PDF - Pan Stanford Publishing

Vol. 2
From the beginning of recorded history it is evident that viruses evolved in our midst. Were they one of the
unwanted gifts bestowed on us as Adam left the Garden of Eden? Our sudden nudity exposed our fragility and
ever since we have had to survive them while continually seeking defenses.
The present volume focuses on creating virus alerts or hand-held detectors to bring to the field during
an epidemic, when possible, or tools for the healthcare worker to rapidly diagnose the patient’s ailment.
The authors describe the conventional cell cultures and molecular biology methodologies, while introducing
state-of-the-art multidisciplinary biosensors. This book is not a manual, nor a set of protocols, nor a textbook,
but a lucid glimpse into the advances of virus diagnostic research. Included are a variety of topics that
encompass world health issues, local folklore, such as associating outbreaks with witchcraft, problems in
getting healthcare workers to the outbreak areas, and insights in viral diagnostic pitfalls.
Robert S. Marks earned his Ph.D. from the Weizmann Institute of Science and did his
postdoctoral research at the University of Cambridge. He is a full professor at the Department of
Biotechnology Engineering, the Ben-Gurion University of the Negev, Israel, and is affiliated to the
National Institute for Biotechnology in the Negev and the Ilse Kats Centre for Nanotechnology.
He is currently a program coordinator for the NRF CREATE program “Nanomaterials for Water
and Energy Management” through MSE at the Nanyang Technological University. Prof. Marks has
published in viral immunosensors and has extensive experience in biosensors. He has developed
new sensor configurations, such as establishing diagnostics based on luminescence emitted
by primed neutrophils, and is the editor-in-chief of the 2007 two-volume Wiley Handbook in
Biosensors and Biochips as well as author of more than 100 papers and numerous chapters.
Amadou Alpha Sall is a virologist and has a Ph.D. in public health. He received his scientific
education in France at the universities Paul Sabatier, Toulouse, Paris-Sud, Orsay, and Pierre et
Marie Curie, Paris. Currently he is the head of the Arboviruses and Viral Hemorrhagic Fever unit,
director of the WHO collaborating center, and scientific director of Institut Pasteur de Dakar,
which belongs to the Institut Pasteur International Network. His research focuses primarily on
ecology and evolution of arboviruses and viral hemorrhagic fever. He has published more than
80 papers and book chapters and presented more than 100 scientific papers in international
conferences. Dr. Sall is a recipient of the Senegal Presidential Award for Science and is a member
of the Senegal National Academy of Science and Technology.
V313
ISBN 978-981-4364-43-0
Marks | Lobel | Sall
Leslie Lobel earned his B.A., summa cum laude, in chemistry from Columbia College of Columbia
University and attended the Medical Scientist Training Program at the College of Physicians and
Surgeons of Columbia University, earning his M.D. and Ph.D. in 1988. He was awarded a Helen
Hay Whitney Fellowship for postdoctoral training. After postdoctoral work in the laboratory of
H. Robert Horvitz at MIT, he returned to the Department of Medicine at Columbia University
before moving to the Department of Virology at Ben Gurion University, where he set up a
laboratory of immunovirology and viral therapeutics in 2003. His work includes studies on the
profile of the immune response to various viral diseases.
Viral Diagnostics
The book you have in your hands illustrates a variety of challenges that bug-hunters try to solve. It is an
outstanding collection of the insights and expertise of an interdisciplinary group of researchers from all
walks of life: virologists, physicians, immunologists, electrochemists, physicists, computer scientists,
biotechnologists, epidemiologists, molecular biologists, all working at the forefront of diagnostics in fields
that cross scientific boundaries. Notwithstanding a dire moment as that of the recent Ebola outbreak in West
Africa that saddens us all, we must more than ever peregrinate across oceans, and take the fight to them, as
these invisible and exotic but deadly enemies know no barriers and constantly invade our lives. The coming
epidemics and killer pandemics require us to continuously innovate in areas of prevention, detection, and
therapy.
