Principles and Practice of Clinical Virology SIXTH EDITION Principles and Practice of Clinical Virology, Sixth Edition © 2009 John Wiley & Sons Ltd ISBN: 978-0-470-51799-4 Edited by A J Zuckerman, J E Banatvala, B D Schoub, P D Griffiths and P Mortimer Principles and Practice of Clinical Virology SIXTH EDITION Edited by Arie J Zuckerman UCL Medical School, London, UK Jangu E Banatvala Guy’s, King’s and St Thomas’ School of Medicine, London, UK Barry D Schoub National Institute of Virology, Sandringham, South Africa Paul D Griffiths UCL Medical School, London, UK Philip Mortimer Health Protection Agency, London, UK A John Wiley & Sons, Ltd., Publication This edition first published 2009 © 2009 John Wiley & Sons Ltd Wiley-Blackwell is an imprint of John Wiley & Sons, formed by the merger of Wiley’s global Scientific, Technical and Medical business with Blackwell Publishing Registered office: John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK Other Editorial Offices 9600 Garsington Road, Oxford, OX4 2DQ, UK 111 River Street, Hoboken, NJ 07030-5774, USA For details of our global editorial offices, for customer services and for information about how to apply for permission to reuse the copyright material in this book please see our website at www.wiley.com/wiley-blackwell The right of the author to be identified as the author of this work has been asserted in accordance with the Copyright, Designs and Patents Act 1988 All rights reserved No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by the UK Copyright, Designs and Patents Act 1988, without the prior permission of the publisher Wiley also publishes its books in a variety of electronic formats Some content that appears in print may not be available in electronic books Designations used by companies to distinguish their products are often claimed as trademarks All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners The publisher is not associated with any product or vendor mentioned in this book This publication is designed to provide accurate and authoritative information in regard to the subject matter covered It is sold on the understanding that the publisher is not engaged in rendering professional services If professional advice or other expert assistance is required, the services of a competent professional should be sought The contents of this work are intended to further general scientific research, understanding, and discussion only and are not intended and should not be relied upon as recommending or promoting a specific method, diagnosis, or treatment by physicians for any particular patient The publisher and the author make no representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties, including without limitation any implied warranties of fitness for a particular purpose In view of ongoing research, equipment modifications, changes in governmental regulations, and the constant flow of information relating to the use of medicines, equipment, and devices, the reader is urged to review and evaluate the information provided in the package insert or instructions for each medicine, equipment, or device for, among other things, any changes in the instructions or indication of usage and for added warnings and precautions Readers should consult with a specialist where appropriate The fact that an organization or Website is referred to in this work as a citation and/or a potential source of further information does not mean that the author or the publisher endorses the information the organization or Website may provide or recommendations it may make Further, readers should be aware that Internet Websites listed in this work may have changed or disappeared between when this work was written and when it is read No warranty may be created or extended by any promotional statements for this work Neither the publisher nor the author shall be liable for any damages arising herefrom Library of Congress Cataloging-in-Publication Data: Principles and practice of clinical virology / edited by Arie J Zuckerman [et al.] – 6th ed p ; cm Includes bibliographical references and index ISBN 978-0-470-51799-4 Virus diseases Medical virology I Zuckerman, Arie J [DNLM: Virus Diseases WC 500 P957 2008] RC114.5.P66 2008 616.9 101—dc22 2008040268 A catalogue record for this book is available from the British Library ISBN: 978-0-470-51799-4 Typeset in 9/11 Times Roman by Laserwords Private Limited, Chennai, India Printed in Singapore by Fabulous Printers Pte Ltd First Impression 2009 Contents List of Contributors Preface xi xiii Past, Present and Future of Clinical Virology: An Overview Diagnostic Approaches Katie Jeffery and Emma Aarons xv Introduction Electron Microscopy Histology/Cytology Virus Isolation Serology Molecular Amplification Techniques Recommended Diagnostic Investigations 20 Future Trends 22 Viral Transmission: Infection Acquired by the Blood-borne Route 29 Will Irving Introduction 29 Prevention of Exposure through Infection Control 30 Prevention of Infection through Specific Pre- and Post-exposure Policies 30 Patient-to-patient Transmission 30 Patient-to-HCW Transmission 32 HCW-to-patient Transmission 36 Viral Transmission: Infection Acquired by All Other Routes (Respiratory, Eye–Nose–Mouth, Inoculation and Faeco-orally) 43 Philip Rice Introduction 43 Measles, Mumps and Rubella 44 Cytomegalovirus 47 Varicella Zoster Virus 48 Herpes Simplex Virus 53 Noroviruses 54 Rotavirus 56 Parvovirus B19 56 Respiratory Viruses 58 Emerging Virus Infections Brian W.J Mahy Introduction 69 Factors Contributing to Emergence Future Directions 77 69 69 Vaccinology Francis E Andre and Hugues H Bogaerts 81 Introduction 81 Burden of Viral Diseases and their Reproductive Rates 82 The Immune System and its Role in Natural and Artificially-induced Immunity 83 Discovery of Protective Antigens in Pathogens 85 Presentation of Protective Antigens through Vaccines and Types of Vaccine 86 Research and Development on Vaccines and their Commercial Introduction 86 Social Marketing of Introduced Vaccines 88 Planning and Implementation of Vaccination Programmes 89 Surveillance of Disease Incidence and Adverse Events Before and After Implementation of Vaccination 89 Rectification of Publicized Falsehoods and Maintenance of Vaccination Coverage 89 Viral Vaccines on the Horizon and the Roadblocks to Future Vaccine Development 90 Closing Comments 91 Herpes Simplex Virus Type and Type Marianne Forsgren and Paul E Klapper Morphology 95 Replication 97 Epidemiology 103 Viral Diagnosis 105 Antiviral Chemotherapy 108 95 vi Contents Clinical Features, Diagnosis and Management Concluding Remarks 128 Varicella Zoster Judith Breuer 112 133 Introduction 133 The Virus 133 Epidemiology 142 Clinical Features 143 Diagnosis of VZV Infection 148 Treatment 151 Prevention 153 Cytomegalovirus Paul D Griffiths 12 Hepatitis Viruses 273 Tim J Harrison, Geoffrey M Dusheiko and Arie J Zuckerman 161 Introduction 161 The Virus 161 Epidemiology 166 Routes of Infection 167 Pathogenesis 168 Clinical Features 173 Diagnosis 175 Management 180 Prevention 183 Treatment 185 Introduction Hepatitis A Hepatitis E Hepatitis B Hepatitis D Hepatitis C 273 275 280 282 307 309 13 GB Virus C (GBV-C) and Torque Teno Virus (TTV) 321 Shigeo Hino Introduction 321 GB Virus C (GBV-C) 321 Torque Teno Virus (TTV) 325 Epstein–Barr Virus Tanzina Haque and Dorothy H Crawford Introduction 199 The Virus 199 Epidemiology 204 EBV-associated Diseases 205 EBV Infection in the Immunocompromized Host Vaccine Development 218 Worldwide Distribution of KSHV in the General Population 247 Transmission 249 Clinical Manifestations 251 Pathogenesis 254 Diagnostic Assays 261 Antiviral Therapy 263 199 215 10 Roseoloviruses: Human Herpesviruses 6A, 6B and 223 Katherine N Ward and Duncan A Clark Introduction 223 Biology of the Viruses 223 Epidemiology and Pathogenesis 228 Disease Associations 231 Laboratory Diagnosis 236 Antiviral Therapy 240 Concluding Remarks 240 11 Kaposi’s Sarcoma-associated Herpesvirus (Human Herpesvirus 8) 245 Cornelia Henke-Gendo, Abel Viejo-Borbolla and Thomas F Schulz Introduction 245 Origin and Evolution of KSHV 245 14 Rotaviruses Ulrich Desselberger and Jim Gray 337 Introduction 337 Rotavirus Structure, Genome and Gene–Protein Assignment 337 Classification 337 Replication 338 Pathogenesis 342 Immune Responses and Correlates of Protection 343 Illness, Diagnosis and Treatment 343 Epidemiology 344 Vaccine Development 345 15 Viruses other than Rotaviruses Associated with Acute Diarrhoeal Disease 355 Jim Gray and Ulrich Desselberger Introduction 355 Enteric Adenoviruses 357 Noroviruses and Sapoviruses (Human Caliciviruses) 358 Astroviruses 363 Gastrointestinal Viruses Not Regularly Associated with Acute Diarrhoeal Disease 364 16 Influenza Maria Zambon and Chris W Potter 373 Contents Introduction 373 Viral Variation 380 Virus Classification 384 Pathogenesis 385 Clinical Features 388 Diagnosis of Infection 391 Treatment and Prevention 396 Other Clinical Manifestations 477 Diagnosis 477 Treatment 481 Prevention 482 Future Prospects 483 17 Parainfluenza Viruses 409 Stelios Psarras, Nikolaos G Papadopoulos and Sebastian L Johnston Introduction 409 Taxonomy 409 Structure and Physical Properties 410 Receptors, Virus Entry and Host Range 411 Replication 414 Viral Transmission, Incubation and Shedding 416 Pathogenesis 417 Antigenicity and Immunity 418 Epidemiology 420 Clinical Features 423 Diagnosis 425 Prevention 428 Treatment 429 18 Respiratory Syncytial Virus Caroline Breese Hall vii Introduction 463 Description and Characteristics of the Virus 464 Pathogenesis 468 Immune Response 469 Epidemiology 470 Clinical Features 471 Respiratory Infections 471 Ocular Infections 474 Gastrointestinal Infections 475 Haemorrhagic Cystitis 475 Adenoviruses Infections in Immunocompromized Patients 475 Introduction 489 Taxonomy 489 Physical Properties 492 Incubation and Transmission 492 Host Range 493 Pathogenesis 493 Immunity 495 Epidemiology 496 Clinical Features 497 Diagnosis 498 Prevention and Treatment 500 21 Coronaviruses and Toroviruses J.S Malik Peiris and L.L.M Poon 441 Introduction 441 The Virus 441 Epidemiology 442 Pathogenesis 444 Immunity 445 Clinical Features 446 Diagnosis 450 Management 452 Prevention 453 19 Adenoviruses Marcela Echavarr´ıa 20 Rhinoviruses 489 Nikolaos G Papadopoulos, Maria Xatzipsalti and Sebastian L Johnston 511 Introduction 511 The Viruses 511 Initiation of Infection and Pathogenesis 517 Epidemiology 519 Clinical Features 520 Diagnosis 523 RT-PCR 524 Prophylaxis: Active and Passive Immunization 525 Therapy 526 Acknowledgements 526 22 Measles Virus 533 Sibylle Schneider-Schaulies and Volker ter Meulen 463 Introduction 533 The Virus 533 Virus Morphology 535 Genome Structure 535 MV Protein Functions 536 The Replication Cycle 538 Biological Properties of the Measles Virus 540 Epidemiology and Relatedness of Different Virus Isolates 541 Clinical