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Ebola Virus Disease From Origin to Outbreak Adnan I Qureshi AMSTERDAM • BOSTON • HEIDELBERG • LONDON NEW YORK • OXFORD • PARIS • SAN DIEGO SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO Academic Press is an imprint of Elsevier Academic Press is an imprint of Elsevier 125 London Wall, London EC2Y 5AS, UK 525 B Street, Suite 1800, San Diego, CA 92101-4495, USA 50 Hampshire Street, 5th Floor, Cambridge, MA 02139, USA The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, UK Copyright © 2016 Elsevier Inc. All rights reserved. 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). Notices Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers may 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. 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. ISBN: 978-0-12-804230-4 British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library Library of Congress Cataloging-in-Publication Data A catalog record for this book is available from the Library of Congress For information on all Academic Press publications visit our website at http://store.elsevier.com/ Publisher: Sara Tenney Acquisition Editor: Jill Leonard Editorial Project Manager: Fenton Coulthurst Production Project Manager: Karen East and Kirsty Halterman Designer: Ines Maria Cruz Typeset by TNQ Books and Journals www.tnq.co.in Printed and bound in the United States of America Contributors Dr. Adnan I. Qureshi, M.D. Zeenat Qureshi Stroke Institute, St Cloud, MN, USA and Zeenat Qureshi Clinical Neurosciences Institute, Conakry, Guinea. Dr. Omar Saeed, M.D. Clinical Research Fellow, Zeenat Qureshi Stroke Institute, St Cloud, MN, USA Dr. Morad Chughtai, M.D. Clinical Research Fellow, Zeenat Qureshi Stroke Institute, St Cloud, MN, USA and Zeenat Qureshi Clinical Neurosciences Institute, Conakry, Guinea. Dr. Nauman Jahangir, M.D. Clinical Research Fellow, Zeenat Qureshi Stroke Institute, St Cloud, MN, USA Dr. Mohammad R. Afzal, M.D. Clinical Research Fellow, Zeenat Qureshi Stroke Institute, St Cloud, MN, USA Dr. Ahmad A. Malik, M.D. Clinical Research Fellow, Zeenat Qureshi Stroke Institute, St Cloud, MN, USA Dr. Mushtaq H. Qureshi, M.D. Clinical Research Fellow, Zeenat Qureshi Stroke Institute, St Cloud, MN, USA Dr. Ihtesham A. Qureshi, M.D. Clinical Research Fellow, Zeenat Qureshi Stroke Institute, St Cloud, MN, USA and Zeenat Qureshi Clinical Neurosciences Institute, Conakry, Guinea. xi Author Biographies DR ADNAN IQBAL QURESHI Dr Qureshi is a professor of neurology, neurosurgery, and radiology at University of Minnesota. He has written over 550 scientific publications in prestigious journals including the New England Journal of Medicine, Lancet, Archives of Internal Medicine, Critical Care Medicine, Neurology, American Journal of Medicine, and Circulation. In addition, he has made over 1300 presentations in various national and international meetings. He has also been invited as a visit- ing professor to universities in the United States and abroad. He is the editor of several textbooks and serves on editorial boards for several peer-review jour- nals. He is the principal investigator of a large multinational clinical trial funded by National Institutes of Health. He laid the foundation of the Zeenat Qureshi Institutes in several countries. Since its inauguration, the institutes have led the way in cutting-edge research in epidemiology, clinical trials, and basic research. Most recently, he laid the foundation of Zeenat Qureshi Clinical Neurosciences Institute in Conakry, Guinea. The institute has performed tow studies on Ebola virus disease survivors. The first one has been published in “Clinical Infectious Disease.” DR OMAR SAEED Dr Omar Saeed graduated from a medical school in Pakistan after which he pursued his interest in the field of medicine focusing on neurology and neu- roimaging. He was given the opportunity to work with Dr Adnan Qureshi at the Zeenat Qureshi Stroke Institute where he worked as a clinical research fellow. His main interests were stroke, intracerebral hemorrhage, and neuro- imaging among others. During his time at the stroke institute, Dr Saeed has coauthored several scientific publications in prestigious journals including Journal of Neurosurgery, Journal of Cerebrovascular Disease and Stroke, Journal of Neuroimaging, and Journal of Vascular and Interventional Neurol- ogy. He was also given the opportunity to present at both national and inter- national forums including the International Stroke Conference and The World Masters China Tour and Neuro Interventional International Forum. Further- more, Dr Saeed has coauthored numerous research abstracts presented at the International Stroke Conference and the American Academy of Neurology xiii xiv Author Biographies Annual meeting. His future hopes are to continue focusing on both the clinical and research side of medicine. He served as the primary coordinator for the book on Ebola virus disease. DR MORAD CHUGHTAI Dr Morad Chughtai graduated Summa Cum Laude from American University of Antigua College of Medicine in 2014. As a medical student, he served