Complete Handbook

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RECOGNITION AND TREATMENT OF ANAPHYLAXIS
Signs of anaphylaxis
Anaphylaxis causes respiratory and/or cardiovascular signs or symptoms AND involves other organ systems such as skin or GI tract, with:
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Management of anaphylaxis
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CONTACT DETAILS FOR AUSTRALIAN, STATE AND
TERRITORY GOVERNMENT HEALTH AUTHORITIES
Australian Government health authorities

Australian Government Health

State and Territory Government health authorities
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What’s new? –
Changes introduced
in this edition of
the Handbook
See Chapter 1.1
8527 AusImmun COVER 5.0 2
COMPARISON OF THE EFFECTS OF DISEASES AND THE SIDE EFFECTS OF VACCINES

DISEASE EFFECT OF DISEASE SIDE EFFECT OF VACCINE
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ADVERSE EVENTS FOLLOWING IMMUNISATION
Commonly observed adverse events following immunisation with vaccines used in the
National Immunisation Program (NIP) schedule and what to do about them
The following information can be photocopied and given as post-vaccination advice.
All the common adverse events following immunisation are usually mild and transient and treatment is not usually required. If the adverse event following
immunisation is severe or persistent, or if you are worried about yourself or your child’s condition, see your doctor or immunisation clinic nurse as soon as possible
or go to a hospital. Adverse events may be reported via ADRAC, State and Territory Health Authorities or via immunisation service providers.
Diphtheria-tetanus-pertussis (acellular) Haemophilus influenzae type b vaccine (Hib) Hepatitis A vaccine (HepA) (Indigenous Hepatitis B vaccine (HepB)
DTPa-containing vaccines and dTpa children NT, QLD, SA, WA)
(adolescent/adult) vaccines
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swelling at injection site swelling at injection site swelling at injection site swelling at injection site
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In children the following may also occur:

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generally unhappy
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Pneumococcal vaccines (conjugate Inactivated poliomyelitis vaccine Rotavirus vaccine Varicella vaccine (VV)
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site, occasionally other parts of the body
Key to table
DTPa diphtheria-tetanus-pertussis acellular (infant/child formulation) IPV inactivated poliomyelitis vaccine
dTpa diphtheria-tetanus-pertussis acellular (adolescent/adult formulation) MenCCV meningococcal C conjugate vaccine
HepA hepatitis A vaccine MMR measles-mumps-rubella vaccine
HepB hepatitis B vaccine 7vPCV 7-valent pneumococcal conjugate vaccine
Hib Haemophilus influenzaeUZQFCWBDDJOF 1310.1PS1315
23vPPV WBMFOUQOFVNPDPDDBMQPMZTBDDIBSJEFWBDDJOF
HPV human papillomavirus vaccine Rotavirus rotavirus vaccine
Influenza influenza or flu vaccine VV varicella vaccine
What to do to manage injection site discomfort

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Managing fever after immunisation

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Copyright
© Australian Government 2008
Paper-based publication
This work is copyright. Apart from any use permitted under the Copyright Act 1968, no part may
be reproduced by any process without written permission from the Commonwealth. Requests
and inquiries concerning reproduction and rights should be addressed to the Commonwealth
Copyright Administration, Attorney-General’s Department, Robert Garran Offices, National
Circuit, Canberra, ACT, 2600 or posted at: http://www.ag.gov.au/cca
ISBN 1-74186-483-6
Electronic documents
This work is copyright. You may download, display, print and reproduce this material in unaltered
form only (retaining this notice) for your personal, non-commercial use, or use within your
organisation. Apart from any use as permitted under the Copyright Act 1968, all other rights are
reserved. Requests for further authorisation should be directed to the Commonwealth Copyright
Administration, Attorney-General’s Department, Robert Garran Offices, National Circuit,
Canberra, ACT, 2600 or posted at: http://www.ag.gov.au/cca
Online ISBN: 1-74186-484-4
Publication Approval Number: 2923
Disclaimer
While every effort has been made to check drug dosage recommendations in this Handbook, it is
still possible that errors have been missed. Furthermore, dosage recommendations are continually
being revised and new adverse events recognised.
Trade names used in this publication are for identification purposes only. Their use does not
imply endorsement of any particular brand of drug or vaccine. This Handbook is a general guide
to appropriate practice subject to clinician’s judgement in each individual case. It is designed
to provide information to assist decision making using the best information available at date
of National Health and Medical Research Council approval (11 October 2007). The Australian
Government Department of Health and Ageing does not accept any liability for any injury, loss or
damage incurred by use of or reliance on the information.
The NHMRC
The National Health and Medical Research Council (NHMRC) is Australia’s leading funding body
for health and medical research. The NHMRC also provides the government, health professionals
and the community with expert and independent advice on a range of issues that directly affect
the health and well being of all Australians.
The NHMRC provided support to this project through its Guidelines Assessment Register (GAR)
process. The GAR consultant on this project was Biotext Pty Ltd. These Guidelines, apart from
Chapters 3.7 and 3.9, were approved by the Chief Executive Officer of the NHMRC under Section
14A of the National Health and Medical Research Council Act, 1992 on 17 July 2007. The remaining
two chapters were approved on 11 October 2007.
The ATAGI
The Australian Technical Advisory Group on Immunisation (ATAGI) was established by the then
Minister for Health and Family Services in 1998 to provide expert technical and scientific advice on
the Immunise Australia Program and to work cooperatively with the NHMRC on issues such as the
The Australian Immunisation Handbook.
The Handbook
This Handbook is published approximately every three years but changes to the recommendations or
schedule may occur between publications. The Handbook and any changes between publications are
available on the website: www.immunise.health.gov.au. This hardcopy version of the Handbook does
not contain any references — these are available on the electronic version.
Ninth Edition January 2008
ii The Australian Immunisation Handbook 9th Edition

PREFACE
The 9th edition of The Australian Immunisation Handbook was prepared by the
Australian Technical Advisory Group on Immunisation of the Australian Government
Department of Health and Ageing.
Members of the Australian Technical

Advisory Group on Immunisation
Chair
Professor Terry Nolan, Paediatrician and Epidemiologist and Head, School of
Population Health, The University of Melbourne, VIC.
Members
Ms Jenny Bourne, Assistant Secretary, Targeted Prevention Programs Branch,
Population Health Division, Australian Government Department of Health and
Ageing, ACT.
Ms Sue Campbell-Lloyd, Manager, Immunisation Unit, AIDS/Infectious Diseases
Branch, NSW Health, NSW.
Dr Grahame Dickson, Medical Officer, Drug Safety and Evaluation Branch,
Therapeutic Goods Administration, Australian Government Department of Health
and Ageing, ACT.
Dr Nicole Gilroy, Staff Specialist, Infectious Diseases, Westmead Hospital, Centre
for Infectious Diseases and Microbiology, Western Sydney Area Health Service, and
Infectious Diseases Physician, BMT Network, NSW.
Dr Jeffrey Hanna, Medical Director, Communicable Disease Control, Tropical
Population Health Unit, Queensland Health, QLD.
Ms Jenni Howlett, State President, Child Health Association, TAS.
Clinical Professor David Isaacs, Paediatrician, Department of Immunology and
Infectious Diseases, The Children’s Hospital at Westmead, NSW.
Ms Ann Kempe, Surveillance Manager, CCRE in Child and Adolescent Immunisation,
Murdoch Children’s Research Institute, Royal Children’s Hospital, VIC.
Dr Rosemary Lester, Assistant Director, Public Health Branch, Communicable Disease
Control Unit, Department of Human Services, VIC.
Professor Peter McIntyre, Professor of Paediatrics and Preventive Medicine, The
University of Sydney, and Director, National Centre for Immunisation Research and
Surveillance of Vaccine Preventable Diseases, The University of Sydney and The
Children’s Hospital at Westmead, NSW.
Dr Joanne Molloy, General Practitioner, Medical Officer of Health, City of Greater
Geelong, and Immunisation Program Manager, GP Association of Geelong, VIC.
Associate Professor Michael Nissen, Director of Infectious Diseases and Clinical
Microbiologist, Unit Head of Queensland Paediatric Infectious Disease Laboratory,
and Associate Professor in Biomolecular, Biomedical Science and Health, Royal
Children’s Hospital, QLD.
Preface iii
Dr Rod Pearce, General Practitioner, Medical Officer of Health, Eastern Health
Authority, Adelaide and GP Immunisation Advisor, Adelaide Central and Eastern
Division of General Practice, SA.
Dr Peter Richmond, Senior Lecturer, University of Western Australia, School of
Paediatrics and Child Health, and General Paediatrician and Paediatric Immunologist,
Princess Margaret Hospital for Children, WA.
Dr Sue Skull, Paediatrician, Clinical Epidemiologist and Public Health Physician, and
Senior Lecturer, Department of Paediatrics, The University of Melbourne, VIC.
Secretary
Ms Letitia Toms, Director, Immunisation Policy Section, Targeted Prevention Programs
Branch, Population Health Division, Australian Government Department of Health
and Ageing, ACT.
Secretariat support, Australian Technical

Advisory Group on Immunisation
Ms Brigid Dohnt, Mrs Claire Kellie, Ms Jacinta Holdway, Mr John Mohoric,
Ms Sally Warild.
Technical Editors
Dr Jane Jelfs, Immunisation Handbook and Policy Support Coordinator, National
Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases,
The University of Sydney and The Children’s Hospital at Westmead, NSW.
Dr Kristine Macartney, Senior Research Fellow, National Centre for Immunisation
Research and Surveillance of Vaccine Preventable Diseases, The University of Sydney
and The Children’s Hospital at Westmead, NSW.
Handbook Technical Support

Ms Catherine King, Information Manager, National Centre for Immunisation Research
and Surveillance of Vaccine Preventable Diseases, The University of Sydney and The
Children’s Hospital at Westmead, NSW.
Ms Donna Armstrong, Communications Officer, National Centre for Immunisation
Research and Surveillance of Vaccine Preventable Diseases, The University of Sydney
and The Children’s Hospital at Westmead, NSW.
Technical Writers
Dr Julia Brotherton, Dr Tony Gherardin, Ms Heather Gidding, Dr Kate Hale, Dr Jeffrey
Hanna, Ms Anita Heywood, Professor David Isaacs, Dr Jane Jelfs, Ms Ann Kempe,
Dr Kristine Macartney, Professor Peter McIntyre, Mr Robert Menzies, Dr Joanne
Molloy, Dr Helen Quinn, Dr Yashwant Sinha, Dr Nicholas Wood.
iv The Australian Immunisation Handbook 9th Edition

Acknowledgments
Associate Professor Ross Andrews Dr Amanda Leach
Professor Graeme Barnes Dr Julie Leask
Professor Richard Benn Professor Raina MacIntyre
Associate Professor Beverley Biggs Professor Barrie Marmion
Professor Julie Bines Dr Helen Marshall
Dr Ian Boyd Dr Brad McCall
Professor Anthony Brown Dr Treasure McGuire
Professor Margaret Burgess Ms Cathlyn McInnes
Dr Jim Buttery Dr Moira McKinnon
Professor Jonathan Carapetis Dr Jodie McVernon
Dr Louise Causer Dr Ann Mijch
Ms Patricia Coward Professor Kim Mulholland
Dr Angela Dean Dr Neil Parker
Dr Ki Douglas Ms Karen Peterson
Ms Barbara Eldred Ms Susie Prest
Mr Lloyd Ellis Professor William Rawlinson
Professor Kevin Forsyth Dr Jenny Royle
Professor Lyn Gilbert Dr Tilman Ruff
Dr Mike Gold Ms Andrea Schaffer
Dr Robert Hall Dr Rosalie Schultz
Dr Alan Hampson Dr Christine Selvey
Professor Mark Harris Dr Linda Selvey
Ms Trish Harris Ms Barbara Steadman
Dr Bronwen Harvey Dr John Sullivan
Dr Bob Kass Mr Sean Tarrant
Dr Heath Kelly Dr Diana Thomas
Dr Vicki Krause Dr Bruce Thorley
Dr Andrew Langley Dr Melanie Wong
Dr Glenda Lawrence Dr Margaret Young
Preface v
Contents
PART 1: VACCINATION PROCEDURES 1

Introduction to The Australian Immunisation Handbook 1
1.1 What’s new? 3
1.2 An overview of vaccination – preface to Chapters 1.3–1.5 7
1.3 Pre-vaccination procedures 8
1.3.1 Preparing an anaphylaxis response kit 8
1.3.2 Effective cold chain: transport, storage and handling of vaccines 8
1.3.3 Valid consent 12
1.3.4 Pre-vaccination screening 14
1.3.5 Catch-up 21
1.4 Administration of vaccines 39
1.4.1 Occupational health and safety issues 39
1.4.2 Equipment for vaccination 39
1.4.3 Route of administration 41
1.4.4 Preparation for vaccine administration 43
1.4.5 Vaccine injection techniques 44
1.4.6 Recommended injection sites 45
1.4.7 Positioning for vaccination 47
1.4.8 Identifying the injection site 51
1.4.9 Administering multiple vaccine injections at the same visit 56
1.5 Post-vaccination procedures 58
1.5.1 Immediate after-care 58
1.5.2 Adverse events following immunisation 58
1.5.3 Documentation of vaccination 66
1.5.4 The Australian Childhood Immunisation Register 67
PART 2: Vaccination for special risk groups 70

2.1 Vaccination for Aboriginal and Torres Strait Islander people 70
2.2 Vaccination for international travel 75
2.3 Groups with special vaccination requirements 84
2.3.1 Vaccination of children who have had a serious adverse event
following immunisation (AEFI) 84
2.3.2 Vaccination of women planning pregnancy, pregnant or
breastfeeding women, and preterm infants 84
2.3.3 Vaccination of individuals with impaired immunity due to disease
or treatment 90
2.3.4 Vaccination of recent recipients of normal human immunoglobulin 102
2.3.5 Vaccination of patients following receipt of other blood products
including blood transfusions 102
2.3.6 Vaccination of patients with bleeding disorders 104
2.3.7 Vaccination before or after anaesthesia/surgery 104
2.3.8 Vaccination of those at occupational risk 104
vi The Australian Immunisation Handbook 9th Edition

2.3.9 Vaccination of immigrants to Australia 108
2.3.10 Vaccination of inmates of correctional facilities 108
2.3.11 Vaccination of men who have sex with men 108
2.3.12 Vaccination of injecting drug users 109
PART 3: Vaccines listed by disease 110

3.1 Australian bat lyssavirus infection and rabies 110
3.2 Cholera 120
3.3 Diphtheria 124
3.4 Haemophilus influenzae type b (Hib) 131
3.5 Hepatitis A 139
3.6 Hepatitis B 149
3.7 Human papillomavirus 164
3.8 Immunoglobulin preparations 175
3.9 Influenza 184
3.10 Japanese encephalitis 195
3.11 Measles 201
3.12 Meningococcal disease 213
3.13 Mumps 223
3.14 Pertussis 227
3.15 Pneumococcal disease 240
3.16 Poliomyelitis 251
3.17 Q fever 257
3.18 Rotavirus 265
3.19 Rubella 274
3.20 Smallpox 283
3.21 Tetanus 288
3.22 Tuberculosis 297
3.23 Typhoid 303
3.24 Varicella 309
3.25 Yellow fever 322
3.26 Zoster (herpes zoster) 329
Contents vii
Appendix 1: Contact details for Australian, State and Territory Government
health authorities and communicable disease control 332
Appendix 2: Handbook development 334
Appendix 3: Products registered in Australia but not currently available 339
Appendix 4: Components of vaccines used in the National Immunisation
Program 340
Appendix 5: Commonly asked questions about vaccination 344
Appendix 6: Definitions of adverse events following immunisation 360
Appendix 7: Glossary of technical terms 364
Appendix 8: List of commonly used abbreviations 369
Appendix 9: Dates when vaccines became available in Australia 372
Appendix 10: Summary table – procedures for a vaccination encounter 375
Index 378
viii The Australian Immunisation Handbook 9th Edition

Index of Tables
Table 1.3.1: Pre-vaccination screening checklist 16

Table 1.3.2: Responses to relevant conditions or circumstances identified
by the pre-vaccination screening checklist 17
Table 1.3.3: Live attenuated parenteral and oral vaccines 20
Table 1.3.4: False contraindications to vaccination 21
Table 1.3.5: Number of vaccine doses that should have been administered
by the current age of the child (table to be used in conjunction
with Catch-up Worksheet) 28
Table 1.3.6: Minimum dose intervals for NIP vaccines for children <8 years
of age (table to be used in conjunction with Catch-up Worksheet) 29
Table 1.3.7: Minimum age for the first dose of vaccine in exceptional
circumstances 30
Table 1.3.8: Recommendations for Hib catch-up vaccination for children
<5 years of age when doses have been delayed or missed 33
Table 1.3.9: Recommendations for pneumococcal catch-up vaccination for
low-risk children (including Indigenous children living in ACT,
NSW, VIC and TAS) <2 years of age, when doses have been
delayed or missed 34
Indigenous children <2 years of age in NT, QLD, SA and WA,
when doses have been delayed or missed 35
children ≤5 years of age with underlying medical conditions 36
Table 1.3.12: Catch-up schedules for individuals ≥8 years of age 38
Table 1.4.1: Route of administration for vaccines commonly used in
Australia 42
Table 1.4.2: Recommended needle size, length and angle for administering
vaccines 45
Table 1.5.1: Clinical features which may assist differentiation between a
vasovagal episode and anaphylaxis 62
Table 1.5.2: Doses of intramuscular 1:1000 (one in one thousand)
adrenaline for anaphylaxis 64
Table 1.5.3: Contact details for notification of AEFI 66
Table 2.2.1: Dose and routes of administration of commonly used vaccines
in adult travellers (≥15 years of age) 80
Table 2.2.2: Recommended lower age limits of travel vaccines for children 82
Table 2.3.1: Vaccinations in pregnancy 86
Table 2.3.2: Recommendations for vaccinations for solid organ transplant
(SOT) recipients 95
Contents ix
Table 2.3.3: Post-transplantation vaccination schedules for allogeneic and
autologous haematopoietic stem cell transplant recipients 98
Table 2.3.4: Immunological categories based on age-specific CD4 counts
and percentage of total lymphocytes 99
Table 2.3.5: Recommended intervals between either immunoglobulins or
blood products and MMR, MMRV or varicella vaccination 103
Table 2.3.6: Recommended vaccinations for those at risk of occupationally
acquired vaccine-preventable diseases 105
Table 3.1.1: Summary of Australian bat lyssavirus and rabies post-
exposure treatment for non-immune individuals 117
Table 3.5.1: Recommended dosages and schedules for use of the
inactivated hepatitis A vaccines 143
Table 3.5.2: Recommended doses of normal human immunoglobulin
(NHIG) to be given as a single intramuscular injection to close
contacts of hepatitis A cases 146
Table 3.6.1: Hepatitis B and hepatitis A/hepatitis B combination
vaccination schedules 155
Table 3.6.2: Accelerated hepatitis B vaccination schedules 156
Table 3.6.3: Post-exposure prophylaxis for non-immune individuals
exposed to an HBsAg positive person 162
Table 3.9.1: Recommended doses of influenza vaccine 189
Table 3.11.1: Management of significant measles exposure using
vaccination or normal human immunoglobulin (NHIG) 212
Table 3.12.1: Early clinical management of suspected meningococcal disease 220
Table 3.14.1: Recommended antimicrobial therapy and chemoprophylaxis
regimens for pertussis in infants, children and adults 236
Table 3.15.1: Summary table – pneumococcal vaccination schedule for
children ≤9 years of age (see also Section 1.3.5, Catch-up) 245
Table 3.15.2: Underlying medical conditions predisposing children ≤9 years
of age to IPD 246
Table 3.15.3: Revaccination with 23vPPV for people ≥10 years of age 248
Table 3.17.1: Interpretation and action for serological and skin test results 261
Table 3.18.1: Age limits for dosing of oral rotavirus vaccines 269
Table 3.21.1: Guide to tetanus prophylaxis in wound management 294
Table 3.24.1: Recommendations for varicella vaccination with monovalent
VV (currently available), and once MMRV vaccines are available 313
Table 3.24.2: Zoster immunoglobulin-VF (ZIG) dose based on weight 320
Table 3.25.1: Yellow fever endemic countries 324
x The Australian Immunisation Handbook 9th Edition

Index of Figures
Figure 1.3.1: Catch-up Worksheet for children <8 years of age 27

Figure 1.4.1: The cuddle position for vaccination of a child <12 months of age 47
Figure 1.4.2: Positioning an infant on an examination table for vaccination 48
Figure 1.4.3: Positioning an older child in the cuddle position 49
Figure 1.4.4: Positioning a child in the straddle position 50
Figure 1.4.5: Diagram of the muscles of the thigh showing the anatomical
markers to identify the recommended (vastus lateralis)
injection site 52
Figure 1.4.6: Photograph of the thigh showing the recommended (vastus
lateralis) injection site 52
Figure 1.4.7: Diagram showing the anatomical markers to identify the
ventrogluteal injection site 53
Figure 1.4.8: Photograph with infant prone across carer’s lap, showing
markers to identify the ventrogluteal injection site 54
deltoid injection site 55
Figure 1.4.10: A subcutaneous injection into the deltoid area of the upper arm
using a 25 gauge, 16 mm needle, inserted at a 45° angle 55
Figure 1.4.11: Recommended technique for giving multiple vaccine injections
to an infant <12 months of age into the anterolateral thigh 56
Figure 3.4.1: aemophilus influenzae type b (Hib) notifications, presumed
H
Hib hospitalisations and deaths of children aged 0 to 4 years
from Hib, Australia 1993 to 2005 133
Figure 3.5.1: Notifications of hepatitis A in Australia, 1991 to 2006 140
Figure 3.6.1: The influence of age of infection with the hepatitis B virus on
the likelihood of becoming a hepatitis B carrier 150
Figure 3.7.1: The dynamic relationship between HPV infection and
cervical health 167
Figure 3.9.1: Influenza notification rates 2003–2005 and hospitalisation
rates 2002/2003 to 2004/2005, Australia, by age group 186
Figure 3.10.1: Map of the Torres Strait 196
Figure 3.14.1: Pertussis notifications by year of onset, Australia 1993–2005 228
Figure 3.17.1: Q fever notifications and hospitalisations, Australia, 1993 to
2005, by month of diagnosis or admission 258
Contents xi
xii The Australian Immunisation Handbook 9th Edition
PART 1: VACCINATION PROCEDURES
Introduction to The Australian

Immunisation Handbook
For more than 200 years, since Edward Jenner first demonstrated that vaccination
offered protection against smallpox, the use of vaccines has continued to
reduce the burden of many bacterial and viral diseases. As a result of successful
vaccination programs, deaths from tetanus, diphtheria, Haemophilus influenzae
type b and measles are now extremely rare in Australia.1
Vaccination not only protects individuals, but also others in the community, by
increasing the general level of immunity and minimising the spread of infection. It
is vital that healthcare professionals take every available opportunity to vaccinate
children and adults. It is also important that the public be made aware of the
proven effectiveness of immunisation to save lives and prevent serious illness.
The purpose of The Australian Immunisation Handbook is to provide clinical
guidelines for health professionals on the safest and most effective use of
vaccines in their practice. These recommendations are developed by the
Australian Technical Advisory Group on Immunisation (ATAGI) and endorsed
by the National Health and Medical Research Council (NHMRC).
The Handbook provides clinical recommendations based on the best scientific
evidence available at the time of publication from published and unpublished
literature. Further details regarding the Handbook revision procedures are
described in Appendix 2. Where specific empiric evidence was unavailable,
recommendations were formulated using the best available expert opinion
relevant to Australia. The reference lists for all chapters are included in the
electronic version of the Handbook which is available via the Immunise Australia
website (www.immunise.health.gov.au). The electronic version of the Handbook
has additional information regarding recommendations in the new vaccine
chapters, including systematic reviews of the literature.
In some instances, the NHMRC recommendations differ from vaccine product
information sheets (PI); these differences are detailed in the relevant vaccine
chapters under the heading ‘Variations from product information’. Where a
variation exists, the NHMRC recommendation should be considered best practice.
The information contained within the Handbook was correct at the time of
printing. However, the content of the Handbook is reviewed regularly. The 9th
edition of The Australian Immunisation Handbook will remain current unless
amended electronically via the Immunise Australia website or until the 10th
edition of the Handbook is published.
Introduction 1
ELECTRONIC UPDATES to the 9th edition of The Australian
Immunisation Handbook will be available at:
www.immunise.health.gov.au
References
Full reference list available on the electronic Handbook or website
http://immunise.health.gov.au.
2 The Australian Immunisation Handbook 9th Edition

1.1 What’s new?
Changes introduced in this edition of the Handbook
1.1 What’s new?

All chapters have been updated and revised where necessary. The 9th edition
introduces new vaccines, changes to the schedules, changes to recommendations
and procedures regarding the administration of vaccines, and changes to the
presentation of the Handbook. Some changes made since the publication of the
hard copy of the 8th edition of the Handbook in September 2003, and before the
9th edition, were available online on the Immunise Australia website and are not
described below.
The term Australian Standard Vaccination Schedule (ASVS) is no longer used in
the Handbook.
The National Immunisation Program (NIP) is used throughout the Handbook and
refers to funded vaccines as they appear on the National Immunisation Program
(NIP) schedule. The NIP schedule may change over time and is available via the
Immunise Australia website (www.immunise.health.gov.au).
New chapters and chapters which no

longer appear in the Handbook
• Three new chapters have been included in the Handbook – 3.7 Human
papillomavirus, 3.18 Rotavirus and 3.26 Zoster.
• There are 4 new appendices in the Handbook. These are ‘Handbook
development’ (Appendix 2); a list of vaccines which are registered in
Australia but either not currently available or no longer available in Australia
(Appendix 3); a list of major components in the vaccines in the National
Immunisation Program (Appendix 4); and a table that is a summary of
procedures for a vaccination encounter (Appendix 10).
• Two chapters have been deleted: anthrax and plague. For information about
anthrax, please go to the Australian Government website www.health.gov.au
and use the index option to select the anthrax fact sheet.
• Three chapters previously in the 8th edition, botulism, cytomegalovirus and
respiratory syncytial virus, have been incorporated into the immunoglobulin
chapter (3.8 Immunoglobulin preparations).
Overview of major changes to existing

recommendations and procedures
Part 1
• The layout of Part 1 has been altered from previous editions of the Handbook
into 3 chapters which are described in Chapter 1.2 An overview of vaccination.
The new layout applies to Chapter 1.3 Pre-vaccination procedures (including
cold chain, consent, pre-vaccination screening and catch-up); Chapter 1.4
What's new? 3
Administration of vaccines (including route, needle size and injection site); and
Chapter 1.5 Post-vaccination procedures (including adverse events following
immunisation, and the recording of vaccinations).
• Advice on preparing an anaphylaxis response kit has been added to pre-
vaccination procedures, Chapter 1.3.
• The pre-vaccination screening checklist and assessment table have been
revised and recommended steps for screening added to the section,
Chapter 1.3.
• The cold chain guidelines have been updated in Chapter 1.3 and the
recommendations summarised to reflect and reference the National Vaccine
Storage Guidelines: Strive for 5.
• The valid consent section has been redrafted and updated.
• The recommended anatomical site for intramuscular (IM) administration of
vaccines in infants <12 months of age is the anterolateral thigh.
• The recommended anatomical site for IM administration of vaccines in those
≥12 months of age is the deltoid.
• The ventrogluteal area is included as an alternative anatomical site for the
administration of vaccines at any age. This is based on published data. It is
important that vaccine providers using this site are trained in the recognition
of the relevant anatomical landmarks.
• The recommended needle size and length for IM injection is 23 or 25 gauge,
25 mm in length.
• The recommended angle of insertion of the needle for IM administration of
vaccines is 90º to the skin surface.
• Injection techniques have been described in more detail with additional
photographs and/or diagrams demonstrating positions and the
recommended anatomical sites.
• Catch-up schedules have been updated for vaccines in the National
Immunisation Program and practical tools to assist with catch-up added.
• A table of catch-up schedules for individuals aged ≥8 years has been included.
• Information on reporting of adverse events following immunisation has been
updated to reflect recent changes to the national reporting arrangements.
• Information on the Australian Childhood Immunisation Register has been
updated.
• The table previously in the 8th edition Handbook entitled ‘Information on
vaccines exposed to different temperatures’ has been deleted as some of the
information is no longer considered valid.
• Management of anaphylaxis with 1:10 000 adrenaline is no longer
recommended; use of 1:1000 adrenaline is recommended.

• Tools to photocopy include the pre-vaccination checklist, catch-up work
sheet, and Appendix 10 Summary table – procedures for a vaccination encounter.
Part 2
1.1 What’s new?

• Recommendations for groups with special vaccination requirements (Chapter
2.3) have undergone substantial revision and incorporate new tables and
separate sections for pregnant and breastfeeding women and women
planning pregnancy, preterm infants, people with impaired immunity,
oncology patients and transplant recipients.
• Recommendations for immunisation of certain occupational groups have
been expanded (Chapter 2.3).
• A comprehensive table outlining the suggested intervals between receipt
of either a blood product or an immunoglobulin-containing product and
administration of either measles, mumps, rubella or varicella vaccines is
included (Chapter 2.3).
Part 3
Chapters 3.3 Diphtheria and 3.21 Tetanus
• For adults requiring a primary course of dT, dTpa is recommended for the
first dose followed by 2 doses of dT (or dTpa only if dT is unavailable).
Chapter 3.6 Hepatitis B

• For preterm babies, recommendations for hepatitis B vaccination have been
revised.
Chapter 3.8 Immunoglobulin preparations

• Botulism, cytomegalovirus and respiratory syncytial virus are now incorporated
into this chapter.
Chapter 3.9 Influenza

• For children aged 6 months to <3 years the dose of influenza vaccine is 0.25 mL.
• It is recommended that all Aboriginal and Torres Strait Islander people aged
≥15 years receive annual influenza vaccination.
• It is recommended that children ≥6 months of age and adults with a chronic
neurological condition receive annual influenza vaccination.
Chapters 3.11 Measles, 3.13 Mumps and 3.19 Rubella

• The second dose of MMR vaccine is recommended at 18 months of age, not at
4 years of age.
• The use of MMRV vaccines, when available, is discussed.
What's new? 5
Chapter 3.12 Meningococcal disease
• Close household contacts of a case of invasive meningococcal disease should
be vaccinated as well as receiving antibiotic prophylaxis.
Chapter 3.14 Pertussis

• For adults requiring a primary course of dT, dTpa is recommended for the
first dose followed by 2 doses of dT (or dTpa only if dT is unavailable).
• A new table detailing antibiotic prophylaxis for pertussis cases and their
contacts has been included.
Chapter 3.15 Pneumococcal disease

• Children ≤9 years of age with specified underlying medical conditions should
receive 2 doses of 7-valent pneumococcal conjugate vaccine followed by a
dose of 23-valent pneumococcal polysaccharide vaccine.
• Recommendations for revaccination of adults with 23-valent pneumococcal
polysaccharide vaccine have been revised and tabulated.
Chapter 3.24 Varicella

• When combination measles, mumps, rubella and varicella vaccine/s (MMRV)
become available, it is recommended that varicella vaccination be given at
12 months of age, using MMRV.
• Administration of a second dose of varicella-containing vaccine in children
aged <14 years is recommended to minimise the risk of breakthrough disease.
Chapter 3.25 Yellow fever

• Yellow fever vaccine is now recommended for travellers (provided there are
no contraindications) going to urban and/or rural areas of endemic countries.

1.2 An overview of vaccination –
preface to Chapters 1.3–1.5
The following sections of Part 1 (Chapters 1.3–1.5) describe chronologically the

steps involved around a vaccination encounter, starting with pre-vaccination
requirements (Chapter 1.3), then administration of vaccines (Chapter 1.4) and
post-vaccination considerations (Chapter 1.5).
Chapter 1.3 describes the steps required in preparing for a vaccination encounter.
This includes preparation of an anaphylaxis response kit and effective cold
chain management (transport, storage and handling of vaccines) as described
in National Vaccine Storage Guidelines: Strive for 5. The next section discusses
obtaining valid consent and is followed by information on comprehensive
vaccination – preface
1.2 An overview of
to Chapters 1.3–1.5
pre-vaccination health screening, including a standard screening checklist and
summary tables of precautions and contraindications to vaccination. The chapter
ends with a section on how to manage catch-up vaccination. The section is
divided into two categories; the first for children <8 years of age and the second
for people ≥8 years of age.
Chapter 1.4 provides detailed sections on the administration of vaccines. This
chapter discusses occupational health and safety issues and the equipment
required for vaccination. Techniques for vaccine administration, including the
route and site of vaccine administration, positioning, identifying the vaccination
site, and methods for administering multiple vaccine injections at the same visit
are described in detail.
Chapter 1.5 provides readers with information on post-vaccination care,
including immediate after-care and the recognition and management of adverse
events following immunisation (AEFI), including anaphylaxis. There are also
sections on how to report AEFI, documentation of vaccination, and details about
the Australian Childhood Immunisation Register.
A summary of the key points discussed in these chapters is provided in the table
in Appendix 10, Summary table – procedures for a vaccination encounter. This is
suitable for photocopying for training and auditing purposes.
An overview of vaccination – preface to Chapters 1.3–1.5 7

1.3 Pre-vaccination procedures
The following sections discuss steps and procedures that should occur before a
vaccination encounter. In addition, Appendix 10, Summary table – procedures for a
vaccination encounter provides a table summarising the procedures described in
this chapter.
1.3.1 Preparing an anaphylaxis response kit

The availability of protocols, equipment and drugs necessary for the
management of anaphylaxis should be checked before each vaccination session.
An anaphylaxis response kit should be on hand at all times and should contain:
• adrenaline 1:1000 (minimum of 3 ampoules – check expiry dates),
• minimum of three 1 mL syringes and 25 mm length needles (for IM injection),
• cotton wool swabs,
• pen and paper to record time of administration of adrenaline, and
• laminated copy of Recognition and treatment of anaphylaxis (back cover of
this Handbook).
Section 1.5.2 provides details on recognition and treatment of adverse events

following immunisation.
1.3.2 Effective cold chain: transport,

storage and handling of vaccines1,2
The cold chain is the system of transporting and storing vaccines within the
temperature range of +2°C to +8°C from the place of manufacture to the point of
administration.
All immunisation service providers should be familiar with and adhere to the
National Vaccine Storage Guidelines: Strive for 5. This publication can be accessed
free of charge from http://www.immunise.health.gov.au/internet/immunise/
publishing.nsf/Content/provider-store
The National Vaccine Storage Guidelines: Strive for 5 contain specific details
on setting up the infrastructure for a vaccination service, and immunisation
service providers should refer to this to ensure that satisfactory equipment and
procedures are in place before commencing vaccination services. The Guidelines
also provide instructions on how to best transport vaccines from the main storage
facility to outreach or external clinics using a cooler.
With correct temperature monitoring and adherence to the cold chain Guidelines,
any problems in vaccine storage should be detected early and handled
appropriately before compromised vaccine is administered.

Purpose-built vaccine refrigerators (PBVR) are the preferred means of storage
for vaccines. Domestic refrigerators are designed and built for food and drink
storage, not for the special temperature needs of vaccines.
Cyclic defrost and bar refrigerators are not recommended because they produce
wide fluctuations in internal temperatures and regular internal heating.
Bar refrigerators, in particular, should not be used because of the risk of freezing,
temperature instability and susceptibility to ambient temperatures.
If the only alternative is to use a domestic refrigerator for vaccine storage,
modification of the refrigerator is essential to reduce the risk of adverse vaccine
storage events. Please refer to the cold chain Guidelines for further information.
The following checklist summarises the ongoing activities required by
immunisation service providers to ensure optimal storage of vaccines:
(a) Ensure one staff member is designated as administrator of vaccines and
vaccine storage; only one staff member should be responsible for refrigerator
thermostat controls at any one time.
(b) Name a back-up vaccine administrator, to take responsibility for vaccines in
the absence of the primary vaccine administrator.
(c) Ensure your healthcare service has a written Vaccine Management policy
and protocol which, as a minimum, should include:
• how and when to monitor and record the minimum and maximum
temperatures of the vaccine refrigerator,
• how to check the accuracy of the thermometer and/or the data logger,
1.3 Pre-vaccination
and how and when to change the thermometer battery,
procedures
• how to order and receive vaccines and rotate stock,
• how to store the vaccine, diluents and ice/gel packs correctly in the
refrigerator,
• how to maintain the refrigerator including a regimen of regular servicing,
• what steps to take if the refrigerator temperature goes outside +2°C
to +8°C, including identification of a cold chain breach, response
procedures, documentation, recording and prevention of recurrences,
• how to manage the vaccines during a power failure,
• how to pack a portable cooler properly, including correct conditioning of
ice packs/gel packs,
• training required for staff handling vaccines.
(d) Storage of all vaccines:
• Maintain refrigerator temperature between +2°C to +8°C, check and record
the current plus minimum/maximum temperatures at least daily or
immediately before vaccines are used.
Pre-vaccination procedures 9
• Twice-daily temperature checks will give a better indication of any
problems in the refrigerator’s function and temperature fluctuations over
the course of the day.
• Keep the door closed as much as possible.
• Ensure one person is responsible for adjusting refrigerator controls and
that all staff are appropriately trained to ensure continuous monitoring.
• Establish and document protocols for response to cold chain breaches.
• A vaccine storage self-audit should be undertaken by the clinic/practice
at least every 12 months.
• Most vaccines must be protected from freezing. Diluents must also be
protected from freezing, as freezing could cause tiny cracks within the wall
of the diluent container. Protect all vaccines from UV and fluorescent light.
• If vaccines have been exposed to temperatures below +2°C or above
+8°C, follow the practice protocol for response to a breach of the
cold chain. Isolate vaccines and contact the State/Territory health
authority for advice on the National Immunisation Program vaccines
and the manufacturer/supplier for privately purchased vaccines.
Recommendations for the discarding of vaccines may differ between
health authorities and manufacturers. Do not discard any vaccines until
you discuss the necessary actions.
• Perform monthly vaccine stocktake, ensure vaccines with the shortest
expiry date are stored at the front of the refrigerator, record and dispose
of vaccines that have passed the ‘expiry date’.
• Order appropriate levels of stock to ensure the refrigerator is not
overcrowded and that sufficient doses of vaccine are available until the
arrival of the next order. Monthly usage from previous years can assist
with more accurate ordering.
• Ensure all reception staff are familiar with and adhere strictly to the
practice vaccine delivery protocols, including timely unpacking of
vaccines.
• Ensure people purchasing vaccines from a pharmacy understand the
need to handle/transport the vaccines correctly.
• Minimum/maximum thermometers and/or loggers should be checked for
accuracy (calibrated) annually. Refer to manufacturer for assistance. Change
the battery in digital minimum/maximum thermometers every 12 months.
• Ensure the refrigerator is placed out of direct sunlight and the
manufacturer’s instructions for air circulation around the back and sides
are followed.
• Ensure the refrigerator is in a secure area accessible to staff only.

• Ensure the power source is marked clearly in a way to prevent the
refrigerator from being accidentally unplugged or turned off.
• During a power failure, monitor the temperature of your refrigerator.
If vaccines are at risk, use alternative storage arrangements with
appropriate monitoring.
(e) Using a purpose-built vaccine refrigerator (PBVR):
• PBVRs maintain a stable, uniform and controlled cabinet temperature
unaffected by ambient air temperature, and have a defrost cycle that
allows defrosting without rises in cabinet temperature.
• PBVRs have a standard alarm and safety feature alert and good
temperature recovery.
• Ensure that the PBVR does not constantly display minimum/maximum
and ambient temperatures. Separate minimum/maximum temperatures
must be used to monitor the refrigerator. There are some PBVRs that
require a daily data-logger download to view temperature data.
• PBVRs should alarm if temperatures outside +2°C to +8°C are reached.
• Some PBVRs have a back-plate that may vary in temperature during the
defrost cycle. Ensure vaccines are kept 4 cm from the back-plate. Check
with PBVR manufacturer to ensure that vaccines can be stored in the
bottom of the refrigerator.
• In the event of a power failure, PBVRs with glass doors will lose their
cool temperature quickly. Ensure the protocol for responding to power
1.3 Pre-vaccination
failures is up-to-date and that staff are aware of the procedures.
procedures
• Do not overstock or crowd the vaccines by overfilling the shelves. Allow
space between stock for air circulation.
• If very small amounts of vaccine are stored in a PBVR it is necessary to
add thermal mass (such as bottles of water) to the vacant space to ensure
even temperature is maintained throughout the refrigerator.
• If a chart recorder is used, the chart recorder paper must be changed
every 7 days and stored in a safe place for auditing purposes.
(f) Using a domestic refrigerator:
• Fill the lower drawers and the door with plastic bottles/containers filled
with water.
• Get to know the temperatures throughout the refrigerator by monitoring
and recording to identify any ‘cold spots’.
• Store the vaccines in an enclosed plastic container, in their original
packaging, and label the containers clearly.
• Vaccines must never be stored in the door of the refrigerator.
• Ensure each domestic refrigerator has a Celsius digital minimum/
maximum thermometer, with the thermometer probe placed inside
vaccine packaging, inside and near the back of an enclosed plastic
container. A temperature recording chart is also required.
Cold chain breaches
Do not use vaccines exposed to temperatures below +2°C or above +8°C

without obtaining further advice. Do not discard these vaccines. Isolate
vaccines and contact the State/Territory health authorities for advice on the
National Immunisation Program vaccines and the manufacturer/supplier
for privately purchased vaccines. Recommendations for the discarding of
vaccines may differ between health authorities and manufacturers. Do not
discard any vaccines until you discuss the necessary actions.
1.3.3 Valid consent

Valid consent can be defined as the voluntary agreement by an individual to a
proposed procedure, given after appropriate and reliable information about the
procedure, including the potential risks and benefits, has been conveyed to the
individual.3-7
For consent to be legally valid, the following elements must be present:8

• It must be given by a person with legal capacity, and of sufficient intellectual
capacity to understand the implications of being vaccinated.
• It must be given voluntarily.
• It can only be given after the relevant vaccine(s) and their potential risks and
benefits have been explained to the individual.
• The individual must have sufficient opportunity to seek further details or
explanations about the vaccine(s) and/or their administration.
Consent should be obtained before each vaccination, once it has been established
that there are no medical conditions that contraindicate vaccination.
Consent on behalf of a child or adolescent

In general, a parent or legal guardian of a child has the authority to consent to
vaccination of a child.3,7 A child in this context is defined as being under the age
of 18 years in all States and Territories except New South Wales, where the age
is 14 years, and in South Australia and the Northern Territory, where the age is
16 years.
If they are of sufficient age and maturity to understand the proposed procedure and
the risks and benefits associated with same, children at younger ages may be able to
provide consent for procedures such as vaccination. Please refer to your own State
or Territory immunisation service provider guidelines for more information.

Should a child or adolescent refuse vaccinations for which a parent/guardian has
given consent, the child’s wishes should be respected and the parent/guardian
informed.3
Consent on behalf of people with impaired decision-making ability

A responsible adult family member, preferably with authority to make medical
decisions, may give consent for vaccination of an adult with a significant
disability. For example, this may occur for influenza vaccination of an elderly
person with dementia.
Resources to help communicate the risks and benefits of vaccines

Plain language should be used in communicating information about vaccines
and their use to an individual. The individual must be allowed to ask for further
information and have time to make a decision about whether to consent or not.9,10
It is preferable that printed information is available to supplement any verbal
explanations.11 The summary table Comparison of the effects of diseases and the side
effects of vaccines inside the front cover of this Handbook provides some basic
information necessary to communicate the risks and benefits of vaccination. The
table can be photocopied and used freely as required.
More detailed information concerning vaccines and their use is available from the
following sources:
• www.immunise.health.gov.au
The Immunise Australia website includes ‘Common questions and answers
(fact sheets)’, ‘Understanding childhood immunisation’ and links to State
1.3 Pre-vaccination
and Territory Health Department websites. Several of these sites offer
procedures
multilingual fact sheets.
• www.ncirs.usyd.edu.au
The National Centre for Immunisation Research and Surveillance of Vaccine
Preventable Diseases website includes fact sheets related to specific vaccines,
vaccine-preventable diseases and vaccine safety.
See also Appendix 5, Commonly asked questions about vaccination.
Evidence of consent
General practice or public immunisation clinics
Consent may be given either in writing or verbally, according to the protocols
of the health facility, but it must meet the criteria for valid consent. Evidence
of verbal consent should be documented in the clinical records. If a standard
procedure is routinely followed in a practice or clinic, then a stamp, a sticker or a
provider’s signature indicating that the routine procedure has been followed, may
be used. For paperless medical records, a typed record of verbal consent may be
made in the patient’s file, or a copy of written consent scanned into the file.
Consent is often given and recorded at the first vaccination visit. Explicit verbal
consent is required before subsequent vaccinations even when written consent
has been given at previous vaccination encounters.
School-based vaccination programs
Consent is often given for the entire vaccination program and is valid for the
number of doses to be given during a school-based vaccination program.
In school-based (and other large-scale) vaccination programs, the parent or
guardian usually does not attend with the child on the day the vaccination is
given, and written consent from the parent or guardian is desirable in these
circumstances. However, if further clarification is required, verbal consent may
be sought by telephone from the parent or guardian by the immunisation service
provider. This should be clearly documented on the child’s consent form. Older
adolescents may be able to provide their own consent for vaccinations.12 However,
the vaccination program may vary between jurisdictions. Please refer to your own
State or Territory immunisation service provider guidelines for more information.
1.3.4 Pre-vaccination screening

Immunisation service providers should perform a pre-vaccination health screen
of all recipients to determine:
• if there are any contraindications or precautions to the vaccines that are to be
administered, and
• whether alternative or additional vaccines should be considered.
For some individuals, alterations to the routinely recommended vaccines may be

necessary to either eliminate or minimise the risk of adverse events, to optimise an
individual’s immune response, or to enhance the protection of a household contact
against vaccine-preventable diseases.
Such changes to the recommended vaccines may require discussion with an
immunisation expert such as the local immunisation coordinator or a medical
practitioner with expertise in vaccination.

Steps for pre-vaccination screening
A comprehensive pre-vaccination health screening is necessary to assess a
person’s medical fitness for vaccination and to determine whether a different
vaccine schedule may be recommended. Follow these steps to complete the
screening process:
1. Provide the person to be vaccinated or the parent/carer with the Pre-
vaccination screening checklist (Table 1.3.1). NB. Some of the questions in
this checklist are deliberately non-specific so as to elicit as much important
information as possible.
• The pre-vaccination screening checklist may be photocopied and handed
to the parent/carer or person to be vaccinated just before vaccination.
• It may also be photocopied and displayed in the clinic/surgery for easy
reference for the immunisation service provider.
2. When any of the conditions or circumstances are identified by using the
pre-vaccination screening checklist, refer then to Table 1.3.2 which lists the
specific issues pertaining to these conditions or circumstances and provides
the appropriate action with a rationale.
3. Where necessary, further expert advice should be sought from a medical
practitioner with expertise in vaccination, the immunisation section within
your State or Territory health authority, or your local Public Health Unit (see
Appendix 1, Contact details for Australian, State and Territory Government health
authorities and communicable disease control).
1.3 Pre-vaccination
4. No one should be denied the benefits of vaccination by withholding vaccines
for inappropriate reasons (see Table 1.3.4 False contraindications to vaccination).
procedures
Table 1.3.1: Pre-vaccination screening checklist
Pre-vaccination screening checklist

This checklist helps your doctor/nurse decide about vaccinating you or your child.
Please tell your doctor/nurse if the person about to be vaccinated:
is unwell today
has a disease which lowers immunity (eg. leukaemia, cancer, HIV/AIDS)
or is having treatment which lowers immunity (eg. oral steroid medicines
such as cortisone and prednisone, radiotherapy, chemotherapy)
has had a severe reaction following any vaccine
has any severe allergies (to anything)
has had any vaccine in the past month
has had an injection of immunoglobulin, or received any blood
products or a whole blood transfusion within the past year
is pregnant
has a past history of Guillain-Barré syndrome
was a preterm infant
has a chronic illness
has a bleeding disorder
A different vaccine schedule may be recommended if the person to be vaccinated:

identifies as an Aboriginal or Torres Strait Islander
does not have a functioning spleen
is planning a pregnancy or anticipating parenthood
is a parent, grandparent or carer of a newborn
lives with someone who has a disease which lowers immunity (eg. leukaemia, cancer,
HIV/AIDS), or lives with someone who is having treatment which lowers immunity (eg.
oral steroid medicines such as cortisone and prednisone, radiotherapy, chemotherapy)
Note: Please ask your doctor/nurse questions about this information or any
other matter relating to vaccination before the vaccines are given.
Before any vaccination takes place, the immunisation service provider will ask you:
Did you understand the information provided to you about immunisation?
Do you need more information to decide whether to proceed?
Did you bring your/your child’s vaccination record card with you?
It is important for you to receive a personal record of your or your child’s
injections. If you do not have a record, ask your immunisation service provider
to give you one. Bring this record with you every time you or your child visit
for vaccination. Make sure your doctor/nurse records all vaccinations on it.
Your child may need this record to enter childcare, preschool or school.

Conditions or circumstances identified using
the pre-vaccination screening checklist
The recommended responses for immunisation service providers to any
conditions or circumstances identified by the pre-screening checklist is
summarised in Table 1.3.2. NB. Only vaccines recommended on the National
Immunisation Program schedule are included in Table 1.3.2. For information on
other vaccines, refer to the relevant chapter within this Handbook (Part 3) or to
vaccine product information. For reference, Table 1.3.3 provides a classification of
live attenuated vaccines.
Table 1.3.2: Responses to relevant conditions or circumstances identified by the

pre-vaccination screening checklist
Condition or circumstance Action Rationale13-15
Unwell today: Defer all vaccines To avoid an adverse event
• Acute febrile illness until afebrile. in an already unwell child,
(current T ≥38.5°C). NB. Children with minor or to avoid attributing
illnesses (without acute symptoms to vaccination.
• Acute systemic illness.
systemic symptoms/signs)
should be vaccinated.
Has a disease which Seek expert advice The safety and effectiveness
lowers immunity or before vaccination of the vaccine may be
receiving treatment which (see Appendix 1). suboptimal in people with
lowers immunity. NB. People living with impaired immunity.
See Section 2.3.3, someone with lowered
Vaccination of individuals immunity should be
1.3 Pre-vaccination
with impaired immunity vaccinated, including
procedures
due to disease or treatment. with live viral vaccines.
Anaphylaxis following Do not vaccinate. Anaphylaxis to a
a previous dose of the See also ‘Contraindications previous dose of vaccine
relevant vaccine. to vaccination’ below. is a contraindication to
receiving the vaccine.
A severe (anaphylactic) Do not vaccinate (seek Anaphylaxis to a
allergy to a vaccine specialist advice as vaccine component is
component. per Appendix 1). a contraindication to
Refer to Appendix 4 See also ‘Contraindications receiving the vaccine.
for vaccine component to vaccination’ below.
checklist.
Received live parenteral Delay live vaccines The immune response to a
vaccine or BCG vaccine by 4 weeks. live viral vaccine may interfere
in past 4 weeks. with the response to a second
live viral vaccine if given
within 4 weeks of the first.
Has had any blood Make a return appointment Antibodies within these
product in the past for this vaccination, products may interfere
7 months, or has had IM and send a reminder with the immune response
or IV immunoglobulin later if necessary. to these vaccines.
in the past 11 months.
Refer to Table 2.3.5
Recommended
intervals between either
immunoglobulins or blood
products and MMR, MMRV
or varicella vaccination.
Is pregnant. Live vaccines* should be There is insufficient evidence
Refer to Table 2.3.1 deferred until after delivery. to ensure the safety of
Vaccinations in pregnancy. Conception should administering live vaccines
be deferred until at during pregnancy or within
least 28 days after 28 days before conception.
administration of live NB. Influenza vaccine
viral vaccines. Inactivated is recommended for
vaccines are generally pregnant women.
not contraindicated Vaccination of household
in pregnancy. contacts of pregnant
women should be
completed according to
the NIP schedule.
History of Guillain-Barré Risks and benefits of People with a history of
syndrome (GBS). influenza vaccine should GBS may be at risk of
See Chapter 3.9, Influenza. be weighed against the recurrence of the condition
potential risk of GBS following influenza vaccine.
recurrence (seek specialist
advice as per Appendix 1).
Was born preterm. Preterm infants born at Preterm infants may be at
See Section 2.3.2, <28 weeks’ gestation or increased risk of vaccine-
Vaccination of women <1500 g birth weight preventable diseases (eg.
planning pregnancy, require an extra dose of invasive pneumococcal
pregnant or breastfeeding PRP-OMP Hib vaccine disease (IPD)), and may not
women, and preterm infants. at 6 months of age. mount an optimal immune
Preterm infants born response to certain vaccines
at <28 weeks’ gestation (eg. hepatitis B, PRP-OMP).
and/or with chronic lung
disease require extra
pneumococcal vaccinations.
Preterm infants born at
<32 weeks’ gestation or
<2000 g birth weight may
require an extra dose of
hepatitis B vaccine.

Has a severe or These people should People with a severe or
chronic illness. receive pneumococcal chronic illness may be at
See Chapter 2.3, Groups vaccine and annual increased risk of vaccine-
with special vaccination influenza vaccination. preventable diseases (eg.
requirements. If there is significantly IPD) but may not mount an
impaired immunity, optimal immune response
they should not receive to certain vaccines.
live vaccines, but
inactivated vaccines
should be considered
(seek expert advice).
Has a bleeding disorder. The subcutaneous route Intramuscular injection
See Section 2.3.6, could be considered as may lead to haematomas
Vaccination of patients an alternative to the in patients with disorders
with bleeding disorders. intramuscular route of haemostasis.
(seek specialist advice
as per Appendix 1).
Identifies as an Aboriginal See the National Some groups of Indigenous
or Torres Strait Islander. Immunisation Program people are at increased risk
See Chapter 2.1, Vaccination Indigenous schedules. of some of the vaccine-
for Aboriginal and Torres preventable diseases.
Strait Islander people.
Does not have a Check vaccination status Individuals with an absent
functioning spleen. for pneumococcal, or dysfunctional spleen
See Section 2.3.3, meningococcal and are at an increased risk of
1.3 Pre-vaccination
Subsection 2.3.3.5, Hib vaccinations. severe bacterial infections,
Individuals with functional most notably IPD.
procedures
or anatomical asplenia.
Is planning a pregnancy or Ensure prospective parents Vaccinating before pregnancy
anticipating parenthood. have been offered vaccines may prevent maternal illness
recommended for their age- which could affect the infant,
group including 2nd dose of and may confer passive
MMR if born after 1966, and immunity to the newborn.
dTpa† (unless they have had NB. Advise women not to
a previous dose of dTpa). become pregnant within
28 days of receiving
live viral vaccines.
Is a parent, grandparent Ensure parents, People in close contact are
or carer of a newborn. grandparents and carers the most likely sources
of a newborn have been of vaccine-preventable
offered all vaccines diseases, in particular
recommended for their pertussis, in the newborn.
age-group including dTpa
(unless they have had a
previous dose of dTpa).
Lives with someone who Ensure all vaccines (in Household members are
has impaired immunity. particular MMR, varicella the most likely sources
and influenza vaccines) of vaccine-preventable
recommended for their diseases among people
age-group have been with impaired immunity
offered to household (who often are unable to
members of people with be vaccinated, especially
impaired immunity. with live viral vaccines).
* Live attenuated vaccines are classified in Table 1.3.3 below.