Manifestations 542 The Pathogenesis of Measles and its Complications 545 Diagnosis 551 Management 552 Prevention 552 viii Contents 23 Rubella 561 Jennifer M Best, Joseph P Icenogle and David W.G Brown Historical Introduction 561 The Virus 562 Postnatally Acquired Infection 565 Congenitally Acquired Infection 569 Laboratory Techniques and Diagnosis 576 Prevention—Rubella Vaccination 580 24 Mumps Pauli Leinikki 593 Introduction 593 The Virus 593 Pathogenesis 595 Clinical Picture 595 Laboratory Diagnosis 597 Epidemiology and Control 598 25 Enteroviruses Philip D Minor and Peter Muir 601 Introduction 601 The Viruses 601 Pathobiological and Clinical Aspects of Human Enteroviruses 608 Laboratory Diagnosis of Enterovirus Infections 615 Prevention and Treatment of Enterovirus Infections 617 Future Prospects 620 26 Poxviruses Peter B Jahrling 625 Introduction 625 Virus Characteristics 625 Clinical Aspects of Orthopoxvirus Infections 627 Diagnosis 632 Medical Management 634 Other Poxviruses Infecting Humans 635 Diagnosis 637 27 Alphaviruses Graham Lloyd 643 Introduction 643 The Virus 643 Spectrum of Diseases Caused by Alphaviruses 647 Diagnosis of Alphavirus Infections 647 Management and Prevention 647 Alphaviruses Associated with Fevers and Polyarthritis 648 Alphaviruses Associated with Encephalitis 656 Other Alphaviruses 661 28 Flaviviruses Barry D Schoub and Marietjie Venter 669 Introduction 669 Properties of the Virus 670 Yellow Fever 672 Other Members of the ‘Unassigned’ Subgroup of Flaviviruses 678 Dengue 679 Zika 684 Japanese Encephalitis 684 St Louis Encephalitis 687 West Nile Virus 688 Murray Valley Encephalitis 690 Tick-borne Encephalitis 691 Omsk Haemorrhagic Fever 694 Kyasanur Forest Disease 694 Powassan Virus 695 29 Bunyaviridae Robert Swanepoel and Felicity J Burt Introduction 699 The Virus 700 Laboratory Diagnosis 703 Genus Orthobunyavirus 706 Genus Phlebovirus 711 Genus Nairovirus 717 Genus Hantavirus 721 Bunyaviruses Unassigned to Genus 699 726 30 Arenaviruses Colin R Howard 733 Introduction 733 Ultrastructure of Arenaviruses and Infected Cells 735 Chemical Composition 737 Replication 739 Diagnosis of Human Arenavirus Infections 740 Antigenic Relationships 741 Clinical and Pathological Aspects 741 Persistent Infection 743 Pathology of Arenavirus Infections: General Features 744 Other Arenavirus Infections 750 Summary 751 31 Filoviruses Susan P Fisher-Hoch Introduction 755 Epidemiology 756 Ecology 761 Transmission and Risk Factors Clinical Spectrum 763 763 755 Contents Laboratory Diagnosis 764 Patient Management 765 Past Infection and Persistence 766 Virology 766 Animal Models 767 Serological Studies 768 Pathogenesis and Immunology 768 Control 769 Perspective 770 32 Rabies and Other Lyssavirus Infections Mary J Warrell Polyomavirus-specific Immune Response 845 Treatment of Polyomavirus-associated Diseases 847 Acknowledgements 848 35 Human Parvoviruses Kevin E Brown 777 Introduction 777 History 777 Classification 778 Virus Structure 778 Replication 780 Inactivation of Virus and Stability of Vaccine Antigen 781 Epizootiology and Epidemiology 781 Incidence of Human Rabies 783 Pathogenesis 783 Immunology 785 Routes of Infection 786 Clinical Features of Rabies in Animals 787 Clinical Features in Humans 787 Diagnosis 794 Management of Human Rabies 796 Pathology 796 Human Rabies Prophylaxis 797 Control of Animal Rabies 800 33 Papillomaviruses Dennis McCance 853 Introduction 853 Human Parvovirus B19 (B19V) 854 Pathogenesis 856 Epidemiology 858 Clinical Features 859 Laboratory Diagnosis 863 Treatment and Prevention 865 36 Human Retroviruses Robin A Weiss 869 Introduction 869 Retrovirus Replication and Genomes 869 Taxonomy 870 Human and Zoonotic Retrovirus Infections 870 Retroviral Vectors 872 37 The Human T-lymphotropic Viruses Graham P Taylor 807 Introduction 807 Classification 807 Physical and Chemical Properties 807 Serology 811 Viral Replication 811 Natural History of HPV Infections 812 Pathogenesis 813 Diagnosis 817 Treatment 818 Vaccination 819 34 The Human Polyomaviruses Kristina Dăorries ix 875 Introduction 875 History 875 The Virus 876 Diagnosis 879 Viral Variation 880 Epidemiology 881 Transmission 883 HTLV-associated Disease 884 Pathogenesis 886 Treatment 889 Prevention of Disease 891 HIV and HTLV Co-infection 891 38 Human Immunodeficiency Viruses 897 Deenan Pillay, Anna Maria Geretti and Robin A Weiss 823 Classification and Detection 823 Virion Structure and Composition 823 Virus Life Cycle 823 State of Human Polyomavirus Infection 833 Diagnostic Evaluation of Polyomavirus-associated Disease 843 Introduction and Classification 897 Epidemiology 899 Replication 900 Host Genetic Determinants for HIV/AIDS 903 Viral Dynamics and Pathogenesis 903 Immune Responses 905 The Laboratory Diagnosis of HIV Infection 906 The Natural History of HIV Infection and Its Clinical Manifestations 909 x Contents Antiretroviral Therapy—A Historical Perspective 916 Monitoring of Antiretroviral Therapy and Resistance 917 Antiretroviral Drug Classes 921 Transmission of Drug Resistance 929 Prevention 929 Vaccines 932 39 Human Prion Diseases John Collinge Introduction to Prions and Historical Perspective 939 Structural Biology of Prions 940 Normal Cellular Function of PrP 943 Prion Strains 943 Neuronal Cell Death in Prion Disease 945 The ‘Species Barrier’ 945 Pathogenesis 946 Animal Prion Diseases 947 Aetiology and Epidemiology of Human Prion Disease 948 Clinical Features and Diagnosis 949 Molecular Diagnosis of Prion Disease 959 Pre-symptomatic and Antenatal Testing 960 Prevention and Public Health Management 960 Prognosis and Treatment 961 Concluding Remarks 962 Useful Websites 962 939 Index 969 1000 monkeypox (contd.) rodent reservoir 72 smallpox relationship 630 treatment 635 monkeypox virus 625, 630 host, distribution 626 phylogeny 626 transmission 630 monkeys filovirus infections 755–756, 756–761, 763, 767–768 see also primates monocytes EBV infection 204 rhinovirus infection 495–496 Mononegavirales 373, 409, 441, 535, 766 Monongahela virus 704 mononuclear cells, atypical, EBV infection 208, 208, 210 Monospot test 210–211 Mopeia virus 734, 736, 739 antigenic relationships 741 Morbillivirus 410, 410, 535 viruses included 535 mortality, infectious diseases, USA 69, 70 mosquito-borne viruses bunyaviruses 701 control strategies 677, 678, 684, 686–687 flaviviruses 672, 673 dengue 680–681 yellow fever 674, 675 Rift Valley fever virus 712–713 see also specific mosquito genera motavizumab, RSV infection prevention 454 mouse L cells, arenavirus culture 739 MPL (3-O -desacyl-4’-monophosphoryl lipid A) 84–85 Mucambo virus 659, 660 mucociliary clearance (nasal), rhinovirus infections 493 mucosal disease virus group 670 mucosal oedema, rhinovirus infection 493, 495 mucus secretion, rhinovirus infection pathogenesis 493, 495 Muju virus 704, 722 Muleshoe virus 704 Multicentre AIDS Cohort Study (MACS) 17 multicentric Castleman’s disease (MCD) 245 clinical features 253–254 KSHV replication 257 plasma-cell and hyaline vascular variants 253 multidrug resistance gene (MDR1) 889–890 multinucleated giant cells HTLV-1 infection 876 measles virus infection 540, 543, 544, 549 VZV infections 137, 138, 140, 141, 144, 148, 149 multiple analyser systems 22 multiple sclerosis (MS) coronavirus role 522 HBV vaccine and 90 HHV-6 association 231, 234 pathogenesis 522 mumps 593–600 antibodies 594, 595 Subject Index assays 597 IgM 597 arthralgia/joint involvement 597 children 598 clinical features 595–597 community outbreaks 46 complications 596–597 endocardial fibroelastosis 597 epidemiology 598–599 hearing defect 597 history 593 hospital outbreaks 46 immunity 598 incubation period 52, 595 interferon role 595 laboratory diagnosis 597–598 antibody assays 597 virus detection 597–598 meningitis and encephalitis 595, 596–597 military personnel 593, 597 myocarditis 597 nosocomial infection 45–46 oophoritis 597, 598 orchitis 597, 598 pancreatitis 597 parotitis 595–596, 596 pathogenesis 595, 595 pathology 595 pregnancy 597 prevalence reduction by vaccination 83 reinfections 598 required vaccination coverage 82 seasonal variations 598 secondary viraemia 595 transmission route 46 vaccination 598–599 infection incidence reduction 46 meningitis risk 598–599 problems eliminated by 599 status affecting clinical features 596 virus strains 598–599 mumps virus 593–594 antigenic structure 594 classification 593 excretion/shedding 595, 596 F protein (F0, F1, F2) 594 genetic variation between strains 594 genome (negative-sense RNA) 593 genomic organization 594 growth in cell culture 595, 597 HN glycoproteins 593–594 isolation/detection 597–598 Jeryl Lynn strain 598 Leningrad–Zagreb strain 598 M protein 594 NP protein 593, 594 Paramyxovirus member cross-reaction 594 physical characteristics 50 polymerase complex 593 proteins 593, 594 receptor 594 replicative cycle 594 Rubini strain 599 serotype 598 SH protein 594 structure and physical properties 593, 594 transmission 52, 595 Urabe strain 598 vaccine strains 598–599 V antigen 594 murine hepatitis coronavirus (MHV) 512, 515, 517, 522 receptors 517, 518 murine leukaemia virus (MuLV) 872 murine noroviruses 359 murine PIV1 (MPIV1) 410 Murray Valley encephalitis 690–691 Murray Valley encephalitis virus 673, 690–691 Murutucu virus 702, 710 muscle fasciculation, rabies 790 mutation, of viruses 70–71 myalgic encephalomyelitis see chronic fatigue syndrome Mycobacterium avium-intracellulare (MAI) complex 912 Mycobacterium tuberculosis, in HIV infection 912 mycosis fungoides, HTLV-1 and 886 myelin breakdown, acute measles post-infectious encephalitis (AMPE) 548 inflammatory mediator cross-reaction 522 myelin basic protein (MBP) 548 myelitis, herpes zoster complication 147 myelopathy HTLV-1 associated see HTLV-associated myelopathy/tropical spastic paraparesis (HAM-TSP) HTLV-2 886 myelosuppression, CMV causing 175 myocarditis adenovirus infections 477 coxsackievirus group B (CVB) 609, 610–611 enterovirus infections 610–611, 612 mumps 597 neonatal enteroviral 611 myoclonic jerks, SSPE 544, 545 myoedema, rabies 790 myoglobinuria, influenza 390 myopathy chronic inflammatory, enteroviruses causing 612 idiopathic inflammatory, TTV infection and 330 myositis, influenza 390 myristic acid, enteroviruses 603 N Nairobi sheep disease virus 703, 721 Nairovirus 699, 717–721 biochemical properties 700 members and vectors 703 Nanoviridae 325 nasopharyngeal carcinoma (NPC), EBV and 199, 206, 213–215 clinical features 214 diagnosis 214, 215 seroepidemiology and pathogenesis 213–214 treatment and prevention 214–215 Subject Index WHO classification 214 national immunization days (NIDs), polio 618 natural history of viral infections 17 natural killer (NK) cells arenavirus infections 742 CMV protein interference 171–172, 172 evasion, KSHV infected cells 261 HBV clearance 292 Ndumu virus (NDUV) 644, 646 necrotizing enterocolitis, coronaviruses 522 needlestick injuries 32 HBV infection