Pan Stanford Series on the High-Tech of Biotechnology
Volume 2
VIRAL DIAGNOSTICS
Advances and Applications edited by
Robert S. Marks
Leslie Lobel
Amadou Alpha Sall
Pan Stanford Series on the High-Tech of Biotechnology
Volume 2
VIRAL DIAGNOSTICS
Pan Stanford Series on the High-Tech of Biotechnology
Robert S. Marks
Series Founding Editor
Avram and Stella Goldstein-Goren Department of Biotechnology Engineering
National Institute for Biotechnology Engineering
Ilse Katz Institute for Nanoscale Science & Technology
Ben Gurion University of the Negev
Israel
Titles in the Series
Published
Forthcoming
Vol. 1
Nanoantenna: Plasmon-Enhanced
Spectroscopies for Biotechnological
Applications
Vol. 4
Nanomaterials for Water
Management: Signal Amplification
for Biosensing from Nanostructures
Marc Lamy de la Chapelle and
Annemarie Pucci, eds.
Robert S. Marks and
Ibrahim Abdulhalim, eds.
2013
978-981-4463-47-8 (Hardcover)
978-981-4463-48-5 (eBook)
978-981-4303-61-3 (Hardcover)
978-981-4303-62-0 (eBook)
Vol. 2
Viral Diagnostics: Advances and
Applications
Robert S. Marks, Leslie Lobel,
and Amadou Alpha Sall, eds.
2015
978-981-4364-43-0 (Hardcover)
978-981-4364-44-7 (eBook)
Vol. 3
Electrochemical Biosensors
Serge Cosnier, ed.
2015
978-981-4411-46-2 (Hardcover)
978-981-4411-47-9 (eBook)
Vol. 5
Luminescent Biosensors
Gerald Thouand and Robert S. Marks,
eds.
Vol. 6
Fibre-Optic Immunosensors and
Biosensors
Robert S. Marks, ed.
Pan Stanford Series on Renewable Energy — Volume 2
Pan Stanford Series on the High-Tech of Biotechnology
Volume 2
VIRAL DIAGNOSTICS
Advances and Applications editors
Preben Maegaard
Anna Krenz
Wolfgang Palz
edited by
Robert S. Marks
Leslie Lobel
Amadou Alpha Sall
The Rise of Modern Wind Energy
Wind Power
for the World
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Published by
Pan Stanford Publishing Pte. Ltd.
Penthouse Level, Suntec Tower 3
8 Temasek Boulevard
Singapore 038988
Email: [email protected]
Web: www.panstanford.com
British Library Cataloguing-in-Publication Data
A catalogue record for this book is available from the British Library.
Viral Diagnostics: Advances and Applications
c 2015 Pan Stanford Publishing Pte. Ltd.
Copyright All rights reserved. This book, or parts thereof, may not be reproduced in any
form or by any means, electronic or mechanical, including photocopying,
recording or any information storage and retrieval system now known or to
be invented, without written permission from the publisher.
For photocopying of material in this volume, please pay a copying
fee through the Copyright Clearance Center, Inc., 222 Rosewood Drive,
Danvers, MA 01923, USA. In this case permission to photocopy is not
required from the publisher.
ISBN 978-981-4364-43-0 (Hardcover)
ISBN 978-981-4364-44-7 (eBook)
Printed in the USA
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Viral Diagnostics: Advances and Applications is dedicated to
the newly opened Lee Kong Chian School of Medicine, Nanyang
Technological University’s joint medical school with Imperial
College London in Singapore, with a vision to “Redefine Medicine
and Transform Healthcare”.
We wish it a fruitful and successful journey.