as a teacher’s assistant for multiple subjects throughout the duration of his basic science education, including anatomy, physiology, biochemistry, genetics, patho- physiology, and neurosciences. After obtaining his medical degree, he worked under the instruction of Dr Adnan I. Qureshi as a clinical research fellow for a year’s duration. During that time, he coauthored several peer-reviewed publications, one being published in the prestigious journal, Clinical Infectious Diseases. He received an award at APPNA annual meeting in 2015 for his work on Ebola virus disease sur- vivors. Subsequently, he obtained a fellowship from the Rubin Institute of Advanced Orthopedics, Sinai hospital in Baltimore, Maryland. He currently serves as an ortho- pedic research fellow, where he is a coinvestigator of several prospective clinical trials, among other projects. He hopes to carry his passion of teaching and research throughout his medical career and eventually practice in an academic setting. DR NAUMAN JAHANGIR Dr Nauman Jahangir completed his medical studies in Pakistan and after com- pleting his postgraduate training in Pakistan, he perused his dream of training in the US as a neurologist. Dr Jahangir had the opportunity to do many clini- cal rotations at prestigious hospitals. He started at the Zeenat Qureshi Stroke Institute as a clinical research fellow in 2014. During his time at Zeenat Qureshi Stroke Institute, Dr Jahangir worked diligently and was able to publish many peer-review articles in medical journals. He presented multiple medical abstracts at both the International Stroke Conference and the American Academy of Neurology annual meeting where he presented posters and oral presentations. With all these efforts, Dr Jahangir was accepted as a neurology resident at Southern Illinois University where he is continuing his efforts to save lives. DR MOHAMMAD R. AFZAL Dr Mohammad Rauf Afzal is working as a clinical research fellow at Zeenat Qureshi Stroke Institute. His research interests include stroke epidemiology, intra-arterial and intravenous thrombolytic use in acute ischemic stroke and neurocritical care. His work has been presented at International Stroke Confer- ence (ISC) and American Academy of Neurology (AAN) annual meeting. He has also coauthored scientific publications in prestigious journals. Along with his research activities, Dr Afzal is also working as an assistant to core image analyst and as an assistant to primary study coordinator in Hennepin County Medical Author Biographies xv Center (HCMC) Minneapolis, MN, for Antihypertensive Treatment of Acute Cerebral Hemorrhage-II trial. DR AHMED A. MALIK Dr Ahmed Malik is a medical doctor by education and is currently a clinical research fellow at the Zeenat Qureshi Stroke Institute. After completing some undergraduate coursework at SUNY Stony Brook University, Dr Malik, guided by a desire to understand health care in the developing world, went to the Shifa College of Medicine in Islamabad, Pakistan, to complete his medical education. Upon his return to the US, he worked on a volunteer basis with doctors at private clinics before joining Zeenat Qureshi Stroke Institute. As a clinical research fellow at Zeenat Qureshi Stroke Institute, Dr Malik has worked under the mentorship of Dr Adnan I. Qureshi to author numerous scientific research papers published in renowned medical journals. Dr Malik has also p resented scientific research papers at national and international medical conferences, is a reviewer for the World Jour- nal of Pediatrics, and a contributor to the Journal of Vascular and Interventional Neurology. In his free time, he likes to write and is currently writing a few works of fiction for publication. DR MUSHTAQ H. QURESHI Dr Mushtaq Qureshi is working as a senior clinical research fellow at Zeenat Qureshi Stroke Institute. He has authored and coauthored several scientific pub- lications which are published in various prestigious journals. He has also made several platform and poster publications in various national and international meetings. Currently, he is the managing editor of Journal of Vascular and Inter- ventional Neurology and also serves in the role of the head of imaging department in a large phase III clinical trial, which is funded by National Institutes of Health. DR IHTESHAM A. QURESHI Dr Ihtesham A. Qureshi is a clinical research fellow in neurology at Zeenat Qureshi Stroke Institute. His research mainly includes stroke and cerebrovas- cular diseases, neurointervention, and Ebola virus disease. He has few scien- tific publications in prestigious journals like Plos One, Elsevier, and F1000 Research. He was also a former medical field doctor at Doctors without Bor- ders/Medecins Sans Frontieres and was involved in operational research on tuberculosis and malaria. He is the principal investigator for the first study ever done to assess memory decline among Ebola virus disease survivors using mini- mental scale examination. He is also the principal investigator for the first study done to identify persistence of Ebola virus in the synovial fluid among Ebola virus disease