† See Chapter 3.3, Diphtheria, Chapter 3.14, Pertussis or Chapter 3.21, Tetanus for further
information.
Table 1.3.3: Live attenuated parenteral and oral vaccines

Live attenuated parenteral vaccines Live attenuated oral vaccines
Viral Bacterial Viral Bacterial
MMR BCG Oral rotavirus vaccine Oral typhoid vaccine
MMRV
Varicella vaccine (VV)
Monovalent
rubella vaccine
Yellow fever
Contraindications to vaccination
There are only 2 absolute contraindications applicable to all vaccines:
(i) anaphylaxis following a previous dose of the relevant vaccine, and
(ii) anaphylaxis following any component of the relevant vaccine.
There are 2 further contraindications applicable to live (both parenteral and

oral) vaccines:
(iii) Live vaccines should not be administered to individuals with impaired
immunity, regardless of whether the impairment is caused by disease
or treatment. The exception is that, with specialist advice, MMR can be
administered to HIV-infected individuals in whom impaired immunity
is mild. (See Section 2.3.3, Vaccination of individuals with impaired immunity
due to disease or treatment, and individual vaccine chapters.)
(iv) In general, live vaccines should not be administered during pregnancy,
and women should be advised not to become pregnant within 4 weeks of
receiving a live vaccine (see Table 2.3.1 Vaccinations in pregnancy).

False contraindications to vaccination
Conditions listed in Table 1.3.4 below are not contraindications to vaccination.
People with these conditions should be vaccinated with all recommended
vaccines.
Table 1.3.4: False contraindications to vaccination
The following conditions are not contraindications to any of the

vaccines in the National Immunisation Program schedule:
• mild illness without fever (T <38.5°C),
• family history of any adverse events following immunisation,
• past history of convulsions,
• treatment with antibiotics,
• treatment with locally acting (inhaled or low-dose topical) steroids,
• replacement corticosteroids,
• asthma, eczema, atopy, hay fever or ‘snuffles’,
• previous pertussis-like illness, measles, rubella, mumps or meningococcal disease,
• prematurity (vaccination should not be postponed),
• history of neonatal jaundice,
• low weight in an otherwise healthy child,
• any neurological conditions including cerebral palsy and Down syndrome,
• contact with an infectious disease,
• child’s mother is pregnant,
1.3 Pre-vaccination
• child to be vaccinated is being breastfed,
• woman to be vaccinated is breastfeeding,
procedures
• recent or imminent surgery,
• poorly documented vaccination history.
1.3.5 Catch-up
Every opportunity should be taken to review an individual’s vaccination history
and, based on documentation, administer the appropriate vaccine(s). If the
individual has not received vaccines scheduled in the National Immunisation
Program appropriate for his/her age, plan and document a catch-up schedule and
discuss this with the individual. The assessment of vaccination status should be
based on the schedule for the State/Territory in which the individual is residing.
The objective of catch-up vaccination is to complete a course of vaccination and
provide optimal protection as quickly as possible. The information and tables
below will assist in planning a catch-up schedule. If the immunisation service
provider is still uncertain about how to plan the catch-up schedule, expert advice
should be sought (see Appendix 1, Contact details for Australian, State and Territory
Government health authorities and communicable disease control).
An on-line ‘catch-up calculator’ is available at
www.health.sa.gov.au/immunisationcalculator
This calculator is regularly updated for all catch-up scenarios relevant to the
NIP. For non-NIP vaccines or complicated catch-up scenarios, expert advice
should be sought (see Appendix 1, Contact details for Australian, State and
Territory Government health authorities and communicable disease control).
To calculate a catch-up schedule, the on-line calculator requires the child’s date
of birth, State of residence, past vaccination history and Indigenous status.
The calculator can be used for children ≤7 years of age (the age up to which
vaccinations will be recorded on the ACIR) and can calculate catch-up schedules
for children from all States and Territories. For recently arrived immigrants,
the World Health Organization web site www.who.int/countries/en lists an
immunisation schedule (where provided by that particular country) and may
supplement information regarding which vaccines a child/adult may have
received (see also Section 2.3.9, Vaccination of immigrants to Australia).
Alternatively, the instructions and guidelines below will assist in the manual
calculation of a catch-up schedule.
Determining a vaccination history

Individuals with incomplete vaccination records
The most important requirement for assessment of vaccination status is to have
written documentation of vaccination. The approach of providers to the problem
of inadequate records should be based on the age of the individual, whether
previous vaccines have been given in Australia or overseas, and the vaccines
being considered for catch-up.
Vaccines given from 1 January 1996

The Australian Childhood Immunisation Register (ACIR) commenced on 1
January 1996 and all vaccinations given to children since then should be available
from the ACIR. If the parent states that vaccines not recorded on the ACIR have
been given, every effort should be made to contact the relevant immunisation
service provider. If confirmation from the nominated provider or the ACIR
cannot be obtained, and no written records are available, the vaccines should be
considered as not received, and the child should be offered a catch-up course of
vaccination appropriate for age (see Section 1.3.5). Parents can obtain an ACIR
Immunisation History Statement from Medicare (see Section 1.5.4).
Older children and adolescents <18 years of age

No vaccination information is recorded on the ACIR after a child turns 7 years
of age, but any information already held is retained. The information will relate
only to vaccines received between birth and the 7th birthday. The ACIR Enquiry
Line can be contacted on 1800 653 809 and any record held for an individual who

is ≥7 years of age can be made available to an immunisation service provider or
parent/carer.
In older children and adolescents, alternative sources of documentation (such
as personal health records) will be needed, but are less likely to be available
with increasing age. Individuals who do not have personal vaccination records
may seek evidence of past vaccination from their parents, their past and present
healthcare providers or immunisation service providers, including Local
Government immunisation service providers. Those born after 1990 may have
some vaccinations recorded on the ACIR (see Section 1.5.4).
For most vaccines, there are no adverse events associated with additional doses
in immune individuals. In the case of diphtheria and tetanus vaccines, additional
doses may occasionally be associated with an increase in local adverse events
in immune individuals (see Chapter 3.3, Diphtheria, Chapter 3.14, Pertussis or
Chapter 3.21, Tetanus). However, the benefits of protection against pertussis are
likely to outweigh the risk of an adverse reaction.
Adults (≥18 years of age)

In adults, written documentation of previous vaccination history may not be
available. It is important, however, to seek information of any previous doses
of diphtheria and tetanus vaccines, and of pneumococcal polysaccharide
vaccination in the previous 5 years, as increased local reactions may occasionally
occur in immune individuals (see Chapter 3.3, Diphtheria, Chapter 3.15,
Pneumococcal disease or Chapter 3.21, Tetanus). Additional doses of MMR,
varicella, IPV or hepatitis B vaccine are rarely associated with significant adverse
1.3 Pre-vaccination
events in adults.
procedures
Guidelines for planning catch-up vaccination
There are a number of tables in this section which are designed to help plan a
catch-up schedule if not using the on-line calculator.
• Figure 1.3.1 is a worksheet for calculating and recording which vaccines are
required, the number of doses outstanding and the timing of these doses.
• Table 1.3.5 can be used to assess the number of doses a child would have
received if they were on schedule. Check under the current age of the child
to see how many doses they should have already received and use that
number of doses as the starting point for calculating a catch-up schedule. For
example, a child who is 18 months old now should have received 3 doses of
DTPa, 3 doses of IPV etc.
• Table 1.3.6 lists the minimum interval between doses.
• Tables 1.3.8–1.3.11 are for calculating catch-up for Hib and pneumococcal
vaccination.
If documentation cannot be produced, assume that the vaccine has not been given
previously, unless contact can be made with the immunisation service provider.
• Vaccine doses should not be administered at less than the recommended
minimum interval16 (see Table 1.3.6).
• In exceptional circumstances, where early vaccination is required, Table 1.3.7
indicates the minimum age that the first dose of a vaccine may be given.
• Doses administered earlier than the minimum interval should not be
considered as valid doses and should be repeated as appropriate using
Table 1.3.5.
• When commencing the catch-up schedule, the standard scheduled interval
between doses may be reduced or extended, and the numbers of doses
required may reduce with age. For example, from 15 months of age, only 1
dose of (any) Hib vaccine is required.
• As a child gets older, the recommended number of vaccine doses may change
(or even be omitted from the schedule), as the child becomes less vulnerable
to specific diseases.
• For incomplete or overdue vaccinations, build on the previous documented
doses.
Never start the schedule again, regardless of the interval since the last dose.
• If more than 1 vaccine is overdue, 1 dose of each due or overdue vaccine

should be given now. Further required doses should be scheduled after the
appropriate minimum interval (see Table 1.3.6).
• A catch-up schedule may require multiple vaccinations at a visit. Give all the
due vaccines at the same visit – do not defer. See Section 1.4.9 for procedures
for administering multiple injections at the same visit.
• The standard intervals and ages recommended in the NIP schedule should be
used once the child or adult is up-to-date with the schedule.
• Some individuals will require further doses of antigens that are available only
in combination vaccines. In general, the use of the combination vaccine(s)
is acceptable, even if this means the number of doses of another antigen
administered exceeds the required number.
• If different Hib vaccines are inadvertently used in the primary series, then
3 doses (of any Hib vaccine) are required at 2, 4 and 6 months of age, with a
booster at 12 months of age (see Chapter 3.4, Haemophilus influenzae type b).
NB. Routine rotavirus vaccine ‘catch-up’ of older children is not recommended.

Infants should commence the course of rotavirus vaccination within the
recommended age limits for the first dose. It is also necessary to ensure that
doses are not given beyond the upper age limits for the final dose of the vaccine
course (see Chapter 3.18, Rotavirus).

Interruption to a vaccination
• If the process of administration of a vaccine given parenterally (IM or SC) is
interrupted (eg. by syringe-needle disconnection) the whole dose should be
repeated as soon as practicable.
• If an infant regurgitates or vomits part of a dose of oral rotavirus vaccine,
it is not necessary to repeat the dose. Therefore, the regurgitated (and
incomplete volume) dose is still considered as the valid dose (see Chapter
3.18, Rotavirus).
Determining a catch-up schedule for children <8 years of age

A catch-up schedule for a child <8 years of age should be planned by taking into
account the guidelines above and using Table 1.3.5. The Catch-up Worksheet
(Figure 1.3.1) provides a method of recording these steps. All catch-up vaccines
administered to children aged <7 years should be reported as soon as is
practicable to the ACIR.
Using the Catch-up Worksheet

1. Record the child’s details including date of birth and current age in the top
left corner of the worksheet.
2. For each vaccine, determine how many doses have been received and the
date that the last dose was given. Record this on the worksheet.
3. Refer to Table 1.3.5 to check how many doses of each vaccine are required for
the child’s current age. Enter this number in the appropriate column of the
worksheet.
1.3 Pre-vaccination
4. Assess other factors that may affect the type or number of vaccines required,
procedures
including:
• anaphylaxis to any vaccine or one of its components (that vaccine is
contraindicated),
• impaired immunity due to disease or treatment (see Chapter 2.3, Groups
with special vaccination requirements),
• identifying as an Aboriginal or Torres Strait Islander (see Chapter 2.1,
Vaccination for Aboriginal and Torres Strait Islander people),
• children with an underlying medical risk condition which predisposes
them to invasive pneumococcal disease (see Chapter 3.15, Pneumococcal
disease),
• a reliable history of previous varicella infection (varicella vaccine not
required), and
• babies born at <32 weeks’ gestation (see Hib vaccine and hepatitis B vaccine
catch-up below).
Record any relevant factor in the ‘comments’ column beside the relevant
vaccine.
5. If any variations to the schedule are necessary due to recorded factors (eg.
a child with impaired immunity may require different vaccines), adjust the
‘number of doses required’ accordingly.
6. For each vaccine, compare the ‘last dose given’ with the number required for
the child’s current age.
7. If the child has already received the number of doses required, the relevant
‘dose number due now’ and ‘further doses’ cells should be crossed through.
8. If the number of the ‘last dose given’ is less than the number required, a dose
of the relevant vaccine should be administered now, and recorded in the
‘dose number due now’ cell. If this dose still does not complete the required
doses, enter the further dose numbers in the ‘further doses’ cell.
9. Refer to Table 1.3.6 to determine the recommended minimum intervals
required between doses and record in the relevant ‘further doses’ cells.
10. Convert this information into a list of proposed appointment dates, detailing
vaccines and dose number needed at each visit on the Catch-up Worksheet.
11. Record this catch-up schedule in your provider records and provide a copy to
the parent/carer.

Figure 1.3.1: Catch-up Worksheet for children <8 years of age
CATCH-UP WORKSHEET
Name: Last dose Number Dose Further Comments
given of doses number doses
Dose required due now Interval
DOB: number at current or date
and date age*
Age:
DTPa
Poliomyelitis
(IPV)
Hepatitis A
Hepatitis B
Hib
7vPCV &
23vPPV
MenCCV
MMR
Rotavirus DO NOT give after
upper age limits
for each dose.
1.3 Pre-vaccination
See Table 3.18.1.
Varicella
procedures
CATCH-UP APPOINTMENTS
Date Vaccines Interval to next dose Comments
& Dose
number
* See step 5 ‘Using the Catch-up Worksheet’ above.
Table 1.3.5: Number of vaccine doses that should have been administered by
the current age of the child (table to be used in conjunction with Catch-up
Worksheet)
VACCINE CURRENT AGE

0–<2mo 2–<4mo 4–<6mo 6–<12mo 12–18mo >18mo–<4yr 4yr–<8yr
DTPa* 1 2 3 3 3 4
Poliomyelitis
1 2 3 3 3 4†
(IPV)
Hepatitis A‡ 1‡ 2‡ 2‡
Hepatitis B birth
dose 2 3 4 4 4 4
given§
birth
dose not 1 2 3^ 3 3 3
given
Hib Complex – see Table 1.3.8 for Hib vaccine catch-up
7vPCV & Complex – see Tables 1.3.9, 1.3.10 and 1.3.11
23vPPV for pneumococcal vaccine catch-up
MenCCV 1 1 1
MMR 1 2 2
Rotavirus# There are specific age
limits as per Chapter 3.18, NO CATCH-UP
Rotavirus, Table 3.18.1.
Varicella 1 1
* Some children may have received 4 doses of DTP by 18 months of age, especially if moved
from overseas. These children will require a 5th dose of DTPa at 4 years of age.
† If the 3rd dose of IPV is given after 4 years of age, a 4th dose is not required. However, if
using a combination vaccine it is acceptable to receive a 4th dose.
‡ Indigenous children resident in NT, QLD, SA and WA only. Dependent on jurisdiction,
the 1st dose is given at 12–18 months of age followed by the 2nd dose 6 months later at
18–24 months of age. Consult relevant State/Territory authorities for advice regarding
catch-up in children older than 2 years of age.
§ Birth dose should be given within 7 days of birth. Although a birth dose of hepatitis B
vaccine is recommended for all infants, a catch-up dose is not necessary if it was not given.
Even if the birth dose was given, a further 3 doses of hepatitis B vaccine are required.
^ Some States/Territories schedule a 3rd dose (or the 4th dose) of hepatitis B vaccine at
6 months of age rather than 12 months.
# There is no catch-up for rotavirus vaccine (see Chapter 3.18, Rotavirus).

Table 1.3.6: Minimum dose intervals for NIP vaccines for children <8 years of
age (table to be used in conjunction with Catch-up Worksheet)
Vaccine Minimum Minimum Minimum

interval interval interval
between dose between dose between dose
1&2 2&3 3&4
DTPa* 4 weeks 4 weeks 6 months
Poliomyelitis (IPV) 4 weeks 4 weeks 4 weeks†
Hepatitis A 6 months
(Indigenous children in NT,
QLD, SA & WA only)
Hepatitis B
If first dose given at birth 4 weeks 8 weeks 8 weeks
or at ≤7 days after birth‡
If first dose is not given at birth 4 weeks 8 weeks
or at >7 days after birth§
Hib (PRP-OMP) See Table 1.3.8 Hib vaccine catch-up
Hib (PRP-T)
Pneumococcal (7vPCV) See Tables 1.3.9, 1.3.10, 1.3.11
Pneumococcal vaccine catch-up
MenCCV^
MMR# 4 weeks
1.3 Pre-vaccination
Rotavirus** Rotarix 4 weeks
procedures
RotaTeq 4 weeks 4 weeks
Varicella 4 weeks
* If DTPa is only available in combination with other antigens (eg. DTPa-IPV, DTPa-hepB-
IPV-Hib or DTPa-HepB-IPV), these formulations can be used where necessary for primary
course or catch-up doses in children <8 years of age.
† If the 3rd dose of IPV is given after 4 years of age, a 4th dose is not required. However, if
using a combination vaccine, it is acceptable to receive a 4th dose.
‡ If dose given at birth or within 7 days of birth (considered dose 1 for this table), then 3
subsequent doses should be given.
§ If dose 1 is not given at birth or within 7 days of birth, then it should be given at 2 months
of age, followed by a further 2 doses.
^ The schedule is a single dose given at 12 months of age. Alternative schedules are available
for children <12 months of age (see Chapter 3.12, Meningococcal disease).
# MMR vaccine may be given from 9 months of age if in contact with case, but dose must be
repeated at 12 months of age.
** Consult Chapter 3.18, Rotavirus, Table 3.18.1 for upper age limits for administration of
rotavirus vaccines. Catch-up is not recommended.
Table 1.3.7: Minimum age for the first dose of vaccine in exceptional
circumstances*
Vaccine Minimum age for first Minimum age accepted as

dose in exceptional valid by ACIR
circumstances
DTPa 6 weeks 6 weeks
Poliomyelitis (IPV) 6 weeks 6 weeks
Hepatitis A 12 months 12 months
(Indigenous children in
NT, QLD, SA & WA only)
Hepatitis B 6 weeks 6 weeks
Hib (PRP-OMP) 6 weeks 6 weeks
Hib (PRP-T) 6 weeks 6 weeks
MenCCV 6 weeks† 12 months
MMR 9 months ‡
11 months
Pneumococcal (7vPCV) 6 weeks 6 weeks
Rotavirus 6 weeks not stated
Varicella 9 months§ (Varilrix) not stated
12 months^ (Varivax)
* Exceptional circumstances may include infants/children being vaccinated before overseas

travel, or opportunistic vaccination following early attendance to a provider. These ages
may differ from routinely recommended ages of administration under the NIP.
† If 2 doses of MenCCV are given before 12 months of age, then a booster dose should be
given at 12 months of age (see Chapter 3.12, Meningococcal disease).
‡ MMR vaccine may be given from 9 months of age if in contact with case, but dose must be
repeated at 12 months of age.
§ If a child receives varicella vaccine at <12 months of age, a further dose should be given at
18 months of age.
^ Receipt of at least 1 dose of varicella vaccine is recommended from 12 months of age.

Catch-up guidelines for individual vaccines
• DTPa
Monovalent pertussis vaccine is not available in Australia. If a child has
received previous doses of DT and requires pertussis catch-up, then DTPa or
DTPa-combination vaccines can be used provided that no more than 6 doses of
diphtheria and tetanus toxoids are given before the 8th birthday.
NB. If no birth dose of hepatitis B vaccine was given, and a DTPa-hepatitis
B-containing combination vaccine is used, there should be a minimum interval of
8 weeks between doses 2 and 3.
• Hepatitis B vaccine
If the infant received the birth dose of hepatitis B vaccine, catch-up doses can be
given 4–8 weeks apart.
If the infant did not receive the birth dose, a catch-up of this dose is not
necessary. In this circumstance, hepatitis B vaccination should commence at
2 months of age. There should be a minimum interval of 8 weeks between doses 2
and 3.
In preterm babies under 32 weeks’ gestation at birth or <2000 g birth weight, it
is recommended to give hepatitis B vaccine at 0, 2, 4 and 6 months of age, and
either:
(a) measure anti-HBs at 7 months of age and give a booster at 12 months of age if
antibody titre is <10 mIU/mL, or
(b) give a booster at 12 months of age without measuring the antibody titre.
1.3 Pre-vaccination
(See also Section 2.3.2, Vaccination of women planning pregnancy, pregnant or
procedures
breastfeeding women, and preterm infants and Chapter 3.6, Hepatitis B).
• Hib vaccine
The recommended number of doses and recommended intervals of Hib vaccines
vary with the vaccine type and with the age of the child (see Table 1.3.8). PRP-
OMP is the Hib formulation contained in Liquid PedvaxHIB and COMVAX.
PRP-T is the Hib formulation contained in Hiberix and Infanrix hexa.
Where possible, the same brand of Hib vaccine should be used for all doses. If
different Hib vaccines are used in the primary series, then 3 doses (of any Hib
vaccine) are required at 2, 4 and 6 months of age, with a booster at 12 months of
age. Only 1 dose (of any Hib vaccine) is required after 15 months of age.
When PRP-OMP is used in an extremely preterm baby (<28 weeks’ gestation
or <1500 g birth weight), an additional dose should be given at 6 months of
age, ie. doses should be given at 2, 4, 6 and 12 months of age (see Section 2.3.2,
Vaccination of women planning pregnancy, pregnant or breastfeeding women, and
preterm infants).
• MMR vaccine
If no previous documented doses have been given, catch-up for MMR consists of
2 doses given at least 4 weeks apart.
• MenCCV
MenCCV is recommended on the NIP for children at 12 months of age. If no
dose was received at ≥12 months of age or if all doses have been received at
<12 months of age, a single dose of any meningococcal conjugate vaccine is
recommended (see Chapter 3.12, Meningococcal disease).
• 7vPCV
The number of doses and recommended intervals of 7vPCV for catch-up vary
with the age of the child, health and Indigenous status of the child, as well as the
State/Territory of residence (see Tables 1.3.9, 1.3.10 and 1.3.11 below).
Low-risk children (including all Indigenous children) aged ≥2 years of age do not
require catch-up.
If <2 years of age at presentation, use Table 1.3.9 for low-risk children (including
Indigenous children living in the Australian Capital Territory, New South Wales,
Victoria and Tasmania) and Table 1.3.10 for Indigenous children residing in the
Northern Territory, Queensland, South Australia and Western Australia. Table
1.3.11 provides catch-up details for children aged ≤5 years with an underlying
medical condition. Please also refer to Chapter 3.15, Pneumococcal disease for
further details.
• Poliomyelitis vaccine
If no previous documented doses of poliomyelitis vaccine have been given, give
3 doses of IPV or IPV-containing vaccines at least 4 weeks apart. (Previous doses
of OPV are interchangeable with IPV.)
If the third dose of IPV is administered before 4 years of age, give the fourth
(booster) dose at either the 4th birthday or 4 weeks after the third dose, whichever
is later. If the third dose is given after the 4th birthday, a fourth dose is not
required. However, if the use of combination vaccines is necessary, a further IPV-
containing dose may be given.
• Rotavirus vaccine
recommended age limits for the first dose, that is by either 12 or 14 weeks of age
depending on the vaccine to be used. It is recommended that vaccine doses are
not given beyond the upper age limits specified in Table 3.18.1, Chapter 3.18,
Rotavirus.
• Varicella vaccine
If a child receives varicella vaccine at <12 months of age, a further dose should be
given at 18 months of age.

Table 1.3.8: Recommendations for Hib catch-up vaccination for children
<5 years of age when doses have been delayed or missed
Previous Age at Type 1st dose 2nd dose 3rd dose Booster dose
vaccination presentation of Hib
history vaccine to
be used
0 doses 3–6 months PRP-OMP Give now 1 month Not needed 12 months of age
later
PRP-T Give now 1 month 1–2 months 12 months of age

later later
7–11 months PRP-OMP Give now 2 months Not needed 12 months of

later age or 2 months
after 2nd dose
(whichever is
later)
PRP-T Give now 2 months Not needed 12 months of

later age or 2 months
after 2nd dose
(whichever is
later)
12–14 months PRP-OMP Give now Not needed Not needed 2 months later
PRP-T Give now Not needed Not needed 18 months of age
15–59 months PRP-OMP Give now Not needed Not needed Not needed
or PRP-T
1 previous 3–6 months PRP-OMP PRP-OMP Give now Not needed 12 months of age
dose (given at previously
least 4 weeks given
1.3 Pre-vaccination
previously)
PRP-T Either Give now 1–2 months 12 months of age
procedures
PRP-OMP later
or PRP-T
previously
given
7–14 months PRP-OMP Previously Give now Not needed 12 months of

or PRP-T given age or 2 months
after 2nd dose
(whichever is
later)
15–59 months PRP-OMP Previously Not needed Not needed Give now*
or PRP-T given
2 previous 12–59 months PRP-OMP Previously Previously Not needed At least 2

doses of PRP- or PRP-T given given months after last
OMP dose*
2 previous 7–14 months PRP-OMP Previously Previously At least 1 12–18 months

doses of or PRP-T given given month after of age, at least
PRP-T (or last dose 2 months after
1 of each of last dose
PRP-OMP
and PRP-T) 15–59 months PRP-OMP Previously Previously Not needed At least 2
or PRP-T given given months after last
dose*
*A booster dose is not needed if the last previous dose was given at >15 months of age.
Table 1.3.9: Recommendations for pneumococcal catch-up vaccination for low-
risk children (including Indigenous children living in ACT, NSW, VIC and
TAS) <2 years of age, when doses have been delayed or missed
CATEGORY Previous doses Age at 1st dose 2nd dose 3rd dose
of 7vPCV presentation 7vPCV 7vPCV 7vPCV
All non- None 3–6 months Give now 1 month later 1–2 months

Indigenous later*
children
7–17 months Give now 1–2 months Not needed
and later*
Indigenous 18–23 months Give now Not needed Not needed

children living in
1 previous 5–11 months Previously Give now 1–2 months
ACT, NSW, VIC
dose (given at given later*
and TAS
least 4 weeks
previously) 12–23 months Previously Give now Not needed
given
2 doses 7–11 months Previously Previously Give now

given given
12–23 months Previously Previously Not needed

given given
* Catch-up doses of 7vPCV can be given a minimum of 1 month apart to infants aged
<12 months. For children aged ≥12 months, there should be a 2 month interval between
doses of 7vPCV.

Indigenous children <2 years of age in NT, QLD, SA and WA, when doses have
been delayed or missed
CATEGORY Previous Age at 1st dose 2nd dose 3rd dose 23vPPV*
doses of presentation 7vPCV 7vPCV 7vPCV
7vPCV
Indigenous None 3–6 months Give now 1 month 1–2 18–24 months of age
children living later months
in NT, QLD, later†
SA and WA
7–17 months Give now 1–2 Not 18–24 months of age
months needed or 2 months after
later† 2nd dose of 7vPCV
(whichever is later)
18–23 months Give now Not Not 18–24 months of age

needed needed or 2 months after
1st dose of 7vPCV
1 dose 5–11 months Previously Give now 1–2 18–24 months of age
(given given months
at least later†
4 weeks
previously) 12–23 months Previously Give now Not 18–24 months of age
given needed or 2 months after
2nd dose of 7vPCV
2 doses 7–11 months Previously Previously Give now 18–24 months of age
given given
12–23 months Previously Previously Not 18–24 months of age

given given needed or 2 months after
1.3 Pre-vaccination
2nd dose of 7vPCV
procedures
* The timing of 23vPPV varies between States and Territories. Contact your State or Territory
health authority for the appropriate timing.
† Catch-up doses of 7vPCV can be given a minimum of 1 month apart to infants aged
<12 months. For children aged ≥12 months, there should be a 2 month interval between
doses of 7vPCV.
Table 1.3.11: Recommendations for pneumococcal catch-up vaccination for children ≤5 years of age* with underlying medical conditions
CATEGORY Previous Age at 1st dose 2nd dose 3rd dose Booster dose 7vPCV 23vPPV
doses of presentation 7vPCV 7vPCV 7vPCV
7vPCV
None 3–6 months Give now 1 month 1–2 12 months of age 4–5 years of age
later months
later†
7–11 months Give now 1–2 Not 12 months of age or 2 months after 2nd 4–5 years of age
months needed dose of 7vPCV (whichever is later)
later†
12–59 months Give now 2 months Not Not needed 4–5 years of age or 2 months after 2nd
later needed dose of 7vPCV (whichever is later)
Children ≤5 1 dose 5–6 months Previously Give now 1 month 12 months of age 4–5 years of age
years of age given later
with underlying
7–11 months Previously Give now Not 12 months of age or 2 months after 2nd 4–5 years of age
medical
given needed dose of 7vPCV (whichever is later)
conditions
12–59 months Previously Give now Not Not needed 4–5 years of age or 2 months after 2nd
given needed dose of 7vPCV (whichever is later)

2 doses 7–11 months Previously Previously Give now 12 months of age or 2 months after 3rd 4–5 years of age
given given dose of 7vPCV (whichever is later)
12–59 months Previously Previously Give now Not needed 4–5 years of age or 2 months after 3rd dose
given given of 7vPCV (whichever is later)
3 doses 12–59 months Previously Previously Previously Give now 4–5 years of age or 2 months after booster
given given given dose of 7vPCV (whichever is later)
* Children up to the age of 10 years who, after the 6th birthday, develop asplenia, HIV infection, or a haematological malignancy, or who receive a transplant,
should receive 2 doses of 7vPCV 2 months apart, and a dose of 23vPPV 2 months later. If these children need catch-up doses of 7vPCV, the recommendations
are the same as for the 12–59 month age-group in Table 1.3.11, with a dose of 23vPPV 2 months after the last dose of 7vPCV. See Chapter 3.15, Pneumococcal
disease recommendations and Table 3.15.1
† Catch-up doses of 7vPCV can be given a minimum of 1 month apart to infants aged <12 months. For children aged ≥12 months, there should be
a 2 month interval between doses of 7vPCV.
Catch-up schedules for children ≥8 years
of age, adolescents and adults
Catch-up is much less commonly required for these age groups than for young
children. Nevertheless, issues surrounding booster doses or revaccinations are
common, particularly in adults. People who escaped natural infection as children
and were not vaccinated remain at unnecessary risk of vaccine-preventable
diseases.
If a vaccine course is incomplete, never start the course again, regardless of the
interval since the last dose.
Recommendations on vaccination for adults at occupational risk or in a
special risk group can be found in Chapter 2.3, Groups with special vaccination
requirements.
Use Table 1.3.12 to determine:
• how many doses of a particular vaccine a person should have received to be
considered completely vaccinated (column 2: Doses required),
• deduct any previous doses of the vaccine from that number, and
• go to the appropriate minimum interval column.
For example, a 32-year-old woman who has received only 1 dose of hepatitis B
vaccine, 4 doses of the oral poliomyelitis vaccine, 1 dose of MMR vaccine and 2
doses of DTPw as a child, would require:
• 2 adult doses of hepatitis B, 1 dose given now and a further dose in 8 weeks,
• 1 dose of dT (preferably given as dTpa),
1.3 Pre-vaccination
• no further doses of poliomyelitis vaccine (is fully vaccinated against
procedures
poliomyelitis),
• varicella vaccine if non-immune,
• 1 dose of MMR vaccine.
Where several vaccines are required, eg. dTpa, hepatitis B and poliomyelitis
vaccines, never use the available childhood combination vaccines as the antigen
content differs and may result in a severe adverse event. The childhood
combination vaccines are not registered for use in children aged ≥8 years,
adolescents or adults.
Table 1.3.12: Catch-up schedules for individuals ≥8 years of age
Vaccine Doses required Minimum interval Minimum interval

between Dose 1 between Dose 2
&2 &3
dT (dTpa*) 3 doses 4 weeks 4 weeks
Hepatitis B Aged 3 paediatric doses 4 weeks 8 weeks
8–19 years
Hepatitis B Aged 2 adult doses 4–6 months Not required
11–15 years
only
Hepatitis B Aged 3 adult doses 4 weeks 8 weeks
≥20 years
IPV 3 doses 4 weeks 4 weeks
Human papillomavirus 3 doses 4 weeks 3 months
(females aged
10–26 years only)
MMR 2 doses 4 weeks Not required
Varicella vaccine† At least 1 dose if If 2nd dose given, Not required
aged <14 years a 4 week interval
is required
2 doses if aged 4 weeks Not required
≥14 years
* One of the doses should be given as dTpa (or dTpa-IPV if poliomyelitis vaccination is also
needed) and complete the course with dT. In the unlikely event that dT is not available,
dTpa or dTpa-IPV may be used for all 3 primary doses but this is not routinely recommended as
there are no data on the safety, immunogenicity or efficacy of dTpa for primary vaccination (see also
Chapter 3.14, Pertussis).
† Varicella vaccine should be given to either non-immune people or people with no history
of previous varicella infection. At least 1 dose should be given to those aged <14 years, and
all must receive 2 doses if aged ≥14 years.
References

1.4 Administration of vaccines
1.4.1 Occupational health and safety issues

Standard occupational health and safety guidelines should always be followed
during a vaccination encounter to minimise the risk of needle-stick injury.1
Gloves are not routinely recommended for immunisation service providers. Work
practices should include the use of standard precautions to minimise exposure
to blood and body fluids. If exposure does occur, guidelines for post-exposure
prophylaxis should be followed (refer to Chapters 23 and 24 of the Australian
Government Department of Health and Ageing Infection control guidelines for the
prevention of transmission of infectious diseases in the health care setting).1
A new, sterile, disposable syringe and needle must be used for each injection.
Disposable needles and syringes must be discarded into a clearly labelled,
puncture-proof, spill-proof container that meets Australian standards in order to
prevent needle-stick injury or re-use.1 Always keep sharps containers out of the
reach of children. All immunisation service providers should be familiar with
the handling and disposal of sharps according to the Australian Government
Department of Health and Ageing Infection control guidelines for the prevention of
transmission of infectious diseases in the health care setting, Chapters 14 and 23.1
1.4.2 Equipment for vaccination

Preparing for vaccination
• Depending on the vaccine(s) that are to be administered, and the age and size of
the person to be vaccinated, decide on the appropriate injection site and route,
and the injection equipment required (ie. syringe size, needle length and gauge).
• The equipment chosen will vary depending on whether the vaccine is a
reconstituted vaccine, a vaccine from an ampoule or vial, or a vaccine in a
pre-filled syringe.
Equipment may include:

• medical waste (sharps) container,
• vaccine, plus diluent if reconstitution is required,
• 2 or 3 mL syringe (unless vaccine is in pre-filled syringe),
1.4 Administration
• appropriate drawing-up needle (19 or 21 gauge needle if required, to draw

of vaccines
up through rubber bung and for reconstitution of vaccine),

• appropriate injecting needle (see Table 1.4.2 Recommended needle size, length
and angle for administering vaccines),
• clean cotton wool and hypoallergenic tape to apply to injection site after
vaccination, and
• a rattle or noisy toy for distraction after the injection.
Administration of vaccines 39
Preparing the vaccine
• Wash hands carefully and prepare the appropriate injection equipment for
the vaccine to be administered.
• Ensure that the minimum/maximum thermometer displays temperatures
within the +2°C to +8°C range before removing vaccine from the refrigerator.
• Ensure that the correct vaccine is taken from the refrigerator and that it is within
the expiry date.
• Check that there is no particulate matter or colour change in the vaccine.
• Ensure that the diluent container is not damaged and potentially
contaminated.
PRECAUTIONS:
If a pre-filled syringe is provided, check carefully whether reconstitution
with vaccine (provided in a separate vial) is required.
The diluent of one brand of oral rotavirus vaccine (Rotarix) is provided
in a syringe-like oral plunger. Do not administer this vaccine by injection
(parenteral) after reconstitution.
Both rotavirus vaccines are administered orally.
Preparing vaccine provided in a pre-filled syringe, ampoule or liquid vial

• If the vaccine is in a vial, remove the cap carefully to maintain sterility of the
rubber bung. Do not wipe the rubber bung. Use a 19 or 21 gauge needle to
draw up the recommended dose through the bung.
• If the vaccine is in an ampoule, use a 23 gauge, 25 mm needle to draw up the
recommended dose.
• Needles should be changed after drawing up from a vial with a rubber bung,
but it is not necessary to change needles between drawing up a vaccine from
an ampoule and giving the injection.
• Small air bubbles do not need to be extruded through the needle.
• A needle or syringe that has already been used to inject an individual must
never come into contact with the vial because of the risk of cross-contamination.

Preparing vaccines requiring reconstitution
• Reconstitute the vaccine as needed immediately before administration.
• Never mix other vaccines together in the one syringe (unless that is the
manufacturer’s registered recommendation, eg. Infanrix hexa).
• Never mix a local anaesthetic with a vaccine.
• A sterile 21 gauge needle should be used for reconstitution and a separate 23
or 25 gauge needle, 25 mm in length, should be used for administration of the
vaccine in most circumstances.
• Use only the diluent supplied with the vaccine; do not use sterile water for
injection instead of a supplied diluent. Ensure that the diluent and vaccine
are completely mixed.
• Reconstituted vaccines should be checked for signs of deterioration, such as a
change in colour or clarity.
• Reconstituted vaccines may deteriorate rapidly and, in general, should be
administered as soon as practicable after they have been reconstituted.
• Never freeze a vaccine after it has been reconstituted.
1.4.3 Route of administration

Almost all vaccines are given by either IM or SC injection, and a few vaccines
are given orally. Rotavirus vaccines are only available for oral administration
and must never be injected. Special training is required for intradermal
administration, which is important for several vaccines (see Chapter 3.17, Q
fever and Chapter 3.22, Tuberculosis). Table 1.4.1 below summarises the route of
administration for vaccines commonly used in Australia.
1.4 Administration
of vaccines
Table 1.4.1: Route of administration for vaccines commonly used in Australia
Intramuscular Subcutaneous (SC) IM or SC injection Oral

(IM) injection injection
Diphtheria, tetanus Inactivated polio Influenza vaccine† Rotavirus vaccine
vaccine (dT) vaccine (IPV)* Measles, mumps, Cholera vaccine
Diphtheria, Meningcoccal rubella vaccine Typhoid vaccine
tetanus, acellular polysaccharide (MMR)
pertussis vaccine vaccine (4vMenPV) Rubella vaccine
(DTPa and dTpa) Varicella 23-valent
DTPa- and dTpa- vaccine (VV) pneumococcal
combination Q fever vaccine‡ polysaccharide
vaccines vaccine (23vPPV)
Japanese
Hepatitis A vaccine encephalitis vaccine Rabies vaccine
Hepatitis B vaccine Measles, mumps, (HDCV)
Hepatitis B rubella, varicella Yellow fever vaccine
combination vaccine (MMRV)
vaccines (when available)
Haemophilus
influenzae type b
(Hib) vaccine
Human
papillomavirus
vaccine (HPV)
IPV-containing
combination
vaccines*
7-valent
pneumococcal
conjugate vaccine
(7vPCV)
Typhoid Vi
polysaccharide
vaccine
Meningococcal C
conjugate vaccine
(MenCCV)
Rabies vaccine
(PCECV)
* IPV-containing combination vaccines are administered by IM injection; IPV (IPOL) is administered by SC

injection.
† The IM route is preferred because it causes fewer local adverse events.2
‡ Q fever vaccine should be administered only by specially trained immunisation service providers.

1.4.4 Preparation for vaccine administration
Skin cleaning
Provided the skin is visibly clean, there is no need to wipe it with an antiseptic
(eg. alcohol wipe).3,4 If the immunisation service provider decides to clean the
skin, or if the skin is visibly not clean, alcohol and other disinfecting agents
must be allowed to dry before vaccine injection (otherwise there may be some
increased injection pain).
Distraction techniques
The routine use of distraction, relaxation and other measures have been
shown to reduce distress and pain following vaccination in young children.5-8
Reducing infant distress may enhance parents’ timely attendance for subsequent
vaccinations.
Distraction measures that may decrease discomfort following vaccination in young
children include:5-8
• swaddling and holding the infant securely (but not excessively),
• shaking a noisy toy (for infants and very young children),
• playing music,
• encouraging an older child to pretend to blow away the pain using a windmill
toy or bubbles, or
• administering sweet-tasting fluid orally immediately before the injection
(with parental consent). In infants, 15–20% sucrose drops have been used.
Topical anaesthetic agents, including vapocoolant sprays, are available but to
be effective must be applied at the correct time before vaccine administration.
Topical anaesthetics, such as EMLA, are not recommended for routine use,
but could be considered in a child with excessive fear or dislike of needles,
and require application 30 to 60 minutes before an injection.9 Vapocoolant
sprays are applied 15 seconds before vaccination. Topical lignocaine/prilocaine
is not recommended for children younger than 6 months due to the risk of
methaemoglobinaemia.5 1.4 Administration
of vaccines
1.4.5 Vaccine injection techniques
IM injection technique10,11
• For IM injection, a 25 mm needle should be used in most cases
(see Table 1.4.2 below).
• Depending on the injection site, the limb should be positioned so as to relax
the muscle into which the vaccine is to be injected.
• The 25 mm needle should pierce the skin at an angle of 90° to the skin, and
can be safely inserted to the hub.12 Provided an injection angle of >70° is
used, the needle should reach the muscle layer.13
• Studies have demonstrated that, for most vaccines, local adverse events
are minimised and immunogenicity enhanced by ensuring vaccine is
deposited into the muscle and not into the subcutaneous layer.5,14-17 However,
some vaccines, eg. inactivated poliomyelitis, varicella and meningococcal
polysaccharide vaccines, are only licensed for SC administration.
• A recent clinical trial demonstrated that long (25 mm) needles (with the skin
stretched flat and the needle inserted at 90°) for infant vaccination were
associated with significantly fewer local adverse events while achieving
comparable immunogenicity. Little difference was found between needles
the same length but with different gauges in local adverse events or
immune response.12
• If using a 25 gauge needle for an IM vaccination, ensure the vaccine is injected
slowly over a count of 5 seconds to avoid injection pain and muscle trauma.
• It is not considered necessary to draw back on the syringe plunger before
injecting a vaccine.5 However, if this is done, and a flash of blood appears
in the needle hub, the needle should be withdrawn and a new site selected
for injection.18
• After completing the injection, perform post-vaccination care
(see Chapter 1.5, Post-vaccination procedures).
SC injection technique
• SC injections are usually administered at a 45° angle to the skin.
• The standard needle for administering vaccines by SC injection is a 25 or 26
gauge needle, 16 mm in length.
Intradermal injection technique

For intradermal injection of BCG vaccine or Q fever skin test vaccine, a 26 or
27 gauge, 10 mm needle is recommended. The intradermal injection technique
requires special training, and should be performed only by a trained provider
(see Chapter 3.22, Tuberculosis and Chapter 3.17, Q fever).

Table 1.4.2: Recommended needle size, length and angle for administering
vaccines5,10,12,14,19
Age or size of child/adult Needle type Angle of needle insertion

Infant, child or adult 23 or 25 gauge,* 90° to skin plane
for IM vaccines 25 mm in length†
Preterm babies (<37 weeks’ 23 or 25 gauge,* 90° to skin plane
gestation) up to age 16 mm in length
2 months; very small infants
Very large or obese patient 23 gauge, 38 mm in length 90° to skin plane
Subcutaneous injection 25 or 26 gauge, 45° to skin plane
in all individuals 16 mm in length
* If using a narrow 25 gauge needle for an IM vaccination, ensure vaccine is injected slowly
over a count of 5 seconds to avoid injection pain and muscle trauma.
† The use of short needles for administering IM vaccines may lead to inadvertent
subcutaneous (SC) injection and increase the risk of significant local adverse events,
particularly with aluminium-adjuvanted vaccines (eg. hepatitis B vaccine, DTPa, DTPa-
combinations or tetanus vaccine).
1.4.6 Recommended injection sites

The choice of injection sites depends primarily upon the age of the individual
being vaccinated. The 2 anatomical sites recommended as routine injection sites
are the anterolateral thigh (Figure 1.4.6) and the deltoid muscle (Figure 1.4.9).
All practitioners should ensure that they are familiar with the landmarks used
to identify any anatomical sites used for vaccination. Photographs and diagrams
are provided in this section but are not a substitute for training. Further detail on
identifying the recommended injection sites is provided in Section 1.4.8.
Infants <12 months of age

The vastus lateralis muscle in the anterolateral thigh is the recommended site
for IM vaccination in infants <12 months of age (see Figures 1.4.5 and 1.4.6,
Section 1.4.8).
The ventrogluteal area (see Figures 1.4.7 and 1.4.8, Section 1.4.8) is an alternative
site for IM vaccination of infants. It is important that vaccine providers who
choose to use this site are familiar with the landmarks used to identify it. The
1.4 Administration
reactogenicity and immunogenicity of vaccines given in this site are comparable

to those of vaccines given in the anterolateral thigh.20-22
of vaccines
The deltoid muscle is not recommended for IM vaccination of infants <12 months

of age.
Children ≥12 months of age

The deltoid muscle is the recommended site for IM vaccination in children
≥12 months of age (see Figure 1.4.9, Section 1.4.8).
The ventrogluteal area is an alternative site for IM vaccination of children
≥12 months of age. However, vaccine providers should be familiar with the
landmarks used to identify this site.
The vastus lateralis in the anterolateral thigh may also be used in children
≥12 months of age, but if this site is used, the less locally reactogenic vaccines, eg.
MMR, should be given in the thigh.
Adolescents and adults

The deltoid muscle is the recommended site for IM vaccination in adolescents
and adults (see Figure 1.4.9, Section 1.4.8).
The anterolateral thigh can also be used in older children and adults.
The ventrogluteal area is an alternative injection site. However, vaccine providers
should be familiar with the landmarks used to identify this site.
PRECAUTION:
Vaccine injections should not be given in the dorsogluteal site or
upper outer quadrant of the buttock because of the possibility of a
suboptimal immune response.23,24 Immunoglobulin can be administered
intramuscularly into the upper outer quadrant of the buttock, but care must
be taken to ensure that the other quadrants are not used.

1.4.7 Positioning for vaccination
It is important that infants and children do not move during injection of vaccines.
However, excessive restraint can increase their fear and result in increased
muscle tension. The following section describes a variety of positions which may
be used for vaccinating different age groups.
Positioning of infants <12 months of age

• Cuddle position for infants
Position the infant in a semi-recumbent cuddle position on the lap of the
parent/carer. The infant’s arm adjacent to the parent/carer should be restrained
underneath the parent/carer’s arm or against the parent/ carer’s chest. The
knee should be flexed to encourage relaxation of the vastus lateralis for IM
vaccinations. The infant’s other arm must also be held securely (see Figure 1.4.1).
This position can also be used for young children.
Figure 1.4.1: The cuddle position for vaccination of a child <12 months of age
1.4 Administration
of vaccines
Photo courtesy Dr Joanne Molloy, VIC
• Positioning infant on an examination table
An alternative is to lay infants on their backs on an examination table, with the
infant’s feet towards the immunisation service provider, and the parent/carer
beside the provider to immobilise and distract the baby (see Figure 1.4.2).
Keep the infant’s hip and knee flexed by cupping the patella in the non-injecting
hand.
The thumb and index finger of the non-injecting hand may be used to stabilise
the hub of the needle once the needle has been inserted.
Figure 1.4.2: Positioning an infant on an examination table for vaccination
• Prone position across the lap for ventrogluteal vaccination

For ventrogluteal injection, position the child face-down across the parent/
carer’s lap. This allows the hips to be flexed and provides access to the
ventrogluteal area (see Figure 1.4.8).

Positioning of children ≥12 months of age
• Cuddle position for older child
Sit the child sideways on the lap of the parent/carer, with the arm to be injected
held close to the child’s body while the other arm is tucked under the armpit and
behind the back of the parent/carer.
The child’s exposed arm should be secured at the elbow by the parent/carer, and
the child’s legs also secured by the parent/carer (see Figure 1.4.3).
Figure 1.4.3: Positioning an older child in the cuddle position
Photo courtesy Ann Kempe, MCRI, VIC
1.4 Administration
of vaccines
• Straddle position
An older child may be positioned facing the parent/carer with the legs straddled
over the parent/carer’s lap. The child’s arms should be folded in front, with the
parent/carer hugging the child’s body to the parent/carer’s chest. Alternatively,
the child may be positioned to ‘hug’ the parent with the parent’s arms holding
the child’s arms in a reciprocal hug (see Figure 1.4.4). This position allows access
to both deltoids and both anterolateral thighs.
Figure 1.4.4: Positioning a child in the straddle position

• Prone position across the lap for ventrogluteal vaccination
For ventrogluteal injection, position the child face-down across the parent/
carer’s lap (see Figure 1.4.8).
Positioning of older children, adolescents and adults

• Solo sitting position for deltoid injections
Most vaccines can be administered into the deltoid area. Adults should sit in
a straight-backed chair, feet resting flat on the floor with forearms and hands
in a relaxed position on the upper thighs. Keep the arms flexed at the elbow to
encourage the deltoid muscle to relax.
Encourage shoulders to drop by asking the person to raise the shoulders up while
taking a deep breath in and to drop them while breathing out fairly forcefully. Use
distraction to keep muscles relaxed during the procedure, eg. have an interesting
poster or similar for the person to concentrate on during the procedure and ask
him/her to give you a detailed description of what can be seen.
The ventrogluteal and vastus lateralis are alternative sites if needed (see above,
and below).
1.4.8 Identifying the injection site

The choice of injection site depends upon the age of the person, and is discussed
in Section 1.4.6.
The anterolateral thigh (vastus lateralis)

• The infant’s nappy must be undone to ensure the injection site is completely
exposed and the anatomical markers easily identified.
• Position the leg so that the hip and knee are flexed and the vastus lateralis is
relaxed (see Figure 1.4.6).
• The upper anatomical marker is the midpoint between the anterior superior
iliac spine and the pubic tubercle, and the lower marker is the upper part of
the patella.
• Draw an imaginary line between the 2 markers down the front of the thigh.
The correct site for IM vaccination is lateral to the midpoint of this line, in the
outer (anterolateral) aspect (see Figures 1.4.5 and 1.4.6).
• Do not inject into the anterior aspect of the thigh where neurovascular
1.4 Administration
structures can be damaged.

of vaccines
Figure 1.4.5: Diagram of the muscles of the thigh showing the anatomical
markers to identify the recommended (vastus lateralis) injection site (X)
Figure 1.4.6: Photograph of the thigh showing the recommended (vastus

lateralis) injection site (X)
Photo courtesy Lloyd Ellis, RCH, VIC

The ventrogluteal area
NB. This area should not be confused with the dorsogluteal area (buttock).
The ventrogluteal site provides an alternative site for administering vaccines
to a child of any age, especially when multiple injections at the same visit are
required. The ventrogluteal area is relatively free of major nerves and blood
vessels, and the area provides the greatest thickness of gluteal muscle.25,26 There is
a relatively consistent thinness of subcutaneous tissue over the injection site.26,27
• The child’s nappy must be undone to ensure the injection site is completely
exposed and the anatomical markers easily identified by sight and palpation.
Anatomical markers are the anterior superior iliac spine (ASIS), the greater
trochanter of the femur and the iliac crest (see Figure 1.4.7).
• Place the child in a prone position (face-down) on parent/carer’s lap or on
the clinic table/bed with arms tucked against the child’s chest. Allow the
child’s legs to dangle towards the floor (see Figure 1.4.8).
• The knee and hip should be turned inwards to encourage muscle relaxation at
the injection site.
• The injection site should be that which is closest to the immunisation service
provider.
• Place the palm over the greater trochanter (the uppermost bony prominence
of the thigh bone) with the thumb pointing towards the umbilicus. The
index finger points to the anterior superior iliac spine, and the middle finger
is spread so that it aims at the iliac crest, thus creating a ‘V’ outlining the
ventrogluteal triangular area. The injection site is at the centre of this area
(see Figures 1.4.7 and 1.4.8).

ventrogluteal injection site (X) (ASIS = anterior superior iliac spine)
1.4 Administration
of vaccines
Figure 1.4.8: Photograph with infant prone across carer’s lap, showing markers
to identify the ventrogluteal injection site (X)
The deltoid area

It is essential to expose the arm completely from the top of the shoulder to the
elbow when locating the deltoid site (see Figure 1.4.9). Roll up the sleeve or
remove the shirt if needed.
• The injection site is halfway between the shoulder tip (acromion) and the
muscle insertion at the middle of the humerus (deltoid tuberosity).
• Draw an imaginary, inverted triangle below the shoulder tip, using the
identified anatomical markers.
• The deltoid site for injection is the middle of the muscle (triangle)
(see Figure 1.4.9).