The Editors
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Contents
Foreword
Preface
1 Practical Experience with an Integrated Syndromic
Surveillance System in the Medical, Veterinary, Nursing, and
Emergency Response Communities
William Stanhope, Tigi Ward, R. Michael Ragain,
Gary Simpson, and Alan Zelicoff
1.1 More Than Half of All Human Infectious Agents are
Zoonotic
1.2 Syndrome Reporting Information Systems
1.2.1 Examples
1.2.2 Some Successes with SYRIS
1.2.3 Actionable Information: The SYRIS Advantage
1.3 Conflict of Interest Disclosure
2 Environmental Surveillance for Polioviruses in Israel:
Bioerror, Bioterror, or just Mother Nature
Lester M. Shulman, Yossi Manor, Danit Sofer,
and Ella Mendelson
2.1 The Silent Presence or Circulation of Polioviruses in
Poliomyelitis-Free Communities
2.2 Global Eradication of Poliomyelitis
2.3 The Need for Routine Surveillance
2.4 The Program of Environmental Surveillance for
Poliovirus in Israel
2.5 Polioviruses Isolated from Environmental Samples in
Israel
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2.6 Molecular Analysis Yields Epidemiological
Information
2.7 The Contribution of Routine Surveillance toward
Understanding One Potential Route for Reemergence
of Neurovirulent Polioviruses
2.8 Monitoring Silent Poliovirus Infections:
The Contribution of Sewage Surveillance
and Molecular Epidemiology
3 Filoviruses: Deadly Pathogens and Potential Bioweapons
Michael Schümann and Elke Mühlberger
3.1 Emergence of Marburg and Ebola Viruses
3.2 The Virus and the Disease
3.3 Filovirus Biology
3.4 Pathogenesis and Clinical Presentation
3.5 The Bioweapon Potential of Filoviruses
3.5.1 Dissemination and Transmission
3.5.2 Mortality and Impact on Public Health
3.5.3 Public Panic and Social Disruption
3.5.4 Public Health Preparedness
3.5.4.1 Vaccination
3.5.4.2 Treatment
3.5.4.3 Diagnostics
3.6 Future Perspectives
4 Bridging Diagnostics Research, Development, and
Commercialization: Diagnostics for the Developing World
Rosanna W. Peeling
4.1 Lack of Access to Diagnostics as a Contributor to the
Burden of Infectious Diseases
4.2 Role of Diagnostic Tests
4.3 Diagnostic Landscape in the Developing World
4.4 Lack of International and National Regulatory
Standards for Approval of Diagnostics
4.5 The Ideal Diagnostic Tool
4.6 Development of Diagnostic Tests
4.7 Challenges in the Availability of Quality-Assured
Diagnostic Tests in the Developing World
4.8 Opportunities for a Better Future
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4.8.1 Technological Advances