survivors using arthrocentesis technique. With the collaboration with Ebola treatment unit, Donka National Hospital, Conakry, Guinea, he was involved in several Ebola virus disease-related research projects. Acknowledgments A special thanks has to be extended to Fatoumata Binta Diallo and her family who provided motivation, encouragement, and support for the journey to Guinea. The mission of the journey would not be possible without active collaboration of numerous colleagues in Guinea such as Drs L. Béavogui Kézély and Oscar Loua who opened their doors to us as if we were close friends and family. The book is a tribute to the everyday heroes in West Africa which includes every physi- cian, nurse, and medical professional who evaluates hundreds of sick patients on a daily basis not knowing which will be the next Ebola virus-infected patient that may pass the often fatal disease to them. We pray to God Almighty to give strength and blessings to families who have been affected directly or indirectly from the Ebola virus disease outbreak in their backyards. We also hope that in North America and Europe, the spirit of helping fellow humans prevails over the extreme concerns of self-preservation. Each outbreak is a teacher to humanity and lessons are not limited to medical professionals but are valuable to all that form the class of humanity. We hope that this book provides part of the course material required for broad transmission of such a lesson. xvii Chapter 1 Ebola Virus: Nature’s Experiment Gone Wrong Chapter Outline The first global pandemic 2 And then came Ebola virus Mankind vulnerable no pandemic 4 more? 3 References 6 An experiment comprises of dynamic observations made after addition, deletion, or modification of one or more components within the study perimeters. “Nature’s experiment” is a term used to define experiments where humans do not plan addi- tion, deletion, or modification processes or the components of study perimeters. Nature’s experiments range from the evolution of domesticated dogs from wolf ancestors to the extermination of dinosaurs. In medicine, the term has been used to identify observations of human growth made after genetic defects to the study of etiological agents in disease epidemics. While such experiments are usually the basis of creativity and innovation, the uncontrolled nature of dynamic processes leaves us vulnerable to undesirable consequences. Any experiment where unde- sirable effects exceed the benefit of the observation is essentially an experiment “gone wrong.” Nature’s experiments are no exception to such a rule. The Ebola virus infection may have started as a disease within nonhuman primates, initially termed as “green monkey fever,” in order to maintain the fine balance between the number of nonhuman primates and resources available. The competition for survival among nonhuman primates is fierce among the rain forests of Africa as the habitat continues to succumb to the ever-increasing human incursion. Within this “experiment,” less-virulent forms of infectious agents are likely to persist because transmission requires diseased primates to survive long enough to contact one another. Most virulent forms of infectious agents may be their own worst enemy by exterminating the very life sources necessary for survival. But why did the experiment to preserve the African rain forest habitat go so wrong? Why did the Ebola virus start a pandemic in a world already lured to a false sense of security after its victory over smallpox and polio viruses? Why could no one make a vaccine against the virus, centuries after West Africans had developed and practiced smallpox inoculation and well before the colonial rule started using variolation? A West African woman described her childhood Ebola Virus Disease. http://dx.doi.org/10.1016/B978-0-12-804230-4.00001-7 Copyright © 2016 Elsevier Inc. All rights reserved. 1 2 Ebola Virus Disease experience in 1890s, “they used to scratch your arm until the blood came and then they got the fluid from someone who had the smallpox and rubbed it in”?1 During the smallpox epidemic of 1954, Director General Sanner of the Public Health for French West Africa stated, “Time is the only means to diminish the ransom being paid by the people” while awaiting for a cure.1 In contemporary times, the world would also face a rude awakening that it could not stop the growing Ebola virus disease epidemic. THE FIRST GLOBAL PANDEMIC Leonardo Giovanni was the only physician within the fleet of ships that sailed out of Kaffa, Crimea into the Caspian Sea, March 1347. The Italians aboard had a lot to celebrate because they were the lucky few who managed to escape the besieged trading post. The Mongols had launched an attack on Italian merchants in Southern Russia in March 1346. The attack culminated in the siege of last trading station in the region, Kaffa (today Feodosia) in Crimea. The port stayed in Italian hands due to cold winters and mysterious dis- ease decimating the ranks of the Mongol armies. Leonardo had seen numerous funeral proceedings among the besieging armies from the walls of the port town