Figure 1.4.9: Diagram showing the anatomical markers to identify the deltoid
injection site
Subcutaneous injection sites

Subcutaneous injections should be administered either over the deltoid muscle
or over the anterolateral thigh. There are no data to demonstrate any difference
in technique between administration of a SC injection and a deep SC injection.
Figure 1.4.10 demonstrates the recommended technique for any SC injection.
Figure 1.4.10: A subcutaneous injection into the deltoid area of the upper arm
using a 25 gauge, 16 mm needle, inserted at a 45° angle
1.4 Administration
of vaccines
Photo courtesy Ann Kempe, MCRI, VIC
1.4.9 Administering multiple vaccine
injections at the same visit
The location of each separate injection given should be recorded, so that if a local
adverse event occurs, the implicated vaccine(s) can be identified.
Infants <12 months of age

The suitable sites for this age group are the anterolateral thighs and the
ventrogluteal areas. Two vaccines can be given into the same anterolateral thigh,
separated by at least 2.5 cm. However, only 1 vaccine should be given into each
ventrogluteal area.
When 3 or 4 IM vaccines are to be given at the same visit, the options are:
• 2 injections can be administered in the same anterolateral thigh, separated by
at least 2.5 cm (see Figure 1.4.11); further IM vaccines can be given in this way
in the other thigh, or
• 1 injection can be given into each anterolateral thigh and 1 injection can be
administered into each ventrogluteal area.
Figure 1.4.11: Recommended technique for giving multiple vaccine injections

to an infant <12 months of age into the anterolateral thigh

Children ≥12 months of age, adolescents and adults
A single injection can be given into each deltoid muscle.
When 3 or 4 IM vaccines are to be given to a child at the same visit, the options
will depend on the muscle mass of the child’s deltoid.
If the deltoid mass is adequate:
• a further injection can be given into each deltoid muscle (separated by 2.5 cm
from the initial vaccine).
If the deltoid muscle mass is small:
• further injections can be given into either the anterolateral thighs (2.5 cm
apart if 2 vaccines are given in the same thigh), or
• give 1 injection into each ventrogluteal area.
For younger children, the cuddle or straddle position (Figures 1.4.3 and 1.4.4) are
suitable for accessing multiple limbs during the one vaccination encounter.
References
1.4 Administration
of vaccines
1.5 Post-vaccination procedures
1.5.1 Immediate after-care

• Dispose of clinical waste, including sharps and vaccine vials, immediately
after administration of the vaccine and at its point of use. Refer to the State/
Territory health authority for management guidelines for the safe disposal of
clinical waste or refer to the Australian Government Department of Health
and Ageing Infection control guidelines for the prevention of transmission of
infectious diseases in the health care setting.1
• Cover the site quickly with a dry cotton ball and tape as needed.
• Gently apply pressure for 1 or 2 minutes. Do not rub the site as this will
encourage the vaccine to leak back up the needle track, which can cause pain
and may lead to local irritation.
• Remove the cotton wool after a few minutes and leave the injection site
exposed to the air.
• Paracetamol is not routinely used before or at the time of vaccination, but
may be recommended as required for fever or pain.
• To distract the individual and reduce distress, immediately change the position
of the child/person after completing the vaccination, eg. ask the parent/carer
to put the infant over the shoulder and move around with the infant.2
• The vaccinated person and/or parent/carer should be advised to remain in
a nearby area for a minimum of 15 minutes after the vaccination. The area
should be close enough to the immunisation service provider, so that the
individual can be observed and medical treatment rapidly provided if needed.
• Take the opportunity to check the vaccination status of other family members
(as appropriate) and provide (or refer) for catch-up vaccination.
• Record the relevant details of the vaccines given in a record to be retained
by the person or parent/carer, in the surgery/clinic record and, for children
aged <7 years, forward records to the ACIR (see Section 1.5.3, Documentation
of vaccination).
• Before departure, inform the individual or parent/carer, preferably in
writing, of the date of the next scheduled vaccinations.
1.5.2 Adverse events following immunisation

What are AEFI?
An adverse event following immunisation (AEFI) is an unwanted or unexpected
event occurring after the administration of vaccine(s). Such an event may be
caused by the vaccine(s) or may occur by chance after vaccination (ie. it would
have occurred regardless of vaccination). Most vaccines cause minor adverse
events such as low-grade fever, pain or redness at the injection site and these

should be anticipated3 (see the table Comparison of the effects of diseases and the side
effects of vaccines inside the front cover of this Handbook).
1.5 Post-vaccination
The frequency of adverse events can be classified as follows: very common (>10%),
common (1–10%), uncommon (0.1–1%), rare (0.01–0.1%) and very rare (<0.01%).4
procedures
Common adverse events
The following common adverse events should be anticipated following
vaccination.5 They can be distressing for parents/carers, but they do not
contraindicate further vaccination. In general, unless these adverse events are
significant, they do not need to be reported by immunisation service providers
to the Adverse Drug Reactions Advisory Committee (ADRAC) (see Table 1.5.3,
Contact details for notification of AEFI).
Parents/carers should be given advice (preferably written) as part of the consent
procedure on what common adverse events are likely and what they should do
about them (the table inside the back cover of this Handbook, Commonly observed
adverse events following immunisation with vaccines used in the National Immunisation
Program (NIP) schedule and what to do about them, can be used for this purpose).
• DTPa, dTpa, hepatitis B, Hib, IPV and their various combinations may cause
transient minor adverse events including swelling, redness or soreness at the
injection site, and low-grade fever, crying and irritability (in infants).
• There is an increased risk of more extensive local adverse events after booster
doses of DTPa and DTPa-combination vaccines.6 A local adverse event that
involves extensive limb swelling should be reported. For the definition of
extensive limb swelling, see Appendix 6, Definitions of adverse events following
immunisation.
• MMR vaccine may be followed 5 to 12 days later by a fever lasting 2 or
3 days, malaise and/or rash. This is not infectious. Fever >39.4°C is very
common, occurring in 5 to 15% of vaccinees, 5 to 12 days after vaccination.
• Human papillomavirus vaccine may cause mild injection site adverse events
(pain, swelling and erythema) and, occasionally, headache, fever and nausea.
• Influenza vaccine may cause soreness at the injection site. Fever, malaise, and
myalgia occur less commonly.
• The 7vPCV causes low-grade fever and/or mild pain at the injection site in
about 10% of infant recipients. The 23-valent pneumococcal polysaccharide
vaccine (23vPPV) causes mild local adverse events in up to half the adult
recipients.
• MenCCV is generally well tolerated. Very common (>10%) adverse events
are pain, redness and swelling at the injection site, fever, irritability, anorexia
and headache.
Post-vaccination procedures 59
• Varicella vaccine may cause mild local soreness and swelling. A mild
maculopapular or papulovesicular rash occurs in up to 5% of vaccinated
children (see also Chapter 3.24, Varicella).
• Injection site nodules are not uncommon. They are fibrous remnants of the
body’s interaction with the vaccine components (usually an adjuvant) in the
muscle, and they may remain for many weeks after the vaccination. Injection
site nodules do not require any specific treatment.
• Oral rotavirus vaccine may cause mild fever and/or diarrhoea (see
Chapter 3.18, Rotavirus).
Managing common adverse events

Advice to parents on common adverse events
Vaccine injections may result in soreness, redness, itching, swelling or burning
at the injection site for 1 to 2 days. Paracetamol might be required to ease the
discomfort.
Managing fever after vaccination

Routine use of paracetamol at the time of vaccination is no longer recommended.
If an infant or child has a fever of >38.5°C following vaccination, paracetamol can
be given. The dose of paracetamol is 15 mg/kg/dose of paracetamol liquid, up to
a maximum daily dose of 90 mg/kg per day in 4 to 6 divided doses for up to 48
hours.
Preventing AEFI
The key to preventing uncommon or rare adverse events is to screen each person
to be vaccinated using pre-vaccination screening (Tables 1.3.1 and 1.3.2) to
ensure that the person does not have a condition which either increases the risk
of an adverse event or is a contraindication to vaccination. The correct injection
technique is also important. Immunisation service providers should also check
the relevant chapters of this Handbook or the product information supplied
with the vaccine for more details on precautions and contraindications for each
vaccine they are to administer.
Uncommon and rare AEFI

Some vaccines have been shown to cause uncommon or rare adverse events,
although the rate is always hundreds to thousands times less frequent than the
disease complications. Examples are given below.
Rare, late events shown to be causally related to some vaccines

The use of oral poliomyelitis vaccine (OPV) in Australia was discontinued in
2005. OPV can rarely cause vaccine-associated paralytic poliomyelitis (VAPP).
The incidence is 1 in 2.4 million doses of OPV, which means that Australia would
have expected 1 case of VAPP every 3 years when OPV was in use. However,

the reported incidence of VAPP was only 1 case every 8 to 9 years in Australia.7
VAPP does not occur from vaccination with IPV or IPV-containing vaccines.
Vaccines containing diphtheria and tetanus have been described as causing
brachial neuritis, with an incidence of approximately 1 in 100 000 (adults).
procedures
Events where evidence demonstrates no
causal link with immunisation
There is epidemiological evidence which indicates that there is no causal
association between immunisation and the following events:
• sudden infant death syndrome (SIDS) and any vaccine,8-10
• autism and MMR vaccine,11-14
• multiple sclerosis and hepatitis B vaccine,15-18
• inflammatory bowel disease and MMR vaccine,19
• diabetes and Hib vaccine,20-22
• asthma and any vaccine.23
Management of an immediate AEFI

Observation after vaccination
Recipients of vaccines should remain under observation for a short interval
to ensure that they do not experience an immediate adverse event. It is
recommended that recipients remain in the vicinity of the place of vaccination
for at least 15 minutes. Severe anaphylactic reactions usually have a rapid onset;
most life-threatening adverse events begin within 10 minutes of vaccination.
The most serious immediate AEFI is anaphylaxis. However, in adults and older
children, the most common immediate adverse event is a vasovagal episode
(fainting), either immediately or soon after vaccination. Because fainting after
vaccination can lead to serious consequences, anyone who complains of giddiness
or light-headedness before or after vaccination should be advised to lie down
until free of symptoms. Most faints following vaccination occur within 5 minutes,
and 98% occur within 30 minutes. Adults should, therefore, be warned of the risk
of driving or operating machinery for at least 30 minutes after vaccination.24
Children who have had a serious adverse event (other than a contraindication,
such as anaphylaxis) to a previous vaccine may subsequently be vaccinated under
close medical supervision. Check with State/Territory health authorities for more
information (see Section 2.3.1, Vaccination of children who have had a serious adverse
event following immunisation and Appendix 1, Contact details for Australian, State and
Anaphylaxis and vasovagal episodes

Anaphylaxis following routine vaccination is very rare, but can be fatal.
All immunisation service providers must be able to distinguish between
anaphylaxis, convulsions and fainting.
Fainting (vasovagal episode) is relatively common after vaccination of adults and
adolescents, but infants and children rarely faint. Sudden loss of consciousness in
young children should be presumed to be an anaphylactic reaction, particularly
if a strong central pulse is absent. A strong central pulse (eg. carotid) persists
during a faint or convulsion.
The features listed in Table 1.5.1 may be useful in differentiating these 2 conditions.
If the diagnosis is unclear and anaphylaxis is considered, management for this
should be instituted with the prompt administration of adrenaline.
Table 1.5.1: Clinical features which may assist differentiation between a

vasovagal episode and anaphylaxis
Vasovagal episode Anaphylaxis

ONSET Immediate, usually within Usually within 15 minutes,
minutes of or during but can occur within hours,
vaccine administration. of vaccine administration.
Symptoms/ Skin Generalised pallor, Skin itchiness, generalised
Signs cool, clammy skin. skin erythema (redness),
urticaria (weals) or
angioedema (localised
oedema of the deeper
layers of the skin or
subcutaneous tissues).
Respiratory Normal respiration; may be Cough, wheeze, stridor,
shallow, but not laboured. or signs of respiratory
distress (tachypnoea,
cyanosis, rib recession).
Cardiovascular Bradycardia, weak/ Tachycardia, weak/absent
absent peripheral pulse, peripheral and carotid pulse.
strong carotid pulse. Hypotension – sustained
Hypotension – usually and no improvement
transient and corrects without specific treatment.
in supine position.
Neurological Feels faint, light-headed. Sense of severe anxiety
Loss of consciousness – and distress.
improves once supine or Loss of consciousness – no
head down position. improvement once supine
or head down position.
Signs of anaphylaxis
Anaphylaxis is a severe adverse event of rapid onset, characterised by sudden
respiratory compromise and/or circulatory collapse. Early signs include
involvement of the skin, eg. generalised erythema, urticaria and/or angioedema
(swelling), and/or gastrointestinal tract, eg. diarrhoea, vomiting. In severe
cases, there is circulatory collapse with alteration in the level of consciousness,

hypotension and weak or absent pulses, and/or marked respiratory compromise
from upper airway oedema or bronchospasm.
Immunisation service providers should be able to recognise all the following
symptoms and signs of anaphylaxis:
procedures
• cutaneous, such as the rapid development of widespread urticarial lesions
(circumscribed, intensely itchy weals with erythematous, raised edges and
pale, blanched centres) and/or erythema and/or angioedema (soft tissue
swelling usually affecting the face and/or limbs),
• upper airway obstruction, such as hoarseness and stridor, resulting from
angioedema of the hypopharynx, epiglottis and larynx,
• lower airway obstruction, such as subjective feelings of retrosternal tightness,
and dyspnoea with audible expiratory wheeze from bronchospasm,
• limpness and pallor, which are signs of hypotension in infants and young
children,
• profound hypotension in association with other signs of cardiovascular
disturbance, such as sinus tachycardia or severe bradycardia, absent central
pulses and reduced peripheral circulation, and/or
• abdominal cramps, diarrhoea and/or vomiting.
Management of anaphylaxis
Rapid IM administration of adrenaline is the cornerstone of treatment of
anaphylaxis.
Anaphylaxis occurs without warning, usually within 15 minutes of giving a
vaccine. A protocol for the management of anaphylaxis, adrenaline, and 1 mL
syringes must always be immediately at hand whenever vaccines are given.
• If the patient is unconscious, lie him/her on the left side and position to keep
the airway clear. If the patient is conscious, lie supine in ‘head down and feet
up’ position (unless this results in breathing difficulties).
• Give adrenaline by IM injection (see below for dosage) for any signs of
anaphylaxis with respiratory and/or cardiovascular symptoms or signs.
Adrenaline is not required for generalised non-anaphylactic reactions (such
as skin rash or angioedema). If in doubt, IM adrenaline should be given.
• If there is no improvement in the patient’s condition by 5 minutes, repeat
doses of adrenaline every 5 minutes until improvement occurs.
• If oxygen is available, administer by facemask at a high flow rate.
• Call for assistance. Never leave the patient alone.
• Begin expired air resuscitation for apnoea, check for a central pulse. If pulse
is not palpable, commence external cardiac massage (ECM).
• All cases should be admitted to hospital for further observation and
treatment.
• Document the time and dose of adrenaline given.
Experienced practitioners may choose to use an oral airway if the appropriate

size is available, but its use is not routinely recommended unless the patient is
unconscious.
Antihistamines and/or hydrocortisone are not recommended for the emergency
management of anaphylaxis.
Adrenaline dose
Adrenaline 1:1000 (one in one thousand)
Adrenaline 1:1000 contains 1 mg of adrenaline per mL of solution in a 1 mL
glass vial. Adrenaline 1 in 10 000 is no longer recommended for the treatment
of anaphylaxis. The use of 1:1000 adrenaline is recommended because it
is universally available. Use a 1 mL syringe to improve the accuracy of
measurement when drawing up small doses.
The recommended dose of 1:1000 adrenaline is 0.01 mL/kg body weight
(equivalent to 0.01 mg/kg or 10 µg/kg) up to a maximum of 0.5 mL, given by
deep IM injection (not the deltoid). Adrenaline 1:1000 must not be administered
intravenously. Table 1.5.2 lists the dose of 1:1000 adrenaline to be used if the exact
weight of the individual is not known.
Table 1.5.2: Doses of intramuscular 1:1000 (one in one thousand) adrenaline for
anaphylaxis
Less than 1 year 0.05–0.1 mL

1–2 years (approx. 10 kg) 0.1 mL
13 years and over (over 40 kg) 0.5 mL
The dose of 1:1000 (one in one thousand) adrenaline may be repeated every 5
minutes as necessary until there is clinical improvement.
Reporting AEFI
Surveillance for adverse events following immunisation is an integral part of a
national vaccination program. Through surveillance, it is hoped to detect changes
in the rates of known adverse events and any adverse events that either were
previously undocumented, or result from program errors, such as incorrect
vaccine schedule, delivery or storage.

Any serious or unexpected adverse event following immunisation should
be reported. Providers should use clinical judgement and common sense
in deciding which adverse events to report, and parents/carers should
procedures
be encouraged to notify the immunisation service provider or health
authorities of an AEFI.
Any of the adverse events listed in Appendix 6, Definitions of adverse events following
immunisation should be reported. No time limit has been set to report AEFI.
Notification of an adverse event does not necessarily imply a causal association
with vaccination, as some events may occur coincidentally following vaccination.
Immunisation service providers are also advised to report any adverse events
of concern that do not fit into any of the categories listed in Appendix 6. They
should be reported as ‘other reactions’ with a full description of the adverse
event. This will enable new and unexpected AEFI to be identified.
How should AEFI be reported?

AEFI are notifiable directly to the relevant health authority in Australian Capital
Territory, New South Wales, Northern Territory, Queensland, South Australia,
Victoria and Western Australia. In Tasmania, AEFI should be reported using the
Adverse Drug Reactions Advisory Committee (ADRAC) blue card.
AEFI are notifiable conditions in Australian Capital Territory, New South Wales,
Northern Territory, Queensland, South Australia, Victoria and Western Australia
and must be reported directly to the relevant health authority (see Table 1.5.3
below). These State and Territory health authorities then forward AEFI
notifications to ADRAC.
The Adverse Drug Reactions Advisory Committee (ADRAC) receives reports
of unexpected and serious adverse events for all medicines, including
vaccines. Any person (medical or non-medical) can report an AEFI to ADRAC
by telephoning the numbers listed in Table 1.5.3 below, or by filling in a blue
card or completing a web-based report (https://www.tgasime.health.gov.au/
SIME/ADRS/ADRSLodg.nsf/wNotification?OpenForm).
Additional blue cards are available from:
The Secretary
Adverse Drug Reactions Advisory Committee
PO Box 100
Woden ACT 2606
Telephone: 1800 044 114 or on-line at www.tga.gov.au/adr/bluecard.htm
ADRAC will forward copies of individual reports of AEFI with vaccines on the
National Immunisation Program schedule to those States/Territories that have
follow-up surveillance. In addition, reports from ADRAC and State/Territory
Health Departments are aggregated and published in Communicable Diseases
Intelligence.25
Table 1.5.3: Contact details for notification of AEFI
State/Territory Report adverse events Telephone number

directly to:
*Australian ACT Health Department 02 6205 2300
Capital Territory
*New South Wales NSW Public Health Units Contact your local Public Health Unit,
found under ‘Health’ in the White Pages
*Northern Territory NT Department of Health 08 8922 8044
and Community Services
*Queensland Queensland Health 07 3234 1500
*South Australia Department of Health 08 8226 7177
In SA, parents can also report 1300 364 100 (24 hours)
adverse events by calling
Tasmania ADRAC Use blue card
*Victoria Department of Human 1300 822 924
Services, SAEFVIC
*Western Australia State Health Department 08 9321 1312
* AEFI are notifiable in these States/Territories and health professionals should report
directly to their respective Health Department as listed above.
1.5.3 Documentation of vaccination

A personal health record should be established for each vaccinee and newborn
infant, and kept by that person or the parent/carer. The parent/carer should be
urged to present the record every time a child is seen by a health professional.
The following details should be recorded in the personal health record, and in the
clinical file:
• the vaccinee’s full name and date of birth,
• the details of the vaccine given, including the dose, brand name, batch
number, and site of administration,
• the name of the person providing the vaccination,
• the date of vaccination, and
• the date the next vaccination is due.
If the vaccinee is a child <7 years of age, the Australian Childhood Immunisation

Register (ACIR) must also be notified of the vaccination details (see ‘The
Australian Childhood Immunisation Register’ below).

1.5.4 The Australian Childhood Immunisation Register
The Australian Childhood Immunisation Register (ACIR) is a national database
for recording details of vaccinations given to children <7 years of age who live
in Australia. It commenced on 1 January 1996 and is administered by Medicare
procedures
Australia under the legislative mandate of the Commonwealth Health Insurance
Act 1973 Part IVA. Section 46B of the Health Insurance Act specifies how the ACIR
is to be implemented and managed. Section 46E sets out the provisions for giving
both de-identified and identified information to recognised immunisation service
providers and other specified agencies.
Children enrolled in Medicare are automatically included on the ACIR. Children
not enrolled in Medicare will be included when an immunisation service
provider sends details of a vaccination to the ACIR. No vaccination information
is recorded on the ACIR after a child turns 7 years of age, but any information
already held is retained. The information will relate only to vaccines received
between the ages of birth and the 7th birthday. The ACIR Enquiry Line can be
contacted on 1800 653 809 (free call) and any record held for an individual who is
≥7 years of age can also be made available to an immunisation service provider
or parent/carer.
The ACIR provides an important means of accountability and evaluation of
the childhood vaccination program. It is the primary means of determining
vaccination coverage at national, State/Territory and local levels. It also provides
a central vaccination history for each child that is accessible to any Australian
immunisation service provider wishing to assess vaccination status. Since 1998,
data held on the ACIR have been used to determine a family’s entitlement to the
Child Care Benefit and Maternity Immunisation Allowance family assistance
payments. It is, therefore, important that vaccination data are submitted to the
ACIR promptly.
Reporting to ACIR
Immunisation service providers should send to the ACIR details of all NIP and
private vaccinations given to children <7 years of age. Vaccination details may
be submitted by sending data electronically via Medicare Australia’s on-line
claiming facility, Electronic Data Interchange (EDI) on the Internet, or by using
a paper form. Providers in Queensland and the Northern Territory currently
sending data to the ACIR via their State/Territory Health Department should
continue to do so. Providers in all other States/Territories should send data
directly to the ACIR.
A child’s vaccination record can also be updated with vaccination details where
the vaccination was performed by another immunisation service provider,
including those given while the child was overseas, by completing and sending
an Immunisation History form to Medicare Australia. Forms are available on the
ACIR website at www.medicareaustralia.gov.au/providers/forms/acir.htm.
When relevant, immunisation service providers should complete the Conscientious
Objection and Medical Contraindication forms and forward to the ACIR.
For further information about the ACIR and reporting vaccination information,
see ‘The ACIR Internet site’ below. In addition, assistance on any reporting issues
can be obtained from the ACIR Enquiry Line, 1800 653 809 (free call).
Immunisation History Statement

Immunisation History Statements, which contain details of all vaccines
administered to the child and recorded on the ACIR, and those that may be
missing, are automatically generated when a child turns 12 months, 2 and 5 years
of age and on completion of the childhood vaccination schedule. Statements will be
mailed to the address most recently recorded on the ACIR for that child.
Parent/carers can also get a Statement at any other time:
• on-line at www.medicareaustralia.gov.au,
• from their local Medicare office,
• by calling 1800 653 809 (free call).
Immunisation History Statements can be used when proof of vaccination is

needed. For example, Statements can be used to meet vaccination requirements for:
• primary school enrolment – a sentence will be displayed at the bottom of the
statement that says the child has received all the vaccinations required by
5 years of age, and/or
• eligibility for the Child Care Benefit and Maternity Immunisation Allowance;
an up-to-date status for the Family Assistance Office will be displayed.
Recording details of a deceased child

The ACIR should be notified of a deceased child to prevent an Immunisation
History Statement being sent to bereaved parents/carers. Advice of a child’s
death can be provided by calling 1800 653 809 (free call), or by sending details
on practice stationery. Details should include the child’s name, address, date of
birth, Medicare number and date of death.
Children who have moved to live overseas

A child who has moved overseas can be removed from the ACIR by sending
details to the ACIR by fax, phone or secure site email. This prevents the child’s
name continuing to appear on ACIR reports of overdue children.
Ascertaining individual vaccination status

Parents/carers can telephone the ACIR on 1800 653 809 (free call) for information
about their child’s vaccination status, regardless of where the child’s vaccination
was given. Immunisation service providers can also request a child’s vaccination
status by telephone.

Vaccination coverage and other reports
ACIR reports assess progress towards national targets, and help to identify areas
with low vaccination levels and assist in planning vaccination programs.
procedures
Practices that are registered for the General Practice Immunisation Incentive
(GPII) scheme can receive quarterly reports on vaccination coverage for children
within that practice. Other reports, including those that identify a child’s
vaccinations and due/overdue details, are available through the secure area of
the ACIR Internet site to approved immunisation service providers.
The ACIR Internet site

The ACIR Internet site has 2 main parts, a general information area and a secure
area. The Internet address for the ACIR is www.medicareaustralia.gov.au. Any
person with Internet access may view the ACIR site for general vaccination
information and statistics.
Approved immunisation service providers are able to access the secure area of
the ACIR Internet site and obtain a range of statistical and identified reports.
These reports are available, depending on the access level granted to the provider,
and enable approved providers to view a child’s vaccination details, record
vaccination information and access a range of other reports. To register for access
to the secure area of the ACIR Internet site, providers should complete the online
request form at http://www.medicareaustralia.gov.au/providers/programs_
services/acir/index.htm. Further information or assistance may be obtained by
calling the ACIR Internet Helpline on 1300 650 039 (free call).
References
PART 2: Vaccination for
special risk groups
2.1 Vaccination for Aboriginal and

Torres Strait Islander people
Aboriginal and Torres Strait Islander people historically had a very high
burden of infectious diseases, including those for which vaccines were
subsequently developed. These high rates of disease in the early period of
European colonisation were mainly due to a lack of previous exposure and
acquired immunity,1 and in more recent years have been associated with lower
standards of living and poorer access to water, housing and health care.2 For
some vaccine-preventable diseases (VPDs), such as diphtheria, polio, tetanus,
hepatitis B, measles, mumps and rubella, vaccination has been very successful in
eliminating or substantially reducing disease in all Australians, and has made a
substantial contribution to improvements in Aboriginal and Torres Strait Islander
child mortality in recent decades.3 For some other VPDs, in particular invasive
pneumococcal disease and influenza in adults, greater burdens of illness still
occur in Indigenous compared to non-Indigenous people and remain a major
cause of illness and death.3 Detailed information on the current status of VPDs
and vaccination status in Aboriginal and Torres Strait Islander people is available
elsewhere.3
This chapter discusses the vaccines for which there are different
recommendations for Aboriginal and Torres Strait Islander people in at least
some parts of Australia. These are, for children, BCG, hepatitis A, Haemophilus
influenzae type b, and pneumococcal vaccines, and, for adults, influenza and
pneumococcal polysaccharide vaccines.
CHILDREN
BCG vaccine and tuberculosis
In the past, Aboriginal and Torres Strait Islander people have suffered from
much higher rates of tuberculosis, more than 20 times the rate of non-Indigenous
Australian-born people in some areas.4 While there have been substantial
improvements in disease rates in recent decades, tuberculosis remains more
common in Indigenous than non-Indigenous Australian-born people in many
parts of Australia, particularly northern and central Australia.5,6 Although there
is uncertainty about the efficacy of BCG in preventing pulmonary tuberculosis,
it provides substantial protection against disseminated forms of the disease
in young children.7 BCG is therefore recommended for Aboriginal and Torres
Strait Islander neonates in regions of high incidence (Northern Territory, far
northern Queensland, some regions of both Western Australia and South

Australia), where infants are at higher risk of acquiring this serious, and often
fatal, condition. State and Territory guidelines should be consulted where BCG is
being considered for neonates <2.5 kg in weight. Nevertheless, as the incidence
of pulmonary tuberculosis in adults and the risk of disseminated tuberculosis in
infants decreases, the risk of severe complications of BCG, documented in native
peoples elsewhere, may become a significant consideration.8 State/Territory
health authorities should be consulted to determine the recommendations for
particular areas. It is usually administered to eligible infants by hospital staff
(ie. midwives or nurses who have been specially trained) soon after delivery.
Injection technique is particularly important for BCG vaccination which must be
administered intradermally. Adverse events, such as regional lymphadenitis, are
less common when administration is performed by trained staff.9 See Chapter
3.22, Tuberculosis for more information.
Aboriginal and Torres

Strait Islander people
2.1 Vaccination for
Haemophilus influenzae type b
Before the introduction of an effective Haemophilus influenzae type b (Hib)
vaccine, not only was the incidence of invasive Hib disease very high in
Aboriginal and Torres Strait Islander children, particularly in more remote
areas, it also occurred at a younger age than in non-Indigenous children. Thus, a
vaccine to prevent Hib disease in Aboriginal and Torres Strait Islander children
needed to be immunogenic as early as possible in infancy. The vaccine known
by the abbreviation PRP-OMP (PedvaxHIB or COMVAX) is more immunogenic
at 2 months of age than the other conjugate Hib vaccines, and so was the
preferred Hib vaccine for Aboriginal and Torres Strait Islander children from
the inception of the Hib vaccination programs in 1993. Since then, there has
been a dramatic decline of Hib disease in Aboriginal and Torres Strait Islander
children.10,11 The experience in other high incidence populations indicates that
it is important to continue to use PRP-OMP vaccine in Aboriginal and Torres
Strait Islander populations demonstrated to be at highest risk, as in central and
northern Australia. However, the available data indicate that Indigenous children
in areas of low incidence, and non-Indigenous children, have a pattern of Hib
disease which is adequately covered by a vaccine not prompting significant
immune response until after the second dose.12 New combination vaccines
which include a Hib (PRP-T) component have the advantage of reducing the
number of injections required. Therefore, in the Northern Territory, Queensland,
South Australia and Western Australia, all Aboriginal and Torres Strait Islander
children should receive a Hib vaccine with a PRP-OMP component, while
Indigenous children in other jurisdictions, and non-Indigenous children, may
receive either PRP-T or PRP-OMP Hib vaccines (see Chapter 3.4, Haemophilus
influenzae type b). State/Territory health authorities should be contacted about the
vaccination schedule for each jurisdiction.
Vaccination for Aboriginal and Torres Strait Islander people 71

Hepatitis A
Hepatitis A infection has been shown to be very common in Aboriginal and
Torres Strait Islander children across northern Australia.13-15 Although the
symptoms of infection in early childhood are usually mild or absent, cases
complicated by liver failure and death have been reported among Indigenous
children in far north Queensland15 and the Kimberley13 and recorded
hospitalisation rates have been found to be at least 50 times higher in Indigenous
compared to non-Indigenous children.3 A vaccination program for Indigenous
children was introduced in north Queensland in 1999, which resulted in
substantial decreases in disease rates not only in Indigenous but also in non-
Indigenous children, suggesting a substantial herd immunity effect.16 Vaccination
is now recommended for Aboriginal and Torres Strait Islander children in those
jurisdictions with high incidence: the Northern Territory, Queensland, South
Australia and Western Australia (see Chapter 3.5, Hepatitis A). Two doses should
be given, commencing in the second year of life. As the exact recommended
ages of administration vary between States and Territories, jurisdictional health
authorities should be contacted about their vaccination schedules.
Pneumococcal vaccines
Some of the highest rates of invasive pneumococcal disease (IPD) ever reported
in the world were in young central Australian Aboriginal children before the
availability of the conjugate vaccine,17 and very high rates were also reported
in Indigenous children in other parts of northern Australia.18,19 High rates of
pneumococcal pneumonia have also been documented in central Australian
children,20 and Streptococcus pneumoniae has been implicated in the high rates of
otitis media.21 In response to this, the 7-valent pneumococcal conjugate vaccine
(7vPCV) was made available for Aboriginal and Torres Strait Islander children
from 2001. As well as higher rates of IPD, a wider range of serotypes is responsible
for disease in Aboriginal and Torres Strait Islander children, resulting in a lower
percentage of cases (below 60%) caused by serotypes included in the 7vPCV.18,19
Therefore, a booster dose of 23-valent pneumococcal polysaccharide vaccine at
18–24 months of age, following the primary course of 7vPCV, is recommended in
areas of high incidence, ie. the Northern Territory, Queensland, South Australia
and Western Australia. See Chapter 3.15, Pneumococcal disease for more information.
There has been a rapid decline in invasive pneumococcal disease in Indigenous
children since the introduction of the pneumococcal vaccines in 2001.22
ADULTS
Influenza
Influenza and/or pneumonia is the primary cause of around 2.5% of deaths in
Aboriginal and Torres Strait Islander people, the vast majority being adults.2
The disease burden is greatest in the elderly, with hospitalisation and death
more than twice as frequent in Indigenous adults aged ≥50 years, compared

to non-Indigenous adults.3 Younger Indigenous adults suffer an even greater
relative burden than non-Indigenous younger adults, at least 7 times higher
for hospitalisations, and 28 times higher for death,3 probably related to a high
prevalence of risk factors such as diabetes, renal disease and excessive alcohol use.2
The most common complication of influenza is secondary bacterial pneumonia,
and influenza vaccine has been shown to be effective in preventing pneumonia
and death in the elderly.23 Therefore, yearly influenza vaccination is
recommended for all Aboriginal and Torres Strait Islander adults aged ≥15 years.
Pneumococcal polysaccharide vaccine

Studies in far north Queensland and the Kimberley have demonstrated a
favourable impact of the 23-valent pneumococcal polysaccharide vaccine
(23vPPV) on rates of invasive pneumococcal disease in Indigenous adults,18,24,25
Aboriginal and Torres

Strait Islander people
2.1 Vaccination for
but, at a national level, disparities in disease rates between Indigenous and non-
Indigenous adults remain. As is the case for influenza and pneumonia, rates of
invasive pneumococcal disease are highest in older Indigenous adults, with rates
around 4 times higher in Indigenous compared to non-Indigenous adults aged
≥50 years.3 Rates in younger adults are slightly lower, but the relative difference
between Indigenous and non-Indigenous is much greater, around 12 times higher
in Indigenous compared to non-Indigenous adults aged 25–49 years.3 This has
been attributed to a high prevalence of at-risk conditions such as diabetes, renal
disease and excessive alcohol use.26
23vPPV is recommended for all Aboriginal and Torres Strait Islander people
aged ≥50 years, and for those aged 15–49 years who have high-risk underlying
conditions, and has been funded nationally for people in these categories since
1999. Eligibility for Indigenous adults may be broader than this in some regions;
jurisdictional health authorities should be contacted for further information. A
single revaccination is recommended after 5 years, and a second revaccination is
recommended in some circumstances. See Chapter 3.15, Pneumococcal disease for
more details.
Other vaccines
The first ever outbreak of Japanese encephalitis (JE) in Australia occurred in the
remote outer islands of the Torres Strait in 1995. JE vaccine was first offered to
the residents of these islands in late 1995 and, since then, the vaccine has been
integrated into the childhood vaccination schedule commencing at 12 months of
age (see Chapter 3.10, Japanese encephalitis).27
Service delivery
General Practitioners, Aboriginal Community Controlled Health Services,
Community Health Services, the Royal Flying Doctor Service and State/Territory
Corrective Services all provide substantial levels of vaccination services to
Aboriginal and Torres Strait Islander people, and are important to the success of
programs to vaccinate Indigenous people. While vaccination coverage estimates
Vaccination for Aboriginal and Torres Strait Islander people 73

vary over time and between communities, a relatively consistent finding
has been higher coverage in Aboriginal and Torres Strait Islander people in
remote compared to urban areas.28,29 Recent estimates suggest that, for vaccines
recommended for both Indigenous and non-Indigenous people, coverage is as
high or higher in Indigenous people as non-Indigenous people,3 but vaccination
is more frequently delayed.30 Coverage for vaccines recommended only for
Aboriginal and Torres Strait Islander people is generally lower than for vaccines
which are funded for all people in a particular age group.31 This points to the
importance of identification of Indigenous status, particularly in mainstream
health services, and particularly in urban areas. The use of patient information
systems to record Indigenous status and schedule preventive health services has
the potential to increase opportunistic vaccination and enable the provision of
patient reminders, with improved coverage and timeliness.32
References

2.2 Vaccination for international travel
Introduction
The number of Australians who travel overseas has increased steadily over
recent years and now between 3.5 and 4.5 million exits are made annually.
Although many of these trips are to countries where health risks exist, the
majority of Australians travelling overseas do not seek pre-travel health
advice.1 Every year, Australian travellers are injured, become ill, or even die,
while travelling abroad. Some of the infectious diseases that cause some of this
morbidity and mortality are preventable through vaccination.2,3
There is a range of travel vaccines that target infectious diseases that are more
common in different or less-developed environments, and therefore travel
itineraries should be assessed for the level of risk for these diseases.3 Factors
such as the interval between the initial presentation and the departure date,
destination, length of stay, activities during travel, type of accommodation,
personal medical history, age of the traveller, previous vaccination status and
financial constraints, all have a potential impact on vaccine recommendations. It
is important to identify travellers who may be at increased risk for travel related
illness, such as pregnant women, children, people with chronic systemic illness
or people with impaired immunity. Recent immigrants and their Australian-born
children are at particular risk of acquiring some of these infections when they
return to their country-of-origin to visit relatives and friends.4
international travel
2.2 Vaccination for
Infections acquired by travellers
Common infections acquired by travellers include those which follow ingestion
of contaminated food or water.2,5 Most of these are diarrhoeal diseases due to
enteric pathogens, but infections with extra-intestinal manifestations, such as
hepatitis A and typhoid, are also acquired this way. Vaccines are available for
cholera, hepatitis A and typhoid.
Insect-borne (particularly mosquito) infections, such as malaria and dengue,
are important causes of fever in Australian travellers returning from endemic
areas, southeast Asia and Oceania in particular.5 Japanese encephalitis occurs
throughout much of Asia and probably throughout Papua New Guinea. Yellow
fever occurs only in parts of Africa and Central and South America, while tick-
borne encephalitis occurs in parts of Europe and Asia. Vaccines are available for
Japanese encephalitis, yellow fever and tick-borne encephalitis.
Vaccine-preventable infections transmitted via respiratory droplets include
influenza, invasive meningococcal disease and measles; influenza may be the most
frequent vaccine-preventable infection among travellers.6 Tuberculosis, although
rare, is mostly acquired by expatriates who live in high-risk areas for long periods.
Vaccination for international travel 75

Blood-borne infections, such as hepatitis B, hepatitis C and human
immunodeficiency virus (HIV), may pose a threat to some Australian travellers.
In remote areas of some countries, there is the possibility that these viruses
are transmitted by healthcare workers using non-sterile medical equipment.
Hepatitis B vaccine is relevant to many travellers.
Travellers may be exposed to a variety of other exotic infections such as
rabies from dog (and other mammal) bites in many countries, schistosomiasis
after swimming in African lakes, and leptospirosis after rafting or wading in
contaminated streams. Of these, only rabies can be prevented by vaccination.
Practical aspects of travel vaccine administration

Consider each traveller individually, in the context of the specific itinerary. There
is no ‘correct’ list of vaccines for any single country. Ideally the vaccinations
should be started early, to minimise any adverse events around the time of
departure and allow sufficient time for adequate immunity to develop.
First, consider routine vaccines; all travellers should be up-to-date with
current standard vaccine recommendations. Then consider any other vaccines
that may be relevant to the individual’s usual health status, occupation or
lifestyle (eg. pneumococcal polysaccharide vaccine for an elderly person,
hepatitis B vaccine for a first aid officer). These should be offered before
consideration of the travel vaccines.
Travel vaccines should be considered according to risk. Priority should be given
to vaccines for diseases that are common and of significant impact (such as
influenza and hepatitis A), and to those diseases which, although less common,
have severe potential adverse outcomes (such as Japanese encephalitis and
rabies). Booster doses should be considered where appropriate (see Table 2.2.1);
a ‘rapid schedule’ for a combined hepatitis A/B vaccine is available for those
≥16 years of age with limited time before travel (see the appropriate vaccine
chapters). For children, consider the lower age limits for recommendation of
selected vaccines (see Table 2.2.2).
It is important to document travel vaccines appropriately, not only in the clinic’s
record but also in a suitable record that can be carried by the traveller.
Vaccines
All intending travellers should have been vaccinated according to the
recommended vaccination schedule for the traveller’s age. All children should
be vaccinated according to the National Immunisation Program (NIP) schedule.
In exceptional circumstances, the NIP vaccines may be administered at the
minimum age rather than the recommended age (see Section 1.3.5, Catch-up,
Table 1.3.7 Minimum age for the first dose of vaccine in exceptional circumstances).
Children vaccinated using the minimum age rather than the recommended age
may require extra vaccine doses to ensure adequate protection. The minimum

interval between doses must be adhered to (see Section 1.3.5, Catch-up, Table 1.3.6
Minimum dose intervals for NIP vaccines for children <8 years of age).
Measles
Most measles outbreaks now follow infection imported by inadequately
vaccinated young travellers. Therefore, Australians born during or since 1966
who have not received 2 doses of a measles-containing vaccine should be
vaccinated with MMR before travelling. Varicella vaccine should be offered to
travellers who have not had clinical disease or where serology demonstrates
lack of immunity (remembering that 2 doses, separated by at least a month, are
required by those ≥14 years of age).
Tetanus
Adult travellers should be adequately protected against tetanus before departure,
particularly if there could be delays in accessing health services. They should
receive a booster dose of dT if more than 10 years have elapsed since the last
dose. Protection against pertussis may also be offered at this opportunity (as
dTpa) if no previous dose of dTpa has been given.
Poliomyelitis
All travellers should be age-appropriately immunised against polio. If
travelling to countries where wild polio virus still exists (Afghanistan, India,
Nigeria, and Pakistan), inactivated poliomyelitis vaccine (IPV) should be
offered to those who have not completed a 3-dose primary course of any
polio vaccine, and a single booster dose should be given to those who have
2.2 Vaccination for
previously completed the primary course. For an up-to-date list of affected
countries see http://www.polioeradication.org.
Influenza and pneumococcal disease

Travellers aged ≥65 years, and those with any medical risk factor, should
receive the seasonal influenza vaccine and should have received the 23-valent
pneumococcal polysaccharide vaccine. All travellers should consider influenza
vaccine, especially when heading to the northern hemisphere winter.
Hepatitis B
All children and adolescents should have been vaccinated against hepatitis B
according to the NIP schedule. As they could be exposed to hepatitis B virus
during unplanned medical procedures, all travellers intending to spend a month
or more in Central and South America, Africa, Asia or Oceania should be
vaccinated against hepatitis B.

Hepatitis A
Hepatitis A vaccine should be given to all travellers ≥1 year of age travelling to
moderately to highly endemic countries (including all developing countries).
There is no place for the routine use of normal human immunoglobulin to
prevent hepatitis A in travellers (see Chapter 3.5, Hepatitis A).
Typhoid
Typhoid vaccine should be given to travellers ≥2 years of age travelling to endemic
regions, which include the Indian subcontinent, most southeast Asian countries,
many south Pacific nations and Papua New Guinea (see Chapter 3.23, Typhoid).
Cholera
Cholera vaccination is rarely indicated for travellers,3 as the risk of acquiring
cholera is extremely low, and the protection is of relatively short duration. It is
only indicated for those travellers at considerable risk, such as those working
in humanitarian disaster situations. However, it can also be considered for
those travellers with achlorhydria and for those at increased risk of severe or
complicated diarrhoeal disease (see Chapter 3.2, Cholera).
Certification of cholera vaccination has been abandoned globally, and no
countries have official entry requirements for cholera vaccination (see Chapter
3.2, Cholera).
Rabies
Travellers to rabies-endemic regions should be advised of the risk, and to avoid
close contact with either wild or domestic animals, and they should be advised
on what to do should they be either bitten or scratched by an animal while
abroad (see Chapter 3.1, Australian bat lyssavirus infection and rabies and also refer
to the World Health Organization website www.who.int).
Pre-travel (ie. pre-exposure) rabies vaccination (or, if appropriate, booster doses)
is recommended for expatriates and travellers who will be spending prolonged
periods (ie. more than a month) in rabies-endemic areas. (NB. This time interval,
of more than a month, is arbitrary, and rabies has occurred in travellers following
shorter periods of travel). Vaccination before travel simplifies the management of
a subsequent exposure because fewer doses of vaccine are needed, and because
rabies immunoglobulin (which is often difficult or even impossible to obtain in
many developing countries) is not required.
Japanese encephalitis
Vaccination is recommended for travellers spending a month or more in either
the rural areas of Asia or in Papua New Guinea, particularly if travel is during
the wet season and/or there is considerable outdoor activity and/or the
standard of accommodation is suboptimal. Vaccination is also recommended for
expatriates spending a year or more in Asia, even if much of the stay is in urban
areas (see Chapter 3.10, Japanese encephalitis).

Meningococcal infections
All children ≥12 months of age and all teenagers should have received the
meningococcal C conjugate vaccine. In addition, the tetravalent meningococcal
polysaccharide vaccine (4vMenPV) is recommended for those who intend
travelling to parts of the world where epidemics of meningococcal disease occur,
in particular the ‘meningitis belt’ of sub-Saharan Africa.7 Of note, large epidemics
of meningococcal meningitis occurred in Delhi, India, in 1966, 1985 and 2005.8
The Saudi Arabian authorities require that all pilgrims attending the annual
Hajj have evidence of recent vaccination with 4vMenPV9 (see Chapter 3.12,
Meningococcal disease).
Yellow fever
The World Health Organization no longer routinely reports on yellow fever
‘infected areas’. Rather, the yellow fever vaccine is now recommended for
travellers to yellow fever-endemic countries, in particular those that have
reported yellow fever since 1950 (see Chapter 3.25, Yellow fever, Table 3.25.1 Yellow
fever endemic countries).10
Briefly, provided there is no specific contraindication, the vaccine is
recommended for all those ≥9 months of age travelling anywhere in any country
in West Africa, and for all those ≥9 months of age travelling outside urban areas
of all other yellow fever-endemic countries (see Table 3.25.1).
Tuberculosis
Vaccination is generally recommended for tuberculin-negative children <5 years
2.2 Vaccination for
of age who will be living in developing countries for more than 3 months.
There is less evidence of the benefit of vaccination in older children and adults,
although consideration should be given to vaccination of tuberculin-negative
children <16 years of age who may be living for long periods in high-risk
countries (defined as having an incidence ≥100 per 100 000 population) (see
Chapter 3.22, Tuberculosis).
Tick-borne encephalitis
This disease is prevalent in central and northern Europe and across northern Asia
during the summer months. The vaccine is available only through Special Access
Scheme arrangements in Australia.

Table 2.2.1: Dose and routes of administration of commonly used vaccines in adult travellers (≥15 years of age)
Vaccine Brand name Main constituents Dose Route Primary schedule Duration of immunity/booster
(adults) (adults) recommendations
Hepatitis A Avaxim 160 EIA U inactivated HAV 0.5 mL IM 0, 6 to 12 months All probably give life-long immunity.
antigen
Havrix 1440 1440 EIA U inactivated HAV 1 mL IM 0, 6 to 12 months
antigen
VAQTA Adult 50 U inactivated HAV 1 mL IM 0, 6 to 18 months
antigen
Hepatitis A/B Twinrix (720/20) 720 EIA U inactivated 1 mL IM 0, 1, 6 months , or A completed series probably gives
†
combined HAV antigen and 20 µg 0, 7, 21 days, and 12 months life-long immunity to both hepatitis
recombinant hepatitis B A and B.
virus surface antigen
Hepatitis Vivaxim* 25 µg S. typhi 1 mL IM Single dose A dose of monovalent hepatitis A
A/ typhoid NB. Only polysaccharide and 160 EIA combined vaccine given 6–36 months later
combined for use in people U inactivated HAV antigen vaccine probably gives life-long immunity. The
≥16 years of age duration of protection against typhoid
is probably 3 years.
Hepatitis B Engerix-B 20 µg hepatitis B surface 1 mL IM 0, 1, 6 months, or A completed series probably gives

antigen protein 0, 1, 2, 12 months, or life-long immunity.
†
0, 7, 21 days, and 12 months
H-B-VAX II 10 µg hepatitis B surface 1 mL IM 0, 1, 6 months
antigen protein
Influenza Various 15 µg haemagglutinin of 2 0.5 mL IM Single dose As different strains circulate from year
current influenza A and 1 to year, annual vaccination with the
influenza B strains current formulation is necessary.
Japanese JE-VAX Inactivated Japanese 1 mL SC 0, 7, 28 days Boosters at 3-yearly intervals.

encephalitis encephalitis virus
Measles- Priorix Live attenuated measles- 0.5 mL IM/SC Australians born during or since 1966
mumps-rubella mumps-rubella viruses who do not have documented evidence
of having received 2 doses of a measles-
containing vaccine should receive at
least 1 dose of MMR before travel.
Vaccine Brand name Main constituents Dose Route Primary schedule Duration of immunity/booster
(adults) (adults) recommendations
Meningococcal Mencevax ACWY 50 µg capsular 0.5 mL SC Single dose Revaccinate 3–5-yearly if at
(tetravalent or polysaccharides from N. continuing risk.
polysaccharide) meningitidis serogroups A,
Menomune C, W135 & Y
Rabies Mérieux 2.5 IU inactivated rabies 1 mL IM/SC 0, 7, 28 days If at continued high risk of exposure,
(pre-exposure Inactivated Rabies virus antigens either measure rabies antibody
prophylaxis) Vaccine titres (and boost if titres reported as
Rabipur 2.5 IU inactivated rabies 1 mL IM 0, 7, 28 days inadequate) or give single booster
Inactivated Rabies virus antigens dose 2-yearly.
Vaccine
Tetanus, ADT Booster ≥20 IU tetanus toxoid, ≥2 IU 0.5 mL IM Provides protection for 10 years.
diphtheria (dT) diphtheria toxoid
Boostrix ≥20 IU tetanus toxoid, ≥2 IU 0.5 mL IM Providing pertussis (as well as
+ pertussis or diphtheria toxoid, purified tetanus and diphtheria) immunity is
(dTpa) Adacel antigens of B. pertussis preferred.
Typhoid Vivotif Oral Live attenuated typhoid A single Oral Days 1, 3 and 5 (+/– day 7)‡ Repeat 3-dose course after 3 years if
bacteria capsule 3 doses given initially; 4-dose course
after 5 years if 4 doses given initially.
Typherix
25 µg purified Vi capsular 0.5 mL IM Single dose Booster doses at 3-yearly intervals
or polysaccharide
Typhim Vi
Yellow fever Stamaril Live attenuated yellow fever 0.5 mL IM/SC Single dose 10-yearly boosters if at ongoing risk.
virus
* Vivaxim is registered for use in people aged ≥16 years.

† This ‘rapid’ schedule should be used only if there is very limited time before departure to endemic regions.
‡ A fourth capsule of oral typhoid vaccine can be given on day 7 (see Chapter 3.23, Typhoid).

2.2 Vaccination for
Vaccinating the traveller with special risk factors
See Chapter 2.3, Groups with special vaccination requirements and the specific vaccine chapters for recommendations for travellers
who are either pregnant or have impaired immunity. Children should receive the relevant travel vaccines, according to age (see
Table 2.2.2). Particular effort should be made to encourage the families of recent migrants to Australia to seek health advice before
travelling to their country of origin to visit relatives and friends.11
Table 2.2.2: Recommended lower age limits of travel vaccines for children
Vaccine Lower age limit Dose/route Primary schedule Comments
Hepatitis A
Avaxim 2 years 0.5 mL IM 0, 6 to 12 months Recommended for travel to developing countries.

Havrix Junior 2 years 0.5 mL IM 0, 6 to 12 months
VAQTA Paediatric/ Adolescent 1 year 0.5 mL IM 0, 6 to 18 months
Hepatitis A/B combined
Twinrix Junior (360/10) 1 year 0.5 mL IM 0, 1, 6 months Recommended for travel to developing countries.
Twinrix (720/20) 1 year 1.0 mL IM *0, 6 to 12 months

JE-VAX 1 year 1–3 years of age: 0, 7, 28 days Recommended for travellers spending more than 4 weeks in
0.5 mL SC rural areas of Asia and Papua New Guinea, or those staying
>3 years of age: 0, 7, 28 days in urban areas of Asia for more than 1 year.
1.0 mL SC
Meningococcal ACW135Y
Mencevax ACWY 2 years 0.5 mL SC Single dose Revaccinate 3–5-yearly if at continuing risk.
or Menomune Should be preceded by MenCCV by at least 2 weeks.
Rabies
Pre-exposure: The doses of rabies vaccines for pre-exposure are the same
Mérieux No lower age limit 1.0 mL IM/SC 0, 7, 28 days for both children and adults (1.0 mL).
Rabipur 1.0 mL IM 0, 7, 28 days

Vaccine Lower age limit Dose/route Primary schedule Comments
Typhoid
Vivotif Oral 6 years Oral capsule One capsule on days 1, 3, Recommended for travel to developing countries.
(oral live vaccine) and 5 (+/– day 7)† Do not give live oral vaccine with antibiotics or anti-
malarials. Do not give within 8 hours of inactivated oral
cholera vaccine.
Typherix or Typhim Vi (parenteral 2 years 0.5 mL IM Single dose
vaccine)
Yellow fever
Stamaril 9 months 0.5 mL IM/SC Single dose Yellow fever vaccine is contraindicated in infants <9 months
of age.
* This schedule is not recommended if prompt protection against hepatitis B is required.

† A fourth capsule of oral typhoid vaccine can be given on day 7 (see Chapter 3.23, Typhoid).
Further information
It should be noted that information on travellers’ risks is changing constantly. Up-to-date knowledge requires an understanding
of the changing epidemiology of a variety of infectious and emerging diseases. The World Health Organization’s comprehensive
publication International Travel and Health is available at www.who.int/ith and the CDC’s publication Health Information for
International Travel, 2005–2006 (the ‘Yellow Book’) is available at www.cdc.gov/travel/index.htm. As recommendations for specific
countries change frequently, such sources should be checked regularly.
References
Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.

2.2 Vaccination for
2.3 Groups with special
vaccination requirements
This chapter considers the use of vaccines in people who have special vaccination
requirements, those who may experience more frequent adverse events, and
those who may have a suboptimal response to vaccination. Recommendations for
vaccination of those at occupational risk are also included.
2.3.1 Vaccination of children who have had a serious

adverse event following immunisation (AEFI)
Children who have had a serious AEFI (other than a contraindication, such as
anaphylaxis) may be subsequently vaccinated under close medical supervision
(see Appendix 6, Definitions of adverse events following immunisation). Not all States
and Territories offer an adverse event immunisation clinic. However, in States or
Territories where there are no clinics, there is often a paediatrician or infectious
diseases specialist who will review families who have concerns regarding future
vaccinations following a previous adverse event.
To make an enquiry, or for more information about making a referral to a
vaccination serious adverse events service, please go to the website below:
http://immunise.health.gov.au/internet/immunise/publishing.nsf/Content/
provider-reactions.
2.3.2 Vaccination of women planning pregnancy,

pregnant or breastfeeding women, and preterm infants
(i) Women planning pregnancy
The need for measles, mumps, rubella, varicella, diphtheria, tetanus and
pertussis vaccination should be assessed as part of any pre-conception health
check. Where previous vaccination history or infection is uncertain, relevant
serological testing should be undertaken to ascertain immunity. Influenza vaccine
is recommended routinely and pneumococcal vaccination is recommended
for women with risk factors, including smokers. Women receiving live viral
vaccines must be advised against falling pregnant within 28 days of vaccination.
Please refer to individual disease chapters for more information about primary
vaccination for these diseases.