4.8.2 More Funding and More Players
4.8.3 Increased Efforts at Capacity Building
4.9 Bridging Research, Product Development, and
Commercialization
5 Oropouche Fever: An Overview of the Epidemiological and
Molecular Aspects in the Brazilian Amazon Region
Pedro F. C. Vasconcelos and Marcio R. T. Nunes
5.1 Oropouche Outbreaks
5.2 The Oropouche Virus
5.3 Geographic Distribution
5.4 Molecular Biology of the OROV
6 Is Avian Influenza Subtype H5N1 a Cause for Concern?
A Critical Analysis
Alan P. Zelicoff
6.1 Specter of Panzootics
6.2 The Nature of Influenza A Predisposes It to Pandemics
6.3 A Brief History of the H5N1 Panzootic and Human
Cases
6.4 Review of Epidemiology of H5N1 in Humans
6.4.1 The Basis of the Concern for H5N1 as a
Pandemic Threat
6.4.2 Critique of the Pandemic Hypothesis
6.5 Are There Asymptomatic H5N1 Infections?
6.6 Do Humans Have Some Immunity to H5N1?
6.7 Experimental Data: Vaccination and Challenge
Experiments in Animals Using H5N1
6.8 Transmission of Reassortment Variants of H5N1
6.9 Was the 1918 Pandemic Different from Others?
7 Diagnostics of Viral Respiratory Diseases
Tamar Amir, Guy Gubi, and Leslie Lobel
7.1 Viral Respiratory Diseases
7.2 Respiratory Viruses
7.3 Diagnostic Techniques
7.3.1 Immunoassays
7.3.2 Molecular Techniques
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x Contents
7.3.3 Multiplex PCR-Based Assays in Use Today
7.3.4 Point-of-Care Tests
8 Reverse Genetics as a Tool for Detection of
Negative-Stranded RNA Viruses
Pavel Naumenko, Leslie Lobel, and Robert S. Marks
8.1 Dangerous Viruses Easily Accessible
8.2 Negative-Stranded RNA Viruses
8.2.1 Genome Structure
8.3 Reverse Genetics System Development
8.4 Choosing the Promoter
8.5 Applications
8.6 Detection of Negative-Stranded RNA Viruses
8.7 Reverse Genetics–Based Detection
8.8 Where Do We Go from Here?
9 Diagnostics of Ebola Hemorrhagic Fever Virus
Ariel Sobarzo, Robert S. Marks, and Leslie Lobel
9.1 Ebola Virus
9.2 Etiology and Epidemiology
9.3 Disease Transmission and Clinical Behavior
9.4 Therapy
9.5 The Fear of Ebola
9.6 Current Methods in Ebola Diagnostics
9.6.1 Culture Virus Isolation
9.6.2 Electron Microscopy
9.6.3 Serological Assays
9.7 Nucleic Acid–Based Techniques
9.8 Engineered Recombinant Proteins
9.9 New Trends in Ebola Diagnostics
9.10 Future Diagnostics
9.11 The Effort Continues
10 Pathogen Detection Using Spatially Focused Microwaves
and Metal-Enhanced Fluorescence
Kadir Aslan and Chris D. Geddes
10.1 Ultrafast and Sensitive Detection of Anthrax with
Focused Microwave and Metal-Enhanced
Fluorescence
10.2 Metal-Enhanced Fluorescence
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Contents
10.3 Microwave-Accelerated Metal-Enhanced
Fluorescence
10.3.1 Proof-of-Principle Demonstration of the
MAMEF Technique
10.3.2 Application of the MAMEF Technique to
Pathogen Detection Based on DNA
Hybridization Assays
10.4 Spatially Focused Microwaves and Metal-Enhanced
Fluorescence for Pathogen and Virus Detection
10.5 Summary and Future Outlook
11 Lyssavirus Surveillance and Diagnostics: Focus on Africa
Wanda Markotter and Louis H. Nel
11.1 Introduction
11.2 The Etiological Agent
11.3 Lyssaviruses in Africa
11.4 Pathogenesis of Lyssaviruses
11.5 Lyssavirus Diagnostics
11.5.1 Detection of Negri Bodies
11.5.2 Fluorescent Antibody Test
11.5.3 Enzyme-Linked Immunosorbent Assay
11.5.4 Direct Rapid Immunohistochemical Test
11.5.5 Rapid Lateral Flow
Immunochromatography
11.5.6 Detection of Lyssavirus RNA
