New and Evolving Infections of the 21st Century

New and Evolving Infections of the

21 ^st Century

I. W. Fong & Ken Alibek

New and Evolving

Infections of the

21 ^st Century

I. W. Fong

Professor of Medicine University of Toronto Toronto, ON MB1W8 Canada

fungi@smh.toronto.on.ca

Ken Alibeck

Executive Director, Center of Biodefense George Mason University

Manassas, VA 20110 USA

kalibek@gmu.edu

Cover illustration: APImages

Library of Congress Control Number: 2006921352

ISBN-10: 0-387-32647-2 e-ISBN-10: 0-387-32830-0 ISBN-13: 978-0387-32647-4 e-ISBN-13: 978-0387-32830-0 Printed on acid-free paper.

© 2007 Springer Science + Business Media, LLC

All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer Science + Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden.

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Contents

Section I: Evolving Infectious Diseases

1. West Nile Virus in the Americas

Lyle R. Petersen, John T. Roehrig, and James J. Sejvar

1.1. Virology . . . 3

1.1.1. Virus Structure . . . 3

1.1.2. Genome . . . 3

1.1.2.1. E-protein . . . 4

1.1.2.2. Nonstructural Proteins . . . 6

1.1.3. Genetics and Virulence . . . 8

1.2. Epidemiology . . . 9

1.2.1. Ecology . . . 9

1.2.1.1. Vectors . . . 9

1.2.1.2. Vertebrate Hosts . . . 11

1.2.2. Geographic Spread . . . 12

1.2.2.1. United States and Canada . . . 12

1.2.2.2. Latin America . . . 12

1.2.3. Incidence of Human Infection and Illness . . . 15

1.2.3.1. United States . . . 15

1.2.3.2 Canada . . . 16

1.2.4. Risk Factors for Infection, Severe Disease, and Death . . . 17

1.2.5. Non-Mosquito Transmission Routes . . . 18

1.2.5.1. Blood Transfusion . . . 18

1.2.5.2. Organ Transplantation . . . 18

1.2.5.3. Intrauterine Transmission . . . 19

1.2.5.4. Other Transmission Modes . . . 19

1.3. Clinical Spectrum . . . 20

1.3.1. West Nile Fever . . . 20

1.3.2. Neuroinvasive Disease . . . 21

1.3.2.1. Meningitis . . . 23

1.3.2.2. Encephalitis . . . 23

1.3.2.3. Weakness and Paralysis . . . 24

1.3.3. Other Clinical Manifestations . . . 27

1.3.3.1. Ocular Manifestations . . . 27

1.3.3.2. Miscellaneous Manifestations . . . 28

1.3.4. Clinical Illness in Special Population Groups . . . 28

1.3.4.1. Children . . . 28

1.3.4.2. Immunocompromised Patients . . . 28

v

1.4. Diagnosis . . . 29

1.4.1. Antibody Detection . . . 29

1.4.1.1. IgM ELISA . . . 29

1.4.1.2. IgG ELISA . . . 30

1.4.1.3. Neutralization Test . . . 30

1.4.2. Antigen Detection . . . 31

1.4.2.1. Antigen-Capture ELISA . . . 31

1.4.2.2. Immunohistochemical Staining . . . 31

1.4.3. Detection of Viral Genomic Sequences . . . 31

1.4.3.1 Nucleic Acid Amplification Test (NAAT) . . . 31

1.4.4. Other Laboratory, Radiologic, and Electrodiagnostic Findings . . . 33

1.5. Management . . . 34

1.6. Prevention . . . 36

1.6.1. Human Personal Protection . . . 36

1.6.2. Mosquito Control . . . 37

1.6.3. Vaccines . . . 37

1.6.4. Screening of Blood Donations . . . 38

1.7. Future Directions . . . 38

1.7.1. Surveillance . . . 38

1.7.2. Diagnosis and Treatment . . . 39

1.7.3. Prevention . . . 39

References . . . 40

2. Hantavirus Cardiopulmonary Syndrome: A New Twist to an Established Pathogen Frederick T. Koster and Howard Levy 2.1. Virology. . . 57