after 33, 34 HIV infection after 33, 33 negative predictive value 16 Negishi virus 673 Negri bodies 778, 779, 784, 796 nelfinavir, HIV infection 926, 927 neonatal infections CMV infection see cytomegalovirus (CMV) infection, perinatal CMV screening 180 coxsackievirus group B (CVB) 612 echoviruses 612 enterovirus infections 612 hepatitis B 293 HSV 124–127 RSV 448 rubella 570 varicella (chickenpox) 145–146 nephropathia epidemica 722 Nepuyo virus 702, 710 nerve cells, latent HSV infections 99–100 neural cell adhesion molecule (NCAM), rabies virus 783–784 neuralgia, post-herpetic, herpes zoster 133, 139, 147 neuraminidase HPIV see human parainfluenza virus(es) (HPIVs) influenza virus see influenza virus neuraminidase inhibitors (drugs) influenza 396, 398–399 structure 397 virus resistance 399 neurological complications/disease EBV infection 209 HHV-6/HHV-7 infections 232, 234, 240–241 HSV-2 infection 123 neuromuscular junctions, rabies virus infection 783 neuromyasthenia see chronic fatigue syndrome neuronal dysfunction, rabies 784 neuronal specific enolase (NSE), sporadic CJD 950 neurotrophin receptor (p75 ), rabies virus receptor 784 neutralization tests dengue 680, 683 enteroviruses 616 neutrophilia, HPIV infection 418 neutrophils 83 nevirapine HIV infection 925–926 post-exposure prophylaxis in HCWs 35 Newcastle disease virus (NDV) 410, 413 new variant Creutzfeldt–Jakob disease (nvCJD) 72, 954 see also variant Creutzfeldt–Jakob disease (vCJD) New York virus 704 NFAT1 (nuclear factor of activated T cells) HTLV-1 886, 887 JC virus binding 828 NF-κB activation, KSHV infection 259 HTLV-1 infection pathogenesis 886, 887 JC virus binding 828 rhinovirus infections 494 Ngari virus 702, 706–707 nicotinic acetylcholine receptors, rabies virus 783 Nidovirales 511 Nipah virus 75–76, 410, 424 non-Hodgkin’s lymphomas (NHL) in AIDS, EBV and 217 EBV association 206 HHV-6 association 231 in HIV infection 915–916 JC virus association 846 non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTIs) 921, 924–925 adverse effects 925 mechanism of action 925 metabolism/interactions 925–926 resistance 925, 925, 929 K103N and Y181C 925 second-generation 925 normal human immunoglobulin (NHIG) adenovirus infections 482 hepatitis A prevention 279 parvovirus B19V infection 865 noroviruses (NoVs) 355, 358–363 antibodies 361–362, 362 classification 359 diagnosis 55 diversity, genogroups and evolution 362 epidemiology 356, 361–362 by age 357 gastroenteritis due to clinical features/course 358, 361 pathogenesis 360 prevention 363 genome (positive sense ssRNA) 359, 360 GII-2 (Snow Mountain) strain 361 host genetic resistance 362 immune response 361 incubation period 54 laboratory diagnosis 360–361 nosocomial infections 54–55 management 55 outbreaks in hospitals 54 persistence in environment 49, 55 physical characteristics 50 proteins, structure/function 361 receptors 362 replication and cell culture 359–360 structure 356, 359 transfection of RNA 359 1001 transmission routes 55, 362 Norwalk virus (NV) 358 genome 359, 360 nosocomial infections/transmission 43–68 adenovirus 61 blood-borne infections see blood-borne viruses (BBVs) blood-contaminated instruments 32 CCHF virus 718 CJD 953–954 CMV 47–48 coronavirus (CoV) 521 Ebola haemorrhagic fever 760, 763 factors increasing 43 hepatitis C 32 HHV-6 230 HIV infection, prevention 931–932 HPIV 424 HSV 53–54 influenza 58–60 Lassa fever 748, 749, 750 Marburg haemorrhagic fever 756 measles 44–45 mumps 45–46 noroviruses 54–55 organ/tissue transplantation 32 parainfluenza virus 60–61 parvovirus B19 56–58 prevention 43–44 renal haemodialysis 32 respiratory viruses 58–63 risk minimisation strategies 30 rotavirus 56, 345 RSV 62–63, 443–444, 455, 455 rubella 46–47 SARS-CoV 61–62 VZV see varicella zoster virus (VZV) ward closures 43, 54, 55, 57 NoV see noroviruses (NoVs) 5’ nuclease oligoprobes, PCR 10, 11 nucleic acid detection blood/blood products 31 HSV 106–107 influenza virus 394 nucleic acid sequence-based amplification 13–14 nucleic acid sequencing, automated 20 nucleoside analogues hepatitis B 300–301, 306 HSV infections 108 JC virus infection 847 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) 921, 922–924 adverse events 922–923 HAM treatment 890 mechanism of action 922–923 resistance 921, 923–924, 924 M184V mutation see lamivudine Q151M mutation 924 nutlin 3a 263 Nyando virus 702, 708 O obesity, adenovirus infections associated 477 Ockelbo disease 648, 649 1002 Octomer binding protein (OCT-1) 98 ocular defects, congenital rubella syndrome (CRS) 572, 573–574, 574, 575 ocular infections see eye infections oligodendrocytes, in PML 840 Oliveros virus 734, 751 Omsk haemorrhagic fever 694 Omsk haemorrhagic fever virus (OHFV) 669, 673, 694 oncogenesis see cancer, oncogenesis mechanisms Oncovirinae 870 o’nyong-nyong virus 652–653 oophoritis, mumps 597, 598 ophthalmic herpes zoster 146, 147, 153 optical immunoassays (OIAs), RSV infection 451 oral hairy leukoplakia (OHL) EBV association 199, 218, 912 HIV infection 912 oral infections/lesions HIV infection 912 HSV see herpes simplex virus (HSV) infection oral rehydration solution (ORS) 344, 344, 356 Oran virus 704 orchitis mumps 597, 598 smallpox 629 orf 635–636 host, distribution 626 Oriboca virus 702, 710 ‘original antigenic sin’ 138, 382 Oropouche virus 702, 709–710 Orthobunyavirus 699, 706–711 members and transmission 702 Orthomyxoviridae 373 Orthomyxovirus, physical characteristics 50 Orthopoxvirus 625, 626 orthopoxviruses 625–635 antibodies and serology 633 antigens 626 A-type inclusions 627 B-type inclusions 632 cell culture 632 genome (dsDNA) 626–627 hosts, distribution and disease 626 immunofluorescence (IF) 633 lateral bodies 625–626, 627 mRNA and transcription 627 PCR 633, 634 phylogenetic relationships 626 replication 626–627, 630, 635 structure/morphology 625–626, 627 orthopoxvirus infections 627–632 clinical features 627–632 diagnosis 632–634 immunodiagnosis 633 laboratory diagnosis and specimens 632 management 634–635 nucleic acid diagnosis 633–634 passive immunization 635 phenotypic diagnosis 632–633 treatment (antivirals) 635 vaccination 634–635 Subject Index see also cowpox; monkeypox; smallpox oseltamivir HPIV infection 429–430 influenza 60, 398 H5N1 399 structure 397 Ossa virus 702, 710 osteitis deformans, measles virus associated 545 osteomyelitis, in smallpox 629 otitis media acute, rhinovirus infection complication 497–498 with effusion (OME) coronavirus infection 520 rhinovirus infection 497 influenza 390 RSV infection 448 otosclerosis, measles virus associated 545 outcome of viral infections, host factors affecting ‘owl’s eye’ intranuclear inclusions 161, 176–177 oxygen, supplemental RSV infection 452 SARS prevention recommendations 62 P p53 adenovirus as vector 482 BK virus oncogenicity 843 inactivation, HTLV-1 infection 886 inhibition, KSHV infection 257 JC virus TAg interference 842 KSHV infection treatment 263 Paget’s disease, measles virus associated 545 pain, zoster-associated see zoster-associated pain (ZAP) palivizumab, RSV infection 63 prevention 454–455 pancreatitis acute, coxsackievirus group B 614 mumps 597 P antigens, receptor for B19V 857–858 panuveitis, HSV 118 Papillomavirus 807 papillomaviruses 807–822 cell/tissue culture 811–812 chemical properties 807–810 classification 807, 808 clinical features of infection 807 diagnosis 817–818 early (E) proteins 808–809 genome (dsDNA) 807–810, 809, 810–811 late (L) proteins 808–809, 811 mRNA transcription 808–809 natural history of infections 812–813 persistence in environment 49 physical characteristics 50, 807–810 proteins 808, 810, 810–911 replication 811–812 serology 811 structure 807, 808 supergroups (A-E) 807, 808 transmission 813 vaccination 819–820 virus-like particles (VLPs) 811 see also human papillomavirus (HPV) Papovaviridae 807, 823 papovaviruses persistence in environment 49 see also human polyomaviruses; papillomaviruses pappataci fever 711 parainfluenza viruses 409–439 animal infections 417 animal viruses 409–410 antigenicity and immunity 418–420 cell culture and tissue tropism 416 chemokines and cytokines 417 detection 425–427 infections incubation period 52, 416 inflammation due to 417, 418 mortality 60 nosocomial 60–61 pathogenesis 417–418 prevention 428–429 seasonal outbreaks 60 see also human parainfluenza virus(es) (HPIVs) life cycle 411, 412 physical characteristics 50 receptors, attachment and host range 411–414 replication 414–416 shedding 417 structure and properties 410–411, 412 taxonomy 409–410, 410 transmission 52, 60–61, 416–417 paralysis, acute flaccid 609 West Nile fever 690 Paramyxoviridae 409, 410, 441, 593 emerging viruses 76 Paramyxovirinae 409, 410 Paramyxovirus, physical characteristics 50 paramyxoviruses new/emerging 75–76 replication 415 Paran´a virus 734 parapoxvirus, host, distribution 626 parapoxvirus infections 635–636 clinical features 635–636 diagnosis, and control 636 pathogenesis 635 parasympathetic nervous system, rhinovirus infection pathogenesis 495 paravaccinia 635 parechoviruses see human parechoviruses (HPeVs) Parkinson’s disease 390 parotid gland, mumps 595–596 parotitis, mumps 595–596, 596 particle agglutination assays 4–5 Parv4 virus 853, 854 Parvoviridae 853 Parvovirinae 853 groups/classification 853, 854 Parvovirus, physical characteristics 50 parvovirus B19 see human parvovirus B19 (B19V) Subject Index parvoviruses 853–867 acute diarrhoeal disease 365 animal 853, 862, 865 autonomous 853, 854 emerging/new 74 genomic organization 854–855, 855 human see human parvovirus B19 (B19V) structure 356 passive T-cell immunotherapy, CMV 185 Pasteur, Louis 81, 777 pathogen-associated molecular patterns (PAMPs) 83, 84 pattern recognition receptors (PRRs) 83, 84, 547 Pc (proportion of persons immune) 82 pegylated interferon see interferon penciclovir herpes zoster 152 HSV infection 111 structure 109 penile cancer, HPV and 815 ‘pentaplex’ assay 12 pentosan polyphosphate, CJD 961 ‘peptide assay’, HIV 908 peramivir influenza 398 structure 397 Pergamino virus 704 pericarditis, enteroviral 616 perinatal infections, tests for 21 persistence of viruses in environment 49 pertussis, prevalence reduction by vaccination 83 pertussis syndrome, adenovirus serotypes 472, 473 Peste-des-ruminants virus (PPRV) 535 Pestivirus 669, 670 pharyngeal obstruction, EBV infection 209 pharyngitis EBV infection 208 Lassa fever 748 pharyngoconjunctival fever (PCF), acute 471, 472 adenovirus serotypes 472, 474 phenotypic assays antiretroviral drug resistance 918–919, 919, 920 antiviral resistance detection 19, 19 phlebotomus fever 711 Phlebovirus 699, 711–717 members and vectors 703 phobia, rabies 788, 790 phobic spasms, rabies 788, 789 Phocine distemper virus ( PDV) 535 phylodynamics, HIV 900 Pichinde virus 734, 737 antigenic relationships 741 genome 740 picobirnaviruses 365–366 gastrointestinal disease 365–366 Picornaviridae 277, 364, 489, 601 genera 601 Picornavirus, physical