11.5.7 Virus Isolation
11.5.8 Antibody Detection
11.6 Challenges for the Developing World
12 Detection of Human Pathogens under Basic Laboratory
Conditions by DNA Hybridization Arrays
Roman Wölfel
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13 Differentiation between Viral and Bacterial Respiratory
Infections Using Chemiluminescence of Polymorphonuclear
Leukocytes
263
Daria Prilutsky, Mark Last, Leslie Lobel,
and Robert S. Marks
13.1 The Innate Immune System and Participating Cells 263
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Contents
13.2 Phagocytosis as a First-Line Defense Mechanism
against Pathogens
13.2.1 Respiratory Burst: Mechanisms,
Localization, and Techniques for Detection
13.2.1.1 Main mechanisms, products and
enzymes of the respiratory burst
13.2.1.2 Techniques used to measure
reactive oxygen species
13.2.1.3 Localization of the
luminol-dependent CL reaction
13.2.1.4 Stimulation of the respiratory
burst
13.2.2 Priming
13.2.3 Characterization of the Dynamic
Component Chemiluminescent Approach
for Assessment of Functional States of
Phagocytes
13.2.4 Components of Chemiluminescent
Kinetics
13.3 Functional States of Phagocytes
13.3.1 Dynamic Assessment of Phagocytes’
Functional States
13.3.1.1 fMLP priming
13.3.1.2 Aging as a priming factor
13.3.2 Functional States of Phagocytes Associated
with Different Clinical States
13.3.3 Phagocytic Function in Viral Infection
13.3.4 Phagocytic Function in Bacterial Infection
13.4 Data Mining Techniques in Clinical Groups’
Differentiation
13.5 Differentiation between Viral and Bacterial
Respiratory Infections Using a Chemiluminescent
Approach
13.5.1 Description of an Experiment
13.6 Data Mining Algorithms and CL Information Can
Differentiate between Clinical Groups and Assess
Functional States of Phagocytes
13.7 Prospects
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Contents
14 Phage Display for Viral Diagnostics
Danit Atias, Leslie Lobel, and Robert S. Marks
14.1 Phage Display for Advanced Diagnostics
14.2 Biology of Phages
14.3 Filamentous Phages
14.3.1 Structure of the Filamentous Phage Virion
14.3.2 Life Cycle of the Filamentous Phage
14.3.3 Filamentous Phage Display
14.4 T7 Phage: Structure of the Virion
14.4.1 Life Cycle of T7
14.4.2 T7 Phage Display
14.5 Principles and Applications of Phage Display
14.5.1 Phage Display of Natural Peptides
14.5.2 Phage Display of Random Peptides
14.5.3 Phage Display of Proteins or Protein
Domains
14.5.4 Multiple-Display Phages
14.6 Use of Phage-Displayed Epitopes for Viral
Diagnostics
14.6.1 ELISA and Phage Display
14.6.2 Dot Blot Assay and Phage Display
14.6.3 PCR, Immuno-PCR, and Phage Display
14.6.4 Electrochemical Phage Immunosensors
14.7 Prospects for Use of Phage Display in Biosensors
and Biochips
15 Nanolithography and Biochips’ Role in Viral Detection
Inbal Tsarfati-BarAd and Levi A. Gheber
15.1 The Need for Portable Biochips for Viral Detection
15.2 Arrayed Biosensors: Biochips
15.3 The Need for Miniaturization
15.4 Nanolithography
15.5 SPM-Based Nanolithography Methods
15.5.1 Nanografting
15.5.2 Dip-Pen Nanolithography
15.5.3 Nano–Fountain Pen
15.6 Problems Associated with Miniaturization
15.7 Conclusions
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Contents
16 Optical Fiber Immunosensors and Genosensors for the
Detection of Viruses
Yael Liebes and Robert S. Marks
16.1 Issues in Biothreat Detection
16.2 Optical Fibers as Optical Transducers: Why Optical
Fibers to Begin With?