2.1.1. Classification and Characteristics . . . 57

2.1.2. Viral Replication . . . 58

2.2. Pathophysiology and Animal Models . . . 61

2.2.1. Cell Entry . . . 61

2.2.2. Virulence . . . 62

2.2.3. Cellular Targets for HV . . . 63

2.2.4. Pathology and Pathogenesis . . . 64

2.2.5. Role of the T-Cell Response . . . 65

2.2.6. Immunity . . . 67

2.2.7. Animal Models . . . 69

2.3. Epidemiology and Transmission . . . 70

2.3.1. Epidemiology . . . 70

2.3.2. Transmission . . . 70

2.4. Clinical Spectrum . . . 73

2.4.1. Asymptomatic or Mild Infection . . . 73

2.4.2. Incubation Period . . . 74

2.4.3. Clinical Presentation of HCPS. . . 74

2.4.3.1. Febrile Phase . . . 74

2.4.3.2. Cardiopulmonary Phase . . . 75

2.4.3.3. Convalescent Phase . . . 76

2.4.4. Clinical Presentation of HFRS . . . 76

vi Contents

2.5. Diagnosis of Acute Infection . . . 77

2.6. Current Management . . . 77

2.7. Prevention . . . 80

2.8. Future Directions . . . 81

References . . . 82

3. Human Ehrlichioses and Anaplasmosis Jere W. McBride and David H. Walker 3.1. Human Ehrlichioses (Human Monocytotropic and Ehrlichiosis Ewingii) . . . . 93

3.1.1. Taxonomy . . . 93

3.1.2. Morphology . . . 93

3.1.3. Genetic, Antigenic, and Phenotypic Characteristics . . . 96

3.1.4. Pathogenesis and Immunity . . . 98

3.1.5. Emergency, Epidemiology, and Transmission . . . 102

3.1.6. Clinical Spectrum . . . 104

3.1.7. Laboratory Diagnosis . . . 105

3.1.8. Treatment and Prevention . . . 106

3.2. Human Anaplasmosis . . . 107

3.2.1. Taxonomy . . . 107

3.2.2. Morphology . . . 107

3.2.3. Genetic, Antigenic, and Phenotypic Characteristics . . . 108

3.2.4. Pathogenesis and Immunity . . . 110

3.2.5. Emergency, Epidemiology and Transmission . . . 114

3.2.6. Clinical Spectrum . . . 115

3.2.7. Laboratory Diagnosis . . . 115

3.2.8. Prevention and Treatment . . . 116

3.3. Future Directions . . . 117

References . . . 117

4. Cross-Species Transmission of Poxviruses Mike Bray 4.1. Introduction: The Poxvirus Family . . . 129

4.1.1. The Poxvirus “Survival Strategy” . . . 134

4.1.2. Measures and Countermeasures . . . 135

4.1.3. Maintenance Hosts and Cross-Species Transmission . . . 138

4.1.4. Barriers to Cross-Species Transmission . . . 139

4.2. Poxviruses That Cause Human Disease . . . 140

4.2.1. Orthopoxvirus . . . 141

4.2.1.1. Variola Virus . . . 142

4.2.1.2. MonkeyPox Virus . . . 143

4.2.1.3. Vaccinia Virus . . . 144

4.2.1.4. CowPox Virus . . . 145

4.2.1.5. Ectromelia Virus . . . 146

4.2.1.6. CamelPox Virus . . . 147

4.2.1.7. Other Orthopoxviruses . . . 147

4.2.2. Yatapoxvirus . . . 148

4.2.3. Parapoxvirus . . . 149

4.2.4. Molluscipoxvirus . . . 150

Contents vii

4.3. Genera that have not Caused Human Disease . . . 151

4.3.1. Leporipoxvirus . . . 151

4.3.2. Capripoxvirus . . . 152

4.3.3. Suipoxvirus . . . 153

4.3.4. Avipoxvirus . . . 154

4.4. Newly Identified Poxvirus Genera . . . 155

4.5. Conclusion . . . 155

References . . . 156

Section II: Newly Recognized Human Viruses 5. The Severe Acute Respiratory Syndrome Kwok-Yung Yuen, Samson S.Y. Wong, and J.S. Malik Peiris 5.1. Introduction . . . 163

