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EBOLA AND MARBURG VIRUSES Second Edition Anthrax, Second Edition Mad Cow Disease Malaria, Second Edition Antibiotic-Resistant Bacteria Meningitis, Second Edition Avian Flu Botulism, Second Edition Mononucleosis, Second Edition Campylobacteriosis Pelvic Inflammatory Cervical Cancer Disease Chicken Pox Plague, Second Edition Cholera, Second Edition Polio, Second Edition Dengue Fever and Other Prostate Cancer Hemorrhagic Viruses Rabies Diphtheria Rocky Mountain Spotted Ebola Fever Encephalitis Rubella and Rubeola Escherichia coli Salmonella Infections, Second SARS, Second Edition Edition Smallpox Gonorrhea, Second Edition Staphylococcus aureus Hantavirus Pulmonary Infections Syndrome Streptococcus (Group A), Helicobacter pylori Second Edition Hepatitis Streptococcus (Group B) Herpes Syphilis, Second Edition HIV/AIDS Tetanus Infectious Diseases of the Toxic Shock Syndrome Mouth Trypanosomiasis Infectious Fungi Tuberculosis Influenza, Second Edition Tularemia Typhoid Fever Legionnaires’ Disease West Nile Virus, Second Leprosy Edition Lung Cancer Whooping Cough Lyme Disease Yellow Fever EBOLA AND MARBURG VIRUSES Second Edition Tara C. Smith, Ph.D. Consulting Editor Hilary Babcock, M.D., M.P.H., Infectious Diseases Division, Washington University School of Medicine, Medical Director of Occupational Health (Infectious Diseases), Barnes-Jewish Hospital and St. Louis Children’s Hospital Foreword by David L. Heymann World Health Organization Ebola and Marburg Viruses, Second Edition Copyright © 2011 by Infobase Publishing All rights reserved. No part of this book may be reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, or by any information storage or retrieval systems, without permission in writing from the publisher. For information, contact: Chelsea House An imprint of Infobase Publishing 132 West 31st Street New York NY 10001 Library of Congress Cataloging-in-Publication Data Smith, Tara C., 1976– Ebola and Marburg viruses / Tara C. Smith — 2nd ed. p. cm. — (Deadly diseases and epidemics) Includes bibliographical references and index. ISBN-13: 978-1-60413-252-6 (hardcover : alk. paper) ISBN-13: 978-1-4381-3577-9 (e-book) 1. Ebola virus disease. 2. Marburg virus disease I. Title. QR201.E16S656 2011 614.5’7—dc22           2010032999 Chelsea House books are available at special discounts when purchased in bulk quantities for businesses, associations, institutions, or sales promotions. Please call our Special Sales Department in New York at (212) 967-8800 or (800) 3228755. You can find Chelsea House on the World Wide Web at http://www.chelseahouse.com Text design by Terry Mallon Cover design by Takeshi Takahashi Composition by Mary Susan Ryan-Flynn Cover printed by Bang Printing, Brainerd, MN Book printed and bound by Bang Printing, Brainerd, MN Date printed: November 2010 Printed in the United States of America 10 9 8 7 6 5 4 3 2 1 This book is printed on acid-free paper. All links and Web addresses were checked and verified to be correct at the time of publication. Because of the dynamic nature of the Web, some addresses and links may have changed since publication and may no longer be valid. Table of Contents Foreword David L. Heymann, World Health Organization 1. A Modern Plague 6 8 2. Marburg Virus Emerges 12 3. Ebola in Africa and Beyond 17 4. General Characteristics of the Viruses 35 5. Ecology of the Viruses 43 6. Methods of Detection and Treatment 58 7. Developing a Vaccine 66 8. Other Hemorrhagic Fevers 75 Notes 85 Glossary 86 Bibliography 92 Further Resources 97 Index 98 Foreword Communicable diseases kill and cause long-term disability. The microbial agents that cause them are dynamic, changeable, and resilient: They are responsible for more than 14 million deaths each year, mainly in developing countries. Approximately 46% of all deaths in the developing world are due to communicable diseases, and almost 90% of these deaths are from AIDS, tuberculosis, malaria, and acute diarrheal and respiratory infections of children. In addition to causing great human suffering, these high-mortality communicable diseases have become major obstacles to economic development. They are a challenge to control either because of the lack of effective vaccines, or because the drugs that are used to treat them are becoming less effective because of antimicrobial drug resistance. Millions of people, especially those who are poor and living in developing countries, are also at risk from disabling communicable diseases such as polio, leprosy, lymphatic filariasis, and onchocerciasis. In addition to human suffering and permanent disability, these communicable diseases create an economic burden—both on the workforce that handicapped persons are unable to join, and on their families and society, upon which they must often depend for economic support. Finally, the entire world is at risk of the unexpected communicable diseases, those that are called emerging or re-emerging infections. Infection is often unpredictable because risk factors for transmission are not understood, or because it often results from organisms that cross the species barrier from animals to humans. The cause is often viral, such as Ebola and Marburg hemorrhagic fevers and severe acute respiratory syndrome (SARS). In addition to causing human suffering and death, these infections place health workers at great risk and are costly to economies. Infections such as Bovine Spongiform Encephalopathy (BSE) and the associated new human variant of Creutzfeldt-Jakob disease (vCJD) in Europe, and avian influenza A (H5N1) in Asia, are reminders of the seriousness of emerging and re-emerging infections. In