16.2.1 Optical Fibers: Pros and Cons
16.2.2 The Basic Physics behind Optical Fiber
Operation
16.2.2.1 Snell’s law and TIR
16.2.3 Relevance of Optical Fibers as a Waveguide
to Chemiluminescence
16.2.4 Evanescent Wave Principles Useful in
Fluorescence-Based Optical Fiber Sensors
16.3 Bioreceptor Immobilization: Chemical Modification
to Optical Fibers
16.3.1 Immobilization to Solid Supports
16.3.2 Immobilization via Functional
Group-Terminated Silane Reagents
16.3.3 Immobilization via Electrochemical
Procedures
16.3.4 Immobilization via an Avidin–Biotin Bridge
16.4 Signal Measurements: State-of-the-Art
Photodetectors
16.4.1 Evolution of Photodetector
Instrumentations
16.5 Fiber Optic Immunosensors Applications for Use in
Viral Infections
16.5.1 Biosensors under Research or
Development: Antibody Detection
16.5.1.1 Detection of anti-West Nile virus
IgG antibodies
16.5.1.2 Detection of viral antibodies
using an “electroptode”
16.5.2 Virus Detection
16.5.2.1 Newcastle disease virus
16.5.2.2 MS2 bacteriophage
16.5.3 Detection of Oligionucleotides
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Contents
16.6 Commercial Products
16.7 Issues in Developing Fiber Optic–Based
Immunosensors
16.8 The Future Role of Optical Fiber Biosensors
17 Aptamers, a New Class of Binders, with Particular Focus on
Diagnostics and Bioactivity in the Field of Virology
Andreas Kage and Leslie Lobel
17.1 General Facts about Aptamers
17.2 Selection Procedures
17.3 Aptamers for Analytical Purposes (Detection and
Quantification)
17.4 Polyvalent, Polyspecific Aptamer Constructs
17.5 Aptamers for Therapeutic Purposes
17.6 Aptamers in Virology
17.6.1 General Facts about Aptamers in Virology
17.6.2 Next Steps into the Future of Aptamers in
Virology
17.7 AptaRes AG: MonoLex Aptamers
18 Pseudotyped Viruses: A New Sero-Diagnostic Tool
Jean-Michel Garcia
18.1 Brief Historical Review of Pseudotyped Viruses
18.2 Present Lentiviral Production Technologies and
Their Limitations
18.3 Pseudoparticles Characterization and Titration
18.4 Applications to a Neutralization-Based
Sero-Diagnostic Assay
18.5 Perspectives for the Use of Pseudoparticles in
Serology and Other Applications
19 Nucleic Acid Isothermal Amplification Technologies and
Point-of-Care Diagnostics
Tanya M. Ferguson and Angelika Niemz
19.1 Isothermal Amplification Technologies
19.1.1 Target Detection via RNA Transcription
19.1.2 Target Detection via DNA Replication
19.1.3 Target Detection via Strand Displacement
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Contents
19.2 NAAT-NAAT-Compatible End-Point Detection
Platforms Suitable for Point-of-Care in
Low-Resource Settings
20 Recent Ebola and Marburg Viral Hemorrhagic Fever
Outbreaks in Uganda: The Need for Quick, Reliable
Diagnostic Tests
Julius Julian Lutwama
20.1 Introduction
20.2 Outbreak Experience
20.2.1 The 2000–2001 Ebola Outbreaks: Gulu,
Masindi, and Mbarara Districts
20.2.2 The 2007 Marburg Outbreaks in the
Kamwemge District
20.2.3 The 2007–2008 Ebola Outbreak in the
Bundibugyo District
20.3 The Challenges
20.3.1 Time Spent on Receiving Information and
Time Spent before a Response Is Made
20.3.2 Time Spent without Confirmation of an
Outbreak
20.3.3 Numbers of People Infected and Deaths
20.3.4 Numbers of Health Workers Infected and
Deaths
20.3.5 The Need for Quick Diagnostic Tests
20.3.5.1 The needed capacities
20.3.5.2 Infrastructural capacities
20.3.6 Trained Personnel
20.3.7 Availability of Funds
20.3.8 The Complexity of the Present Tests and
the Need for Simplification
20.4 Way Forward for Uganda
21 Amperometric Immuno- and DNA Sensors for Rapid and
Specific Identification of Viruses
Rodica E. Ionescu, Serge Cosnier, Vasile Magearu,
and Robert S. Marks
21.1 Introduction
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21.2 Theoretical Aspects for Amperometric Enzyme
Biosensors
21.2.1 Introduction to Basic Electrochemical
Principles
21.2.2 Voltammetry
21.2.3 Amperometry
21.2.4 Amperometric Biosensors’ Classes
21.2.4.1 First class of amperometric
biosensors
21.2.4.2 Second class of amperometric
biosensors
21.2.4.3 Third class of amperometric
biosensors
21.3 Classification of Amperometric Biosensors
21.3.1 Immunosensors