(ii) Pregnancy
Although the use of most vaccines during pregnancy is not usually
recommended on precautionary grounds, there is no convincing evidence that
pregnancy should be an absolute contraindication to the use of any vaccine,
particularly inactivated vaccines. The only exception is vaccinia virus (smallpox
vaccination), which has been shown to cause fetal malformation. There is some
evidence, however, that fever per se is teratogenic.1,2 With the exception of the use
of influenza vaccine, the NHMRC takes the conservative position that the use of
vaccines during pregnancy might cause fever and should be avoided other than
in situations of increased risk, where the benefits of protection from vaccination
outweigh the risks. Eliminating the risk of exposure to vaccine-preventable
diseases during pregnancy (eg. by changing travel plans, avoiding high-risk
behaviours or occupational exposures) is an alternative to vaccination.
Live attenuated vaccines are contraindicated for pregnant women because of
the hypothetical risk of harm to the fetus should transmission occur. If a live
attenuated vaccine is inadvertently given to a pregnant woman, or if a woman
becomes pregnant within 4 weeks of vaccination, she should be counselled
about the potential transmission, albeit extremely unlikely, to the fetus. There is,
however, no indication to consider termination of a pregnancy in this situation.
The following table may be used as a guide to the recommended use of
vaccinations in pregnancy. Information regarding pregnancy status in women of
reproductive age should be part of the routine pre-vaccination screening checklist
(see Section 1.3.4, Pre-vaccination screening).
Groups with special vaccination requirements 85

Table 2.3.1: Vaccinations in pregnancy
Live attenuated vaccines
Bacterial Recommendation Comments
BCG vaccine Contraindicated. Hypothetical risk only. BCG has not been shown to cause fetal damage.
(Live attenuated strain
M. bovis)
Rotavirus vaccine Contraindicated. Rotavirus vaccine can be safely administered to household contacts of pregnant women.
Not registered for use in adults.
Oral typhoid vaccine Contraindicated. Studies in animals are inadequate but available data show no evidence of an increased
occurrence of fetal damage with oral live attenuated vaccine. Inactivated typhoid Vi
polysaccharide vaccine is preferred.
Live attenuated vaccines
Viral Recommendation Comments
Measles-mumps- Contraindicated. Hypothetical risk only. Despite concerns that attenuated rubella vaccine virus might cause
rubella (MMR) vaccine congenital abnormalities, rubella vaccine (either monovalent or as MMR) has been given to
pregnant women (usually inadvertently) without harm to the fetus. Even though the rubella
vaccine virus can infect the fetus if given in early pregnancy, there is no evidence that it causes
congenital rubella syndrome in infants born to susceptible mothers vaccinated during pregnancy

and, in particular, rubella vaccination during pregnancy is not an indication for termination.3
Women of child-bearing age should avoid pregnancy for 28 days after vaccination.
It is standard practice to test all pregnant women for immunity to rubella, and to vaccinate
susceptible women as soon as possible after delivery (preferably using MMR).
Smallpox vaccine Contraindicated. Should not be given to women who are pregnant or considering becoming pregnant.
Pregnancy should be avoided for 3 months after vaccination.
Varicella vaccine Contraindicated. Hypothetical risk only. Congenital varicella syndrome has (to date) not been identified in
women who have been inadvertently vaccinated in early pregnancy.4 This provides some
reassurance of the safety of the vaccine.
Women of child-bearing age should avoid becoming pregnant for 28 days after vaccination.
Yellow fever vaccine Contraindicated, unless travelling to yellow fever Hypothetical risk only. Yellow fever vaccine has been given to a large number of pregnant
endemic area. women with no adverse outcomes.5 Pregnant women who travel to a yellow fever-endemic
area against medical advice should receive yellow fever vaccine.
The administration of yellow fever vaccine in early pregnancy is not an indication for termination.
Inactivated vaccines
Bacterial Recommendation Comments
Cholera (oral) vaccine Not recommended. Inadequate information on safety of oral cholera vaccine in pregnancy.
Adolescent/adult Recommended for pregnant women who work Data on use of adolescent/adult formulation dTpa during pregnancy are not available, so it
formulation dTpa in close contact with infants eg. childcare, should be given in pregnancy only when the possible advantages outweigh the possible risks
vaccine
neonatal units. to the fetus. All women who are planning pregnancy should be encouraged to receive a single
dose of dTpa before pregnancy; if not given before pregnancy, it should be given as soon as
possible after delivery.
Haemophilus influenzae Recommended for pregnant women at increased Available clinical data suggest that it is unlikely that use of Hib vaccine in pregnant women
type b (Hib) vaccine risk of Hib disease (eg. hyposplenia, asplenia). would have any deleterious effects on the pregnancy.
Meningococcal C Recommended for pregnant women at increased Although no clinical study data are available on the use of MenCCV in pregnant women, it is
conjugate vaccine risk of meningococcal disease (eg. hyposplenia, unlikely that it would have any deleterious effects on the pregnancy.
(MenCCV)
asplenia), or possible exposure to serogroup C.
Meningococcal Recommended for pregnant women at increased No documented adverse events in either pregnant women or their newborns when vaccinated
polysaccharide vaccine risk of meningococcal disease who have not been with 4vMenPV administered in the second and third trimesters of pregnancy. The number of
(4vMenPV)
vaccinated with 4vMenPV in the past 3 years (eg. pregnant vaccinees reported in the literature is small.
hyposplenia, asplenia), or possible exposure to
serogroup A, W135 or Y.
7-valent pneumococcal Not recommended. Vaccination during pregnancy has not been evaluated for potential harmful effects to mother or
conjugate vaccine fetus. Although unlikely to result in adverse effects, the vaccine is currently only registered for
(7vPCV)
use in children ≤9 years of age.
23-valent Recommended for pregnant women at increased No adverse effects when administered in pregnancy. Data are limited to clinical trials and
pneumococcal risk of invasive pneumococcal disease (IPD) (eg. deferral of vaccine is recommended unless there is an increased risk of IPD. Women of
polysaccharide vaccine
(23vPPV) asplenia, impaired immunity, chronic illness, CSF reproductive age with known risk factors for IPD (including smokers) should be vaccinated
leak) who have not received 23vPPV in the past before planned pregnancy.
5 years (and provided they have not received 2
previous doses).
Q fever vaccine Not recommended. Safety of use in pregnancy has not been established.
Typhoid Vi In pregnant women travelling to endemic There is no evidence of risk to the fetus from vaccination with Vi polysaccharide vaccine.
polysaccharide vaccine countries where water quality and sanitation
is poor.

Viral Recommendation Comments
Hepatitis A vaccine Recommended for susceptible pregnant Hepatitis A vaccine should only be given to pregnant women who are non-immune and where
women travelling to areas of moderate to high there is a clear indication. As for any inactivated viral vaccines, although data are limited, no
endemicity or who are at increased risk of adverse effects on the developing fetus are expected.
exposure through lifestyle factors, or where
severe outcomes may be expected (eg. pre-
existing liver disease).
Hepatitis B vaccine Recommended for susceptible pregnant women Hepatitis B vaccine should only be given to pregnant women who are non-immune and where
for whom this vaccine would otherwise be there is a clear indication. As for any inactivated viral vaccines, although data are limited, no
recommended. adverse effects on the developing fetus are expected.
Human papillomavirus Not recommended. There are no concerns that HPV vaccines are teratogenic and animal studies have found no
(HPV) vaccine evidence of teratogenicity or adverse fetal outcomes. However, where vaccine has inadvertently
been administered during pregnancy, further doses should be deferred until after delivery.
Influenza vaccine Recommended for all pregnant women who There is no evidence of congenital defects or adverse effects on the fetus of women who are
will be in the second or third trimester during vaccinated against influenza in pregnancy.
the influenza season, including those in the first
trimester at the time of vaccination.
Japanese encephalitis Recommended for pregnant women at risk of No adverse effects on pregnancy have been attributed to JE vaccine, whereas JE infection is

(JE) vaccine acquiring JE. associated with miscarriage.
Inactivated polio Recommended for pregnant women at risk IPV should only be given to pregnant women when clearly indicated. There is no convincing
vaccine (IPV) of poliovirus exposure (eg. travel to endemic evidence of risk to the fetus from IPV administered in pregnancy.
countries).
Rabies vaccine Recommended for pregnant women for whom Pregnancy is never a contraindication to rabies vaccination in situations where there is a
this vaccine would otherwise be recommended significant risk of exposure (related to occupation or travel), or where there has been a possible
(eg. travellers to rabies endemic countries). exposure to rabies virus or Australian bat lyssavirus.
Toxoids and immunoglobulins
Tetanus/diphtheria Recommended for pregnant women. Toxoids are safe in pregnancy.

toxoid
Pooled or Recommended for susceptible pregnant women There is no known risk to the fetus from passive immunisation of pregnant women with
hyperimmune exposed to: measles, hepatitis A, hepatitis B, immunoglobulins.
immunoglobulins
rabies or Australian bat lyssavirus, varicella
viruses and tetanus.
Contact between pregnant women and individuals
who have recently received live vaccines
Although there is no risk of transmission of the MMR vaccine viruses (MMR
vaccine viruses are not transmissible), and an almost negligible risk of
transmission of varicella vaccine virus, there is a very small risk of transmission
of the rotavirus vaccine viruses to a susceptible pregnant woman. However, there
is no evidence that there is any risk to the fetus if pregnant women are in contact
with recently vaccinated individuals. Therefore, it is safe to administer varicella
vaccine and rotavirus vaccine to household contacts of pregnant women.
(iii) Breastfeeding and vaccination

The rubella vaccine virus may be secreted in human breast milk and transmitted
to breastfed infants but, where infection has occurred in an infant, it has been
mild. Otherwise, there is no evidence of risk to the breastfeeding baby if the
mother is vaccinated with any of the live or inactivated vaccines described in
this Handbook. Breastfeeding does not adversely affect immunisation and is not a
contraindication for the administration of any vaccine to the baby.
(iv) Preterm babies

Preterm (premature) infants have a special need for protection and, despite their
immunological immaturity, they generally respond well to vaccines. Provided they
are well and there are no contraindications to vaccination they should be vaccinated
according to the recommended schedule at the usual chronological age.6-14
Routine childhood vaccines can cause an increase in apnoea in preterm babies
vaccinated in hospital, particularly babies still requiring special care, but these
are generally self-limiting and do not affect the clinical course.8 Preterm babies in
hospital should be monitored for apnoea or bradycardia for up to 48 hours post
vaccination.6-8 Vaccinations have not caused an increase in apnoeas in babies at
home, and are not associated with an increased risk of SIDS.6-8
• Vaccines as recommended on the National Immunisation Program (NIP)
schedule
Preterm babies produce good antibody responses to most vaccines in the NIP.
They should be vaccinated at the standard recommended ages without correction
for prematurity.14
• Pneumococcal vaccines
All preterm babies born at less than 28 weeks’ gestation or with chronic lung
disease should be offered the 7-valent pneumococcal conjugate vaccine at 2, 4
and 6 months of age, with a fourth dose at 12 months of age, and a 23-valent
pneumococcal polysaccharide vaccine booster at 4–5 years of age (see Chapter
3.15, Pneumococcal disease).

• Haemophilus influenzae type b vaccine
Some smaller preterm babies do not respond as well as term babies to PRP-OMP
(Liquid PedvaxHIB or COMVAX) Hib vaccine.9-14 When PRP-OMP is used in an
extremely preterm baby (<28 weeks’ gestation or <1500 g birth weight), an extra
dose of vaccine should be given at 6 months of age (ie. doses should be given at
2, 4, 6 and 12 months of age) (see Chapter 3.4, Haemophilus influenzae type b).
• Hepatitis B vaccine
Preterm babies do not respond as well to hepatitis B-containing vaccines as
term babies.7,12,13,15 Thus, for babies born at <32 weeks’ gestation or <2000 g birth
weight, it is recommended to give vaccine at 0, 2, 4 and 6 months of age and
either:
(See Chapter 3.6, Hepatitis B.)
• Influenza vaccine
Preterm infants with ongoing problems at 6 months of age, particularly
respiratory, cardiac or neurological disease, should receive influenza vaccine.
2.3.3 Vaccination of individuals with impaired

immunity due to disease or treatment16-18
The vaccination of individuals with impaired immune systems presents several
problems. First, the immune response to vaccines may be inadequate and,
second, there is a risk that some live vaccines may themselves cause progressive
infection. Degrees of impaired immunity vary from insignificant to profound,
and this should be taken into account when considering a vaccination schedule,
as should the risk of acquiring the vaccine-preventable diseases.
Although it may seem logical to give higher or more frequent doses of vaccines
to these patients, in many cases there are insufficient data to advocate such
measures. Because of the uncertainty of the immune response in some patients
with impaired immunity, it may be useful to measure post-vaccination antibody
titres in groups such as children who have received haematopoietic stem cell
transplants (see ‘2.3.3.3 Re-vaccination following haematopoietic stem cell
transplantation (HSCT)’ below).
Administration of certain vaccines is a priority for some patients with medical
conditions that increase the risk from infectious diseases, even in the absence
of specific immune defects. These include: the use of influenza vaccine in
individuals with severe asthma, chronic lung disease, congenital heart disease,
diabetes and Down syndrome; pneumococcal conjugate vaccine in children

with renal failure, persistent nephrotic syndrome and certain anatomical
abnormalities; and pneumococcal polysaccharide vaccine in adults with
certain chronic medical conditions. See the appropriate chapters for current
recommendations.
Live viral and bacterial vaccines

Although most live vaccines are contraindicated in patients with significantly
impaired immunity, the risk of progressive infection varies. The following is a list
of current recommendations:
• Vaccines for smallpox (vaccinia virus) and tuberculosis (BCG) are always
contraindicated.
• Live vaccines such as MMR and varicella vaccines must not be given to
people with severely impaired immunity, but are safe to be given to the
siblings or other household contacts of such people.
• MMR and varicella vaccines may be given to children with HIV infection
with mildly impaired immunity (see ‘2.3.3.4 HIV-infected individuals’
below).
• Travellers with impaired immunity should not receive oral typhoid vaccines.
Use parenteral typhoid Vi polysaccharide vaccine instead.
• Yellow fever vaccine is contraindicated in travellers with impaired
immunity going to endemic countries. If they must proceed with the travel,
they should obtain a letter from a doctor, clearly stating the reason for
withholding the vaccine. The letter should be formal, signed and dated, and
on the practice’s letterhead.
Household contacts vaccinated with live vaccines who

live with a person who has impaired immunity
Healthy siblings and household contacts of children with impaired immunity
should be vaccinated with MMR, varicella and rotavirus vaccines (where
indicated) to prevent them from infecting the children with impaired
immunity. Although there is no risk of transmission of the MMR vaccine
viruses, and an almost negligible risk of transmission of varicella vaccine
virus, there is a small risk of transmission of the rotavirus vaccine viruses
(see Chapter 3.18, Rotavirus and Chapter 3.24, Varicella). Annual influenza
vaccination is recommended for contacts (including children ≥6 months of age)

of people with impaired immunity.

Influenza and pneumococcal vaccines
Morbidity and mortality from influenza and invasive pneumococcal disease
are increased in all people with severely impaired immunity. Annual influenza
vaccination should be given to all people ≥6 months of age with severely
impaired immunity. Such individuals should also receive either the 7-valent
pneumococcal conjugate vaccine (7vPCV), or 23-valent pneumococcal
polysaccharide vaccine (23vPPV), depending on their age (see Chapter 3.15,
Pneumococcal disease). Although the immune response to 23vPPV may be
suboptimal in those who most need protection, the vaccine is nevertheless
strongly recommended for these individuals.
While it may seem logical to give 7vPCV followed by 23vPPV to adults with
impaired immunity, studies evaluating the effectiveness of such a regimen are
not yet available.
Impaired immunity associated with corticosteroid administration

In adults, daily doses of oral corticosteroids in excess of 60 mg of prednisolone
(or equivalent) and, in children, doses in excess of either 2 mg/kg per day for
more than a week or 1 mg/kg per day for more than 4 weeks, are associated with
significantly impaired immunity. However, even lower doses may be associated
with some impairment of the immune response.19
Children on daily doses of ≤2 mg/kg per day of systemic corticosteroids for
less than 1 week, and those on lower doses of 1 mg/kg per day or alternate-day
regimens for periods of up to 4 weeks, may be given live viral vaccines.
Children receiving >2 mg/kg per day or ≥20 mg per day in total of prednisolone
(or equivalent) for >14 days can receive live viral vaccines after corticosteroid
therapy has been discontinued for at least 1 month.
For adults treated with systemic corticosteroids in excess of 60 mg per day, live
vaccines (such as MMR and varicella vaccines) should be postponed until at least
3 months after treatment has stopped.
2.3.3.1 Oncology patients16,20-24

• Paediatric and adult patients undergoing cancer chemotherapy who have
not completed a primary vaccination schedule before diagnosis
Live viral vaccines, including varicella and MMR vaccines, are contraindicated
in cancer patients receiving immunosuppressive therapy and/or with
poorly controlled malignant disease. These vaccines may be administered
to seronegative children at least 3 months after completion of chemotherapy
and/or high-dose steroid therapy, provided the underlying malignancy is in
remission. Administration of live viral vaccines (MMR, varicella or MMRV
[when available]) should be deferred if blood products or immunoglobulins have
been recently administered (see Table 2.3.5 Recommended intervals between either
immunoglobulins or blood products and MMR, MMRV or varicella vaccination).

Influenza vaccination is recommended annually in all cancer patients ≥6 months
of age and should be started as close to the time of cancer diagnosis as possible.
During chemotherapy, and for 6 months afterwards, patients may receive
inactivated vaccines (eg. DTPa if <8 years old, Hib if <5 years old, hepatitis B,
IPV) according to the routine vaccination schedule, but it should be remembered
that patients are unlikely to mount a full immune response while they are on
therapy. Antibody responses to hepatitis B should be checked 4 weeks after
completing the third dose and, where antibody titres are <10 IU/mL, HBsAg
carriage should be investigated. If HBsAg negative, then patients should be
given a fourth double dose of vaccine or a further 3 doses of vaccine at monthly
intervals (see Chapter 3.6, Hepatitis B).
Vaccines should not be administered during times of severe neutropenia

(absolute neutrophil count <0.5 x 109/L), to avoid precipitating an acute
febrile episode.
Pneumococcal vaccination is recommended in oncology patients with an increased

risk of invasive pneumococcal disease (IPD), especially patients with underlying
haematological malignancies (multiple myeloma, Hodgkin’s lymphoma, non-
Hodgkin’s lymphoma, chronic lymphocytic leukaemia). In patients ≥10 years
of age, 23vPPV should ideally be given as early as possible after diagnosis and
before chemotherapy and/or radiotherapy is initiated.25,26 When this is not
practicable, vaccination should be given after completion of chemotherapy.27 For
children <10 years of age with haematological malignancies, primary and catch-
up pneumococcal vaccination should be administered as detailed in Table 1.3.11
Recommendations for pneumococcal catch-up vaccination for children ≤5 years of age with
underlying medical conditions (see footnote accompanying this Table).
Any deviations from these guidelines should be discussed with an oncologist.
• Paediatric and adult patients with cancer who have completed cancer
therapy and have received a primary course of vaccination before diagnosis
The following schedule of booster vaccination is recommended if the patient
is well and infection-free 6 months after chemotherapy, and if the underlying
disease is in remission:
• DTPa if <8 years of age (use dT or adolescent/adult formulation dTpa if

≥8 years of age),
• MMR, IPV, hepatitis B, 7vPCV and Hib (if <5 years of age or with previous
splenectomy/hyposplenism).
These vaccines may be given without checking antibody titres beforehand, and
may be given together on 1 day. Measles and rubella antibody status should be
checked 6 to 8 weeks after vaccination. Patients who have not seroconverted
should receive a further dose.

Children who are seronegative to varicella-zoster virus, especially those with
acute lymphoblastic leukaemia, should receive a 2-dose schedule of varicella
vaccine, at least 3 months after chemotherapy has been ceased.28 Administration
of live vaccines (MMR, varicella or MMRV [when available]) should be deferred
if blood products or immunoglobulins have been recently administered (see
Table 2.3.5 Recommended intervals between either immunoglobulins or blood products
and MMR, MMRV or varicella vaccination).
2.3.3.2 Solid organ transplant recipients23

For solid organ transplant (SOT) recipients, depending on the transplanted
organ, and to prevent rejection, differing doses of immunosuppressive agents
are needed, which may influence the effectiveness of vaccines. Where possible,
children undergoing solid organ transplantation should be vaccinated well
before transplantation, and inactivated vaccines can be used 6 to 12 months after
transplantation. Live vaccines are contraindicated in most post-transplantation
protocols due to concerns of disseminated infection, although data in this
population are limited. Recommended vaccinations for child and adult SOT
recipients are given in Table 2.3.2.

Table 2.3.2: Recommendations for vaccinations for solid organ transplant (SOT) recipients
Vaccines recommended before Vaccines recommended after Comments
transplantation transplantation if not given
beforehand
Vaccine Child Adult Child Adult
Hib vaccine Yes Yes If possible complete vaccination at least
6 weeks before transplantation.23
Hepatitis A vaccine Yes Yes, if seronegative Yes Yes, if seronegative Recommended for all
seronegative SOT recipients.
Hepatitis B vaccine Yes Yes, depending on Yes Yes, depending on Recommended for all
serological status serological status seronegative SOT recipients.
Accelerated schedules can be
used (see Table 3.6.2 Accelerated
hepatitis B vaccination schedules).
Influenza vaccine Annual vaccination starting before transplantation for people ≥6 months of age.
7-valent pneumococcal Yes, if <10 years Yes, if <10 years The primary schedule should be
conjugate vaccine of age of age completed before transplantation.
(7vPCV) For children <10 years of age, 7vPCV
should be administered as detailed
in Table 1.3.11 Recommendations for
pneumococcal catch-up vaccination
for children ≤5 years of age with
underlying medical conditions (see
footnote accompanying this Table).
23-valent Yes Yes Yes Yes See Table 3.15.3 Revaccination with
pneumococcal [If <10 years [If <10 years 23vPPV for people ≥10 years of age.
polysaccharide vaccine of age see of age see
(23vPPV) Table 1.3.11.] Table 1.3.11.]

Vaccines recommended before Vaccines recommended after Comments
transplantation transplantation if not given
beforehand
Vaccine Child Adult Child Adult
Inactivated poliovirus Yes Yes, if no booster Yes Yes, if no booster The primary schedule should be
vaccine (IPV) in past 10 years in past 10 years completed before transplantation.
Diphtheria-tetanus- Yes Yes, provided Yes Yes, provided The primary schedule should be
pertussis vaccine dTpa has not been dTpa has not been completed before transplantation.
given previously given previously
(DTPa for children
<8 years of age; dTpa
for people ≥8 years of
age)
Meningococcal C Yes, if ≥1 Yes Yes, if ≥1 Yes
conjugate vaccine year of age year of age
(MenCCV)
Meningococcal Yes, if >2 years Yes Yes, if >2 years Yes Give 4vMenPV at an interval of at

polysaccharide vaccine of age of age least 2 weeks after MenCCV.
(4vMenPV)
MMR vaccine Yes Yes, Contraindicated The primary schedule should be
unless 2 previous completed before transplantation
documented doses provided the recipient is no longer
on immunosuppressive therapy.
Varicella vaccine Yes Yes Contraindicated Vaccination should be completed before
transplantation provided the recipient is
no longer on immunosuppressive therapy.
2.3.3.3 Re-vaccination following haematopoietic
stem cell transplantation (HSCT)29-33
Haematopoietic stem cells are sourced from peripheral blood, bone marrow or
umbilical cord. Protective immunity to vaccine-preventable diseases is partially or
completely lost following either allogeneic or autologous stem cell transplantation.
Impaired immunity following allogeneic transplantation is caused by a combination
of the preparative chemotherapy given before transplantation, graft-versus-host
disease (GVHD), and immunosuppressive therapy following transplantation.
Persisting impaired immunity is common, particularly in patients with chronic
GVHD. Immunity is also impaired in autologous stem cell transplant recipients due
to high-dose chemotherapy and radiotherapy, but GVHD is not a concern as donor
and recipient are the same. In most cases, autologous transplant recipients will
recover their immunity more quickly than allogeneic transplant recipients.
Separate transplant schedules for autologous and allogeneic transplant recipients
have not been supported in published guidelines because of limited data. For
practical purposes, a similar schedule is therefore recommended, regardless of
donor source (peripheral blood, bone marrow or umbilical cord), preparative
chemotherapy (ablative or reduced intensity), or transplant type (allogeneic or
autologous).32,34
HSCT recipients with ongoing GVHD or remaining on immunosuppressive
therapy should not be given live vaccines. Chronic GVHD (cGVHD) is associated
with functional hyposplenism and patients are therefore susceptible to infections
with encapsulated organisms, especially Streptococcus pneumoniae. For patients
with cGVHD who remain on active immunosuppression, antibiotic prophylaxis
is recommended.35
The immune response to vaccinations is usually poor during the first
6 months after HSCT. Donor immunisation with hepatitis B, tetanus, Hib and
pneumococcal conjugate vaccines before stem cell harvesting has been shown to
elicit improved early antibody responses in HSCT recipients vaccinated in the
post-transplantation period.36-39 However, practical and ethical considerations
currently limit the use of donor immunisation.
Routine serological testing for several infectious agents increases costs,
and antibody levels conferring protective immunity are poorly defined.
For those vaccines that are recommended for all HSCT recipients (tetanus,
diphtheria, polio, influenza, pneumococcal, Hib), pre-vaccination testing is not
recommended as the response to a primary course of these vaccines is generally
adequate. The serological response to pneumococcal polysaccharide vaccine is
less predictable. Pneumococcal serology is only available in a few specialised
laboratories and is not routinely recommended. Immunity testing before and
after vaccination for hepatitis B, measles, rubella and varicella is recommended,
as antibody levels will determine the need for revaccination.34
A recommended schedule of vaccination is outlined in Table 2.3.3.31,32,34

Table 2.3.3: Post-transplantation vaccination schedules for allogeneic and
autologous haematopoietic stem cell transplant recipients32,34
Vaccine Months after HSCT Comments
12 14 24
Diphtheria-tetanus- Yes Yes Yes For recipients ≥8 years of age, give first
pertussis dose as dTpa followed by 2 doses dT. If
(DTPa for children dT unavailable, dTpa may be used for all
<8 years of age; dTpa for 3 doses.
people ≥8 years of age)
Hib Yes Yes Yes
Hepatitis A Not routinely recommended, see Chapter 3.5, Hepatitis A.
Hepatitis B Yes Yes Yes High dose (H-B-VAX II dialysis

formulation) vaccine is recommended.
Influenza Annual vaccination for life, starting 6 months post HSCT, for people ≥6 months
of age.
MMR No No Yes Vaccination of measles or rubella

seronegative HSCT recipients at
24 months post HSCT is recommended,
provided that immunosuppressive
therapy has been discontinued, there is
no chronic GVHD, and cell-mediated
immunity has been reconstituted.
MenCCV Yes, ≥1 People ≥1 year of age should receive 1

year of dose of MenCCV.
age
4vMenPV Yes, People ≥1 year of age should receive 1

≥2 years dose of MenCCV (as above). This should
of age (see be followed by a dose of 4vMenPV
comment) when ≥2 years of age or, if already aged
>2 years, give after an interval of at least
2 weeks following the MenCCV.
7vPCV Although there are limited data on the effectiveness of 7vPCV in HSCT recipients,
vaccination is recommended for children ≤9 years of age starting 6 months post
HSCT (see Table 3.15.1 Summary table – pneumococcal vaccination schedule for
children ≤9 years of age).
23vPPV Yes See Table 3.15.3 Revaccination with

23vPPV for people ≥10 years of age.
Adjunctive antibiotic prophylaxis is
recommended for patients with chronic
GVHD.
IPV Yes Yes Yes
Varicella vaccine No No Yes Vaccination of seronegative HSCT

recipients at 24 months post HSCT
is recommended, provided that
immunosuppressive therapy has been
discontinued, there is no chronic GVHD,
and cell-mediated immunity has been
reconstituted.

2.3.3.4 HIV-infected individuals
Vaccination schedules for HIV-infected patients should be determined by the
patient’s age, degree of impaired immunity (CD4 count) and the risk of infection.
Children with perinatally acquired HIV differ substantially from adults as
immunisation and first exposure to vaccine antigens occurs after HIV infection,
whereas for adults, most vaccines are inducing a secondary immune response.40
HIV-infected individuals of any age who are well controlled on combination
antiretroviral therapy (undetected or low viral load with good preservation of
CD4 lymphocyte count) are likely to respond well to vaccines.
HIV-infected patients should be vaccinated as follows:
• Diphtheria-tetanus-pertussis (DTPa/dTpa), Hib and IPV vaccines – use the
standard schedule.41
• MMR vaccine should be routinely administered to HIV-infected children
at 12 months of age unless they have severely impaired immunity. Table
2.3.4 shows age-specific definitions of moderately and severely impaired
immunity. Measles may cause severe disease in HIV-infected children and
children with severely impaired immunity who are exposed to measles
should, therefore, be given normal immunoglobulin (in a dose of 0.5 mL/kg),
regardless of their vaccination status.40
• While varicella vaccine is contraindicated in adults with HIV, its use may
be considered for asymptomatic or mildly affected children ≥12 months and
<13 years of age.42 The Advisory Committee on Immunization Practices
(ACIP) recommends use of the vaccine, given in 2 doses, 3 months apart, in
children with age-specific CD4 T-lymphocyte percentages greater than 25%.43
Table 2.3.4: Immunological categories based on age-specific CD4 counts and

percentage of total lymphocytes44
Category <12 months 1–5 years ≥6 years

CD4 per % CD4 per % CD4 per %
µL µL µL
No evidence ≥1500 ≥25 ≥1000 ≥25 ≥500 ≥25
of impaired
immunity
Moderately 750–1499 15–24 500–999 15–24 200–499 15–24

impaired
immunity
Severely <750 <15 <500 <15 <200 <15
impaired
immunity

• Pneumococcal disease, both respiratory and invasive, is a frequent cause of
morbidity in HIV-infected children and adults. Infants and children <10 years
of age should be vaccinated with the 7vPCV (see Table 3.15.1 Summary table –
pneumococcal vaccination schedule for children ≤9 years of age) and older children
and adults should be vaccinated with the 23vPPV (see also Chapter 3.15,
Pneumococcal disease).45,46
• Influenza vaccine is recommended even in symptomatic HIV-infected adults
and children.47-49 Viral loads may increase after vaccination, but CD4 counts
are unaffected and the benefits exceed the risk.50-53
• Hepatitis B vaccine is safe to use, but the immunological response may be
poor. HIV-positive adults should receive 3 doses of the H-B-VAX II dialysis
formulation and HIV-positive children should receive 3 doses of Engerix-B
adult formulation. Antibody level should be measured at the completion
of the vaccination schedule. Because many HIV-positive men who have sex
with men may already have been exposed to the hepatitis B and hepatitis
A viruses, their susceptibility should be determined in order to avoid
unnecessary vaccination.
• Susceptible HIV-infected individuals should be vaccinated against hepatitis A.54
• BCG must not be given to HIV-infected children or adults because of the risk
of disseminated BCG infection.
• Yellow fever and oral live attenuated typhoid vaccines should not be given to
HIV-infected individuals. Vi polysaccharide typhoid, Japanese encephalitis
and rabies vaccines are safe and can be used for the usual indications (see
Chapter 2.2, Vaccination for international travel).
2.3.3.5 Individuals with functional or anatomical asplenia55,56

Individuals with an absent or dysfunctional spleen are at an increased risk of
fulminant bacteraemia, most notably pneumococcal, for the rest of their lives.57
• Pneumococcal vaccination
All individuals with functional or anatomical asplenia should be vaccinated
against invasive pneumococcal disease. In elective splenectomy, the vaccination
should be completed, if possible, 2 weeks before the operation; in unplanned
splenectomy, the vaccination should commence when the patient has recovered
from the surgery.58
Children ≤5 years of age with functional or anatomical asplenia should be given
the age-appropriate course of pneumococcal vaccines for medical-risk children
(see Table 3.15.1 Summary table – pneumococcal vaccination schedule for children
≤9 years of age and Section 1.3.5, Catch-up).
Children who develop functional or anatomical asplenia between 6 and ≤9 years
of age should be given 2 doses of 7vPCV 2 months apart, followed by a dose of
23vPPV 2 months later.

Individuals ≥10 years of age with functional or anatomical asplenia should be
given:
• an initial dose of 23vPPV,
• revaccination with 23vPPV 5 years after the initial dose (of 23vPPV), and
• 1 further revaccination (third dose) should be given at either 5 years after
the first revaccination or at 50 years (Indigenous adults) or 65 years (non-
Indigenous adults) of age, whichever is later.
It should be noted that the above regimens cannot provide prolonged protection
against all invasive pneumococcal disease. It is particularly important that
individuals with functional or anatomical asplenia are informed of the altered
immune status associated with asplenia and the increased life-long risk of
severe bacterial infection, that they should seek urgent medical assessment for
any febrile illness, and that they should always wear a medical alert bracelet or
necklace.
NB. Children ≤5 years of age with splenic dysfunction, most frequently due
to sickle cell disease, should also be treated with daily doses of penicillin V,
commencing before the age of 4 months and continuing until 5 years of age
(penicillin V 125 mg twice daily, increasing to 250 mg twice daily when they
reach 4 years of age).
• Meningococcal vaccination
All individuals ≥1 year of age with functional or anatomical asplenia should be
vaccinated with a single dose of MenCCV, although the vaccine can be given
from 6 weeks of age (see also Chapter 3.12, Meningococcal disease). This should
be followed by a dose of the 4vMenPV at ≥2 years of age (see also Chapter 3.12,
Meningococcal disease). If MenCCV is given, a period of at least 2 weeks should
elapse before 4vMenPV is administered. A single revaccination with 4vMenPV is
recommended 3 to 5 years later.
• Hib vaccination
Children should be up-to-date with Hib vaccination. A single dose of Hib vaccine
is recommended for splenectomised adults.
2.3.3.6 Individuals with autoimmune diseases

Adults with conditions such as systemic lupus erythematosus (SLE), rheumatoid

arthritis (RA) and multiple sclerosis (MS) should be given influenza and
pneumococcal polysaccharide vaccines, due to potential morbidity and mortality
from infection, despite the potential for reduced immunogenicity in some
patients (described below).59-61
For conditions such as SLE and RA, theoretical concerns that vaccines may
exacerbate or cause these diseases have not been substantiated, despite a number
of sporadic case reports. There is potential for reduced immunogenicity of
vaccines, due to both immunosuppressive therapies and the underlying disease.62

Small controlled studies suggest that approximately one-third of patients with
SLE or RA receiving immunosuppressive therapies may mount a lower antibody
response to influenza and pneumococcal vaccines compared with healthy
controls.60,62 A small proportion of patients may mount very little or no response
to the pneumococcal vaccine.60 Importantly, clinical and laboratory measures
of disease activity, and the choice, duration and dose of immunosuppressive
therapies, do not predict who these poor responders will be.60,62,63 In a study
involving 149 patients with RA taking immunosuppressive agents, including
tumour necrosis factor (TNF) blockers, and 47 healthy controls, patients on TNF
blockers showed similar responses to pneumococcal vaccination to controls.63
Patients treated with methotrexate (as monotherapy or with TNF blockers) had a
reduced antibody response to vaccination.63
There is clear evidence that multiple sclerosis is not exacerbated by influenza
vaccination, and either insufficient or no evidence that other vaccines increase
this risk.64
2.3.4 Vaccination of recent recipients of

normal human immunoglobulin
The immune response to live viral vaccines (with the exception of yellow fever
vaccine) may be inhibited by normal human immunoglobulin. The interval
recommended is dependent on the type of immunoglobulin given (see Table 2.3.5
Recommended intervals between either immunoglobulins or blood products and MMR,
MMRV or varicella vaccination).
When hyperimmune globulin is used against a specific infection, such as varicella,
vaccination against other live viruses need not be deferred. Specialist advice
should be sought if high-dose or intravenous immunoglobulins have been used.
2.3.5 Vaccination of patients following receipt of

other blood products including blood transfusions
People who have received a blood transfusion, including mass blood
transfusions, do not require revaccination. However, following the receipt of any
blood product, including plasma or platelets, an interval of 3 to 7 months should
elapse, dependent on the blood product transfused, before vaccination with an
MMR, MMRV or varicella vaccine (see Table 2.3.5 Recommended intervals between
either immunoglobulins or blood products and MMR, MMRV or varicella vaccination).
An interval is suggested because there may be low levels of antibodies present in
the blood product that may impair the immune response to the live vaccine.

Table 2.3.5: Recommended intervals between either immunoglobulins or blood
products and MMR, MMRV or varicella vaccination65
Route Dose
IU or mL Estimated Interval

mg IgG/kg (months)
Blood transfusion:
Washed RBCs IV 10 mL/kg Negligible 0
RBCs, adenine-saline IV 10 mL/kg 10 3

added
Packed RBCs IV 10 mL/kg 20–60 5
Whole blood IV 10 mL/kg 80–100 6
Cytomegalovirus immunoglobulin IV 3 mL/kg 150 6
Hepatitis A prophylaxis IM 0.5 mL (<25 kg) 3

(as NHIG) 1.0 mL (25–50 kg)
2.0 mL (>50 kg)
Hepatitis B prophylaxis IM 100 IU 10 3

(as HBIG) 400 IU
ITP (as NHIG [Intravenous]) IV 400 8
ITP (as NHIG [Intravenous]) IV 1000 10
ITP or Kawasaki disease IV 1600–2000 11

(as NHIG [Intravenous])
Measles prophylaxis (as NHIG): (max. dose 15 mL)

Standard IM 0.2 mL/kg 5
Immunocompromised IM 0.5 mL/kg 6
Plasma or platelet products IV 10 mL/kg 160 7
Rabies prophylaxis (as RIG) IM 20 IU/kg 22 4
Replacement (or therapy) of immune IV 300–400 9

deficiencies (as NHIG [Intravenous],
various doses)
Rh (D) IG (anti-D) IM 0
Tetanus (as TIG for IM use) IM 250 IU (given within 10 3

24 hrs of injury)
500 IU (>24 hrs after 20

injury)
Varicella prophylaxis (as ZIG) IM 200 IU (0–10 kg) 5

400 IU (11–30 kg)
600 IU (>30 kg)

2.3.6 Vaccination of patients with bleeding disorders
Intramuscular injection may lead to haematoma formation in patients with
disorders of haemostasis, and to pressure necrosis, muscle contractures or
nerve compression in patients with severe coagulopathies. Children with
inherited coagulopathies should receive factor replacement before intramuscular
injection. Unless warfarin doses are known to be stable, patients receiving this
anticoagulant should have prothrombin times measured before intramuscular
injections, which should be deferred if the INR (international normalised ratio) is
greater than 3.0. Patients with platelet counts of less than 50 x 109/L should not
receive intramuscular injections.
The subcutaneous route could be considered as an alternative to the
intramuscular route in patients with bleeding disorders; seek expert advice.19
2.3.7 Vaccination before or after anaesthesia/surgery

Recent or imminent surgery is not a contraindication to vaccinations and recent
vaccination is not a contraindication to surgery (see Section 1.3.4, Pre-vaccination
screening). There are no randomised controlled trials providing evidence of
adverse outcomes with anaesthesia and surgery in recently vaccinated children.
It is possible that the systemic effects from recent vaccination, such as fever and
malaise, may cause confusion in the post-operative period. Elective surgery
and anaesthesia may be postponed for 1 week after inactive vaccination and
for 3 weeks after live attenuated viral vaccination in children, and routine
vaccination may be deferred for 1 week after surgery.66
A patient who receives any blood products during surgery will need to be
informed of the need to delay any vaccinations (see Table 2.3.5 Recommended
intervals between either immunoglobulins or blood products and MMR, MMRV or
varicella vaccination).
2.3.8 Vaccination of those at occupational risk

Certain occupations, particularly those associated with healthcare, are associated
with an increased risk of some vaccine-preventable diseases.67,68 Furthermore,
some infected workers, particularly healthcare workers and childcare workers,
may transmit infections such as influenza, rubella, measles, mumps, varicella and
pertussis to susceptible contacts with the potential for serious health outcomes.
Many infectious diseases, measles in particular, are highly infectious several days
before symptoms become apparent.
Where workers are at significant occupational risk of acquiring a vaccine-
preventable disease, the employer should implement a comprehensive occupational
vaccination program which includes a vaccination policy, current staff vaccination
records, provision of information about the relevant vaccine-preventable diseases,
and the management of vaccine refusal (which should, for example, include
reducing the risk of a healthcare worker (HCW) transmitting disease to a vulnerable

patient). Employers should take all reasonable steps to encourage non-immune
workers to be vaccinated.
Current recommended vaccinations for people at risk of occupationally acquired
vaccine-preventable diseases are listed in Table 2.3.6.
Standard precautions should be adopted where there is risk of occupational
exposure to blood and body fluids. Preventive measures include the appropriate
handling and disposal of sharps, and the donning of gloves, when handling body
fluids, and goggles/face shields, when splashes are likely.
If a non-immune person is exposed to a vaccine-preventable disease, post-
exposure prophylaxis should be administered where indicated.
Table 2.3.6: Recommended vaccinations for those at risk of occupationally

acquired vaccine-preventable diseases*
OCCUPATION DISEASE/VACCINE
HEALTHCARE WORKERS (HCW)
All HCW: Hepatitis B
including all workers and students directly involved Influenza
in patient care or the handling of human tissues Pertussis (dTpa,
provided dTpa has not
been given previously)
MMR (if non-immune)†
Varicella (if seronegative)
HCW who work with remote Indigenous communities Vaccines listed for ‘All
in NT, QLD, SA and WA; medical, dental and nursing HCW’, plus hepatitis A
undergraduate students (in some jurisdictions)
HCW who may be at high risk of exposure to Vaccines listed for ‘All
drug-resistant cases of tuberculosis HCW’, plus BCG
THOSE WHO WORK WITH CHILDREN
All those working with children including: Pertussis (dTpa,
Childcare and preschool staff (including childcare students) provided dTpa has not
been given previously)
Correctional staff working where infants/
children cohabitate with mothers MMR (if non-immune)†
Varicella (if seronegative)

School teachers (including student teachers)

Outside school hours carers
Child counselling services workers
Youth services workers
Childcare and preschool staff Vaccines listed for
‘All those working
with children’ plus
hepatitis A vaccine

CARERS
Carers of people with intellectual disabilities Hepatitis A
Hepatitis B
Staff of nursing homes and long-term care facilities Influenza
Providers of home care to people at risk of high influenza morbidity Influenza
EMERGENCY AND ESSENTIAL SERVICE WORKERS
Police and Emergency Workers Hepatitis B, influenza
Armed Forces personnel Hepatitis B, influenza
(and other vaccines
relevant to deployment)
Staff of correctional facilities Hepatitis B, influenza
LABORATORY PERSONNEL
Laboratory personnel handling veterinary specimens or Q fever
working with Q fever organism (Coxiella burnetii)
Laboratory personnel handling either bat Australian bat lyssavirus
tissues or ABL or rabies virus (ABL) and rabies
Laboratory personnel routinely working Anthrax‡
with other infectious agents Vaccinia poxviruses
Poliomyelitis
Typhoid
Yellow fever
Meningococcal disease
WORKING WITH SPECIFIC COMMUNITIES
Workers who live with or make frequent visits to remote Hepatitis A
Indigenous communities in NT, QLD, SA and WA
Workers assigned to the outer Torres Strait Islands Japanese encephalitis
for a month or more during the wet season

WORKING WITH ANIMALS
Veterinarians, veterinary students, veterinary nurses Q fever
Australian bat lyssavirus
(ABL) and rabies
Agricultural college staff and students exposed to high-risk animals Q fever
Abattoir workers and contract workers in Q fever
abattoirs (excluding pig abattoirs)
Livestock transporters
Sheep shearers and cattle, sheep and dairy farmers
Those culling/processing kangaroos or camels
Tanning and hide workers
Goat farmers
Livestock saleyard workers
Those handling animal products of conception
Those who come into regular contact with bats Australian bat lyssavirus
(both flying foxes and microbats), bat-handlers, (ABL) and rabies
bat scientists, wildlife officers, zoo curators
Poultry workers, and others handling poultry, including those who Influenza
may be involved in culling during an outbreak of avian influenza
OTHERS EXPOSED TO HUMAN TISSUE, BLOOD, BODY FLUIDS OR SEWAGE
Embalmers Hepatitis B, BCG
Sex industry workers Hepatitis A
Hepatitis B
Workers who perform skin penetration Hepatitis B
procedures, eg. tattooists, body-piercers
Funeral workers and other workers who have regular contact with Hepatitis B
human tissue, blood or body fluids and/or used needles or syringes
Plumbers or other workers in regular contact with untreated sewage Hepatitis A
* Work activities, rather than job title, should be considered on an individual basis to ensure
an appropriate level of protection is afforded to each worker.

† All adults born during or since 1966 should have evidence of either receiving 2 doses
of MMR vaccine or immunity. Adults born before 1966 are considered to be immune due
to extensive measles circulating widely in the community during this period of time (see
Chapter 3.11, Measles).
‡ People with a repeated risk of exposure or working with large quantities or concentrations
of Bacillus anthracis cultures. For information regarding anthrax vaccination, please contact
the Office of Health Protection in the Australian Government Department of Health and
Ageing, Canberra.

2.3.9 Vaccination of immigrants to Australia69
Vaccination status is not routinely assessed in children and adults entering
Australia as refugees or immigrants. They may be incompletely vaccinated
according to the Australian schedule or have incomplete records of vaccination.
The World Health Organization website www.who.int/countries/en lists
immunisation schedules for most countries and may provide some information
regarding vaccine schedules.
• If an immigrant has no valid documentation of vaccination, the standard
‘catch-up’ schedule should be commenced. Serological testing to determine
the need for specific vaccinations is not recommended in the absence of
documented vaccination. If a child is ≥12 months of age, the first doses of
DTPa, hepatitis B, IPV, MMR, MenCCV, 7vPCV and Hib vaccines can be
given at the same visit. For details, see Section 1.3.5, Catch-up.
• If there is a valid record of vaccination, the history of previous doses should
be taken into account when planning a catch-up vaccination schedule.
• Immigrant adults need to be targeted for vaccination, especially against
rubella using MMR. This is particularly important for women of child-
bearing age.
• All vaccines administered to children <7 years of age should be documented
on the ACIR, including those for children not enrolled with Medicare and
vaccinations documented pre-arrival.
• ACIR History Statements can be issued after documentation of overseas
vaccination(s) have been recorded on ACIR.
• The Australian Government Department of Immigration and Citizenship
(DIAC) may in some circumstances be able to provide information regarding
vaccine(s) administered to refugees before entering Australia.
2.3.10 Vaccination of inmates of correctional facilities

Inmates of correctional facilities are at risk of acquiring influenza, hepatitis A and
hepatitis B, and should be vaccinated against these infections (see Chapter 3.5,
Hepatitis A, Chapter 3.6, Hepatitis B and Chapter 3.9, Influenza).70,71
2.3.11 Vaccination of men who have sex with men

Men who have sex with men are at risk of acquiring hepatitis A and hepatitis B,
and should be vaccinated against these infections (see Chapter 3.5, Hepatitis A
and Chapter 3.6, Hepatitis B).

2.3.12 Vaccination of injecting drug users
Injecting drug users are at risk of acquiring hepatitis A and hepatitis B, and
should be vaccinated against these infections (see Chapter 3.5, Hepatitis A and
Chapter 3.6, Hepatitis B).
References

PART 3: Vaccines listed by disease
3.1 Australian bat lyssavirus

infection and rabies
Virology
Australian bat lyssavirus (ABL) and rabies virus are members of the family
Rhabdoviridae, genus Lyssavirus. There are 7 known genotypes within the genus
Lyssavirus; ABL (genotype 7) is more closely related to rabies virus (genotype 1)
than any of the other 6 genotypes.
Clinical features
Based on the 2 recognised human cases of ABL infection, it has to be assumed
that ABL has the same clinical features as rabies. The incubation period of
rabies is usually 3 to 8 weeks, but can range from as short as a week to, on rare
occasions, several years. The risk of rabies is higher, and the incubation period
shorter, after severe and multiple wounds proximate to the central nervous
system (such as on the head and neck) and in richly innervated sites (such as the
fingers).
Typically, in the prodromal phase of rabies, which lasts up to 10 days, the patient
may experience non-specific symptoms such as anorexia, cough, fever, headache,
myalgia, nausea, sore throat, tiredness and vomiting.1 Paraesthesiae and/
or fasciculations at or near the site of the wound may be present at this stage.
Anxiety, agitation and apprehension may also occur.
Most rabies patients present with the furious or encephalitic form.1 In the
encephalitic phase, objective signs of nervous system involvement include
aerophobia, hydrophobia, bizarre behaviour, disorientation and hyperactivity.
Signs of autonomic instability such as hypersalivation, hyperthermia and
hyperventilation may occur.1 The neurological status of the patient deteriorates
over a period of up to 12 days, and the patient either dies abruptly from cardiac
or respiratory arrest, or lapses into a coma. Rabies is almost invariably fatal.
Epidemiology
Rabies is endemic throughout much of Africa, Asia, the Americas and Europe,
where the virus is maintained in certain species of mammals.1 Australia, New
Zealand, Japan, Papua New Guinea and Pacific Island nations are free of
endemic rabies. Human rabies characteristically follows a bite from a rabid
animal, most frequently a dog, but in some parts of the world, other animals,
such as jackals and bats, are important sources of exposure. In countries where
rabies vaccination of domestic animals is widespread (North America and
Europe), wild animals such as raccoons and foxes are important reservoirs.1

Cases of rabies after animal scratches, the licking of open wounds or saliva
contact with intact mucous membranes are very rare.2,3 Cases have been recorded
lyssavirus infection
after exposure to aerosols in a laboratory and in caves infested with rabid bats,
3.1 Australian bat

and cases have been reported following tissue transplantation from donors who
and rabies
died with undiagnosed rabies.1
Although rabies in travellers is rare, such cases – always fatal – continue to be
reported in the medical literature.4,5 Travellers to rabies-endemic regions should
be advised of the risk and to avoid close contact with either wild or domestic
animals; this is particularly important for children. They should be advised
about pre-travel (ie. pre-exposure) rabies vaccination (or, if appropriate, booster
doses), and they should be advised on what to do should they be either bitten or
scratched by an animal while abroad.
In Australia, 2 cases of a fatal rabies-like illness caused by ABL have been
reported, one in 1996 and the other in 1998.6 Both patients had been bitten
by bats. Evidence of ABL infection has since been identified in all 4 species
of Australian fruit bats (flying foxes) and in several species of Australian
insectivorous bats. It should therefore be assumed that all Australian bats have
the potential to be infected with ABL.
Rabies vaccine
• Mérieux Inactivated Rabies Vaccine – Sanofi Pasteur Pty Ltd. Each 1.0 mL
monodose vial of lyophilised vaccine contains at least 2.5 IU inactivated
rabies virus; 100–150 µg neomycin; ≤70 mg human serum albumin; trace of
phenol red (indicator). 1.0 mL distilled water as diluent.
• Rabipur Inactivated Rabies Virus Vaccine – CSL Biotherapies/Novartis

Vaccines. Each 1.0 mL monodose vial of lyophilised vaccine contains at least
2.5 IU inactivated rabies virus; trace amounts of neomycin, chlortetracycline
and amphotericin B; may contain trace amounts of bovine gelatin. May
contain traces of egg protein. 1.0 mL distilled water as diluent.
The Mérieux vaccine is a lyophilised, stabilised suspension of inactivated Wistar

rabies virus that has been cultured on human diploid cells and then inactivated
by beta-propiolactone. This human diploid cell vaccine (HDCV) is coloured off-
white, but after reconstitution with the diluent it turns a pinkish colour due to
the presence of phenol red. The vaccine does not contain a preservative.
Rabipur is a lyophilised, stabilised suspension of inactivated Flurey LEP rabies
virus that has been cultured on purified chick embryo cells and then inactivated
by beta-propiolactone. This purified chick embryo cell vaccine (PCECV) does not
contain a preservative.
The above two vaccines, and other tissue culture vaccines, are interchangeable.
Australian bat lyssavirus infection and rabies 111

Rabies immunoglobulin
• Imogam Rabies – Sanofi Pasteur Pty Ltd (human rabies immunoglobulin).
Each 1.0 mL contains IgG class human rabies antibodies with a minimum
titre of 150 IU; 22.5 mg glycine; 1 mg sodium chloride. It is supplied in 2 mL
and 10 mL vials.
Human rabies immunoglobulin (HRIG) is prepared by cold ethanol fractionation

from the plasma of hyperimmunised human donors.
Transport, storage and handling

Transport according to National Vaccine Storage Guidelines: Strive for 5.7 Rabies
vaccine, diluent and HRIG should be transported and stored at +2°C to
+8°C. Do not freeze. Reconstituted vaccine should be used immediately after
reconstituting. The HRIG should be used immediately once the vial is opened.
Dosage and administration

NB. The doses of rabies vaccines are the same for both children and adults.
(i) Pre-exposure prophylaxis

The dose of rabies vaccine for pre-exposure prophylaxis is 1.0 mL by IM injection,
on days 0, 7 and 28. (HDCV can also be given by the subcutaneous (SC) route.)
(ii) Post-exposure treatment

The dose of rabies vaccine for post-exposure treatment is 1.0 mL by IM injection,
on days 0, 3, 7, 14 and 28–30. (HDCV can also be given by the SC route.) The dose
of HRIG is 20 IU/kg body mass by infiltration around the wounds; the remainder
of the dose should be administered by IM injection.
Recommendations
(i) Pre-exposure prophylaxis for Australian bat lyssavirus infection and rabies
Rabies vaccine is effective and safe when used for pre-exposure prophylaxis
for rabies.8 Although data on the effectiveness of rabies vaccine as prophylaxis
against ABL infection are limited, the available animal data9 and clinical
experience support its use. Pre-exposure prophylaxis simplifies the management
of a subsequent exposure because fewer doses of vaccine are needed and
because HRIG is not required. (Rabies immunoglobulin is often difficult, or even
impossible, to obtain in many developing countries.)

Pre-exposure prophylaxis with rabies vaccine is recommended for:
• people in Australia liable to receive bites or scratches from bats (this includes
bat handlers, veterinarians, wildlife officers and others who come into direct
3.1 Australian bat

contact with bats),
and rabies
• expatriates and travellers who will be spending prolonged periods (ie. more
than a month) in rabies-endemic areas. (NB. This time interval, of more than
a month, is arbitrary, and rabies has occurred in travellers following shorter
periods of travel),5
• people working with mammals in rabies-endemic areas, and
• research laboratory personnel working with live lyssaviruses.
Pre-exposure prophylaxis for both ABL infection and rabies, for all ages, consists
of a total of 3 IM (IM or SC if HDCV is used) injections of 1 mL of rabies vaccine,
the second given 7 days after the first, and the third given 28 days after the first.
Although the third dose can be given at 21 days,1 there are no data to support
the use of an even more accelerated schedule for those with limited time before
travel to a rabies endemic area.
Doses should be given in the deltoid area, as rabies neutralising antibody titres
may be reduced after administration in other sites. In particular, vaccine should
never be given in the buttock, as failure of pre-exposure prophylaxis has been
reported when given by this route.
Because the antibody response is reported as satisfactory after the pre-exposure
prophylaxis regimen, routine serological testing to confirm seroconversion is not
necessary. However, people with impaired immunity who are at risk of exposure
to ABL or rabies should have their antibody titres determined 2 to 3 weeks after
the third dose of vaccine.
Booster doses of rabies vaccine are recommended for immunised people who
have ongoing exposure to either ABL or rabies. People who work with live
lyssaviruses in research laboratories should have rabies antibody titres measured
every 6 months. If the titre is reported as inadequate (<0.5 IU/mL), they should
have a booster dose. Others with occupational exposures to bats in Australia,
and those who are likely to be exposed to potentially rabid animals in endemic
countries, should have rabies antibody titres measured every 2 years. If the titre is
reported as inadequate, they should have a booster dose. Alternatively, a booster
dose may be offered every 2 years without determining the antibody titre.
Intradermal pre-exposure prophylaxis

There are no data on the protection provided by intradermal (ID) rabies
vaccination for the prevention of ABL infection. Therefore, ID pre-exposure
administration of rabies vaccine should not be used for pre-exposure prophylaxis of ABL.
Antibody titres are lower and wane more rapidly after ID compared to either IM
or SC administration of rabies vaccine, and there may be a slow initial immune

response following exposure to rabies virus in those given ID rabies vaccine.10
For these 2 reasons, it is strongly recommended that the IM (IM or SC if HDCV is
used) route be used for pre-exposure prophylaxis.
However, the cost of IM (IM or SC if HDCV is used) rabies vaccination may be
prohibitive for some travellers. In this circumstance, ID rabies vaccination, using
a dose of 0.1 mL on days 0, 7 and 28, may be considered, provided that:
• it is given by those with not only expertise in, but also regular practice of, the
ID technique,
• it must not be administered to anyone known to have impaired immunity,
• it must not be administered to those taking either chloroquine or other
antimalarials structurally related to chloroquine (eg. mefloquine) at either the
time of, or within a month following, vaccination,
• any remaining vaccine is discarded at the end of the session during which the
vial is opened, and
• the rabies antibody level should be checked 2 to 3 weeks following
completion of the pre-exposure course of ID vaccine.
The use of the ID route for rabies vaccination is the practitioner’s own
responsibility, as rabies vaccines are not licensed for use via this route in Australia.
The ID route should never be used to administer rabies vaccine by practitioners who
only occasionally provide travel medicine services.
(ii) Post-exposure treatment for Australian bat lyssavirus and rabies exposures
Rabies vaccine and HRIG are effective and safe when used for post-exposure
treatment following rabies exposures. Although data on the effectiveness of
rabies vaccine and HRIG as post-exposure treatment against ABL infection
are limited, the available animal data9 and clinical experience support its use.
The essential components of post-exposure treatment for either ABL or rabies
exposures are prompt local wound management and, for people who have not
previously been vaccinated, administration of HRIG and rabies vaccine as soon
as is practicable.8 Both HRIG and rabies vaccine are available for post-exposure
treatment from the relevant State/Territory health authorities (see Appendix 1,
Contact details for Australian, State and Territory Government health authorities and
communicable disease control).
Post-exposure treatment should be considered whenever a bite, scratch or
mucous membrane exposure to saliva from any Australian bat has occurred,
regardless of the extent of the bite or scratch, the time lapsed since the exposure,
the species of bat involved, and even if the bat was apparently normal in
appearance and behaviour. (Although ABL is more likely to be found in bats that
either appear unwell or are behaving abnormally,11 it has to be assumed that any
bat is potentially infected with ABL.)

However, exposure to bat blood, urine or faeces, or to a bat that has been dead
for more than 4 hours, does not warrant post-exposure treatment.
Where post-exposure treatment for a potential exposure to ABL is indicated,
3.1 Australian bat

the bat should, if possible, without placing others at risk of exposure, be
and rabies
kept and arrangements promptly made for testing by the relevant State/
Territory veterinary or health authority. Following the wound management,
the administration of HRIG and rabies vaccine can be withheld if the result
(concerning the bat’s ABL status) will be available within 48 hours of the
exposure; if the result will not be available within 48 hours, full post-exposure
treatment should begin as soon as is practicable. Where a bat is tested at a
reference laboratory and later found to be negative for ABL, then post-exposure
treatment for individuals exposed to that bat can be discontinued.
The relevant State/Territory health authority should be contacted about any
animal bite or scratch sustained in a rabies-endemic area. Dogs and monkeys
comprise the usual exposures in Asia, Africa and Central and South America,
but exposures to other mammals must also be assessed for potential rabies
transmission. If a traveller presents >10 days after being bitten or scratched by
either a dog or cat in an endemic country, and it can be reliably ascertained that
the animal has remained healthy (>10 days after the exposure), post-exposure
treatment is not required;8,12 otherwise, a complete course of treatment should
be administered, even if there has been a considerable delay in reporting the
incident.
Immediate and thorough washing of all bite wounds and scratches with soap
and water, and the application of a virucidal preparation such as povidone-
iodine solution after the washing, is an important measure in the prevention of
ABL infection and rabies.1 Consideration should be given at this stage of wound
management to the possibility of tetanus and other wound infections, and
appropriate measures taken. Primary suture of a bite from a potentially rabid
animal should be avoided. Bites should be cleaned, debrided and well infiltrated
with HRIG (see below).
a) Use of rabies vaccine in post-exposure treatment

Following the local wound management, the subsequent post-exposure
treatment for either ABL or rabies exposures consists of: (i) a total of 5 doses of
1.0 mL of rabies vaccine given by IM (IM or SC if HDCV is used) injection; and
(ii) HRIG (see below).
The volume of rabies vaccine administered to infants and children is the same
as that given to adults (ie. 1.0 mL). The first dose of vaccine is given as soon
as is practicable (day 0), and subsequent doses are given on days 3, 7, 14 and
28–30; deviations of a few days from this schedule are probably unimportant.8 In
adults and children, the vaccine should be administered into the deltoid area, as
administration in other sites may result in reduced neutralising antibody titres.

In infants <12 months of age, administration into the anterolateral aspect of the
thigh is recommended.
Serological testing to measure response is unnecessary except in unusual
circumstances, such as when the patient is known to have impaired immunity.
In such cases, the antibody titre should be measured 2 to 3 weeks after the dose
given at 28–30 days and a further dose given if the titre is reported as inadequate.
b) Use of rabies immunoglobulin in post-exposure treatment

Rabies has occurred in people who have received post-exposure rabies vaccine
without rabies immunoglobulin being infiltrated in and around the wound.13
Therefore, post-exposure treatment should always include the infiltration of HRIG
in and around wounds at the same time as the first dose of rabies vaccine, the only
exceptions being people with documented evidence of either completion of the
pre-exposure prophylaxis regimen or adequate rabies antibody titres. These
people should receive vaccine only (see below).
A single dose of HRIG is given to provide localised anti-rabies antibody
protection while the patient responds to the rabies vaccine. It should be given
at the same time as the first post-exposure dose of vaccine (day 0). If not given
with the first vaccine dose, it may be given up to day 7, but should not be given
any later in the vaccination course. From day 8 onwards, an antibody response to
rabies vaccine is presumed to have occurred.
The dose of HRIG for all age groups is 20 IU per kg body mass. HRIG should be
infiltrated in and around all wounds using as much of the calculated dose as possible,
and the remainder administered intramuscularly at a site away from the injection
site of rabies vaccine. If the wounds are severe and the calculated volume of
HRIG is inadequate for complete infiltration of all wounds (eg. extensive dog
bites in a young child), the HRIG should be diluted in saline to make up an
adequate volume for the careful infiltration of all wounds.
However, many bat bites occur as small puncture wounds on the fingers;8 such
exposures are probably high-risk exposures because of the extensive nerve
supply to the fingers and hand. Therefore, although infiltration of HRIG into
finger wounds is likely not only to be technically difficult but also to be painful
for the recipient, it must be undertaken. As much of the calculated dose of HRIG
as possible should be infiltrated into finger and hand wounds using either a
25 or 26 gauge needle. To avoid the development of a compartment syndrome,
the HRIG should be infiltrated very gently, and should not cause the adjacent
finger tissue to go frankly pale or white. If necessary, a ring-block using a local
anaesthetic may be required.

Table 3.1.1: Summary of Australian bat lyssavirus and rabies
post-exposure treatment for non-immune individuals
3.1 Australian bat
Treatment Immediate (Day 0) Follow-up
and rabies
Local treatment Thorough wound cleansing
Rabies vaccine 1.0 mL 1.0 mL on days 3, 7, 14, 28–30
Human rabies 20 IU/kg – no later than Do not give later than
immunoglobulin 7 days after the first 7 days after the first
(150 IU/mL) rabies vaccine dose rabies vaccine dose
c) Post-exposure treatment of previously vaccinated people

People who have either completed a recommended course of pre-exposure
prophylaxis, or previous post-exposure treatment, or who have documented
adequate rabies neutralising antibodies, require a modified post-exposure
treatment regimen if potentially exposed to either rabies virus or ABL. Local
wound management as described above must be carried out, and a total of 2
doses of rabies vaccine (1.0 mL each) should be given by IM (IM or SC if HDCV
is used) injection on day 0 and day 3. HRIG is not necessary in these cases.
In cases where the vaccination status is uncertain because the documentation
of a full course of rabies vaccine is not available, the standard post-exposure
treatment regimen (HRIG plus 5 doses of rabies vaccine) should be administered.
d) Post-exposure treatment commenced overseas

Australians travelling abroad who are exposed to a potentially rabid animal
may be given post-exposure treatment with vaccines not available in Australia.
However, it is very likely that they will receive a cell culture derived vaccine,
all of which (including both vaccines available in Australia) are considered
interchangeable.14
Therefore, if a person has received a cell culture-derived vaccine abroad, the
standard post-exposure treatment regimen should be continued in Australia with
either HDCV or PCECV. If the post-exposure treatment was started overseas
but HRIG was not given, and the person presents in Australia within 7 days
of commencing post-exposure treatment, HRIG should be given as soon as is
practicable (and within 7 days of the first rabies vaccine). If the person presents
in Australia 8 days or more after commencing post-exposure treatment, then
HRIG should be withheld.
Contraindications
There are no contraindications to post-exposure treatment in a person with a
possible exposure to either ABL or rabies.
A person with an anaphylactic sensitivity to eggs, or to egg proteins, should not
receive PCECV; HDCV should be used instead.

Adverse events
Cell culture-derived vaccines are generally well tolerated. In a large study, the
following adverse events were reported after administration of HDCV to adults:
sore arm (15 to 25% very common), headache (5 to 8% common), malaise, nausea
or both (2 to 5% common); and allergic oedema (0.1% uncommon).14 Similar
adverse event profiles have been reported for the PCECV; these reactions occur at
the same rates in children.14
Although anaphylactic reactions are rare (approximately 1 per 10 000
vaccinations) following administration of HDCV, approximately 6% (common)
of people receiving booster doses may experience allergic reactions.14 The
reactions typically occur 2 to 21 days after a booster dose, and are characterised
by generalised urticaria, sometimes with arthralgia, arthritis, oedema, nausea,
vomiting, fever and malaise. These reactions are not life-threatening; they have
been attributed to the presence of beta-propiolactone-altered human albumin in
the implicated vaccines.14 NB. HDCV contains human albumin, whereas PCECV
does not.
Management of adverse events

Once initiated, rabies prophylaxis should not be interrupted or discontinued
because of local reactions or mild systemic reactions. Such reactions can usually
be managed with simple analgesics.
Because ABL infection and rabies are lethal diseases, the recommended
vaccination regimens, in particular the post-exposure treatment regimen, should
be continued even if a significant allergic reaction occurs following a dose of
rabies vaccine. Antihistamines can be administered in an attempt to ameliorate
any subsequent reactions. A patient’s risk of developing either ABL infection or
rabies must be carefully considered before deciding to discontinue vaccination.
Use of steroids and immunosuppressive agents

Corticosteroids and immunosuppressive agents can interfere with the
development of active immunity and, therefore, if possible, should not be
administered during post-exposure treatment. A person who either has an
immunosuppressing illness or is taking immunosuppressant medications should
have his/her rabies antibody titres checked 2 to 4 weeks after completion of the
vaccination regimen (see above).
Use in pregnancy
Pregnancy is never a contraindication to rabies vaccination. Follow-up of 202
Thai women vaccinated during pregnancy did not indicate either increased
medical complications or birth defects.15

Variations from product information
Neither of the product information sheets (of the 2 vaccines available in
3.1 Australian bat
Australia) mentions that they can be used for both pre-exposure prophylaxis and
post-exposure treatment for ABL exposures.
and rabies
The HDCV product information recommends a routine sixth dose at 90 days in
the post-exposure treatment regimen. This dose is not considered necessary on
a routine basis but a further dose should be offered to a person with impaired
immunity who has an inadequate antibody level following the standard regimen.
It also recommends a pre-exposure booster after a year; boosters are usually
recommended in Australia after 2 years (see above).
Rabies in Indonesia
No cases of Bali-acquired rabies have ever been reported in the medical literature
despite many people being bitten and scratched by animals in Bali every year.
Therefore, post-exposure treatment following animal bites sustained in Bali is
currently not warranted, but obviously this situation could change.
However, rabies still exists in other parts of Indonesia including the islands of
Flores, Sulawesi, Sumatra, Ambon and Kalimantan. Post-exposure treatment is
necessary for any animal bite or scratch sustained in any of these locations. Any
doubts or concerns about the need for post-exposure treatment following animal
bites should be discussed with the State/Territory public health authority.
References

3.2 Cholera
Bacteriology
Vibrio cholerae is a motile, curved Gram-negative bacillus and differences in the
O antigens have led to the description of more than 150 serogroups, only two
of which have been found to cause cholera. Cholera is caused by enterotoxin
producing V. cholerae of serogroups O1 and O139 (sometimes referred to as the
‘Bengal’ strain). Serogroup O1 includes 2 biotypes (classical and El Tor), each of
which includes organisms of Inaba, Ogawa and Hikojima serotypes. The ability
of V. cholerae to persist in water is determined by the temperature, pH, salinity
and availability of nutrients; it can survive under unfavourable conditions in a
viable dormant state.1 Transmission predominantly occurs when people ingest
faecally contaminated food or water.
Clinical features
Cholera is an acute bacterial infection that is generally characterised by the
sudden onset of painless, profuse, watery diarrhoea. If untreated, more than half
the severe cases will die. Mild cases also occur, as does subclinical infection.1
The cholera toxin does not produce intestinal inflammation. The cholera toxin
induces secretion of increased amounts of electrolytes into the intestinal lumen,
resulting in mild to severe dehydration and, in some cases, metabolic acidosis.
Epidemiology
Cases of cholera in Australia (about 2 to 6 cases a year) almost always occur in
individuals who have been infected in endemic areas of Asia, Africa, the Middle
East, South America or parts of Oceania.2-4 The disease is usually transmitted
via food and water contaminated with human excreta. Shellfish obtained from
contaminated waters have also been responsible for outbreaks.1
In 1977, a locally acquired case led to the discovery of V. cholerae in some rivers
of the Queensland coast.5 Because of this, health workers should be aware that
sporadic cases of cholera may, on rare occasions, follow contact with estuarine
waters.
As the incubation period of the disease may extend up to 5 days, surveillance
of household contacts or those exposed to a possible common source should be
maintained for 5 days from the date of last exposure. Stool cultures (cultured
using specific media) may be taken from close contacts if required. Food handlers
should not be allowed to return to work until 2 consecutive stool samples, taken
at least 24 hours apart, are negative. Contacts should also be advised to maintain
high standards of personal hygiene to avoid becoming infected. Cases should be
reported immediately to the public health authorities (for contact details, refer

to Appendix 1, Contact details for Australian, State and Territory Government health
Vaccines
• Dukoral – Sanofi Pasteur Pty Ltd (inactivated whole-cell V. cholerae O1
in combination with a recombinant cholera toxin B subunit (rCTB)). Each
3.0 mL liquid vaccine dose vial contains heat and formalin inactivated Inaba,
Ogawa, classic and El Tor strains of V. cholerae O1, 2.5 x 1010 vibrios of each,
combined with 1.0 mg rCTB. The buffer consists of a sachet of effervescent
granules of anhydrous sodium carbonate, sodium bicarbonate, anhydrous
citric acid, sodium citrate, saccharin sodium and raspberry flavour.
Trials of the safety, immunogenicity and efficacy of oral vaccines, both killed and
live attenuated, have been carried out in the United States, Bangladesh, Thailand,
3.2 Cholera
Indonesia, Chile, Peru and Switzerland.6-12
Trials of the inactivated vibrio combined with rCTB vaccine have been done
mainly in Bangladesh and Peru.9,13-16 In Bangladesh, a 2-dose regimen showed
protective efficacy of 44% in children 2 to 6 years of age and 76% in adults at the
end of 1 year, and 33% and 60%, respectively, after 2 years. The studies in Peru
showed an overall efficacy of 61% in 2–65-year-olds. A recent study undertaken
during a mass oral cholera vaccination program in Mozambique concluded that 1
or more doses of the inactivated oral cholera vaccine was 78% protective.17
To date, there is no vaccine marketed to protect against infection with V. cholerae
O139. A killed oral whole cell cholera bivalent vaccine (against both serogroups
O1 and O139) is currently being evaluated in Vietnam.18,19
A study in short-term Finnish tourists20 showed that the inactivated oral cholera
vaccine also provided a 60% reduction in diarrhoea caused by heat-labile toxin
producing enterotoxigenic E. coli (LT-ETEC). A study in Bangladesh, an endemic
area, showed 67% protection against LT-ETEC for 3 months only.21 It can be
expected that the inactivated vaccine will reduce the proportion of travellers’
diarrhoea that is caused by LT-ETEC. Approximately 30 to 40% of travellers to
developing countries contract travellers’ diarrhoea, with an average of 20% of
cases caused by LT-ETEC; hence, the 60% efficacy of the oral inactivated vaccine
against LT-ETEC could be expected to prevent around 10 to 12% of travellers’
diarrhoea.22 However, in Australia this vaccine is only registered for the
prevention of cholera.

Transport according to National Vaccine Storage Guidelines: Strive for 5.23 Store in a
refrigerator at +2°C to +8°C. Do not freeze. Protect from light.
Cholera 121
For adults and children over the age of 6 years, Dukoral is administered orally
after dissolving the buffer granules in 150 mL of water and adding the vaccine
to the solution. Two doses are required, given a minimum of 1 week and up to
6 weeks apart. If the second dose is not administered within 6 weeks, re-start the
vaccination.
For children aged 2–6 years, Dukoral is administered orally after dissolving
the buffer granules in 150 mL of water. Half the solution is then poured away
and the entire content of the vaccine vial is mixed with the remaining 75 mL.
Children aged 2–6 years should receive 3 doses of the vaccine. Doses are to
be administered with a minimum interval of 1 week between doses up to
a maximum interval of 6 weeks. If an interval of more than 6 weeks occurs
between any of the doses, re-start the vaccination.
Food and drink should be avoided for 1 hour before and 1 hour after
administration of the inactivated cholera vaccine, as it is acid labile.
The inactivated oral cholera vaccine can be given at the same time as other travel
vaccines. However, there should be an interval of at least 8 hours between the
administration of the inactivated oral cholera and oral typhoid vaccines, as the
buffer in the cholera vaccine may affect the transit of the capsules of oral typhoid
vaccine through the gastrointestinal tract.
Adults and children >6 years of age should receive a single booster dose after
2 years and children 2–6 years of age should receive a booster dose 6 months
after completion of the primary course.
Recommendations
Despite the endemicity of cholera in some countries often visited by Australians,
routine cholera vaccination is not recommended as the risk to travellers is very
low. Careful and sensible selection of food and water is of far greater importance
to the traveller than vaccination.
Immunisation should be considered for people at increased risk of diarrhoeal
disease, such as those with achlorhydria, and for people at increased risk of
severe or complicated diarrhoeal disease, such as those with poorly controlled
or otherwise complicated diabetes, inflammatory bowel disease, HIV/AIDS or
other conditions resulting in impaired immunity, or significant cardiovascular
disease. It could also be considered for humanitarian disaster workers.
Vaccination against cholera is not an official requirement for entry into any
foreign country.

Contraindications
The only contraindications to the use of cholera vaccine are:
• anaphylaxis following a previous dose of the vaccine,
• anaphylaxis following any component of the vaccine,
• inactivated oral cholera vaccine is not recommended for children
<2 years of age.
Precautions
• Postpone administration during either an acute febrile illness or acute
gastrointestinal illness with persistent diarrhoea or vomiting, until recovered.
• Although the vaccine is not contraindicated in immune impaired individuals,
including HIV-infected individuals, data on effectiveness in this population is
limited.
3.2 Cholera
• There should be an interval of at least 8 hours between the administration
of the inactivated oral cholera and oral typhoid vaccines, as the buffer in the
cholera vaccine may affect the transit of the capsules of oral typhoid vaccine
through the gastrointestinal tract.
Adverse events
The inactivated oral vaccine is uncommonly (<1%) associated with mild
gastrointestinal disturbances.
Use in pregnancy
There is inadequate information on the use of inactivated oral cholera vaccines
during pregnancy and breastfeeding.24

None.
References
Cholera 123
3.3 Diphtheria
Bacteriology
Diphtheria is an acute illness caused by toxigenic strains of Corynebacterium
diphtheriae, a Gram- positive, non-sporing, non-capsulate bacillus. The exotoxin
produced by C. diphtheriae acts locally on the mucous membranes of the
respiratory tract or, less commonly, on damaged skin, to produce an adherent
pseudomembrane. Systemically, the toxin acts on cells of the myocardium,
nervous system and adrenals.
Clinical features
The incubation period is 2 to 5 days. The disease is communicable for up to 4 weeks,
but carriers may shed organisms for longer. Spread is by respiratory droplets
or by direct contact with skin lesions or articles soiled by infected individuals.
Pharyngeal diphtheria is characterised by an inflammatory exudate which forms
a greyish or green membrane in the upper respiratory tract which can cause
acute severe respiratory obstruction. Diphtheria toxin can cause neuropathy and
cardiomyopathy, which may be fatal. The introduction of diphtheria antitoxin in the
1890s reduced the death rate to about 10%, but the mortality has not been further
reduced by the use of antibiotics and other modern treatments.1 Effective protection
against diphtheria is achieved by active immunisation with diphtheria vaccine.
Epidemiology
In the early 1900s, diphtheria caused more deaths in Australia than any other
infectious disease, but increasing use of diphtheria vaccines since World War
II has led to its virtual disappearance.2 The current epidemiology of diphtheria
in Australia is similar to that in other developed countries. Almost all recent
cases in the United Kingdom and the United States have been associated with
imported infections.3 Hence, there is still the possibility of an imported case
occurring in Australia, particularly from developing countries, as occurred in
2001 when a case, acquired in East Timor, was notified in Australia.4 There is now
little possibility of acquiring natural immunity or boosting declining immunity
with subclinical infection. It is therefore important for Australians to retain high
levels of immunity through high vaccination coverage.
Disruption of vaccination programs following the collapse of the Soviet Union
resulted in the re-emergence of diphtheria throughout the Newly Independent
States. From 1991 to 1996, there were more than 140 000 cases and more than
4000 deaths.5 Cases also occurred in neighbouring European countries and in
visitors to the area. Mass vaccination eventually brought the epidemic under
control.6,7 This experience illustrates the importance of maintaining high levels of
vaccination coverage against diphtheria.

Vaccines
Diphtheria toxoid is available in Australia only in combination with tetanus and
other antigens.
The acronym DTPa, using capital letters, signifies child formulations of
diphtheria, tetanus and acellular pertussis-containing vaccines. The acronym
dTpa is used for adolescent/adult formulations which contain substantially
lesser amounts of diphtheria toxoid and pertussis antigens (see formulations).
Formulations for children aged <8 years
• Infanrix hexa – GlaxoSmithKline (DTPa-hepB-IPV-Hib; diphtheria-

tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis vaccine-
Haemophilus influenzae type b (Hib)). The vaccine consists of both a 0.5 mL
pre-filled syringe containing 30 IU diphtheria toxoid, 40 IU tetanus toxoid,
25 µg pertussis toxoid (PT), 25 µg filamentous haemagglutinin (FHA), 8 µg
pertactin (PRN), 10 µg recombinant HBsAg, 40 D-antigen units inactivated
polioviruses type 1 (Mahoney), 8 D-antigen units type 2 (MEF-1) and 32
D-antigen units type 3 (Saukett) adsorbed onto aluminium hydroxide/
phosphate; phenoxyethanol as preservative; traces of formaldehyde,
polymyxin and neomycin and a vial containing a lyophilised pellet of 10 µg
purified Hib capsular polysaccharide (PRP) conjugated to 20–40 µg tetanus
toxoid. The vaccine must be reconstituted by adding the entire contents of the
syringe to the vial and shaking until the pellet is completely dissolved. May
also contain yeast proteins.
• Infanrix-IPV – GlaxoSmithKline (DTPa-IPV; diphtheria-tetanus-acellular
3.3 Diphtheria
pertussis-inactivated poliomyelitis vaccine). Each 0.5 mL pre-filled syringe
contains 30 IU diphtheria toxoid, 40 IU tetanus toxoid, 25 µg PT, 25 µg FHA,
8 µg PRN, 40 D-antigen units inactivated polioviruses type 1 (Mahoney),
8 D-antigen units type 2 (MEF-1) and 32 D-antigen units type 3 (Saukett)
adsorbed onto aluminium hydroxide; phenoxyethanol as preservative;
traces of formaldehyde, polymyxin and neomycin.
• Infanrix Penta – GlaxoSmithKline (DTPa-hepB-IPV; diphtheria-tetanus-

acellular pertussis-hepatitis B-inactivated poliomyelitis vaccine). Each
0.5 mL pre-filled syringe contains 30 IU diphtheria toxoid, 40 IU tetanus
toxoid, 25 µg PT, 25 µg FHA, 8 µg PRN, 10 µg recombinant HBsAg, 40
D-antigen units inactivated polioviruses type 1 (Mahoney), 8 D-antigen
units type 2 (MEF-1) and 32 D-antigen units type 3 (Saukett) adsorbed onto
aluminium hydroxide/phosphate; phenoxyethanol as preservative; traces of
formaldehyde, polymyxin and neomycin. May also contain yeast proteins.
Diphtheria 125
Formulations for people aged ≥8 years
Adsorbed diphtheria-tetanus vaccine
• ADT Booster – Statens Serum Institut/CSL Biotherapies (dT; diphtheria-

tetanus, adult formulation). Each 0.5 mL pre-filled syringe or monodose vial
contains ≥2 IU diphtheria toxoid and ≥20 IU tetanus toxoid adsorbed onto
0.5 mg aluminium hydroxide.
Combination vaccines
• Adacel – Sanofi Pasteur Pty Ltd (dTpa; diphtheria-tetanus-acellular

pertussis). Each 0.5 mL monodose vial contains ≥2 IU diphtheria toxoid, ≥20
IU tetanus toxoid, 2.5 µg PT, 5 µg FHA, 3 µg PRN, 5 µg pertussis fimbriae
(FIM) 2+3; 1.5 mg aluminium phosphate; phenoxyethanol as preservative;
traces of formaldehyde.
• Adacel Polio – Sanofi Pasteur Pty Ltd (dTpa; diphtheria-tetanus-acellular

pertussis-inactivated poliomyelitis vaccine). Each 0.5 mL monodose vial
contains ≥2 IU diphtheria toxoid, ≥20 IU tetanus toxoid, 2.5 µg PT, 5 µg
FHA, 3 µg PRN, 5 µg FIM 2+3, 40 D-antigen units inactivated polioviruses
type 1 (Mahoney), 8 D-antigen units type 2 (MEF-1) and 32 D-antigen
units type 3 (Saukett); 1.5 mg aluminium phosphate; phenoxyethanol
as preservative; traces of formaldehyde, polymyxin, neomycin and
streptomycin.
• Boostrix – GlaxoSmithKline (dTpa; diphtheria-tetanus-acellular pertussis).

Each 0.5 mL monodose vial or pre-filled syringe contains ≥2 IU diphtheria
toxoid, ≥20 IU tetanus toxoid, 8 µg PT, 8 µg FHA, 2.5 µg PRN, adsorbed
onto 0.5 mg aluminium hydroxide/phosphate; 2.5 mg phenoxyethanol as
preservative. May contain traces of formaldehyde.
• Boostrix-IPV – GlaxoSmithKline (dTpa-IPV; diphtheria-tetanus-acellular

contains ≥2 IU diphtheria toxoid, ≥20 IU tetanus toxoid, 8 µg PT, 8 µg FHA,
2.5 µg PRN, 40 D-antigen units inactivated polioviruses type 1 (Mahoney),
adsorbed onto aluminium hydroxide/phosphate; traces of formaldehyde,
polymyxin and neomycin.
Diphtheria vaccination stimulates the production of antitoxin, which protects

against the toxin produced by the organism. The immunogen is prepared by
treating a cell-free preparation of toxin with formaldehyde, thereby converting it
into the innocuous diphtheria toxoid. Diphtheria toxoid is usually adsorbed onto
an adjuvant, either aluminium phosphate or aluminium hydroxide, to increase

its immunogenicity. Antigens from Bordetella pertussis, in combination vaccines,
also act as an effective adjuvant.
Circulating levels of antitoxin are closely related to protection from diphtheria.
Antitoxin levels of <0.01 IU are poorly protective, 0.01 to 0.1 IU are usually
protective, and titres of >0.1 IU are associated with more certain and prolonged
protection.8 Complete immunisation induces protective levels of antitoxin lasting
throughout childhood but, by middle age, at least 50% of vaccinees have levels
<0.1 IU.9-11 This has been confirmed in Australia by a recent national serosurvey.12
Single low doses of toxoid in previously immunised adults induce protective
levels within 6 weeks.13
Production of DT (CDT vaccine), registered for use in children <8 years of age,
ceased in June 2005.
ADT Booster can be used for the booster dose of dT in people aged ≥8 years or, if
necessary, for the primary dT course (see ‘Variations from product information’).

Transport according to National Vaccine Storage Guidelines: Strive for 5.14 Store at
+2°C to +8°C. Protect from light. Do not freeze.

The dose of diphtheria-containing vaccine is 0.5 mL by IM injection.
Do not mix DTPa-containing vaccines or dT vaccine with any other vaccine in the
same syringe, unless specifically registered for use in this way.
3.3 Diphtheria
Recommendations
(i) Vaccination in childhood
The recommended primary course of vaccination is at 2, 4 and 6 months of age.
A booster dose of DTPa is given at 4 years of age. Immunity to diphtheria will
not be compromised before the booster dose, as the serological response to the
primary course of vaccination is usually sufficient for those years. A second
booster, using the adolescent/adult formulation, dTpa, at 12–17 years of age, is
essential for maintaining immunity to diphtheria in adults. Vaccination against
diphtheria is part of the National Immunisation Program (NIP) schedule,
diphtheria toxoid being given in combination with tetanus toxoid and acellular
pertussis as DTPa vaccine. Before the 8th birthday, DTPa-containing vaccines
should be given, as they contain a larger dose of diphtheria toxoid. After the 8th
birthday, smaller doses of toxoid (dT or adolescent/adult formulation dTpa)
should be given. Dose reduction is necessary because of the increased incidence
of local and systemic reactions to diphtheria toxoid in older children and adults.
For details on the management of children who have missed doses in the NIP
schedule, see Section 1.3.5, Catch-up.
Diphtheria 127
(ii) Vaccination of adults
Individuals who have not received any diphtheria vaccines are also likely
to have missed tetanus vaccination. Three doses of dT should be received at
minimum intervals of 4 weeks, followed by booster doses at 10 and 20 years
after the primary course. It is prudent to give the first of these doses as dTpa, to
also provide boosting to natural immunity from exposure to pertussis, which
is almost universal in unvaccinated adults. In the event that dT vaccine is not
available, dTpa can be used for all primary doses. This is not recommended
routinely because there are no data on the safety, immunogenicity or efficacy of
dTpa in multiple doses for primary vaccination.
All adults who reach the age of 50 years without having received a booster dose
of dT in the previous 10 years should receive a further booster dose of dT, or
preferably dTpa, if this has not been given previously, to also provide protection
against pertussis.
(iii) Other people at special risk

Diphtheria can be a significant risk for travellers to some countries (particularly
southeast Asia, the Newly Independent States of the former Soviet Union,
Baltic countries or eastern European countries). Travellers to high-risk countries
should receive a booster dose of dT (or dTpa) if they have not received one in the
previous 10 years.
Contraindications
The only absolute contraindications to diphtheria vaccine are:
• anaphylaxis following a previous dose of the vaccine, or
• anaphylaxis following any component of the vaccine.
Adverse events
Mild discomfort or pain at the injection site persisting for up to a few days is
common. Uncommon general adverse events following dT vaccine include
headache, lethargy, malaise, myalgia and fever. Acute anaphylactic reactions,
urticaria and peripheral neuropathy very rarely occur (brachial neuritis occurs
in 0.001% of cases). (For specific adverse events following combination vaccines
containing both diphtheria and pertussis antigens, see Chapter 3.14, Pertussis).
The public health management of diphtheria cases

A suspected case of diphtheria is of considerable public health importance, and
should be notified immediately to the State/Territory public health authorities,
who will advise on further management. In general, contacts of a proven or
presumptive diphtheria case will require vaccination (either primary or booster,
depending on vaccination status), and appropriate prophylactic antibiotics.15

Diphtheria antitoxin and penicillin should be given immediately to suspected
cases. Do not wait for bacteriological confirmation of the disease. Diphtheria
antitoxin derived from horse serum is used because sera of sufficient titre are
not available from humans. Due to the presence of foreign protein, diphtheria
antitoxin may provoke acute, severe, allergic reactions or serum sickness.
Consequently, a test dose should be administered, and if there is evidence of
hypersensitivity, it may be necessary to administer diphtheria antitoxin under
corticosteroid, adrenaline, and antihistamine cover. The therapeutic dose of
antitoxin will depend on the clinical condition of the patient, and may be given
either intramuscularly or diluted for administration in an intravenous infusion.
Expert advice should be sought with respect to antitoxin dose and special
arrangements made if hypersensitivity is suspected. This can be coordinated
through the relevant State/Territory health authority (see Appendix 1, Contact
details for Australian, State and Territory Government health authorities and
• Diphtheria antitoxin – This is currently available only through the Special

Access Scheme.
Use in pregnancy
Refer to Chapter 2.3, Groups with special vaccination requirements, Table 2.3.1
Vaccinations in pregnancy.
3.3 Diphtheria
The product information for both Infanrix hexa and Infanrix Penta states that
these vaccines may be given as a booster dose at 18 months of age. NHMRC
recommends that a booster dose of DTPa (or DTPa-containing vaccines) is not
necessary at 18 months of age. However, DTPa-containing vaccine may be used
for catch-up of the primary schedule in children <8 years of age.
The product information for Infanrix-IPV states that this vaccine may be used as
a booster dose for children ≤6 years of age who have previously been vaccinated
against diphtheria, tetanus, pertussis and poliomyelitis. NHMRC recommends
that booster doses of DTPa and IPV be given at 4 years of age; however, this
product may be used for catch-up of the primary schedule or as a booster in
children <8 years of age.
The product information for ADT Booster states that this vaccine is indicated
for a booster dose only in children aged ≥5 years and adults who have
previously received at least 3 doses of diphtheria and tetanus vaccines. NHMRC
recommends that, where a dT vaccine is required for any person ≥8 years of
age, ADT Booster can be used, including for primary immunisation against
diphtheria and tetanus.
Diphtheria 129
The product information for adolescent/adult formulations of dTpa-containing
vaccines states that these vaccines are indicated for booster doses only.
NHMRC recommends that, where dT is unavailable for the primary course,
dTpa can be used.
The product information for Adacel and Boostrix (adolescent/adult formulations
of dTpa) states that these vaccines are recommended for use in those aged
>10 years. However, NHMRC recommends that they may be used in people
aged ≥8 years. The product information also states that dTpa should not be
given within 5 years of a tetanus toxoid-containing vaccine. However, NHMRC
recommends that dTpa vaccines can be administered at any time following
receipt of a diphtheria and tetanus toxoid-containing vaccine.
References

3.4 Haemophilus influenzae type b (hib)
Bacteriology
Haemophilus influenzae is a Gram-negative coccobacillus that is a normal part of
upper respiratory tract flora. Strains isolated from respiratory tract specimens
such as sputum and middle ear or sinus fluid usually do not have a capsule, and
are known as non-typable (NT). Six capsular types (a to f) have been described
and, before the introduction of vaccination against Haemophilus influenzae type
b (Hib), almost all H. influenzae isolates from sterile sites (blood, cerebrospinal
fluid, joint or pleural fluid) were of the b capsular type.
Before Hib immunisation, invasive disease caused by Hib rarely occurred
after the age of 5 years. This was because the prevalence of antibody to Hib
progressively increased from the age of 2 years, thought to be related to exposure
to Hib (or cross-reacting organisms) colonising the nasopharynx or other sites.
Children <2 years of age are usually unable to mount an antibody response to the
type b capsular polysaccharide, even after invasive disease.1
Clinical features
Clinical categories of invasive disease caused by Hib include meningitis,
epiglottitis and a range of other infections such as septic arthritis, cellulitis
and pneumonia. Hib is rarely isolated from the blood without a focal infection
such as the above being evident or developing subsequently. The classical
clinical signs of meningitis – neck stiffness and photophobia – are often not
detected in infants, who present with drowsiness, poor feeding and high fever.
Epiglottitis (inflammation of the epiglottis) presents with respiratory obstruction,
associated with soft stridor and often drooling in a pale, febrile, anxious child
who remains upright to maximise his or her airway. Meningitis and epiglottitis
are almost invariably fatal without appropriate treatment. There are no specific
clinical features of any of the focal infections due to Hib which enable them
to be differentiated from those due to other organisms. However, before the
introduction of Hib vaccines, epiglottitis was due to Hib in over 95% of cases.2
Epidemiology
influenzae type b (hib)
(i) Before Hib vaccination

3.4 Haemophilus
Before the introduction of routine Hib vaccination in 1993, there were at least
500 cases of Hib disease in Australian children <6 years of age every year, and
a total of 10 to 15 deaths.3 Hib meningitis accounted for approximately 60% of
all invasive Hib disease, most cases occurring in children <18 months of age.
The case fatality rate for Hib meningitis was approximately 5%, and up to 40%
of the survivors had neurological sequelae such as deafness and intellectual
impairment.4 Hib epiglottitis was a more common disease presentation than
Haemophilus influenzae type b (Hib) 131

in many other countries,5 and usually occurred in children >18 months of age.
Other manifestations such as cellulitis, septic arthritis and pneumonia occurred
at a similar age to meningitis.6
The incidence of Hib disease in Aboriginal and Torres Strait Islander children,
especially those in remote and rural areas, was considerably higher than in
non-Indigenous children.7 Most importantly, the onset of Hib disease in this
population was at a much younger age, manifesting mostly as meningitis, with
epiglottitis being rare. Rates of death and long-term morbidity following Hib
meningitis were similar to those observed in non-Indigenous children.7
(ii) After the introduction of Hib vaccination

Since Hib vaccines were included in the routine vaccination schedule in 1993,
there has been a reduction of >90% in notified cases of Hib disease from
502 in 1992 to an average of 30 cases per year between 1999 and 2002, with
approximately 15 cases per year currently reported in Australia (see Figure
3.4.1).8 This reduction has been particularly marked in Indigenous children.9
Similar impressive reductions in Hib disease have been seen in other countries
with routine childhood vaccination.5,10 Since Hib disease has become relatively
rare, cases of epiglottitis can no longer be assumed to be due to H. influenzae type
b and, moreover, even when H. influenzae is isolated from a normally sterile site,
it may not be type b. Thus, laboratory confirmation of H. influenzae infection and
serotype should always be sought before vaccination failure is assumed.11,12

Figure 3.4.1: Haemophilus influenzae type b (Hib) notifications, presumed Hib
hospitalisations and deaths* of children aged 0 to 4 years from Hib, Australia
1993 to 2005†8
25 25
Deaths
Hospitalisation rate
Notification rate
20 20
Rate per 100,000 population
Number of deaths
15 15
10 10
5 5
0 0
1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005
Year
* Hospitalisations and deaths include those for Haemophilus meningitis for the period up to
30 June 2005 (hospitalisations) and 31 December 2004 (deaths).
† Notifications where the month of diagnosis was between July 1993 and December 2005;
hospitalisations where the month of admission was between 1 July 1993 and 30 June 2005;
deaths where the date of death was recorded between January 1993 and December 2004.
Vaccines
The first generation Hib vaccines, consisting of purified polysaccharide (PRP)
from the Hib capsule, were not effective in children <18 months of age. A review
of the efficacy data for the second generation Hib vaccines, which consist of PRP
chemically linked (‘conjugated’) to a variety of carrier proteins, found 3 of the 4
Hib vaccines to be immunogenic against invasive Hib disease, PRP-OMP, PRP-T
and HbOC.13 The fourth vaccine, PRP-D, was not found to be highly protective in
high-risk populations, such as Indigenous children.13
There are 2 main groups of carrier proteins associated with a different temporal
3.4 Haemophilus
pattern of PRP antibody response. The vaccine using the outer membrane
protein of Neisseria meningitidis as a carrier protein (PRP-OMP) (COMVAX,
Liquid PedvaxHIB) gives protective PRP antibody responses after the first dose,
and requires only 2 doses to complete the primary course. For this reason, its
main application worldwide has been in populations with a high incidence
of early onset disease.5 Vaccines using other protein carriers such as tetanus
(PRP-T) (Hiberix, Infanrix hexa) and diphtheria (HbOC) toxoids do not achieve
protective PRP antibody levels until at least a second dose has been given, and

require 3 doses to complete primary immunisation. No or minimal immunologic
interference has been observed when children are vaccinated with 7vPCV and
Infanrix hexa at the same immunisation visit.14,15
Many Hib combination vaccines containing acellular pertussis are known to
produce lower Hib antibody responses than similar formulations containing
whole-cell pertussis.16 When administered according to the United Kingdom’s
schedule as 3 primary doses at 2, 3 and 4 months of age without a booster, their
use has been associated with an increased risk of vaccine failure.17 In other
European countries that routinely give a fourth dose around the time of the 1st
birthday, as is included in the Australian schedule, no loss of effectiveness has
been observed.18,19
• Liquid PedvaxHIB – CSL Biotherapies/Merck & Co Inc (PRP-OMP).

Each 0.5 mL monodose vial contains 7.5 µg PRP conjugated to 125 µg
meningococcal protein; liquid formulation with 35 µg borax and 225 µg
aluminium hydroxide.
• Hiberix – GlaxoSmithKline (PRP-T). Each 0.5 mL monodose lyophilised

vaccine contains 10 µg PRP conjugated to 30 µg tetanus toxoid (with a
lactose stabiliser) for reconstitution with 0.9% saline.
Combination vaccines that include Hib
• COMVAX – CSL Biotherapies/Merck & Co Inc (Hib (PRP-OMP)-hepatitis

B). Each 0.5 mL monodose vial contains 7.5 µg PRP conjugated to 125 µg
meningococcal protein, 5 µg hepatitis B surface antigen; 225 µg aluminium
hydroxide; 35 µg borax. May contain yeast proteins.


Transport according to National Vaccine Storage Guidelines: Strive for 5.20 Store
conjugate Hib vaccines at +2°C to +8°C. Do not freeze.

The dose of Hib vaccine is 0.5 mL to be given by IM injection. Conjugate Hib
vaccines may be administered in separate sites on the same day as any of the
other childhood vaccines such as the 7-valent pneumococcal conjugate (7vPCV),
meningococcal serogroup C conjugate (MenCCV), hepatitis B, DTPa-containing
and monovalent IPV (or IPV-containing) vaccines.
Recommendations
(i) Hib vaccine is recommended for all infants from 2 months of age
Immunisation using PRP-OMP (COMVAX or Liquid PedvaxHIB) requires 2
primary doses at 2 and 4 months, followed by a booster at 12 months of age. If
PRP-T (Infanrix hexa or Hiberix) is used, 3 primary doses at 2, 4 and 6 months
are needed, with a booster at 12 months of age.
(ii) Indigenous children living in the Northern Territory,

Queensland, South Australia and Western Australia
Many Indigenous populations experienced high Hib attack rates associated with
early peak disease onset before the introduction of Hib immunisation. While
vaccination has reduced the overall incidence of invasive Hib infection in these
vulnerable groups, increased disease risk during the first year of life remains.
It is therefore important that Aboriginal and Torres Strait Islander children in
jurisdictions (the Northern Territory, Queensland, South Australia and Western
Australia) where such different patterns of Hib disease remain evident continue
to receive PRP-OMP, because of the early antibody response seen with this
vaccine.7 In Alaskan natives, who experienced similar pre-vaccination attack rate
profiles, re-emergence of Hib disease was observed when the Hib vaccine in use
was changed from PRP-OMP to HbOC.21
(iii) Non-Indigenous children and Indigenous children living in

Australian Capital Territory, New South Wales, Tasmania and Victoria
Any licensed Hib vaccine may be used in these children as the period of
3.4 Haemophilus
significant risk does not begin until after 6 months of age. Although there are
limited data on the epidemiology of Hib disease before vaccination in Indigenous
children in south-eastern Australia, available data since vaccination commenced
in 1993 suggest that the epidemiology in these children does not differ
substantially from that in non-Indigenous children living in these areas (NCIRS
data, unpublished).

(iv) Interchangeability of Hib vaccines
It is recommended that the same conjugate vaccine be used for all doses.
However, if necessary, after the first dose, any Hib vaccine may be used to
complete the primary course.22 For primary vaccination, only 2 doses of PRP-
OMP are required, but if any other Hib vaccine is given, a total of 3 doses is
required to complete the primary course.23 This means that if the previous Hib
vaccine type is unknown for any doses, or the same vaccine type is unavailable,
the primary course can be completed with a total of 3 doses of any combination
of registered Hib vaccines. For booster doses and in children >15 months of
age, regardless of previous Hib vaccinations, a single dose of any registered Hib
vaccine is sufficient for protection. Details of catch-up vaccination schedules are
given in Section 1.3.5, Catch-up.
(v) Vaccine failures

Children who have developed confirmed Hib disease after 2 or more doses
of PRP-OMP or 3 or more doses of PRP-T may warrant immunological
investigation. Consultation with an immunologist with paediatric expertise is
recommended.
(vi) Preterm babies

Preterm babies can be immunised at the normal age, without correction for
prematurity24 (see Section 2.3.2, Vaccination of women planning pregnancy, pregnant
or breastfeeding women, and preterm infants). Extremely preterm babies (<28 weeks’
gestation or <1500 g birth weight) who are vaccinated with PRP-OMP should be
given an extra dose at 6 months of age, resulting in a 4-dose schedule at 2, 4, 6 and
12 months of age.25 When other Hib vaccines, including Infanrix hexa, are used,
no change in the usual schedule is required. Preterm babies have been shown to
produce good antibody responses to all the antigens in Infanrix hexa following
administration at 2, 4 and 6 months of age, although the responses to hepatitis B
and Hib are not quite as high as in term babies.
(vii) Splenectomy
Hib is an uncommon cause of post-splenectomy sepsis in adults and children.
Children >2 years of age who have received all scheduled doses of Hib vaccine
do not require a booster dose after splenectomy. A single dose of Hib vaccine is
recommended for other splenectomised individuals who were not vaccinated
in infancy or are incompletely vaccinated. The vaccine should be given 2 weeks
before a planned splenectomy. Subsequent booster doses of Hib vaccine are
not required.26 For other recommendations for asplenic or splenectomised
individuals, see Section 2.3.3, Vaccination of individuals with impaired immunity due
to disease or treatment.

(viii) Allogeneic and autologous haematopoietic
stem cell transplant (HSCT) recipients
These patients should also be considered for Hib vaccination post transplant.
The Hib conjugate vaccine should be administered to recipients at 12, 14, and
24 months after HSCT. See Section 2.3.3, Vaccination of individuals with impaired
immunity due to disease or treatment.
Contraindications
The only contraindications to any of the Hib vaccines are:
• anaphylaxis following a previous dose of any of the vaccines, or
Adverse events
Swelling and redness at the injection site after the first dose are common and
have been reported in up to 5% of vaccinated children. Fever in up to 2%
(common) has also been reported. These adverse events usually appear within
3 to 4 hours and resolve completely within 24 hours. The incidence of these
adverse events declines with subsequent doses, so it is recommended that the
course of vaccination be completed regardless.
The public health management of contacts

of a child with invasive Hib disease
Healthcare workers should be guided by public health authorities in the public
health management of cases of invasive Hib disease.
Household
As the incidence of invasive Hib disease is now very low, rifampicin chemo
prophylaxis is no longer routinely indicated unless the household contains either:
• an infant <7 months of age (regardless of vaccination status), or
• a child aged 7 months to 5 years who is inadequately vaccinated according to
the Hib schedule.
In this case, everybody in the household should receive rifampicin prophylaxis after
a case of invasive Hib disease in any household member, with the exception of
pregnant women for whom ceftriaxone may be used. The recommended dose of
3.4 Haemophilus
rifampicin is 20 mg/kg as a single daily dose (maximum daily dose 600 mg) for
4 days. Neonates (<1 month of age) should receive 10 mg/kg daily for 4 days.

Childcare facilities
Similarly, if the index case attends a child day-care facility for more than 18
hours a week, rifampicin should be given to all children and staff who were
in the same room group (as the case) in the 7 days preceding the case’s onset,
provided that at least one of these close contacts is a child <24 months of age who
is inadequately vaccinated. Although there may have been some intermingling
of all the children at the facility at the beginning and end of the day, this is
usually of a short duration only and not enough to justify extending the use of
rifampicin. Rifampicin prophylaxis is of no value more than 30 days after initial
contact with a case.
Use in pregnancy

The product information for Hib vaccines recommends the vaccine for use in
children aged 2 months to 5 years. NHMRC recommends administration of Hib
vaccine to older people with asplenia or following either allogeneic or autologous
haematopoietic stem cell transplantation.
With the exception of PRP-OMP, the product information for Hib vaccines
recommends use as a booster at 18 months, but the NHMRC regards a booster at
12 months of age as likely to result in an equivalent immune response.
The product information for Infanrix hexa states that this vaccine may be given
as a booster dose at 18 months of age. NHMRC recommends that a booster dose
of DTPa (or DTPa-containing vaccines) is not necessary at 18 month of age.
However, DTPa-containing vaccine may be used for catch-up of the primary
schedule in children <8 years of age.
References

3.5 Hepatitis A
3.5 Hepatitis A
Virology
Hepatitis A is an acute infection of the liver caused by a hepatovirus, the hepatitis
A virus (HAV).1 The virus survives well in the environment – it persists on hands
for several hours and in food kept at room temperature for considerably longer –
and is relatively resistant to heat and freezing.
Clinical features
Hepatitis A is an infection of humans; there is no animal reservoir. HAV is
predominantly transmitted by the faecal-oral route. The infecting dose is
unknown but it is presumed to be low. The incubation period of hepatitis A is
15 to 50 days, with a mean of about 30 days.1 HAV is excreted in faeces for up to
2 weeks before the onset of illness and for at least 1 week afterwards.1
In young children, HAV usually causes either an asymptomatic infection or a
very mild illness without jaundice. Patients with symptomatic illness typically
have a 4 to 10 day prodrome of systemic (fever, malaise, weakness and anorexia)
and gastrointestinal (nausea and vomiting) symptoms. Dark urine is usually
the first specific manifestation of acute hepatitis A, followed a day or 2 later
by jaundice and pale faeces. The prodromal symptoms tend to wane with the
onset of jaundice, although the anorexia and malaise may persist; pruritus and
localised hepatic discomfort or pain may follow.1 The duration of illness varies
but most patients feel better and have normal, or near normal, liver function
tests within a month of the onset of illness. Complications of hepatitis A are
uncommon but include, on rare occasion, fulminant hepatitis.2 Hepatitis A does
not cause chronic liver disease.
The diagnosis is made by detecting anti-HAV IgM in serum during the acute
illness. Anti-HAV IgM is invariably present by the time the patient presents and
persists for 3 to 6 months after the acute illness.1 Serum anti-HAV IgG indicates
past infection (or possibly immunisation) and therefore immunity; it probably
persists for life.
Epidemiology
Hepatitis A was a considerable public health problem in Australia in the
1990s. During this time numerous outbreaks occurred in child day-care centres
and preschools,3 communities of men who have sex with men,4 schools and
residential facilities for the intellectually disabled,5 and communities of injecting
drug users.4 A very large outbreak of hepatitis A associated with the consumption
of raw oysters occurred in New South Wales in 1997 (see Figure 3.5.1).6
However, there has been a marked decline in notifications of hepatitis A in
Australia in recent years (see Figure 3.5.1). This is probably a consequence of
Hepatitis A 139
the liberal use of hepatitis A vaccine among travellers, and those at increased
risk because of lifestyle or occupation. A hepatitis A vaccination program for
Indigenous children in north Queensland that began in 1999 has also contributed
substantially to the decline in notifications.7
Nevertheless, Indigenous Australian children remain at considerably greater
risk, not only of acquiring hepatitis A but also for being hospitalised with the
infection, compared to non-Indigenous children.8 This is particularly true for
Indigenous children residing in other regions of Queensland, the Northern
Territory, South Australia and Western Australia.
Figure 3.5.1: Notifications of hepatitis A in Australia, 1991 to 2006
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Vaccines
• Avaxim – Sanofi Pasteur Pty Ltd (formaldehyde inactivated hepatitis A
virus (GBM strain)). Each 0.5 mL pre-filled syringe contains 160 ELISA units
of hepatitis A virus (HAV) antigens inactivated by formaldehyde; 0.3 mg
aluminium hydroxide; 2.5 µL phenoxyethanol; 12.5 µg formaldehyde; trace
of neomycin.
• Havrix Junior – GlaxoSmithKline (formaldehyde inactivated hepatitis A

virus (HM175 strain)). Each 0.5 mL monodose vial or pre-filled syringe
contains 720 ELISA units of HAV antigens; 0.25 mg as aluminium
hydroxide; 0.5% w/v phenoxyethanol; traces of formaldehyde and
neomycin.
• Havrix 1440 – GlaxoSmithKline (formaldehyde inactivated hepatitis A virus

(HM175 strain)). Each 1.0 mL monodose vial or pre-filled syringe contains
1440 ELISA units of HAV antigens; 0.5 mg aluminium hydroxide; 0.5% w/v
phenoxyethanol; traces of formaldehyde and neomycin.

• Twinrix Junior (360/10) – GlaxoSmithKline (formaldehyde inactivated
hepatitis A virus (HM175 strain) and recombinant hepatitis B vaccine). Each
0.5 mL monodose vial or pre-filled syringe contains 360 ELISA units of
3.5 Hepatitis A
HAV antigens, 10 µg recombinant DNA hepatitis B surface antigen protein;
0.225 mg aluminium phosphate/hydroxide; 0.5% w/v phenoxyethanol;
traces of formaldehyde and neomycin. May contain yeast proteins.
• Twinrix (720/20) – GlaxoSmithKline (formaldehyde inactivated hepatitis

A virus (HM175 strain) and recombinant hepatitis B vaccine). Each 1.0 mL
monodose vial or syringe contains 720 ELISA units of HAV antigens, 20 µg
recombinant DNA hepatitis B surface antigen protein; 0.45 mg aluminium
phosphate/hydroxide; 0.5% w/v phenoxyethanol; traces of formaldehyde
and neomycin. May contain yeast proteins.
• VAQTA Paediatric/Adolescent formulation – CSL Biotherapies/Merck &

Co Inc (formaldehyde inactivated hepatitis A virus (CR326F strain)). Each
0.5 mL monodose vial contains approximately 25 units (U) of hepatitis
A virus protein; 0.225 mg aluminium hydroxide; 35 µg borax; trace of
formaldehyde.
• VAQTA Adult formulation – CSL Biotherapies/Merck & Co Inc

(formaldehyde inactivated hepatitis A virus (CR326F strain)). Each 1.0 mL
monodose vial contains approximately 50 units (U) of hepatitis A virus
protein; aluminium 0.45 mg as aluminium hydroxide; 70 µg borax; trace of
formaldehyde.
• Vivaxim – Sanofi Pasteur Pty Ltd (inactivated hepatitis A virus and typhoid
Vi capsular polysaccharide). Supplied in a unique dual-chamber syringe
which enables the 2 vaccines to be mixed just before administration. Each
1.0 mL dose of mixed vaccine contains 160 ELISA units of inactivated
hepatitis A virus antigens, 25 µg purified typhoid capsular polysaccharide;
0.3 mg aluminium hydroxide; 2.5 µL phenoxyethanol; formaldehyde; traces
of neomycin and bovine serum albumin.
The inactivated hepatitis A vaccines are prepared from HAV harvested from
human diploid cell cultures, which are then purified by ultrafiltration and
chromatography, inactivated by formaldehyde, and then adsorbed onto
aluminium hydroxide adjuvant. Although the vaccines are prepared from
differing strains of HAV, there is only one known serotype; immunity induced by
a particular strain probably provides protection against all strains.1
The Avaxim, Havrix, Twinrix and Vivaxim vaccines contain a preservative,
2-phenoxyethanol. All the vaccines contain minute amounts of residual
formaldehyde. Although the manufacturers use slightly different production
methods and quantify the HAV antigen content in their respective vaccines
Hepatitis A 141
differently, the ‘equivalent’ vaccines of the different manufacturers are
interchangeable.
The inactivated hepatitis A vaccines induce HAV antibodies (anti-HAV) at titres
many-fold greater than that provided by the recommended dose of normal
human immunoglobulin. Although the vaccines are highly immunogenic (see
below), the titres are usually below the detection limits of the routinely available
commercial tests for anti-HAV.1 Therefore, serological testing to assess immunity
after vaccination against hepatitis A is neither necessary nor appropriate. Likewise, it
is also inappropriate to undertake testing if an individual cannot recall if he/she
has been vaccinated against hepatitis A in the past; if no vaccination records are
available, vaccination should be advised.
Hepatitis A vaccines are highly immunogenic in both children and adults, with
virtually universal seroconversion 4 weeks after vaccination.1 Two randomised
clinical trials conducted in the early 1990s showed that the vaccines have a very
high protective efficacy, approaching 100%.9,10 This finding is supported by
the apparent eradication of hepatitis A from Indigenous communities in north
Queensland since the introduction of the vaccination program in the region.7
The duration of immunity and, therefore, protection following vaccination is not
certain. However, vaccine-induced anti-HAV probably persists for many years.
There is no current evidence that booster doses are required; in healthy
individuals, it is quite possible that they will never be required.11

Transport according to National Vaccine Storage Guidelines: Strive for 5.12 Hepatitis
A vaccines should be transported and stored at +2°C to +8°C. Do not freeze.

The inactivated hepatitis A vaccines are administered by IM injection. The
recommended dosages and schedules for use in Australia are given in Table 3.5.1.

Table 3.5.1: Recommended dosages and schedules for use of the inactivated
hepatitis A vaccines
Vaccine Vaccinee’s age Dose Volume Vaccination schedule
3.5 Hepatitis A
(years) (HAV antigen) per dose (mo=months)
(mL)
Monovalent hepatitis A vaccines
Avaxim ≥2 160 EIA U 0.5 0, 6 to 12 mo
Havrix Junior 2– <16 720 EIA U 0.5 0, 6 to 12 mo
Havrix 1440 ≥16 1440 EIA U 1.0 0, 6 to 12 mo
VAQTA Paediatric/ 1– <18 25 U 0.5 0, 6 to 18 mo
Adolescent
VAQTA Adult ≥18 50 U 1.0 0, 6 to 18 mo
Combination hepatitis A/hepatitis B vaccines
Twinrix Junior 1– <16 360 EIA U 0.5 0, 1, 6 mo
(360/10)
Twinrix (720/20) ≥16 720 EIA U 1.0 0, 1, 6 mo
Twinrix (720/20)* 1– <16 720 EIA U 1.0 0, 6 to 12 mo
Twinrix (720/20) †
≥16 720 EIA U 1.0 0, 7, 21 days, 12 mo
Combination hepatitis A/typhoid vaccine
Vivaxim ≥16 160 EIA U 1.0 (mixed 0; a single dose of
vaccine) monovalent adult
formulation hepatitis
A vaccine should be
given at 6 to 36 mo.
* This schedule should not be used for those who require prompt protection against
hepatitis B; for example, if there is close contact with a known hepatitis B carrier.
† This ‘rapid’ schedule should be used only if there is very limited time before departure to
either moderately or highly endemic regions.
Recommendations
To avoid unnecessary vaccination, it is recommended that the following groups
be screened for pre-existing natural immunity to hepatitis A:
• those born before 1950,
• those who spent their early childhood in endemic areas, and
• those with an unexplained previous episode of hepatitis or jaundice. (NB.
Such a previous episode cannot be assumed to be hepatitis A.)
If, upon screening, a person has either total hepatitis A antibodies or anti-HAV
IgG, he/she has presumably had previous, perhaps unrecognised, HAV infection
(or less likely, has been previously immunised) and can be assumed to be
immune and, therefore, does not need hepatitis A vaccination.
Hepatitis A 143
(i) Hepatitis A vaccination is recommended for:
• all travellers to, and all expatriates living in, moderately to highly endemic
areas (including all developing countries)
A single dose of a monovalent hepatitis A vaccine provides protective levels of
anti-HAV for at least a year;1 the second dose is recommended to increase the
duration of protection. As they do not contain live viruses, hepatitis A vaccines
can be administered either simultaneously with, or within a month of, all other
vaccines relevant to international travel.13
There is no place for the routine use of normal human immunoglobulin to
prevent hepatitis A in travellers. It should only be given (at the same time
as hepatitis A vaccine) to those, such as aid-workers about to be deployed in
emergency refugee camps, who will be living in very inadequate circumstances.
Otherwise, it is only recommended for contacts of hepatitis A cases (see ‘The
public health management of contacts of hepatitis A cases’ below).
• Aboriginal and Torres Strait Islander children residing in the Northern
Territory, Queensland, South Australia and Western Australia
Hepatitis A vaccination for these children should commence in the second year
of life. State/Territory health authorities should be contacted about the local
hepatitis A vaccination schedules, including catch-up.
• those whose occupation may put them at risk of acquiring hepatitis A
This includes those who live or work in rural and remote Indigenous
communities, child day-care and preschool personnel, carers of people with
intellectual disabilities, healthcare workers who regularly provide care for
Aboriginal and Torres Strait Islander children, plumbers or sewage workers, and
sex workers.
• those whose lifestyle may put them at risk of acquiring hepatitis A
This includes men who have sex with men, and injecting drug users.
• people with intellectual disabilities
• people chronically infected with either hepatitis B or hepatitis C viruses
• patients with chronic liver disease
Hepatitis A vaccination is recommended for patients with chronic liver disease
of any aetiology. Those with chronic liver disease of mild to moderate severity
mount a satisfactory immune response following vaccination, but those with
end-stage liver disease do not respond as well, and liver transplant recipients
may not respond at all.14,15 Nevertheless, all those with chronic liver disease
should be vaccinated, preferably as early in the course of the disease as possible.

(ii) Combined hepatitis A/hepatitis B vaccines
Combined hepatitis A/hepatitis B vaccines should be considered for:
• expatriates and long-term visitors to developing countries,
3.5 Hepatitis A
NB. Twinrix (720/20) can be administered according to a ‘rapid’ schedule if
there is limited time before departure.16 This consists of a single dose on each
of days 0, 7 and 21. It is important that a fourth dose be given as a booster
12 months after the first dose to ensure longer-term protection.
• medical, dental and nursing undergraduate students,
• men who have sex with men,
• sex industry workers,
• injecting drug users,
• patients with chronic liver disease,
• solid organ transplant recipients (see Table 2.3.2 Recommendations for
vaccinations for solid organ transplant (SOT) recipients),
• people with intellectual disabilities and their carers.
NB. Twinrix (720/20) can be administered in a 2-dose regimen in people 1 to
15 years of age (see Table 3.5.1). However, this regimen should not be used in
those who require prompt protection against hepatitis B; for example, if there is
close contact with a known hepatitis B carrier.
Combined hepatitis A/hepatitis B vaccines can be administered simultaneously
with, or within a month of, all other vaccines relevant to international travel.
(iii) Combined hepatitis A/typhoid vaccine

The combined hepatitis A/typhoid vaccine can be recommended for all
those ≥16 years of age who intend travelling to developing countries, and is
particularly useful for those already immunised against hepatitis B. The vaccine
can be administered simultaneously with, or within a month of, all other vaccines
relevant to international travel.
A single dose of a monovalent adult formulation hepatitis A vaccine 6 to
36 months later is required to provide longer-term protection against hepatitis
A. A booster dose of typhoid capsular polysaccharide vaccine is required after
3 years if there is a continued risk. The combined hepatitis A/typhoid vaccine
may be used as a ‘booster’ vaccine if a person received a previous dose of a
monovalent adult formulation hepatitis A vaccine. This may be given 6 to
36 months after primary vaccination.
Hepatitis A 145
Contraindications
The only contraindications to any of the hepatitis A vaccines are:
• anaphylaxis following a previous dose of any of the hepatitis A vaccines, or
Combination vaccines containing the hepatitis B component are contraindicated
where there is a history of anaphylaxis to yeast.
Adverse events
The most common adverse events following administration of hepatitis A
vaccines are mild local events of a short duration, probably caused by the
aluminium hydroxide adjuvant. About 15% (very common) of adults report
headache and approximately 5% (common) report malaise or fatigue following
vaccination.17 Up to 20% (very common) of children who received either Havrix
or VAQTA experienced soreness at the injection site. In both adults and children,
systemic adverse events such as headache and fever are much less common than
local adverse events.17
Hepatitis A vaccines do not affect liver enzyme levels. They can be safely given to
HIV-infected people, and do not adversely affect either the HIV load or CD4 cell
count.18
The public health management of

contacts of hepatitis A cases
Normal human immunoglobulin (NHIG) can be used to prevent secondary cases
in close contacts of hepatitis A cases. (NB. A hepatitis A IgM positive test in an
adult without either clinical or epidemiological features of hepatitis A should be
considered as a false-positive result.19 In this circumstance, no interventions are
necessary for the close contacts.)
NHIG should be administered to close contacts within 2 weeks (of the last
exposure to the cases) in the doses given in Table 3.5.2; NHIG may not be
effective if given >2 weeks after the exposure.17 ‘Close contacts’ are those who
have had contact with a case during the 2 weeks before, up until 1 week after, the
onset of jaundice, and usually include only household and/or sexual contacts
(but in some circumstances may include close occupational exposure).
Table 3.5.2: Recommended doses of normal human immunoglobulin (NHIG) to

be given as a single intramuscular injection to close contacts of hepatitis A cases
Weight Dose NHIG

Under 25 kg 0.5 mL
25–50 kg 1.0 mL
Over 50 kg 2.0 mL

Although 1 study suggests that hepatitis A vaccine may be effective in preventing
secondary cases of hepatitis A in close contacts,20 there is currently insufficient
evidence to be able to recommend it for this purpose.
3.5 Hepatitis A
Further public health considerations
If a person with hepatitis A was a food-handler by occupation while infectious,
a review of the food-handling procedures in the food establishment should
be undertaken and the staff at the establishment reminded of standard food
and personal hygiene practices.17 If the review identifies issues which raise the
possibility of transmission of HAV, NHIG should be administered to the other
food-handlers in the establishment. State/Territory public health authorities
should determine the need for recall of customers of the establishment for NHIG.
A food-handler with hepatitis A should be excluded from work until at least
1 week after the onset of jaundice.
A single case of hepatitis A associated with a day-care or preschool facility (ie. a
case in an attendee child, a staff member or a household contact of an attendee or
staff member) does not require any mass intervention.3 However, the supervisor
of the facility should be contacted to:
• explore the possibility of within-centre transmission by the case (eg. faecal
accidents, other hygiene control concerns), and
• determine if there could be other cases associated with the facility. In
particular, it should be ascertained whether an attendee child arrived from an
endemic region overseas about a month before the case’s onset, and whether
any other children at the facility have recently been vaguely unwell with a
change in bowel motions.
Should there be any concerns about the potential for further transmission of
hepatitis A virus within the facility, mass interventions (as per 2 or more cases
below) may be considered. The supervisor should be reminded of the relevant
infection control practices that should be in place at all times at the facility,
and that hepatitis A vaccine is routinely recommended for day-care and
preschool staff (unless they have either had hepatitis A in the past or been
vaccinated previously). A useful reference is ‘Staying Healthy in Child Care’
available at http://www.nhmrc.gov.au/publications/synopses/ch43syn.htm.
Two or more cases of hepatitis A (associated with the same day-care or
preschool facility) that occur in different households are strongly suggestive that
transmission of HAV is occurring within that facility.3 These cases may be in
attendee children or staff or household contacts of an attendee or staff member.
As soon as transmission of HAV is recognised within a day-care or preschool
facility, NHIG should be offered to children and susceptible staff in the relevant
age groups (or classes) at that facility. Parents and staff need to be reminded
that live virus vaccines, MMR and varicella vaccines in particular, should not be
administered within 3 months of receiving IM NHIG.3
Hepatitis A 147
Use in pregnancy

None.
References

3.6 Hepatitis B
Virology
Hepatitis B virus (HBV) contains partially double-stranded DNA. The outer
surface of the virus is glycolipid which contains the hepatitis B surface antigen
(HBsAg). Other important antigenic components are hepatitis B core antigen
(HBcAg), and hepatitis B e antigen (HBeAg). HBcAg is not detectable in serum,
but can be detected in liver tissue in people with acute or chronic hepatitis B
infection. Antibodies developed to HBsAg (anti-HBs) indicate immunity, whereas
persistence of HBsAg denotes infectivity, which is greater if HBeAg and HBV
DNA are positive.1
Clinical features
3.6 Hepatitis B
In approximately 30 to 50% of adults, infection causes symptomatic acute
hepatitis, but in young children, particularly those <1 year of age, infection is
usually asymptomatic. The incubation period is 45 to 180 days and the period
of communicability extends from several weeks before the onset of acute illness
usually to the end of the period of acute illness. Acute illness is indistinguishable
from other forms of hepatitis, and symptoms include fever, jaundice, malaise,
anorexia, nausea and vomiting, abdominal pain (especially in the right upper
quadrant), myalgia, and the passage of dark-coloured urine and light-coloured
stools. Jaundice may be preceded by an acute febrile illness with arthralgia or
arthritis and rash, most typical of hepatitis B. During recovery, malaise and
fatigue may persist for many weeks. Fulminant hepatitis occurs in approximately
1% of acute cases.1,2
Following acute infection, 1 to 10% of those infected as adults2,3 and up to 90%
of those infected as neonates1,2 remain persistently infected for many years (see
Figure 3.6.1). Chronically infected carriers of HBV are identified by the long-term
presence (longer than 6 months) of circulating HBsAg.4
Hepatitis B 149
Figure 3.6.1: The influence of age of infection with the hepatitis B virus on the
likelihood of becoming a hepatitis B carrier
(Modified and used with permission from: Edmunds WJ, Medley GF, Nokes DJ, Hall AJ, Whittle HC. The
influence of age on the development of the hepatitis B carrier state. Proceedings. The Royal Society Biological
Sciences.1993;253:197-201.)
Carriers of HBV are capable of transmitting the disease, though often remain
asymptomatic and may not be aware that they are infected. Most of the serious
complications associated with hepatitis B infection occur in HBV carriers.
Chronic active hepatitis develops in more than 25% of carriers, and up to 25% die
prematurely of cirrhosis or hepatocellular carcinoma.1,2
Epidemiology
The prevalence of HBV carriage differs in different parts of the world, and may
be quite variable within countries. Carrier rates vary from 0.1 to 0.2% among
Caucasians in the United States, northern Europe and Australia, 1 to 5% in
the Mediterranean countries, parts of eastern Europe, China, Africa, Central
and South America, and some Australian Aboriginal populations, and greater
than 10% in many sub-Saharan African, southeast Asian and Pacific island
populations.5-7 First-generation immigrants usually retain the carrier rate of
their country of origin, but subsequent generations show a declining carrier rate
irrespective of vaccination.5
Transmission of hepatitis B may result from percutaneous inoculation or mucosal
contact with blood or sexual secretions from an HBsAg-positive individual.
Screening of blood and organ donors has virtually eliminated the risk of
transmission of hepatitis B through blood transfusion and organ transplants.8,9
Saliva may also contain levels of virus which are likely to be infective only if
inoculated directly into tissue (ocular or mucous membranes). Transmission by
inadvertent parenteral inoculation, such as by toothbrush, razor etc., through
close personal contact in households in which 1 or more carriers or other infected
individuals reside, is a low but significant risk.
Routes of transmission include:
• sharing injecting equipment (such as occurs in injecting drug use),
• needle-stick injury, and other types of parenteral inoculation,

• sexual contact (including heterosexual or homosexual intercourse, although
the latter has a higher risk),
• transmission from infected mother to neonate (vertical transmission), usually
occurring at or around the time of birth,
• child-to-child (horizontal) transmission, usually through contact between open
sores or wounds,
• breastfeeding,10
• nosocomial transmission in overseas healthcare facilities if infection control
procedures are unsatisfactory.
Australian vaccination policy

The initial strategy for the control of hepatitis B in Australia commenced in
1988, targeting groups at particular risk of infection for vaccination at birth. In
addition to vaccine, hepatitis B immunoglobulin (HBIG) was given if the mother
3.6 Hepatitis B
was a hepatitis B carrier. In 1990, universal infant vaccination commenced
in the Northern Territory. In 1996, the NHMRC recommended a universal
hepatitis B vaccination program for infants and adolescents. The adolescent
program commenced in some States and Territories in 1997 and the universal
infant program, with the first dose given at birth, began nationally in 2000. The
adolescent program will continue until those immunised for hepatitis B in the
childhood program reach adolescence.
Vaccines
• Engerix-B – GlaxoSmithKline (recombinant DNA hepatitis B vaccine).
Adult formulation – Each 1.0 mL monodose vial contains 20 µg
recombinant hepatitis B surface antigen (HBsAg) protein, adsorbed onto
0.5 mg aluminium hydroxide. Paediatric formulation – Each 0.5 mL
monodose vial contains 10 µg HBsAg protein, adsorbed onto 0.25 mg
aluminium hydroxide. Both formulations contain traces of yeast proteins
and thiomersal (<2 µg/mL). Both are available in packs of 10.
• H-B-VAX II – CSL Biotherapies/Merck & Co Inc (recombinant DNA hepatitis

B vaccine). Adult formulation preservative free – Each 1.0 mL pre-filled
syringe or vial contains 10 µg recombinant HBsAg protein, adsorbed onto
0.5 mg aluminium hydroxide. May contain yeast proteins. Paediatric
formulation preservative free – Each 0.5 mL pre-filled syringe or vial
contains 5 µg recombinant HBsAg protein, adsorbed onto 0.25 mg aluminium
hydroxide. May contain yeast proteins. Both are available in packs of 10.
Dialysis formulation preservative free – Each 1.0 mL vial contains 40 µg
recombinant HBsAg protein, adsorbed onto 0.5 mg aluminium hydroxide.
May contain yeast proteins. Available as single pack only.
Hepatitis B 151
Combination vaccines that include both DTPa and hepatitis B


Other combination vaccines that include hepatitis B
• COMVAX – CSL Biotherapies/Merck & Co Inc (Hib (PRP-OMP)-hepatitis

B). Each 0.5 mL monodose vial contains 7.5 µg PRP conjugated to 125 µg
meningococcal protein, 5 µg hepatitis B surface antigen; 225 µg aluminium
hydroxide; 35 µg borax. May contain yeast proteins.
• Twinrix Junior (360/10) – GlaxoSmithKline (formaldehyde inactivated

hepatitis A virus (HM175 strain) and recombinant hepatitis B vaccine). Each
0.5 mL monodose vial or pre-filled syringe contains 360 ELISA units of
HAV antigens, 10 µg recombinant DNA hepatitis B surface antigen protein;
0.225 mg aluminium phosphate/hydroxide; 0.5% w/v phenoxyethanol;
traces of formaldehyde and neomycin. May contain yeast proteins.
• Twinrix (720/20) – GlaxoSmithKline (formaldehyde inactivated hepatitis

A virus (HM175 strain) and recombinant hepatitis B vaccine). Each 1.0 mL
monodose vial or syringe contains 720 ELISA units of HAV antigens, 20 µg
recombinant DNA hepatitis B surface antigen protein; 0.45 mg aluminium
phosphate/hydroxide; 0.5% w/v phenoxyethanol; traces of formaldehyde
and neomycin. May contain yeast proteins.

Hepatitis B vaccines are prepared using recombinant technology. After
purification, the HBsAg protein is adsorbed onto elemental aluminium (as
hydroxide and/or phosphate). Preservatives, including thiomersal, may be
added. Hepatitis B vaccines may contain up to 1% yeast proteins (but no yeast
DNA).
Thiomersal-free vaccines, such as H-B-VAX II preservative free paediatric
formulation, are now available and are recommended for administration to
newborns and infants.11 Engerix-B paediatric formulation contains a trace amount
of thiomersal (<2 µg/mL). All other infant and childhood hepatitis B-containing
combination vaccines, such as Infanrix Penta, Infanrix hexa, COMVAX and
Twinrix Junior (360/10), are thiomersal-free.

3.6 Hepatitis B
+2°C to +8°C. Do not freeze.

Monovalent hepatitis B vaccines are white, slightly opalescent liquids. Any
visible change in the product, such as an amorphous flocculent or a granular
precipitate may indicate incorrect storage conditions.
(i) Administer by deep IM injection.
(ii) 3-dose regimen
For children and young adults <20 years of age, a total of 3 doses of 0.5 mL of
paediatric formulation is recommended. The optimal interval is 1 month between
the first and second doses and a third dose 5 months after the second dose. The
use of longer time intervals between doses does not impair the immunogenicity
of hepatitis B vaccine, especially in adolescents and young children.13,14 The
minimum interval between the second and third doses is 2 months.
(iii) For adults ≥20 years of age, a full course of hepatitis B vaccine consists of 3
doses of 1 mL of adult formulation. There should be an interval of 1 to 2 months
between the first and second doses with a third dose 2 to 5 months after the
second dose (this schedule applies to both Engerix-B and H-B-VAX II). The
minimum interval between the second and third doses is 2 months.
This induces protective levels of neutralising antibody against hepatitis B
virus in more than 90% of adults. The frequency of seroconversion increases
progressively from approximately 35% after the first injection to more than
90% after the third injection. There is evidence of immunity (anti-HBs) in most
vaccinated subjects after administration of 2 doses of the 3-dose vaccine regimen.
However, the third dose is necessary to increase the percentage of responders
and to provide long-term protection.
Hepatitis B 153
(iv) Alternative 2-dose regimens
A randomised controlled trial, involving 1026 adolescents, demonstrated that
adolescents 11–15 years of age who received 2 doses of the adult formulation at 0
and 4–6 months, developed similar protective antibody levels to those vaccinated
using the paediatric formulations in the standard 3-dose regimen administered at
0, 1 and 6–12 months.15
An open label comparative study in adults found increased compliance among
those receiving a 2-dose schedule (86%) over those who completed the 3-dose
schedule (18%). Antibody responses were found to be similar among the 2
groups.16
A 2-dose schedule used in the 11–15 years age group will improve compliance
and provide comparable immunogenicity to that of a 3-dose paediatric schedule.
Adolescents (11–15 years of age) can be vaccinated with H-B-VAX II 10 µg (adult
formulation) or Engerix-B 20 µg (adult formulation) in a 2-dose regimen of 0 and
4–6 months (H-B-VAX II) or 0 and 6 months (Engerix-B). In older adolescents
up to the age of 19 years, in whom compliance with a 3-dose paediatric dosing
schedule is in doubt, a 2-dose schedule using an adult formulation may also be
used in order to improve protection.
When protection is required against both hepatitis A and hepatitis B in children
1–15 years of age, administration of Twinrix (720/20) in a 2-dose regimen at 0
and 6–12 months results in protective antibody levels for both hepatitis A and
hepatitis B (see Table 3.6.1).

Table 3.6.1: Hepatitis B and hepatitis A/hepatitis B combination vaccination
schedules
Vaccine Age Dose (HBsAg Volume Schedule (mo=months)

protein)
Monovalent hepatitis B vaccines
Engerix-B <20 years 10 µg 0.5 mL 0, 1, 6 mo (3-dose
(paediatric) schedule)
Engerix-B (adult) 11–15 years 20 µg 1.0 mL 0, 6 mo (2-dose schedule)
Engerix-B (adult) ≥20 years 20 µg 1.0 mL 0, 1, 6 mo (3-dose
schedule)
H-B-VAX II <20 years 5 µg 0.5 mL 0, 1, 6 mo (3-dose
(paediatric) schedule)
H-B-VAX II (adult) 11–15 years 10 µg 1.0 mL 0, 4–6 mo (2-dose
3.6 Hepatitis B
schedule)
H-B-VAX II (adult) ≥20 years 10 µg 1.0 mL 0, 1, 6 mo (3-dose
schedule)
H-B-VAX ≥20 years 40 µg 1.0 mL 0, 1, 6 mo (3-dose
II (dialysis schedule)
formulation)
Combination hepatitis A/B vaccines
Twinrix (720/20)* 1– <16 years 20 µg 1.0 mL 0, 6–12 mo (2-dose
schedule)
Twinrix Junior 1– <16 years 10 µg 0.5 mL 0, 1, 6 mo (3-dose
(360/10) schedule)
Twinrix (720/20) ≥16 years 20 µg 1.0 mL 0, 1, 6 mo (3-dose
schedule)
* This schedule should not be used for those who require prompt protection against
hepatitis B; for example, if there is close contact with a known hepatitis B carrier.
Hepatitis B 155
(v) Accelerated schedule
Engerix-B formulations (paediatric and adult) and Twinrix (720/20) are
registered for use in accelerated schedules. Accelerated schedules should only
be used if there is very limited time before departure to endemic regions (see
Table 3.6.2).
Table 3.6.2: Accelerated hepatitis B vaccination schedules*
Vaccine Age Dose (HBsAg Volume Schedule (mo=months)

protein)
Engerix-B <20 years 10 µg 0.5 mL 0, 1, 2, 12 mo
(paediatric)
Engerix-B (adult) ≥20 years 20 µg 1.0 mL 0, 1, 2, 12 mo
or
0, 7, 21 days, 12 mo
Twinrix (720/20) ≥16 years 20 µg 1.0 mL 0, 7, 21 days, 12 mo
* As higher seroprotective rates are seen after the 0, 1, 2 month schedule, it is recommended
that the 0, 7, 21 days schedule be used only in adults and only in exceptional circumstances.
In both schedules, a booster dose at 12 months is recommended for long-term protection.
Recommendations
(i) Infants and young children
A birth dose of thiomersal-free monovalent hepatitis B vaccine, followed by
doses given in combination vaccines (such as DTPa-hepB, DTPa-hepB-IPV,
DTPa-hepB-IPV-Hib or Hib (PRP-OMP)-hepB) at 2, 4 and either 6 or 12 months,
is recommended for all children.
The rationale for the universal birth dose is not only to prevent vertical
transmission from a carrier mother (recognising that there may be errors or
delays in maternal testing, reporting, communication or appropriate response),
but also to prevent horizontal transmission in the first months of life from a
carrier among household or other close contacts.17 The birth dose should be given
as soon as the baby is physiologically stable, and preferably within 24 hours of
birth. Every effort should be made to administer the vaccine before discharge
from the obstetric hospital.
Extensive experience indicates that the birth dose of hepatitis B vaccine is
very well tolerated by newborn infants. It does not interfere with either the
establishment or maintenance of breastfeeding, and it is not associated with
an increased risk of either fever or medical investigation for sepsis in the
newborn.18-20
If an infant has missed the birth dose and is aged 8 days or older, a catch-
up schedule is not required. A primary course of a hepatitis B-containing

combination vaccine should be given at 2, 4 and either 6 or 12 months of age
(provided the mother is HBsAg negative).
NB. All babies (preterm or term) of carrier mothers must be given a birth dose of
hepatitis B vaccine and HBIG.
Management of infants born to hepatitis B carrier mothers

Routine antenatal screening for HBsAg is essential for correct implementation
of the strategy to prevent newborn infants from becoming infected with, and
therefore carriers of, HBV. It also has benefits of enabling appropriate follow-
up and management of a carrier, identification of the immune status of other
household members, and protection of those who are susceptible to HBV
infection. Infants born to HBsAg positive mothers should be given HBIG and
a dose of thiomersal-free monovalent hepatitis B vaccine on the day of birth.
The dose of HBIG is 100 IU to be given by IM injection. Administration of
HBIG is preferable within 12 hours of birth, as its efficacy decreases markedly if
3.6 Hepatitis B
administration is delayed beyond 48 hours after birth.
The first dose of monovalent hepatitis B vaccine should be given at the same
time as HBIG, but in the opposite anterolateral thigh, as soon as possible –
preferably within 24 hours of birth, and definitely within 7 days. This regimen
results in seroconversion rates of more than 90% in neonates, despite concurrent
administration of HBIG. If concurrent administration is not possible, vaccination
should not be delayed beyond 7 days after birth as (providing it is given early)
vaccine alone has been shown to be effective in preventing carriage.21 Three
subsequent doses of a multivalent/combination vaccine should be given at 2,
4 and either 6 or 12 months of age (depending on the vaccine used), so that the
infant is given a total of 4 doses of hepatitis B-containing vaccines.
Preterm babies
Preterm babies do not respond as well to hepatitis B-containing vaccines as term
babies.22-25 Thus, for babies at <32 weeks’ gestation or <2000 g birth weight, it is
recommended to give vaccine at 0, 2, 4 and 6 months of age and either:
(ii) Adolescents
Vaccination of adolescents 10 to 13 years of age is recommended for all those
in this age group who have not already received a primary course of hepatitis
B vaccine. Please refer to your State/Territory health authority for further
information (see Appendix 1, Contact details for Australian, State and Territory
Hepatitis B 157
(iii) Adults for whom hepatitis B vaccination is recommended
Note: the combined hepatitis A/hepatitis B vaccine should be considered for susceptible
individuals in the groups marked with an asterisk (*).
• Household contacts of acute and chronic hepatitis B carriers
There is a low, but definite, risk of transmission from a person with acute or
chronic hepatitis B. This can be reduced by avoiding contact with blood or other
body fluids and not sharing household items which can penetrate skin (such as
combs, nail brushes, toothbrushes and razors).
The risk of contacts acquiring hepatitis B infection varies according to the HBeAg
status of the carrier, and with cultural and socioeconomic factors. However, it
should be recognised that in many situations, family members may have been
exposed by the time the risk is recognised. Testing before planned vaccination
is recommended for such families, as well as for members of families who have
migrated from high prevalence countries.
• Sexual contacts
Susceptible (anti-HBc and anti-HBs negative) sexual partners of patients
with acute hepatitis B should be offered post-exposure HBIG and hepatitis B
vaccination; both should be initiated within 14 days of the last sexual contact.
Susceptible partners of asymptomatic carriers should also be offered vaccination.
Hepatitis B is relatively common in clients of sexual health services and
vaccination should be offered to susceptible individuals at the time of first
attendance.
*Sexually active men who have sex with men should be vaccinated, unless
they are already HBsAg positive or have serological evidence of immunity. The
combined hepatitis A/hepatitis B vaccine may be appropriate for men who have
sex with men, if they are not immune to either disease, as they are at increased
risk of both.
• Haemodialysis patients, HIV-positive individuals and other adults with
impaired immunity
Dialysis patients, HIV-positive individuals and other adults with impaired
immunity should be given a larger than usual dose of hepatitis B vaccine. Adults
should be given either (i) 1 mL of normal adult formulation in each arm on each
occasion (double dose), or (ii) a single dose of dialysis formulation vaccine on
each occasion, at 0, 1 and 6 months. HIV-positive children should receive 3 doses
using an adult formulation.
• *Injecting drug users
Injecting drug users who have not been infected with hepatitis B should be
vaccinated.

• Recipients of certain blood products
Screening of all blood donors for HBsAg has greatly decreased the incidence of
transfusion-related hepatitis B virus infection. However, patients with clotting
disorders who receive blood product concentrates have an elevated risk of
hepatitis B virus infection, and should therefore be vaccinated.
• *Individuals with chronic liver disease and/or hepatitis C
Hepatitis B vaccination is recommended for those in this category who are
seronegative for hepatitis B.26
• *Residents and staff of facilities for people with intellectual disabilities
Vaccination of carers, staff and susceptible residents is recommended in both
residential and non-residential care of people with intellectual disabilities.
• Individuals adopting children from overseas
These children should be tested for hepatitis B, and if they are HBsAg positive,
3.6 Hepatitis B
members of the adoptive family should be vaccinated.
• *Liver transplant recipients
If seronegative for hepatitis B, such individuals should be vaccinated
before transplantation as they may be at increased risk of infection from the
transplanted organ.
• *Inmates and staff of long-term correctional facilities
Inmates are at risk of hepatitis B because of the prevalence of homosexual
intercourse, injecting drug use and amateur tattooing in some correctional
facilities. Therefore, they should be screened upon incarceration, and vaccinated
if susceptible.
• Healthcare workers, ambulance personnel, dentists, embalmers, tattooists
and body-piercers
The risk to such workers differs considerably from setting to setting in different
parts of Australia, but it is recommended that all staff directly involved in patient
care,27 embalming, or in the handling of human blood or tissue, be vaccinated. In
addition, standard precautions against exposure to blood or body fluids should
be used as a matter of routine.
• Others at risk
• Police, members of the armed forces and emergency services staff should
be vaccinated if they are assigned to duties which may involve exposure.
• Funeral workers and other workers who have regular contact with
human tissue, blood or body fluids and/or used needles or syringes.
• People travelling to regions of intermediate or high endemicity, either
long-term or for frequent short terms, should be vaccinated.
Hepatitis B 159
• Staff of child day-care centres will normally be at minimal risk of
hepatitis B. If advice on risk is sought, the enquiry should be directed to
the local public health authority.
• Contact sports generally carry a low risk of hepatitis B infection.
Vaccination is nevertheless encouraged.
• As the risk in Australian schools is very low,28 vaccination of classroom
contacts is seldom indicated. Nevertheless, vaccination of all children and
adolescents should be encouraged.
• Sex industry workers.
(iv) Serological confirmation of post-vaccination immunity

Post-vaccination serological testing 4 to 8 weeks after completion of the primary
course is recommended only for those in the following categories:
• those at significant occupational risk (eg. healthcare workers whose work
involves frequent exposure to blood and body fluids),
• those at risk of severe or complicated disease (eg. people with impaired
immunity, and individuals with pre-existing liver disease not related to
hepatitis B),
• those in whom a poor response to hepatitis B vaccination is expected (eg.
haemodialysis patients),
• sexual partners and household contacts of recently notified hepatitis B
carriers.29
Anti-HBs and HBsAg levels should be measured in infants born to known
HBsAg/HBeAg positive carrier mothers 3 to 12 months after completing the
primary vaccine course. If anti-HBs levels are adequate and HBsAg is negative,
then children are considered to be protected.29
(v) Non-responders to primary vaccination

If adequate anti-HBs levels (≥10 mIU/mL) are not reached after the third dose,
the possibility of HBsAg carriage should be investigated. Those who are HBsAg
negative and do not respond should be offered further doses. These can be given
as either a fourth double dose or a further 3 doses at monthly intervals, with
further testing at least 4 weeks after the last dose.
There is limited evidence from several trials that HBsAg negative healthcare
workers, who are non-responders to a primary course of vaccination and
subsequent intramuscular booster schedule, as above, may respond to 5µg of
Engerix-B (0.25 mL of the adult formulation) administered intradermally at
fortnightly intervals (up to 4 doses) with anti-HBs levels measured before each
dose to assess for seroconversion.30-32 Persistent non-responders should be informed
that they are not protected and should minimise exposures, and about the need for
HBIG within 72 hours of parenteral exposure to HBV (see Table 3.6.3 Post-exposure
prophylaxis for non-immune individuals exposed to an HBsAg positive person).

Individuals who are at significant occupational risk who have a documented
history of a primary course of hepatitis B vaccine, but it is not known whether
they ever seroconverted, and they now have an antiHBs level <10 mIU/mL,
should be given a single booster dose of vaccine and have their anti-HBs level
checked 4 weeks later. If the anti-HBs level is <10 mIU/mL, regard the individual
as a non-responder, give 2 further doses of hepatitis B vaccine at monthly
intervals, and re-test for anti-HBs levels at least 4 weeks after the last dose.
(vi) Booster doses

Although vaccine-induced antibody levels decline with time and may become
undetectable, booster doses are not recommended in immunocompetent
individuals after a primary course, as there is good evidence that a completed
primary course of hepatitis B vaccination provides long-lasting protection. This
applies to children and adults, including healthcare workers and dentists.33-39
However, booster doses are recommended for individuals with impaired
3.6 Hepatitis B
immunity, in particular those with either HIV infection or renal failure. The time
for boosting in such individuals should be decided by regular monitoring of anti-
HBs levels at 6 to 12-monthly intervals.33
(vii) Interchangeability of vaccines

Although switching of brands is not recommended, in cases where the brand of
vaccine used for previous doses is not known, any age-appropriate formulation
may be used as there is no reason to believe that use of a different brand will
compromise immunogenicity or safety.
(viii) Post-exposure prophylaxis for hepatitis B

Following significant exposure (percutaneous, ocular, or mucous membrane) to
blood or potentially blood-contaminated secretions, the source individual should
be tested for HBsAg as soon as possible.
If the person exposed has not been previously vaccinated against hepatitis B, his/her
anti-HBs level and HBsAg should be determined immediately. If the person exposed
is anti-HBs negative, and the source is either HBsAg positive, or cannot be identified
and tested rapidly, administer a single dose of HBIG of 100 IU for children weighing
up to 30 kg (about 5 years of age) and 400 IU for all others, within 72 hours. Also
give hepatitis B vaccine (by IM injection into either the deltoid or anterolateral thigh,
depending on age) as soon as possible, but within 7 days of exposure. Two further
doses of vaccine should be given, 1 and 6 months after the first dose.
For previously vaccinated people exposed to either an HBsAg positive source
or a source whose hepatitis B status cannot be determined, post-exposure
prophylaxis is not necessary if there was a documented protective response (anti-
HBs level ≥10 mIU/mL) at any time after vaccination. If the response to previous
vaccination is unknown, the anti-HBs level should be determined as quickly as
possible. If the anti-HBs level is <10 IU/mL and HBsAg is negative, HBIG and
vaccine should be administered as above.
Hepatitis B 161
In most instances, it is advisable to offer a course of hepatitis B vaccine to a non-
immune healthcare worker sustaining a needle-stick injury or other potential
hepatitis B exposure, since the injury or exposure itself is evidence that they work
in an area with a significant risk of exposure.
Table 3.6.3: Post-exposure prophylaxis for non-immune individuals exposed to

an HBsAg positive person
Type of exposure Hepatitis B immunoglobulin Vaccine
Perinatal 100 IU by IM Single dose 0.5 mL by IM Immediately
(exposure of injection within 12 injection after birth
babies during hours of birth, (preferably
and after birth) preferably within 24 hours,
immediately no later than
after birth 7 days*) then at
2, 4, and either
6 or 12 months
of age
Percutaneous/ 400 IU by IM Single dose 0.5 mL or 1 mL Within 7 days*
ocular injection within 72 hours by IM injection and at 1 and
or mucous 100 IU if body depending 6 months after
membrane weight <30 kg on age first dose
Sexual 400 IU by IM Single dose 0.5 mL or 1mL Within 14 days*

injection within 14 days by IM injection and at 1 and
of sexual contact depending 6 months after
on age first dose
* The first dose can be given at the same time as HBIG, but should be administered at a
separate site.
Contraindications
The only absolute contraindications to hepatitis B vaccine are:
• anaphylaxis following a previous dose of hepatitis B vaccine, or
Adverse events
• Adverse events after hepatitis B vaccination are transient and minor, and
include soreness at the injection site (5%, common), fever (usually low
grade, 2–3%, common), nausea, dizziness, malaise, myalgia and arthralgia.
Fever can be expected in neonates immunised with hepatitis B vaccine
(0.6–3.7%, common).
• Anaphylaxis has been reported very rarely in adults. Although various
adverse events such as demyelinating diseases, Guillain-Barré syndrome
and arthritis have been reported, there is no evidence of a causal relationship
with hepatitis B vaccination.40,41 There have been a few reports of generalised

febrile reactions attributed to yeast allergy, and exceptional instances of
polyarteritis nodosa have been reported.
• The World Health Organization Global Advisory Committee on Vaccine
Safety states that “multiple studies and review panels have concluded
that there is no link between MS [multiple sclerosis] and hepatitis B
vaccination”.42
• The vaccine produces neither therapeutic effects nor adverse events in
hepatitis B virus carriers. It is safe in those already immune to hepatitis B.
Use in pregnancy
3.6 Hepatitis B
necessary at 18 month of age. However, DTPa-containing vaccine may be used
Hepatitis B immunoglobulin (HBIG)

Hepatitis B immunoglobulin (HBIG) is prepared from plasma donated through
routine blood bank collection. Samples are selected on the basis that they contain
high levels of antibody to HBsAg. As stocks of HBIG are very limited, use should
be strictly reserved for those who are at high risk, such as babies born to hepatitis
B carrier mothers and healthcare workers who are exposed to the blood of
HbsAg positive individuals through occupational exposure. Requests should be
directed to the Australian Red Cross Blood Service in your State/Territory (see
Chapter 3.8, Immunoglobulin preparations ‘Availability of immunoglobulins’).
HBIG is given by IM injection.
• Hepatitis B Immunoglobulin-VF – CSL Bioplasma (160 mg/mL

immunoglobulin (IgG) prepared from human plasma containing high levels
of antibody to surface antigen of the hepatitis B virus). 100 IU and 400 IU
ampoules, with the actual volume stated on the label on the vial.
References
Hepatitis B 163
3.7 Human papillomavirus
Virology and HPV classification

Human papillomaviruses (HPVs) are small, non-enveloped viruses that have
circular double-stranded DNA. HPVs infect and replicate within cutaneous and
mucosal epithelial tissues, most commonly involving the skin or anogenital tract.
HPVs are designated as specific types according to sequence variation in the
major genes.
There are 40 distinct HPV genotypes that affect the genital tract; of these, 15
genotypes (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, 82) are designated
as ‘high-risk’ as they are causally associated with the development of cervical
cancer. HPV genotypes 16 and 18 are the causative agents in 70 to 80% of
all cervical cancers. HPV genotypes 6 and 11 are among the HPV genotypes
designated as ‘low-risk’ (for cancer), and are associated with 90% of genital warts
and 100% of recurrent respiratory papillomatosis (RRP) cases.1,2
High-risk genital HPV genotypes are associated with a spectrum of other
anogenital diseases, including vulval, vaginal, penile and anal cancers, and their
precursors. In addition, genital HPV genotypes are associated with extragenital
diseases, including some squamous cell carcinomas of the head and neck (high-
risk HPV types) and recurrent respiratory papillomatosis (HPV types 6 and 11).
Persistent HPV infection is a necessary precursor of cervical cancer, but is not
sufficient in itself to cause the disease.3 For pre-cancerous lesions to form and
progress to cancer, the crucial event appears to be HPV DNA integration into the
host cell genome, which interferes with the expression and regulation of proteins
responsible for normal cell growth and repair.4 Malignancy due to build-up of
sufficient mutations for cellular transformation usually requires 10 to 20 years,
but has been reported to occur in under 2 years.5
Clinical features
HPV infection is often subclinical but, dependent upon the infecting HPV
genotype, may result in lesions that include cutaneous warts, genital warts,
cervical and other anogenital tract dysplasias and cancers, and respiratory
papillomatosis. Most genital HPV infections are cleared (no longer detectable)
within 12 to 24 months (the median duration for high-risk genotypes is 7
to 10 months).6-9 In a minority of infections, estimated at 3 to 10%, the virus
persists.10

Epidemiology
HPV infection
Transmission of HPV occurs through contact with infected skin or mucosal
surfaces, primarily via sexual contact for the genital HPV genotypes.
Transmission may rarely occur by other mechanisms, such as laryngeal infection
of infants during birth.11 There is a high probability of transmission following
sexual exposure to a person with a productive HPV infection, estimated to be
50 to 80%, after unprotected sexual intercourse.12-14 However, sexually active
adolescents and young adults may remain naïve to all 4 vaccine HPV genotypes
or be infected with a non-vaccine HPV genotype.
HPV infection rates vary greatly between geographic regions, but it is estimated
that up to 79% of women worldwide will be infected with at least one genital
type of HPV at some point in their lives.15,16 HPV infection rates are highest
among young women, usually peaking soon after the age when most young
women become sexually active.17 Australian data show that, among women
currently aged 16–19 years, the median age of first intercourse is 16 years.18
Although comprehensive risk-prediction models for HPV exposure are not
available, an increasing number of lifetime sex partners is consistently found
to be associated with HPV acquisition.19-24 A US population-based study of
women aged 18–25 years found genital HPV infection in 14.3% of women with
one lifetime sex partner, 22.3% with 2 lifetime sex partners, and 31.5% with
more than 3 lifetime partners.25 Australian women aged 16–19 years report a

median number of 2 lifetime sexual partners, women aged 20–29 years a median
of 4.3 lifetime sexual partners, and those aged 30–39 years a median of 4.7
lifetime sexual partners.26 Although its sensitivity is somewhat limited, HPV
seroprevalence measured using serum anti-HPV antibody levels can be used
to estimate cumulative lifetime exposure to specific types of HPV infection.27 In
a study of women in Finland, Dillner et al (1996) described a linear increase in
the risk of HPV16 seropositivity of 4% for every additional sex partner, ranging
from 4% for 1 lifetime partner to 35% among those with 6 or more partners.24
Similarly, HPV18 seroprevalence was observed to increase linearly at the rate of
3% per partner from 4% for 1 lifetime partner up to 24% for 6 or more partners.
In the US, population data indicate that 25% of women aged 20–29 years are
seropositive for HPV16.28 An increasing number of sexual contacts on the part of
their male partner is also associated with HPV acquisition in women.29
Human papillomavirus 165

Cervical abnormalities
Cervical infection with HPV causes a range of pathological responses depending
on the genotype of HPV. These range from no reaction, carriage of HPV without
cytological changes, to a variety of cellular changes in the cervix. Histologically,
the cervical abnormalities have been referred to as cervical intraepithelial
neoplasia (CIN), with 3 grades of severity: CIN1 (mild dysplasia), CIN2
(moderate dysplasia) and CIN3 (severe dysplasia/carcinoma in situ). CIN3
and AIS (adenocarcinoma in situ) are immediate precursors of cervical cancer.
CIN2 represents a mix of low-grade and high-grade lesions (and hence it is
treated as a high-grade lesion). Cytologically, under the Australian Modified
Bethesda System, the term Low-grade Squamous Intraepithelial Lesion (LSIL)
encompasses changes thought to be due to HPV and mild dysplasia, and the
term High-grade Squamous Intraepithelial Lesion (HSIL) encompasses the
former categories of moderate dysplasia, severe dysplasia and carcinoma in
situ. Guidelines for the interpretation and treatment of screen-detected cervical
abnormalities are published by the NHMRC.12
Every year in Australia, approximately 90 000 women have an LSIL detected
and 15 000 women have an HSIL detected through Pap screening.12 The
incidence of both lesions peaks in women aged 20–24 years. In addition, there
are approximately 20 000 hospital admissions per year for cervical dysplasia
and carcinoma in situ. This is an underestimate of the burden of disease, as
the investigation and management of cervical lesions are mostly carried out as
outpatient procedures, either in the private or public sector. For procedures in
the private sector, Medicare has processed, over the past 10 years, claims for
an average of approximately 104 000 examinations of the lower genital tract by
colposcopy and 14 600 combined colposcopy procedures per year. As well as
physical side effects and complications from treatment for cervical abnormalities,
there is consistent evidence that receipt of an abnormal Pap smear result, and
the subsequent investigation and management, is associated with a considerable
psychosocial burden.30-35
It was originally thought that there was an inevitable progression from low-
grade abnormalities to high-grade abnormalities to cervical cancer. It is now
recognised that LSIL cytology is a manifestation of acute HPV infection, and
that most LSIL regresses over time.12 The absolute risk of cancer associated with
a high-grade abnormality is difficult to determine from available observational
data, but is estimated at less than 1% per year.36 Figure 3.7.1 summarises the
dynamic relationship between HPV infection and cervical health.

Figure 3.7.1: The dynamic relationship between HPV infection and cervical
health

(Figure courtesy of the Australian Government Department of Health and Ageing.)
Cervical cancer
Cancer of the uterine cervix is the second most common cause of cancer among
women worldwide.37 However, Australia has one of the lowest mortality rates
from cervical cancer in the world.38 In 2002, the age standardised incidence
rate in Australia was 6.8 per 100 000 and, in 2004, the mortality rate was 1.9 per
100 000, with an estimated 750 cases, 1800 hospitalisations and 250 deaths each
year from cervical cancer.39 This low incidence can be attributed to the success of
the National Cervical Screening Program, with cervical cancer in Australia now
occurring predominantly in unscreened or under-screened women. The largest
decline in cervical cancers has been observed for those of squamous origin,
with the incidence of adenocarcinomas being essentially unchanged. This has
been attributed to sampling difficulties in obtaining cells from the area where
adenocarcinoma arises, problems in pathological interpretation, and variations in
clinical investigation and treatment.12
Other anogenital cancers

High-risk HPV types (predominantly types 16 and 18) are also implicated in 50
to 90% of other anogenital cancers in both women and men, including cancers of
the vulva, vagina, anus, and penis, although these types have almost no role in

causing non-malignant lesions (see below). In Australia in 2001, there were 252
vulvar cancers (2.6 per 100 000), 62 vaginal cancers (0.6 per 100 000) and 225 anal
cancers (1.2 per 100 000) diagnosed.40
Non-malignant lesions
Genital warts are a common manifestation of HPV type 6 and 11 infection.
Genital warts can cause significant psychological morbidity. In Australia, 4.0%
of men and 4.4% of women aged 16–59 years report ever being diagnosed
with genital warts.41 These prevalence estimates translate into approximately
36 000 cases in Australia. The cumulative lifetime risk of genital warts has
been estimated at 10%.42,43 Peak attack rates occur in young women aged
15–24 years.44 An analysis of data from the BEACH cross-sectional survey
of national GP activity found that, between April 2000 and March 2003,
consultations for genital warts in women aged 12–49 years occurred at a rate of
0.17 per 100 encounters.45 Severe morbidity from genital warts, as measured by
hospitalisation, is uncommon and peaks in women 20–24 years of age (26 per
100 000) (AIHW National Hospital Morbidity Database 2006). Morbidity not
causing hospitalisation includes recurrence and a range of local complications.
Worldwide, the best epidemiological data on genital wart incidence comes from
the United Kingdom.2
Exposure to HPV types 6 and 11 at birth can also cause recurrent respiratory
papillomatosis in children. This relatively rare disease, with an estimated
incidence of 4 per 100 000 children,46,47 is characterised by repeated growth of
warts in the respiratory tract requiring repeated surgery. Adults can also develop
recurrent respiratory papillomatosis.
Type-specific HPV epidemiology

Worldwide, approximately 50% of cervical cancers contain HPV16 DNA and 16%
contain HPV18 DNA.48,49 Among cervical adenocarcinomas, 70% contain HPV
16 or 18 DNA, with HPV18 being relatively more common (37.7%) than HPV16
(31.3%).48 HPV16 has been detected in 48% of HSILs, 19% of LSILs and 2% of
cytologically normal women. HPV18 has been detected in 7% of HSILs, 6% of
LSILs and 0.7% of cytologically normal women.50-52 The low-risk HPV types 6
and 11 have been detected in 6.2% and 3.2% of LSILs respectively and each type
in 0.1% of cytologically normal women.51,52
Australian studies indicate that the 5 most frequent HPV genotypes identified in
553 cervical cancers were HPV16 (60%), HPV18 (20%), HPV45 (5%), and HPV39
and HPV73 (2.3% each).53-57 Best available Australian data indicate that HPV16
and HPV18 are, respectively, responsible for approximately 60%/20% of cervical
cancers and 37%/8% of high-grade cervical abnormalities.53,54

Vaccines
HPV vaccines have been developed using recombinant DNA technology based
on virus-like particles (VLPs), which are not infectious and do not have any
cancer-causing potential.
There are 2 HPV vaccines registered for use in Australia. The bivalent vaccine,
2vHPV vaccine (CERVARIX), contains VLPs of HPV genotypes 16 and 18, and
is administered as a 3-dose schedule at 0, 1 and 6 months. The quadrivalent
vaccine, 4vHPV vaccine (GARDASIL), is administered at 0, 2 and 6 months and
contains VLPs of HPV genotypes 16, 18, 6 and 11.
• CERVARIX – GlaxoSmithKline (human papillomavirus vaccine –

recombinant protein particulate (VLP) vaccine containing the major capsid
(L1) protein of HPV types 16 and 18). Each 0.5 mL monodose pre-filled
syringe or vial contains 20 µg each of HPV types 16 and 18 adjuvanted
with AS04 (AS04 is comprised of 500 µg aluminium hydroxide and 50 µg of
3-O-desacyl-4’-monophosphoryl lipid A [MPL]); 4.4 mg sodium chloride;
624 µg sodium dihydrogen phosphate dihydrate.
• GARDASIL – CSL Biotherapies/Merck & Co Inc (human papillomavirus

vaccine – recombinant protein particulate (VLP) vaccine containing the
major capsid (L1) protein of HPV types 6, 11, 16 and 18). Each 0.5 mL
monodose pre-filled syringe or vial contains 20, 40, 40 and 20 µg of HPV
types 6, 11, 16 and 18, respectively, adsorbed onto 225 µg aluminium

hydroxyphosphate sulphate; 9.65 mg of sodium chloride; 780 µg of
L-histidine; 50 µg of polysorbate 80; 35 µg of sodium borate. May also
contain yeast proteins.
It is important to note that HPV vaccines are prophylactic vaccines (ie. designed
to prevent initial HPV infection). In women who are already infected with HPV
types covered by the vaccines before vaccination (ie. HPV DNA positive), the
vaccines do not treat infection or prevent disease caused by that type.58
In women HPV DNA negative and HPV seronegative for relevant types, both
vaccines are highly effective at preventing persistent type-specific infection and
related cervical disease (~90–100%).59-62 The 4vHPV vaccine also has established
efficacy against external genital lesions (warts, and vulval and vaginal
dysplasias) in women. Vaccine efficacy against external genital lesions related to
HPV 6, 11, 16 or 18 in women who were naïve to vaccine types at the beginning
of the trials and who received 3 doses was 99% (95% CI: 95–100%).
Compared to HPV DNA negative and HPV seronegative women, vaccine efficacy
(VE) in women who received vaccine regardless of HPV status at baseline
and may, therefore, have had previous infection, was much lower. Against
HPV16/18-related CIN2/3 or worse, VE was 44% (95% CI: 31–55%) at a mean
of 3 years follow-up63 and against high-grade CIN caused by any HPV type it

was 18% (95% CI: 7–29%).63 However, vaccine efficacy is expected to be higher
over a longer duration of follow-up, as the proportion of disease due to incident
infection (where vaccination has an effect) increases compared to the proportion
of disease due to infection/disease at baseline (which is not affected by the
vaccine). These data reflect the reduced impact of vaccinating women in whom a
proportion will already have been infected with HPV, eg. older women who are/
have been sexually active. Vaccine efficacy estimates in populations including
women already infected with HPV at baseline have not yet been published for
2vHPV vaccine, but a similarly reduced impact, compared with an HPV naïve
population, can be anticipated.
It is possible that HPV vaccines may provide some protective efficacy against
disease due to types closely related to types 16 and 18, in particular HPV31 and
HPV45, but published data supporting this hypothesis are currently limited to
infection endpoints only and are imprecise.60,64-66
When given as a 3-dose series, HPV vaccines elicit neutralising antibody titres
many times higher than those observed following natural infection.67-69 Antibody
responses peak at month 7 (1 month after dose 3) at titres between 7 and 150
times greater than following natural infection, depending upon the HPV type
and vaccine.59,62,70,71 Following an initial decline, they appear to plateau at 18
to 24 months, remaining stable for at least 5 years at levels above or at least
equivalent to those seen following natural infection.58,60,62,70 It should be noted
that there is no standard serological assay for detecting HPV antibodies and
no protective titre has been established. Therefore, absolute titres achieved (as
reported in the randomised trials) are not directly comparable between 2vHPV
and 4vHPV vaccines. Similarly, differences in methodologies and the populations
examined make direct comparisons of published 4vHPV and 2vHPV vaccine
efficacy estimates difficult.
Overall, seroconversion occurs in 99 to 100% of those vaccinated.58,60,61 The duration
of immunity after vaccination is not yet known (but is of at least 5 years’ duration);
hence, it is possible that booster doses may be required in the future.58,60,62
There are currently no clinical efficacy data available in males or in pre-adolescent
females (as collection of genital specimens is not appropriate). Antibody response
to both 4vHPV and 2vHPV vaccination has been evaluated in pre-adolescent
and adolescent females (9–15 years of age and 10–14 years of age, respectively).
In males, antibody response has only been studied for 4vHPV, and only in
the age group 9–15 years, through immunological bridging studies.72,73 Young
males and females administered 4vHPV vaccine and females aged 10–14 years
administered 2vHPV vaccine produce antibody responses that are at least 2-fold
higher compared to women in whom clinical efficacy has been demonstrated.
The peak antibody levels achieved following vaccination decrease with age.
Immunobridging studies for older women (aged >26 – ≤45 years) administered
the 2vHPV demonstrate antibody titres in a comparable range to women in the
15–25 year age group who are in the plateau phase of long-term follow-up.

These data were current at the time of publishing The Australian Immunisation
Handbook.

+2°C to +8°C. Do not freeze. Protect from light.

The dose of 2vHPV vaccine is 0.5 mL administered by IM injection. The
recommended schedule is 0, 1 and 6 months. The second dose of 2vHPV can be
administered between 1 and 2.5 months after the first dose.
The dose of 4vHPV vaccine is 0.5 mL administered by IM injection. The
recommended schedule is 0, 2 and 6 months. In clinical studies, efficacy for
4vHPV vaccine has been demonstrated in individuals who have received all
3 doses within a 1 year period. Where flexibility in the recommended dosing
schedule is unavoidable, the second dose should be administered at least
1 month after the first dose and the third dose should be administered at least
3 months after the second. There is no need to repeat earlier doses. Give missing
dose(s) as soon as is practicable, making efforts to complete doses within
12 months.
4vHPV vaccine has been administered concomitantly with hepatitis B vaccine in
clinical trials, with no reduction in immunogenicity of either vaccine observed.

There are no clinical data regarding concomitant administration of either
2vHPV or 4vHPV vaccine with adolescent/adult formulation dTpa or varicella
vaccine, but there is no reason to expect any adverse outcomes if they are given
simultaneously, using different injection sites.
Recommendations
Both vaccines are recommended to provide protection against oncogenic HPV
type 16 and/or 18 cervical disease. If protection against genital warts is desired,
the 4vHPV vaccine provides protection against HPV types 6 and 11, which are
associated with more than 90% of these lesions.67 (See also ‘Vaccines’ above.)
(i) Females aged 10–13 years (Safety-Grade B)(Efficacy-

no data)(Immunogenicity-Grade B)67
HPV vaccine is recommended for females 10–13 years of age. Currently only the
4vHPV vaccine is on the NIP schedule for females aged 12–13 years. Please refer
to your State/Territory health authority for further information (see Appendix
1, Contact details for Australian, State and Territory Government health authorities and

(ii) Females aged 14–18 years (Safety-Grade B)(Efficacy-
Grade B)(Immunogenicity-Grade B)67
HPV vaccine is also recommended for females 14–18 years of age. While some
females in this age group will already have commenced sexual activity, the
majority will not yet be infected with a HPV vaccine type.
(iii) Females aged 19–26 years (Safety-Grade A)(Efficacy-

Grade A)(Immunogenicity-Grade A)67
HPV vaccine is also recommended for females 19–26 years of age.
In females in this age group who have never had sexual intercourse the vaccine
efficacy will be comparable to younger women, and HPV vaccination is
recommended. In sexually active females 19–26 years of age, the overall benefit
from HPV vaccination is likely to be less; however, past or current infection with
all HPV types covered by the vaccine is unlikely.
NB. The absolute benefit of HPV vaccine to an individual sexually active woman
cannot be determined clinically, as appropriate tests to detect both previous and
current HPV infection with vaccine types are not available.
In all sexually active women, the most important preventive intervention against
cervical disease remains regular Pap screening. Vaccination is not an alternative
to Pap screening but is complementary. The National Cervical Screening Program
recommends routine screening with Pap smears every 2 years for all women
between the ages of 18 (or 2 years after first sexual intercourse, if later) and
69 years.
(iv) Females aged ≥27 years (Safety 2vHPV vaccine-Grade B; 4vHPV vaccine-no

data)(Efficacy-no data)(Immunogenicity 2vHPV-Grade B; 4vHPV-no data)67
2vHPV vaccine is registered for use in females 27–≤45 years of age on the basis
of safety and bridging immunogenicity data. The extent of benefit that can
be expected to be derived from the use of HPV vaccine in this age group will
depend upon past sexual history and the likelihood of new sexual partners in the
future (ie. an assessment of likely past and future HPV exposure) and the sexual
behaviour of her male partner(s). HPV-related cervical infection and Pap test
abnormalities peak in women aged <30 years in Australia.
4vHPV vaccine is not registered for use in females over the age of 27 years as
there are no safety or efficacy data to support its use in this age group.
In all sexually active women, the most important preventive intervention against
cervical disease remains regular Pap screening. Vaccination is not an alternative
to Pap screening but is complementary. The National Cervical Screening Program
recommends routine screening with Pap smears every 2 years for all women
between the ages of 18 (or 2 years after first sexual intercourse, if later) and
69 years.

For women who have recently been diagnosed with cervical dysplasia, or have
been treated for this in the past, HPV vaccine will have no impact on current
disease, but may prevent future dysplasia due to a different HPV vaccine type.
(v) Males [For males aged 9–15 years (Safety 4 vHPV vaccine-

Grade B; 2vHPV vaccine-no data)(Efficacy-no data)(Immunogenicity
4vHPV vaccine-Grade B; 2vHPV vaccine-no data)]67
4vHPV vaccine is licensed for use in males aged 9–15 years. 4vHPV vaccine
produces high antibody titres in pre-adolescent and adolescent males but it is
not known whether vaccination of males can either prevent transmission of HPV
or provide protection against genital HPV infection, genital warts, anogenital
dysplasia or anogenital cancers. 2vHPV vaccine is not registered for use in males.
There is no recommendation for vaccination of males at this time due to the lack
of clinical efficacy data.
Contraindications
The only absolute contraindications to HPV vaccine are:
• anaphylaxis to any vaccine component. The 4vHPV vaccine may contain
minute amounts of yeast proteins.
Precautions

People with impaired immunity
There are limited clinical trial data available for this group. However, as HPV
vaccines are not live vaccines, they can be administered to women who are
immunosuppressed as a result of disease or medications. The immune response
and vaccine efficacy might be less than in individuals who are immunocompetent
(see Chapter 2.3, Subsection 2.3.3, Vaccination of individuals with impaired immunity
due to disease or treatment).
Adverse events
Both the 2vHPV and 4vHPV vaccines are generally safe and well tolerated. A
variety of comparators were used in clinical trials of 2vHPV and 4vHPV, but
data comparing vaccine adverse events with an aluminium-containing placebo
are available for both vaccines and are quoted below for common local adverse
reactions. More detailed information about adverse events occurring in the
vaccine trials is available from the product information for 2vHPV vaccine and
from the US FDA for 4vHPV.75
In clinical trials of the 2vHPV vaccine, the most commonly reported adverse
events were injection site pain 78%, swelling ~26% and erythema ~30%
compared to ~53%, ~8% and 11% in the aluminium hydroxide placebo group.
Incidence of injection site pain decreased across the 3 doses, whereas there was

a slight increase in the reported proportion with swelling and erythema after
successive doses.
In clinical trials of the 4vHPV vaccine the most commonly reported adverse
events were injection site pain ~81%, swelling ~24% and erythema ~24%,
compared to ~75%, ~16% and ~18% in the aluminium-containing placebo group.
The incidence of injection site pain was approximately equal across the 3 doses,
whereas there was a modest increase in the reported proportion with swelling
and erythema after successive doses.
HPV vaccines are well tolerated by those who have already been exposed to the
HPV types included in the vaccine.
Use in pregnancy
HPV vaccine should not be given during pregnancy (see Chapter 2.3, Subsection
2.3.2, Vaccination of women planning pregnancy, pregnant or breastfeeding women, and
preterm infants).
It should be noted that there is no evidence from animal studies, or among HPV
vaccine trial participants who inadvertently became pregnant, of teratogenicity
or of adverse fetal outcomes and, therefore, HPV vaccination during pregnancy
is not an indication for termination.
Where vaccine has inadvertently been administered during pregnancy, further
doses should be deferred until after delivery.
Use during lactation

HPV vaccine may be given while lactating (see Chapter 2.3, Subsection 2.3.2,
Vaccination of women planning pregnancy, pregnant or breastfeeding women, and
preterm infants).
In trials, 995 nursing mothers received 4vHPV vaccine or placebo, and no relation
between vaccination and adverse events was observed. The effect on breastfed
infants of the administration of 2vHPV vaccine to their mothers has not been
evaluated in clinical studies. It is not known whether HPV vaccine antigens or
HPV antibodies are excreted in human milk.

None.
References

3.8 Immunoglobulin preparations
Introduction
Passive immunity can be provided by administration of human
immunoglobulin.1-3 The protection afforded is immediate, but is transient
and lasts for only a few weeks, as the half-life of IgG, the major constituent, is
between 3 and 4 weeks.
There are 2 types of immunoglobulin, normal and specific. It is important

to recognise that separate immunoglobulin preparations are provided for
intramuscular (IM) use and for intravenous (IV) use. These have different
properties, and the preparations should be given only by the recommended
route. Administration of IM immunoglobulin by the IV route will lead to
severe reactions.
• Normal human immunoglobulin (NHIG)

This is derived from the pooled plasma of blood donors. It contains antibody to
microbial agents which are prevalent in the general population.
• Specific immunoglobulins
Specific immunoglobulin preparations are obtained from pooled blood
donations from patients convalescing from the relevant infection, donors recently
vaccinated with the relevant vaccine, or those who, on screening, have been
found to have sufficiently high antibody concentrations. These blood-derived
specific immunoglobulins therefore contain concentrations of antibody to an
individual organism or toxin at a higher titre than would be present in normal
immunoglobulin.
Donors of blood used for the production of NHIG and specific immunoglobulin
products are screened and products treated to minimise the risk of the
immunoglobulin preparations containing HIV, hepatitis A, hepatitis B or
hepatitis C viruses, or parvovirus. Two dedicated pathogen inactivation steps
are incorporated into the manufacturing process. A pasteurisation step is usually
3.8 Immunoglobulin
used during manufacture. The risk of prion transmission remains theoretical.

preparations
Potential interaction with vaccines

Live attenuated virus vaccines
• Immunoglobulin preparations can interfere with the response to live
attenuated virus vaccines by preventing vaccine strain viral replication after
vaccine administration. Therefore, administration of live attenuated virus
vaccines, such as measles and varicella vaccines, should be deferred for at
Immunoglobulin preparations 175

least 3 months after the IM administration of NHIG, and for at least 9 months
after the administration of NHIG (intravenous).4 For the same reason,
administration of immunoglobulin products should be deferred if possible
until at least 2 weeks after a vaccine has been given, unless it is essential that
immunoglobulin be given. However, Rh (D) immunoglobulin (anti-D) does
not interfere with the antibody response to MMR vaccines and the two may
be given at the same time in different sites with separate syringes or at any
time in relation to each other (see Chapter 2.3, Groups with special vaccination
requirements, Table 2.3.5 Recommended intervals between either immunoglobulins
or blood products and MMR, MMRV or varicella vaccination).
• Inactivated vaccines such as tetanus, hepatitis B or rabies may be
administered concurrently with immunoglobulin preparations, or at any time
after, using separate syringes and separate injection sites to induce passive/
active immunity. This usually would occur when there has been actual or
possible acute exposure.
Availability of immunoglobulins
CSL Bioplasma supplies NHIG for IM use. Rabies immunoglobulin can be
obtained only upon application from State/Territory health authorities.
Respiratory syncytial virus (RSV) monoclonal antibody (Synagis; Abbott
Australia) is available commercially.
The specific immunoglobulins and the CSL Bioplasma NHIG for IV use, which
are derived from Australian donated plasma, can be obtained only from the
Australian Red Cross Blood Service (ARCBS) with permission from a ARCBS
medical officer. The Red Cross Blood Service can be contacted by telephone (ACT
02 6206 6006; NSW 02 9229 4444; NT 08 8927 7855; QLD 07 3835 1333; SA 08 8422
1200; TAS 03 6230 6230; VIC 03 9694 0111; WA 08 9325 3333). The Australian Red
Cross Blood Service supplies these products free of charge.

All immunoglobulins must be protected from light and stored at +2°C to +8°C.
Do not freeze.
Normal human immunoglobulin (NHIG) – intramuscular use

NHIG is prepared by plasma fractionation of blood collected from volunteer
donors by the Australian Red Cross Blood Service. It is a sterile solution of
immunoglobulin, mainly IgG, and contains those antibodies commonly present
in adult human blood. In Australia, NHIG is supplied as a 16% solution, in the
United States as a 16.5% solution, and in the United Kingdom as a 10% solution.

• Normal Immunoglobulin-VF (human) (NHIG) – CSL Bioplasma. A
sterile preservative-free solution of immunoglobulin G (IgG) 160 mg/mL
prepared from Australian blood donations and made available through the
Australian Red Cross Blood Service. It is supplied in 2 mL and 5 mL vials
for IM injection.
Administration
NHIG should be given by deep IM injection using a large (19 or 20) gauge
needle. The NHIG should be introduced slowly into the muscle, to reduce pain.
This product should not be administered intravenously because of possible
severe adverse events, and hence an attempt to draw back on the syringe after
IM insertion of the needle should be made in order to ensure that the needle is
not in a small vessel. A special product for IV use (NHIG (intravenous)) has been
developed for patients requiring large doses of immunoglobulin.
Recommendations
Immunoglobulin preparations may be given to susceptible individuals as either
pre-exposure or post-exposure prophylaxis against specific infections. Normal
pooled immunoglobulin contains sufficiently high antibody concentrations to
be effective against hepatitis A and measles. The duration of effect of NHIG is
dose-related. It is estimated that protection is maintained for 3 to 4 weeks with
standard recommended doses of NHIG.
(i) Prevention of hepatitis A (see also Chapter 3.5, Hepatitis A)

NHIG contains sufficiently high levels of antibody against hepatitis A to be able
to prevent or ameliorate infection in susceptible individuals,5 if administered
within 2 weeks of exposure.6
Because the hepatitis A vaccine is readily available, there is no place for the
routine use of NHIG to prevent hepatitis A in travellers. It should be given
(at the same time as a dose of hepatitis A vaccine) only to those, such as non-
immune aid-workers to be deployed within 2 weeks, who will be living in very
inadequate circumstances.7,8
(ii) Prevention of hepatitis B

3.8 Immunoglobulin
See Chapter 3.6, Hepatitis B, under ‘Management of infants born to hepatitis B

carrier mothers’ and ‘Post-exposure prophylaxis for hepatitis B’.
preparations
(iii) Prevention of measles (see also Chapter 3.11, Measles)

NHIG contains a sufficiently high concentration of antibody against measles
to be able to prevent or ameliorate infection in susceptible individuals. NHIG
should be given as soon as possible and within 7 days of exposure. Passive
protection against measles particularly may be required if the exposed individual
has an underlying immunological disorder (HIV/AIDS, immunosuppressive

therapy), or to control an outbreak of measles among non-immunised
individuals, eg. in a childcare centre. The use of NHIG should be considered in
HIV-positive individuals exposed to a patient with measles.
(iv) Prevention of varicella (see also Chapter 3.24, Varicella)

Zoster immunoglobulin (ZIG) is able to prevent or ameliorate varicella in infants
<1 month of age, in children who are being treated with immunosuppressive
therapy, and in pregnant women.9,10 ZIG should be given as soon as possible, and
preferably within 96 hours, after exposure. ZIG is recommended for non-immune
HIV-positive individuals up to 7 days after exposure to clinical cases of either
varicella or zoster.
If ZIG is unavailable, large doses of NHIG can be given intramuscularly. This
does not necessarily prevent varicella, but it lessens the severity of the disease.
The dose of NHIG is 0.4–1.0 mL per kg body weight given by the IM route.
(v) Immune deficiency

Patients with abnormal antibody production (primary
hypogammaglobulinaemia, multiple myeloma, chronic lymphoblastic
leukaemia) are usually treated with the IV preparation of normal human
immunoglobulin (NHIG (intravenous)).2
However, in some cases, NHIG is given by IM injection in a dose of 400–600 mg/
kg (0.4–0.6 g/kg) every 2 to 4 weeks. The aim of therapy is to maintain serum IgG
levels above 6 g/L. Some patients may receive the IM (160 mg/mL) preparation
subcutaneously.
NB. Skin tests with NHIG should not be undertaken. The intradermal injection of
concentrated immunoglobulin causes a localised area of inflammation which can
be misinterpreted as a positive allergic reaction. True allergic responses to NHIG
given by IM injection are extremely rare.
Contraindications
Hypersensitivity reactions occur rarely but may be more common in patients
receiving repeated injections. It is recommended that NHIG should not be
given to individuals with absolute IgA deficiency, as the small amounts of IgA
in NHIG could theoretically lead to the development of anti-IgA antibodies in
these individuals. NHIG should not be administered to individuals who have
severe thrombocytopenia or any coagulation disorder that would contraindicate
intramuscular injections.
Adverse events and precautions

Local tenderness, erythema and muscle stiffness at the site of injection sometimes
occurs and may persist for several hours after injection. Systemic adverse events
such as mild pyrexia, malaise, drowsiness, urticaria and angioedema may occur
occasionally. Skin lesions, headache, dizziness, nausea, general hypersensitivity
reactions and convulsions may occur rarely.

Anaphylaxis following an injection of NHIG is very rare, but has been reported.
Anaphylaxis is more likely to occur if NHIG for IM use is inadvertently given
intravenously.
Normal human immunoglobulin (NHIG) – intravenous use

Normal human immunoglobulin (intravenous) is usually abbreviated as NHIG
(intravenous).
• Intragam P – CSL Bioplasma. A sterile preservative-free solution of

immunoglobulin G (IgG) 60 mg/mL prepared from Australian blood
donations and made available through the Australian Red Cross Blood
Service. Intragam P contains only trace amounts of IgA, and the final
solution contains 100 mg/mL maltose. It is supplied as 3 g in 50 mL and 12
g in 200 mL bottles (for intravenous use).
• Sandoglobulin NF liquid – CSL Bioplasma (sterile preservative-free

solution of immunoglobulin G (IgG), 120 mg/mL). It is supplied as 6 g in
50 mL and 12 g in 100 mL bottles (for intravenous use). A sterile lyophilised
preparation for reconstitution, containing human gammaglobulin. The
product is reconstituted with sodium chloride 0.9% solution to a sterile 3%
or 6% solution. Available in 6 g vials (for intravenous use).
• Octagam – Octapharma. A sterile preservative-free solution of

immunoglobulin G (IgG) 50 mg/mL prepared from multiple blood donors.
It is supplied as 1 g in 20 mL vials, and as bottles of 2.5 g in 50 mL, 5 g in
100 mL and 10 g in 200 mL (for intravenous use).
The available NHIG (intravenous) preparations in Australia have different

recommendations for dosage and administration and the product information
must be consulted before the use of each individual product. The text below
provides an overview of dosage and administration for NHIG (intravenous).

The infusion should be commenced slowly and the rate increased gradually.
Patients should be closely observed for the duration of the infusion. The patient’s
pulse, blood pressure and respiration rate should be recorded at 15-minute
3.8 Immunoglobulin
intervals, and their temperature every hour. All these observations should also be
preparations
made and recorded before the commencement of the infusion.

The dose for replacement therapy in individuals with immune deficiency is
0.4–0.6 g/kg every 3 to 4 weeks. In Kawasaki disease, a single dose of 2 g/kg
given over at least 6 to 8 hours is recommended, repeated once if fever fails to
resolve within 48 hours. Doses should be calculated to the nearest (next highest)
bottle so as not to waste any immunoglobulin. Giving slightly more than the
calculated dose per kilogram will not be harmful.

Recommendations
(i) Antibody deficiency disorders
NHIG (intravenous) is indicated for patients with antibody deficiency disorders
requiring large doses of immunoglobulin. Therapy in these patients is usually
administered at monthly intervals. NHIG (intravenous) produces higher serum
concentrations of IgG after administration than the IM preparation.2
(ii) Kawasaki disease

In clinical studies, NHIG (intravenous) has been found to be effective in the acute
phase of Kawasaki disease, as it reduces the risk of coronary artery involvement,
and is associated with more rapid resolution of other acute phase features of the
disease.11-15
(iii) Other uses

NHIG (intravenous) has been used in the management of immune
thrombocytopenia,16 Guillain-Barré syndrome,17,18 chronic inflammatory
demyelinating polyneuropathy,18 toxic shock syndrome,19 post-transfusion
purpura, in patients with bacterial infections associated with secondary
immunodeficiency, and in other inflammatory and infective disorders.3
(NB. Some recommendations in this section are not included in the current
registered indications for Intragam P. Potential users of NHIG (intravenous) in
these circumstances should consult the Australian Red Cross Blood Service or the
manufacturer.)
Contraindications
Individuals who are known to have had an anaphylactic or severe systemic
response to NHIG should not receive further immunoglobulin. Individuals with
selective IgA deficiency should not receive immunoglobulin preparations.
Adverse events and precautions

Adverse events with NHIG (intravenous) consist of shivering, headache, chest
and back pains and moderate pyrexia. Severe headache, sometimes attributed
to aseptic meningitis, has also been observed with NHIG (intravenous). This
can be ameliorated by slowing the infusion or by mixing the 60 mg/mL
preparation with an equal volume of normal saline before administration.
There have been isolated reports of renal dysfunction and acute renal failure
following the administration of NHIG (intravenous). To date, anaphylactic
shock has not been experienced with NHIG (intravenous). Subjects with
absolute selective IgA deficiency have an increased risk of severe adverse
events following NHIG (intravenous).

Specific immunoglobulins
These products are used to protect individuals against specific microbial agents
such as hepatitis B,20 rabies and varicella-zoster viruses,9,10 and tetanus toxin.
Each of these specific immunoglobulins is described in more detail in this
Handbook in the chapter or section relevant to these specific infections.
In addition, specific immunoglobulins are available for botulism,
cytomegalovirus (CMV) and respiratory syncytial virus (RSV) as described
below. Adverse events and storage requirements for these specific
immunoglobulins are similar to those for NHIG (IM) and, therefore, are not
repeated here.
Botulism antitoxin (formerly known as

Botulism Immune Globulin, BIG)
Equine antitoxin made in horses has long been used in the treatment of adult
botulism, but has not been shown to be effective in infant botulism.21
Equine antitoxin is manufactured by major vaccine producing companies such as
Chiron. Use in Australia is governed by the Therapeutic Goods Administration’s
Special Access Scheme and physicians wishing to access this stock should
initially contact their State/Territory health authority. Hypersensitivity,
presenting as fever, serum sickness or anaphylaxis, may follow its use. Skin
testing followed by appropriate dosing should be administered according to the
manufacturer’s instructions.
A new intravenous botulinum antitoxin, produced in the USA, reduced the
duration of mechanical ventilation and hospitalisation significantly in infant
botulism.22 It is not currently registered in Australia, but is registered by the US
FDA. The sponsor is Californian Department of Health Services. Access to this
product should be sought through the Special Access Scheme.
CMV immunoglobulin
CMV immunoglobulin is indicated for the prevention of CMV infection in
immunodeficient people at high risk of severe CMV infection, such as after bone
marrow and renal transplants.23-31 The treatment of established CMV infection is
primarily with antivirals such as ganciclovir, and there is scant evidence that the
addition of CMV immunoglobulin improves outcome.25,26,28 It would seem most
3.8 Immunoglobulin
logical to reserve the use of CMV immunoglobulin to treat established CMV

infection in those patients with hypogammaglobulinaemia.
preparations
The product contains no antibacterial agent, and so it must be used immediately

after opening. Any unused portion must be discarded. If the solution has been
frozen, it must not be used. If the use of CMV immunoglobulin is contemplated,
detailed protocols for administration and management of adverse events should
be consulted, in addition to the Product Information.

• CMV Immunoglobulin-VF (human) – CSL Bioplasma (sterile solution of
immunoglobulin prepared from human plasma containing high levels of
antibody to CMV). The plasma protein content is approximately 60 mg/mL
of which at least 98% is IgG immunoglobulin with a CMV immunoglobulin
activity of 1.5 million CMV units per vial. Maltose is added to achieve
isotonicity.
RSV immunoglobulin
Several clinical studies of immunoglobulin against RSV have been conducted
overseas using hyperimmune polyclonal RSV immunoglobulin (RSVIG) derived
from blood donations.32-34 It has been shown to reduce the incidence and severity
of RSV infections when given prophylactically in some babies and infants at
high risk of severe infection. Benefit has been shown for babies and infants with
bronchopulmonary dysplasia (BPD), for those with prematurity without BPD,
and children with haemodynamically significant congenital heart disease.34,35
RSVIG has caused severe cyanotic episodes and poor outcome after surgery in
children with congenital heart disease and is contraindicated in such children.36
RSVIG is not registered in Australia.
A humanised mouse monoclonal antibody to RSV produced by cultured cells
– palivizumab – is now registered in Australia for prevention of serious lower
respiratory tract disease caused by RSV in children at high risk of RSV disease.
This product is given by IM injection each month during periods of anticipated
risk of RSV. Palivizumab was found to reduce the absolute risk of hospitalisation
from about 10% to about 5% for babies born prematurely,37 for babies with
BPD,37 and also for babies with haemodynamically significant congenital heart
disease.35 It has not been shown to reduce the incidence of more severe outcomes
such as the need for ventilation, nor has it been shown to reduce mortality.35,37
Palivizumab is more effective and less costly than RSVIG, but its cost is still
prohibitive. Cost-effectiveness analyses have not shown palivizumab to be cost-
beneficial, and even analysis of sub-groups of children at high risk has not shown
a single subgroup where prophylaxis results in net savings.38,39
• Synagis – Abbott Australia (palivizumab). Supplied in single-use vials of

powder, to be reconstituted with sterile water for injection; 50 mg in 4 mL
vial; 100 mg in 10 mL vial.

Palivizumab is administered by IM injection preferably in the anterolateral thigh,
in a dose of 15 mg/kg once a month. Where possible, the first dose should be
administered before commencement of the RSV season.
Use in pregnancy
References
3.8 Immunoglobulin
preparations

3.9 Influenza
Virology
The influenza viruses are orthomyxoviruses. They are classified antigenically
as types A, B or C, but only influenza A and B are clinically important in
human disease.1 Influenza viruses possess 2 surface glycoprotein antigens,
the haemagglutinin (H) which is involved in cell attachment during infection,
and the neuraminidase (N) which facilitates the release of newly synthesised
virus from the cell. The influenza A viruses can be segregated into subtypes
based on differences in these surface antigens, whereas influenza B cannot be
segregated into subtypes. Antibody against the surface antigens, particularly the
haemagglutinin, reduces infection or severe illness due to influenza.
Both influenza A and influenza B viruses undergo frequent changes in their
surface antigens. Both influenza A and B undergo stepwise mutations of genes
coding for H and N. This results in cumulative changes in influenza antigens, or
‘antigenic drift’. This is responsible for the annual outbreaks and epidemics of
influenza and is the reason that the composition of influenza vaccines requires
annual review. Antigenic shift, defined as a dramatic change in H antigen with
or without a similar change in N, occurs occasionally and unpredictably and
can cause pandemic influenza.1 Pandemic subtypes arise spontaneously from
antigenic shift or as a result of genetic reassortment (mixing) between bird
(avian) or animal viruses and human strains.
Three pandemics are recognised in the 20th century, in 1918 (H1N1), 1957
(H2N2) and 1968 (H3N2). These pandemic strains have gone on to circulate in
the community, with various subtypes causing seasonal influenza and, since
1977, 2 subtypes of influenza A, A (H1N1) and A (H3N2), co-circulating in the
human population together with influenza B. Recently, the avian influenza
virus subtypes, A (H5N1) and A (H9N2), have been observed to cause human
infections. The most notable of these is the A (H5N1) subtype which has become
established in domestic poultry throughout southeast Asia and has spread to
Europe and Africa in either wild birds or domestic poultry. Although growing
numbers of people have contracted the virus by contact with birds and there is
a high mortality rate (of ≥50%), there has been no evidence of ongoing person to
person transmission.
Clinical features
Influenza is transmitted from person to person via virus-containing respiratory
aerosols, droplets produced during coughing or sneezing, or by direct contact
with respiratory secretions.1,2 Influenza virus infection causes a wide spectrum
of disease from minimal or no symptoms, to respiratory illness with systemic
features, to multisystem complications and death from primary viral or

secondary bacterial pneumonia. Severe disease is more likely with advanced
age, lack of previous exposure to antigenically related influenza virus, greater
virulence of the viral strain, chronic conditions such as heart or lung disease,
renal failure and diabetes, chronic neurological conditions, pregnancy, and
3.9 Influenza
smoking. Annual attack rates in the general community are typically 5 to 10%,
but may be up to 20% in some years. In households and ‘closed’ populations,
attack rates may be 2 to 3 times higher.2
In adults, the onset of illness due to influenza is usually abrupt, after an
incubation period of 1 to 3 days, and includes systemic features such as malaise,
feverishness, chills, headache, anorexia, and myalgia. These may be accompanied
by a cough, nasal discharge and sneezing. Fever is a prominent sign of infection
and peaks at the height of the systemic illness. Symptoms are similar for
influenza A and B viruses. However, infections due to influenza A (H3N2)
strains are more likely to lead to severe morbidity and increased mortality than
influenza B or influenza A (H1N1) strains.1,2
The clinical features of influenza A in infants and children are similar to those
in adults. However, temperatures may be higher in children (and may result
in febrile convulsions in the susceptible age group) and otitis media and
gastrointestinal manifestations are more prominent. Infection in neonates may be
associated with more non-specific symptoms.
Complications of influenza include acute bronchitis, croup, acute otitis
media, pneumonia (both primary viral and secondary bacterial pneumonia),
cardiovascular complications including myocarditis and pericarditis,
post-infectious encephalitis, Reye syndrome, and various haematological
abnormalities. Primary viral pneumonia occurs rarely, but secondary bacterial
pneumonia is a frequent complication in individuals whose medical condition
makes them vulnerable to the disease. Such individuals are at high risk in
epidemics and may die of pneumonia or cardiac decompensation.
Epidemiology
In most years, minor or major epidemics of type A or type B influenza
occur, usually during the winter months. In Australia, 85 deaths and 4250
hospitalisations are notified, on average, per year, although this is almost
certainly an underestimate due to failure to recognise the excess mortality
and hospitalisation associated with the disease. Extrapolation from US
estimates, based on more detailed surveillance, suggests 2000 deaths and 10 000
hospitalisations are likely to occur annually in Australia. During epidemics, the
mortality rises, especially among the elderly and people with chronic diseases,
and there is increased morbidity and hospitalisation for pneumonia and
exacerbation of chronic diseases.3
Figure 3.9.1 shows the Australian hospitalisation and notification data for the
period 2003–2005.
Influenza 185
Figure 3.9.1: Influenza notification rates 2003–2005 and hospitalisation rates
2002/2003 to 2004/2005, Australia,* by age group4
90
200
180
160
Rate per 100,000

80 140
120
100
70 80
Notifications 60
Rate per 100,000 population
40
Hospitalisations 20
60 0
0 1 2 3 4
Age (years)
50
40
30
20
10
0
0-4 5-9 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 >=85
Age (years)
* Notifications where the month of diagnosis was between January 2003 and December 2005;
hospitalisations where the month of separation was between 1 July 2002 and 30 June 2005.
Pandemic influenza
It is now recognised that influenza A viruses have evolved in birds and that all
16 subtypes of influenza A persist in the avian reservoir. Occasionally, human
infections may occur, with influenza subtypes not currently present in the human
population, through close contact with infected poultry or poultry products.
These may result, as in the case of recent A (H5N1) infections, in severe or fatal
disease.
Avian influenza viruses are not naturally transmissible from person to person.
However, adaptation to human to human transmission can occur either if an
individual is concurrently infected with a human and an avian influenza virus,
permitting genetic reassortment to occur, or if the virus acquires this ability
via mutation. Genetic studies have shown that avian influenza viruses are the
source of new human pandemic strains and that both these processes resulted in
pandemic influenza in the 20th century.
Vaccines in routine inter-pandemic use will not protect against a pandemic strain
which, by definition, is new and unpredictable. If a pandemic occurs, there
will be a delay in producing a pandemic vaccine. Once the pandemic vaccine
is available, the priority groups and the timing of vaccination may be quite
different from those during inter-pandemic periods. In addition, the number of
vaccine doses required to confer protection and the optimal interval between
doses may differ. The Australian Influenza Pandemic Planning Committee has

developed guidelines for vaccine use and will advise health authorities about
priority groups, dosing schedules and timing of vaccination, should a pandemic
occur.
3.9 Influenza
See http://www.health.gov.au/internet/wcms/publishing.nsf/Content/phd-
pandemic-plan.htm.
Vaccines
The administration of influenza vaccine to individuals at risk of complications
of infection is the single most important measure in preventing or attenuating
influenza infection and preventing mortality. After vaccination, most adults
develop antibody titres that are likely to protect them against the strains of virus
represented in the vaccine. In addition, the individual is protected against many
related variants. Infants, the very elderly, and patients with impaired immunity
may develop lower post-vaccination antibody titres. Under these circumstances,
influenza vaccine may be more effective in preventing lower respiratory tract
involvement or other complications of influenza than in preventing infection.
• Fluad – Delpharm Consultants/Novartis Vaccines (inactivated influenza

vaccine). Each 0.5 mL pre-filled syringe contains 15 µg haemagglutinin of the
3 recommended strains, adjuvanted with MF59C; 0.05 mg thiomersal. May
contain traces of kanamycin, neomycin, formaldehyde and egg protein.
• Fluarix – GlaxoSmithKline (inactivated influenza vaccine). Each 0.5 mL pre-

filled syringe contains 15 µg haemagglutinin of each of the 3 recommended
strains; polysorbate 80/octoxinol 9. May contain traces of thiomersal,
formaldehyde, gentamicin and egg protein.
• Fluvax – CSL Biotherapies (inactivated influenza vaccine). Each 0.5 mL pre-

filled syringe contains 15 µg haemagglutinin of each of the 3 recommended
strains. May contain traces of neomycin, polymyxin and egg protein.
• Fluvirin – Medeva/Ebos Health & Science (inactivated influenza vaccine).

Each 0.5 mL pre-filled syringe contains 15 µg haemagglutinin of the 3
recommended strains. May contain traces of neomycin, polymyxin and egg
protein.
• Influvac – Solvay Pharmaceuticals (inactivated influenza vaccine). Each

0.5 mL pre-filled syringe contains 15 µg haemagglutinin of each of the 3
recommended strains. May contain traces of gentamicin and egg protein.
• Vaxigrip – Sanofi Pasteur Pty Ltd (inactivated influenza vaccine). Each

0.5 mL pre-filled syringe contains 15 µg haemagglutinin of each of the 3
recommended strains. May contain traces of formaldehyde, neomycin and
egg protein.
Influenza 187
• Vaxigrip Junior – Sanofi Pasteur Pty Ltd (inactivated influenza vaccine).
Each 0.25 mL pre-filled syringe contains 7.5 µg haemagglutinin of each of
the 3 recommended strains. May contain traces of formaldehyde, neomycin
and egg protein.
Fluvax and Fluarix each have a marking on the syringe to allow preparation of a
0.25 mL dose suitable for paediatric use.
All the influenza vaccines currently available in Australia are either split virion
or subunit vaccines prepared from purified inactivated influenza virus which
has been cultivated in embryonated hens’ eggs. Split virion and subunit vaccines
are generally considered to be equivalent with respect to safety and efficacy, and
both are substantially free of the systemic reactions sometimes induced by whole
virus vaccines. Because the vaccine viruses are cultivated in embryonated hens’
eggs, the vaccine may contain traces of egg-derived proteins. Manufacturing
processes vary by manufacturer, and different chemicals (formaldehyde or
betapropiolactone) may be used to inactivate the virus. Some influenza vaccines
distributed in Australia contain thiomersal, a mercury-containing compound,
as preservative, and other antibacterials or antibiotics may be used in the
manufacturing process. The product information should be consulted for specific
information.
Influenza vaccines normally contain the 3 recommended strains of virus, 2
current influenza A subtypes and influenza B, representing recently circulating
viruses. The final product contains 15 µg of viral haemagglutinin, the principal
surface antigen, for each virus strain. Vaxigrip Junior contains 7.5 µg of viral
haemagglutinin of each of the 3 recommended strains found in the adult
formulations. The composition of vaccines for use in Australia is determined
annually by the Australian Influenza Vaccine Committee.
Other forms of influenza vaccines (such as live attenuated intranasal vaccine)
have not yet been licensed in Australia.5
The effectiveness of influenza vaccine depends primarily on the age and
immunocompetence of the vaccine recipient and the degree of similarity between
the virus strains in the vaccine and those circulating in the community. In healthy
individuals <65 years of age, influenza vaccine is 70 to 90% effective when the
antigenic match between vaccine and circulating viruses is close.6 Among elderly
people, the vaccine is 30 to 70% effective in preventing all hospitalisation for
pneumonia and influenza for those living outside nursing homes or similar
chronic-care facilities. For those residing in nursing homes, influenza vaccine
is most effective in preventing severe illness, secondary complications and
deaths. In such a population, the vaccine can be 50 to 60% effective in preventing
hospitalisation or pneumonia, and 80% effective in preventing death, even
though the effectiveness in preventing influenza illness may be lower.7 Currently

available influenza vaccines confer protection for about a year. Low levels of
protection may persist for a further year, if the prevalent strain remains the
same or undergoes only minor antigenic drift. To provide continuing protection,
annual vaccination with vaccine containing the most recent strains is necessary.
3.9 Influenza
at +2°C to +8°C. Do not freeze. At the end of each year, vaccine should be
appropriately discarded to avoid inadvertently using a product with incorrect
formulation in the following year.

Shake the pre-filled syringe vigorously before injection. Influenza vaccine is
administered by either IM or SC injection. The IM route causes fewer local
reactions and is preferred.9
Table 3.9.1: Recommended doses of influenza vaccine

Age Dose Number of doses Number of doses*
(first vaccination) (subsequent years)
6 months–<3 years 0.25 mL 2† 1
3–9 years 0.5 mL 2†
1
>9 years 0.5 mL 1 1
* If a child 6 months to ≤9 years of age receiving influenza vaccine for the first time
inadvertently does not receive the second dose within the same year, he/she should have 2
doses administered the following year.7
† Two doses at least 1 month apart are recommended for children aged ≤9 years who are
receiving influenza vaccine for the first time. The same vial should not be re-used for the 2
doses.
Note:
(i) Some influenza vaccines available in Australia are packed in syringes
graduated for measurement of recommended paediatric doses. Vaxigrip Junior
presentation is a 0.25 mL pre-filled syringe ready for use. Fluvax and Fluarix
each have a marking on the syringe to allow preparation of a 0.25 mL dose.
A tuberculin syringe can be used to measure the dose of vaccine not packed
in graduated syringes. Excess vaccine is expelled from the syringe and the
remaining volume injected.
(ii) All the product information sheets have some differences from Table 3.9.1.
Fluvirin does not have a dose recommendation for children <4 years of age. The
safety of Fluad, which is adjuvanted with MF59C, has not been established in
children and it is registered for use only in people ≥65 years of age.
Influenza 189
Vaccination is best undertaken in autumn, in anticipation of winter outbreaks of
influenza. However, vaccination can be given as early as February. In autumn,
the opportunities to provide influenza vaccination to individuals at increased
risk should not be missed when they present for routine care.
As full protection is usually achieved within 10 to 14 days and there is evidence
of increased immunity within a few days, vaccination can still be offered to
adults and children after influenza virus activity has been documented in a
community.
Influenza vaccine can be administered concurrently with other vaccines,
including pneumococcal polysaccharide vaccine and all the scheduled childhood
vaccines.
Recommendations
Annual influenza vaccination is recommended for any person ≥6 months of age
who wishes to reduce the likelihood of becoming ill with influenza.
Influenza vaccination is strongly recommended and should be actively promoted
for the following groups:
1. People at increased risk of complications from influenza infection

(i) All individuals ≥65 years of age3,10-13
Influenza vaccine has been shown to reduce hospitalisations from pneumonia
and all-cause mortality by about half in adults ≥65 years of age.
(ii) All Aboriginal and Torres Strait Islander people ≥15 years of age
Annual influenza vaccine is recommended for Aboriginal and Torres Strait
Islander people ≥15 years of age in view of the substantially increased risk of
hospitalisation and death from influenza and pneumonia (see Chapter 3.15,
Pneumococcal disease). In Aboriginal and Torres Strait Islander people ≥50 years of
age, routine pneumococcal polysaccharide vaccination is also recommended (see
Chapter 2.1, Vaccination for Aboriginal and Torres Strait Islander people and Chapter
3.15, Pneumococcal disease).
(iii) Individuals ≥6 months of age with conditions

predisposing to severe influenza
• Cardiac disease including cyanotic congenital heart disease, coronary artery
disease and congestive heart failure.14,15 Influenza causes increased morbidity
and mortality in children with congenital heart disease and adults with
coronary artery disease and congestive heart failure.14
• Chronic respiratory conditions including:
• Suppurative lung disease, bronchiectasis, and cystic fibrosis.16 Patients
with these diseases are at greatly increased risk from influenza, which
may cause irreversible deterioration in lung function.

• Chronic obstructive pulmonary disease and chronic emphysema. There
is clinical trial evidence that inactivated influenza vaccination has a
clinically important protective effect on influenza-related exacerbations,
and probably an effect on the total of exacerbations in COPD patients.
3.9 Influenza
There is no evidence that inactivated influenza vaccination causes
exacerbations of COPD.16
• Severe asthma. In patients with severe asthma, defined as requiring
frequent hospital visits, annual influenza vaccine is an important part of
routine care.17-19 There are insufficient data from randomised controlled
trials of influenza vaccine to define efficacy across the whole spectrum
of asthma,20 but influenza can cause severe exacerbations of wheezing,
and about 10% of episodes of virus-induced wheezing are attributable to
influenza.
• Other chronic illnesses requiring regular medical follow-up or hospitalisation in the
preceding year, including:
• diabetes mellitus,
• chronic metabolic diseases,
• chronic renal failure,
• haemoglobinopathies, and
• impaired immunity (including drug-induced immune impairment).7,21,22
• Chronic neurological conditions (eg. multiple sclerosis, spinal cord injuries,
seizure disorders or other neuromuscular disorders) that can compromise
respiratory function or the expulsion of respiratory secretions or that can
increase the risk for aspiration.7 NB. Because they can experience severe, even
fatal, influenza, vaccination is particularly important for children ≥6 months
of age with chronic neurological conditions.7
• People with impaired immunity, including HIV infection.23,24 Patients with
impaired immunity, including HIV infection, malignancy and chronic steroid
use, are at greatly increased risk from influenza, although they also have
a reduced immune response to the vaccine. While patients with advanced
HIV disease and low CD4 T-lymphocyte counts may not develop protective
antibody titres, there is evidence that for those with minimal symptoms
and high CD4 T-lymphocyte counts (see Chapter 2.3, Groups with special
vaccination requirements, Table 2.3.4), protective antibody titres are obtained
after influenza vaccination.24 Influenza vaccine has been shown in a clinical
trial to reduce the incidence of influenza in HIV-infected patients,24 and
although viral load may increase transiently, there is no impact on CD4
count.23
• Long-term aspirin therapy in children (aged 6 months to 10 years). Such children
are at increased risk of Reye syndrome after influenza.
Influenza 191
(iv) Pregnant women
It is recommended that influenza vaccine be offered in advance to women
planning a pregnancy, and to pregnant women who will be in the second or third
trimester during the influenza season, including those in the first trimester at
the time of vaccination.25,26 Influenza vaccination is estimated to prevent 1 to 2
hospitalisations per 1000 women vaccinated during the second or third trimester.
(v) Residents of nursing homes and other long-term care facilities

This is due to high rates of transmission and complications during outbreaks.3,9-13,27
(vi) Homeless people and those providing care to them
The living conditions and prevalence of underlying medical conditions among
homeless people will predispose to complications and transmission of influenza.
2. People who may potentially transmit influenza to

those at high risk of complications from influenza
The following groups of people can potentially transmit influenza to high-risk
patients and it has been shown that vaccinating the former protects those at
high-risk:
• staff of nursing homes,
• healthcare providers28 (particularly of patients with impaired immunity),
• staff of long-term care facilities,
• household contacts (including children ≥6 months of age) of individuals in
high-risk groups.
3. People involved in the commercial poultry industry or in

culling poultry during confirmed avian influenza activity29
Vaccination using the current influenza season vaccine composition is
recommended for poultry workers and others in regular close contact with
poultry during an avian influenza outbreak.29 Although routine influenza vaccine
does not protect against avian influenza, there is a possibility that a person who
was infected at the same time with avian and human strains of influenza virus
could allow reassortment of the 2 strains to form a virulent strain that could
spread from human to human (ie. initiate a pandemic).
4. People providing essential services

Vaccination of those who provide essential community services will minimise
disruption of essential activities during influenza outbreaks. Influenza viral
infections can place considerable pressure upon both public and private
healthcare services (see Chapter 2.3, Groups with special vaccination requirements,
Table 2.3.6).

5. Workers in other industries
The cost-effectiveness of influenza vaccination in industry varies from year to
year, depending on the amount of circulating influenza, but the overall impact
3.9 Influenza
over time is judged to be cost-saving in several settings.6,7 Individual industries
should consider the benefits of offering influenza vaccine in the workplace.
6. Travellers
Large tourist groups, especially those including elderly people and those
travelling on cruises, who are likely to be in confined circumstances for days
to weeks, are at risk of influenza, either acquired before departure or from
travel to areas of the world where influenza is currently circulating. Influenza
vaccination, preferably using the strain prevalent in the areas in which they
will be travelling, is recommended if travelling during the influenza season,
especially if it is known before travel that there are high rates or epidemics of
influenza.7
Contraindications
Absolute contraindications to influenza vaccine are:
• anaphylaxis following a previous dose of any influenza vaccine,
• anaphylaxis following any vaccine component,
• individuals with anaphylactic sensitivity to eggs should not be given
influenza vaccine. This includes those who, soon after ingesting eggs,
develop swelling of the lips or tongue, or experience acute respiratory
distress or collapse.
Precautions
Patients with a history of Guillain-Barré Syndrome (GBS) with an onset related in
time to influenza vaccination may be at increased risk of again developing GBS
if given influenza vaccine. The risk should be weighed against the benefits to the
individual patient of influenza vaccination. Because patients with a history of
GBS have an increased likelihood of developing the syndrome again, the chance
of them coincidentally developing the syndrome following influenza vaccination
may be higher than in individuals with no history of GBS.
Adverse events27,30
Local adverse events (induration, swelling, redness and pain) are very common
(>10%).
Fever, malaise and myalgia occur commonly (1–10%). These adverse events may
commence within a few hours of vaccination and may last for 1 to 2 days. In
children <5 years of age, these adverse events may be more pronounced. Post-
vaccination symptoms may mimic influenza infection but current influenza
vaccines do not contain live virus and cannot cause influenza.
Influenza 193
Immediate adverse events (such as hives, angioedema, or anaphylaxis) are a
rare consequence of influenza vaccination. They probably represent an allergic
response to a residual component of the manufacturing process, most likely egg
protein. Individuals with a history of anaphylaxis after eating eggs or a history of
a severe allergic reaction following occupational exposure to egg protein should
not be given influenza vaccine.
An association was shown between influenza vaccine used in the northern
hemisphere from 1992 to 1994 and Guillain-Barré syndrome (GBS), with 1 to
2 cases of GBS occurring per million vaccinated. There has not been an excess
number of cases of GBS reported in Australia in association with influenza
vaccine.31
Use in pregnancy
Influenza vaccine is recommended for pregnant women who will be in the
second or third trimester during the influenza season, including those in the first
trimester at the time of vaccination. See ‘Recommendations’ above.

The product information lists allergy to chicken feathers and some food proteins
as a contraindication, whereas NHMRC recommends that patients with allergies
other than anaphylaxis can be vaccinated.
The product information for Fluarix states the influenza vaccine may be used
in children from 3 months of age. NHMRC recommends influenza vaccine in
children ≥6 months of age.
The product information for some vaccines gives a dose of 0.125 mL for children
3 or 6 months to 2 years old. NHMRC recommends that the lowest dose for any
influenza vaccine is 0.25 mL. This is because influenza vaccine is relatively poorly
immunogenic in infants, and 0.25 mL is the dose recommended in the USA for
children aged ≥6 months where it has been shown to be safe.32
The product information for Fluvirin states that the product should not be given
to children <4 years of age. Although the NHMRC recommends that children as
young as 6 months of age can be vaccinated if they are at risk of complications of
influenza, the suitability of the vaccine formulation for accurate preparation of
0.25 mL doses should be taken into account.
References

3.10 Japanese encephalitis
Virology
Japanese encephalitis (JE) is caused by a mosquito-borne flavivirus.
Clinical features
The disease is typically an acute neurological illness characterised by headache,
fever, convulsions, focal neurological signs and depressed level of consciousness.
It has a high case-fatality rate and there is a high prevalence of neurological
sequelae (up to 50%) in those who survive the acute illness.1 Less commonly, the

disease may present as an acute flaccid paralysis.1 Milder forms include febrile
illness with headache, and aseptic meningitis. It is recognised, however, that
most infections are asymptomatic; published estimates of the symptomatic to
asymptomatic infection ratio vary in different populations from 1:25 to 1:1000.1
Epidemiology
JE is a significant public health problem in many parts of Asia including the
Indian subcontinent, southeast Asia and China.1 In recent years, however, the
disease has extended beyond its traditionally recognised boundaries with, for
example, outbreaks occurring in the Torres Strait and north Queensland in 1995
and 1998.2,3
The JE virus is essentially a zoonosis of pigs and wading birds, and is transmitted
between these animals by Culicine mosquitoes.1 The virus replicates, leading to
a transient high-level viraemia, within these so-called ‘amplifying’ hosts but not
within other large vertebrates such as horses and humans.
Indeed, humans are an incidental host infected when living in close proximity
to the enzootic cycle; this usually occurs in rural areas where there is prolific
breeding of the vectors in flooded rice fields.1
There are two recognised epidemiological patterns of JE.1 In the temperate or
subtropical regions of Asia (northern Thailand, northern Vietnam, Korea, Japan,
Taiwan, China, Nepal and northern India), the disease occurs in epidemics during
the summer or wet season months (April to May until September to October). In
the tropical regions (most of southeast Asia, Sri Lanka, southern India), the disease
is endemic, occurring throughout the year, but particularly during the wet season.1
In some countries (Japan, Taiwan, South Korea, and some provinces of China),
the incidence of JE has declined considerably in recent decades, and it has been
eradicated from Singapore. Immunisation, changes in pig husbandry, a reduction
in land utilised for rice farming, and improved socioeconomic circumstances
have all contributed to these changes.1
Japanese encephalitis 195

In early 1995, 3 cases of JE, 2 of them fatal, occurred on Badu island in the
Torres Strait.2 Subsequent serological surveys showed that JE virus activity was
widespread in many other remote ‘outer’ islands of the Torres Strait (see Figure
3.10.1) at or about that time.2 Although the 1995 outbreak was the first known
incursion of JE virus into Australia, surveillance using sentinel pigs has shown
incursions into the Torres Strait in virtually every wet season (December to May)
since then.
In early 1998, a further case of JE occurred in an unvaccinated Badu resident and
the first ever mainland case of JE occurred in a person working on the west coast
of Cape York.3 However, serological surveys revealed no evidence of JE virus
infection in people in several nearby communities.3 To date, there have been 5
cases of JE acquired in Australia.
An investigation subsequent to the 1995 outbreak of JE in the Torres Strait
documented the presence of the JE virus in the Western Province of Papua New
Guinea.4 A severe case of JE acquired near Port Moresby occurred in early 2004,5
indicating that the JE virus is now probably widespread in Papua New Guinea.
Figure 3.10.1: Map of the Torres Strait. The outer islands are north of the dotted
line
Vaccine
• JE-VAX – Sanofi Pasteur Pty Ltd (Japanese encephalitis virus vaccine
inactivated). Each 1.0 mL reconstituted monodose vial contains
formaldehyde inactivated Japanese encephalitis virus; 0.007% thiomersal;
470 µg gelatin; <100 µg formaldehyde; 5 mg monosodium glutamate; <50
ng mouse brain serum protein.

The JE vaccine available in Australia is an inactivated mouse brain-derived
vaccine manufactured in Japan. However, the manufacturer has recently
discontinued its production and, although the Australian distributor has access
to a stockpile, shortages of the vaccine could occur over the next few years. New
generation JE vaccines are expected in the mid to longer term.
The vaccine is prepared by inoculating mice intracerebrally with Nakayama-
NIH strain JE virus. Infected brains are harvested, homogenised, then
centrifuged. The supernatant is inactivated with formaldehyde and purified by
ultracentrifugation; the suspension is then lyophilised. No myelin basic protein
can be detected at the threshold of the assay (<2 ng/mL).
A randomised clinical trial in Thailand in the early 1980s determined that 2
doses of the inactivated mouse brain-derived vaccine, administered to children

7 days apart, had a protective efficacy of 91%.6 However, immunogenicity studies
have demonstrated that 3 doses of the vaccine are required to ensure adequate
immunity in vaccinees from JE non-endemic areas.7

+2°C to +8°C. Do not freeze. Reconstituted vaccine should be used immediately,
but it can be stored at +2°C to +8°C and used within 8 hours.

JE vaccine is administered by the subcutaneous route. The volume injected is
0.5 mL in 1–3-year-old children and 1.0 mL for all individuals >3 years of age. In
those from non-endemic regions, including Australia, a 3-dose regimen (ie. days
0, 7 and 28) over a month is required. An accelerated schedule of 0, 7 and 14 days
can be used, but this is likely to result in lower antibody levels than the standard
schedule.7 If the accelerated schedule is used, a further dose should, if possible,
be administered 1 to 3 months later.
NB. The volume of the reconstituted vaccine is greater than 1.0 mL. Because the
dose of JE vaccine is 1.0 mL (0.5 mL in 1–3-year-old children) this means a small
portion of the total reconstituted vaccine should be discarded.
Recommendations
(i) Travellers
Although the risk of travellers in Asia acquiring JE is extremely low, there have
been instances of even short-term travellers developing the disease.9 Therefore, all
travellers to Asia (and other tropical regions) must be fully aware of the need to
take appropriate measures to avoid mosquito bites.
The risk of JE to travellers to Asia is determined by the season of travel, the
regions visited, the duration of travel, the extent of outdoors activity and the
extent to which mosquito-avoidance measures are taken.1 Clearly the risk is

greater during prolonged travel to rural areas of Asia during the wet season; it is
probably negligible during short business trips to urban areas.
NB. A recent study has shown that the JE virus is hyperendemic in Bali, that it
causes substantial human illness, and that it circulates year round.10
Therefore JE vaccination is recommended for:
• travellers spending 1 month or more in rural areas of Asia. However, as
JE has occurred in travellers after shorter periods of travel, JE vaccination
should be considered for shorter-term travellers, particularly if the travel is
during the wet season, and/or there is considerable outdoor activity, and/or
the accommodation is not mosquito-proof,9
• for all other travellers spending a year or more in Asia (except Singapore),
even if much of the stay is in urban areas, and
• travellers intending to spend a month or more in Papua New Guinea,
particularly if the travel is during the wet season.
(ii) Residents of Far North Queensland

JE vaccination is recommended for:
• all residents (>1 year of age) of the outer islands in the Torres Strait, and
• all non-residents who will be living or working on the outer islands of the
Torres Strait for a cumulative total of 30 days or more during the wet season
(December to May).
NB. The period of greatest risk is from February to March and the vaccination
course should be completed before February. Those arriving in the outer islands
late in the wet season (ie. in May) have arrived after the risk period and do not
require vaccination. Those visiting the outer islands in the dry season (June to
November) do not require vaccination. Those visiting only the inner islands,
including Thursday Island, do not require vaccination.
(iii) Laboratory personnel

JE vaccination is recommended for all research laboratory personnel who
potentially might be exposed to the virus.
(iv) Booster doses

Single booster doses are recommended at 3-yearly intervals.

Contraindications
• Anaphylaxis following a previous dose of JE vaccine or a significant allergic
reaction, such as generalised urticaria, to a previous dose.
• Anaphylaxis following any component of the vaccine. A past history
of allergic disorders (including urticaria, angioedema, anaphylaxis)
following bee-stings, medications, foods etc. must be considered as possible
contraindications to vaccination.
• The inactivated mouse brain-derived JE vaccine is contraindicated in those <1
year of age.
Precautions

There are few data on the safety and efficacy of JE vaccine in people with impaired
immunity. A small study undertaken in Thailand has documented that HIV-
infected infants respond less well to 2 doses of JE vaccine than do non-infected
infants;11 the response to further doses was not studied.
Adverse events
• Local reactions and minor systemic reactions are common to very common
following vaccination against JE.1 About 20% experience tenderness, redness
and/or swelling at the injection site, and 10% experience systemic reactions
such as fever, headache, being ‘off-colour’, chills, dizziness, aching muscles,
nausea and/or vomiting.
• Although the manufacturing process purifies the infected mouse brain
suspension so that no myelin basic protein can be detected in the vaccine,
serious neurological events following immunisation have been reported. In
1994, 4 cases of severe neurological illness, 2 of which were fatal, were reported
from South Korea, and surveillance in Japan indicates the rate of severe
neurological adverse events following JE vaccination is 1.8 cases per 1 million
doses of vaccine.7
• Hypersensitivity (allergic) reactions are uncommon and occur in about
0.5% (ie. 1 in 200) vaccinees. These reactions include urticaria that is often
widely distributed over the body, angioedema of the limbs, face and throat,
and generalised pruritus (sometimes without a rash). In the early 1990s,
apparently severe allergic reactions to the inactivated mouse brain-derived
JE vaccine were reported from several industrialised countries, including
Australia.7 In a few cases, upper airway swelling with respiratory distress
and hypotension occurred; some had to be hospitalised.
An important feature of the hypersensitivity reactions to JE vaccine is that they
may be delayed for several days, in some cases up to 10 days, after the actual
time of vaccine administration. The risk of these delayed reactions seems to be
increased after the first and second doses, and they appear to be more likely to
occur in those with a history of allergic reactions, especially urticaria.7 Although

the pathogenesis of the more severe hypersensitivity reactions remains uncertain,
there is some evidence that gelatin, added to stabilise the vaccine, may be the
provoking agent.7 As a precaution, vaccinees should ideally remain within access
to medical care for 10 days after vaccination.
Use in pregnancy
Although JE vaccine might pose a theoretical risk to the developing fetus, no
adverse outcomes of pregnancy have ever been attributed to vaccination against
JE. Because JE virus infection during the first and second trimester is also
associated with miscarriage, pregnant women at risk of acquiring JE should be
offered JE vaccine.

The product information states that ‘definitive recommendations cannot be given
on the timing of booster doses at this time’ and that ‘a booster dose may be given
after 2 years’. The NHMRC recommends that single booster doses be given at
3-yearly intervals.
References

3.11 Measles
Virology
Measles is a paramyxovirus, genus Morbillivirus. It is an RNA virus with 6
structural proteins, 3 complexed to the RNA and 3 associated with the viral
envelope. Two of the envelope proteins, the F (fusion) protein and the H
(haemagglutinin) protein, are the most important in pathogenesis. The measles
virus can survive up to 2 hours in air, but is rapidly inactivated by heat, light and
extremes of pH.1,2
Clinical features
Measles is a highly infectious, acute viral illness spread by respiratory secretions,
including air-borne transmission via aerosolised droplets.2 It is infectious from
the beginning of the prodromal period and up to 4 days after the appearance of
the rash. The incubation period is usually 10 to 14 days. The prodrome, lasting 2
to 4 days, is characterised by fever and malaise followed by a cough, coryza and
conjunctivitis. The maculopapular rash typically begins on the face and upper
neck, and then becomes generalised.
Measles is often a severe disease, frequently complicated by otitis media
(in ~9%), pneumonia (in ~6%) and diarrhoea (in ~8%).1,2 Acute encephalitis
occurs in 1 per 1000 cases, and has a mortality rate of 10 to 15%, with 15 to
40% of survivors suffering permanent brain damage.3 Subacute sclerosing
panencephalitis (SSPE) is a late complication of measles, occurring on average
7 years after infection in approximately 0.5 to 1 per 100 000 measles cases.2
3.11 Measles
SSPE causes progressive brain damage and is always fatal. Complications from
measles are more common and more severe in the chronically ill, in children
<5 years of age, and in adults.1 Approximately 60% of deaths from measles are
attributed to pneumonia, especially in the young, while complications from
encephalitis are more frequently seen in adults.1,2 Measles infection during
pregnancy can result in miscarriage and premature delivery but has not been
associated with congenital malformation.1
Epidemiology
Evidence suggests that endemic measles has been eliminated from Australia,
an indigenous measles strain being absent for several years.4 Although measles
outbreaks of limited duration continue to occur, they have usually been linked
to imported cases.5-7 In a recent measles outbreak, linked to an imported case,
25% of notified cases were in children aged 1–4 years, most of whom were not
vaccinated.8 Measles notifications and hospitalisations for the 5 years 2001–2005
have been the lowest recorded in Australia.9,10 In the 30 years (1976–2005) since
measles vaccination was recommended in Australia, there have been 95 deaths
Measles 201
recorded from measles, 1 death in 2004 being the only one recorded since 1995.9-11
High-level vaccination coverage is imperative to maintain measles elimination,
requiring rates for each new birth cohort of >95% for a single dose and >90%
for 2 doses.12 In 2004, the Australian Childhood Immunisation Register (ACIR)
recorded that 93.6% of children aged 2 years (born in 2002) had received at least
1 dose of measles-containing vaccine and 84.8% of children aged 6 years (born
in 1998) had received both doses.13 It is likely that, when corrected for under-
reporting, the target of 95% coverage for 1 dose of measles vaccine is reached
at 2 years, but, if the second dose is not given until 4 years of age, 95% 2-dose
coverage is not achieved.14 Scheduling of the second dose of measles-containing
vaccine at 18 months of age (see ‘Recommendations’ below) will provide 2-dose
protection at an earlier age and may also improve second dose coverage.
Following the National Measles Control Campaign (which took place in 1998
and resulted in 1.7 million primary school children being vaccinated), a national
serosurvey in the first quarter of 1999 showed that 89% of children aged
2–5 years, 94% of those aged 6–11 years, and 91% of those aged 12–18 years,
were immune to measles.15,16 The serosurvey evaluating the young adult MMR
campaign in 2000 showed that those most at risk of measles infection in Australia
were infants <12 months of age, 1–<2-year-olds due to delayed vaccine uptake,
and individuals born in the late 1960s to mid 1980s (especially the 1978–1982
birth cohort).17 Young adults are recognised to be at a greater risk of measles
infection. Many missed being vaccinated as infants (when coverage was low),
while during their childhood a second dose was not yet recommended and
disease exposure was decreasing.18
Worldwide, measles is thought to be the fifth leading cause of childhood
morbidity and mortality with 770 000 deaths estimated to have occurred in
2000. More than half these deaths occurred in Africa.1,19 Following extensive
vaccination campaigns, measles accounted for approximately 454 000 deaths
worldwide in 2004.20 The WHO is overseeing efforts to eliminate measles
worldwide through immunisation and surveillance strategies that aim to
interrupt the circulation of the virus.21
Vaccines
One measles-mumps-rubella (MMR) vaccine is currently available in Australia.
It is anticipated that measles-mumps-rubella-varicella (MMRV) vaccines will
become available in the near future. A monovalent vaccine is available for
rubella where this is specifically required (see Chapter 3.19, Rubella). Separate
administration of measles, mumps or rubella vaccine is not recommended as an
alternative to MMR vaccine and no monovalent vaccines for mumps or measles
are licensed in Australia.
Measles immunity induced by single-dose vaccination provides long-term
immunity in most recipients.1,22 However, approximately 5% of recipients fail to
develop immunity to measles after 1 dose.23 Following a second vaccine dose,

approximately 99% of subjects overall will be immune to measles. Combination
MMRV vaccines have been shown, in clinical trials, to produce similar rates
of seroconversion to all 4 vaccine components compared with MMR and
monovalent varicella vaccines administered at separate injection sites.24,25 Data on
the use of MMRV vaccines are not available for people >12 years of age.
• Priorix (MMR) – GlaxoSmithKline (live attenuated measles virus (Schwarz

strain), RIT 4385 strain of mumps virus (derived from the Jeryl Lynn strain)
and the Wistar RA 27/3 rubella virus strain). Each 0.5 mL monodose of the
reconstituted, lyophilised vaccine contains not less than 103.0 CCID50 (cell
culture infectious dose 50%) of the Schwarz measles, not less than 103.7
CCID50 of the RIT 4385 mumps and not less than 103.0 CCID50 of the Wistar
RA 27/3 rubella virus strains; lactose; neomycin; amino acids; sorbitol and
mannitol as stabilisers.

+2°C to +8°C. Protect from light. Do not freeze. Reconstituted vaccine should be
used immediately, but can be stored at +2°C to +8°C for up to 8 hours before use.

For both children and adults, the dose of MMR is 0.5 mL, administered by either
SC or IM injection.
MMR can be given at the same time as other vaccines (including DTPa, hepatitis
B, MenCCV and varicella), using separate syringes and injection sites. If MMR is
3.11 Measles
not given simultaneously with other live viral parenteral vaccines (eg. varicella
vaccine), they should be given at least 4 weeks apart (see ‘Precautions’ below).27,28
Recommendations
(i) Routine vaccination of children
Two doses of MMR are recommended for all children. The first dose should
be given at 12 months of age and the second dose at 18 months of age. The
minimum interval between doses is 4 weeks.
When MMRV vaccines are available, the 12 month and 18 month doses may be
given as MMRV.
The scheduled age at administration of the second dose of measles-containing
vaccine has been moved from 4 years of age to 18 months of age to provide
earlier 2-dose protection against measles and to improve vaccine uptake
(see ‘Epidemiology’ above). The second dose of measles-containing vaccine
at 18 months of age can be given as either MMR or, when available, MMRV.
Receipt of 2 doses of varicella vaccine (VV) provides increased protection against
Measles 203
varicella, and MMRV, when available, should be preferred over MMR for the
second dose of measles-containing vaccine at 18 months of age. (For further
information, see also Chapter 3.24, Varicella.)
(ii) Vaccination of adults and adolescents

Those born before 1966:
No vaccination is required (unless serological evidence indicates otherwise) as
circulating virus and disease were prevalent before this time suggesting most
people would have acquired immunity from natural infection. However, recent
confirmed cases of measles have occurred in individuals born before 1966 and, if
doubt exists, it may be more expedient to offer vaccination than serological testing.8
Those born during or since 1966:
Infants ≥12 months up to 18 months of age should have documented evidence of
1 dose of MMR (or MMRV when available), or serological evidence of protection
for measles.
Those ≥18 months of age should have documented evidence of 2 doses of MMR
(administered at least 4 weeks apart with both doses administered at 12 months
of age or over), or serological evidence of protection for measles, mumps and
rubella.
Catch-up vaccination of children who have not received MMR or MMRV at
18 months of age should occur at the 4-year-old schedule point, until all the
relevant children have reached 4 years of age. It is also acceptable to use MMRV
in place of MMR at the 4-year-old schedule point. This would have the added
benefit of providing a 2-dose VV schedule to an additional 2.5 birth cohorts of
infants who had received single-dose monovalent VV at 18 months.
There are no increased adverse events from vaccinating those with pre-existing
immunity to 1 or more of the vaccine components.
(iii) Healthcare workers and those who work with children

All workers in these categories who were born during or since 1966 and are
non-immune or who have only received 1 dose of MMR, should be vaccinated
with MMR, and have documented evidence of 2 doses or serological evidence
of protection for measles, mumps and rubella (see ‘Vaccination of adults and
adolescents’ above). (See also Section 2.3, Table 2.3.6 Recommended vaccinations for
those at risk of occupationally acquired vaccine-preventable diseases.)
(iv) Travellers
Those born during or since 1966 should be encouraged to complete the MMR
vaccination schedule (using MMR or MMRV, when appropriate) before
embarking on international travel if they do not have evidence of receipt of 2
doses of MMR (see ‘Vaccination of adults and adolescents’ above).

Infants travelling to endemic countries may be vaccinated with MMR between 9
and 12 months of age. In these cases, another dose of MMR (or MMRV) should be
given at 12 months of age or 4 weeks after the first dose, whichever is later. This
should be followed by the routine administration of the next dose of MMR or MMRV
at 18 months of age. This is because maternal antibodies to measles are known
to persist in many infants until 11 months of age and may interfere with active
immunisation before 12 months of age1 (see ‘Vaccination during an outbreak’ below).
Contraindications
If using MMRV vaccine, additional contraindications relating to the varicella
vaccine component are outlined in Chapter 3.24, Varicella.
(i) Allergy to vaccine components

Vaccination is contraindicated where there has been:
• anaphylaxis following a previous dose of MMR or MMRV, or
Providers should consult the product information regarding vaccine components
when MMRV vaccines are available.
(ii) People with impaired immunity

Measles-, mumps-, rubella- and varicella-containing vaccines are contraindicated
in individuals with impaired immunity. In addition, there are no clinical
trials or post-licensure data to address the safety and immunogenicity of
MMRV in children or adults with impaired immunity. However, based on
recommendations for the component live attenuated vaccine viruses, both MMR
3.11 Measles
and MMRV are contraindicated in the following groups:
• those with primary or acquired cellular immunodeficiency states, including
impaired immunity due to HIV/AIDS or conditions in which normal
immunological mechanisms may be impaired. MMR (but not MMRV)
vaccine can be given to HIV-positive children who do not have impaired
immunity (see ‘Precautions’ below),
• those taking high-dose oral corticosteroids (in children equivalent to either
>2 mg/kg per day prednisolone (≥20 mg per day total) for >1 week or
>1 mg/kg per day for >4 weeks) (see Section 2.3.3, Vaccination of individuals
with impaired immunity due to disease or treatment),
• those receiving high-dose systemic immunosuppressive treatment, general
radiation or x-ray therapy,
• those suffering from malignant conditions of the reticuloendothelial system
(such as lymphoma, leukaemia, Hodgkin’s disease).
Measles 205
(iii) Recent administration of antibody-containing blood product
• The expected immune response to measles, mumps, rubella and varicella
vaccination may be impaired after receipt of antibody-containing blood
products.23,27,29 The duration of interference with the response to measles
vaccination depends on the amount of immunoglobulin contained in each
product, and ranges from 3 to 11 months.27 Vaccination with MMR or MMRV
should be delayed after administration of antibody-containing products
as indicated in Table 2.3.5 (see Section 2.3.5, Vaccination of patients following
receipt of other blood products including blood transfusions).
• After vaccination with MMR or MMRV, immunoglobulin-containing
products should not be administered for 3 weeks unless the benefits
exceed those of vaccination. If immunoglobulin-containing products are
administered within this interval, the vaccinee should either be revaccinated
later at the appropriate time following the product as indicated in Table 2.3.5,
or tested for immunity 6 months later and then revaccinated if seronegative.
• Blood transfusion with washed red blood cells is not a contraindication to
MMR or MMRV vaccinations.
• Rh (D) immunoglobulin (anti-D) does not interfere with the antibody
response to MMR vaccine and may be given at the same time in different
sites with separate syringes or at any time in relation to each other.
(iv) Pregnant women

• If MMR vaccines are given to women of child-bearing age, pregnancy should
be avoided for 28 days30 (see Chapter 3.19, Rubella). Data on the use of MMRV
vaccines in individuals >12 years of age are not available.
Precautions
• MMR can be administered on the same day as other live viral parenteral
vaccines, such as monovalent varicella vaccine. However, if this is not
possible, MMR should be deferred for at least 4 weeks after vaccination with
other live viral parenteral vaccines.
• MMR can be given to asymptomatic or mildly symptomatic HIV-positive
individuals providing they do not have severely impaired immunity.23 (see
Section 2.3.3, Table 2.3.4, Immunological categories based on age-specific CD4
counts and percentage of total lymphocytes). This is because the risk posed by
measles infection is considered to be greater than the likelihood of adverse
events from vaccination.31 As there are no data available on the safety,
immunogenicity or efficacy of MMRV vaccine in HIV-infected children,
MMRV vaccine should not be administered as a substitute for MMR when
vaccinating these children.23,29

• Children on daily doses of ≤2 mg/kg per day of systemic corticosteroids
for <1 week, and those on lower doses of 1 mg/kg per day or alternate-day
regimens for longer periods, may be given live viral vaccines.
• Children receiving >2 mg/kg per day or ≥20 mg per day in total of
prednisolone (or equivalent) for >14 days can receive live viral vaccines after
corticosteroid therapy has been discontinued for at least 1 month.31 Some
experts suggest withholding lower doses of steroids 2 to 3 weeks before
vaccination with live viral vaccines if this is possible29,31 (see Section 2.3.3,
Vaccination of individuals with impaired immunity due to disease or treatment).
• Use of salicylates (aspirin) is not recommended for 6 weeks following
MMRV vaccination. This is because of the association between use of
salicylates during natural varicella infection and Reye syndrome (see Chapter
3.24, Varicella). There is no need to avoid salicylates (aspirin) after MMR
vaccination.
• Thrombocytopenia is a rare adverse event following vaccination with
MMR.2,32,33 Authorities differ in their opinion about whether the risk
of vaccine-associated thrombocytopenia is increased in those who
have previously had immune thrombocytopenia.23,33 Post-marketing
experience of live MMR vaccine in the USA indicates that individuals with
current thrombocytopenia may develop more severe thrombocytopenia
after vaccination. Recent studies found that children with immune
thrombocytopenia before MMR had no vaccine-associated recurrences.32,33
There are no systematic studies of the outcome of a second dose of MMR in
children who developed thrombocytopenia after a first dose.33
• Children with a personal or close family history of seizures or convulsions
3.11 Measles
should be given MMR or MMRV vaccine, provided the parents understand
that there may be a febrile response 5 to 12 days after vaccination.23 Advice
for reducing fever with paracetamol and other measures should be given.
Specialist advice should be sought rather than refusing to provide MMR or
MMRV vaccination.
• Measles virus inhibits the response to tuberculin, so tuberculin-positive
individuals may become tuberculin-negative for up to a month after measles
infection or administration of measles-containing vaccines.23 Mantoux testing
is therefore unreliable for at least 4 weeks after the administration of MMR
or MMRV. As measles infection may cause exacerbation of tuberculosis,
there is a theoretical concern that measles-containing vaccine may exacerbate
tuberculosis. Patients with tuberculosis should be under treatment when
vaccinated.
• Children with egg allergy, even anaphylactic egg allergy, can be safely given
MMR or MMRV vaccine.2,34 Skin testing has been shown to be of no value
in the management of these cases.2 Although measles and mumps (but not
rubella or varicella) vaccine viruses are grown in chick embryo tissue cultures,
Measles 207
it is now recognised that MMR (and MMRV) vaccine contains negligible
amounts of egg protein (see ‘Variations from product information’ below).
• MMR and MMRV vaccines can be administered to susceptible children who
have mild illnesses (eg. diarrhoea or upper respiratory infection), with or
without low-grade fever (<38.5°C).
Adverse events
(If using MMRV vaccine, additional adverse events relating to the varicella
vaccine component are outlined in Chapter 3.24, Varicella.)
• Malaise, fever and/or a rash may occur after MMR vaccination, most
commonly 7 to 10 days (range 5–12 days) after vaccination and lasting about
2 to 3 days. High fever (>39.4°C) occurs in approximately 5 to 15% (common
to very common), and rash occurs in approximately 5% (common) of MMR
vaccinees.1,23 The risk for febrile seizures is approximately 1 case per 3000
doses of MMR vaccine administered.23 Slightly higher rates of fever were
observed in clinical trials of MMRV vaccines, as compared with giving MMR
and monovalent varicella vaccine at the same time but at separate sites.24,25
• A varicelliform rash may occur after vaccination with MMRV (see Chapter
3.24, Varicella ‘Adverse events’). The appearance of a rash after monovalent
varicella vaccine occurs in <5% (common) of vaccinees, and similar rates are
observed with the use of MMRV.35
• Adverse events are much less common after the second dose of MMR and
MMRV than after the first dose.
• Anaphylaxis following the administration of MMR is very rare (less than
1 in 1 million doses distributed).23 Although no cases of anaphylaxis were
reported in MMRV clinical trials, the incidence is likely to be similar to
that occurring with use of MMR. Anaphylaxis after vaccination is likely
due to gelatin or neomycin anaphylactic sensitivity, not egg allergies (see
‘Precautions’ above).
• It is uncertain whether encephalopathy occurs after measles vaccination. If it
does, it is at least 1000 times less frequent than as a complication from natural
infection.1,23
• Other rare adverse events attributed to MMR vaccine include transient
lymphadenopathy and arthralgia (see Chapter 3.19, Rubella). Parotitis has
been reported rarely.23
• Thrombocytopenia (usually self-limiting) has been very rarely associated
with the rubella or measles component of MMR occurring in 3 to 5 per
100 000 doses of MMR vaccine administered.2,23,32,33 This is considerably less
than after natural measles, mumps and rubella infections33 (see also Chapter
3.19, Rubella). Any association with MMRV vaccine is expected to be similar.

• It is recommended that parents/vaccine recipients be advised about
possible symptoms, and given advice for reducing fever, including the use
of paracetamol for fever in the period 5 to 12 days after vaccination. The use
of aspirin after MMRV vaccination is not recommended for 6 weeks (see
Chapter 3.24, Varicella).
• It had been hypothesised that the measles component of the MMR vaccine
may be causally linked with autism, autistic spectrum disorder and
inflammatory bowel disease.36 There has been no credible scientific evidence
to support this claim. Most proponents of the hypothesis have retracted
this claim37 and there is now good evidence to refute it38 (see Appendix 5,
Commonly asked questions about vaccination).
Transmissibility of MMR vaccine viruses

Measles, mumps and rubella vaccine viruses are not transmissible to contacts.23
It is, therefore, safe to vaccinate the healthy siblings of children with impaired
immunity and safe for children with impaired immunity to go to school with
children recently vaccinated with the MMR vaccine. If using MMRV, see Chapter
3.24, Varicella for information about varicella vaccine virus transmission.
The public health management of measles

(i) Definition of a person who is considered not susceptible to measles
A person is considered not susceptible to measles if he/she meets 1 of the
following criteria:
• born during or since 1966 with documented evidence of receiving 2 doses of a
measles-containing vaccine, with both doses of vaccine having been given at
3.11 Measles
≥12 months of age and at least 4 weeks apart. This applies unless serological
evidence indicates otherwise,
• born before 1966 (unless serological evidence indicates otherwise),
• documented evidence of immunity,
• documented evidence of laboratory confirmed measles infection.
NB. These criteria have been revised since publication of the Guidelines for the
control of measles outbreaks in Australia in 2000.39
(ii) Vaccination of measles contacts

As vaccine-induced measles antibody develops more rapidly than that after
natural infection, MMR vaccine can be used to protect susceptible contacts.23 The
incubation period of the vaccine strain (4 to 6 days) is shorter than the incubation
period of wild measles virus (10 to 14 days). To be effective, the vaccine must
be administered within 72 hours of exposure. If there is doubt about a person’s
immunity, vaccine should be given, since there are no ill effects from vaccinating
individuals who are already immune. It must be noted that antibody responses
Measles 209
to the rubella and mumps components are too slow for effective use of vaccine
as prophylaxis after exposure to these infections. Alternatively, MMRV vaccine,
when available, could also be used in this setting if varicella vaccination
is indicated. However, there are no data on the use of MMRV vaccines in
individuals >12 years of age.
Immunoglobulin is available for contacts for whom measles-containing vaccine
is contraindicated (see ‘Use of immunoglobulin to prevent measles’ below), for
infants aged 6–9 months, and for susceptible individuals who did not receive a
measles-containing vaccine within 72 hours of contact (see Table 3.11.1 below).
Isolation of susceptible close contacts by exclusion from school or the workplace
should occur until 14 days after their last exposure39 unless they receive either
the MMR vaccine within 72 hours or immunoglobulin within 7 days of their first
exposure. If they do not receive MMR vaccine or immunoglobulin within these
specified timeframes, they should be excluded.
(iii) Vaccination during an outbreak

During a confirmed measles outbreak, MMR vaccine may be given (on the
direction of public health authorities) to infants between 9 and 12 months of age,
and even to those between 6 and 9 months of age.39 In these cases, another dose of
MMR (or MMRV when available) should be given at 12 months of age or 4 weeks
after the first dose, whichever is later. This should be followed by the routine
administration of the next dose of measles-containing vaccine at 18 months of
age. This is because maternal antibodies to measles are known to persist in many
infants until 11 months of age and may interfere with active immunisation before
12 months of age.1
Children between 12 and 18 months of age who have received 1 dose of measles-
containing vaccine can be offered their second dose early (ie. at least 4 weeks
after the first dose) if they are considered at risk of coming in contact with
measles39 (see ‘Recommendations (i)’ above). If a child receives the second dose
early, he/she is considered to have completed the vaccination schedule and,
therefore, does not require another dose at 18 months of age or beyond, provided
2 doses were given at ≥12 months of age and at least 4 weeks apart.
Any older children, adolescents or adults who are considered susceptible to measles
(see (i) above) during an outbreak should receive MMR (or MMRV if appropriate).
(iv) Use of immunoglobulin to prevent measles

Normal human immunoglobulin (NHIG) should be considered for contacts of
patients with confirmed or suspected measles39 (see Table 3.11.1). If NHIG is
administered by IM injection within 7 days of exposure, it can prevent or modify
measles in non-immune individuals.
The dose of NHIG is 0.2 mL/kg by deep IM injection for healthy children,
adolescents and adults (including pregnant women), and 0.5 mL/kg by deep IM
injection for people with impaired immunity. The maximum dose is 15 mL.

NHIG should be given to exposed individuals if contact was within the previous
7 days in the following instances:
• infants <6 months of age where the infant’s mother is the measles case, or the
infant was born before 28 weeks’ gestation,
• infants 6–9 months of age (see ‘Vaccination during an outbreak’ above),
• all those ≥9 months of age in whom administration of MMR vaccine would
be contraindicated,
• non-immune pregnant women,
• those exposed to measles who have impaired immunity,
• those who have never received a measles-containing vaccine, and who did
not receive a MMR or MMRV vaccine within 72 hours of contact.
Children with impaired immunity, where MMR is contraindicated, should be

given NHIG as soon as possible (within 7 days) after exposure. Testing for measles
antibody does not assist with the decision to use immunoglobulin, since neither
previous vaccination nor demonstrated low-level serum antibody guarantees
immunity to measles in individuals with significantly impaired immunity.23,39
Testing for measles antibody may delay the appropriate use of NHIG. However,
testing may be of value in making a definitive diagnosis of measles.
Infants 6–9 months of age who have direct contact with a person with measles
are at risk of developing complications from the disease, and should be
offered NHIG within 7 days of contact.39 MMR vaccine should then be given
as close as possible to 12 months of age, after an interval of at least 5 months
following the administration of immunoglobulin (see Chapter 2.3, Groups with
3.11 Measles
special vaccination requirements, Table 2.3.5 Recommended intervals between either
immunoglobulins or blood products and MMR, MMRV or varicella vaccination). NHIG
is not usually given to babies <6 months of age, who are protected by passive
maternal antibodies. However, if the mother of an infant <6 months of age does
not have documented evidence of having received 2 doses of MMR, or is the
measles case, the infant should be given NHIG. Similarly, premature infants
(<28 weeks’ gestation) have little or no acquisition of transplacental maternal
antibody, irrespective of the number of doses of MMR the mother has received,
and should also be offered NHIG (see Table 3.11.1).
Measles 211
Table 3.11.1: Management of significant measles exposure using vaccination or
normal human immunoglobulin (NHIG)
Age Action
<6 months NHIG 0.2 mL/kg* IM injection if mother has not received
2 documented doses of MMR, or the mother is the measles
case, or the infant was premature (<28 weeks’ gestation)
≥6–≤9 months NHIG 0.2 mL/kg IM injection*
≥10 months MMR or MMRV vaccine within 72 hours of exposure OR NHIG

0.2 mL/kg IM injection* if 3–7 days after exposure†
* The dose of NHIG is 0.2 mL/kg in immunocompetent individuals and 0.5 mL/kg in those

with impaired immunity.
† Immunoglobulin is not required if the person has received at least 1 measles-containing
vaccine at ≥12 months of age or is assessed as being not susceptible (see (i) ‘Definition of a
person who is considered not susceptible to measles’ above), unless the person has impaired
immunity.
Use in pregnancy
MMR vaccine is not recommended in pregnancy due to the theoretical risk of
transmission of the rubella component of the vaccine to a susceptible fetus.
Pregnancy should be avoided for 28 days after vaccination30 (see Chapter 3.19,
Rubella and Chapter 2.3, Groups with special vaccination requirements, Table 2.3.1
Vaccinations in pregnancy).

The product information recommends that women of child-bearing age should
be advised not to become pregnant for 3 months after vaccination with MMR or
MMRV vaccines, whereas the NHMRC recommends 28 days.30
The product information for Priorix states that people with a history of
anaphylactic or anaphylactoid reactions should not be vaccinated with Priorix,
but it is established that MMR vaccine can be given in this situation.23
References

3.12 Meningococcal disease
Bacteriology
Meningococcal disease is caused by the bacterium Neisseria meningitidis
(N. meningitidis or the meningococcus), a Gram-negative diplococcus. There are
13 known serogroups distinguished by differences in surface polysaccharides of
the outer membrane capsule. Meningococcal serogroups are designated by letters
of the alphabet. Globally, serogroups A, B, C, W135 and Y most commonly cause
disease. Meningococci can be further differentiated by differences in their outer
membrane proteins, which are referred to as serotypes and serosubtypes.1 More
recently, molecular typing has been used to further differentiate meningococci.
In Australia, serogroups B and C occur most frequently. There is no consistent
relationship between serogroup or type and virulence.2,3
Clinical features
Neisseria meningitidis can cause meningitis, septicaemia or a combination of the
two. Other localised infections, including pneumonia, arthritis and conjunctivitis,
may also occur but are uncommon. Septicaemia, with or without meningitis,
can be particularly severe. The overall mortality risk is high (about 10%) despite
appropriate antibiotic therapy.
N. meningitidis is carried and transmitted only by humans. There are no known
animal reservoirs. Asymptomatic respiratory tract carriage of meningococci is
present in about 10% of the population, and the prevalence may be higher when
groups of people occupy small areas of living space.2-8 Recent studies indicate
that there may be a number of factors which contribute to the increased risk
of contracting meningococcal disease, including exposure to smokers, recent
illness, living in crowded conditions and multiple intimate kissing partners.4-8
People with inherited disorders of phagocytosis associated with properdin
deficiency or absence of the terminal components of complement, as well as
individuals with functional or anatomical asplenia, have an increased risk of
meningococcal infection.1
The disease is transmitted via respiratory droplets, and has an incubation
period of between 1 and 10 days, but commonly 3 to 4 days.4 The capacity of
3.12 Meningococcal
meningococcal disease to have a fulminant and rapidly fatal course in previously

healthy (and usually young) individuals causes it to be greatly feared. Intensive
disease
public health follow-up is required after each single case to conduct contact
tracing and to institute appropriate public health measures for contacts. As a
result of all these factors, this disease causes widespread community alarm and
generates significant media interest.9
Meningococcal disease 213

Epidemiology
Meningococci cause both sporadic and epidemic disease throughout the world.
Serogroup A disease occurs predominantly in developing populations such
as those in Africa and Asia, while serogroup B is the major cause of sporadic
meningococcal disease in most developed countries. Serogroup C disease has a
more cyclic pattern of occurrence, and increased in incidence in the 1990s in some
developed countries such as Australia and the United Kingdom.4 Serogroup
C meningococci have also been occasionally associated with small clusters of
meningococcal disease cases in schools, universities and nightclubs in Australia
over the past 10 years.10-15
As in other temperate climates, meningococcal disease cases occurring
in Australia tend to follow a seasonal trend, the majority of cases being
reported during late winter and early spring. The overall notification rate of
meningococcal disease to the National Notifiable Diseases Surveillance System
increased gradually from 1.8 per 100 000 in 1991, to a peak of 3.5 per 100 000 in
2001, but declined to 1.8 per 100 000 in 2005.16 There are considerable differences
noted in the incidence of meningococcal disease between States and Territories,
with 5.4 cases per 100 000 notified from the Northern Territory to 1.9 per 100 000
reported for Queensland during 2005.16 These figures include meningococcal
disease cases which were diagnosed on clinical grounds alone, and those cases
that were confirmed by laboratory methods such as culture, serology or nucleic
acid testing of clinical material. In 2005, 369 cases were reported nationally, of
which 345 were laboratory confirmed.16,17 The majority of laboratory-confirmed
meningococcal cases were serogroup B (73%) and serogroup C (14.5%).17 There
has been a steady decline in serogroup C meningococcal disease among the
0–18 years age group since the 2003 introduction of routine meningococcal C
vaccination and catch-up programs in this age group.18
Meningococcal disease can occur in any age group, but the majority of cases
occur in those <5 years of age, with a secondary peak seen in the 15–24 years
age group. In Australia, meningococcal disease in the <5 years age group is
due predominantly to infection with serogroup B meningococci; very few cases
of serogroup C meningococcal disease are now seen in this age group.17 In the
15–19 years age group, both serogroup B and C disease were seen before the
introduction of the meningococcal C conjugate vaccine in 2003.
In contrast to Australia, New Zealand has, over the past 14 years, experienced
an epidemic of meningococcal disease which has been almost exclusively
associated with a particular strain of serogroup B (B:4:P1.7b,4).19,20 Meningococcal
disease rates in NZ rose from 1.5 cases per 100 000 during 1989–1990 to 14.5
cases per 100 000 in 2003.19 A meningococcal B outer membrane vesicle vaccine
(MeNZB™), currently being used in New Zealand, is only effective against the
serotype and serosubtype of the New Zealand serogroup B strain and is not
available in Australia.20

Vaccines
There are 2 different types of meningococcal vaccine: the meningococcal C
conjugate vaccines (MenCCV) and the tetravalent meningococcal polysaccharide
vaccines (4vMenPV). The differences between these 2 types of vaccines lie in the
different way that each vaccine stimulates an immune response.
Other than the New Zealand specific vaccine, there is currently no vaccine
effective against serogroup B meningococcal disease although extensive research
is being undertaken in this area.
CONJUGATE VACCINES
Meningococcal C conjugate vaccines (MenCCV)
• Meningitec – Wyeth Australia Pty Ltd (meningococcal serogroup

C–CRM197 conjugate vaccine). Each 0.5 mL monodose vial contains 10 µg
N. meningitidis serogroup C oligosaccharide conjugated to approximately
15 µg of a non-toxic Corynebacterium diphtheriae CRM197 protein;
aluminium phosphate.
• Menjugate Syringe – CSL Biotherapies/Novartis Vaccines (meningococcal

serogroup C–CRM197 conjugate vaccine). Lyophilised powder in a monodose
vial with a pre-filled diluent syringe. Each 0.5 mL dose of reconstituted
vaccine contains 10 µg N. meningitidis serogroup C polysaccharide conjugated
to 12.5–25 µg of a non-toxic Corynebacterium diphtheriae CRM197 protein; 1.0 mg
aluminium hydroxide. 5 or 10 monodose packs also available.
• NeisVac-C – Baxter Healthcare (meningococcal serogroup C–tetanus toxoid

protein conjugate vaccine). Each 0.5 mL pre-filled syringe contains 10 µg
N. meningitidis serogroup C polysaccharide conjugated to 10–20 µg of
tetanus toxoid protein; 0.5 mg aluminium hydroxide. 10 or 20 monodose
packs available.
In January 2003, the Australian Government commenced the National

Meningococcal C Vaccination Program which provided free MenCCV to all children
who turned 1 to 19 years of age during 2003. MenCCV was also added to the
National Immunisation Program (NIP) schedule at 12 months of age at that time.
3.12 Meningococcal
MenCCVs confer protection only against serogroup C disease. In these vaccines,

an oligo- or polysaccharide antigen is chemically linked (ie. ‘conjugated’) to a
disease
carrier protein. Conjugation changes the nature of the antibody response from
a T cell-independent to a T cell-dependent response. The T cell help results in
improved antibody responses, especially in young children, greater functional
activity, and induction of immunological memory, probably resulting in long-
term protection.

In the United Kingdom, 98 to 100% of infants given 3 doses of MenCCV in
a 2, 3 and 4 month schedule developed protective antibody titres after the
third dose,21,22 but evidence of waning immunity and vaccine failures led to a
booster dose being recommended for children vaccinated according to the 2,
3 and 4 month schedule of MenCCV,23 which has now been altered to a 3-dose
schedule at 3, 4 and 12 months of age.24 In Australia, although some children
have received MenCCV before 12 months of age, this was according to a 2, 4,
6 month schedule and there is no evidence of vaccine failure. NHMRC, therefore,
does not recommend recall for a booster dose in children previously vaccinated
before 12 months of age (unless they have inherited defects of properdin or
complement, or functional or anatomical asplenia – see ‘Recommendations’
below).
In children >12 months of age, a single dose of MenCCV appears sufficient to
induce protective antibody responses. In children 12–18 months of age receiving
a single dose of MenCCV, 91 to 100% achieved serum bactericidal antibodies
(SBA) titres ≥1:8.25 In older children, seroconversion rates increase with age: 96%
of 3-year-olds, 98% of 4–5-year-olds, and 98% of 14–17-year-olds achieved SBA
titres ≥1:8 after a single dose.25 In those children aged ≥1 year who have received
only a single dose of the meningococcal C conjugate vaccine, the duration of
immunity and the need for booster doses is not yet known. The Netherlands
routinely vaccinates with MenCCV at 14 months of age, and data from 2002
onwards currently indicates that vaccination after the 1st birthday results in
longer protection than multiple doses in infancy.26
POLYSACCHARIDE VACCINES
Meningococcal polysaccharide vaccines (4vMenPV)
• Mencevax ACWY – GlaxoSmithKline (serogroup A, C, W135 and Y

meningococcal polysaccharide vaccine). Each 0.5 mL monodose of the
reconstituted lyophilised vaccine contains 50 µg of each polysaccharide;
lactose. 10-dose vials in packs of 50 contain 0.25% phenol as a preservative.
Saline diluent for each vial.
• Menomune – Sanofi Pasteur Pty Ltd (serogroup A, C, W135 and Y

meningococcal polysaccharide vaccine). Each 0.5 mL monodose
of the reconstituted lyophilised vaccine contains 50 µg of each
polysaccharide; lactose.
4vMenPVs provide protection against serogroups A, C, W135 and Y. The

vaccine induces antibodies in 10 to 14 days in 90% of recipients >2 years of age.
Immunity decreases markedly during the first 3 years following a single dose of
vaccine, particularly in infants and young children. However, clinical protection
persists for at least 3 years in school children and adults.

The duration of immunity is further complicated by the induction of
immunological hyporesponsiveness to the serogroup C component following
repeated vaccination with 4vMenPV, as revaccination results in a reduced
antibody response compared with the primary immunisation.27 This
phenomenon has been noted in both children and adults.28-31 The demonstration
of subsequent hyporesponsiveness has led to the concern that vaccinating low-
risk individuals may reduce the effectiveness of revaccination in a subsequent
high-risk situation, although this has not been clinically demonstrated. This
hyporesponsiveness can be overcome with MenCCV, although additional doses
of the conjugate vaccine may be required in young children.32,33 There is little
response to the serogroup C component of the 4vMenPV before 18 months of age
and little response to serogroup A before 3 months of age.34,35

Meningococcal C conjugate vaccines
Transport according to National Vaccine Storage Guidelines: Strive for 5.36 Storage of
all MenCCVs should be at +2°C to +8°C. Do not freeze. Protect from light.
The product information for NeisVac-C states that this vaccine can be stored at
+25°C for a period of up to 9 months but must not be returned to the refrigerator.
Meningococcal polysaccharide vaccines

+2°C to +8°C. Do not freeze. Protect from light. Reconstituted vaccine should
be used immediately but may be stored in the refrigerator at +2°C to +8°C, and
must be discarded if not used within 8 hours.

The MenCCV dose is 0.5 mL given by IM injection. Do not mix MenCCV with
other vaccines in the same syringe. Experience from the use of the conjugate Hib
vaccines suggests that the different brands of the MenCCVs are interchangeable.
MenCCVs may be administered simultaneously with other vaccines in the NIP
(see ‘Variations from product information’ below). MenCCVs are registered for
use in Australia from 6 weeks of age.
3.12 Meningococcal

The 4vMenPV dose is 0.5 mL, administered by SC injection. 4vMenPVs are
disease
approved for use in Australia in children ≥2 years of age, adolescents and adults.
Administration of MenCCV after administration of 4vMenPV

There are limited data available on the length of time that should lapse before
administration of MenCCV after giving 4vMenPV. The NHMRC recommends a
period of 6 months before the conjugate vaccine is given.21,37

Administration of 4vMenPV after administration of MenCCV
On occasion, both MenCCV and 4vMenPV are recommended (eg. asplenia). If
MenCCV is given first, a period of ≥2 weeks should lapse before 4vMenPV is given.
Recommendations
(i) Routine vaccination
It is recommended that a single dose be given to all children at the age of
12 months.
Vaccination before 12 months of age is not recommended, except in infants
with inherited defects of properdin or complement, or functional or anatomical
asplenia (see (ii) below). Infants, other than those described in the circumstances
below, who receive dose(s) of vaccine at <12 months of age, should be given
a further dose at 12 months of age or 4 weeks after the last dose, whichever is
later. However, it is not necessary to recall older children who received 3 doses
of MenCCV before 12 months of age, as there has been no evidence to date of
vaccine failure in infants vaccinated according to a 2, 4, 6 month schedule (see
‘Vaccines’ above).
(ii) Vaccination of people at high risk for meningococcal disease

The vaccine is also recommended for:
• close (household or household-like) contacts of meningococcal disease
cases due to serogroup C, >2 months of age, who have not previously been
vaccinated (refer to ‘The early clinical and public health management of
meningococcal disease’ below),
• control of outbreaks caused by serogroup C (refer to ‘The early clinical and
public health management of meningococcal disease’ below),
• laboratory personnel who frequently handle N. meningitidis, who should also
receive 4vMenPV,
• those >6 weeks of age with inherited defects of properdin or complement,
or functional or anatomical asplenia. When MenCCV is given to these
individuals at <12 months of age, in addition to a booster dose of MenCCV at
12 months of age, a dose of 4vMenPV is recommended at ≥2 years of age.
Under the circumstances as described above, a child under the recommended age
of 12 months requiring vaccination should receive doses as follows:
• Infants <6 months of age require 2 doses of 0.5 mL, given at least 8 weeks
apart, followed by a booster dose at 12 months of age.
• Children 6–11 months of age require 1 dose of 0.5 mL, followed by a booster
dose at 12 months of age or 8 weeks after the first dose, whichever is later.

Routine vaccination with 4vMenPV is not recommended. However, it is
recommended in the following situations:
• people who intend travelling to parts of the world where epidemics of group
A, W135 or Y disease are frequent (a current list of those countries is available
from the World Health Organization at either http://www.who.int/ith or
http://www.who.int/disease-outbreak-news/),
• close (household or household-like) contacts, ≥2 years of age, of cases of
serogroup A, W135 or Y meningococcal disease,
• control of outbreaks caused by serogroup A, W135 or Y. A Cochrane review
examined the use of polysaccharide vaccine for the prevention of serogroup
A meningococcal meningitis. The review assessed 8 randomised controlled
trials and the protective effect from the vaccine was consistent across all the
trials with a vaccine efficacy of around 95%,38
• laboratory personnel who frequently handle N. meningitidis, who should also
receive MenCCV,
• those ≥2 years of age with inherited defects of properdin or complement, or
functional or anatomical asplenia, who should also receive MenCCV, and
• pilgrims attending the annual Hajj (Saudi Arabian authorities require a valid
certificate of vaccination as a condition to enter the country).
A single revaccination with 4vMenPV is indicated for people at continued high

risk of infection (such as those living in epidemic areas, and those with impaired
immunity as defined above), particularly children first vaccinated before 4 years
of age. As antibody levels decline rapidly over 2 to 3 years, revaccination
should be given 3 to 5 years later. Data regarding the benefit of subsequent
revaccinations with 4vMenPV are unavailable at this time.
Contraindications
The only absolute contraindications to MenCCV are:
• anaphylaxis following a previous dose, or
• anaphylaxis following any component of the vaccine
3.12 Meningococcal
Previous serogroup C disease is not a contraindication to administration of

MenCCV.
disease

The only absolute contraindications to 4vMenPV are:
• anaphylaxis following any vaccine component.

Adverse events
Very common (>10%) adverse events caused by MenCCVs are pain, redness
and swelling at the site of injection, fever, irritability, anorexia and headaches.
There are some age-related differences in the type of adverse event following
vaccination, with systemic adverse events tending to decrease with increasing
age, and local adverse events tending to increase with increasing age. Headache
is more likely to be reported in the adolescent age group. Serious general adverse
events are rare.37

Local reactions to 4vMenPV include erythema, induration, tenderness, pain and
local axillary lymphadenopathy. However, they are usually mild and infrequent.
Fever and chills occur in approximately 2% (common) of young children, and
may persist for 48 hours or longer, but significant general adverse events are rare.
The early clinical and public health

management of meningococcal disease
Prompt diagnosis and emergency treatment of cases of suspected meningococcal
disease are life-saving. If a diagnosis of meningococcal disease is suspected,
the patient should be immediately given parenteral (usually IM) penicillin and
transferred to hospital. The relevant Public Health Unit must be contacted as
soon as possible.4
Table 3.12.1: Early clinical management of suspected meningococcal disease

The patient should Age <1 year 300 mg benzylpenicillin
receive immediate
benzylpenicillin Age 1–9 years 600 mg benzylpenicillin
(usually IM). Age ≥10 years 1200 mg benzylpenicillin
The patient should be transferred to hospital urgently.
The relevant Public Health Unit should be notified promptly, so that
appropriate public health management can be initiated.
Guidance on the early clinical and public health management of

cases of invasive meningococcal disease has been developed by the
Communicable Diseases Network of Australia, and is available at
http://www.health.gov.au/pubhlth/cdi/pubs/pdf/mening_guide.pdf.4
Contrary to popular belief, a patient with meningococcal disease is not a good
transmitter of the disease. Rather, it is carrier(s) passing on the bacteria to other
susceptible individuals who may cause further cases of meningococcal disease.
Further cases may develop in household contacts in particular. The risk of
secondary cases is greatest in the first 7 days, and may persist for many weeks
after contact. The public health management of close contacts includes

information, clearance antibiotics and vaccination. Clearance antibiotics should
be offered to all identified close contacts regardless of previous vaccination
history. Clearance antibiotics are not recommended for healthcare workers unless
they were engaged in either mouth-to-mouth resuscitation or were not wearing a
mask while intubating a case.
Non-vaccinated close contacts of a proven vaccine-preventable strain of invasive
meningococcal disease should be advised in writing by their local Public Health
Unit to visit their usual healthcare provider at the next available opportunity to
receive the appropriate vaccine.4
Antibiotics that reduce or eliminate nasopharyngeal carriage of N. meningitidis
include ceftriaxone, ciprofloxacin and rifampicin.
• Ceftriaxone is administered as a single IM dose of 250 mg for adults and
125 mg for children <12 years of age. Although it is considerably more
expensive, ceftriaxone has a number of advantages over rifampicin: it is
more likely to eradicate pharyngeal carriage, it eliminates problems with
compliance and it is the preferred chemoprophylaxis for pregnant women.
• Ciprofloxacin in a single oral dose of 500 mg is effective and safe, but it
should not be given to children <12 years of age, or to pregnant women.
• Rifampicin is given to children and adults in an oral dose of 10 mg/kg
(maximum dose of 600 mg) twice daily for 2 days. The recommended dose
for infants <1 month of age is 5 mg/kg twice daily for 2 days. Pharyngeal
carriage will be eliminated in 75 to 90% of recipients unless the strain is
resistant to rifampicin. The side effects of rifampicin should be explained,
including orange-red discolouration of contact lenses, urine and tears,
possible interference with the contraceptive pill, and interference with the
metabolism of many other drugs including warfarin, phenobarbitone and
phenytoin. Rifampicin is not recommended for use in pregnant women.
A potential outbreak of meningococcal disease in an institutional or community

setting is a public health emergency needing a rapid response from clinicians
and public health practitioners. The decision to control an outbreak with a
vaccination program should be made by the appropriate Public Health Unit,
following the Guidelines for the early clinical and public health management of
meningococcal disease in Australia.4 If vaccination is indicated and the organism
3.12 Meningococcal
responsible is serogroup C, MenCCV should be used in preference to 4vMenPV.
Use in pregnancy
disease

Although no clinical study data are available on the use of MenCCV in pregnant
women, it is unlikely that it would have any deleterious effect on the pregnancy.
Routine pregnancy testing before vaccination is not justified.

Studies of vaccination with meningococcal and other polysaccharide vaccines
during pregnancy have not documented adverse events in either pregnant
women or newborns.1,39,40 The number of pregnant vaccinees who received
4vMenPV as reported in the literature is small. A North American study of
109 women who received the 4vMenPV vaccine between 30 and 38 weeks’
gestation reported no birth defects.39 A further study of 34 pregnant women in
the US who received 4vMenPV during their second and third trimester revealed
no teratogenicity and the infants were assessed for 2 years after birth. No
developmental abnormalities were detected.40

The product information for meningococcal C conjugate vaccines state
that, under the age of 12 months, either 2 (NeisVac-C) or 3 (Meningitec and
Menjugate) doses of vaccine are required. The NHMRC recommends that
meningococcal C vaccination is not required before 12 months of age (unless
specifically indicated).
The NeisVac-C product information states that the vaccine should not be
administered with pneumococcal conjugate vaccine, hepatitis B vaccine
and PRP-OMP Haemophilus influenzae type b vaccine unless ‘medically
important’. However, the NHMRC states that the vaccine may be administered
simultaneously with other vaccines in the NIP. There have been recent
publications citing the coadministration of MenCCV with other combination
vaccines and it was found to be immunogenic and safe.41,42
The product information for all 3 conjugate vaccines states that there are no data
on the use of MenCCVs in lactating women, whereas the NHMRC does not
consider breastfeeding in a healthy woman a reason for not vaccinating.
The Meningitec product information states that an allergic reaction following
a previous dose is a contraindication to further doses, whereas the NHMRC
states that only an anaphylactic adverse event following a previous dose is a
contraindication.

The NHMRC recommends revaccination with 4vMenPV within 3 to 5 years
of a previous dose in the situations detailed in ‘Recommendations’ above.
The Mencevax ACWY product information states within 2 to 3 years, and
the Menomune product information gives no recommended interval before
revaccination.
References

3.13 Mumps
Virology
3.13 Mumps
Mumps is a paramyxovirus, genus Rubulavirus, with a single-stranded RNA
genome. It is rapidly inactivated by heat, formalin, ether, chloroform and
ultraviolet light.1
Clinical features
Mumps is an acute viral illness with an incubation period of 14 to 25 days.2
Asymptomatic infection occurs in one-third of cases.3 Symptomatic disease
ranges from mild upper respiratory symptoms to widespread systemic
involvement.3 A high proportion of mumps infections involve non-specific
symptoms including fever, headache, malaise, myalgia and anorexia.4 The
characteristic bilateral, or occasionally unilateral, parotid swelling occurs in 60
to 70% of clinical cases.4 Benign meningeal signs appear in up to 15% of cases,
but permanent sequelae are rare. Nerve deafness is one of the most serious of the
rare complications (1 in 500 hospitalised cases). Orchitis (usually unilateral) has
been reported in up to 20% of clinical mumps cases in post-pubertal males, but
subsequent sterility is rare. Symptomatic involvement of other glands and organs
has been observed less frequently (pancreatitis, oophoritis, hepatitis, myocarditis,
thyroiditis, mastitis).1,4 Patients may be infectious from 6 days before parotid
swelling to 9 days after.2 Mumps encephalitis has been reported to range as high
as 1 in 200 cases, with a case-fatality rate of around 1.0%.
Mumps infection during the first trimester of pregnancy may result in
spontaneous abortion.3,4 Maternal infection is not associated with an increased
risk of congenital malformation.3,4
Epidemiology
Mumps is reported worldwide, and is a human disease. