Vaccines: Expert Consult

3690 Pages·2012·127.4 MB·English

by  Stanley A. Plotkin MD, Walter Orenstein MD, Paul A. Offit MD

05. 10. 12 I nt r oduct oi n

Vaccines, 6th Edition
By Stanley A. Plotkin, MD, Walter Orenstein, MD and Paul A. Offit, MD
Key Features
Gain a complete understanding of each disease,
including clinical characteristics, microbiology,
pathogenesis, diagnosis, and treatment, as well
an epidemiology and public health and regulatory
issues.
Update your knowledge of both existing vaccines
and vaccines currently in the research and
development stage.
Getting started
Get complete answers on each vaccine, including
To start browsing, use the table of contents on the left.
its stability, immunogenicity, efficacy, duration of
Click to expand the contents of a section or chapter.
immunity, adverse events, indications,
Clicking the chapter or section title itself will take you to
contraindications, precautions, administration with
that section. Alternatively, search the book using the
other vaccines, and disease-control strategies.
search function above, or look up a term in the complete
Analyze the cost-benefit and cost-effectiveness of
index.
different vaccine options.
For further information on Expert Consult, view a demo of
Clearly visualize concepts and objective data
the site.
through an abundance of tables and figures.
Website Features
Consult the book from any computer at home,
in your office, or at any practice location.
Instantly locate the answers to your clinical
questions via a simple search query.
Quickly find out more about any bibliographical
citation by linking to its MEDLINE abstract.
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Vaccines
Sixth Edition

Stanley A. Plotkin, MD
Emeritus Professor of Pediatrics, University of Pennsylvania
Emeritus Professor, Wistar Institute
Former Chief, Division of Infectious Diseases, The Children's Hospital of Pennsylvania, PA, USA
Former Medical and Scientific Director, Pasteur Merieux Connaught (now Sanofi Pasteur), Marnes-la-Coquette,
France
Walter A. Orenstein, MD, DSC (HON)
Professor of Medicine, Pediatrics, and Global Health, Emory University
Associate Director Emory Vaccine Center, Atlanta, GA
Former Deputy Director for Immunization Programs, Bill & Melinda Gates Foundation, Seattle, WA
Former Director, National Immunization Program, CDC, Atlanta, GA, USA
Paul A. Offit, MD
Chief, Division of Infectious Diseases, Director, Vaccine Education Center, The Children's Hospital of
Philadelphia
Professor of Pediatrics, Maurice R. Hilleman Professor of Vaccinology, Perelman School of Medicine, The
University of Pennsylvania, PA, USA
Elsevier Inc., 2013
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Front Matter
Vaccines

“Vaccination cottage” near the home of Edw ard Jenner in Berkeley, England, w here he administered smallpox vaccine to thousands
of the rural poor.
(Photo by Stanley A. Plotk in.)

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Part of a 20-km w all erected in 1720 in Provence to prevent people escaping a plague epidemic in Marseilles from spreading
disease. The photo show s a guardhouse.
(Photo by Stanley A. Plotk in.)

Detroit Industry, North Wall, 1933 (fresco) by Diego Rivera (1886-1957)
Courtesy of Detroit Institute of Arts, USA/The Bridgeman Art Library.

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Benjamin Jesty's tombstone, East Dorset. Jesty successfully inoculated his w ife and tw o sons against smallpox using cow pox in
1774, 22 years before Jenner's f irst smallpox inoculation.
From: Benjamin Jesty: Dorset's Vaccination Pioneer by Patrick J Pead, Timefile Books, 2009.

Vaccines
SIXTH EDITION
STANLEY A. PLOTKIN, MD, Emeritus Professor of Pediatrics, University of Pennsylvania
Emeritus Professor, Wistar Institute
Former Chief, Division of Infectious Diseases, The Children's Hospital of Pennsylvania, PA, USA
Former Medical and Scientific Director, Pasteur Merieux Connaught (now Sanofi Pasteur), Marnes-la-Coquette,
France
WALTER A. ORENSTEIN, MD, DSc (Hon), Professor of Medicine, Pediatrics, and Global Health, Emory
University
Associate Director Emory Vaccine Center, Atlanta, GA
Former Deputy Director for Immunization Programs, Bill & Melinda Gates Foundation, Seattle, WA
Former Director, National Immunization Program, CDC Atlanta, GA, USA
PAUL A. OFFIT, MD, Chief, Division of Infectious Diseases, Director, Vaccine Education Center, The Children's
Hospital of Philadelphia
Professor of Pediatrics, Maurice R. Hilleman, Professor of Vaccinology, Perelman School of Medicine, The
University of Pennsylvania, PA, USA
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University of Pennsylvania, PA, USA