21.3.2 DNA Sensors
21.4 Viral Detection Using Amperometry
21.4.1 Variola Virus
21.4.2 Retroviridae Family
21.4.2.1 Bovine leukemia virus
21.4.3 The Orthomyxoviridae Family
21.4.3.1 Parainfluenza and influenza A
viruses
21.4.4 The Flaviviridae Family
21.4.4.1 Japanese encephalitis virus
21.4.4.2 West Nile virus
21.4.4.3 Hepatitis C virus
21.4.4.4 Bovine viral diarrhea virus
21.4.5 The Hepadnaviridae Family
21.4.5.1 Hepatitis B virus
21.4.6 The Bunyaviridae Family
21.4.6.1 Hantaviruses
21.4.7 The Paramyxoviridae Family
21.4.7.1 Newcastle disease virus
21.5 Future Directions
Index
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Foreword
Although the immediate genesis of this volume was the unique
and very practical international Viralcheck Workshop held in Dakar,
Senegal, in June 2008, it represents a signpost along the path begun
by Leslie Lobel and Robert Marks years ago at the Ben-Gurion
University of the Negev in Israel. The path through the jungle of
infectious diseases does not end with the workshop or with this
volume. As a result of their shared interest in infectious disease
surveillance, diagnosis, and therapy, Lobel and Marks established
individual scientific collaborations across the African continent,
first simply as a means of collecting reagents to facilitate their
development of advanced countermeasures back in the lab. They
soon recognized the extraordinary skill and dedication of their
collaborators in Africa and their desperate need for tools to fight
disease. Together with their new colleagues, they defined unique
challenges on the continent, including too few diagnostic tools,
too little training and integration of new technologies, and too
little continuity among infectious disease programs—many very
good—already ongoing in Africa. Thus, at the Senegal workshop
in 2008, the Bio-Africa Research Network (BARN) was born. Its
purpose—“Research to directly address the local needs of Africans
with respect to infectious diseases.” Today, Lobel and Marks have
strong scientific and human relationships in Senegal, Uganda, and
South Africa and budding ones in Ethiopia, Kenya, Mali, Madagascar,
Tanzania, and Ghana, obviously spanning both English- and Frenchspeaking regions. This book serves as a record of these activities and
underscores their value.
Here, the authors have brought together a set of chapters
at once educational and interesting, technologically cutting edge,
and practical. They begin with real-world examples of the impact,
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epidemiology, and control of naturally occurring infectious diseases,
which extends from the popularized filovirus family of viruses to
the timely influenzas and from field and laboratory diagnostics and
global surveillance to the business side of medical countermeasures:
research, development, and commercialization. Part one of the book
provides the historic and contemporary underpinnings for the hard
technical and field work that must follow, all with the goal of
enhancing capacity in the developing world.
The two middle parts cover proven methods of diagnosis of
infectious disease. First, classical antigen-antibody reactions that
have been used for well-known agents (Ebola hemorrhagic fever
virus, the Lyssaviridae, and the common viral respiratory killers)
are described. Then, an in-depth and balanced description of new
technologies is provided, some still not fielded: phage display,
biochips, optical fiber-based systems, chemiluminescence, and DNA
hybridization arrays. The chapters in these two sections clearly
delineate the power of the biotech revolution’s weapons and the
point-of-care diagnostics that will have a huge impact on the
battles against infectious disease. While the technologies are being
developed in universities and start-up companies of the developed
world, holding the workshop in the developing world underscored
their global promise. Therefore, in the course of the book, the
reader is transitioned from the challenges of confronting common
and emerging infectious diseases in the developing world to the
enormous promise of the biotech revolution and back to the
laboratory where the hard work must be done.
Advanced Detection of Viral Pathogens is extraordinarily timely
and near the working edge geographically and chronologically as the
biotech revolution roars through the developed world and infectious
diseases continue to burn through the developing world and beyond,
killing 14 million humans per year globally. It would have been
easy for Drs. Lobel and Marks to simply continue their very useful
technical and clinical activities in the comfort of their university, but
they had a vision. And they acted on their vision. I have admired
their work at the bench, developing diagnostic tools and therapeutic
antibodies. I have watched them articulate their vision to the good
people who helped with early funding of their activities in Africa.
I will always respect them for rolling up their sleeves, leaving the
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comfort of their university campus, building human relationships,
and gaining the trust of their colleagues . . . all based on the common
language of science and medicine and powered by the will to
make a difference in the developing world. This volume is a lasting
monument to the power of the synergies that can be found when
good science and good human relationships are brought together by
those who care enough to make the effort.
Dave Franz
October 22, 2014
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Preface
Dear Reader,
From the beginning of recorded history it is evident that viruses
evolved in our midst. Were they one of the unwanted gifts as Adam
left the Garden of Eden? Our sudden nudity exposed our fragility and
ever since we have had to survive them while continually seeking
defenses.
The book you have in your hands illustrates a variety of
challenges we bug-hunters try to overcome. Indeed, we have
gathered here insights and expertise of an interdisciplinary group
of researchers from all walks of life: virologists, physicians,
immunologists, electrochemists, physicists, computer scientists,
biotechnologists, epidemiologists, molecular biologists, all working
in fields that cross scientific boundaries—working at the forefront
of diagnostics.
Notwithstanding a dire moment as that of the recent Ebola
outbreak in West Africa that saddens us all, we must more than
ever peregrinate across oceans, and take the fight to them, as
these invisible and exotic but deadly enemies know no barriers
and constantly invade our lives. The coming epidemics and killer
pandemics require us to continuously innovate in areas of prevention, detection and therapy. However, the present volume focuses
on creating virus alerts or hand-held detectors to bring to the
field during an epidemic, when possible, or tools for the healthcare
worker to rapidly diagnose the patient’s ailment. We describe the
conventional cell cultures and molecular biology methodologies,
while introducing state-of-the-art multidisciplinary biosensors. This
book is not a manual, nor a set of protocols, nor a textbook, but
our glimpse into the advances of virus diagnostic research. Included
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Preface
are a variety of topics that encompass world health issues, local
folklore, such as associating outbreaks with witchcraft, problems
in getting healthcare workers to the outbreak areas and insights in
viral diagnostic pitfalls.
The concept of this book came about in Dakar, 2008, during a
“Viralcheck” workshop the co-editors organized, where researchers
from around the world came to test their respective diagnostic
kits with samples provided by the Institute Pasteur in Dakar. The
workshop introduced the participants to the difficulties involved in
testing “real-life” samples, where discrepancies, data inconsistencies
and inappropriateness for local use of tests were discovered. As I
write this preface in my stay in Singapore at the CREATE laboratories
where dozens of cases of dengue have occurred just meters away
from us, my friends Amadou Alpha Sall and Leslie Lobel and our
other colleagues are busy each in their own way to help fight
this terrible wrath (Ebola) hitting humanity. I conclude that the
timeliness of our book is mind-boggling. Finally, I would like to
express my gratitude and thank all my co-authors, participants of
Viralcheck, Dakar, Senegal, and our more than patient publisher, and
of course, you the reader, in showing your interest in a topic that will
never stop to concern all of us.
Robert S. Marks
Ben Gurion University of the Negev
October 2014