe illness from the flu. All of these data are factored Fine 1995). In the past 10 years, a resurgence in TB research
in at the end of each season to prepare for the next season to has resulted in the development of many new experimen-
estimate which strains should be included in the annual vac- tal vaccines. More than 15 (8 in phase II/III, 7 in phase I) of
cine (CDC 2015). these new vaccines have entered or completed clinical trials,
The 20142015 influenza season received much media most showing a better protective immune response than BCG
attention as the CDC released reports that more than 80% of (Evans 2013). Development of an effective TB vaccine focuses
influenza A (H3N2) strains were antigenically different from on many designs: (1) activation of T cellbased immunity;
the available vaccine component. Given this new information, (2) block transmission of Mycobacterium tuberculosis (Mtb)
in March 2015, the FDA Vaccine Advisory Committee reported by inducing immune response that limits tissue damage or
that the U.S. influenza vaccine composition for the 20152016 prevents infection by enhancing host antimicrobial response
season would include influenza A/California/7/2009(H1N1), occurring early in infection; and (3) antibody-mediated
A/Switzerland/9715293/2013 (H3N2, replacing A/Texas/ immunity by humoral responses as well as the specific role of
50/2012 from 2014), and B/Phuket/3073/2013 (Yamagata). B cells in TB immunity.
The quadrivalent vaccines will include all of these as well as The consensus on how to develop anti-infective vaccines
B/Brisbane/60/2008 (Victoria) (ACIP 2015). against TB requires better characterization of Mtb surface
In June 2015, the CDC advised vaccine developers of influ- constituents, the use of Mtb bacteria that resemble bacilli
enza outbreaks with the H5N1 strain in Africa, the Middle released by a patient with active pulmonary TB, and an exper-
East, and Asia. In November 2014, Canadian officials reported imental model with a very low dose of active bacteria being
highly pathogenic avian influenza (HPAI) H5N2 detection in given to the patient (Delogu 2014). Progress on the next
birds. Novel HPAI viruses have been found in wild birds and generation of TB vaccines will require creative testing and
poultry in the United States. These viruses now include new research to answer the many questions involved.
H5N1 reassortant viruses, H5N8, and H5N2. The Q-Pan H5N1
vaccine is cross-reactive with the H5N1 viruses, but not the Meningococcus
poultry H5N2 or H5N8 viruses. Production of the Q-Pan H5N1 Development and widespread use of quadrivalent vaccines
vaccine is anticipated in 2016, with availability for vaccination (Menactra, Sanofi Pasteur; Menveo, GlaxoSmithKline) against
in mid-2017 (CDC 2015). meningococcal serogroups A, C, Y, and W (based on the poly-
Even when the seasonal flu vaccine is not an exact match, saccharide outer capsule of bacteria) have shown the impact
it can still provide protection against different but related of these vaccines on preventing life-threatening diseases.
viruses that also cause respiratory illness. Although not However, a meningococcal serogroup B (MenB) vaccine has
100% effective against illness, the seasonal flu vaccine does remained a difficult challenge because the outer capsule of
provide protection against potentially serious disease. For this serogroup is poorly immunogenic and closely resem-
this reason, even when the match is suboptimal, an annual bles polysaccharides in human cells. With introduction of
seasonal flu vaccine is still routinely recommended for all the quadrivalent vaccine, MenB remains a leading cause of
patients older than 6 months unless contraindications exist. bacterial meningitis among certain groups, specifically peo-
ple living together in places like college dorms and boarding
Tuberculosis schools. In 20132014, two major U.S. universities, Princeton
Once considered a disease of the past, tuberculosis (TB) has and University of California Santa Barbara, had outbreaks of
reemerged in the past 30 years as a major threat in many parts MenB (CDC 2015).
of the world. In 2013, the CDC reports suggested that more Because of the low incidence of MenB, vaccine efficacy
than one-third of worlds population was infected with TB, and estimates in clinical studies were based on demonstration of
an estimated 9 million people became sick with the disease. immune response, as measured by serum bactericidal activity
The most recent WHO report estimates 1.5 million deaths using human complement (hSBA), against a few MenB strains.
in 2014 and an incidence of 9.6 million TB cases. New tools In studies supporting U.S. licensure, immunogenicity was
are urgently needed to control TB at a global level, and the assessed by the proportion of subjects who achieved a 4-fold
availability of an effective vaccine could help reduce TB inci- or greater increase in hSBA titer for each the strains tested.
dence and mortality. The WHO reports a goal of introducing The two new (licensed in 2015) MenB vaccines in the United

States are Trumenba (Pfizer), a three-dose series; and Bexsero
(Novartis), a two-dose series. In February 2015, the Advisory
Committee on Immunization Practices (ACIP) officially rec-
ommended use of MenB vaccines among certain groups of
individuals 10 years or older at increased risk of MenB.
ADVANCES IN VACCINE DELIVERY

Researchers are conducting preclinical studies using vaccine
delivery methods other than routine intramuscular injections.
Although some vaccines already have an alternative delivery
route (rotavirus-oral), most vaccines require needlesticks,
which for some patients is a major deterrent to getting rou-
tine vaccinations. Administration by needle and syringe also
places vaccination efforts solely in the hands of trained
health care professionals, which may be a constraint to vac-
cine access in many settings. New developments in vaccine Figure 2-1. Microneedle patch.
administration techniques, including transdermal, mucosal, Reprinted from the CDC website.
and inhalation delivery, may appeal to those with a needle
phobia or a low threshold for pain and potentially simultane-
ously improve vaccination rates. The CDC, NIH, and FDA lead
major efforts to broaden administration options to boost vac-
cine uptake (HHS 2014). Transdermal
The CDC, in partnership with industry and academia, demon-
Inhalation strated that novel microneedle technology can deliver
Aerosolized drug delivery has been highly successful in the rotavirus vaccine to animals. A microneedle patch has been
treatment of pulmonary diseases, specifically in the arena of developed and tested to deliver measles and rubella vaccine
asthma and cystic fibrosis, where it is considered standard (Edens 2013). In addition, NIH-supported researchers are
of care. Medications other than corticosteroids (e.g., opioids, developing an influenza patch that uses microneedles, which
dihydroergotamines, insulin) have all had successful tri- could be sent by mail for patients to administer to themselves
als in treating various conditions when given by aerosolized (Figure 2-1). This low-cost, single-use patch can be applied
delivery. easily and quickly and should not require refrigeration. More
An inhaled measles vaccine is the further along in drug than 100 adults recently completed an acceptability and
development than other inhaled vaccine candidates. In 1983, usability test for researchers, and clinical trials are set to
Dr. Albert Sabin published the first successful use of aero- start in late 2015 (Norman 2014).
solized measles vaccine. Since then, other trials have shown In addition to emerging technology of the microneedle,
that vaccine delivery in this manner provided a superior the FDA recently approved the use of one specific jet injector
boosting response compared with vaccination by injection device supported by the Biomedical Advanced Research and
in school-aged children (Bennett 2002; Dilraj 2000). At the Development Authority for administering a specific influ-
time of these studies, a major challenge to further develop- enza vaccine. This is the first needle-free delivery system
ment of the aerosolized vaccine was the need for new delivery approved by the FDA for administration of inactive influenza
devices. New, efficient, portable devices able to deliver dry vaccine. Only one influenza vaccine has been approved to
powder inhalants and liquid aerosols have been developed, use with the needleless injector (marketed as PharmaJet
but only in the past 5 years have these devices been incorpo- Stratis Needle-Free Injection system): AFLURIA, a trivalent
rated into clinical trials for testing of vaccine delivery. inactivated influenza vaccine, providing protection against
Vaccination by inhalation is a promising new method for influenza A (H1N1, H3N2) and influenza B (CDC) (Figure 2-2).
immunization. Already used in large populations, it appears Although data analyses show that vaccination with this new
to be a feasible method for mass vaccination. Recent devel- method provides a level of immune protection similar to the
opments in device innovation have made reliable, portable same vaccine administered by needle, current approval is only
aerosol dosing in mass campaigns possible. Improvement in for adults 1864 years of age. Previously, these jet injectors,
delivery to infants and in the development of vaccines that invented in the 1960s, were used successfully to mass
do not require refrigeration (i.e., dry powders) that are stable vaccinate against smallpox and other endemic diseases.
at room temperatures could make inhalation the preferred This technology, although not new, appears to provide
route of administration for several vaccines in the future another option for effective and easily tolerable vaccine
(Laube 2014). delivery.

infection at mucosal sites, where it is believed most patho-
gens initiate infection. The mucosal epithelium, which
covers about 400 m2 of surface in humans, is protected
by specialized antibodies and resident immune cells. To
optimize vaccine/adjuvant combinations for mucosal
immunity, NIH/National Institute of Allergy and Infectious
Diseases is funding two promising approaches at the pre-
clinical stage. A primary goal is to develop several vaccines
that are administered intranasally, sublingually, or orally to
elicit protective cellular and humoral immune responses at
these sites (HHS 2014).
First, an influenza vaccine combined with an innate
immune activating adjuvant was given sublingually to mice,
Figure 2-2. Needleless injector. where it induced high levels of protective antibody responses.
Reprinted from: PharmaJet. Second, vaccine candidates for both HSV-2 and RSV given
intranasally (and co-delivered with novel oral nanoemulsion
adjuvants) have shown great promise in eliciting a greater
mucosal immune response than intranasal alone. Both of
Mucosal
these novel approaches have led to further investigation of
The idea of mucosal immunity became important when
mucosal immunity and discovery of yet another new vaccine
vaccine researchers began to realize that intramuscular
delivery method (HHS 2014).
vaccine likely did not provide optimal protection against
Patient Care Scenario

A 17-year-old female adolescent (weight 50 kg) is Contractions are stopped by standard institutional
admitted to the high-risk obstetrics/gynecology unit for protocol, but the pediatric infectious disease team is con-
observation for symptoms of preterm labor and worsening sulted with respect to positive screening regarding any
URI symptoms, making it difficult to breathe at home. She prophylactic measure that should be taken for this child.
is 32 weeks gestation, and preliminary prenatal screen- Assuming the availability of maternal vaccines, which one
ing shows the following: of the following treatment options would be best to initi-
ate at this time in the mother?
Urine culture with 100,000 colonies GBS, 1+ glucose on
urinalysis, all other studies negative A. CMV
Blood culture negative B. RSV
Vaginal swab positive for HSV, type 2 (800,000 copies by C. HSV
PCR)
D. GBS
Nasal and oral swab RSV and HSV, type 1 positive by PCR
(no quantity given)
ANSWER C
The first step in treating this mother would be ade- therapy unless undiagnosed heart or pulmonary condition
quate treatment of her UTI. During delivery, she will need develops after birth. Answer C is most correct assuming
to receive ampicillin prophylaxis, and she should be given the mother received intrapartum antibiotics for her GBS
ampicillin at this time to decrease GBS bacterial burden (standard of care)
in her urine. She could be a candidate for GBS vaccina-
1. Belshe RB, Leone PA, Bernstein DI, et al. Efficacy
tion because of positive urine at this time. If appropriate
results of a trial of a herpes simplex vaccine. N Engl J
antibiotics are given to the mother during delivery, vac-
Med 2012;366:34-43.
cination may not be warranted. Given her positive HSV
status both in oral and vaginal areas, the infant could 2. Faucette AN, Unger BL, Gonik B et al. Maternal vac-
be at high risk of transmission of HSV, and the mother cination: moving the science forward. Hum Reprod
would be a candidate for HSV vaccination. No CMV test- Update 2015;21:119-35.
ing is performed on neonates until birth, and none has
3. Lindsey B, Kampmann B, Jones C. Maternal immu-
been done on the mother thus far; hence, she is not a can-
nization as a strategy to decrease susceptibility to
didate for vaccination consideration at this time. This
infection in newborn infants. Curr Opin Infect Dis
infant is at low risk of severe RSV infection, even though
2013;26:248-53.
the mother is positive, and should not be vaccinated. The
child would not currently meet the criteria for palivizumab

American Academy of Pediatrics (AAP). Respiratory
Practice Points syncytial virus. In: Kimberlin DW, Brady MT, Jackson
Vaccines are a vital component of routine health and MA, et al, eds. Red Book: 2015 Report of the Committee
preventive care. Pharmacists play a vital role in encour- on Infectious Diseases. Elk Grove Village, IL: AAP,
aging patients to obtain routine vaccinations, such as 2015:667-76.
influenza and pneumococcal, and are often responsi-
ble for administering vaccines. New data analyses are Anderson LJ, Dormitzer PR, Nokes DJ, et al. Strategic
available showing that pharmacists should now assist priorities for respiratory syncytial virus (RSV) vaccine
in educating both patients and prescribers on potential development. Vaccine 2013;31:S209-15.
vaccines that could be of benefit in special populations Anderson P, Doherty TM. The success and failure of BCG
and new routes of vaccine delivery that could increase implications for a novel TB vaccine. Nat Rev Microbiol
patient compliance.
2005;3:656-62.
Current vaccines in development could further protect
patients against some of the most common and endemic Arama C, Troye-Blomberg M. The path of malaria vaccine
infections to date, including malaria and EBOV for travel- development: challenges and perspectives. J Intern Med
ers, HIV, and MRSA. 2014;275:456-66.
Maternal vaccinations are anticipated to be beneficial
in decreasing early infant morbidity AND mortality for Beeson JG, Fowkes FJI, Reiling L, et al. Correlates of
common neonatal infections including RSV, HSV, CMV, and protection for Plasmodium falciparum malaria vaccine
GBS. Each of these infections carries a high risk of devel- development: current knowledge and future research. In:
opmental complications when transmitted to neonates/ Corradin H, Engers H, eds. Malaria Vaccine Development:
infants. Over 40 Years of Trials and Tribulations 2014:80-104.
Pharmacists should be aware of recent advances in the Beigi RH, Fortner KB, Munoz FM, et al. Maternal immunization:
meningococcal vaccine, specifically with the addition of
opportunities for scientific advancement. Clin Infect Dis
MenB, and which patients meet the criteria for vaccination.
2014;59:S408-14.
The ever-changing face of the annual influenza vaccine
appears to be having a major change again in the 2016 Belshe RB, Leone PA, Bernstein DI, et al. Efficacy results
2017 flu season because we are learning more about what of a trial of a herpes simplex vaccine. N Engl J Med
viruses are causing the most problematic disease. 2012;366:34-43.
Needle-less delivery methods for vaccine administration
will hopefully increase patient compliance with vaccina- Black S, Margari I, Rappuoli R. Preventing newborn infection
tion exponentially because fear of being stuck is the No. 1 with maternal immunization. Sci Transl Med 2013;5:ps11
excuse patients give for not receiving routine vaccines.
Boppana SB, Rivera LB, Fowler KB, et al. Intrauterine
The evolution of vaccine therapy changes at least annually,
transmission of cytomegalovirus to infants of
if not more often. Pharmacists are encouraged to review
the CDC website to stay up to date on immunization infor-
women with preconceptional immunity. N Engl J Med
mation, including information about pipeline vaccines.
2001;344:1366-71.
Brown J, Excler JL, Kim JH. New prospects for a preventive

HIV-1 vaccine. J Virus Erad 2015;1:78-88.
CONCLUSION Brown ZA, Wald A, Morrow RA, et al. Effect of serologic

Vaccines are one of the most profound achievements of bio- status and cesarean delivery on transmission rates
of herpes simplex virus from mother to infant. JAMA
medical science and public health. Spanning more than 200
2003;289:203-9.
years of research and development, 10 infectious diseases
have been at least 90% eradicated in the United States because Cannon MJ, Schmid DS, Hyde TB. Review of cytomegalo-
of vaccines. Using promising new scientific approaches, virus seroprevalence and demographic characteristics
associated with infection. Rev Med Virol 2010;20:202-13.
researchers are building on the successful history of vacci-
nation against infectious diseases and expanding research Chia WN, Goh YS, Renia L. Novel approaches to identify
to maternal immunization programs. Further advancement of protective malaria vaccine candidates. Front Microbiol
already established vaccines is also occurring by the addition 2014;5:586.
of immune-activating adjuvants. Finally, the advancing tech- Chung E, Sen J. The ongoing pursuit of a prophylactic HSV
nology of vaccine delivery allows pharmacists to continue their vaccine. Rev Med Virol 2012;22:285-300.
efforts as advocates for widespread vaccination programs for
Cooper CL, Bavari S. A race for an Ebola vaccine: promises
all patients, which should expand access and availability. and obstacles. Trends Microbiol 2015;23:65-6.
Daum RS, Spellberg B. Progress toward a Staphylococcus

REFERENCES
aureus vaccine. Clin Infect Dis 2012;54:560-7.
Agnandji ST, Lell B, Fernandes JF, et al, for the RTS,S
Clinical Trials Partnership. A phase 3 trial of RTS,S/ Delogu G, Manganelli R, Brennan MJ. Critical research
AS01 malaria vaccine in African infants. N Engl J Med concepts in tuberculosis vaccine development. Clin
2012;367:2284-95. Microbiol Infect 2014:20:S59-65.