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Copyright

An imprint of Elsevier Inc.
© 2013, 2008, 2004, 1999, 1994, 1988 Saunders, an imprint of Elsevier Inc. All rights reserved.
First edition 1988, Second edition 1994, Third edition 1999, Fourth edition 2004, Fifth edition 2008
No part of this publication may be reproduced or transmitted in any form or by any means, electronic or
mechanical, including photocopying, recording, or any information storage and retrieval system, without
permission in writing from the publisher. Details on how to seek permission, further information about the
Publisher's permissions policies and our arrangements with organizations such as the Copyright Clearance
Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions .
This book and the individual contributions contained in it are protected under copyright by the Publisher (other
than as may be noted herein).
Chapter 17 entitled ‘Inactivated influenza vaccines’ is in the public domain.
Chapter 18 entitled ‘Influenza vaccine – live’ is in the public domain.
Chapter 24 entitled ‘Plague vaccines’ © Crown Copyright 2011 Dstl
Chapter 28 entitled ‘Poliovirus vaccine – live': Bruce Aylward's portion of the contribution is © World Health Org.
Chapter 32 entitled ‘Smallpox and vaccinia’: Mayo retains copyright to their original artwork.
Chapter 41 entitled ‘Biodefense and special pathogen vaccines’ is in the public domain.
Chapter 44, Dengue vaccines. Scott B. Halstead, Stephen J. Thomas. Disclaimer: The opinions or assertions
contained herein are the private views of the author (S.J.T.) and are not to be construed as reflecting the official
views of the United States Army or the United States Department of Defense. Research was conducted in
compliance with the Animal Welfare Act and other federal statutes and regulations relating to animals and
experiments involving animals and adhered to the principals stated in the Guide for the Care and Use of
Laboratory Animals, NRC Publication, 1996 edition. One author (S.J.T.), as an employee of the United States
Army, has been assigned to work on dengue vaccine co-development efforts with numerous commercial
entities, some mentioned in this article. The author discloses these relationships not because there is a conflict
of interest but for transparency.
Chapter 49 entitled ‘Hepatitis E virus vaccines’ is in the public domain.
All material in Chapter 73 entitled ‘Regulation and testing of vaccines’ is in the public domain, with the
exception of any borrowed figures or tables.
Chapter 75, Regulation of vaccines in developing countries. Lahouari Belgharbi, Nora Dellepiane, David J.
Wood. Disclaimer: The authors are staff members of the World Health Organization. The authors alone are
responsible for the views expressed in this publication, which do not necessarily represent the decisions,
policy, or views of the World Health Organization.
Chapter 77 entitled ‘Legal issues’ is in the public domain.
Notices
Knowledge and best practice in this field are constantly changing. As new research and experience broaden
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our understanding, changes in research methods, professional practices, or medical treatment may become
necessary.
Practitioners and researchers must always rely on their own experience and knowledge in evaluating and
using any information, methods, compounds, or experiments described herein. In using such information or
methods they should be mindful of their own safety and the safety of others, including parties for whom they
have a professional responsibility.
With respect to any drug or pharmaceutical products identified, readers are advised to check the most
current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be
administered, to verify the recommended dose or formula, the method and duration of administration, and
contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of
their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient,
and to take all appropriate safety precautions.
To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any
liability for any injury and/or damage to persons or property as a matter of products liability, negligence or
otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the
material herein.
British Library Cataloguing in Publication Data
A catalogue record for this book is available from the British Library
ISBN-13: 9781455700905
Ebook: 9781455737987
Printed in China
Last digit is the print number:987654321
Content Strategist: Sue Hodgson, Belinda Kuhn
Content Development Specialist: Joanne Scott
Content Coordinator: Sam Crowe
Project Manager: Julie Taylor
Design: Stewart Larking
Illustration Manager: Jennifer Rose
Illustrator: Oxford Illustrators/Ethan Danielson
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Foreword
I was born in 1955, the year that the Salk polio vaccine went into wide distribution. If you talk to anyone old
enough to remember the scourge of polio and the terror it engendered, you begin to get a sense of just how
remarkable that breakthrough was and how it changed the lives of millions of people for the better.
That event changed the world. I grew up in an environment where vaccines for polio, diphtheria, whooping cough,
and other contagious diseases were simply taken for granted. Yet, if you go to India's state of Bihar, you can
still see that same fear in the eyes of parents as they worry about their children falling victim to polio. How is it
possible that more than a half-century after Salk's vaccine, polio remains endemic in three countries and has
still yet to be eradicated?
Some of this is attributable to the biology of the pathogen. But, as significantly, a lack of political will and a
failure of health systems to deliver polio vaccines to children at risk for this crippling disease underlie our
inability to go from 99% reduction in cases to our true goal – 100% eradication of this scourge. I'm optimistic we
can get there, but only if we combine the best of medicine, logistics, education and community outreach.
