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Manual of
Childhood
Infections
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Manual of
Childhood
Infections
Third edition

Chief Editor
Mike Sharland
Professor of Paediatric Infectious Diseases,
St George’s Hospital, London, UK

1
1
Great Clarendon Street, Oxford OX2 6DP.
Oxford University Press is a department of the University of Oxford.
It furthers the University’s objective of excellence in research, scholarship,
and education by publishing worldwide in
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With offices in
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Oxford is a registered trade mark of Oxford University Press
in the UK and in certain other countries
Published in the United States
by Oxford University Press Inc., New York
© The Royal College of Paediatrics and Child Health 2011
The moral rights of the author have been asserted
Database right Oxford University Press (maker)
First published 2011
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,
without the prior permission in writing of Oxford University Press,
or as expressly permitted by law, or under terms agreed with the appropriate
reprographics rights organization. Enquiries concerning reproduction
outside the scope of the above should be sent to the Rights Department,
Oxford University Press, at the address above
You must not circulate this book in any other binding or cover
and you must impose this same condition on any acquirer
British Library Cataloguing in Publication Data
Data available
Library of Congress Cataloging-in-Publication-Data
Data available
Typeset by Glyph International, Bangalore, India
Printed in Great Britain
on acid-free paper through
Ashford Colour Press Ltd, Gosport, Hampshire
ISBN 978–0–19–957358–5
10 9 8 7 6 5 4 3 2 1
Oxford University Press makes no representation, express or implied, that the
drug dosages in this book are correct. Readers must therefore always check the
product information and clinical procedures with the most up-to-date published
product information and data sheets provided by the manufacturers and the most
recent codes of conduct and safety regulations. The authors and publishers do not
accept responsibility or legal liability for any errors in the text or for the misuse or
misapplication of material in this work. Except where otherwise stated, drug dosages
and recommendations are for the non-pregnant adult who is not breastfeeding.
v

Foreword by Professor
Terrence Stephenson
President of The Royal College of
Paediatrics and Child Health,
United Kingdom

I am delighted to write a foreword for the third edition of The Manual of


Childhood Infections. The last edition was ten years ago. This new edition
has been completely re-written and updated. The aim of the book is to
provide a practical, evidence-based handbook approach to the manage-
ment of both common and unusual infections in children. The editorial
board found nearly two hundred authors to write the one hundred and
twenty chapters of this new edition. The book has been written by paedia-
tricians, microbiologists and a wide range of international experts in paedi-
atric infectious diseases. The book is aimed at both trainee and practising
hospital and community based paediatricians, nursing and other medical
staff caring for children in the United Kingdom, Europe and internation-
ally. It provides an up-to-date reference guide, including common differ-
ential diagnoses, practical management hints and information for over one
hundred drugs. The overall aim of the book is to improve the evidence-
base for the management of childhood infections.
In the United Kingdom, a recent confidential enquiry into maternal and
child health notes infection still to be the largest single cause of death in
children dying of an acute illness. Overall, infection was a contributory
cause in at least twenty per cent of all childhood deaths, and this was over
one quarter of all deaths in children between one and four years of age.
Despite the success of recent immunisation campaigns, nearly two thirds of
these deaths are still due to bacterial infection. Prompt diagnosis of serious
bacterial infections remains a major challenge in paediatrics globally. In
both healthy children and in those with underlying medical conditions,
still too many children die of unrecognised infections, particularly children
with long-term medical conditions, including prematurity. There is still
much to be done to prevent nosocomial and opportunistic infections.
Paediatricians also have a duty in not over-treating or over-managing
children with minor, self-limiting infectious illness. There has been a rise
of around forty per cent of short stay admissions to hospital of less than
two days in England in the last decade. The majority of these are for minor
illnesses, particularly infections that could be managed more appropriately
in the community. Antibiotics remain a precious and finite resource. The
rise of antimicrobial resistance is now recognised by the UK Departments
of Health, the European CDC and World Health Organization as a major
threat to human health in the future. The antibiotic ‘pipeline’ particularly
for agents acting against gram negative infections, is worryingly sparse.
Gram negative resistance is becoming increasingly common in hospital
vi FOREWORD BY PROFESSOR TERRENCE STEPHENSON

acquired infection and the optimal use of our current antibiotics becomes
ever more important. Prudent use of antibiotics and antibiotic stewardship
are ever more necessary now. Imported infections and new global
pandemics will remain a continued threat, so the Manual also highlights
the early recognition and prompt management of less common infections.
The new edition has been produced in collaboration with the European
Society for Paediatric Infectious Diseases (ESPID) and the Royal College
welcomes the development of collaborative educational initiatives
between the United Kingdom and Europe.
vii

Foreword by Professor
Ulrich Heininger
President of the European Society for
Paediatric Infectious Diseases (ESPID)

The European Society for Paediatric Infectious Diseases is delighted to


be working in partnership with the Royal College of Paediatrics and Child
Health in this third edition of the Manual of Childhood Infections – the
Blue Book. This edition has a strong European and global focus and has
tried to define the evidence-base for the management of common child-
hood infectious diseases. There is still much variation in the practice and
management of childhood infections across Europe today. ESPID accepts
and welcomes this diversity of care, much of which reflects cultural differ-
ences in child care across Europe. Moreover, there are variations in the
prevalence of specific infectious diseases and variations in antimicrobial
resistance patterns across Europe. Clearly evidence-based guidelines will
continue to vary across European countries for many years to come.
This manual has therefore attempted to be a synthesis of the published
evidence, collating wherever possible, Cochrane and other systematic
reviews, and has as its core an up to date evidence base. It does not aim to
replace local, regional or country-specific guidance for either the hospital
or office-based paediatrician but rather has been produced as a teaching
tool for trainees across Europe, and for practising paediatricians. It should
be used as a source to check, look up or think about the management
plan, the differential diagnosis or recent epidemiology. In many cases,
chapters define clearly what we do not know, and authors have tried to
outline areas of important research for the future. ESPID hopes to be
taking forward some of these ideas through its new research committee.
The Blue Book also recognises that antimicrobial dosing varies considerably
across Europe. The drug, the dose and the duration of treatment are often
poorly evidence-based in paediatrics, especially in neonatal medicine.
The Blue Book formulary again, does not replace local guidelines, but is
designed to be a short, easy to use, pragmatic and reasonable summary
of the published evidence for each drug. It is hoped that further work
in defining variations in guidelines, drug dosing and indication, can be
fed into initiatives such as the European Medicines Agency’s Priority Drug
List. Collaborative research projects across Europe will hopefully in time
improve the evidence-base for both old and new antimicrobials used in
children.
viii FOREWORD BY PROFESSOR ULRICH HEININGER

The Blue Book is part of ESPID’s mission, aiming at improving the


education of paediatricians and the optimal management of infectious
diseases. We recognise that not everyone will agree with everything
written in this edition and we encourage your comments, suggestions for
improvements and contributions for the next edition. The Blue Book is
still a relatively new venture (on its third edition whereas the Red Book
is on its twenty seventh edition) but I am confident that over time it will
become a core part of the management of paediatric infectious diseases
across Europe.
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ix

Contents
Section editors xiv
Contributors xv
Abbreviations and symbols xxiv

Section 1 Clinical syndromes


1 Antibiotics and resistance 3
2 Antifungal drugs 10
3 Antiparasitics 20
4 Antivirals 25
5 Bone and joint infections 38
6 Cardiac infections: endocarditis 44
7 Cardiac infections: myocarditis and pericarditis 54
8 Central venous catheter infections 68
9 Chronic fatigue syndrome 73
10 Congenital infections 77
11 Conjunctivitis 90
12 Diarrhoea and vomiting 97
13 Emerging and re-emerging infections 102
14 Encephalitis 107
15 Enlarged lymph nodes 116
16 Haemolytic-uraemic syndrome 131
17 Healthcare-associated infections 137
18 Acute hepatitis 148
19 Human immunodeficiency virus infection 153
20 Immunocompromised children with infection 163
21 Infection control in community settings 172
22 Intra-abdominal infections 178
23 Invasive fungal infection 193
x CONTENTS

24 Investigating the child with possible


immunodeficiency 204
25 Kawasaki disease 214
26 Laboratory diagnosis of infection 220
27 Lower respiratory tract infection 230
28 Mastoiditis, quinsy, and brain abscess 240
29 Meningitis 247
30 Neonatal infection 262
31 Ocular infections 270
32 Periodic fever syndromes 282
33 Pyrexia of unknown origin 287
34 Rash: making a diagnosis 292
35 Refugees and internationally adopted children 303
36 Sepsis syndrome 308
37 Sexually transmitted infections 320
38 Skin and soft tissue infections 327
39 Toxic shock syndrome 334
40 Trauma, bites, and burns 344
41 Travelling abroad with children 350
42 The unwell child returning from abroad 357
43 Urinary tract infection 364
44 Upper respiratory tract infections 373
45 Zoonoses 383

Section 2 Specific infections


46 Adenovirus 394
47 Amoebiasis 401
48 Anaerobic infections 407
CONTENTS xi

49 Arboviruses 416
50 Ascariasis 425
51 Aspergillosis 434
52 Botulism 448
53 Brucellosis 452
54 Campylobacter 456
55 Candidiasis 460
56 Cat scratch disease 464
57 Chicken pox—varicella zoster 467
58 Chlamydia 475
59 Cholera 483
60 Clostridium difficile infection 487
61 Cryptosporidiosis 496
62 Cytomegalovirus 499
63 Diphtheria 505
64 Enteroviruses and parechoviruses 508
65 Epstein–Barr virus 517
66 Escherichia coli diarrhoea 521
67 Giardiasis 523
68 Gonococcal infection 527
69 Gram-negative bacteria 531
70 Haemophilus influenzae 537
71 Hand, foot, and mouth disease 542
72 Head lice (pediculosis) 544
73 Helicobacter pylori 548
74 Helminthiases 553
75 Hepatitis B 564
76 Hepatitis C 571
xii CONTENTS

77 Herpes simplex virus 1 and 2 576


78 Human herpesviruses 6 and 7 583
79 Human papillomavirus 587
80 Influenza and parainfluenza 595
81 Legionella 600
82 Leishmaniasis 603
83 Listeriosis 609
84 Lyme disease 613
85 Malaria 616
86 Measles 624
87 Meningococcal disease 628
88 Molluscum contagiosum and other poxviruses 637
89 Mumps 640
90 Mycoplasma 644
91 Non-tuberculous mycobacterial infection 649
92 Norovirus 655
93 Parvovirus 659
94 Pertussis 664
95 Plague 670
96 Pneumocystis pneumonia (PcP) 674
97 Polio 678
98 Rabies 683
99 Respiratory syncytial virus 687
100 Rotavirus 692
101 Rubella 696
102 Scabies 701
103 Schistosomiasis 705
104 Shigellosis 710
CONTENTS xiii

105 Staphylococcal infections including MRSA 713


106 Streptococcal infections 721
107 Syphilis 730
108 Tetanus 735
109 Threadworm 738
110 Tinea 741
111 Toxocariasis 747
112 Toxoplasmosis 749
113 Tuberculosis 753
114 Typhoid and paratyphoid—enteric fever 759
115 Typhus 764
116 Viral haemorrhagic fevers 771
117 Yellow fever 778
118 Yersiniosis 783

Appendices
Appendix 1 The contribution of infectious diseases
to neonatal and childhood deaths in
England and Wales 786
Appendix 2 Guidance on infection control in
school and other childcare settings 792
Appendix 3 Immunization of the normal and
immunocompromised child 797
Appendix 4 Notification and surveillance of
infectious diseases 803
Appendix 5 Blue Book Formulary 810
Index 863
xiv

Section editors

Andrew Cant Paul T. Heath


Consultant in Paediatric Reader and Honorary Consultant
Immunology and Infectious in Paediatric Infectious Diseases,
Diseases, Great North Children’s St George’s, University of London,
Hospital, Newcastle, UK London, UK
Graham Davies Hermione Lyall
Consultant Paediatric Consultant Paediatrician,
Immunologist, Great Ormond Infectious Diseases, Chief of
Street Hospital for Children, Service for Paediatrics, Imperial
London, UK College Healthcare NHS Trust, UK
David Elliman Andrew J. Pollard
Consultant in Paediatrics, Professor of Paediatric
Great Ormond Street Hospital Infection and Immunity,
for Children, London, UK University of Oxford and
Honorary Consultant Paediatrician,
Susanna Esposito Oxford Children’s Hospital,
Director of the Pediatric Infectious Oxford, UK
Diseases Unit, Università degli
Studi di Milano, Fondazione IRCCS Mary Ramsay
Ca’ Granda Ospedale Maggiore Consultant Epidemiologist and
Policlinico, Milan, Italy Head, Immunisation, Hepatitis and
Blood Safety Department,
Adam Finn Health Protection Agency Centre
David Baum Professor of for Infections,
Paediatrics; Head, Unit of Child London, UK
Health, Department of Clinical
Sciences, University of Bristol; Andrew Riordan
Director, South West Medicines Consultant in Paediatric Infectious
for Children Local Research Diseases and Immunology,
Network; Honorary Consultant Alder Hey Children’s NHS
Paediatrician, Bristol Royal Foundation Trust, Liverpool, UK
Hospital for Children, UK
Delane Shingadia
Jim Gray Consultant in Paediatric Infectious
Consultant Medical Diseases, Great Ormond Street
Microbiologist, Birmingham Hospital for Children,
Children’s Hospital London, UK
NHS Foundation Trust and
Birmingham Women’s
NHS Foundation Trust, UK
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