Douek DC, Kwong PD, Nabel GJ, et al. The rational design Kaufmann SHE, McElrath MJ, Lewis DJM, et al. Challenges
of an AIDS vaccine. Cell 2006;124:677-81. and responses in human vaccine development. Curr Opin
Immunol 2014;28:18-26.
Evans TB, Brennan MJ, Barker L, et al. Preventive vaccines
for tuberculosis. Vaccine 2013;31:B223-6. Kenneson A, Cannon MJ. Review and meta-analysis of
the epidemiology of congenital cytomegalovirus (CMV)
Faucette AN, Unger BL, Gonik B, et al. Maternal vaccination: infection. Rev Med Virol 2007;17:253-76.
moving the science forward. Hum Reprod Update 2015;
21:119-35. Kmietowicz Z. Ebola vaccine trial results are extremely
promising, says WHO. BMJ 2015;351:h4192.
Fine PE. Variation in protection by BCG: implications of
and for heterologous immunity. Lancet 1995;346:1339-45. Laube B. The expanding role of aerosols in systemic drug
delivery, gene therapy and vaccination: an update. Transl
Folaranmi T, Rubin L, Martin SW, et al. Use of serogroup B Respir Med 2014;2:3.
meningococcal vaccines in persons aged >10 years
Lindsey B, Kampmann B, Jones C. Maternal immunization
at increased risk for serogroup B meningococcal dis-
as a strategy to decrease susceptibility to infection in
ease: recommendations of the Advisory Committee on
newborn infants. Curr Opin Infect Dis 2013;26:248-53.
Immunization Practices, 2015. MMWR 2015;64:608-12.
Lorenz V, Karanis G, Karanis P. Malaria vaccine development
Fowler VG Jr, Proctor RA. Where does a Staphylococcus
and how external forces shape it: an overview. Int J Environ
aureus vaccine stand? Clin Microbiol Infect 2014;20
Res Public Health 2014;11:6791-807.
(suppl 5):66-75.
Manicklal S, Emery VC, Lazzarotto T, et al. The silent global
Gall SA. Maternal immunization to protect the mother burden of congenital cytomegalovirus. Clin Microbiol Rev
and neonate. Expert Rev Vaccines 2005;4:813-8. 2013;26:86-102.
Gershon AA. Varicella zoster vaccines and their impli- Marzi A, Robertson SH, Haddock E, et al. VSV-EBOV rapidly
cations for development of HSV vaccines. Virology protects macaques against infection with the 2014/15
2013;435:29-36. Ebola virus outbreak strain. Science 2015;349:739-42.
Girard MP, Osmanov Sk, Kieny MP. A review of vaccine Modjarrad K, Giersing B, Kaslow DC, et al; Group WRVCE.
research and development: the human immunodeficiency WHO consultation on respiratory syncytial virus vaccine
virus (HIV). Vaccine 2006;24:4062-81. development report from a World Health Organization
meeting held on 23-24 March 2015. Vaccine 2016;34:190-7.
Grohskopf LA, Sololow LZ, Olsen SJ, et al. Prevention and
Control of Influenza with Vaccines: Recommendations Munoz FM, Ferrieri P. Group B Streptococcus vaccination in
of the Advisory Committee on Immunization Practices, pregnancy: moving toward a global maternal immuniza-
United States, 2015-2016 Influenza Season. MMWR 2015; tion program. Vaccine 2013;31S:D46-D51.
64:818-825.
Nair H, Nokes DJ, Gessner BD, et al. Global burden of
Gruber MF. Global and national initiatives to facilitate acute lower respiratory infections due to respiratory
studies of vaccines in pregnant women. Clin Infect Dis syncytial virus in young children: a systematic review and
2014;59:S395-9. meta-analysis. Lancet 2010;375:1545-55.
Hammer SM, Sobieszczyk ME, Janes H, et al. HVTN 505 National Vaccine Advisory Committee (NVAC). The National
Study Team. Efficacy trial of a DNA/rAd5 HIV-1 preventive Vaccine Advisory Committee: reducing patient and
vaccine. N Engl J Med 2013;369:2083-92. provider barriers to maternal immunizations. Public Health
Rep 2015;130:10-42.
Healy CM, Baker CJ. Prospects for prevention of childhood
infections by maternal immunization. Curr Opin Infect Dis OConnell RJ, Kim JH, Corey L, et al. Human immunodeficiency
2006;19:271-6. virus vaccine trials. Cold Spring Harb Perspect Med
2012;2:a007351.
Henao-Restrepo AM, Longini IM, Egger M, et al. Efficacy
and effectiveness of an rVSV-vectored vaccine express- Pass RF, Zhang C, Evans A, et al. Vaccine prevention of
ing Ebola surface glycoprotein: interim results from the maternal cytomegalovirus infection. N Engl J Med
Guinea ring vaccination cluster-randomized trial. Lancet 2009;360:1191-9.
2015;386:857-66. Pharmaceutical Research and Manufacturers of America
(PhRMA). Medicines in Development. Vaccines: a report
Institute of Medicine (IOM). (US) Committee to Study
on the prevention and treatment of disease through
Priorities for Vaccine Development. Vaccines for the
vaccines 2013 report.
21st Century: A Tool for Decision Making. Stratton KR,
Durch JS, Lawrence RS, eds. Washington, DC: National Rubens M, Ramamoorthy V, Saxena A, et al. HIV vaccine:
Academies Press (US), 2000. recent advances, current roadblocks, and future
directions. J Immunol Res 2015;2015:560347.
Kaech SM, Wherry EJ, Ahmed R. Effector and memory T-cell
differentiation: implications for vaccine development. Nat Schleiss MR, Bierle CJ, Swanson EC, et al. Vaccination with a
Rev Immunol 2002;2:251-62. live attenuated cytomegalovirus devoid of a protein kinase R

inhibitory gene results in reduced maternal viremia and
improved pregnancy outcome in a guinea pig congenital
infection model. J Virol 2015;89:9727-38.
Shinefield H, Black S, Fattom A, et al. Use of a staphylo-

coccus aureus conjugate vaccine in patients receiving
hemodialysis. N Engl J Med 2002;346:491-6.
Spellberg B, Daum R. Development of a vaccine

against Staphylococcus aureus. Semin Immunopathol
2012;34:335-48.
Tinto H, DAllesandro U, Sorgho H, et al, for the RTS,S Clinical

Trials Partnership. Efficacy and safety of RTS,S/AS01
malaria vaccine with or without booster dose in infants
and children in Africa: final results of a phase 3, individu-
ally randomized, controlled trial. Lancet 2015;386:31-45
U.S. Department of Health and Human Services (DHHS).

National Vaccine Plan Implementation: Protecting the
Nations Health Through Immunization - 2014a.
U.S. Department of Health and Human Services (DHHS). The

Annual Reports of the State of the National Plan 2014b.
Verani JR, McGee L, Schrag SJ, et al. Prevention of perinatal

group B streptococcal disease revised guidelines from
CDC, 2010. MMWR 2010;59(RR10):1-36.
Wang C, Zhang X, Bialek S, et al. Attribution of congenital

cytomegalovirus infection to primary versus non-primary
maternal infection. Clin Infect Dis 2011;52:e11-3.
WHO. Global Tuberculosis Report 2015 October 2015.

2015a
WHO. Status Report on Artemisinin and ACT Resistance.

2015b.
Zaman K, Roy E, Arifeen SE, et al. Effectiveness of maternal

influenza immunization in mothers and infants. N Engl J
Med 2008;359:1555-64.
Zhu XP, Muhammad ZS, Wang JG, et al. HSV-2 vaccine: cur-
rent status and insight into factors for developing an
efficient vaccine. Viruses 2014;6:371-90.

21. You have been asked by your international travel division B. Microneedle administration by a patch is available
to deliver an update on necessary vaccinations for fami- for patients and can be mailed directly to the
lies traveling to various regions of the world for extended employees office.
stays. Specifically, your division seeks guidance on an C. A needleless influenza vaccine requires only a single
update for malaria, Ebola virus (EBOV), and tuberculosis injector per administrator and is available to those
(TB). Which one of the following statements is best to 1864 years of age.
provide in your update? D. Alternative routes of vaccine delivery have
not proved cost-effective and should not be
A. The TB vaccine has been deemed safe and greater
considered.
than 80% effective for people traveling to endemic
countries and should be received. 24. Researchers studying a new vaccine for the prevention
B. When studied postexposure, the EBOV vaccine was of staphylococcal disease enrolled 500 patients. Dis-
deemed as effective in preventing infection in all age ease rates were 78.3% in the placebo group and 48.7%
groups exposed compared with those who received in the treatment group. Which one of the following best
vaccine before exposure. describes the number needed to treat with the new vac-
C. The RTS,S vaccine against malaria appears to be the cine to prevent infection?
most highly efficacious of the vaccines developed A. 3
for use in children and infants. B. 7
D. Ring vaccination was shown to be the most effective C. 10
method in preventing EBOV. D. 30
22. A 17-year-old male adolescent comes to your pharmacy 25. Which one of the following vaccine features would be
to request information on the potential for an HIV vac- best to consider as part of a vaccination program against
cine. He reports being treated for chlamydia/gonorrhea malaria?
in the past 18 months and having received an annual
A. Ability to overcome the hosts complex antigenic
influenza vaccine. He has heard about local recruit-
variation and genetic variation.
ment for HIV vaccine studies and wonders how when the
B. Development of a single antigenic component that
vaccine will be available. Which one of the following edu-
will induce an effective immune response to the
cation points is best to give this patient?
different stages of the malaria life cycle.
A. Currently, not enough patients are enrolled in C. Increase in the hosts ability to convert appropriate
studies to determine the efficacy or safety of HIV antibody response in order to kill the parasite.
studies. D. Ability to induce more than one type of host immune
B. The safety of HIV vaccines has not been response, including cell-mediated and humoral
established, so use caution before considering components.
enrollment.
26. Assuming vaccine availability, which one of the following
C. It is better to avoid high-risk behaviors, use
patients would be the best candidate to receive a mater-
condoms during sex, and regularly consult your
nal vaccine?
primary care physician.
D. Vaccine developers are challenged by HIVs ability to A. A mother who is positive for herpes simplex virus
genetically self-alter and replicate its own immunity. type 1 (HSV-1), 29 weeks gestation, who has had six
recurrences in the past 14 months before pregnancy
23. You are charged with developing a new protocol for
and was placed on valacyclovir prophylaxis during
the employee vaccination program at your hospital.
pregnancy.
You would like to include alternative administration
B. A cytomegalovirus (CMV)-positive mother who is
techniques for vaccines, specifically for the influenza
placed on bed rest at 22 weeks gestation and is at
vaccine, in order to increase compliance rates. Which
risk of preterm delivery before week 32.
one of the following is the best education point to pro-
C. A mother worried about respiratory syncytial
vide to employees?
virus (RSV) who is at 26 weeks gestation with
A. The only approved delivery methods for influenza twins who are positive for severe congenital heart
vaccine administration are intramuscular disease (hypoplastic left heart syndrome and
(inactivated influenza vaccine) and inhaled (live ventricular septal defect) and due to be delivered
attenuated influenza vaccine [LAIV]). at week 30.

D. A group B Streptococcus (GBS)-positive mother who A. No alternative vaccine delivery methods are
is at 32 weeks gestation and has been hospitalized currently available for this patient.
twice for magnesium infusions to stop preterm B. The LAIV may be given intranasally, but all other
labor. vaccines need to be given either subcutaneously or
intramuscularly.
27. Which one of the following patient groups showed the
C. The patient should delay the catch-up vaccines until
most benefit when treated with EBOV vaccine?
non-injectable administration is available.
A. Patients older than 12 years administered the D. All vaccines should be administered by injectable
vaccine before exposure. route regardless of availability because efficacy is
B. Patients younger than 65 years administered the greater with that route of administration.
EBOV vaccine at any time during exposure.
31. A randomized controlled trial is comparing a new vaccine
C. Patients older than 18 years who lived in any EBOV
for influenza with the existing quadrivalent inactivated
area administered the vaccine before exposure.
vaccine. The study is designed to detect a minimum 15%
D. Patients of all ages administered the EBOV vaccine difference in response rates between the groups, if one
because they showed a decreased risk of acquiring exists (p0.05). Which one of the following changes in
infection. the study parameters would best ensure that the study
28. Your hospital infection control department is looking at detects a minimum 10% difference in response?
case rates of Staphylococcus aureus bacteremia in oth- A. Decrease the sample size
erwise healthy individuals to determine which patients B. Increase the sample size
to target for S. aureus immunization when a vaccine C. Select a p<0.1 as the cutoff for statistical
becomes available. For this strategy, which one of the significance
following patient groups would be best to target? D. Change the design to an observational study
A. Patients at high risk of invasive infection from 32. At birth, a full-term neonate is small for gestational
community-acquired S. aureus age, with hepatosplenomegaly, mild hypotonia, and a
B. Patients with immunocompromise few scattered petechiae. Laboratory evaluation reveals
C. Patients at risk of hospital-acquired staphylococcal thrombocytopenia and elevated ALT. A test for CMV DNA
infections PCR performed on a saliva specimen is positive. The
D. All infants younger than 1 year primary care physician asks how mother-to-child trans-
29. A 24-year-old woman sees her obstetrician early in the mission may have occurred. Which one of the following
course of her first pregnancy. After hearing an overview best answers this question?
of the routinely recommended maternal vaccinations, A. The mother acquired a primary CMV infection during
she asks the physician about the benefits of receiving pregnancy.
these vaccinations. Which one of the following is the B. The mother previously had a CMV infection that was
best education point to give this patient in regards to reactivated during pregnancy.
maternal vaccination? C. The mother, who had serologic evidence of previous
A. The risk of vertical transmission of infection from CMV infection, became infected with a different
mother to fetus is not significantly reduced. CMV strain during pregnancy.
B. Although the mother does receive immunologic D. Any one of the above may have resulted in mother-
protection from infection as a result of vaccination, to-child transmission.
it is not necessary because pregnancy is not 33. When seeking to reduce the burden of severe RSV infec-
typically considered a high-risk state of health. tion in high-risk infants through passive immunization,
C. The newborn infant benefits from passive humoral which one of the following infants would be considered
immunity that occurs by transplacental passage of the best candidate for immunoprophylaxis with palivi-
maternal antibodies. zumab during RSV season?
D. Vaccines have been shown to be ineffective in
A. A 7-month-old girl born at full term who is small for
pregnant women.
gestational age.
30. A 7-year-old patient with severe epidermolysis bullosa B. A 6-month-old boy born at 30 weeks gestational age
needs routine vaccinations (part of a catch-up sched- who no longer requires respiratory support.
ule). His care team asks you about the availability of C. A 3-month-old full-term girl with hemodynamically
non-injectable vaccine delivery to avoid the pain this insignificant congenital heart disease.
patient has with intramuscular injections. Which one of D. A 15-month-old boy born at 31 weeks gestational
the following is best to recommend for this patient? age who continues to require supplemental oxygen.

34. A full-term infant presents on day of life 16 with poor oral 37. A 5-year-old boy is known to have had contact with a
intake and lethargy. Physical examination reveals that person confirmed to have multidrug-resistant (MDR)
the infant, who becomes inconsolably irritable, has a pulmonary TB. The boy is healthy and has no signifi-
full fontanelle. He has no sign of rash. Lumbar puncture cant medical history. Born outside the United States, he
is performed, and an elevated WBC is found in the CSF. received the Bacillus Calmette-Gurin (BCG) vaccine as
The CSF is also tested by PCR, and HSV DNA is detected. an infant. Which one of the following is best to recom-
Which one of the following intravenous acyclovir regi- mend for initial evaluation of this patient for TB infection?
mens is best to recommend for this patient?
A. Place a tuberculin skin test (TST) and interpret the
A. 30 mg/kg/day in three divided doses for 21 days; result as if he had no history of receiving BCG.
if a repeat HSV DNA PCR on CSF is negative, B. Place a TST and interpret the result using a
discontinue all antiviral therapy. classification scale adjusted for patients who have
B. 60 mg/kg/day in three divided doses for 21 days; received BCG.
if a repeat HSV DNA PCR on CSF is negative, C. Obtain a blood sample for an interferon-gamma
discontinue all antiviral therapy. release assay (IGRA).
C. 60 mg/kg/day in three divided doses for 21 days; if a D. Obtain chest radiography to determine the presence
repeat HSV DNA PCR on CSF is negative, transition of active vs. latent disease.
to oral acyclovir for a 3-month suppressive course.
38. A new study compared infection acquisition rates in sub-
D. 60 mg/kg/day in three divided doses for 21 days; if a
jects given a new S. aureus vaccine with rates in subjects
repeat HSV DNA PCR on CSF is negative, transition
who did not receive the vaccine. Subjects in both groups
to oral acyclovir for a 6-month suppressive course.
were examined at 3, 6, and 12 months for any new infec-
35. A 12-year-old boy presents for annual influenza vacci- tion caused by S. aureus, as detected by culture. Results
nation. He is healthy, with no significant medical history (total n=1100) showed that the mean rate of infection
and no known allergies. His mother asks that he receive from the three time points was 51.5% (2.5%) for non-
the best formulation of influenza vaccine. Which one of vaccinated patients and 33.7% (3.5%) for those receiv-
the following is best to recommend for this patient? ing the vaccine (p=0.005 using the t-test). Which one of
the following best describes the results of this study?
A. Intranasal quadrivalent live-attenuated influenza
vaccine A. No clinically important difference occurred in mean
B. Intramuscular trivalent inactivated influenza vaccine incidence of infection in the two groups.
C. Intramuscular quadrivalent inactivated influenza B. Follow-up of 12 months is probably not long enough
vaccine to show significance.
D. Any vaccine formulation with FDA label approval for C. The absolute risk reduction with the vaccine was
his age greater than 10%.
D. The number needed to treat to prevent one
36. A 28-year-old woman in her 39th week of gestation
staphylococcal infection was 8.
presents to the hospital in labor with no rupture of mem-
branes. She has received appropriate prenatal care 39. When given the opportunity to review alternative methods
throughout the pregnancy and has had no complica- of administering vaccines, which route has effectiveness
tions. At 36 weeks gestation, her screen for GBS was that is most likely to approach that of standard routes
negative. During her previous pregnancy, her GBS screen such as intramuscular or subcutaneous?
was positive at 37 weeks gestation, and she received
A. Inhalation
intrapartum antibiotic prophylaxis before giving birth to
B. Transdermal jet injector
a healthy full-term boy. Which one of the following is best
C. Microneedle
to recommend for this patient?
D. Intranasal
A. Intrapartum antibiotic prophylaxis is not indicated
40. According to current data, which novel vaccine shows
because her GBS screen during this pregnancy was
the most promise to be available for patients by 2020?
negative.
B. She should receive intrapartum antibiotic prophylaxis A. HSV
because she has a history of being a GBS carrier. B. EBOV
C. The GBS screen should be repeated on admission C. HIV
to the labor and delivery unit due to her previous D. CMV
positive status.
D. Cesarean section should be performed to lower the
risk of mother-to-child transmission of GBS.

Learner Chapter Evaluation: Vaccine Development and Future Targets.
Strongly agree 31. Design an effective strategy for developing a new
vaccine.
Agree 32. Develop an appropriate strategy to determine which

Neutral of the newer vaccines can be considered for frontline
Disagree health care employees and/or patients.
Strongly disagree 33. Evaluate current evidence to determine the appropriate-
ness of maternal vaccinations.
20. The content of the chapter met my educational needs.
34. Devise a guideline for alternative vaccine administration
21. The content of the chapter satisfied my expectations. to pediatric and adult patients.
22. The author presented the chapter content effectively. 35. Please provide any specific comments related to any
23. The content of the chapter was relevant to my practice perceptions of bias, promotion, or advertisement of com-
and presented at the appropriate depth and scope. mercial products.
24. The content of the chapter was objective and balanced. 36. Please expand on any of your above responses, and/or
provide any additional comments regarding this chapter:
25. The content of the chapter is free of bias, promotion, or
advertisement of commercial products.
26. The content of the chapter was useful to me.
27. The teaching and learning methods used in the chapter
were effective.
28. The active learning methods used in the chapter were
effective.
were effective.

Passive Immunization
By Ann M. Philbrick, Pharm.D., BCPS, BCACP
Reviewed by Jenana Halilovic Maker, Pharm.D., BCPS; Ewha Bridget Kim, Pharm.D., BCPS, BCOP; and Elias B. Chahine, Pharm.D.,
BCPS (AQ ID)
LEARNING OBJECTIVES
1. Distinguish the unique features of specific formulations of immunoglobulins.

2. Assess the appropriateness of palivizumab for specific patient populations.
3. Evaluate the warnings, precautions, and contraindications of agents used in passive immunization.
4. Devise a plan for preventing and treating the adverse effects associated with immunoglobulins.
5. Evaluate the appropriateness of hyperimmune globulin therapy for specific patient exposures.
INTRODUCTION
Active and passive immunity are ways in which the body protects
CDI Clostridium difficile infection
itself from infection. Active immunity occurs after the body comes
CLD Chronic lung disease
in direct contact with an antigen and subsequently produces
CMVIG Cytomegalovirus immunoglobulin
mediators of the immune response, consisting of antibodies and
HBIG Hepatitis B immunoglobulin
activated helper and cytotoxic T lymphocytes specific to that anti-
IVIG Intravenous immunoglobulin
gen (CDC 2015a). Examples of active immunity include infection and
PEP Postexposure prophylaxis
immunization.
PIDD Primary immunodeficiency disease
Passive immunity occurs when a foreign antibody is introduced
RSV Respiratory syncytial virus
into the body. The most common form of passive immunity occurs
SCIG Subcutaneous immunoglobulin when a mother passes immunoglobulin (Ig)A antibodies to her fetus
in utero or IgG antibodies during breastfeeding. In other instances,
antibody can be administered to the body directly. Examples of this
include administering tetanus antibodies to exposed individuals so
that they can neutralize the toxins; and administering immunoglobu-
lins or monoclonal antibodies (CDC 2015a) to treat specific infections
or diseases. This chapter focuses on the use of palivizumab and
immunoglobulins in pediatric patients.
PALIVIZUMAB
Palivizumab is a humanized, recombinant monoclonal antibody
(IgG1) directed against the respiratory syncytial virus (RSV) F pro-
tein inhibitor. Under normal circumstances, RSV binds to the host cell
by a G protein. The F protein mediates the fusion of RSV into the host
cell, where it replicates and releases new RSV particles. According
to the prescribing information, palivizumab binds to the F protein on
the host cell, thereby inhibiting the fusion of RSV into the host cell.
Clinical Uses
According to the prescribing information, palivizumab is approved for
the prevention of RSV in pediatric patients who are at high risk of the
disease. Respiratory syncytial virus can cause both upper and lower
PedSAP 2016 Book 1 Immunology 53 Passive Immunization

respiratory tract infections, including bronchiolitis and pneu-
Box 3-1. Recommended Use of
monia. Almost all children will have been exposed to RSV
Palivizumab in Pediatric Patients
by 2 years of age. Most children who acquire RSV infection
will recover within 2 weeks; however, children with immuno- Preterm infants born < 29 weeks gestation and during
RSV season or < 1 year at the start of RSV season
suppression or other at-risk diseases such as chronic lung
Preterm infants with chronic lung disease of
disease (CLD) and congenital heart disease may develop prematuritya
severe infections (CDC 2015b). Children < 12 months with hemodynamically significant
The IMpact-RSV trial was the first study to show congenital heart disease
palivizumabs efficacy against RSV. This randomized, pla- Children with anatomic pulmonary abnormalities or
neuromuscular disorders
cebo-controlled, double-blind trial enrolled 1501 infants and
children with a history of prematurity (35 weeks or less) or
Children who are profoundly immunocompromised
during RSV season
bronchopulmonary dysplasia (BPD) during the 19961997 Navajo and White Mountain Apache Native American
RSV season. When compared with placebo, palivizumab children
decreased the hospitalization rate in all subjects (10.6% vs.
a
Defined as gestational ages < 32 weeks and a requirement of
4.8%; p<0.001), subjects with a history of prematurity without
at least 21% oxygen for at least the first 28 days of life.
BPD (8.1% vs. 1.8%; p<0.001), and subjects with BPD (12.8% RSV = respiratory syncytial virus.
vs. 7.9%; p=0.038) (IMpact-RSV 1998).
Information from: American Academy of Pediatrics (AAP).
The American Academy of Pediatrics has established a Committee on Infectious Diseases and Bronchiolitis Guidelines
policy guide for using palivizumab in pediatric patients at Committee. Updated guidance for palivizumab prophylaxis
among infants and young children at increased risk of hospi-
increased risk of hospitalization for RSV infection (Box 3-1). talization for respiratory syncytial virus infection. Pediatrics
Infants born before 29 weeks gestation, regardless of 2014a;134:415-20.
comorbidities, should receive palivizumab if they are born dur-
ing RSV season or are younger than 12 months at the start of
the season. This age was selected because data suggest that Infants with diseases that impair the lungs ability to
children younger than 29 weeks gestation have a 24 times clear secretions (e.g., neuromuscular disorders, pulmonary
higher risk of RSV hospitalization (AAP 2014b). There is no abnormalities) are considered at high risk of prolonged hos-
evidence to suggest that this population would benefit from pitalization because of RSV and are therefore candidates for
the medication during their second year of life (AAP 2014a). palivizumab therapy during their first year of life. Children with
Infants born at or after 29 weeks gestation may qualify for cystic fibrosis are not considered candidates for palivizumab
palivizumab, depending on their comorbid conditions. One of therapy unless they have evidence of CLD or nutritional com-
these comorbidities is CLD, which, for this guideline, is defined promise (AAP 2014a).
as a gestational age less than 32 weeks, with a requirement of Another disease state that qualifies an infant for palivi-
greater than 21% oxygen therapy for at least the first 28 days zumab therapy is hemodynamically significant congenital
of life (AAP 2014a). These patients should receive palivizumab heart disease. This includes infants with moderate to severe
therapy during their first year of life. Patients who continue to pulmonary hypertension or acyanotic heart disease that
require treatment with corticosteroids, diuretics, or supple- requires treatment for congestive heart failure, as well as car-
mental oxygen during their second year of life in the 6 months diac surgery. Palivizumab is recommended only during the
leading up to the RSV season should receive palivizumab dur- first year of life; however, children who undergo cardiac trans-
ing the RSV season (AAP 2014a). plantation before their second year of life may benefit from
a second year of palivizumab. In addition, surgery requiring
cardiopulmonary bypass has been shown to reduce serum
concentrations of palivizumab by 58% (AAP 2014a). Therefore,
BASELINE KNOWLEDGE STATEMENTS those who receive palivizumab prophylaxis and undergo
this procedure should receive a booster dose of 15 mg/kg.
Readers of this chapter are presumed to be familiar Palivizumab is not recommended in patients with hemody-
with the following: namically insignificant congenital heart disease who are not
Principles of active and passive immunity receiving cardiac therapy; this includes those with secundum
atrial septal defect, small ventricular septal defect, pulmonic
ADDITIONAL READINGS stenosis, uncomplicated aortic stenosis, mild coarctation of
the aorta and patent ductus arteriosus, cardiac lesions cor-
The following free resources have additional back-
rected by surgery, and mild cardiomyopathy that does require
medical treatment (AAP 2014a).
CDC. Principles of Vaccination [homepage on the
Data are limited on the hospitalization rates for RSV in
Internet]. 2015.
infants who undergo hematopoietic stem cell transplant

(HSCT) or solid organ transplantation. However, RSV is IMMUNOGLOBULINS
associated with severe and fatal disease in patients who The administration of immunoglobulin is another form of
are immunosuppressed because of chemotherapy or other passive immunity. The administration of exogenous immu-
conditions. The effectiveness of palivizumab in this popu- noglobulin assists in the treatment of many disease states,
lation is unknown. With the potential benefits outweighing including primary and secondary immunodeficiencies.
the risks, children younger than 24 months who are severely Immunoglobulins are antibodies naturally present in the body
immunocompromised are considered good candidates for in several forms, including IgG, IgA, and IgM. Immunoglobulin
palivizumab therapy (AAP 2014a). G is found in all body fluids, is present in the highest concen-
Finally, although data are limited regarding the burden of trations (around 45 times higher than IgA and 7.59.5 times
RSV infection in Native Americans, palivizumab can be con- higher than IgM), and is primarily responsible for the bodys
sidered for Navajo and White Mountain Apache patients ability to fight infections caused by pathogens such as bacte-
residing in areas where the incidence of RSV infection is high ria, viruses, and fungi (Chapel 2014; Gonzalez-Quintela 2008).
(AAP 2014a). To a lesser extent, IgM and IgA also play a role in immune
For patients taking palivizumab who are hospitalized for response. Immunoglobulin M is present in the blood and
RSV, continued therapy is not recommended because the lymph fluid and is the first antibody made during an infec-
likelihood of disease recurrence is minimal. In addition, no tion. Immunoglobulin A is produced in mucosal membranes
data analyses support using palivizumab during hospital-as- and is often the first line of defense when it comes to foreign
sociated outbreaks of RSV. During outbreaks, the optimal way antigens.
to reduce the spread of RSV is through infectious disease pre- Exogenous immunoglobulin is a biological product that
cautions, including proper hand hygiene and restricted visitor is fractionated from human plasma donations. The com-
access to areas where outbreaks are present (AAP 2014a, mercial formulations of immunoglobulin are pooled from
2014b). thousands of donors. These formulations primarily con-
sist of IgG but may contain other subclasses, including IgA.
Administration Pooling IgG from different donors ensures that the product
In general, palivizumab is administered monthly for a total has a wide range of antibodies to treat an array of diseases
of 5 months, with the first dose in November (just before the (Laguna 2015). When administered, exogenous immunoglob-
RSV season begins) and the last dose in March. This pro- ulin is used either to replace absent immunity or to bolster the
vides protection from RSV into April. Respiratory syncytial bodys natural immune process.
virus seasons can vary in Alaska and Florida, so it is rec- The 12 immunoglobulin formulations available in the United
ommended to use regional surveillance data to determine States are described in Table 3-1. Most of these are designed
the onset of the RSV season and the best time to initiate to be administered intravenously (IVIG), but there are also
palivizumab (AAP 2014a). According to the prescribing infor- formulations for subcutaneous immunoglobulin (SCIG) and
mation, palivizumab is to be given intramuscularly in the intramuscular immunoglobulin injections. Formulations dif-
anterolateral thigh at a dose of 15 mg/kg and is available fer primarily by preparation (liquid or lyophilized powder),
in preservative-free, single-dose vials. If a patient requires concentration of IgG, type of stabilizer, amount of IgA, and
more than 1 mL of palivizumab, it should be administered in osmolality/osmolarity. Immunoglobulin formulations are
divided doses. available as liquid solutions; or as lyophilized powders that
must be reconstituted before administration. Gammagard SD
Adverse Effects comes in kits with sterile water as the diluent; Carimune does
According to the palivizumab prescribing information, the not come with its own diluent but can be mixed with sterile
most commonly associated adverse reactions include water for injection, 0.9% sodium chloride for injection, or 5%
fever (27% vs. 12% in placebo) and rash (25% vs. 10% in pla- dextrose.
cebo). Postmarketing data show an increased rate of severe Stabilizers are added to IVIG formulations to prevent IgG
thrombocytopenia and injection-site reactions with ther- aggregation and dimer and polymer formation during manu-
apy. In addition, palivizumab has been associated with facturing and storage; these stabilizers (e.g., sucrose, sorbitol,
hypersensitivity reactions, including anaphylaxis and anaph- glycine, glucose, maltose, proline) are thought to contribute
ylactic shock, occurring during initial and subsequent doses. to adverse effects. All IVIG formulations have been associ-
Anaphylaxis and severe hypersensitivity reactions warrant ated with renal failure, although renal failure has been most
discontinuation of palivizumab. According to the palivi- established in formulations using sucrose as a stabilizer
zumab prescribing information, continuation of therapy after (Dantal 2013). It has been hypothesized that this is because
less severe hypersensitivity reactions is at the clinical judg- sucrase, the enzyme responsible for metabolizing sucrose,
ment of the provider, and there are no contraindications for is only expressed in the small intestine and therefore, when
the use of palivizumab with other medications or vaccines administered intravenously, cannot be appropriately metab-
(AAP 2014b). olized. This causes sucrose to accumulate in the kidneys

Table 3-1. Immunoglobulin Formulations
Brand Name Form IgA Osmolarity/ Average Wholesale

(Route of Administration) (Stabilizer) (mcg/mL) Osmolality Price ($)
Carimune NF Lyophilized, 3%12% 720 1921074 mOsm/kg 318 (3 g) to 1353.60

(IV) (Sucrose) (12 g)
Flebogamma DIF 5% 5% liquid < 50 240370 mOsm/kg 41.94 (10 mL vial) to
(IV) (Sorbitol) 2013.12 (400 mL vial)
Flebogamma DIF 10% 10% liquid < 100 240370 mOsm/kg 419.40 (50 mL) to
(IV) (Sorbitol) 1677.60 (200 mL)
GamaSTAN S/D 15%18% liquid Not measured Not available 90.52 (2 mL) to 413.56
(IM) (Glycine) (10 mL)
Gammagard liquid 10% liquid < 37 240300 mOsm/kg 391.90 (25 mL) to
(IV) (Glycine) 4702.68 (300 mL)
Gammagard SD Lyophilized < 12.2 636 mOsm/L (5%) 1012.20 (5 g) to
(IV) (Glucose) 1250 mOsm/L (10%) 2024.40 (10 g)
Gammaplex 10% liquid < 10 460500 mOsm/kg 809.70 (100 mL) to
(IV) (Sorbitol, glycine) 3238.80 (400 mL)
Gamunex-C 10% liquid 46 258 mOsm/kg 122.99 (10 mL) to
(IV or SC) (Glycine) 4919.52 (400 mL)
Hizentra 20% liquid 50 380 mOsm/kg 201.60 (5 mL) to
(SC) (Proline) 2016.00 (50 mL)
Octagam 5% liquid < 100 310380 mOsm/kg 154.92 (20 mL) to
(IV) (Maltose) 3873.00 (500 mL)
Privigen 10% liquid 25 320 mOsm/kg 780.00 (50 mL) to
(IV) (Proline) (isotonic) 6240.00 (400 mL)
IM = intramuscular; IV = intravenous; SC = subcutaneous.

Information from: Stein ER, Orange JS, Ballow M, et al. Therapeutic use of immunoglobulins. Adv Pediatr 2010;57:185-218;
and Redbook Online [online database]. Greenwood Village, CO: Truven Health Analytics.
and proximal tubules, leading to hyperosmolality (Rhodes This includes systems using GDH-PQQ (glucose dehydroge-
2014; Dantal 2013). Immunoglobulin-associated renal failure nase pyrroloquinoline quinone) test strips (Ochs 2010).
occurs primarily in patients who have preexisting conditions Immunoglobulin formulations differ in IgA concentra-
that increase the risk of renal failure, including prior failure, tions. All immunoglobulin formulations contain some IgA,
diabetes mellitus, volume depletion, sepsis, proteinemia, and and for most people, the amount is negligible. However,
concomitant use of nephrotoxic agents (Dantal 2013). in patients who are IgA deficient, administering high con-
Hyperglycemia is another issue to consider when using centrations of IgA can lead to the formation of anti-IgA
saccharide-stabilized IVIG formulations. Formulations using antibodies and a potential anaphylactic reaction. Because
glucose, in particular, produce a rapid increase in blood the incidence of this reaction is very low, routine screen-
glucose and insulin concentrations in patients without dia- ing for IgA deficiency before administering immunoglobulin
betes. In patients with diabetes, IVIG formulations with is not recommended. However, an IgA deficiency should
glucose should be used with caution, with particular atten- be considered in a patient who develops an anaphylactic
tion to insulin requirements during and after administration. reaction to a product containing high IgA concentrations
Formulations containing sucrose, maltose, and sorbitol (Rhodes 2014). If an IgA deficiency is diagnosed, IVIG prep-
have no significant effect on blood glucose concentrations. arations with a low IgA concentration should be selected, or
Formulations with maltose can cause falsely elevated read- alternatively, immunoglobulin should be administered sub-
ings in blood glucose monitors that are not glucose-specific. cutaneously, if possible.

The final way in which immunoglobulin formulations dif-
Box 3-2. Common PIDDs Requiring
fer is their osmolarity or osmolality. Hyperosmolar solutions
Immunoglobulin Therapy
are usually older formulations, with osmolarities of 280296
mOsm/kg and higher solute concentrations. As such, they are Antibody deficiencies
more likely to cause local infusion-site reactions and venous X-linked or autosomal agammaglobulinemia
thromboembolism (Rhodes 2014; Ochs 2010). Common variable immunodeficiency disorders
IgG subclass deficiency with IgA deficiency
Clinical Uses Selective IgG subclass deficiency
Immunoglobulin has FDA-approved labeling for only a few
Specific antibody deficiency with recurrent infections
indications, with many clinical uses considered off-label.
Transient hypogammaglobulinemia of infancy
Approved indications include treatment of primary immu- Combined immunodeficiencies
nodeficiency diseases (PIDDs), prevention and control of Severe combined immunodeficiencies (SCIDs)
bleeding in idiopathic thrombocytopenic purpura, prevention
Nuclear factor kappa beta essential modulator (NEMO)
deficiency
of coronary artery aneurysm in Kawasaki disease, treatment
X-linked lymphoproliferative syndromes
of chronic inflammatory demyelinating polyneuropathy, and
Hyper-IgE syndromes
prevention of infection in chronic B-cell lymphocytic leuke- Wiskott-Aldrich syndrome
mia (Dantal 2013). This chapter focuses on replacement Ataxia-telangiectasia patients
therapy for primary and acquired immunodeficiencies and Hyper-IgM syndrome
two off-label uses: measles postexposure prophylaxis (PEP)
and Clostridium difficile infections (CDIs). PIDD = primary immunodeficiency disease.
Information from: Peter JG, Chapel H. Immunoglobulin replace-
Replacement Therapy for Primary ment therapy for primary immunodeficiencies. Immunotherapy
2014;6:853-69.
Immunodeficiencies
Primary immunodeficiency diseases are caused by inherited
defects of the immune system. The more than 230 forms
of PIDD (Al-Herz 2014; Chapel 2014) affect up to 1 in 4000
because it contains live viruses. The mechanism by which
people in the United States (Shehata 2010). Although PIDDs
immunoglobulin benefits during measles PEP is not fully
can be diagnosed at any age, they are typically identified
understood, but it may pertain to the ability of immunoglobu-
at around 6 months of age when maternal IgG diminishes
lin to neutralize the measles virus (Young 2014).
(Shehata 2010). Patients with PIDD have increased sus-
A Cochrane review evaluated the effectiveness of immu-
ceptibility to infections, inflammation, and autoimmunity
noglobulin for measles PEP. This analysis contained seven
(Chapel 2014).
studies (total n=1432) in which IVIG or intramuscular immu-
Two main categories of PIDD are cellular defects and anti-
noglobulin was given as the sole therapy for measles PEP.
body deficiencies. Patients with cellular defects usually
Immunoglobulin formulations decreased the risk of mea-
require replacement of their stem cells; therefore, the treat-
sles by 83% when administered within 7 days of exposure to
ment of choice is HSCT. The other group of patients with
the disease. This represented an absolute risk reduction of
PIDD lack specific antibodies (humoral immunodeficiencies);
37 per 1000 patients and a number needed to treat of 27. In
therefore, the treatment of choice for them is replacement
three studies in this meta-analysis, immunoglobulin prepa-
therapy with immunoglobulin. Although there are two main
rations significantly decreased mortality compared with no
categories of PIDDs, some patients may have a combination
treatment (RR 0.24; 95% CI, 0.130.44). In two studies that
of both components. Common PIDDs requiring immunoglob-
compared immunoglobulin with the measles vaccine, the
ulin therapy are listed in Box 3-2.
measles vaccine appeared to be more effective than immuno-
Because PIDD is a chronic disorder, treatment is lifelong.
globulin for PEP; however, this result is inconclusive because
The goal of therapy is to prevent infections and organ damage
of the limited number of studies (Young 2014). The studies
(Chapel 2014). Targeting a specific IgG serum concentration
in this meta-analysis excluded populations that would most
is only useful in select cases. As a result, the immunoglobu-
benefit from this therapy, including pediatric and immuno-
lin dose must be highly individualized to obtain the desired
compromised patients.
clinical effects. Starting doses vary depending on the type of
A small study completed in Turkey compared IVIG with
PIDD but can be 100600 mg/kg every month (Shehata 2010).
the measles vaccine for PEP. In this setting, the mother of
Measles PEP a patient in a pediatric ward exposed 44 children and 101
A promising use for immunoglobulin is measles PEP, particu- adults to measles. The risk of contagion was high because
larly for children who have not completed the full vaccination the pediatric ward was an open setting with two large rooms
series or who have immunocompromise and therefore can- consisting of 25 and 26 beds each. Of the 44 exposed chil-
not receive the measles, mumps, and rubella (MMR) vaccine dren, 25 (56.8%) were able to provide documentation of a full

measles vaccine series. The remaining patients received the against platelet antigens. Intravenous immunoglobulin can
measles vaccine (10 patients) or IVIG (9 patients), depending neutralize these antibodies (Wong 2015). Additional adverse
on their age and concurrent diseases. At the 21-day follow-up, effects associated with the use of IVIG in ITP include asep-
none of the children had evidence of measles (Tapisiz 2015). tic meningitis and anaphylaxis. Thromboembolism also may
The CDC recommends 400 mg/kg of IVIG as a single dose occur, although it is rare in pediatric patients (Wong 2015).
for measles PEP. Administration of the measles or varicella- Immunoglobulin plays an important role in Guillain-Barr
containing vaccine should be delayed by 8 months (CDC syndrome. Guillain-Barr syndrome is an acute, inflamma-
2015a). tory demyelinating neuropathy characterized by symptoms
such as flaccid paralysis, weakness, diminished deep ten-
C. difficile Infections don reflexes, and, in some cases, respiratory failure requiring
Reductions in the recurrence of CDIs present another ventilator support. Although most patients recover fully,
unique opportunity to use immunoglobulin. C. difficile is a some continue to have sequelae of the disease. Predictors of
gram-positive, toxin-producing bacterium. Toxins A and B are continued symptoms include age younger than 9 years and
responsible for most symptoms associated with CDI and can rapid progression of symptoms. Immunoglobulin hinders the
be very resistant to normal eradication methods. More than humoral and cell-mediated process that leads to destruction
70% of adults worldwide have low antibody titers to C. diffi- of the axons and, in animal models, promotes remyelination.
cile toxins A and B; therefore, immunoglobulin formulations Studies in children, although limited, suggest that IVIG can
may also contain limited quantities of these antibodies (Shah lead to early motor function recovery (Wong 2015).
2015; Johnson 1997). Five pediatric patients with recurrent
CDI were included in the first study to evaluate IVIG for the Adverse Effects
treatment of CDI and were treated with 0.4 mg/kg of IVIG Adverse effects associated with immunoglobulin formu-
every 3 weeks. These patients had complete resolution of lations include fever, chills, flushing, headache, back pain,
symptoms and eradication of toxin B from their stool (Leung chest pain, bronchospasm, nausea, myalgias, and asep-
1991). Additional studies have had mixed outcomes (Shah tic meningitis. More serious, but rarer adverse reactions
2015). Although immunoglobulin may not be a cost-effective include seizures, pulmonary edema, hemolysis, anaphy-
therapy for all CDIs, it can be a viable option for patients who laxis, renal impairment, and thromboembolism (Chapel
are refractory to standard treatment. 2014). Reactions can vary with formulations and route of
administration. Administering immunoglobulin at a slower
Other Uses infusion rate may decrease the occurrence of some adverse
Immunoglobulin has more than 150 off-label uses; this rep- reactions. Historically, there has been a concern regarding
resents about 75% of its clinical use (Wong 2015; Rhodes transmission of bloodborne pathogens with immunoglobulin
2014). One of the primary uses of immunoglobulin in pedi- administration, but the current purification and manufac-
atric patients, outside PIDD, is Kawasaki disease. Kawasaki turing processes have minimized this risk and no cases of
disease is a vasculitis of small- and medium-sized arteries. disease transmission have been reported in the past 20 years
Kawasaki disease can initially cause acute problems, includ- (Chapel 2014). Hypersensitivity reactions, which are rare,
ing fever, rash, and cervical lymphadenopathy, but can then appear as a typical hypersensitivity reaction and warrant dis-
progress to dilation and possibly aneurysm of the coronary continuing the product.
arteries (Wong 2015). The American Heart Association rec-
ommends a one-time dose of 2 g/kg of IVIG within 510 Interactions with Live Virus Vaccines
days of the onset of fever. A meta-analysis showed that IVIG Immunoglobulins can interact with the MMR and varicella
decreased coronary artery abnormality formation at 30 days vaccines. However, immunoglobulins do not interact with
(RR 0.74 [95% CI, 0.610.90]) compared with placebo (Oates- other live virus vaccines, including the live attenuated influ-
Whitehead 2003). enza virus, rotavirus, herpes zoster, yellow fever, and typhoid
Immune thrombocytopenia (ITP) is another disorder vaccines. The IVIG product can interfere with the bodys abil-
for which immunoglobulin may offer therapeutic benefits. ity to produce an immune response to MMR or varicella. If
Immune thrombocytopenia is one of the most common possible, MMR- or varicella-containing vaccines should be
acquired bleeding disorders in children, usually occurring after administered at least 14 days before IVIG therapy is initiated.
a viral illness. Most ITP cases involve mild mucosal bleeding If this is not possible, these vaccines should be delayed until
and are self-limiting. However, some may progress to serious 311 months after IVIG therapy, depending on the indication.
intracranial or GI hemorrhage (Wong 2015). In adults, most When the MMR or the varicella vaccine has been given and
cases of ITP are chronic; therefore, corticosteroids are con- IVIG cannot be delayed by 2 weeks, the vaccine should be
sidered first-line therapy. In children, however, most cases are readministered at the appropriate time, or serologic testing
acute, and IVIG is the treatment of choice. In this acute pro- may be used to determine whether antibodies have formed to
cess, destruction of platelets occurs through autoantibodies the corresponding virus (CDC 2015a).

IG Formulations Infants born to HBV-positive mothers should receive both
As mentioned previously, immunoglobulin can be adminis- hepatitis B immunoglobulin (HBIG) and HBV vaccine within
tered intravenously, subcutaneously, and intramuscularly. 24 hours (preferably within 12 hours) of birth. The HBV vac-
Immunoglobulin is usually administered intravenously. cine schedule remains unchanged, with the second dose at
This route is ideal because it has a rapid onset of action 2 months of age and the third at 6 months of age. Testing for
and allows for larger-volume administration (Peter 2014). HBV transmission should be performed 12 months after the
However, IVIG requires venous access and the potential for final dose, but not in children younger than 9 months of age.
repeated trips to a hospital or infusion center for treatment. Administration of this combination decreases the rate of peri-
Some patients can successfully self-administer IVIG at home. natal transmission of HBV infection by 85%95% (CDC 2015a;
Because SCIG does not require venous access, it has Hsu 2011).
gained popularity. The subcutaneous formulations have For infants whose mothers HBV status is unknown, the full
FDA-approved labeling only for PIDD, but they are often used vaccine series is recommended, with the first dose within 12
off-label. Subcutaneous immunoglobulin can be admin- hours of life. An exception to this rule is in preterm infants
istered twice weekly to biweekly and may be particularly (37 weeks gestation or less) weighing less than 2000 g, who
suitable for patients who receive smaller volumes of admin- should receive the combination of HBV vaccine and HBIG
istration (2030 mL, depending on the formulation) or those within 12 hours of life. Preterm infants weighing less than
with small or poor veins. Another advantage of SCIG is that 2000 g may have a decreased response to the HBV vaccine;
it is associated with decreased adverse reactions, includ- therefore, the vaccine series should be restarted once the
ing hypersensitivity in those who are IgA deficient. However, patient becomes chronologically 1 month of age. In a preterm
the incidence of local injection-site reactions (e.g., redness, infant weighing less than 2000 g whose mothers HBV status
swelling) may be increased (Rhodes 2014). is negative, HBV vaccination can be delayed until the infant
In most instances, IVIG and SCIG are considered equally is chronologically 1 month of age (CDC 2015a). Hepatitis B
efficacious therapies. However, there is debate regarding immunoglobulin is usually well tolerated, with hypotension
whether the conversion is a 1:1 ratio. Subcutaneous immu- and nausea as the most common adverse effects.
noglobulin has a lower AUC than IVIG, so mathematically, to
meet FDA noninferiority standards, a higher dose of SCIG is Rabies Immunoglobulin
necessary. The FDA has approved a dose adjustment coeffi- Rabies is a rare but fatal disease when left untreated. In the
cient of 1.53 to convert IVIG to SCIG. In addition, data analyses United States, rabies is primarily transmitted by infected bats,
show that equivalent or even lower doses of SCIG can elicit but raccoons, foxes, skunks, and coyotes are also considered
IgG concentrations equal to those of IVIG. The choice of con- vectors for the disease. Transmission usually involves being
version method depends on health care system preference. bitten by an infected animal but can also occur by percuta-
Regardless of the method used, when transitioning a patient neous, permucosal, and airborne routes. Symptoms of rabies
between IVIG and SCIG, the patient should be monitored for infection are nonspecific at first and include fever, malaise,
both IgG concentrations and clinical effect (Peter 2014). headache, irritability, nausea, and vomiting. This is followed
The first commercial immunoglobulin formulations were by an acute neurologic phase consisting of hyperexcitability,
given intramuscularly. However, this route has fallen out of hyperactivity, salivation, and a fear of water and air. Patients
favor because of the large volumes required for administra- typically die within 5 days of symptom onset.
tion and the associated pain. Human rabies immunoglobulin is available for use as PEP
in patients who have been exposed to a rabid or potentially
HYPERIMMUNE GLOBULINS rabid animal. The decision to use human rabies immunoglob-
Hyperimmune globulins are similar to immunoglobulin ulin for PEP should be individualized, with consideration for
except that they contain high concentrations of antibodies to the type of animal exposure, characteristics or behavior of the
one specific antigen. Rather than providing general protec- animal, and health department data on local rabies activity.
tion and bolstering the overall immune system, hyperimmune Human rabies immunoglobulin should be used in combi-
globulins protect against a specific disease and are often nation with the rabies vaccine. The rabies vaccine should be
considered after exposure to a particular disease. Several given intramuscularly in the anterolateral thigh in children, in
hyperimmune globulins are available for use in pediatric a series of four doses given on days 0, 3, 7, and 14 of exposure
patients. to the animal. A fifth dose may be considered if the patient
is immunocompromised. Human rabies immunoglobulin
Hepatitis B Immunoglobulin should be given on the day of exposure, or as soon as pos-
Hepatitis B is a bloodborne disease; the hepatitis B virus sible, to provide immediate protection against rabies while
(HBV) has been well established to cause acute and chronic the vaccine begins to take effect. It is unnecessary to give
hepatitis, cirrhosis, and hepatocellular carcinoma. In chil- human rabies immunoglobulin beyond day 8 of rabies expo-
dren, the most common route of transmission is perinatal. sure because by then, the vaccine will be effective. The dose

of human rabies immunoglobulin is 20 international units/kg; infants less than 28 weeks gestation who weigh less than
this should be administered intramuscularly in small volumes 1000 g and who have been exposed to varicella in the hospi-
and, if possible, around the wound site and a site distant to tal. Varicella exposure is defined as direct indoor contact with
the wound. Human rabies immunoglobulin may interfere with an infected person for more than 1 hour.
live-virus vaccines; therefore, the administration of these Varicella zoster immunoglobulin is administered intra-
vaccines should be separated by at least 3 months. Soreness muscularly and should be given within 10 days of exposure.
at the injection site and elevated body temperature are the Dosing is weight based. According to the varicella zoster
most common reported adverse effects. Sensitization with immunoglobulin prescribing information, the dose for new-
repeated doses has been reported, particularly in those who borns weighing 2 kg or less is 62.5 plaque-forming units;
are immunoglobulin deficient. otherwise, the dose is 125 plaque-forming units per 10-kg
weight, up to 625 units. The varicella zoster immunoglobulin
Tetanus Immunoglobulin may only attenuate the disease, meaning the exposed patient
Tetanus is caused by Clostridium tetani and can cause can still be infectious despite the timely administration of
sustained muscle contractions. Tetanus is the only vac- immunoglobulin. In addition, varicella zoster immunoglobu-
cine-preventable disease that is noncommunicable; it is lin can increase the incubation period of varicella disease to
acquired through C. tetani spores found in the environment. If up to 28 days. As a result, isolation precautions may be pru-
left untreated, tetanus can be fatal, either from muscle paraly- dent in children with high-risk exposure.
sis itself or from associated complications such as aspiration In all instances, if varicella is prevented, routine administra-
pneumonia, pulmonary embolism, or dysregulation of the tion of varicella zoster virus vaccine is recommended, when
autonomic nervous system (Hayney 2014). possible. This immunoglobulin has the potential to interact
Tetanus immune globulin can be given to provide passive with all live attenuated virus vaccines; therefore, administra-
immunity in those exposed to the disease. Most cases of tion of these vaccines should be delayed by 3 months. The
exposure to tetanus can be treated with a booster to tetanus most common adverse effects reported with varicella zoster
toxoid vaccine. Administration of tetanus immunoglobulin immunoglobulin are injection-site pain, headache, rash,
with tetanus toxoid is indicated in patients with an unclean fatigue, chills, and nausea. Varicella zoster immunoglobulin
or major wound who have received fewer than three doses contains 40 mcg/mL of IgA; thus, it is contraindicated in IgA-
or an unknown number of tetanus toxoid immunizations. deficient individuals who have had a hypersensitivity reaction
Tetanus immunoglobulin, which is administered intramuscu- to IgA containing immunoglobulin.
larly, should be given at a site separate from tetanus toxoid.
Adverse effects of tetanus immunoglobulin include pain, ten- Cytomegalovirus Immunoglobulin
derness, and stiffness at the injection site. Although cytomegalovirus (CMV) is a fairly benign disease
in the general population, it can be life threatening in immu-
Varicella Zoster Immunoglobulin nocompromised patients, particularly in those who have
Varicella zoster virus causes varicella or chickenpox. In undergone a solid organ transplant or HSCT. The sequelae
children, the most common manifestation of this disease is of a disseminated CMV infection in solid organ transplant
a maculopapular rash resulting in vesicular lesions and even- recipients include late-onset malignancy, acute and chronic
tual crusting. Once the body has been infected, the virus allograph injury, chronic allograph vasculopathy, and death
may return in the form of shingles, which is relatively rare in (Hsu 2011). The highest risk of transmission occurs when a
children. Unfortunately, disseminated disease is a risk with CMV-negative patient receives an organ from a CMV-positive
varicella zoster virus, particularly in immunocompromised donor. This is one of the primary situations in which CMV
patients. Disseminated disease can cause complications immunoglobulin (CMVIG) is warranted.
including aseptic meningitis, transverse myelitis, Guillain- Cytomegalovirus immunoglobulin, which contains anti-
Barr syndrome, thrombocytopenia, hemorrhagic varicella, bodies to CMV, is used in conjunction with other antiviral
purpura fulminans, glomerulonephritis, myocarditis, arthritis, therapies (ganciclovir or valganciclovir). Cytomegalovirus
orchitis, uveitis, iritis, and hepatitis (CDC 2015a). Like mea- immunoglobulin use is more established in solid organ trans-
sles, varicella zoster vaccine is not initiated until 1 year of plantation than in HSCT, but it can be used in both situations
age, and the series is not finished until 46 years of age. In (Hsu 2011). The dose and schedule of CMVIG depend on the
addition, varicella zoster vaccine is a live attenuated vaccine type of transplantation, but it is usually given every 2 weeks
that cannot be given to individuals with immunocompromise after transplantation, with the final dose administered
(CDC 2016). 16 weeks after transplantation. Adverse effects of CMVIG
Postexposure prophylaxis for varicella zoster virus is include flushing, chills, muscle cramps, back pain, chest
indicated in children who are (1) immunocompromised and tightness, fever, nausea, vomiting, hypertension, and tachy-
exposed to varicella, (2) born to a mother who develops vari- cardia. Many of these effects are considered infusion related
cella 5 days before or up to 2 days after delivery, or (3) preterm and may subside if the infusion rate is slowed.

PHARMACIST ROLE immunoglobulins for specific diseases, also work as passive
Pharmacists can play a vital role in the use of passive immu- immunizations for the prevention or PEP of specific diseases.
nity in many areas, including product selection. All of these In all of these instances, clinical pharmacists can play a vital
products are expensive, and cost-effectiveness must be con- role in selecting the product and treating the patient.
sidered when selecting which products a hospital should
stock. For example, it may be tempting to select an IVIG prod- REFERENCES
uct with the lowest wholesale acquisition cost. However, Al-Herz W, Bousfiha A, Casanova JL, et al. Primary immuno-
confounding factors such as pharmacist compounding deficiency disease: an update on the classification from
time and dose and administration time should be consid- the International Union of Immunological Societies expert
committee for primary immunodeficiency. Front Immunol
ered, which influence nursing support time and availability of
2014;5:1-33.
patient turnover in an infusion center. By participating in a
hospitals pharmacy and therapeutics committees, pharma- American Academy of Pediatrics (AAP). Committee
cists can assist in selecting the most cost-effective product on Infectious Diseases and Bronchiolitis Guidelines
Committee. Updated guidance for palivizumab prophy-
for their institution.
laxis among infants and young children at increased risk
Another important function of pharmacists is to verify that
of hospitalization for respiratory syncytial virus infection.
patients who have been prescribed palivizumab or a specific Pediatrics 2014a;134:415-20.
immunoglobulin truly meet the necessary criteria and have
American Academy of Pediatrics (AAP).Committee
no contraindications for receiving that product. Using these on Infectious Diseases and Bronchiolitis Guidelines
products only in patients with an indication can result in a Committee. Updated guidance for palivizumab prophy-
large cost savings to an institution. laxis among infants and young children at increased risk
Finally, pharmacists can play a role in identifying and man- of hospitalization for respiratory syncytial virus infection.
aging the adverse effects associated with these products. Pediatrics 2014b;134:620-38.
For example, they can assist in selecting alternative thera- Centers For Disease Control. Principles of Vaccination. 2015a.
pies for patients who develop adverse reactions associated Centers For Disease Control. RSV Infection and Incidence.
with stabilizers, osmolarity, or IgA content. 2015b.
Centers For Disease Control. 2016 Combined Recommended
CONCLUSION Immunization Schedule for Persons Aged 0 Through 18 ears.
In passive immunization, antibodies are provided for short- Chapel H, Prevot J, Gaspar HB, et al. Primary immune defi-
term protection against infectious diseases. Although this ciencies principles of care. Front Immunol 2014;5:1-12.
occurs naturally through transmission from mother to infant
Dantal J. Intravenous immunoglobulins: in-depth review
transplacentally or through breast milk, it may entail providing of excipients and acute kidney risk injury. Am J Nephrol
exogenous antibodies. Palivizumab, a monoclonal antibody, 2013;38:275-84.
is a form of passive immunization and can prevent RSV infec-
Gonzalez-Quintela A, Alende R, Gude F, et al. Serum levels of
tion in those who are at a particularly high risk of acquiring the immunoglobulins (IgG, IgA, IgM) in a general adult popu-
disease. Immunoglobulins are also a form of passive immuni- lation and their relationships with alcohol consumption,
zation and are used in many diseases, including replacement smoking and common metabolic abnormalities. Clin Exp
therapy for primary and acquired immunodeficiencies, Immunol 2008;151:42-50.
measles PEP, and CDI. Finally, hyperimmune globulins, or Hayney MS. Vaccines, toxoids and other immunobi-
ologics. In: DiPiro JT, Talbert RL, Yee GC, et al, eds.
Pharmacotherapy, A Pathophysiologic Approach, 9th ed.
Practice Points New York: McGraw-Hill, 2014:2007.
Passive immunity is the process of providing antigens to a Hsu JL, Safdar N. Polyclonal immunoglobulins and
patient. This can be done maternally or through products hyperimmune globulins in prevention and manage-
such as monoclonal antibodies, immunoglobulin, and ment of infectious disease. Infect Dis Clin North Am
hyperimmune globulin. 2011;25:773-88.
Palivizumab is indicated for preventing RSV in patients
who are at risk of acquiring the infection. IMpact-RSV Study Group. Palivizumab, a humanized respi-
Immunoglobulin has been used in more than 150 disease
ratory syncytial virus monoclonal antibody, reduces
states. Because PIDDs rely on the use of immunoglobulin, hospitalization from respiratory syncytial virus infection in
they should be prioritized for therapy. high-risk individuals. Pediatrics 1998;102:531-7.
Many hyperimmune globulins exist and can be particularly Johnson S. Antibody responses to clostridial infection in
helpful in specific at-risk populations. humans. Clin Infect Dis 1997;25(suppl 2):S173-7.
Pharmacists can play a vital role in passive immunization,
including product selection, patient prioritization, and Laguna P, Golebiowska-Staroszczyk S, Trazaska M, et al.
management of adverse effects. Immunoglobulins and their use in children. Adv Clin Exp
Med 2015;24:153-9.

Leung DY, Kelly CP, Boguniewicz M, et al. Treatment with
intravenously administered gamma globulin of chronic
relapsing colitis induced by Clostridium difficile toxin.
J Pediatr 1991;118:633-7.
Oates-Whitehead RM, Baumer JH, Haines L, et al.

Intravenous immunoglobulin for the treatment of
Kawasaki disease in children. Cochrane Database Syst
Rev 2003;4:CD004000.
Ochs HD, Siegel J, Young HE. Stabilizers used in intrave-

nous immunoglobulin products: a comparative review.
Pharmacy Practice News. August 2010:1-8.
Peter JG, Chapel H. Immunoglobulin replacement ther-

apy for primary immunodeficiencies. Immunotherapy
2014;6:853-69.
Rhodes RT. Immune globulin: each product is unique. IG

Living. 2014:10-2.
Shah PJ, Vakil N, Kabakov A. Role of intravenous immune

globulin in streptococcal toxic shock syndrome and
Clostridium difficile infection. Am J Health Syst Pharm
2015;72:1013-9.
Shehata N, Palda V, Bowen T, et al. The use of immunoglob-

ulin therapy for patients with primary immune deficiency:
an evidence-based practice guideline. Transfus Med Rev
2010;24:S28-50.
Tapisiz A, Polat M, Kara SS, et al. Prevention of mea-

sles spread on a paediatric ward. Epidemiol Infect
2015;143:720-4.
Wong PH, White KM. Impact of immunoglobulin therapy in

pediatric disease: a review of immune mechanisms. Clin
Rev Allergy Immunol 2015 Jul 4. [Epub ahead of print]
Young MK, Nimmo GR, Cripps AW, et al. Post-exposure

passive immunisation for preventing measles. Cochrane
Database Syst Rev 2014;4:CD010056.

41. Which one of the following patients is the best candidate stable estimated glomerular filtration rate at 52 mL/minute
to receive palivizumab during the respiratory syncytial per 1.73 m2. You would like to initiate intravenous immunoglob-
virus (RSV) season? ulin (IVIG) to treat her Kawasaki disease but are concerned
A. A premature infant (born at 30 weeks 2 days) with about this agents association with acute renal failure.
no apparent health problems 45. Which one of the following products is most likely to
B. A premature infant (born at 31 weeks 3 days) who is cause acute renal failure in C.F.?
5 weeks old and has required 25% oxygen therapy
A. Carimune NF
since birth
B. Octagam
C. A 3-month-old infant with a small ventricular septal
C. Privigen
defect
D. Hizentra
D. A newborn infant with a new diagnosis of cystic
fibrosis but no signs of chronic lung disease (CLD) 46. C.F. has been admitted to the pediatric ICU with presumed
sepsis. Which one of the following antibiotics would place
42. Which one of the following patients is the best candidate
C.F. at highest risk of developing acute renal failure?
for a dose of palivizumab during his or her second year of
life? A. Vancomycin
B. Ertapenem
A. A 13-month-old who has continued to need
C. Ceftazidime
corticosteroids for CLD since birth
D. Ciprofloxacin
B. A 15-month-old (born at 28 weeks 4 days gestation)
with no chronic medical issues 47. A 6-month-old boy receives a diagnosis of a common
C. A 14-month-old with aortic stenosis variable immunodeficiency disorder. The patients older
D. A 16-month-old who had surgery for acyanotic heart sister has an IgA deficiency, and his mother is concerned
disease at age 6 weeks that the patient may develop an adverse reaction to
immunoglobulin. Which one of the following immuno-
43. Which one of the following patients with congenital heart
globulin products is best to recommend for this patient?
disease would most warrant administration of a booster
dose of palivizumab? A. Carimune NF
B. Gammagard SD
A. A 5-month-old whose patent ductus arteriosus was
C. Octagam
repaired
D. Flebogamma DIF
B. An 11-month-old with severe pulmonary
hypertension 48. Your institution is experiencing a shortage of immuno-
C. A 10-month-old who received a cardiac transplant 2 globulin. Which one of the following patients has the
weeks ago highest priority to receive immunoglobulin?
D. A 9-month-old with cardiomyopathy requiring A. A 3-year-old girl with Clostridium difficile infection
chronic medication B. A 6-year-old immunocompetent girl exposed to
44. As a pediatric ICU pharmacist, you see three patients measles at school
with a diagnosis of RSV infection simultaneously in C. A 7-year-old boy with autosomal
December. The father of a patient in your care worries agammaglobulinemia
that this is an RSV outbreak and asks that palivizumab be D. A 5-year-old boy with Guillain-Barr syndrome after
the influenza vaccine
administered to all patients on the unit. Which one of the
following is the best course of action in this situation? 49. A 9-month-old girl with a series of upper respiratory
A. Conduct an in-service on infectious disease infections was recently given a diagnosis of IgG subclass
precautions. deficiency. She will be initiated on Octagam IVIG therapy.
B. Give all patients a booster dose of palivizumab. Which one of the following surrogate markers would best
C. Give patients who appear to have RSV symptoms a determine the success of this patients immunoglobulin
dose of palivizumab. therapy?
D. Place all patients on isolation precautions. A. Increase in serum IgG concentrations
B. Decreased frequency of upper respiratory infections
Questions 45 and 46 pertain to the following case. C. Decreased adverse reactions associated with IVIG
C.F. is a 5-year-old girl with Kawasaki disease. Her medical infusion
history also includes polycystic kidney disease with a D. Decrease in CRP concentrations

Questions 50 and 51 pertain to the following case. 55. A male infant (weight 1580 g) is born at 31 weeks 5 days
J.V. is an 8-month-old boy (weight 8 kg) who has been exposed gestation to a mother whose hepatitis B virus (HBV) sta-
to measles at his day care. Because his sister has a history tus is unknown. Which one of the following is the best
of a small bowel transplant, J.V.s pediatrician wants to pre- course of action regarding administering the hepatitis B
scribe him IVIG for measles postexposure prophylaxis. immunoglobulin (HBIG) and HBV vaccines to this infant?
50. Your hospital formulary contains Privigen. Which one of A. Administer the HBIG and HBV vaccines now.
the following is the most appropriate volume to adminis- B. Administer the HBIG vaccine now and the HBV
ter to J.V.? vaccine at 1 month chronological age.
A. 3.2 mL C. Administer the HBIG vaccine now; the HBV vaccine
B. 6.4 mL is not indicated.
C. 32 mL D. Administer the HBV vaccine now; the HBIG vaccine
D. 64 mL is not indicated.
51. After receiving IVIG today, when would it be best for J.V. 56. A 14-year-old male adolescent presents to the local
to receive the measles vaccine? ED after allegedly being bitten by a bat while vacation-
ing with his family at their cabin. Although the patient
A. 1 year of age.
is convinced he was bitten, no visible bite marks are
B. 16 months of age.
found. The bat is not available for rabies testing. A
C. 2 years of age.
D. 5 years of age. phone call to the local health department informs the
ED care team that several bats in the area have been
52. An 11-year-old boy has received IVIG for X-linked agam- confirmed as being infected with rabies. Which one of
maglobulinemia (an antibody deficiency primary the following is best to recommend regarding adminis-
immunodeficiency disease) since 6 months of age. tering the rabies vaccine and rabies immunoglobulin in
Immediately after his recent transfusion, he has ten- this patient?
derness, warmth, and redness along the vein that was
injected. Which one of the following is best explains this A. Administer rabies immunoglobulin only.
patients new symptoms? B. Administer a four-dose series of rabies vaccine only.
C. Administer a four-dose series of rabies vaccine and
A. The hospital switched its formulary IVIG from
one dose of rabies immunoglobulin.
Privigen to Gammaplex.
D. Administer a five-dose series of rabies vaccine and
B. The patient may have developed acute kidney
one dose of rabies immunoglobulin.
failure.
C. The patient is having a drug interaction with a 57. In which one of the following scenarios would it be
concurrent antibiotic. best to recommend tetanus toxoid alone over tetanus
D. The patient is having a hypersensitivity reaction. immunoglobulin? Assume the patient is a 5-year-old girl
who is otherwise healthy with a potential exposure to
53. You believe that one of your patients is having infusion
tetanus.
reactions associated with recently initiated IVIG ther-
apy. Which one of the following would best decrease the A. A history of one diphtheria, tetanus, and pertussis
occurrence of these adverse effects? (DTaP) vaccine
B. A history of two DTaP vaccines
A. Ask the patient to lie down during IVIG infusion.
C. A history of three DTaP vaccines
B. Decrease the infusion rate.
D. An unknown vaccine history regarding DTaP
C. Switch to a formulation with less IgA.
vaccines
D. Transition the patient to intramuscular
immunoglobulin. 58. Which one of the following patients is the best candidate
to receive the varicella zoster immunoglobulin?
54. Which one of the following patients would be the best
candidate to remain on IVIG as opposed to switching to A. A 7-year-old immunocompetent girl who is up-to-
subcutaneous immunoglobulin? date on all vaccines and is exposed to varicella at
school
A. An 8-year-old girl with a documented IgA deficiency
B. A 4-year-old immunocompetent boy who was
B. A 6-year-old boy who requires a large volume of
exposed to varicella 2 weeks prior
immunoglobulin
C. A preterm infant (weight 954 g) during a hospital
C. A 4-year-old girl with a high occurrence of systemic
outbreak of varicella
adverse reactions to immunoglobulin
D. A term newborn whose mother develops varicella 1
D. A 15-year-old male adolescent who desires more
week after giving birth
independence

59. To evaluate the efficacy of cytomegalovirus immuno-
globulin (CMVIG) in preventing CMV in hematopoietic
stem cell transplant (HSCT) recipients, researchers com-
pleted a retrospective chart review of the past 2 years.
They identified 214 patients with an HSCT who received
CMV prophylaxis, either with valganciclovir alone or
CMVIG and valganciclovir in combination. The CMV
infection rate in the patients taking valganciclovir alone
was 25.6% compared with 10.2% in the combination ther-
apy group. Which one of the following best describes the
number needed to treat with CMVIG to prevent one CMV
infection?
A. 4.
B. 7.
C. 16.
D. 31.
60. A 5-year-old boy receives a measles, mumps, and rubella
(MMR) vaccine today for entry into kindergarten. At the
same appointment, he is given a diagnosis of a second-
ary immunodeficiency disease. To maximize the efficacy
of the MMR vaccine, which one of the following best
depicts the soonest he can receive IVIG?
A. 2 weeks
B. 1 month
C. 6 weeks
D. 2 months

Learner Chapter Evaluation: Passive Immunization.
48. Distinguish the unique features of specific formulations
Strongly agree of immunoglobulins.
Agree 49. Assess the appropriateness of palivizumab for specific
Neutral patient populations.
Disagree 50. Evaluate the warnings, precautions, and contraindica-
Strongly disagree tions of agents used in passive immunization.
51. Devise a plan for preventing and treating the adverse
37. The content of the chapter met my educational needs. effects associated with immunoglobulins.
38. The content of the chapter satisfied my expectations. 52. Evaluate the appropriateness of hyperimmune globulin
39. The author presented the chapter content effectively. therapy for specific patient exposures.
40. The content of the chapter was relevant to my practice 53. Please provide any specific comments related to any
and presented at the appropriate depth and scope. perceptions of bias, promotion, or advertisement of
commercial products.
41. The content of the chapter was objective and balanced.
54. Please expand on any of your above responses, and/or
42. The content of the chapter is free of bias, promotion, or provide any additional comments regarding this chapter:
43. The content of the chapter was useful to me. Questions 5557 apply to the entire learning module.
44. The teaching and learning methods used in the chapter 55. How long did it take you to read the instructional
were effective. materials in this module?
45. The active learning methods used in the chapter were 56. How long did it take you to read and answer the assess-
effective. ment questions in this module?
46. The learning assessment activities used in the chapter 57. Please provide any additional comments you may have
were effective. regarding this module:

Clinical and Practice Updates
Clinical and Practice Updates Panel
Series Editors: Reviewers

Marcia L. Buck, Pharm.D., FCCP, FPPAG Shirley M. Tsunoda, Pharm.D.
Clinical Coordinator Associate Professor
University of Virginia Childrens Hospital Skaggs School of Pharmacy and Pharmaceutical Sciences
Associate Professor University of California San Diego
Department of Pediatrics La Jolla, California
University of Virginia School of Medicine Brenda Winger, Pharm.D., BCPS, BCOP
Clinical Professor
Pharmacy Manager
Virginia Commonwealth University School of Pharmacy
Intermountain Healthcare
Department of Pharmacy Services
Salt Lake City, Utah
University of Virginia Health System
Charlottesville, Virginia Monica A. Puebla, Pharm.D., MBA, MHA, BCPS
Healthcare Professional Reviewer
Kalen B. Manasco, Pharm.D., BCPS
Med-ERRS, Inc.
Clinical Associate Professor Houston, Texas
Department of Clinical and Administrative Pharmacy
University of Georgia College of Pharmacy
Augusta, Georgia TRANSLATING EVIDENCE INTO
PRACTICE: HPV VACCINE
Faculty Panel Chair:
Jennifer Le, Pharm.D., MAS, BCPS-AQ ID, FCCP, FCSHP Authors
Professor of Clinical Pharmacy Nathan Painter, Pharm.D., CDE
University of California, San Diego Associate Clinical Professor of Pharmacy
Skaggs School of Pharmacy and Pharmaceutical Sciences Co-Director, Clinical Pharmacy UCSD Family Medicine Clinics
La Jolla, California University of California, San Diego
Faculty-in-Residence Skaggs School of Pharmacy and Pharmaceutical Sciences
Long Beach Memorial and Miller Childrens Hospital La Jolla, California
Long Beach, California
Stephanie Mayne, MHS
Research Coordinator
Department of Pediatrics
INTERACTIVE CASE ON SOLID ORGAN The Childrens Hospital of Philadelphia
TRANSPLANT IMMUNOLOGY Philadelphia, Pennsylvania
Authors Reviewers
Barrett Crowther, Pharm.D., FAST, BCPS Carlton K.K. Lee, Pharm.D., MPH, FASHP, FPPAG
Pediatric Transplant Clinical Pharmacist Clinical Pharmacy Specialist, Pediatrics
Department of Pharmacy Department of Pharmacy
University Health System The Johns Hopkins Hospital
San Antonio, Texas Associate Professor of Pediatrics
School of Medicine
Leslie Stach, Pharm.D., BCPS John Hopkins University
Solid Organ Transplant Clinical Pharmacist Clinical Professor
Department of Pharmacy School of Pharmacy
Ann and Robert H. Lurie Childrens Hospital of Chicago University of Maryland
Chicago, Illinois Baltimore, Maryland
Nicholas M. Fusco, Pharm.D., BCPS Reviewers
Clinical Assistant Professor Susan McKamy Adams, Pharm.D., BCPS
Pharmacy Practice Lead Clinical Pharmacist Specialist, Pediatrics
University at Buffalo School of Pharmacy Inpatient Pharmacy Department
and Pharmaceutical Sciences Miller Childrens and Womens Hospital of Long Beach
Buffalo, New York Long Beach, California
Melissa Ray, Pharm.D., BCPS
TRANSLATING EVIDENCE INTO PRACTICE: Clinical Pharmacist III
VANCOMYCIN NEPHROTOXICITY UnitedHealth Group
Tampa, Florida
Authors Clinical Assistant Professor of Pharmacy Practice
University of Florida College of Pharmacy
Jennifer Le, Pharm.D., MAS, BCPS-AQ ID, FCCP, FCSHP
Gainesville, Florida
Professor of Clinical Pharmacy
University of California, San Diego The American College of Clinical Pharmacy and the authors
Skaggs School of Pharmacy and Pharmaceutical Sciences thank the following individuals for their careful review of the
La Jolla, California Clinical and Practice Updates chapters:
Faculty-in-Residence
Nicola G. Dahl, Pharm.D.
Long Beach Memorial and Miller Childrens Hospital
Medical Writer
Long Beach, California
Kanab, Utah
Kristen R. Nichols, Pharm.D., BCPPS, BCPS-AQ ID
Ralph H. Raasch, Pharm.D., BCPS, FCCP
Assistant Professor
Associate Professor of Pharmacy (retired)
Pharmacy Practice
Division of Practice Advancement and Clinical Education
Butler University College of Pharmacy & Health Sciences
Eshelman School of Pharmacy
Indianapolis, Indiana
The University of North Carolina at Chapel Hill
Co-Director, Pediatric Antimicrobial Stewardship Program
Chapel Hill, North Carolina
Riley Hospital for Children at Indiana University Health
Indianapolis, Indiana
DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST
Consultancies: Barrett R. Crowther (Walgreens); Jennifer Le (Pfizer, Cempra); Kristen R. Nichols (Indiana State Health Department);
Grants (ASHP); Nathan Painter (American Association of Diabetes Educators); Melissa Ray (Therapeutic Research Center)
Stock Ownership:
Royalties: Carlton K.K. Lee (Elsevier, Inc.)
Grants: Jennifer Le (National Institutes of Health, Pfizer, Astellas and Cubist); Carlton K.K. Lee Grants (Optimer Pharmaceuticals,
Cerexa Pharmaceuticals, Astellas Pharma); Shirley M. Tsunoda (Novartis)
Honoraria:
Other:
Nothing to disclose: Susan M. Adams; Nicholas M. Fusco; Noelle Leung; Stephanie Mayne; Monica A. Puebla; Leslie M. Stach
ROLE OF BPS: The Board of Pharmacy Specialties (BPS) is an autonomous division of the American Pharmacists Association
(APhA). BPS is totally separate and distinct from ACCP. The Board, through its specialty councils, is responsible for specialty
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Other questions regarding recertification should be directed to:
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CONTINUING PHARMACY EDUCATION
AND RECERTIFICATION INSTRUCTIONS
ontinuing Pharmacy Education Credit: The American College of Clinical Pharmacy is accredited by the Accreditation
C
Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education (CPE).
PedSAP: Target Audience: The target audience for PedSAP 2016 Book 1 (Immunology) is pediatric pharmacotherapy specialists
and advanced-level clinical pharmacists caring for pediatric patients with several immunologic and antimicrobial considerations.
Available CPE credits: Purchasers who successfully complete all posttests for PedSAP 2016 Book 1 (Immunology) can earn
9.0 contact hours of continuing pharmacy education credit. The universal activity numbers are as follows: Immunology
0217-0000-16-019-H01-P, 5.0 contact hours; and Clinical and Practice Updates 0217-0000-16-020-H01-P, 4.0 contact hours.
You may complete one or all available modules for credit. Tests may not be submitted more than once.
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Interactive Case: Immunology in Solid
Organ Transplantation
By Barrett Crowther, Pharm.D., FAST, BCPS; and Leslie Stach, Pharm.D., BCPS
Reviewed by Shirley M. Tsunoda, Pharm.D.; Brenda Winger, Pharm.D., BCPS, BCOP; and Monica A. Puebla, Pharm.D., MBA, MHA, BCPS
LEARNING OBJECTIVES
1. Evaluate the differences in vaccine considerations as they apply to candidates for and recipients of solid organ transplan-
tation (SOT).
2. Develop a schedule for catch-up vaccinations for patients with a SOT.
3. Design an appropriate strategy for providing vaccinations to parents and siblings of a SOT recipient.
4. Devise a pharmacotherapeutic plan for SOT recipients based on the individual patients endogenous and passively trans-
ferred antibody status.
5. Develop a plan for managing immunoglobulins and preventing adverse effects using different immunoglobulin preparations.
INTERACTIVE CASE
Click here to begin this PedSAP activity.
AMR Antibody-mediated rejection
CMV Cytomegalovirus
DSA Donor-specific antibody BASELINE KNOWLEDGE STATEMENTS
DTaP Diphtheria, tetanus, and acellular
pertussis vaccine Readers of this chapter are presumed to be familiar with the
Hib Haemophilus influenzae type b following:
IDSA Infectious Diseases Society of Interpreting basic laboratory tests
America Assessing appropriateness of vaccines for healthy children
IIV Inactivated influenza vaccine Understanding the pathophysiology of vaccine-preventable
IVIG Intravenous immunoglobulin diseases
LAIV Live, attenuated influenza vaccine Recognizing the mechanism of action and common
MMR Measles, mumps, and rubella adverse reactions with solid organ transplant maintenance
PCV Pneumococcal conjugate vaccine immunosuppressive agents
(7-valent, 13-valent)
PPSV23 23-valent pneumococcal polysac-
ADDITIONAL READINGS
charide vaccine
PRA Panel of reactive antibody The following free resources have additional background
RSV Respiratory syncytial virus information on this topic:
SCIG Subcutaneous immunoglobulin CDC. Vaccines & Immunization Topics.
SOT Solid organ transplantation Advisory Committee for Immunization Practices. Vaccine
VariZIG Varicella zoster immunoglobulin Recommendations.
Infectious Diseases Society of America. 2013 Clinical
Practice Guideline for Vaccination of the
Immunocompromised Host.
Editors Note: The authors wish to acknowledge the American Society of Transplantation. 2013 Infectious
contribution of Eric M. Tichy, Pharm.D., BCPS, FCCP, Disease Guidelines, 3rd ed.
FAST, who created the outline for this PedSAP feature.
Table of common pediatric laboratory reference values.
PedSAP 2016 Book 1 Immunology 73 Interactive Case: Immunology in Solid Organ Transplantation
1. The day after Christmas, a 9-month-old, former 35-week B. Administer the measles, mumps, and rubella (MMR)
premature boy receives a heart transplant for a complex and varicella vaccines regardless of immune status.
congenital heart defect with heart failure. Four weeks C. Initiate levofloxacin prophylaxis for all bacterial
later, he is ready for discharge home. He was hospital- infections because she has received significant
ized for 3 months while awaiting a transplant and had immunosuppression.
several infections, including Staphylococcus aureus bac- D. Review her vaccination record for meningococcal
teremia and a parainfluenza respiratory viral infection, vaccine ACWY; initiate levofloxacin for prophylaxis
during that period. He is up-to-date with his 6-month of N. meningitidis.
immunizations. The patient will receive the inactivated
3. You are seeing a 12-month-old girl for a follow-up biopsy
influenza vaccine (IIV) before leaving, but his mother
in November 1.5 months after an orthotopic heart trans-
is concerned about respiratory syncytial virus (RSV)
plant. Because influenza season began early, everyone
because the patients 4-year-old sister attends day care.
in the waiting room is wearing a mask. The patient is at
Which one of the following is best to recommend regard-
the office with her mother, 4-year-old sister, and 8-year-
ing palivizumab administration for this child?
old brother. The patient was given a diagnosis of viral
A. Do not administer; standard precautions should be myocarditis at 7 months of age and, within 3 weeks of
sufficient because he is not a less than 29-week hospital admission, was listed as status 1a for a heart
premature infant and no longer has congenital heart transplant. For her maintenance immunosuppression,
disease. she receives tacrolimus (goal 1012), mycophenolate
B. Administer; he recently had a heart transplant, and it (600 mg/m2 every 12 hours), and prednisolone (0.5 mg/
is RSV season. kg/dose every 12 hours). Before transplantation, she
C. Administer; he should have received palivizumab received her 6-month vaccinations. Which one of the
while hospitalized in November and December as following plans is best to recommend for catch-up vacci-
well as continuing treatment as an outpatient. nations for this patient?
D. Do not administer; he should receive the RSV
A. She should receive all of her 12-month vaccinations
vaccine.
including MMR, varicella vaccine, and influenza
2. A 14-year-old girl is admitted for a kidney transplant vaccine because she has school-aged siblings who
from a deceased donor. The patient has end-stage renal may expose her to these infections.
disease caused by renal dysplasia and has received B. She should only receive inactivated influenza
hemodialysis three times a week for the past 2 years vaccine (IIV) because it is flu season and she is
with a baseline SCr of about 5.5 mg/dL. Her last panel of greater than 1 month post-transplantation.
reactive antibody (PRA) measurement 1 month ago was C. She should only receive her inactivated vaccines
class I 25% and class II 46%. She received induction ther- such as Haemophilus influenzae type B (Hib)
apy with methylprednisolone and antithymocyte globulin and pneumococcal conjugate vaccine 13-valent
and cefazolin for surgical antibiotic prophylaxis. Imme- (PCV13) because live vaccines are not indicated
diately after the transplant and during the first 24 hours post-transplantation.
post-transplantation, her SCr measurements were 5.5 D. She should wait until 6 months post-transplantation
mg/dL, 4.3 mg/dL, and 3.5 mg/dL; however, the last two and then receive her entire 12-month vaccinations
measurements were 4.6 mg/dL and 6.7 mg/dL. The sur- including MMR and varicella vaccine.
geons inform you that they are concerned about atypical
4. A 4-year-old girl, a new patient in your liver transplant
hemolytic uremic syndrome/thrombotic microangio-
follow-up clinic, received a deceased donor liver trans-
pathy or hyperacute rejection. The patient receives
plant 1.5 years ago for biliary atresia with a failed Kasai
intravenous immunoglobulin (IVIG) 1 g/kg and rituxi-
procedure. Her immunosuppressive regimen consists
mab 375 mg/m2, and the team suggests blocking the
of tacrolimus 1.5 mg twice daily with a goal concentra-
membrane attack complex with eculizumab. The patient
tion of 68 ng/dL and mycophenolate mofetil 200 mg/
receives her dose before you arrive at the hospital in the
m2/dose twice daily. About 3 months ago, she received
morning. As soon as you arrive at the hospital, which one
a 3-day steroid burst for acute cellular rejection. Her
of the following actions is best to take for this patient?
family recently transferred her from a childrens hospi-
A. Review her vaccination record for meningococcal tal in Atlanta, and her vaccine records are en route. The
vaccine against serotypes ACWY and B; initiate patients mother states that she is hesitant for her daugh-
penicillin VK orally for prophylaxis of N. meningitidis. ter to receive too many vaccines at once. She also says
that her daughter once got the flu from a shot so never 6. A 5-year-old girl has a medical history of a deceased
again received the influenza vaccine. However, because donor renal transplant about 2 years ago for end-stage
the girls healthy cousin was just hospitalized with influ- renal disease caused by a small left solitary kidney at
enza, the mother is now interested in the vaccine. Which birth. The patient also has a history of vesicoureteral
one of the following counseling points is best to provide reflux and hypertension related to transplantation. One
this patients mother? month ago, she received methylprednisolone 10 mg/kg/
day intravenously for 3 days for mild acute cellular rejec-
A. The girl should not receive any vaccines because
tion. Two days ago, she presented to the inpatient acute
she recently had an episode of rejection, which
care unit for a renal biopsy as a workup for recurrent rejec-
might cause her to have another episode.
tion, given her recent increase in SCr. The final biopsy
B. The girl should receive LAIV (live, attenuated
today reveals acute cellular rejection without acute anti-
influenza vaccine) because it is the only influenza
body-mediated rejection (AMR) (negative C4d staining).
vaccine available in the clinic today.
The Luminex assay reveals no evidence of donor-specific
C. The girl should receive IIV; her mother does not need
antibodies. Her maintenance drugs include amlodipine
to receive her vaccine because her daughter will
2.5 mg by mouth daily; sulfamethoxazole/trimethoprim
have full immunity.
400 mg/80 mg by mouth daily; prednisolone 3 mg by
D. The girl should receive IIV and another vaccine in
mouth every Monday, Wednesday, Friday, and Saturday;
1 month to complete her first series of influenza
mycophenolate mofetil 300 mg by mouth twice daily; and
vaccine.
tacrolimus 2 mg by mouth twice daily. According to the
5. A 7-year-old girl presents 3 years after a deceased donor KDIGO guidelines, which one of the following regimens
kidney transplant for end-stage renal disease related to would best treat this patients acute cellular rejection
nephrotic syndrome. She is at the clinic for her yearly visit episode?
and is in good health with no acute issues. Before trans- A. Rituximab.
plantation, the patient took steroids since diagnosis at B. Intravenous rabbit antithymocyte globulin.
2 years of age. She has done relatively well but has had C. Subcutaneous immunoglobulin (SCIG).
some episodes of acute cellular rejection, requiring short D. Plasmapheresis plus intravenous immunoglobulin
3-day courses of pulse intravenous methylprednisolone (IVIG).
in the past 3 years with brief escalations in maintenance
therapy. She has not received many of her vaccinations 7. A 12-year-old African-American girl presents in the
because she was taking steroids before the transplant. kidney transplant clinic. She received a living unrelated
She has received enough maintenance immunosuppres- donor kidney transplant 1 year ago because of end-stage
sion that her physician has not wanted her to receive renal disease secondary to focal segmental glomeru-
vaccinations. She has not received any vaccinations losclerosis. At transplantation, she received induction
since her 1-year-old shots. By looking at her serologies with intravenous basiliximab and has had no rejec-
before transplantation, you conclude that she is pro- tion episodes since transplantation. Her drugs include
tected against MMR and hepatitis B but is not immune tacrolimus 3 mg by mouth twice daily, prednisone 5 mg
to varicella. One week ago, the patient was visited by an by mouth daily, pantoprazole 40 mg by mouth daily,
out-of-state cousin who now has chickenpox. According amlodipine 10 mg by mouth daily, atenolol 25 mg by
to the CDCs recommendations for using varicella zoster mouth daily, and isradipine 2.5 mg by mouth every 6 hours
immunoglobulin (VariZIG), which one of the following as needed for blood pressure greater than 140/90 mm
strategies is best to recommend for this patient? Hg. The patient has a new 2-month-old brother who is
healthy. According to their mother, the patients brother
A. Admit her to the hospital for acyclovir intravenously is due for the following vaccines: inactivated poliovirus
10 mg/kg/dose every 8 hours for a total of 7 days. vaccine (IPV), PCV13, Hib, rotavirus, and diphtheria, tet-
B. Administer acyclovir orally at home together with anus, and acellular pertussis (DTaP). The mother asks
a varicella vaccine to try to confer immunity before you which of these vaccines can safely be administered.
infection. According to the 2013 IDSA clinical practice guideline for
C. Administer VariZIG because she does not have vaccination of the immunocompromised host, which one
immunity, as evidenced by her serology, and it is of the following vaccines is best to recommend for this
less than 10 days from exposure. patients brother?
D. Do not administer VariZIG because the exposure
A. The IPV, PCV13, Hib, and DTaP vaccines but not the
was more than 96 hours ago. She is many years out
rotavirus vaccine.
from transplantation and is therefore at less risk of
B. The PCV13, Hib, rotavirus, and DTaP vaccines but
developing infection from exposure.
not the IPV vaccine.
C. The IPV, PCV13, Hib, and DTaP vaccines but not the One dose of PCV13 at 10 years of age
rotavirus and IPV vaccines. Three doses of Hib vaccine before 6 months of age
D. The IPV, PCV13, Hib, DTaP, and rotavirus vaccines, Four doses of inactive polio vaccine
but the patient should avoid handling her brothers One dose of meningococcal conjugate (MCV4)
diapers for 1 month after vaccinations. vaccine
Two doses of MMR vaccine
8. Three months ago, a 16-year-old white girl received a
Two doses of varicella vaccine
bilateral lung transplant for end-stage lung disease
One dose of influenza vaccine during the most
secondary to cystic fibrosis. Her medical history also
recent influenza season
includes gastroesophageal reflux disease, pancreatic
Three doses of human papillomavirus 4 vaccine
insufficiency, and chronic kidney disease caused by a sig-
nificant history of aminoglycoside therapy. The patients According to the 20152016 CDC immunization schedule
postoperative course was complicated by Aspergillus fla- guidelines, which one of the following strategies is best to
vus and Pseudomonas aeruginosa pneumonia. Five days ensure that this patient is up-to-date on vaccinations for
ago, she was readmitted to the hospital medical ICU for potential liver transplantation?
acute-on-chronic respiratory failure requiring endotra- A. Patient is up-to-date on vaccinations.
cheal intubation and mechanical ventilation. She had B. Give meningococcal serotype group B vaccine.
alveolar infiltrates suggestive of rejection. A transbron- C. Give PPSV23 (23-valent pneumococcal
chial lung biopsy yesterday revealed acute AMR (acute polysaccharide vaccine).
lung injury with neutrophil infiltration of the alveolar D. Give cytomegalovirus (CMV) vaccine.
septae with capillaritis and C4d deposition in the alveo- 10. Yesterday morning, a 5-month-old Hispanic boy received
lar capillaries). Furthermore, the Luminex assay revealed a deceased donor split liver transplant for biliary atresia.
strong de novo donor-specific antibodies to HLA-B44 and He received induction with intravenous basiliximab and
DR53 (mean fluorescence intensity of 5649 and 7034, is receiving a maintenance immunosuppressive regimen
respectively). The patients immunosuppressive regimen of intravenous methylprednisolone and oral tacrolimus.
includes tacrolimus 1.5 mg by mouth twice daily, myco- The transplant donor was a 12-year-old girl. The donor
phenolate sodium 720 mg by mouth twice daily, and was CMV IgG positive, and the recipient was CMV IgG
prednisone 15 mg by mouth once daily. The team decides positive at transplantation. According to the 2013 Amer-
to treat the acute AMR episode with five plasmapheresis ican Society of Transplantation ID guideline, which one
sessions followed by immunoglobulin 100 mg/kg/dose of the following regimens would be the best strategy for
after the first four sessions and 1 g/kg/dose after the final CMV prophylaxis in this patient?
plasmapheresis session. Depending on her response, the
A. Intravenous ganciclovir followed by conversion to
patient may also receive rituximab. When considering the
oral valganciclovir when he is considered stable.
immunoglobulin preparation to select for therapy, which
B. Intravenous ganciclovir for 7 days followed by
one of the following stabilizing agents used in immuno-
conversion to oral ganciclovir.
globulin preparations is best to avoid in this patient?
C. Intravenous ganciclovir for 7 days followed by
A. Maltose. conversion to oral acyclovir with pre-emptive
B. Sucrose. monitoring.
C. Glucose. D. Intravenous cidofovir followed by conversion to oral
D. Proline. brincidofovir when he is considered stable.
9. A 12-year-old Hispanic girl with chronic liver disease sec-

ondary to autoimmune hepatitis (AIH) is hospitalized for
an AIH flare caused by medication nonadherence. The
patient and her grandmother, her primary caregiver, are
being seen for a preliver transplant pharmacotherapy
consultation. The patient has no other significant medical
or surgical history. She takes prednisone, azathioprine,
and phytonadione. Her vaccine records, reviewed as part
of her liver transplant evaluation, show the following:
Three doses of hepatitis B vaccine, with a recent

hepatitis B surface antibody of 100 mIU/mL
One dose of Tdap (tetanus, diphtheria, and acellular
pertussis) vaccine at 11 years of age
Learner Chapter Evaluation: Interactive Case: Immunology in Solid Organ
Transplantation.
12. Evaluate the differences in vaccine considerations as
Strongly agree they apply to candidates for and recipients of solid organ
transplantation (SOT).
Agree
Neutral
13. Develop a schedule for catch-up vaccinations for
Disagree patients with a SOT.
Strongly disagree 14. Design an appropriate strategy for providing vaccina-
tions to parents and siblings of a SOT recipient.
1. The content of the chapter met my educational needs. 15. Devise a pharmacotherapeutic plan for SOT recipients
2. The content of the chapter satisfied my expectations. based on the individual patients endogenous and pas-
sively transferred antibody status.
16. Develop a plan for managing immunoglobulins and pre-
4. The content of the chapter was relevant to my practice venting adverse effects using different immunoglobulin
and presented at the appropriate depth and scope. preparations.
5. The content of the chapter was objective and balanced. 17. Please provide any specific comments related to any
6. The content of the chapter is free of bias, promotion, or perceptions of bias, promotion, or advertisement of
advertisement of commercial products. commercial products.
7. The content of the chapter was useful to me. 18. Please expand on any of your above responses, and/or
8. The teaching and learning methods used in the chapter provide any additional comments regarding this chapter:
were effective.
effective.
were effective.
Translating Evidence into Practice:
Human Papillomavirus Vaccination
By Nathan Painter, Pharm.D., CDE; and Stephanie Mayne, MHS
Reviewed by Carlton K.K. Lee, Pharm.D., MPH; and Nicholas M. Fusco, Pharm.D., BCPS
LEARNING OBJECTIVES
1. Identify groups recommended by the Advisory Committee on Immunization Practices (ACIP) for human papillomavirus
(HPV) vaccination.
2. Analyze the impact of various decision support methods on HPV vaccination.
3. Evaluate the benefits of clinician- and family-focused decision support for decreasing missed opportunities for HPV
vaccination.
TRANSLATING EVIDENCE INTO

PRACTICE
ACIP Advisory Committee on
Immunization Practices Topic Article
CHOP Childrens Hospital of Philadelphia Mayne SL, duRivage NE, Feemster KA, et al. Effect of
DTaP Diphtheria, tetanus, and acellular decision support on missed opportunities for human
pertussis vaccine papillomavirus vaccination. Am J Prev Med
EHR Electronic health record 2014;47:734-44.
HPV Human papillomavirus
HPV-1 Human papillomavirus vaccine On-demand Webcast
dose 1 Click here to begin this PedSAP activity.
HPV-2 Human papillomavirus vaccine Click here to view a transcription of this recorded webcast.
dose 2
HPV-3 Human papillomavirus vaccine
REFERENCES
dose 3
CDC. Epidemiology and Prevention of Vaccine-Preventable
HPV2 Bivalent HPV vaccine (Cervarix)
Diseases, 13th ed. Washington, DC: Public Health
HPV9 9-valent HPV vaccine (Gardasil 9)
Foundation, 2015.
HPV4 Quadrivalent HPV vaccine
(Gardasil) CDC. Human papillomavirus-associated cancersUnited
MCV Meningococcal vaccine States, 2004-2008. Morb Mortal Wkly Rep 2012;61:258-61.
PCV12 Pneumococcal conjugate vaccine CDC. Human papillomavirus vaccination coverage among
PBRN Practice-based research network adolescent girls, 20072012, and postlicensure vaccine
PPSV23 Pneumococcal polysaccharide safety monitoring, 2006 2013United States. Morb
vaccine Mortal Wkly Rep 2013;62:591-5.
Tdap Tetanus, diphtheria, and acellular Fiks AG, Grundmeier RW, Mayne S, et al. Effectiveness of
pertussis vaccine
decision support for families, clinicians, or both on HPV
vaccine receipt. Pediatrics 2013;131:1114-24.
Hughes CC, Jones AL, Feemster KA, et al. HPV vaccine deci-
sion making in pediatric primary care: a semi-structured
interview study. BMC Pediatr 2011;11:74.
PedSAP 2016 Book 1 Immunology 79 Translating Evidence into Practice: Human Papillomavirus Vaccination
Markowitz LE, Hariri S, Lin C, et al. Reduction in human
papillomavirus (HPV) prevalence among young women
following HPV vaccine introduction in the United States,
National Health and Nutrition Examination Surveys, 2003-
2010. J Infect Dis 2013;208:385-93.
Rand CM, Shone LP, Albertin C, et al. National health care

visit patterns of adolescents: implications for delivery
of new adolescent vaccines. Arch Pediatr Adolesc Med
2007;161:252-9.
Satterwhite CL, Torrone E, Meites E, et al. Sexually

transmitted infections among US women and men: prev-
alence and incidence estimates, 2008. Sex Transm Dis
2013;40:187-93.
Vadaparampil ST, Kahn JA, Salmon D, et al. Missed clini-

cal opportunities: provider recommendations for HPV
vaccination for 11-12 year old girls are limited. Vaccine
2011;29:8634-41.
Wong CA, Taylor JA, Wright JA, et al. Missed opportunities

for adolescent vaccination, 2006-2011. J Adolesc Health
2013;53:492-7.
11. The HPV vaccine received an approved indication in C. Randomized controlled trial with individual-level
2006 to prevent HPV infections in female patients; this randomization only
was expanded in 2009 to cover male patients. Which one D. Cross-sectional study
of the following patient and product combinations best
meets the vaccination recommendations of the Advisory Questions 1620 pertain to the following case.
Committee on Immunization Practices (ACIP)? The study by Mayne et al (Effect of decision support on missed
A. A 7-year-old girl, bivalent HPV vaccine (HPV2) opportunities for human papillomavirus vaccination) aimed
B. An 8-year-old boy, quadrivalent HPV vaccine (HPV4) to compare the impact of clinician- versus family-focused
C. A 9-year-old girl, 9-valent HPV vaccine (HPV9) decision support, none, or both on captured opportunities for
D. A 10-year-old boy, HPV2 HPV vaccination.
12. An 11-year-old girl presents to her pediatrician with 16. Which one of the following statements best describes
cough, runny nose, and mild fever for the past 34 days. the greatest limitation of the study?
Her mother brought her to the office for these symptoms A. Randomization of study practices and participants
and for a note excusing her from school because she has was not stratified to provide balance between
missed several days. Which one of the following factors groups.
places this girl most at risk of a missed opportunity to B. Generalizability of the study may be limited because
administer the HPV vaccine? the study was only conducted in Philadelphia and
A. She is currently not feeling well. the surrounding areas.
B. She is not at the appropriate age. C. Statistical models did not control for patient,
C. She is presenting for an acute visit. clinician, and practice characteristics.
D. Her physician may not recommend it. D. The demographic characteristics of the study
groups were very different.
13. Using the Recommended Immunization Schedule pub-
lished by the CDC and endorsed by ACIP, which one of 17. According to the findings of the study, which one of the
the following vaccines presents the best opportunity for following interventions will most likely improve rates of
also administering the HPV vaccine? captured opportunities for HPV vaccination?
A. PCV12 A. Prompt families to visit an educational website

B. PPSV23 before office visits so that they can learn more about
C. DTaP the HPV vaccine.
D. Tdap B. Remind families that their child is due for the HPV
vaccine through phone calls before the visit.
14. An 11-year-old boy presents to his pediatrician for a pre-
C. Provide educational content, vaccine alerts, and
ventive visit. He has not previously received the HPV
performance feedback to clinicians.
vaccine. Which one of the following vaccines is most
D. Provide text message reminders to families about
appropriate to recommend for this patient at this time?
upcoming vaccinations.
A. HPV4
18. Which one of the following statements most accurately
B. HPV2
reflects the results of the study by Fiks et al that differed
C. HPV9
from the results of the study by Mayne et al?
D. HPV4 or HPV9
A. The family-focused intervention improved rates of
15. A researcher wants to determine the effectiveness of
HPV vaccination for dose 1 only.
an intervention to improve adolescent vaccination rates
B. The family-focused intervention improved rates of
targeted to clinicians within primary care practices.
HPV vaccination for doses 2 and 3 only.
The intervention involves implementation of a system
C. The family-focused intervention improved rates of
of electronic health record vaccine alerts. Which study
HPV vaccination for all 3 doses.
design would best answer this research question?
D. The family-focused intervention did not improve
A. Observational cohort study rates of any HPV vaccination dose.
B. Cluster randomized controlled trial
19. Which one of the following statements best describes
the study findings regarding the effectiveness of clini-
cian-focused intervention in different practice settings?
A. The clinician intervention increased captured
opportunities for HPV 1 at preventive visits to a
greater extent at suburban practices than at urban
practices.
B. The clinician intervention increased captured
opportunities for HPV 1 at preventive visits to a
greater extent at urban practices than at suburban
practices.
C. The clinician intervention increased captured
opportunities for all three doses at acute visits at
suburban practices only.
D. The clinician intervention increased captured
opportunities for all three doses at both urban and
suburban practices.
20. In the study by Mayne et al, the researchers used mar-
ginal standardization to transform the logistic regression
model into standardized proportions. Which one of the
following is the most appropriate interpretation of the
standardized proportions?
A. The actual proportion of captured opportunities in
each study arm
B. The expected proportion of captured opportunities if
the entire sample was in the control group
C. The expected proportion of captured opportunities if
the entire sample received both interventions
D. The expected proportion of captured opportunities if
the entire sample was alternately subjected to each
intervention arm or monitored as a control group
Learner Chapter Evaluation: Translating Evidence into Practice:
Human Papillomavirus Vaccination.
30. Identify groups recommended by the Advisory

Strongly agree Committee on Immunization Practices (ACIP) for human
papillomavirus (HPV) vaccination.
Agree
Neutral 31. Analyze the impact of various decision support methods
Disagree on HPV vaccination.
Strongly disagree 32. Evaluate the benefits of clinician- and family-focused
decision support for decreasing missed opportunities
19. The content of the chapter met my educational needs. for HPV vaccination.
20. The content of the chapter satisfied my expectations. 33. Please provide any specific comments related to any
perceptions of bias, promotion, or advertisement of
21. The author presented the chapter content effectively. commercial products.
22. The content of the chapter was relevant to my practice 34. Please expand on any of your above responses, and/or
and presented at the appropriate depth and scope. provide any additional comments regarding this chapter:
24. The content of the chapter is free of bias, promotion, or
were effective.
effective.
were effective.
Translating Evidence into Practice:
Vancomycin-Associated Nephrotoxicity
By Jennifer Le, Pharm.D., MAS, BCPS-AQ ID, FCCP, FASHP; and
Kristen Nichols, Pharm.D., BCPS-AQ ID, BCPPS
Reviewed by Susan McKamy Adams, Pharm.D., BCPS; and Melissa Ray, Pharm.D., BCPS
LEARNING OBJECTIVES
1. Analyze the vancomycin pharmacokinetic and pharmacodynamic exposure parameters associated with nephrotoxicity in
pediatric versus adult patients.
2. Assess the significance of three variables associated with vancomycin nephrotoxicity in pediatric patients, and evaluate
the strength of design of studies evaluating these variables.
3. Evaluate the risks, benefits, and practical implications of various vancomycin therapeutic drug monitoring strategies for
pediatric patients.
4. Apply current best evidence to optimize vancomycin dosing while minimizing nephrotoxicity in pediatric patients.
TRANSLATING EVIDENCE INTO PRACTICE

ABBREVIATIONS IN THIS FEATURE
Topic Article
AUC Area-under-curve
AUC0-24 Area-under-curve over 24 hours Topic Article: Le J, Ny P, Capparelli EVC, et al. Pharmacodynamic
characteristics of nephrotoxicity associated with vancomycin use
BAL Broncho-alveolar lavage
in children. J Ped Infect Dis 2015;4:e109-16.
CL Clearance
Cmax Peak or maximum concentration On-demand Webcast
Cmin Trough or minimum concentration Click here to begin this PedSAP activity.
CXR Chest radiograph Click here to view a transcription of this recorded webcast.
IQR Interquartile range
Ke Elimination rate constant REFERENCES
PK Pharmacokinetics Akcan-Arikan A, Zappitelli M, Loftis LL, et al. Modified RIFLE cri-
CART Classification and regression tree teria in critically ill children with acute kidney injury. Kidney Int
MRSA Methicillin-resistant 2007;71:1028-35.
Staphylococcus aureus
Anderson BJ, Holford NH. Mechanism-based concepts of size
NONMEM Non-linear mixed effects modeling
and maturity in pharmacokinetics. Annu Rev Pharmacol Toxicol
Q Every 2008;48:303-32.
RUL Right upper lobe
SMX/TMP Sulfamethoxazole/trimethoprim Anderson BJ, Holford NH. Understanding dosing: children are small
adults, neonates are immature children. Arch Dis Childhood
Vd Volume of distribution
2013;98:737-44.
WT Weight
Bosso JA, Nappi J, Rudisill C, et al. Relationship between vancomy-
cin trough concentrations and nephrotoxicity: a prospective
multicenter trial. Antimicrob Agents Chemother 2011;55:5475-9.
Bulitta JB, Landersdorfer CB, Huttner SJ, et al. Population phar-

macokinetic comparison and pharmacodynamic breakpoints of
ceftazidime in cystic fibrosis patients and healthy volunteers.
Antimicrob Agents Chemother 2010;54:1275-82.
PedSAP 2016 Book 1 Immunology 85 TranslatingEvidenceintoPractice:Vancomycin-AssociatedNephrotoxicity

Carreno JJ, Kenney RM, Lomaestro B. Vancomycin- Mahmood I. Prediction of drug clearance in children: impact
associated renal dysfunction: where are we now? of allometric exponents, body weight, and age. Ther Drug
Pharmacotherapy 2014;34:1259-68. Monit 2007;29:271-8.
Cies JJ, Shankar V. Nephrotoxicity in patients with vancomy- Marsot A, Boulamery A, Bruguerolle B, et al. Vancomycin:
cin trough concentrations of 15-20 mug/ml in a pediatric a review of population pharmacokinetic analyses. Clin
ICU. Pharmacotherapy 2013;33:392-400. Pharmacokinet 2012;51:1-13.
Eiland LS, English TM, Eiland EH 3rd. Assessment of van- McKamy S, Hernandez E, Jahng M, et al. Incidence and risk
comycin dosing and subsequent serum concentrations in factors influencing the development of vancomycin neph-
pediatric patients. Ann Pharmacother 2011;45:582-9. rotoxicity in children. J Pediatr 2011;158:422-6.
Frymoyer A, Hersh AL, Coralic Z, et al. Prediction of van- Neely MN, Youn G, Jones B, et al. Are vancomycin trough
comycin pharmacodynamics in children with invasive concentrations adequate for optimal dosing? Antimicrob
methicillin-resistant Staphylococcus aureus infections: a Agents Chemother 2014;58:309-16.
Monte Carlo simulation. Clin Ther 2010;32:534-42.
Pai MP, Neely M, Rodvold KA, et al. Innovative approaches
Hidayat LK, Hsu DI, Quist R, et al. High-dose vancomycin to optimizing the delivery of vancomycin in individual
therapy for methicillin-resistant Staphylococcus aureus patients. Adv Drug Deliv Rev 2014;77:50-7.
infections: efficacy and toxicity. Arch Intern Med
2006;166:2138-44. Patel K, Crumby AS, Maples HD. Balancing vancomycin effi-
cacy and nephrotoxicity: should we be aiming for trough
Jeffres MN, Isakow W, Doherty JA, et al. A retrospective anal- or AUC/MIC? Paediatr Drugs 2015;17:97-103.
ysis of possible renal toxicity associated with vancomycin
in patients with health care-associated methicillin- Pottel H, Mottaghy FM, Zaman Z, et al. On the relationship
resistant Staphylococcus aureus pneumonia. Clin Ther between glomerular filtration rate and serum creatinine in
2007;29:1107-15. children. Pediatr Nephrol 2010;25:927-34.
Knoderer CA, Nichols KR, Lyon KC, et al. Are elevated van- Pottel H, Vrydags N, Mahieu B, et al. Establishing age/sex
comycin serum trough concentrations achieved within the related serum creatinine reference intervals from hospi-
first 7 days of therapy associated with acute kidney injury tal laboratory data based on different statistical methods.
in children? J Ped Infect Dis 2014;3:127-31. Clin Chim Acta 2008;396:49-55.
Kralovicova K, Spanik S, Halko J, et al. Do vancomycin serum Ragab AR, Al-Mazroua MK, Al-Harony MA. Incidence and
levels predict failures of vancomycin therapy or nephrotox- predisposing factors of vancomycin-induced nephrotoxic-
icity in cancer patients? J Chemother 1997;9:420-6. ity in children. Infect Dis Ther 2013;2:37-46.
Le J, Bradley JS, Murray W, et al. Improved vancomycin Rybak M, Lomaestro B, Rotschafer JC, et al. Therapeutic
dosing in children using area under the curve exposure. monitoring of vancomycin in adult patients: a consen-
Pediatr Infect Dis J 2013;32:e155-63. sus review of the American Society of Health-System
Pharmacists, the Infectious Diseases Society of America,
Le J, Ngu B, Bradley JS, et al. Vancomycin monitoring in and the Society of Infectious Diseases Pharmacists. Am J
children using bayesian estimation. Ther Drug Monit Health Syst Pharm 2009;66:82-98.
2014;36:510-8.
Schumacher GE, Barr JT. Bayesian approaches in pharma-
Le J, Vaida F, Nguyen E, et al. Population-based pharmacokinetic decision making. Clin Pharm 1984;3:525-30.
cokinetic modeling of vancomycin in children with renal
insufficiency. J Pharmacol Clin Toxicol 2014;2:1017-26. Spiegelhalter DJ, Myles JP, Jones DR, et al. Bayesian meth-
ods in health technology assessment: a review. Health
Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guide- Technol Assess 2000;4:1-130.
lines by the infectious diseases society of america for the
treatment of methicillin-resistant Staphylococcus aureus Totapally BR, Machado J, Lee H, et al. Acute kidney injury
infections in adults and children: executive summary. Clin during vancomycin therapy in critically ill children.
Infect Dis 2011;52:285-92. Pharmacotherapy 2013;33:598-602.
Lodise TP, Lomaestro B, Graves J, et al. Larger vancomy- van Hal SJ, Lodise TP, Paterson DL. The clinical signifi-
cin doses (at least 4 g per day) are associated with an cance of vancomycin minimum inhibitory concentration in
increased incidence of nephrotoxicity. Antimicrob Agents Staphylococcus aureus infections: a systematic review and
Chemother 2008;52:1330-6. meta-analysis. Clin Infect Dis 2012;54:755-71.
Lodise TP, Patel N, Lomaestro BM, et al. Relationship

between initial vancomycin concentration-time profile and
nephrotoxicity among hospitalized patients. Clin Infect Dis
2009;49:507-14.

21. According to studies of children and adults, which one C. Concomitant use of tobramycin, AUC over 24 hours of
of the following is most likely to be associated with van- 800 mcg-hr/mL or greater, and stay in the pediatric ICU
comycin nephrotoxicity? D. Stay in the pediatric ICU, dose of 60 mg/kg/day or
A. Trough concentration of 10 mcg/mL or greater greater, and trough concentration of 15 mcg/mL
B. Dosage 60 mg/kg/day in children (or greater than 4 or greater
g/day in adults) 24. You are designing a multicenter study to evaluate fac-
C. AUC over 24 hours of 600 mcg-hr/mL or greater tors associated with ototoxicity in hospitalized children
D. Therapy duration of more than 1 week receiving vancomycin therapy. You would like to explore
22. As a peer reviewer for a medical journal, you are critically 10 variables of interest (including both categorical and
evaluating a submitted manuscript. The pharmacoki- continuous variables) using a non-parametric test to
netic-pharmacodynamic study used population-based create a model that predicts the dichotomized outcome
modeling and post hoc Bayesian analysis to estimate of ototoxicity. Through this analysis, you will construct
individual patient peak and trough concentrations. a diagram that visually represents decisions to show
Which one of the following statements best describes the most important factors associated with ototoxicity.
the type of data needed to conduct the bayesian analysis When statistically significant, breakpoints will be derived
in this study? for continuous variables. Which one of the following best
A. Educated guess of inter- and intra-subject variability describes this type of analysis?
for clearance A. Classification and regression tree
B. Published population-based values for clearance B. Kaplan-Meier
and volume of distribution C. Univariate regression modeling
C. Patient-specific dosing history and predicted serum D. Cox regression analysis
concentrations
25. Given the methods presented in the journal article, which
D. Known pharmacokinetic parameters and measured
one of the following best describes the analysis method
drug concentrations
and program used for the population-based pharmacoki-
23. An 8-year-old boy (height 52 inches, weight 57 lb) is netic modeling that capitalized on the use of sparse data?
admitted to the hospital for a health careassociated
pneumonia with possible empyema. He has no signifi- A. Bayesian estimation
cant medical history except cephalexin use for a skin B. Classification and regression tree
infection 1 month before admission. He is current on his C. Kaplan-Meier
routine childhood immunizations. On admission, sputum D. Non-linear mixed effects
and blood cultures were obtained, and he was initiated
on vancomycin 400 mg intravenously every 6 hours Questions 2628 pertain to the following case.
and tobramycin 200 mg intravenously every 24 hours. C.K. is a 10-year-old boy (height 56 inches, weight 36 kg) with
On hospital day 2, he experienced respiratory distress a history of mitral stenosis, recent fatigue, and fevers. During
requiring admission to the pediatric ICU for close moni- hospital admission, he receives a diagnosis of infective endo-
toring. After 8 days of antibiotic therapy, the patients SCr carditis. C.K.s blood cultures are positive for MRSA by S.
increased from 0.6 mg/dL (baseline on admission day) to aureus and mecA rapid diagnostic tests; traditional culture
1.3 mg/dL. His SCr was 1.21.4 mg/dL for 3 days before and susceptibility results are pending. C.K. is initiated on van-
it declined, returning to normal values after 7 days. After comycin therapy for the treatment of his MRSA endocarditis.
the third dose of vancomycin therapy, the measured true
26. To assess C.K.s vancomycin exposure at steady state,
trough concentration was 16 mcg/mL, and AUC over 24
which one of the following most accurately describes
hours was 815 mcg-hr/mL. According to the multivari-
when it would be best to obtain plasma vancomycin
ate regression analysis in the presented journal article,
concentrations?
which one of the following risk factors most likely indi-
cates nephrotoxicity in this patient? A. 1 hour after the end of a 1-hour infusion
A. Concomitant use of tobramycin, trough concentration B. Just before a dose
of 10 mcg/mL or greater, and vancomycin therapy for C. After the distribution phase and just before the next
more than 1 week dose to calculate AUC0-24 by the clearance method
B. Recent cephalexin use, AUC over 24 hours of 800 D. Every hour to calculate AUC0-24 by the trapezoidal
mcg-hr/mL or greater, and stay in the pediatric ICU method

27. Susceptibility testing for C.K.s S. aureus isolate shows 30. Which one of the following is best to recommend for
a vancomycin MIC of 2 mg/L. Which one of the follow- J.M. to optimally balance the need for minimum effec-
ing AUC0-24 exposures would best target the treatment tive vancomycin exposure with the assessed risk of
of C.K.s endocarditis, and which is the potential nephro- nephrotoxicity?
toxic risk of this exposure?
A. Decrease the dose to achieve an AUC target of 200
A. 400 mg-hr/L or greater, no increased risk 799 mg-hr/L.
B. 400 mg-hr/L or greater, increased risk B. Continue the current dose to achieve an AUC target
C. 800 mg-hr/L or greater, no increased risk of 400 mg-hr/L or greater.
D. 800 mg-hr/L or greater, increased risk C. Increase the dose to achieve an AUC target of 800
mg-hr/L or greater.
28. Every 6 hours, C.K. receives vancomycin 540 mg infused
D. Substitute another antibiotic for vancomycin
over 1 hour. His SCr is 0.59 mg/dL. Which one of the fol-
because the desired AUC is 800 mg-hr/L or greater.
lowing best describes C.K.s patient-specific AUC0-24?
Day Time Dose (mg) Concentration (mg/L)

0500, 1100,
1 540
1700, 2300
0500, 1100,
2 540
1700, 2300
3 0500, 1100 540
3 0730 26
3 1045 13.7
A. 135 mg-hr/L
B. 350 mg-hr/L
C. 540 mg-hr/L
D. 720 mg-hr/L
Questions 29 and 30 pertain to the following case.
J.M. is a 6-year-old boy (weight 22 kg) with acute hematoge-

nous osteomyelitis of the right femur. Initial surgical bone
and blood cultures show S. aureus resistant to oxacillin and
clindamycin but susceptible to vancomycin (MIC of 0.5 mg/L
or less). J.M. has been receiving vancomycin 550 mg intra-
venously every 6 hours based on previous therapeutic drug
monitoring. On day 9 of treatment, J.M.s repeat blood cul-
tures remain negative; he is afebrile, with decreased pain, and
he can walk about the unit with some assistance. His CRP
has decreased from 21.9 mg/L to 8 mg/L. Serum vancomy-
cin concentrations at 3 hours and 6 hours after the start of a
1-hour infusion are 35 mg/L and 17.6 mg/L.
29. Which one of the following is the best assessment of
J.M.s vancomycin exposure related to efficacy and
nephrotoxicity?
A. Exposure is adequate to treat infection without
significant risk of nephrotoxicity.
B. Both trough concentration and AUC indicate
unnecessary risk of nephrotoxicity.
C. The trough concentration, but not the AUC, indicates
unnecessary risk of nephrotoxicity.
D. The AUC, but not the trough concentration,
increases the risk of nephrotoxicity within an
acceptable range.

Learner Chapter Evaluation: Translating Evidence into Practice:
Vancomycin Toxicity.
As you take the posttest for this chapter, also evaluate the Questions 5254 apply to the entire learning module.
materials quality and usefulness, as well as the achievement
of learning objectives. Rate each item using this 5-point scale: 52. How long did it take you to read the instructional materi-
als in this module?
Strongly agree 53. How long did it take you to read and answer the assess-
Agree ment questions in this module?
Neutral 5 4. Please provide any additional comments you may have
Disagree regarding this module:
Strongly disagree
35. The content of the chapter met my educational needs.

36. The content of the chapter satisfied my expectations.
38. The content of the chapter was relevant to my practice
and presented at the appropriate depth and scope.
4 0. The content of the chapter is free of bias, promotion, or
were effective.
4 3. The active learning methods used in the chapter were
effective.
4 4. The learning assessment activities used in the chapter
were effective.
Use the 5-point scale to indicate whether this chapter pre-

pared you to accomplish the following learning objectives:
46. Analyze the vancomycin pharmacokinetic (PK) and

pharmacodynamic exposure parameters associated
with nephrotoxicity in pediatric versus adult patients.
47. Assess the significance of three variables associated
with vancomycin nephrotoxicity in pediatric patients,
and evaluate the strength of design of studies evaluat-
ing these variables.
4 8. Evaluate the risks, benefits, and practical implications of
various vancomycin therapeutic drug monitoring strate-
gies for pediatric patients.

49. Apply current best evidence to optimize vancomycin
dosing while minimizing nephrotoxicity in pediatric
patients.
50. Please provide any specific comments related to any
perceptions of bias, promotion, or advertisement of
commercial products.
51. Please expand on any of your above responses, and/or
provide any additional comments regarding this chapter:

PedSAP 2016-2018 Releases
Title Release Date BCPPS Test Deadline ACPE Test Deadline
Immunology May 16, 2016 September 15, 2016 May 14, 2019
Pediatric Critical Care September 15, 2016 January 17, 2017 September 14, 2019
Research Ethics/
January 17, 2017 May 15, 2017 January 14, 2020
Study Design
Pediatric Emergencies May 15, 2017 September 15, 2017 May 14, 2020
Sedation and
September 15, 2017 January 16, 2018 September 14, 2020
Analgesia
Pediatric Oncology January 16, 2018 May 15, 2018 January 14, 2021
Fluids/Electrolytes/ May 15, 2018 September 17, 2018 May 14, 2021
Nutrition
Neonatal and Pediatric September 17, 2018 January 15, 2019 September 14, 2021
Sepsis
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Releases are available singly or as an eight-book series over 3 years. Topics for the series are designed to cover the content outline
for the Board Certified Pediatric Pharmacy Specialist examination administered by the Board of Pharmacy Specialties.
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PEDIATRIC

AMERICAN COLLEGE OF CLINICAL PHARMACY

BOOK FORMAT AND CONTENT

For ordering information or questions, write or call:

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To cite PedSAP properly:

PedSAP is a registered trademark of the American College of Clinical Pharmacy.

Routine Childhood Immunization Series Interactive Case: Immunology in Solid Organ

Vaccine Development and Future Targets Translating Evidence into Practice:

PedSAP 2016 Book 1 Immunology iii Table of Contents

Series Editors: Reviewers

Grants: Elias B. Chahine (Cubist); Scott James (NIH/NIAID)

Other questions regarding recertification should be directed to:

Board of Pharmacy Specialties

BCPPS test deadline: 11:59 p.m. (Central) on May 16, 2016.

1. Distinguish the considerations for administering live versus inactivated vaccines.

PedSAP 2016 Book 1 Immunology 7 Routine Childhood Immunization Series

PedSAP 2016 Book 1 Immunology 8 Routine Childhood Immunization Series

PedSAP 2016 Book 1 Immunology 9 Routine Childhood Immunization Series

PedSAP 2016 Book 1 Immunology 10 Routine Childhood Immunization Series

Vaccines as a Disease Cause Alternative Schedules

PedSAP 2016 Book 1 Immunology 11 Routine Childhood Immunization Series

PedSAP 2016 Book 1 Immunology 12 Routine Childhood Immunization Series

What vaccinations are best to administer to this patient

Vaccine Vaccine Indicated? Notes

PedSAP 2016 Book 1 Immunology 13 Routine Childhood Immunization Series

PedSAP 2016 Book 1 Immunology 14 Routine Childhood Immunization Series

PedSAP 2016 Book 1 Immunology 15 Routine Childhood Immunization Series

PedSAP 2016 Book 1 Immunology 16 Routine Childhood Immunization Series

PedSAP 2016 Book 1 Immunology 17 Routine Childhood Immunization Series

PedSAP 2016 Book 1 Immunology 18 Routine Childhood Immunization Series

PedSAP 2016 Book 1 Immunology 19 Routine Childhood Immunization Series

PedSAP 2016 Book 1 Immunology 20 Routine Childhood Immunization Series

PedSAP 2016 Book 1 Immunology 21 Routine Childhood Immunization Series

PedSAP 2016 Book 1 Immunology 22 Routine Childhood Immunization Series

PedSAP 2016 Book 1 Immunology 23 Routine Childhood Immunization Series

CDC. Parents Guide to Childhood Immunizations. 2015a.

CDC. Withdrawal of rotavirus vaccine recommendation.

PedSAP 2016 Book 1 Immunology 24 Routine Childhood Immunization Series

PedSAP 2016 Book 1 Immunology 25 Routine Childhood Immunization Series

Reagan-Steiner S, Yankey D, Jeyarajah J, et al. National,

Retraction ileal-lymphoid nodular hyperplasia, non-

Roberts W, Harford M. Immunization and children at risk for

Robinson CL. Advisory Committee on Immunization

Rosenblatt AE, Stein SL. Cutaneous reactions to vaccina-

Rubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA clinical

Ruderfer D, Krilov LR. Vaccine-preventable outbreaks: still

Satterwhite CL, Torrone E, Meites E, et al. Sexually trans-

Schmitt BD; for Seattle Childrens Hospital Research

Seither R, Masalovich S, Knighton CL, et al. Vaccination cov-

PedSAP 2016 Book 1 Immunology 26 Routine Childhood Immunization Series

PedSAP 2016 Book 1 Immunology 27 Routine Childhood Immunization Series

PedSAP 2016 Book 1 Immunology 28 Routine Childhood Immunization Series

PedSAP 2016 Book 1 Immunology 29 Routine Childhood Immunization Series

PedSAP 2016 Book 1 Immunology 30 Routine Childhood Immunization Series

10. The learning assessment activities used in the chapter