Success here would be a milestone for civilization. It's difficult, but within our grasp.
Similarly, S. pneumoniae has been studied for more than a century. Nevertheless, invasive pneumococcal
disease kills more than 800,000 children each year. The most effective strategy currently available to reduce the
burden of disease is vaccination.
There has been significant progress, as well. The vaccine for measles was licensed in the 1960s, but its uptake
was frustratingly slow in many places. Even 30 years after its introduction, three-quarters of a million children
were dying from measles every year. However, since 2000, measles vaccine coverage has substantially
increased, and measles deaths have declined by about 80 percent. This translates into more than 1,500
children each day who live instead of die because the measles vaccine is being delivered regularly almost
everywhere in the world.
The simple truth is vaccines save lives.
They are overwhelmingly safe, remarkably cost-effective, and remain the single best tool we have in global
health. They protect the human potential that is sapped by rampant sickness in developing countries. As a
result, vaccines are one of the best means we have to promote not just global health, but global development.
If vaccines are this singularly important tool, then the 6th edition of Vaccines is a singularly important resource
in extending the power of prevention to the largest possible audience worldwide. It is an honor to have been
asked to write a short introduction to the latest edition.
It is also an honor to be able to speak to the scientists, researchers, and medical and public health
professionals who will take up this volume. Your work matters tremendously. At a time when irresponsible
claims and groundless rumors about vaccines sometimes garner equal attention to the facts, it is vitally
important to have informed advocates for the power – and the necessity – of comprehensive vaccination
worldwide.
As I sit down to write this in mid 2012, it is an exciting time in the field of vaccines.
This year, we witnessed a remarkable event as donors pledged more than $4 billion to the Global Alliance for
Vaccines and Immunization (GAVI), even in the face of a global financial crisis. The generosity of governments,
foundations, and private sector entities that participated in this pledging round will substantially expand the
ability of poor countries to vaccinate their children and result in the saving of more than 4 million lives. This is
very encouraging.
On the research front, we are seeing for the first time some promising signs in the decades-long search for an
AIDS vaccine. Similarly, we are seeing progress on a crucial vaccine for malaria. The need for this in the
poorest parts of the world cannot be overstated. The devastating costs of malaria in lives lost, sickness,
diminished capacity, and reduced productivity are all but incalculable.
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diminished capacity, and reduced productivity are all but incalculable.
Last year, new vaccines for pneumococcus and rotavirus were introduced in some poor countries. Significantly,
the time lag between vaccine introduction in rich countries and their availability in poor countries was shortened
from a shameful decade plus to only a few years.
The world also saw the introduction of the first-ever vaccine developed specifically for the developing world – a
meningococcal A conjugate vaccine that can end a terrifying threat for millions of people who live in Africa's
meningitis belt.
With almost a dozen vaccine candidates in clinical trials, research to increase the range and efficacy of
tuberculosis vaccines is finally showing promising results.
But much remains to be done. We need new vaccines. The work to develop effective vaccines for malaria and
HIV must press on.
We need better vaccines. The currently licensed BCG vaccine for tuberculosis has been administered 4 billion
times over the last 90 years. It is safe and it protects against severe disease in infants. However, its efficacy is
quite limited and it does not protect against adult pulmonary TB. Other vaccines such as the oral polio vaccine
(OPV), the Rotavirus vaccine, and other orally administrated vaccines are often less effective in children living in
extreme poverty.
We need better understanding of mechanistic immune markers that correlate with protection that would help in
faster discovery and introductions of improved vaccines.
We need to secure faster vaccine introduction and adoption of currently approved vaccines. We are still facing a
significant number of unreached children resulting in an intolerable number of deaths when we know we have the
medicines to prevent them.
We need more affordable vaccines, particularly for developing countries. The high cost of producing vaccines
such as the pneumococcal conjugate vaccine and the human papilloma virus (HPV) vaccine is an obstacle to
incorporating these highly effective vaccines into the immunization programs of developing countries with the
highest burden of disease.
Watching the super-human efforts necessary to maintain the cold-chain for vaccine delivery in rural and poor
settings convinces me that while we can, and should, make near-term improvements in the mechanics of
delivery, the need for advances in thermostability must remain a priority if we are to provide the poor world with
the vaccines that almost everyone in the developed world takes for granted.
Vaccines have become a passion of mine because of the irrefutable benefits they offer to the entire world. It is a
matter of singular importance that we use every tool at our disposal to continue to develop, improve, and deploy
these miracles of science. It is a matter of the most basic human justice that we do all we can to extend these
live-saving drugs throughout the globe.
In this, Vaccines remains an indispensable guide to the enhancement of the well-being of our world.
Bill Gates
Bill Gates is the founder and co-chair of the Bill & Melinda Gates Foundation and the Chairman of Microsoft
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