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Manual of
Childhood
Infections
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Oxford Specialist Handbooks in
Infectious Disease
Infectious Disease Epidemiology
Manual of Childhood Infections 4e
Manual of
Childhood
Infections
Fourth edition

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

1
1
Great Clarendon Street, Oxford, OX2 6DP,
United Kingdom
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. Oxford is a registered trade mark of
Oxford University Press in the UK and in certain other countries
© Royal College of Paediatrics & Child Health & European Society of Paediatric
Infectious Diseases 2016
The moral rights of the author‌have been asserted
First Edition published as Manual of Childhood Infections, 1996
Second Edition published as Manual of Childhood Infections, 2001
Third Edition published 2011
Fourth Edition published 2016
Impression: 1
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, by licence 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 work in any other form
and you must impose this same condition on any acquirer
Published in the United States of America by Oxford University Press
198 Madison Avenue, New York, NY 10016, United States of America
British Library Cataloguing in Publication Data
Data available
Library of Congress Control Number: to follow
ISBN 978–0–19–872922–8
Printed in Great Britain by
Ashford Colour Press Ltd, Gosport, Hampshire
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
the 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 breast-feeding
Links to third party websites are provided by Oxford in good faith and
for information only. Oxford disclaims any responsibility for the materials
contained in any third party website referenced in this work.
v

Foreword to
the fourth edition
We are very pleased to write a foreword for the fourth edition of the Blue
Book on Childhood infections. The last edition was around five years ago
and this new edition has again been re-written and updated. The book
provides a clinical evidence-based handbook approach to the management
of both common and unusual infections in children. The Editorial Board
has nearly 200 authors writing the 120 chapters of this new edition. The
book has been written by paediatricians, microbiologists, and a wide range
of international experts in paediatric infectious disease. 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 internationally. It aims to provide an up-to-date reference guide
including common differential diagnoses, medical management, and infor-
mation on over 100 medicines.
The aim of the book is to improve the evidence-based management to
a child’s infection. This new edition has short abstracts, key references,
and key learning points which are now fully updated. Recent immunisation
campaigns have substantially reduced rates of serious bacterial infection in
children yet new and emerging infections remain a very serious concern.
Rates of hospital-acquired infection are now a serious threat to children and
much remains to be done to reduce nosocomial infection. Antimicrobial
resistance has been flagged by the World Health Organization as one of
the three greatest threats to human health. New chapters on antimicrobial
stewardship demonstrate the way forward for reducing the inappropriate
antibiotic prescribing that drives this very serious problem.
The development of an eBook format now provides a bedside approach
to the practical management of common infections. All paediatricians
should be encouraged to manage a child’s infection using this practical, sim-
ple evidence-based approach.
The European Society for Paediatric Infectious Diseases is very pleased
to be working in partnership with the Royal College of Paediatrics and Child
Health. This edition has an ever-increasing international focus. There is still
considerable variation of practice and management of children’s infection.
Much of this reflects cultural differences and child care practice across
Europe. There is still some variation in practice that cannot necessarily be
explained just by altered prevalence of infections and resistance pattern.
Although evidence-based guidelines will vary across European countries,
the manual is an attempt to be a synthesis of published evidence of sys-
tematic reviews providing the core basic evidence. The Blue Book has been
produced as a teaching tool for trainees internationally and for practising
paediatricians. It can be used as a source to look up, check, or think about
management plans, differential diagnosis, or recent epidemiology. In most
chapters, sections define what is new and what is coming. The Blue Book
also acts to identify future research priorities and aims to encourage collab-
oration across Europe.
vi FOREWORD TO THE FOURTH EDITION

The Blue Book also recognizes that antimicrobial dosing varies consid-
erably across Europe. For this new edition an evidenced approach to the
formulary has been produced and for the first time will provide information
about grading the level of evidence for antimicrobials. The Blue Book again
does not aim to replace national or local formularies but provides a prag-
matic and reasonable summary of the evidence base for each drug.
Professor Neena Modi (RCPCH)
Professor Adam Finn (ESPID)
vii

Contents

Section editors xii


Contributors xiv
Symbols and abbreviations xxi

Section 1 Clinical syndromes


1 Antibacterials   3
2 Antifungals   11
3 Antiparasitics   23
4 Antivirals   31
5 Antimicrobial stewardship   43
6 Bacterial meningitis   49
7 Bone and joint infections   65
8 Cardiac infections   70
9 Central venous catheter infections   93
10 Chronic fatigue syndrome 100
11 Congenital infections 103
12 Diarrhoea and vomiting 112
13 Emerging infections and pandemic preparedness 117
14 Encephalitis 125
15 Enlarged lymph nodes 135
16 Ocular infections 148
17 Immunocompromised children with infection 160
18 Immunization of the immunocompromised child 171
19 Infection control in the community 183
20 Infection control in the hospital 188
21 Laboratory diagnosis of infection 199
22 Lower respiratory tract infection 210
viii CONTENTS

23 Neonatal infections 220


24 Hereditary autoinflammatory diseases 228
25 Pyrexia of unknown origin 234
26 Rash 242
27 Gram-positive bacteria 257
28 Gram-negative infections 263
29 Refugees and internationally adopted children 269
30 The unwell child returning from abroad 274
31 Sepsis syndrome 281
32 Sexually transmitted infections 293
33 Skin and soft tissue infections 300
34 Investigating the child with possible
immunodeficiency 309
35 Invasive fungal infection 326
36 Toxic shock syndrome 334
37 Trauma, bites, and burns 344
38 Travelling abroad with children 350
39 Urinary tract infection 357
40 Upper respiratory tract infections 366
41 Zoonoses 377

Section 2 Specific infections


42 Adenovirus 389
43 Amoebiasis 396
44 Anaerobic infections 402
45 Arboviruses 411
46 Ascariasis 420
47 Aspergillosis 429
48 Botulism 442
49 Brucellosis 446
CONTENTS ix

50 Campylobacter 450
51 Candidiasis 454
52 Cat scratch disease 461
53 Chickenpox—varicella-zoster 464
54 Chlamydia pneumoniae infection 474
55 Chlamydia psittaci infection 477
56 Chlamydia trachomatis infection 479
57 Cholera 484
58 Clostridium difficile 488
59 Conjunctivitis 497
60 Cryptosporidiosis 504
61 Cytomegalovirus 507
62 Dermatophytoses: tinea capitis, corporis,
pedis, and unguium 513
63 Diphtheria 520
64 Enteroviruses (including rhinoviruses)
and parechoviruses 524
65 Rhinovirus 533
66 Giardiasis 537
67 Gonococcal infection 541
68 Haemolytic–uraemic syndrome 545
69 Haemophilus influenzae 554
70 Viral haemorrhagic fevers 560
71 Hand, foot, and mouth disease 568
72 Helicobacter pylori 572
73 Hepatitis A and E 576
74 Hepatitis B 582
75 Hepatitis C 589
76 Herpes simplex virus 1 and 2 594
77 Human immunodeficiency virus infection 602
x CONTENTS

78 Helminthiases 613
79 Epstein–Barr virus 624
80 Influenza and parainfluenza 628
81 Threadworms 633
82 Kawasaki disease 637
83 Legionella 643
84 Leishmaniasis 648
85 Listeriosis 655
86 Lyme disease 659
87 Malaria 662
88 Measles 671
89 Meningococcal disease 676
90 Mumps 684
91 Non-tuberculous mycobacterial infection 689
92 Mycoplasma infections 696
93 Head lice (pediculosis) 704
94 Norovirus 709
95 Other fungal infections 715
96 Human papillomavirus 723
97 Parvovirus 730
98 Pertussis 737
99 Plague 745
100 Pneumococcal disease 750
101 Pneumocystis pneumonia 757
102 Polio 764
103 Molluscum contagiosum and other poxviruses 769
104 Prion diseases 773
105 Rabies 780
106 Respiratory syncytial virus 785
107 Human herpesvirus 6 and 7 790
CONTENTS xi

108 Rotavirus 795


109 Rubella 799
110 Salmonellosis 804
111 Scabies 810
112 Schistosomiasis 814
113 Shigellosis 819
114 Staphylococcal infections, including
meticillin (INN)-resistant Staphylococcus aureus 823
115 Streptococcal infections 832
116 Syphilis 840
117 Tetanus 846
118 Tick-borne encephalitis 851
119 Toxocariasis 856
120 Toxoplasmosis 859
121 Tuberculosis 864
122 Typhoid and paratyphoid—enteric fever 871
123 Typhus 877
124 Yellow fever 885
125 Yersiniosis 890
126 Kingella kingae 894

Appendix 1╇ Morbidity and mortality from infection╇ 901


Appendix 2╇Guidance on infection control in
school and other childcare settings╇ 908
Appendix 3╇Variation in immunization schedules
in Europe╇ 913
Appendix 4╇ Blue book antimicrobial dosing guide╇ 922
Index╇ 967
xii

Section editors

Karina Butler Carlo Giaquinto


Department of Infectious Diseases Department of Women and
& Immunology, Our Lady’s Child Health, University of
Children’s Hospital Crumlin and Padova, Italy
UCD School of Medicine and
Medical Sciences, Dublin, Ireland Jim Gray
Department of Microbiology,
Andrew Cant Birmingham Children’s Hospital,
Department of Paediatric Birmingham, UK
Immunology, Allergy and Infectious
Diseases, Great North Children’s Ronald de Groot
Hospital, Newcastle, UK Department of Paediatrics,
Radboudumc Amalia Children’s
Ron Dagan Hospital, Nijmegen,
Pediatric Infectious Disease Unit, The Netherlands
Soroka University Medical Center,
and Faculty of Health Sciences, Paul Heath
Ben-Gurion University of the Paediatric Infectious Diseases
Negev, Beer-Sheva, Israel Research Group, Institute of
Infection and Immunity, St
Graham Davies George’s, University of London,
Great Ormond Street Hospital, London, UK
London, UK
Terho Heikkinen
David Elliman Department of Paediatrics,
Whittington Health, Haringey University of Turku, Turku, Finland
Children Community Health
Services, St Ann’s Hospital, Ulrich Heininger
London, UK Paediatric Infectious Diseases and
Vaccinology, University Children’s
Susanna Esposito Hospital Basel, Switzerland
Paediatric Highly Intensive Care
Unit, Fondazione IRCCS Ca’ Philipp Henneke
Granda Ospedale Maggiore Center for Chronic
Policlinico, University of Milan, Immunodeficiency (CCI) and
Milan, Italy Center for Pediatrics, Medical
Center, University of Freiburg,
Adam Finn Germany
School of Clinical Sciences,
University of Bristol, Bristol, UK Shamez Ladhani
Public Health England, London,
Manolis Galanakis UK; Paediatric Infectious Diseases
Paediatric Infectious Diseases Unit, Research Group, Institute of
Heraklion University Hospital, Infection and Immunity,
Crete, Greece St George’s, University of London,
London, UK
 SECTION EDITORS xiii

Irja Lutsar Emmanuel Roilides


Institute of Medical Microbiology, 3rd Department of Paediatrics,
University of Tartu, Tartu, Estonia Medical Faculty, Aristotle
University School of Health
Hermione Lyall Sciences, Hippokration Hospital,
Department of Paediatrics, Thessaloniki, Greece
St Mary’s Hospital, London, UK
Pablo Rojo
Federico Martinon Torres Pediatric Infectious Disease Unit,
Translational Pediatrics and Department of Pediatrics, Hospital
Infectious Diseases, Hospital 12 de Octubre, Madrid, Spain
Clínico Universitario de Santiago
de Compostela, Santiago, Spain Mike Sharland
Department of Paediatrics,
Andrew Pollard St George’s University Hospital,
Department of Paediatrics, London, UK
University of Oxford, Oxford, UK
Delane Shingadia
Mary Ramsay Department of Infectious Diseases,
Immunisation, Hepatitis and Blood Great Ormond Street Hospital,
Safety Department, Public Health London, UK
England, London, UK
Steve Tomlin
Andrew Riordan Children’s Medicine Service,
Alder Hey Children’s NHS Evelina London, Guy’s and
Foundation Trust, Liverpool, UK St Thomas’ NHS Foundation Trust,
London, UK
Fernanda Rodrigues
Infectious Diseases Unit & Maria Tsolia
Emergency Service, Coimbra Faculty of Medicine, National
Children’s Hospital, Coimbra, and Kapodistrian University of
Portugal Athens, Greece
xiv

Contributors

Lei Ang Tim Brown


Department of Microbiology, Rare and Imported Pathogens
Royal University Hospital, Laboratory, Public Health England,
Saskatoon, Saskatchewan, Canada UK
Charalampos Antachopoulos Penelope Bryant
3rd Department of Paediatrics, Infectious Diseases Unit,
Medical Faculty, Aristotle Department of General Medicine,
University School of Health The Royal Children’s Hospital,
Sciences, Hippokration Hospital, Melbourne and Murdoch
Thessaloniki, Greece Children’s Research Institute,
Department of Paediatrics,
Alasdair Bamford University of Melbourne, Australia
Paediatric Infectious Disease,
Great Ormond Street Hospital, Jim Buttery
London, UK Infection and Immunity, Monash
Children’s Hospital, Murdoch
Shalom Ben-Shimol Children’s Research Institute,
Pediatric Infectious Disease Department of Paediatrics,
Unit, Soroka University Medical Monash University, Melbourne,
Center and The Faculty of Health Australia
Sciences, Ben-Gurion University of
the Negev, Beer-Sheva, Israel Hsin Chi
Division of Infectious Diseases,
Jolanta Bernatoniene Department of Paediatrics,
Paediatric Infectious Disease & MacKay Children’s Hospital,
Immunology Department, Bristol Tapei, Taiwan
Royal Hospital for Children,
Bristol, UK Nan-Chang Chiu
Department of Paediatrics,
Maria Bitsori MacKay Children’s Hospital,
Department of Paediatrics, Taipei, Taiwan
Heraklion University Hospital,
Crete, Greece GeorgI Christov
Great Ormond Street Hospital,
Jan Bonhoeffer London, UK
Paediatric Infectious Diseases and
Vaccinology, University Children’s Theresa Cole
Hospital Basel, Switzerland Royal Children’s Hospital,
Melbourne, Australia
Paul Brogan
UCL Institute of Child Health, and Richard Cooke
Great Ormond Street Hospital University of Liverpool,
NHS Trust, London, UK Merseyside, UK
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