characteristics 50 picornaviruses genome 277, 277 rhinoviruses see rhinoviruses structure 356 pigs (swine) hepatitis E transmission 282 influenza virus 384 Japanese encephalitis transmission 685 Nipah virus 75–76 TTV infections 328–329, 329 Pirital virus 734, 751 plaque reduction assay 19 plaque reduction neutralization test (PRNT) arenaviruses 741 dengue virus 680, 683 plasmablasts, KSHV-infected 254 plasma leakage dengue haemorrhagic fever 682 hantavirus infections 725 platelet counts, congenital rubella syndrome 573 pleconaril poliomyelitis therapy 620 rhinovirus infections 501 PMEO-DAPym, hepatitis B treatment 305 Pneumocystic carinii pneumonia (PCP) 897, 912 pneumomediastinum, rabies 789 pneumonia adenoviruses 471, 474 atypical, serological tests 21, 22 giant cell (Hecht), in measles 544 HPIV infection 421, 423 HSV nosocomial 54 influenza 389–390 measles 473, 543, 544, 552 rhinovirus infection 498 RSV 446–447 SARS 521–522, 526 secondary bacterial in influenza 389–390, 396 in RSV infection 448 varicella 144, 144 pneumonitis CMV 174, 175, 912 HPIV infection 417 varicella (chickenpox) 152, 154 pneumothorax, adenoviruses 471 Pneumovirinae 410, 410, 441 Pneumovirus 410, 410, 441 podophyllin, HPV treatment 818 Pogosta disease 648, 649 point mutation assays (PMAs) 20 point-of-care testing (PoCT) HIV infection 907–908 influenza virus 394 polio-like illnesses 609, 613 poliomyelitis 601, 620 abortive 609 clinical features 609–610 CNS infection 609 diagnosis 615, 616–617 global eradication programme 618 in India 618 mortality 609 Nigerian outbreaks 618, 619 outbreaks 617, 619 paralytic 609–610 pathogenesis 609 1003 prevalence reduction by vaccination 83 prevention 617–620 re-emergence after eradication 620 re-introduction after vaccine use 618 supplementary immunization activities (SIAs) 618 treatment 620 vaccine-associated paralytic (VAPP) 617, 619 vaccines/vaccination 617–620 efficacy concerns 618–619 eradication programme problems 618–619 global eradication programme and 618 inactivated (IPV) 617, 619 IPV replacement of OPV 619 manufacture 619–620 oral 617, 618, 620 required coverage 82 resistance to use 618 Sabin 617 Salk 617 schedule 618 stopping of vaccination 619 type I and vaccines 619 poliovirus (PV) antigenic structure 603–604 capsid structure 603, 604 cell culture 608, 615, 617 characteristics 608 circulating vaccine-derived (cVDPV) 619 classification 607, 607 containment after eradication 619–620 genome organization 605, 606 genotypes, eradication and 618 host range 609 isolation/detection 615 as laboratory virus 619 non-polio enteroviruses differentiation 616–617 PCR 616–617 persistence in environment 49 persistence in tissues (CNS) 610 proteins and protein structure 602, 603, 604 PV1 603 PV2 603, 604, 618 PV3 604, 617 receptor (PVR) 83, 604–605 recombinant 619 recombination of vaccine strain with enterovirus 71 replication 605–606 shedding 617, 619 structure 602, 602 wild-type vs vaccine strains 617 see also enteroviruses; poliomyelitis polyarthritis, alphaviruses associated 648–656 polyethylene glycol (PEG) 300 polyethylene glycol (PEG)-IFN see under interferon polymerase chain reaction (PCR) 1, 3, 8–13 automation, HSV detection 106–107 clinical specimen preparation commercial assays 9–10, 10 consensus, emerging infections 73 contamination 12–13 controls (positive and negative) 12–13, 13 1004 polymerase chain reaction (PCR) (contd.) conventional product, detection dUTP use 13 false-negative results 9, 12 inhibitors in situ, HSV 107 multiplex 9, 10, 12 HPIV 427 HSV 106 micro-bead suspension array 15 physical organization of laboratory 13 primers 9, 11 principle 8, quantification 9–10, 10, 12, 17 quantitative competitive (qcPCR) random primer 73 real-time 10–12, 11, 12 adenoviruses 479–480 advantages/disadvantages 12 HSV 106 influenza virus 394 KSHV 262 noroviruses 55 orthopoxviruses 633, 634 respiratory virus infections 58 reverse-transcription see reverse transcription PCR (RT-PCR) sensitivity 12 specificity 10 viral antigen detection polymerase slippage, HPIV 415–416 Polyomaviridae 823 Polyomavirus new/emerging viruses 74 physical characteristics 50 polyomavirus-associated nephropathy (PVAN) 838 diagnosis 844–845 treatment 848 polyomaviruses see human polyomaviruses Pongola virus 702, 707–708 population increases, emerging infections and 71 porcine endogenous virus (PERV) 872 porcine enteric calicivirus (PEC) 359 porcine enteric transmissible gastroenteritis virus 518 Porpoise morbillivirus (PMV) 535 positive predictive value 16 posterior root ganglia, latent VZV infections 141, 146 post-exposure risk assessment, blood-borne viruses, in HCWs 34, 34–35 post-herpetic neuralgia (PHN), VZV 133, 139, 147 post-poliomyelitis syndrome 610 post-transplant lymphoproliferative disease (PTLD) 216–217 post-vaccinal encephalomyelitis (PVE), rabies vs 791 post-vaccinial encephalitis 634 postviral fatigue syndrome see chronic fatigue syndrome Powassan virus 673, 695 Poxviridae 625 Subject Index poxviruses 625–642 antigens 638 A-type inclusions 627 B-type inclusions 632 cell-associated virion (CEV) 627 classification 625 diagnosis 632–634, 637–638 extracellular enveloped virus (EEV) 626 intracellular enveloped virion (IEV) 627 intracellular mature virus (IMV) 626 lateral bodies 625–626, 627 molluscum contagiosum due to 636–637 mRNA and transcription 627 orthopoxvirus infections 627–635 parapoxvirus infections 635–636 pathogenic for humans 626 phylogenetic relationships 626 physical characteristic/stability 638 replication 626–627, 630 structure/morphology 625–626, 627 tanapox 637 see also orthopoxviruses; smallpox pradefovir mesylate, hepatitis B 305 pRb (retinoblastoma protein) inactivation in KSHV infection 257, 258 JC virus TAg interference 842 repression in HPV infections 810 prediction of viral infections, by molecular techniques 16–17 pre-emptive therapy adenovirus infections 482 CMV infection 186, 189, 189–190 pregabalin, herpes zoster pain 153 pregnancy aciclovir 152 BK polyomavirus 845 CMV infection see cytomegalovirus (CMV) infection herpes zoster 147 HPV infection and genital warts 817 HSV infections 126 infectious mononucleosis 209 influenza 390–391 JC virus (JCV) 837 Lassa fever 749 Marburg or Ebola haemorrhagic fever 764, 765 measles vaccine contraindicated 554 mumps 597 parvovirus B19 infection 58, 862 rashes in 21 rubella (infection) see rubella rubella vaccination 582, 582–583 varicella (chickenpox) 141, 145–146, 155 varicella zoster immune globulin (VZIG) 155 VZV reactivation 53 yellow fever vaccine 678 prenatal diagnosis, rubella 578, 580 prenylation inhibitors, hepatitis D 309 pre-programmed cellular suicide 84 primate foamy virus (PFV) 871 primates Chikungunya virus (CHIKV) 650–651 filovirus infections 755, 756–761, 763, 767–768 hepatitis E virus 280–281 HIV origin 897–898 KSHV origin and related viruses 245–246 monkeypox 72 new/emerging viruses 72, 76 rhinovirus infections 493 Rift Valley fever virus 716 rubella virus infection 565 TTV infections 327 as virus vectors 76 primate T-cell lymphotropic virus (PTLV) 876, 883 prion diseases 939–968 acquired 949, 950, 952–957, 960 see also kuru; variant Creutzfeldt–Jakob disease (vCJD) aetiology and epidemiology 948–949 animal 939, 947 clinical features and diagnosis 949–959, 950 human 939, 948–949 iatrogenic see Creutzfeldt–Jakob disease (CJD) incubation period 948–949 inherited 949, 950, 957–959 initiation/entry route 947 lesion profiles 943 lymphoreticular tissue 946, 947 molecular diagnosis 959–960 neuronal cell death 945 pathogenesis 946–947 pre-symptomatic/antenatal testing 960 prevention and public health 960–961 PRION-1 trial 961 prognosis and treatment 961 sporadic 949–952, 950, 959 see also Creutzfeldt–Jakob disease (CJD) prion protein (PrP) 940 β-sheet state 942 conserved genes 946 copper metabolism role 940, 944 folding 940, 941, 942, 942 gene see PRNP glycosylation 940, 941, 944 mice lacking (Prnp 0/0 ) 943, 945 monoclonal antibodies 961 neuronal signalling role 943 neurotoxicity mechanism 945 normal cellular function 943 octapeptide repeat insertion (OPRI) 957, 959 PrP OPRI 959 PrP27−30 940 PrP102L 957 PrPA117V 957 PrPC 940 apoptosis role 945 conversion to PrPSc 940, 941, 952 destabilization, diseases 941 expression interference 961 minor conformations 941 molecules binding, CJD treatment 961 N-/C-terminal regions 940 structure 940–941 PrPD178N 957–958 PrPE200K mutation 958–959 PrPL 945 Subject Index PrPSc 940 elevated in mice 945 experimental formation 941–942 in follicular dendritic cells 947 formation 941 glycoforms 944 human types 943–944 sporadic CJD 948, 952 structure 941 subcellular localization 942 tonsillar 960–961 transmission 944, 960–961 types 1–4 952, 957 vCJD 952, 955 recombinant, bacterial expression 942–943 self-propagation 941–942, 942, 946 single polypeptide/different phenotypes 944 species, differences 945–946 structures 940–943, 941 transgenic mice expressing hamster PrP 946 transgenic mice expressing human PrP 952, 957 transmission 944 prions definition 940 entry route 947 molecular strain typing 944, 944, 952 neuro-invasion 947 occupational risks 961 protein-only hypothesis 940, 942, 943, 944 Sc237 hamster 945, 946 species barrier 945–946, 949 crossing 946 species-strain barrier 946 strains 943–945 structural biology 940–943 transmissible mink encephalopathy 943 hyper (HY) and drowsy (DY) 943 transmission barrier 946 unified hypothesis 943 yeast 944 PRNP gene 948 129 MM 948, 949, 956 129 MV 956 analysis, in CJD 949, 950, 951, 957, 959 carriers of mutations 960 coding mutations 940, 952 codon 129 genotype 952, 960 kuru 952 sporadic CJD 952 codon 129 heterozygosity 948, 952 conserved 946 kuru 952–953 mutations absent in vCJD 948 mutations and polymorphisms 957–959, 958 sporadic CJD 948 see also prion protein (PrP) progressive multifocal leukoencephalopathy (PML) 823, 831, 840–841 astrocytes 841, 842, 843, 845 biopsy 843 cellular immune response 846–847 clinical features and risk factors 840 definition scheme 844 diagnosis 843, 844 duration/progression and outcome 841 HAART effect 840, 841, 847 in HIV infection 840, 841, 844, 914 IgM antibodies 846 immune response in 846 immunocompromised patients 835 JC virus spread to CNS 835 JCV viruria 837 pathogenesis/lesion development 840, 841 transcriptional control region (TCR) type 833 treatment 847 promoter-insertion hypothesis 307 Prospect Hill virus 704, 722 protease inhibitors (PIs) 921, 925–928 D30N and L90M mutants 920 first-generation 926 HIV infection 903, 917 mechanism of action 925 mutations/resistance 920 new drugs 926 resistance/mutations 926, 926, 927 protective antigens 85–86 protein phosphatase 2A (PP2A) 842 proteinuria, haemorrhagic fever with renal syndrome (HFRS) 724 PrP see prion protein (PrP) pseudocowpox 635 host, distribution 626 ptosis, herpes zoster 147 pulmonary oedema, smallpox 629 ‘pulvinar sign’, vCJD 955 Punta Toro virus 703, 711–712 pure red cell aplasia, parvovirus B19V infection 862–863 Puumala virus 704, 722, 724, 725 Q quadriparesis, rabies 790 qualitative detection of viruses 16 quality control, molecular amplification techniques 15, 16 quasispecies, viral 18, 523 quinacrine, CJD 961 R rabies 777–806 aerophobia 788 alternative names 777 animals 798 bats 782, 783, 787, 801 clinical features 787 control 800–801 diagnosis 795 dogs 777, 782, 783, 787, 796, 801 foxes 781, 782, 801 immune response 785 incubation period 787 raccoons 782, 801 recovery and chronic infection 787, 791–792 treatment 796 vampire bats 783, 787, 790, 801 antibodies 1005 detection methods 795 IgM and IgG 785, 795 neutralizing 785–786 autonomic stimulation 789 biochemical tests 791 bites 781, 783, 786, 787–788, 798 management after 800 brain biopsy 795, 797 brain infection process 784 cellular immune response 785 children 797 ‘classical’ 788 clinical diagnosis 791 clinical features 787–794 complications 789, 790 countries/areas free of 780, 781 diagnosis 794, 794–795 immunofluorescence 794, 795 intra vitam 794–795 post-mortem 795 differential diagnosis 790, 790–791 ‘early death’ phenomenon 785 encephalitis/encephalomyelitis clinical features 788 diagnosis 794 immune response 785 pathology 796–797 enzootic infection 781, 801 epidemiology/epizootiology 781–783 furious (agitated) 788–789, 789 differential diagnosis 790 global distribution 780, 781–783 haematological tests 791 history 777–778 hydrophobia 777, 788–789, 790 pathophysiology 789 immune response 785 assays 786 immunoglobulin (RIG) 798, 799, 800 immunology 785–786 immunosuppressive effect of 785 incidence 783 incubation period 785, 787–788 infection routes 786, 798 interferon-α effect 785 management 796 after bites 800 meningoencephalomyelitis 796 mortality 789, 796 Negri bodies 778, 779, 784, 796 neurological investigations 791 paralytic (dumb) 788, 789–790 differential diagnosis 790, 791 outbreak (Trinidad) 790 pathogenesis 780, 783–785 pathology 796–797 phobia 788, 790 pneumomediastinum 789 prodromal symptoms 788 prophylaxis 797–800 recovery 791–792 respiratory features 789 spasms 788, 789 sylvatic (wildlife), control 801 transmission 781, 786, 798 1006 rabies (contd.) aerosol 786 bites 798 human to human 786 routes 786 see also rabies, bites transplacental 786 vaccine-induced 786 vaccines 797–800 for animals 801 animal species/behaviour and 798 antigen stability 781 booster doses 797–798, 800 developing countries 800 duck embryo 791–792 efficacy against rabies-related viruses 799–800 eight-site intradermal regimen 800 exposure confirmation 798 ‘failures’ 799 four-site intradermal regimen 800 historical aspects 777–778 human diploid cell (HDCV) 778, 797, 800 immune response to 785–786 infection site affecting 798 Pasteur’s 777, 778 post-exposure 796, 797, 798–800 post-exposure, decision to use 798 post-exposure, efficacy 799 post-exposure in vaccinated patients 799 pre-exposure 796, 797–798 primary post-exposure 799 purified chick embryo cell (PCEC) 792, 797 purified Vero cell (PVRV) 792, 797 recombinant 801 recovery after 791–792 regimens 796, 797, 799 Semple brain tissue 777, 800 side effects 800 two-site intradermal regimen 800 viraemia 784 wound treatment 799 rabies-related viruses human infections 792–793 vaccine efficacy 799–800 see also European bat lyssaviruses (EBLV) rabies virus 779 antigens 784, 785 detection 794–795 assembly, maturation and release 781, 785 attachment and fusion 780, 783–784 brain infection 784 centrifugal spread from brain 784–785 classification 778 genome (negative-sense ssRNA) 778 G (glycoprotein) protein 778, 780 host gene expression downregulated 784 inactivation 781 infection routes 786, 798 intracellular transport 780 isolation/identification 794–795 L protein (RNA polymerase) 778, 780 M (matrix) protein 778, 780 N (nucleoprotein) protein 778, 785 Subject Index P (phosphoprotein) protein 778, 780, 784 replication 780–781 inhibition by interferon-α 785 sites 784–785 RNA polymerase 778, 780 RNP complex 778, 780–781 shedding 784 stability 781 structure 778, 779, 780 transmission see rabies, transmission transport to brain 784 vectors/reservoirs 781–783 raccoons, rabies 782, 801 raltegravir (RAL) 922, 929 Ramsay–Hunt syndrome 146 RANTES 417 rapamycin, KSHV infection 263 rapid immunofluorescent focus inhibition test (RIFFIT), rabies 786 rash(es) Barmah Forest virus (BFV) 655 Chikungunya virus infection 651 Crimean–Congo haemorrhagic fever 719 EBV infection 209 HHV-6 infections 232 human parvovirus B19 (B19V) 856, 860, 860 Lassa fever 748 measles 543, 544, 547 monkeypox 630 o’nyong-nyong virus 652 in pregnancy 21 Ross River virus infection 653 rubella 566 congenital rubella syndrome (CRS) 572, 573, 574 rubelliform, enteroviruses causing 613 serological testing 22 Sindbis virus infection 649 smallpox 143, 628 varicella (chickenpox) 143–144, 146 West Nile fever 690 reassortment of viruses 71, 86 receptor-destroying enzyme (RDE), HPIV infection 426 recombinant immunoblot assay (RIBA), HCV 273, 311 recombination of viruses 71 HIV 918 KSHV 246 Relenza see zanamivir renal dysfunction, mumps 597 renal haemodialysis blood-borne virus transmission 32 screening assays 20 renal transplant recipients adenovirus infections 476 BK virus infection 837 CMV disease prognosis 169 CMV infection prevention 183–184 Reoviridae 365 reoviruses, acute diarrhoeal disease 365 representational difference analysis (RDA), emerging viruses 73–74 reproductive rates of viruses (Ro) 82, 89 see also basic reproductive rate/number (Ro) respiratory rate, RSV infection 447 respiratory secretions, smallpox 628 respiratory syncytial virus (RSV) 441–461 adsorption 442 antigenic variation 442 classification 441 cp (cold passage)/ts (temperature sensitive) mutants 453, 454 cytopathic changes 450–451 detection see respiratory syncytial virus (RSV) infection, diagnosis discovery 441 gene variants (polymorphisms) 450 genome (negative-sense RNA) 441 glycoproteins (F and G) 441–442 antibodies to 442, 445, 446 monoclonal antibody to F 454 vaccine development 454 isolation 450–451 persistence in environment 49, 444, 455 physical characteristics 50 replication 442 shedding 62, 449 strains A and B 442 structure/morphology 441, 442 transmission 52, 62–63, 443–444 prevention 62 to/by HCWs 444 respiratory syncytial virus (RSV) infection acute complications 448 antibodies 446 detection 452 IgA 445 IgM and IgG 445, 452 maternal 445 neutralizing 442, 445 bronchiolitis 443, 444–445, 445, 446–447, 453 children 441, 443, 446–447, 449 clinical features 446–448 children at increased risk 449 older children/adults 450 primary infection 447–448 co-infections 448 cytopathology 446 diagnosis 63, 450–452 enzyme immunoassays 451 immunofluorescence 4, 451, 451 PCR 451 serologic 451–452 elderly 450 epidemiology 441, 442–444, 447 of HCWs 444 immunity to 445–446 cellular 446 humoral 445–446 innate 445, 446 Th1 and Th2 responses 446, 450 immunocompromised patients 449 incubation period 52, 444 infants 444, 446–447, 448, 449 immunization 454 influenza vs 450 management 63, 452–453 mortality 444 Subject Index neonates 448 nosocomial 62–63, 443–444 prevention 455, 455 otitis media 448 outbreak size 443 passive immunization 454 pathogenesis 444–445, 446 pathology 444–445, 445 pneumonia 446–447 prevention 453–455 infection control 455, 455 repeated 449, 450 seasonal 442, 444 sequelae 449–450 vaccines 446, 453–455 live-virus (cp or ts) 453–454 subunit 453, 454 respiratory tract infections adenoviruses 463, 471, 473–474 enteroviral 613 influenza see influenza parainfluenza viruses see human parainfluenza virus(es) (HPIVs) RSV infections see respiratory syncytial virus (RSV) infection respiratory viruses diagnosis 4, 58 nosocomial infections 58–63 seasonal epidemics 58 Respirovirus 409, 410 Restan virus 702, 710 restriction enzyme analysis (REA), adenoviruses 480 restriction fragment length polymorphism (RFLP), orthopoxviruses 633 retinal necrosis acute HSV 118, 126 VZV 147–148 progressive outer (PORN) 148 rapidly progressive herpetic 148 retinitis CMV 190, 912 varicella 147–148 retinoblastoma protein see pRb (retinoblastoma protein) retinopathy, congenital rubella syndrome (CRS) 570, 574 Retroviridae 870 classification 18 retroviruses 869–873 animal diseases 871 animals/species infected 869 env gene 870 ‘fossil’ infections 870, 872 gag gene 870 gag-pol precursor 870 genera 870, 871 genes 870 genome (ssRNA) 869–870, 870 genome integration 872 human endogenous (HERVs) 872 infections 870–872 long terminal repeats (LTRs) 870 low-level, DNA detection 871 murine 871 pol gene 870 replication 869–870, 870 reverse transcriptase 869 SU protein 870 taxonomy 870, 872 TM protein 870 as vectors for gene therapy 869, 872–873 zoonotic infections 869, 870–872 see also HIV; HTLV reverse genetics technology Ebola virus infections 766, 769 HPIV vaccine development 428 influenza vaccine development 399, 403 measles virus (recombinant) 535 RSV vaccine development 454 reverse transcriptase (RT) 869 discovery 871, 875 reverse transcription nested PCR (RT-nPCR), rubella 577, 578, 580 reverse transcription PCR (RT-PCR) alphaviruses 647 bunyaviruses 705 Chikungunya virus 652 coronaviruses 523, 524 dengue virus 683 EIA with (RT-PCR-EIA), HPIV 427 GBV-C 324, 325 hantaviruses 726 HCV infection 311 HPIV 427 Lassa virus 750 measles 551 noroviruses 55 rabies virus 795 RSV infection 451 reverse vaccinology 85 Reye’s syndrome HPIV causing 424 influenza 390, 396 varicella (chickenpox) and 145 RGD motif adenoviruses 467 KSHV glycoprotein 255 Rhabdoviridae 778 rhesus monkey papillomavirus type 814 Rhesus monkeys, ZEBOV (Ebola Zaire virus) 767 rhesus rotavirus (RRV) 343 rheumatoid arthritis, parvovirus B19V role 861 rhinoviruses 489–510 2A protease and 3C protease 492 antigenicity 490–491 canyon 490, 491 ‘canyon hypothesis’ 491 capsid 489–490 cell culture 498 cell lines, growth 495 cytopathic effects 493, 498–499 electron microscopy 490 enteroviruses relationship 489 genome (positive-sense ssRNA) 489, 491, 492 groups A and B 489, 496 history/discovery 489 1007 host range 493 HRV-2 490 HRV-14 603 HRV-87 489, 496 incubation period 493 internal ribosome entry site (IRES) 491 isolation 498–499 major and minor groups 489, 491 mRNA 491 persistence in environment 49, 492, 493 physical characteristics 50, 492 ‘pocket’ and ‘pocket factor’ 490 proteins 490, 490 receptors 491 replication 491–492, 493, 498 RNA polymerase 491 serotypes 496 shedding 492 structure 489–492, 490 taxonomy 489 transgenic murine model 493 translation 492 transmission 492–493, 496 as vectors 491 VP1-VP4 490, 501 rhinovirus infections antibodies IgG and IgA 495 neutralizing 499 asthma exacerbation 495, 497–498 atopy and 496 bronchitis, bronchiolitis and pneumonia 498 cellular immunity 495–496 children 496, 497 chronic 493 clinical features 497–498, 498 cold temperature exposure and 496 common colds 489, 496–497 complications 497–498 in COPD 492, 495, 498 cytokines/kinins and chemokines produced 494, 495 diagnosis 498–499 ELISA 499 haemagglutination inhibition (HI) 499 nucleic acid detection 499, 500 PCR 499, 500 serology 499 virus isolation 498–499 epidemiology 496–497 immunity/immune response 495–496 immunocompromised people 497 incubation period 497 morbidity 497 nasal secretions 493–494 pathogenesis 493–495, 494 prevention 500–502 primary site of infection 493 treatment 494, 500–502, 501 targets/strategies 492, 494, 495, 501 vaccine decavalent 500 obstacle to development 500 viraemia 493 1008 ribavirin 314 adenovirus infection 481, 482 Bolivian haemorrhagic fever 747–748 coronavirus infections and SARS 526 Crimean–Congo haemorrhagic fever 720 hepatitis C 314–315 HPIV infection 429 influenza 396, 398 Lassa fever 750 measles 552 mechanism of action 398, 452, 482 RSV infection 452 side effects 315, 398, 452, 482, 750 structure 397 riboprobes 14 Rickettsia conorii infection 720 Rift Valley fever virus, and infection 701, 703, 712–717 abortion 716 antibodies 717 clinical features 713, 714, 715–716 detection/identification 705 diagnosis and investigations 716–717 differential diagnosis 717 Egypt epidemics 713–714, 715 encephalitis 715–716 epidemiology 712–714 geographical distribution 712 haemorrhagic form 715 haemostatic derangement 715, 716 infection route 715 Kenya outbreaks 712, 714 mosquito vectors 712–713, 714 ocular disease 715 outbreaks and epidemics 712, 713 pathogenesis of infection 716 pathology 716, 717 Saudi Arabia and Yemen 714 South Africa/Zimbabwe 712 transmission cycles 713 treatment 716 vaccine 717 rimantadine influenza 60, 396–398 side effects 398 structure 397 Rinderpest virus (RPV) 535 ring sores 635 Rio Bravo virus 672, 673 Rio Mamore virus 704 Rio Segundo virus 704 ritonavir boosting, protease inhibitors 926 HIV infection 925, 926 rituximab 217 RNA editing, HPIV 415–416 RNA interference, filovirus infection therapy 766 RNA replicons, HPIV vaccine development 429 RNA viruses nucleic acid sequence-based amplification 13–14 rapid evolution 881 Ro (basic reproductive rate) see basic reproductive rate/number (Ro) Subject Index Rocio virus 669, 673, 678–679 rodents arenaviruses 733, 734, 742 LCMV 741–742, 745 control, Lassa fever control 750 cowpox transmission 631, 632 Ebola (Zaire) virus model 767 filovirus infections 767, 770 hantavirus transmission 73, 75, 721–722, 723 monkeypox reservoir 72 persistent virus infections (arenaviruses) 733, 742 roseola infantum (exanthem subitum) 232 Roseolovirus 224 roseoloviruses 223–244 see also human herpesvirus (HHV-6); human herpesvirus (HHV-7) Ross River virus (RRV), and infection 644, 644, 653–654 clinical disease 653–654 diagnosis and isolation 654 epidemiology and host range 653 pathogenesis 654 rubella differential diagnosis 567 vaccine 654 rotaviruses 337–353 antibodies 338, 342, 343 classification 337–338 double-layered particles (DLPs) 338, 339, 343 electron microscopy 338, 343, 356 G1-G4 types 345 G9 type 345 G and P types 338, 343–344 gene–protein assignments 340–341 genes 340–341 genome (dsRNA) 337, 339 genomic drift/shift 345 groups 337–338 groups A, B, and C 345 infections in children 343 clinical features and diagnosis 343–344, 355 epidemiology 337, 344–345 immune response and IgA 343 incubation period 52, 343 mortality 337, 343 nosocomial 56, 345 pathogenesis 342, 342–343 seasonal 56 treatment 344, 344 NSP4 (enterotoxin) 341, 342 nursery strains 343 persistence in environment 49, 56 proteins (VP1-VP3) 337, 339, 340–341 replication 338–339, 342 structure 337, 338, 339 transmission 52, 338 triple-layered particles (TLPs) 338 vaccines 56, 85, 345–346 intussusception cases 344, 345 lamb strain LLR (live attenuated) 346 live attenuated 345–346 monovalent 346 pentavalent 346 tetravalent 345 viroplasms 339 VP4 and VP7 338, 340, 341 Royal Free disease see chronic fatigue syndrome RT-PCR see reverse transcription PCR (RT-PCR) rubella 561–592 antibodies 561, 565, 568, 569 detection 576–577 loss in congenital rubella 579–580 post-vaccination 580 see also rubella, IgG; rubella, IgM antibody screening tests 576 clinical features 566 complications 566–567 congenital see congenital rubella syndrome (CRS) developing countries 566, 585–586, 586 diagnosis/laboratory techniques 576–580 congenitally acquired infection 578–580 enzyme immunoassay (EIA) 576 oral fluid/dried blood spots 577 prenatal 578, 580 serological 576–577, 579 serological in women exposed to RV 577, 578 serological in women with rubella-like illness 577–578 virus detection 577, 579 differential diagnosis 567, 567–568 epidemiology 565–566 fetal infection after reinfection of mother 569 see also congenital rubella syndrome (CRS) global distribution 564, 565–566 haemagglutination inhibition test 561, 579–580 HCW susceptibility 46 historical events 561, 562 IgA, after vaccination 580 IgG 569, 575, 577, 578 after vaccination 580 avidity 576–577 persistence in infant 579 IgG1, detection 579 IgM 568, 569, 570, 575, 577, 578 after vaccination 580 detection 576, 579 immune response 565, 568, 568–569, 570 immunity 569, 580–581 immunoglobulin (therapeutic) 578 immunosuppression associated 568 incubation period 52, 561 isolation of infants 576 neonatal 570 nosocomial 46–47 pandemics 566 pathogenesis 566 placental infection and 569 post-infectious encephalitis 567 postnatally acquired infection 565–569 pre-conceptual 570–571 Subject Index in pregnancy 46, 561 after first trimester 570 diagnosis/laboratory tests 577–578 first trimester 562, 569, 570 gestational age and 570, 571 management 578 see also congenital rubella syndrome (CRS) prenatal diagnosis 578, 580 rash 566 reinfection 569, 581 diagnosis 578 risk to fetus 570–571 vaccination 580–586 adverse reactions 581 contraindications 581–582 developing countries 585–586, 586 efficacy and reinfection 581 Europe 584–585 failures 581 immune response 580–581 joint disease after 567, 581 low/intermediate uptake rates 584, 586 monitoring efficacy, seroprevalence 583 other vaccines with 582 pregnancy 582, 582, 582–583 prevalence reduction by 83, 583, 584, 584, 585 programmes 583–586 required coverage 82 in UK 583–584, 584 in USA 583 WHO recommendations 585, 585–586 vaccines attenuated, development 580 RA27/3 strain 564, 565, 580 viraemia 568 virological features, clinical feature correlation 568, 568–569 rubella virus (RV) alphaviruses similarity 562 in amniotic fluid 580 antigenic characteristics 565 assembly and release 564–565 attachment and infection process 564 cell culture 561 clades and genotypes 564 classification 562 C protein 564 in CSF 570 cytopathic effect 565, 577 detection 577 E1 and E2 proteins 562, 564, 565 excretion 569–570, 581 in fetal blood 580 G+C content of RNA 562 genetic variation 562, 564 genome (positive-sense ssRNA) 562, 563 global distribution 564 growth in cell culture 565 interference assay 561 nonstructural proteins 562, 563 origin 71 p150 and p90 564 pathogenicity for animals 565 persistence 569–570 physical characteristics 51, 565 polyprotein (p200) 564 replication 564–565 stability 565 structural proteins 563 structure 562 subgenomic RNA 564 teratogenicity 565, 569 transcription 563 translation 563 transmission 52, 566 vaccine strain (RA27/3) 564, 565, 580 Rubivirus 562 Rubulavirus 410, 410, 593 ‘rule of six’ replication 415, 535 Russian spring summer encephalitis virus (RSSEV) 673, 693 S Saaremaa virus 704 Sabi´a virus 734, 751 sacral ganglia, herpes zoster 146 St Louis encephalitis see St Louis encephalitis (under St) saliva CMV in 167, 176 EBV in 206, 215 HHV-6 in 228, 229 HIV in, testing 907 KSHV in 250, 255 samples/specimens 20 antibody detection for PCR storage 20 viral antigen detection Sandfly fever Naples virus 703, 711 Sandfly fever Sicilian virus 703, 711 sandfly fever viruses 700, 703, 711 Sangassou virus 704 SAP (signalling lymphocytic activation molecule associated protein) 216 sapoviruses (SaVs) 355, 358–363 antibodies 361–362, 362 classification 359 diversity and evolution 362 epidemiology 361–362 by age 357 patterns 361–362 gastroenteritis clinical course/features 358, 361 pathogenesis 360 prevention 363 genome 359, 360 immune response 361 laboratory diagnosis 360–361 replication and cell culture 359–360 structure 356, 359 transmission routes 362 saquinavir, HIV infection 926, 927 SARS 43 asymptomatic 520 clinical features 365, 521–522 diagnosis 523 1009 elderly 522 emergence 519 epidemiology 519–520 first cases 71, 519 Hong Kong outbreak 61, 62, 71 incubation period 521 mortality 71, 522 nosocomial infections 61–62 prevention/precautions 62 WHO recommendations 62 passive immunization 525–526 pathogenesis and pathology 523 pneumonia 521–522, 526 re-emergence 525 ‘super-spreading incidents’ 519, 520 susceptibility, genetic polymorphisms 523 transmission of virus 519–520 treatment 526 vaccine 525 see also SARS-CoV SARS associated virus 7, persistence in environment 49 SARS-CoV 511 antigenic structure 517 classification 511 continued circulation, evidence lacking 520 detection/identification 74, 523 genome organization 516 host range and civet SARS-like virus relation 518–519 isolation and culture 524 origin 76–77 persistence in environment 62 receptor (ACE2) 518 re-emergence 61 spike protein, monoclonals to 525–526 transmission 61–62, 519–520 aerosol and droplets 520 see also SARS SARS-like coronavirus in bats 519 in civets 518, 519, 520, 525 SaV see sapoviruses (SaVs) scabies, Norwegian, HTLV-1 and 885 SCH 503034, hepatitis C treatment 316 schizophrenia 390 SCID-hu mouse, VZV infection model 136, 140 scrapie 939, 947 atypical 947 screening assays 20, 20 ‘scrum pox’ 116 seasonal infections common colds 496 HPIV infections 422, 422 influenza 388, 388–389, 391 rotaviruses 56 RSV 442, 444 seizures see convulsions ‘self’ antigens, tolerance 743–744 self-fluorescing amplicon concept, PCR 10, 12 Semliki Forest virus (SFV) 644, 644, 646, 661–662 Semliki Forest virus complex origins and distribution 650 viruses included 644 1010 Sendai virus (SeV) 410, 414–415 HPIV vaccine and 428 replication 414–415 sensitivity of tests 15, 16 sensory nerves, VZV latency 141, 146, 147 Seoul virus 704, 722, 723, 725 Sepik virus 673 sepsis, varicella associated 144 septic shock, smallpox 629 serology 3–8 advantages/disadvantages antibody detection 5–7 first-line tests 22 interpretation 7–8 nonvirological with virological 20 tests not indicated, conditions 21 viral antigen detection 3–5 serum neutralization (SN), adenoviruses 480 severe acute respiratory disease see SARS severe immunodeficiency (SCID), norovirus/sapovirus gastrointestinal infections 361 sexual transmission adenoviruses 477 CMV 167, 168 EBV 206 HBV 283 HIV 899, 930, 931 HPV 813, 814 HSV 103, 104 HTLV 883–884 KSHV (HHV-8) 250–251 SH2 (src-homology) domain 216 shellfish, hepatitis A transmission 276 shell vial assay VZV 149 shingles see herpes zoster ‘shipyard eye’ 474 shock, Ebola haemorrhagic fever 769 Shokwe virus 702, 707 Shuni virus 702, 711 Siadenovirus 464 sialic acid analogues, HPIV infection treatment 429 sialic acid receptors adenoviruses 467 BKV 825 influenza virus 378, 379, 386 JC virus 824 mumps virus 594 parainfluenza viruses 411–412, 417 sialoglycoproteins, HPIV binding 412, 414 Siberian tick-borne encephalitis virus (S-TBEV) 692 sickle cell disease, parvovirus B19V associated aplastic crisis 861 signalling, KSHV proteins 260 signal transducer and activation of transcription (STAT1) 357 simian haemorrhagic fever virus (SHFV), Ebola Reston co-infection 761 simian immunodeficiency virus (SIV) 931, 932 SIVcpz 897 simian T-lymphotropic viruses (STLV-1, STLV-2) 76, 876, 880 Subject Index simian virus (SV5) 410, 414 Simplexvirus 95, 96 Sindbis-like virus 659 Sindbis virus (SINV) 644, 644, 648–649 infection, rubella differential diagnosis 567 single radial haemolysis (SRH) technique, influenza 395 Sin Nombre-like viruses 723 Sin Nombre virus 73, 704, 722 see also hantaviruses SIV/HIV chimaera 931 sixth disease (exanthem subitum) 232 Sjăogrens syndrome 886 skin biopsy, rabies diagnosis 794, 795 skin infections, HSV 116, 127 SLAM (signalling lymphocytic activation molecule) see CD150 (SLAM) slapped cheek disease (fifth disease) 856, 859–860 ‘slim’ disease 899 slow virus infection 939 see also prion diseases small anellovirus (SAV) 326 genome 326, 327 small interfering RNA (siRNA), coronavirus infection treatment 526 smallpox 627–630 animal models and pathogenesis 629 bioterrorism and 625 cause of death 629 classic (ordinary) 628 clinical features and lesions 628–629 diagnosis 632 eradication 81–82, 91, 628 flat-type 628 forms and presentations 628–629 Global Eradication Programme 634 haemorrhagic-type 628 host, distribution 626 immunity 629 incubation period 628 modified-type 628–629 Rao classification 628–629 rash 628 varicella vs 143 sine eruptione 629 transmission 627–628 vaccination 634–635 adverse events and encephalitis 634 cost-effectiveness 91, 91 discovery, cowpox use 81 mandatory 90 modified vaccinia ankara (MVA) strain 634–635 strains 634 Snow Mountain strain of NoV 361 Snowshoe hare virus 702, 708–709 solid organ transplant recipients see transplantation (organ/tissue) recipients sorivudine (BVaraU), herpes zoster 152–153 ‘source drying’, concept 89 spasms, rabies 788, 789 specificity of tests 15, 16 specimens see samples/specimens spindle cells, endothelial cell-derived, KSHV infection 252 splenic rupture, EBV infection 209 Spondweni virus 673 Spumavirinae 870 spumaviruses 871, 872 squamous cell carcinoma (SCC), epidermodysplasia verruciformis and 813 SRSV (small round structure virus) 52 ST-246, vaccinia vaccinatum treatment 635 Staphylococcus aureus methicillin-resistant 23 pneumonia in influenza 390 ‘starry sky’ appearance 212, 213 STAT1, interferon response, HPIV infections 419–420 STAT2, interferon response, HPIV infection 420 stem cell transplant patients HTLV-1 infection treatment 890 screening assays before transplant 20 see also haematopoietic stem cell transplant (HSCT) recipients ‘sterilizing immunity’ 84 HSV 112 steroid therapy HPIV infection 429 infectious mononucleosis 211 see also corticosteroids Stevens-Johnson syndrome 117 St Louis encephalitis 687–688 control 688 diagnosis 687–688 epidemiology and clinical features 687 St Louis encephalitis virus (SLEV) 673, 687–688 vectors, host range 687 strand displacement amplification (SDA) 14 Strongyloides stercoralis 885–886 subacute sclerosing panencephalitis (SSPE) 544–545 clinical course/features 544 diagnosis 552 immunological aspects 550–551 pathogenesis 549–551, 550 risk factors 544 treatment 552 virological aspects 549–550 see also measles subacute spongiform encephalopathies see prion diseases subconjunctival haemorrhages 613 subtypes/clades cell tropism 897–898 circulating recombinant forms (CRFs) 897 sudden infant death syndrome (SIDS), influenza 391 supplementary immunization activities (SIAs), polio 618 surgeons HBV infection 37 HCV infection 37 HIV infection 38 survivin (apoptosis regulator) 259, 825, 840 sustained viral response (SVP) 17–18 swine see pigs (swine) Subject Index SYBR green 9, 10 syncytium HIV-1 897, 901 HPIVs 413, 417 HTLV-1 causing 876 RSV infection 442 syphilis, blood donation testing 31 systemic lupus erythematosus (SLE), TTV infection and 330 T Tacaiuma virus 702, 710 Tacaribe virus 734, 734 antibodies 742 infection, therapy 747 Tahyna virus 702, 709 tamarins, GVB-C 321, 322 Tamiflu see oseltamivir tanapox 637 host, distribution 626 Tanganya virus 704 Taq DNA polymerase 10 TaqMan oligoprobes 10, 11, 683 TATA binding protein CMV transcription 163 HPV transcription 810 TATA box, JC virus 827, 832 Tataguine virus 703, 726 T cells see T lymphocytes telbivudine, hepatitis B 303 telithromycin, rhinovirus infections 500 tenofovir disoproxil fumarate (TDF) hepatitis B 303–304 HIV infection 922, 923, 931 side effects 304 Tensaw virus 702, 707 teschoviruses 601 tetanus, prevalence reduction by vaccination 83 tethrin 901 Thailand virus 704, 722 thoracic ganglia, latent VZV infections 141, 146 Thottapalyam virus 704, 723 throat, sore EBV infection 208, 211 filovirus (Marburg/Ebola) infections 764 thrombocytopenia Ebola haemorrhagic fever 765 rubella 567 thrombocytopenic purpura, congenital rubella syndrome 573 thymidine kinase (TK) CMV 165 HSV 108, 109, 111 VZV, mutants 153 thymosin, hepatitis B therapy 305 thyroid autoantibodies 575 tickbite fever 720 tick-borne bunyaviruses 701, 703 tick-borne encephalitis 691–694 control 693–694 diagnosis 693 epidemiology 692–693 mortality 692 vaccines 694 ‘tick-borne encephalitis serocomplex’ 691 tick-borne encephalitis virus (TBEV) 691–694 characteristics 691–692 detection, monoclonal antibodies 692 distribution and vector 673, 691, 692 E protein 671 subtypes 691, 692 transmission 692 tick-borne flaviviruses 672 ticks bunyavirus transmission 701, 703 CCHF virus 718 control strategies 720 time-resolved fluorescence assay (TRFA) Tinaroo virus 702, 710 tipranavir, HIV infection 927–928 tissue factor (TF) expression, Ebola haemorrhagic fever 769 T lymphocytes activation, X-linked lymphoproliferative syndrome 216 adenovirus infections 470 apoptosis Ebola haemorrhagic fever 769 rabies 784, 785 smallpox 629 cytotoxic see CD8+ cells; cytotoxic T cells dengue haemorrhagic fever 683 helper HTLV-1 infection 887–888 see also CD4+ cells; Th1 and Th2 (below) HHV-6A and HHV-6B tropism 225 HHV-7 tropism 226 immunosuppression/‘tolerance’, LCMV infections 742, 743–744 Japanese encephalitis virus tropism 685 rhinovirus infection 495–496 RSV infections 446, 450 Th1 measles 547 RSV infections 446 Th2 measles 547 RSV infections 446, 450 vaccine-mediated protection from SARS 525 see also cell-mediated immunity (CMI) TMC278, HIV infection 925 Togaviridae 562, 643, 669 see also alphaviruses Togavirus, physical characteristics 51 Toll-like receptors (TLRs) 83, 84 measles 547 rhinovirus infections 496 RSV infection 445 tongue tremor 746, 747 tonsillar biopsy, vCJD 955–956, 956 Topografov virus 704, 722 topoisomerase II, induced by CMV 165 TORCH screen 21, 21 toroviruses 511–531 antigenic structure 517 assembly of virions 516 classification 511 1011 enteric 514 enteric infections 522 genome organization 516, 516 HE protein 512, 514, 517 proteins 512, 514 structure and electron microscopy 511–512, 514, 515 transcription and replication 514–516, 516 see also coronaviruses Torque teno virus (TTV) see TTV Torres bodies 677 Toscana virus 703, 711 toxic epidermal necrolysis 117 tracheal obstruction, EBV infection 209 tracheobronchitis, influenza 386, 389 trade, dengue transmission 681 trailer complementary (TrC) promoter, HPIV 415 transcriptional activators CMV 831 hepatitis B virus 286, 307 HTLV-1, Tax 831, 886 human polyomaviruses (JC virus; BKV) 830, 831 LANA-1 in KSHV infection 257 transcription regulatory sequence (TRS), coronaviruses 515 transforming growth factor (TGF-β), JC virus (JCV) 828 transfusion transmitted infections (TTIs) incidence and mortality 31 see also blood/blood-product transfusions ‘transfusion-transmitted virus’ see TTV α-trans-inducing factor (α-TIF) 98 transmissible gastroenteritis coronavirus (TGEV) 513, 525 receptors 517 transmissible mink encephalopathy (TME) 939, 943, 947 transmissible spongiform encephalopathies see prion diseases transmission of viruses blood/blood products see blood-borne viruses body fluids associated, precautions 29 genetic analysis 18 nosocomial see nosocomial infections/transmission prediction, molecular techniques 18 routes (respiratory/faeco-oral) 43–68 transplantation (organ/tissue) blood-borne virus transmission 32 CMV transmission 168, 168 HHV-6 transmission 230 HTLV transmission 891 KSHV transmission 251, 252 LCMV transmission 745 transplantation (organ/tissue) recipients adenovirus infections 476 antibody detection tests HHV-6 infection 235 HPIV infections 424 KSHV infection 252, 254 RSV infection 449 see also individual organ transplants 1012 travellers arenavirus infections 740 dengue fever 681 emerging infections and 71 flavivirus infections 670 HBV vaccination 294 hepatitis A virus vaccine 279–280 Japanese encephalitis 686 yellow fever vaccine 678 travellers’ diarrhoea, Aichi virus associated 364 tricyclic antidepressants, herpes zoster pain 153 trigeminal ganglia, latent VZV infections 141, 146 Trocara virus (TROCV) 644 TTMV see TTV-like mini virus (TTMV) TTV 73–74, 321, 325–332, 326 classification 325–326 detection and PCR 333 diseases associated 330 genome (antisense ssDNA) 321, 325, 326, 327, 331, 332, 332 ORFs 329, 331, 331 genotype Ia 329, 330 HCV co-infection 330 HIV co-infection 330 HPV co-infection 330 in lower animals 327, 329, 329 in nonhuman primates 327 pathogenicity 329, 330 pathology 329 PCR 333 phylogenic analysis 328 prevalence 321 proteins 331–332 replication 329, 330 target cells 329–330 transcriptional control 331 transmission routes 329, 330 TTV group of viruses 326–327 TT virus (TTV) see TTV TTV-like mini virus (TTMV) 325–326, 326 genome 326, 327 viral load in HIV infection 330 tuberculosis HIV infection and 912 HTLV infections and 885 Tula virus 704, 722 tumour necrosis factor-alpha (TNF-α), TNF-308, dengue haemorrhagic fever 683 tumours see cancer; individual tumour types Turlock virus 702, 710 Tzanck cells 148, 149 U Uganda S virus 673 ultrasound scanning, CMV infection 182 Una virus (UNAV) 644, 662 upper respiratory tract infections adenoviruses 471, 472 coronaviruses 520–521 HPIV 420, 423 rhinovirus 493 RSV infection 448 Subject Index uracil, synthetically-modified pyrimidine bases, HPIV 430 urine adenoviruses 477 BK polyomavirus (BKV) DNA 833, 834, 836–837, 844 CMV detection 175–176 JC virus (JCV) DNA 833, 834–835 USA infection reduction by vaccination 83 mortality of infectious diseases 69, 70 rubella vaccination 583 Usutu virus 673 Uukuniemi group of viruses 700, 703, 717 Uukuvirus 699 uveitis, HTLV-1 885, 891 V vaccination infection reduction by 83 minimum coverage to stop transmission 82, 82 optimal 82 programmes, planning/implementation 89 targeting of specific groups 89 UK programme/service 89 see also vaccinology vaccines activities for market introduction of 88, 88 administration routes 86, 87 adverse events 89 antigen dose 86 cost-effect and cost-saving 91, 91 coverage maintenance 89–90 development historical 85 routes 86 future developments 90 international campaigns and opinions 90 ‘killed’ whole-virion 86 live attenuated 86, 89 non-replicative (inactivated) 86 R&D 86–87, 87 regulatory approval 87 replicative 86 safety and efficacy 86–87, 89 social marketing 88, 88 types 86 see also individual virus infections vaccinia generalized, after vaccination 634 host, distribution 626 post-vaccinial encephalitis 634 vaccinia immune globulin (VIG) 635 vaccinia virus modified vaccinia ankara (MVA) strain 634–635 persistence in environment 49 smallpox vaccination 634 vaccinology 81–93 adverse events 89 burden of disease and reproductive rates 82, 83 disease incidence surveillance 89 future vaccine developments 90 historical aspects 81–82 immune system and artificial immunity 83–85 planning/implementation of programmes 89 principles/practice 82 protective antigen discovery 85–86 protective antigen presentation 86 publicized falsehood rectification 89–90 research and development 86–87, 87 reverse 85 social marketing of vaccines 88, 88 see also vaccination valaciclovir (Valtrex) CMV infection 182, 186 prophylaxis 186, 187–188 herpes zoster 152, 154 HSV infections 109, 113, 114, 117 HSV meningitis 124 structure 109 varicella (chickenpox) 151 valganciclovir (VGCV) CMV infections 181, 189 HSV infections 111 vampire bats, rabies 787, 790, 801 variant Creutzfeldt–Jakob disease (vCJD) 72, 944, 947, 950, 954–956 aetiology and epidemiology 948–949 age of onset 955 BSE association 954 characteristics/diagnosis 950 clinical onset and features 954–955 epidemic 948 first cases 954 incubation period 949, 955, 957 kuru relationship 956 lymphoreticular infection 955–956 molecular diagnosis 959, 960 neuroinvasion 956 neuropathology 955, 956 pathogenesis 960–961 PRNP 129MM and susceptibility 948, 949, 956 PRNP 129VM 956 prognosis and treatment 961 ‘pulvinar sign’ 955 secondary (iatrogenic) 956–957 sporadic CJD vs 956, 957 tonsillar biopsy 955–956, 956, 960–961 transmission 948–949, 960 varicella (chickenpox) 133 children 142, 144 treatment 151–152 clinical features 143–146 complications 144–146 congenital syndrome 145, 145, 152 diagnosis see varicella zoster virus (VZV), detection/diagnosis encephalitis 144–145 epidemiology 48, 142–143 haemorrhagic 144 immunocompromised patients 144, 152 incubation period 52, 143 infants 142 neonates 145–146 pathogenesis of infection 139–141, 140 Subject Index pneumonia associated 144, 144 pneumonitis 152, 154 pregnancy 141, 145–146, 155 prevention 153–156 rash 143–144, 146 recovery and immunity after 141 re-infection 138, 141 required vaccination coverage 82, 82 secondary cases, treatment 151–152 significant exposure (definition) 152 skin lesions 140, 141, 143–144 crusting 140, 144 treatment 151–152 tropical countries and 142 see also varicella zoster virus (VZV) varicella zoster immune globulin (VZIG) 49, 154 dosages 155 efficacy and limitations 154–155 neonatal infections and children 146 pregnancy 155 recommendations/indications 154, 154 varicella zoster virus (VZV) 139 3B3 epitope 149 monoclonal antibodies 138, 148 antibodies to 138–139, 148, 149–150 age prevalence 142, 143 IgG 138, 139, 146 IgM 138, 139, 151 maternal 146 neutralizing 151 antigens 137–138 detection 4, 149–150, 150 HSV cross-reactivity 150 antiviral drug resistance 153 assembly and release (exocytosis) 136 attachment and infection process 136 breakthrough infection 49, 53 capsids 136 cytology 148 cytopathic effect 137, 137, 149 detection/diagnosis 148–151 complement fixation test 150 direct techniques 148 DNA detection 148–149 electron microscopy 148 enzyme immunoassay 150–151 immunofluorescence 148, 150 isolation of VZV 149 PCR 139, 148–149 serology 149–151 gene expression (IE, E and L) 136 genes and proteins 135, 135–136, 141–142 genome (dsDNA) 133–136, 137, 143 HSV homology 134–136 open reading frames 135, 136 organization/sequence 133–134, 134 single nucleotide polymorphisms 137–138 glycoproteins 136, 149 gE 136 HSV cross-reactivity 138, 150 growth in cell culture 137 HCWs and 48–53 HIV co-infection 914 immune response to infection 138–139 cell-mediated 138–139, 142 humoral see varicella zoster virus (VZV), antibodies to immunity in HCWs 48 infection process 140 infections see herpes zoster; varicella (chickenpox) latent infection 133, 141–142, 146 molecular epidemiology 143 MSP-VZV 138 multinucleated cells and inclusions 137, 138, 140, 141, 144, 148, 149 nosocomial infections 48–53 costs 48 management 49 Oka strain 53, 138, 155 genotyping 143 wild-type genome sequence comparison 155 passive immunization 154–155 pathogenesis of infection 139–141, 140 pathogenicity for animals 139 physical characteristics 50 post-exposure prophylaxis 156 prevention of infections 153–156 reactivation 133, 141, 142, 146 in pregnancy 53 synchronous with HSV 107 see also herpes zoster receptors 136 recombinant genotypes 137–138, 143 re-infection with 138, 141 replication 136 rolling circle mechanism 136 shedding 149 strain variation 137–138 structure/morphology 133–136, 134 T-cell response 138–139, 142 tegument proteins 136 TK mutants 153 transmission 52, 139–140, 142 airborne 49, 139 rates to HCWs 48–49 treatment of infections see herpes zoster; varicella (chickenpox) vaccination 49, 155–156 HCWs 49, 51, 53 live attenuated vaccine 49, 53 post-exposure 51 pre-exposure 51, 53 rash post-vaccine 49 reduced nosocomial infections 48 required vaccination coverage 82, 82 vaccines 133, 155–156 efficacy, benefits 155–156 Oka 152, 155, 156 viral load 149 Varicellovirus 95, 96 variola major 626, 628 variola minor 626, 628 variola sine eruptione 629 variolation 81, 90 variola virus 625 antigens 629 host range 627 1013 phenotypic diagnosis 632–633 transmission/infectivity 627–628 see also smallpox vascular endothelial growth factor (VEGF) KSHV infection 252, 263 rhinovirus infection 495 vectors, viruses as adenoviruses 482 measles virus 535 retroviruses 869, 872–873 vectors of viruses, increased contact, emerging infections 74–77 Venezuela haemorrhagic fever 750–751 Venezuelan equine encephalitis virus (VEEV) 643, 644, 646, 659–661 clinical disease 660–661 IgG and IgM 661 origins and distribution 659–660, 660 pathogenesis, diagnosis and control 661 vesicular stomatitis virus, recombinant 770 Vesiculovirus 778 VIDISCA (virus discovery based on cDNA-AFLP) 523 viral interference 414 viral quasispecies 18, 523 viral shedding, qualitative detection of virus 16 viramidine, hepatitis C 315 virologists, communication with physicians 22 viroplasms, rotaviruses 339 ‘virtual phenotyping’ 20 virus amplification, in hospitals 43 viruses persistence in environment 49 physical characteristics 50–51 virus isolation 2–3, VITROS ECi assay, HIV 908 VLA-2, echovirus receptor 605 VX-950, hepatitis C treatment 316 W Wanowrie virus 703, 726 Warthin–Finkeldy cells 543 warts genital 814, 816, 817 laryngeal 813, 815 plantar 813, 817 Wesselsbron virus 673, 679 West Caucasian bat virus 779 Western blotting HIV infection 906–907 HTLVs 879, 880 western equine encephalitis virus (WEEV) 643, 644, 658–659 clinical disease 658 diagnosis 659 epidemiology and host range 658, 659 prevention and control 659 western tick-borne encephalitis virus (W-TBEV) 692, 693 West Nile fever clinical features 690 control 690 diagnosis and antibodies 688, 690 1014 West Nile fever (contd.) epidemics and outbreaks 689–690 epidemiology 689–690 meningoencephalitis 75 neuro-invasive disease 688, 690 rubella differential diagnosis 567 West Nile virus (WNV) 75, 669, 673, 688–690 characteristics and host range 688–689 isolation 690 lineages (I-IV) 688 NY99 prototype 688 transmission cycle 689 vectors 688, 689 Whataroa virus (WHAV) 644 wheezing, recurrent, RSV infection 449–450, 454 Whitewater Arroyo virus 734, 738, 751 detection 741 infections 751 whole-genome sequencing, influenza virus 395 whooping cough, vaccination coverage reduction 90 winter vomiting disease 54 woodchuck hepatitis virus (WHV) 284 World Health Organization (WHO) detection/response on infections 23 poliomyelitis eradication programme 618 rabies vaccine recommendations 800 rubella vaccination recommendations 585, 585–586, 586 SARS prevention recommendations 62 WU virus 74 Wyeomyia virus 702, 707 X xenotropic MuLV-related virus (XMRV) 872 xenotropic murine leukaemia related virus (XMRV) 77 X-linked lymphoproliferative syndrome (X-LPS) 216 Subject Index vector 674 see also flaviviruses Y yattapox virus, host, distribution 626 yeast prions 944 yellow fever 672, 674–678 abortive infection 676 age and gender affecting 677 clinical features 676–677 control 677–678 diagnosis 677 differential diagnosis 676 ‘enzootic forest cycle’ 674 epidemics 674 epidemiology 672, 674–676 Africa 674, 675 Americas 674, 675, 677 haemorrhagic diathesis 676 history 672 incubation period 676 ‘jungle yellow fever cycle’ 674, 676 mortality 676 surveillance for 677 transmission cycles 674, 676 universal/mass immunization 678 ‘urban yellow fever cycle’ 676, 677 vaccine 677–678 contraindications 678 French neurotropic 678 pregnancy 678 production volume 678 side effects 678 viraemia 676 yellow fever virus 672, 674–678 17D vaccine strain 672, 678 Asibi strain 672 detection 677 distribution and vector 673 genotypes 676 isolation/cell lines 677 prM and E proteins 676 transmission 672 Z zalcitabine HAM treatment 890 HIV infection 916 zanamivir HPIV3 infection 413 HPIV infection 429 influenza 60, 398 structure 397 zidovudine adult T-cell leukaemia treatment 890 HAM treatment 890 HIV infection 916, 923 vertical transmission prevention 930 prophylactic 930, 931 resistance 923, 924, 930 Zika fever 684 Zika virus 673, 684 zinc preparations, rhinovirus infections 500 Zinga virus 713 zoonotic infections influenza see influenza A virus; influenza virus retroviruses 869 see also individual animals/vectors zoster see herpes zoster zoster-associated pain (ZAP) 147 treatment 152, 153 zosteriform herpes simplex (cutaneous HSV) 116 zoster immunoglobulin (ZIG) 154 zoster sine herpete 146 Zovirax see aciclovir ... sequence-based amplification (NASBA), transcription mediated amplification (TMA), strand displacement amplification (SDA) and branched chain DNA (bDNA) not require any specialized thermal cycler A number... the author shall be liable for any damages arising herefrom Library of Congress Cataloging-in-Publication Data: Principles and practice of clinical virology / edited by Arie J Zuckerman [et al.]... interpretation of results in a clinical setting may be difficult A number of commercial kits and automated systems are now available, with the advantages of improved quality control and reduced inter-laboratory