and had attributed these occurrences to the wrath of God and cold weather. But, the winters had been an ideal breeding ground for disease due to close proxim- ity among individuals huddled in close quarters with limited aeration to survive the cold. Leonardo would also be a witness to perhaps the first biological war- fare effort with dead corpses infected with disease being catapulted across the walls by the Mongols. His friend Gabriele de’ Mussi summarized the events as “Whereupon the Tartars (Mongols), worn out by this pestilential disease, and falling on all sides as if thunderstruck, and seeing that they were perishing hope- lessly, ordered the corpses to be placed upon their engines and thrown into the city of Kaffa. Accordingly were the bodies of the dead hurled over the walls, so that the Christians were not able to hide or protect themselves from this danger, although they carried away as many as possible and threw them into the sea.”2 For now, Leonardo rejoiced with his companions as they approached the port of Constantinople in May 1347. Three of the sailors were sick and one had died during the journey and Leonardo had been responsible for the care of these sail- ors. After transferring the sick sailors to local infirmaries, Leonardo chose to spend a few days in the city. It had been a long and arduous winter followed by a hectic and rushed journey and Leonardo had numerous reasons to feel exhausted. By the third day, Leonardo was exhausted and weak beyond reasons and had developed a high fever and chills. He noticed prominent and painful swelling in his groin and axillary regions. He felt utterly unable to walk and his compan- ions took him to the local infirmary. Leonardo recognized the person lying on the next bed as one of the sailors that he had taken care of who now appeared moribund. The sailor’s fingers were black-colored and the skin had started to erode from nails onward. Leonardo saw himself as a mirror image of his patient. Ebola Virus: Nature’s Experiment Gone Wrong Chapter | 1 3 By evening, Leonardo slipped in and out of consciousness. He was able to piece together that he had acquired the disease by direct contact with sick sail- ors. There were others out there who had helped him care for his crew members and they needed to be warned of the impending risk. But Leonardo did not live to warn his companions. He was found dead in the infirmary by the next morning. Leonardo did not witness the horrifying events that were to follow as the disease spread through his companions and their contacts into Constantino- ple. By July, ships arriving in Alexandria from Constantinople had spread the disease into North Africa and the Middle East. By the second week of September, ships arriving at the port of Marseilles from Constantinople carrying Leonar- do’s peers sealed the fate of Europe. The Black Death also known as bubonic plague had come to ravage Europe like no natural calamity or wars to follow. The initial descriptions refer to this plague as the “great pestilence.” In a poem composed around 1350, Simon de Covinus described the great pestilence as the mors atra (literally black or terrible death).3 In the coming centuries, the term “Black Death” will be coined either because of translation of the term mors atra or from the identification of blue–black spots that developed on the skin of infected persons.3,4 Cities like Pistoia in Italy tried to implement rules and regulations on city inhabitants, closely resembling present principles of quarantine. Travel to any plague-infected area and return was forbidden. No linen or woolen goods were imported into the city and no corpses were bur- ied in the city. However, the city succumbed to Black Death despite strict enforcement of such rules. Today, historians wonder why the disease spread so quickly, a phenomenon that cannot be explained by direct contact or travel routes. The disease overcame natural and man-made fortifications with con- siderable ease. By the time, plague died down, 25 million people, 60% of all European population, had perished with it.5–7 What caused the plague would continue to mystify researchers and philoso- phers alike in the centuries to come. The disease was caused by the bacteria Yersinia pestis transmitted by fleas.8 The bacteria would be discovered by Alexandre Yersin in Hong Kong in 1894. A member of the French Colonial Health Service investigating the outbreak, he isolated from buboes the bacteria that was later named Yersinia pestis after him. MANKIND VULNERABLE NO MORE? The next 600 years would see the development and availability of advanced hospital care, highly trained personnel, antimicrobial agents, infection-control strategies, and global coordination efforts turn the world into an impregnable fortress against mass spread of diseases called epidemics. The global eradica- tion of smallpox symbolized the ultimate victory of mankind over disease. The World Health Organization, Resolution WHA33.3 on May 8, 1980, declared, “the world and its peoples have won freedom from smallpox, which was a most

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