addition, many of these infections have the potential to cause pandemics, which are a constant threat to our economies and public health security. Science has given us vaccines and anti-infective drugs that have helped keep infectious diseases under control. Nothing demonstrates 6 Foreword the effectiveness of vaccines better than the successful eradication of smallpox, the decrease in polio as the eradication program continues, and the decrease in measles when routine immunization programs are supplemented by mass vaccination campaigns. Likewise, the effectiveness of anti-infective drugs is clearly demonstrated through prolonged life or better health in those infected with viral diseases such as AIDS, parasitic infections such as malaria, and bacterial infections such as tuberculosis and pneumococcal pneumonia. But current research and development is not filling the pipeline for new anti-infective drugs as rapidly as resistance is developing, nor is vaccine development providing vaccines for some of the most common and lethal communicable diseases. At the same time, providing people with access to existing anti-infective drugs, vaccines, and goods such as condoms or bed nets—necessary for the control of communicable diseases in many developing countries—remains a great challenge. Education, experimentation, and the discoveries that grow from them are the tools needed to combat high mortality infectious diseases, diseases that cause disability, or emerging and re-emerging infectious diseases. At the same time, partnerships between developing and industrialized countries can overcome many of the challenges of access to goods and technologies. This book may inspire its readers to set out on the path of drug and vaccine development, or on the path to discovering better public health technologies by applying our current understanding of the human genome and those of various infectious agents. Readers may likewise be inspired to help ensure wider access to those protective goods and technologies. Such inspiration, with pragmatic action, will keep us on the winning side of the struggle against communicable diseases. David L. Heymann Assistant Director General Health Security and Environment Representative of the Director General for Polio Eradication World Health Organization Geneva, Switzerland 7 1 A Modern Plague In 1967 a mysterious infection hit laboratory workers in Marburg, Germany, and Belgrade, in the former Yugoslavia. Twenty-five workers, busily carrying out research on the polio virus, came down with a similar set of symptoms: fever, diarrhea, vomiting, shock, and eventually circulatory system collapse. The fear spread when individuals who had contact with these scientists also became ill. Two doctors and a nurse who took care of the workers came down with the same infection, as did an autopsy attendant and the wife of a veterinarian who worked at the initial facility. Doctors were puzzled. Initially they thought it may have been typhoid fever, a bacterial infection caused by Salmonella typhi, due to the nausea and vomiting patients experienced. However, no bacteria could be isolated from the sick workers. More frighteningly, many of the patients were experiencing severe bleeding. It was difficult for the doctors and nurses treating them to even draw blood, as needle puncture sites simply started to bleed. In all, 31 people were infected and 7 (23%) of them died from the disease. Tests were being conducted in earnest to find the agent causing the disease, but they came back negative for most of the common infectious suspects. Finally, using a powerful microscope, scientists were able to see what appeared to be a previously undescribed type of virus in the tissues of animals infected with blood from human patients. This new virus was confirmed and named Marburg, after the city where most of the cases had originated. The virus was found to exhibit a morphology (shape) unlike any previously known virus. Because of this, it was placed into a new group, termed the Filoviridae. While one group of scientists was trying to determine the causative agent, another group was working on an examination of the epidemiology of the outbreak—looking at patterns that were common to the patients in order to determine the origin of the infection. Investigators determined that all of the 8 A Modern ChapterTitle Plague Figure 1.1 Scanning electron micrograph of the Ebola virus. Its thread-like appearance led to its designation as a “filovirus.” (Centers for Disease Control and Prevention) primary cases—those who had gotten ill from the original source, rather than the doctors and nurses who were infected by the ill individuals—all worked in various aspects of polio vaccine development. They also all had direct contact with blood, organs, and cell cultures from Cercopithecus aethiops monkeys—“African green monkeys”— which had been imported from Uganda. These monkeys were used mainly for the production of kidney cell cultures, which were used to grow the polio virus in order to produce vaccine.1 This outbreak was the world’s first introduction to the filovirus family, but far from its last. A SECOND FILOVIRUS In 1976, almost a decade after the initial outbreak, both the Democratic Republic of the Congo (formerly Zaire) and Sudan were experiencing devastating outbreaks of a deadly hemorrhagic (bleeding) fever. Because travel was difficult in and around the areas of Sudan and the Democratic Republic of the Congo, outsiders were still unaware of the outbreaks weeks after they began. In fact, the epidemics were largely over by the time teams of scientists from the Centers for Disease Control and Prevention (CDC) 9