5.2. Sequence of Events . . . 163

5.3. Epidemiological Characteristics . . . 164

5.4. General Virology . . . 166

5.5. Clinical Findings . . . 172

5.6. Laboratory Diagnostics . . . 173

5.7. Pathology and Immunology . . . 174

5.8. Animal Models and Koch’s Postulates . . . 175

5.9. Clinical Management . . . 176

5.9.1. Antivirals and Immunomodulators . . . 177

5.9.2. Passive and Active Immunization . . . 178

5.10. Laboratory Safety, Community and Hospital Infection Control . . . 182

References . . . 183

6. Newly Identified Human Herpesviruses: HHV-6, HHV-7, and HHV-8 Laurie T. Krug, Chong-Gee Teo, Keiko Tanaka-Taya, and Naoki Inoue 6.1. HHV-6 and HHV-7. . . 197

6.1.1. Biology . . . 197

6.1.1.1. Cell Tropism and Viral Entry . . . 197

6.1.1.2. Gene Expression and Replication . . . 198

6.1.1.3. Latency and Reactivation . . . 199

6.1.1.4. Immune Responses and Immune Evasion . . . 201

6.1.1.5. Pathogenesis . . . 202

6.1.1.6. Animal Models . . . 203

6.1.2. Epidemiology . . . 203

6.1.2.1. Primary Infection . . . 203

6.1.2.2. Transmission . . . 204

6.1.2.3. Proposed Disease Associations . . . 205

6.1.3. Clinical Spectrum . . . 205

6.1.3.1. Exanthem Subitum (Roseola) . . . 205

6.1.3.2. Encephalitis . . . 206

6.1.3.3. Post-transplantation Disease . . . 206

viii Contents

6.1.4. Management and Prevention . . . 208

6.1.4.1. Antivirals . . . 208

6.1.4.2. Transplantation Management . . . 208

6.2. HHV-8 . . . 208

6.2.1. Biology . . . 208

6.2.1.1. Cell Tropism and Viral Entry . . . 208

6.2.1.2. Latency and Reactivation . . . 209

6.2.1.3. Immune Response and Immune Evasion . . . 210

6.2.1.4. Pathogenesis . . . 216

6.2.1.5. Animal Models . . . 222

6.2.2. Epidemiology . . . 226

6.2.2.1. Seroepidemiology . . . 226

6.2.2.2. HHV-8 Genotypes . . . 229

6.2.2.3. Transmission . . . 231

6.2.3. Clinical Spectrum . . . 234

6.2.3.1. Primary Infection . . . 234

6.2.3.2. Kaposi’s Sarcoma . . . 235

6.2.3.3. Primary Effusion Lymphoma (PEL) . . . 238

6.2.3.4. Castleman’s Disease . . . 239

6.2.3.5. Other Lymphoproliferative Disorders . . . 240

6.2.3.6. Other Neoplastic Disorders . . . 240

6.2.3.7. Other Diseases . . . 240

6.2.4. Management . . . 241

6.2.4.1. Antivirals . . . 241

6.2.4.2. Anti-retroviral Protease Inhibitors . . . 242

6.2.4.3. Other Approaches . . . 242

References . . . 242

Section III: Emerging Viruses in Asia 7. Nipah and Hendra Viruses Encephalitis Khean Jin Goh, Kum Thong Wong, and Chong Tin Tan 7.1. Introduction . . . 279

7.2. Hendra Virus Infection . . . 279

7.2.1. Epidemiology . . . 280

7.2.2. Clinical Features . . . 280

7.2.3. Diagnosis . . . 281

7.2.4. Pathology . . . 281

7.3. Nipah Virus Infection . . . 281

7.3.1. Epidemiology . . . 282

7.3.2. Clinical Features . . . 284

7.3.3. Investigations . . . 285

7.3.4. Treatment and Outcome . . . 287

7.3.5. Relapsed and Late-Onset Encephalitis . . . 287

7.3.6. Pathology . . . 287

7.3.7. Pathogenesis . . . 289

7.4. Conclusion . . . 290

References . . . 290

Contents ix

8. Enterovirus 71 Encephalitis

Luan-Yin Chang, Shin-Ru Shih, Li-Min Huang, and Tzou-Yien Lin

8.1. Virology . . . 295

8.1.1. Virological Classification of Enterovirus 71 . . . 295

8.1.2. General Characteristics of Enterovirus . . . 296

8.1.3. Virion Structure of Enterovirus . . . 296

8.1.4. Replication Cycle of Enterovirus . . . 297

8.1.5. Genotypes and Neurovirulence of EV71 . . . 297

8.2. Transmission and Incubation Period . . . 298

8.2.1. Route of Transmission . . . 298

8.2.2. The Rate of Household Transmission . . . 299

8.2.3. Incubation Period . . . 300

8.3. Epidemiology . . . 300

8.3.1. Worldwide Epidemiology . . . 300

8.3.2. Epidemiology in Taiwan . . . 301

8.4. Clinical Spectrum . . . 303

8.4.1. Asymptomatic Infection . . . 304

8.4.2. Stage 1: Uncomplicated EV71 Illness . . . 304

8.4.3. Stage 2: Complicated EV71 Illness with CNS Involvement . . . 305

8.4.3.1. EV71 Aseptic Meningitis . . . 305

8.4.3.2. EV71 Encephalitis . . . 306

8.4.3.3. Polio-like Syndrome . . . 306

8.4.3.4. Encephalomyelitis . . . 306

8.4.3.5. Image Studies for CNS Involvement . . . 306

8.4.4. Stage 3: Cardiopulmonary Failure or Pulmonary Edema . . . 307

8.4.4.1. Pathogenesis of EV71-related Cardiopulmonary Failure . . . 308

8.4.5. Stage 4: Convalescence and Long-term Sequelae . . . 310

8.4.6. Factors Associated with Complications . . . 310

8.4.7. EV71 Versus Coxsackievirus A16 . . . 310

8.5. Diagnosis . . . 311

8.5.1. Virus Isolation and Identification . . . 311

8.5.2. Gene Chips . . . 311

8.5.3. Serology Test . . . 312

8.5.3.1. Neutralizing Antibody . . . 312

8.5.3.2. EV71 IgM . . . 312

8.6. Management . . . 313

8.6.1. Stage-based Management . . . 314

8.6.2. Antiviral Agents . . . 314

8.6.2.1. Inhibitors of Virion Attachment for Enteroviruses . . . 315

8.6.2.2. Inhibitors of Uncoating for Enteroviruses . . . 316

8.6.2.3. Pleconaril (VP 63843) and Novel Anti-EV71 Agents . . . 316

8.7. Prevention . . . 318

8.7.1. Hand Washing and Isolation . . . 318

8.7.2. EV71-related Disease and Laboratory Surveillance . . . 319

8.7.3. Vaccination . . . 319

8.8. Future Directions . . . 320

References . . . 320

x Contents

Contents xi

9. Avian Influenza Viruses and Pandemic Influenza Menno Douwe de Jong

9.1. Introduction . . . 327

9.2. Virology. . . 328

9.2.1. Biological Properties . . . 328

9.2.2. Classification . . . 329

9.2.3. Natural Hosts . . . 329

9.2.4. Determinants of Host Range . . . 329

9.2.5. Antigenic Variation and The Emergence of Pandemic Influenza Strains. . . 331

9.2.5.1. Antigenic Drift . . . 331

9.2.5.2. Antigenic Shift . . . 331

9.3. Pathogensis of Avian Influenza . . . 332

9.3.1. Avian Influenza Virus Infections in Natural Hosts . . . 332

9.3.2. Viral Determinants of Pathogenicity . . . 333

9.3.3. Host Factors . . . 336

9.4. Avian Influeza Viruses Infecting Humans . . . 337

9.4.1. Pandemics of the 20

Century. . . 337

9.4.2. H7N7 Viruses . . . 339

9.4.3. H7N3 Viruses . . . 341

9.4.4. H9N2 Viruses . . . 342

9.4.5. H5N1 Viruses . . . 343

9.4.5.1. Outbreaks of Influenza H5N1 in Poultry and Humans . . . 343

9.4.5.2. The Clinical Spectrum of Human H5N1 Infections . . . 344

9.4.5.3. The Evolution of H5N1 Viruses, 1997–2004 . . . 347

9.5. Laboratory Diagniosis of Avian Influenza. . . 349

9.5.1. Virus Isolation . . . 349

9.5.2. Antigen Detection . . . 350

9.5.3. RT-PCR. . . 350

9.5.4. Serology . . . 351

9.6. Treatment and Prevention. . . 352

9.6.1. Antiviral Treatment . . . 352

9.6.2. Infection Control and Prophylaxis . . . 354

9.6.3. Vaccination . . . 356

9.7. Pandemic Preparedness and Future Directives . . . 356

References . . . 359

Index . . . . 369

Contributors

Ken Alibek

Executive Director and Distinguished Professor of Medical Microbiology and Immunology

The National Centre for Biodefense George Manson University Mike Bray

Biodefense Clinical Research Branch, Office of Clinical Research

National Institute of Allergy and Infectious Diseases

National Institutes of Health Bethesda, Maryland Dr. Luan-Yin Chang

Division of Pediatric Infectious Diseases, Department of Pediatrics

National Taiwan University Hospital College of Medicine

National Taiwan University Taipei 100, Taiwan Jeremy Farrar FRCP DPhil

Clinical Reader University of Oxford Director University of Oxford Research Unit Hospital for Tropical Diseases

Ho Chi Minh Tu, Viet Nam Ignatius Wellington (Bill) Fong Professor of Medicine

Division of Infectious Diseases 30 Bond St.

Toronto, Ont., M5B 1W8.

Dr. Khean Jin Goh Department of Medicine Faculty of Medicine University of Malaya

Pantai Valley, 50603 Kuala Lumpur, MALAYSIA

Li-Min Huang

Professor, Division of Pediatric Infectious Diseases

Dept. of Pediatrics National Taiwan University Hospital

College of Medicine, National Taiwan University Taipei 100, Taiwan

Naoki Inoue, PhD

Chief, Laboratory of Herpesviruses Department of Virology I

National Institute of Infectious Disease Tokyo 162-8640, Japan

Dr. Menno de Jong

Oxford University Clinical Research Unit Hospital for Tropical Diseases

Ho Chi Minh City, Viet Nam Fred Koster

Lovelace Respiratory Research Institute Albuquerque, NM

Dr. Laurie T. Krug

Department of Microbiology and Immunology Yerkes National Primate Research Center Emory University

Atlanta, GA, 30329 Howard Levy Eli Lilly and Company Lilly Corporate Center Indianapolis, IN Tzou-Yien Lin

Professor, Division of pediatric Infectious Disease

Dept. of Pediatrics, Chang Gung Children’s Hospital

Chang Gung University Taoyuan 333, Taiwan Jere W. McBride, PhD

Department of Pathology, Center for Biodefense and Emerging Infectious Diseases

Sealy Center for Vaccine Development University of Texas Medical Branch Galveston, Texas

Dr. Malik Peiris

Dept. of Microbiology, University Pathology bldg

Queen Mary Hospital Hong Kong

xiii

xiv Contributors

Dr. Lyle Peterson

Division of Vector-borne Infectious Diseases Centers for Disease Control and Prevention Fort Collins, CO 80522

Dr. John Roehrig

Division of Vector-borne Infectious Disease Fort Collins, CO, 80522

Dr. James Sejvar

Division of Viral and Rickettsial Diseases Centers for Disease Control and Prevention Atlanta, GA 30333

Shin-Ru Shih

Professor, Clinical Virology Laboratory Chang Gung Memorial Hospital, and School of

Medical technology Tao-Yuan 333 Taiwan Chong Tin Tan

Professor and Head, Division of Neurology University of Malaya, Neurology Laboratory Kuala Lumpur 50603

Keiko Tanaka-Taya

Infectious Disease Surveillance Centre National Institute of Infectious Diseases Shinjuku-ku, Tokyo, 162-8640, Japan

Chong-Gee Teo

Sexually Transmitted and Blood Borne Virus Laboratory

Health Protection Agency London, UK, NW9 5HT David H. Walker, MD Department of Pathology

University of Texas Medical Branch-Galveston Galveston, Texas 77555

Kum Thong Wong Professor & Consultant, Head Dept. of Pathology, Faculty of Medicine University of Malaya

50603 Kuala Lumpur, Malaysia Samson SY Wong

Department of Microbiology The University of Hong Kong University Pathology Building

Queen Mary Hospital, Pokfulam, Hong Kong Kwok-Yung Yuen

Department of Microbiology

The University of Hong Kong

University Pathology Building

Queen Mary Hospital

Pokfulam, Hong Kong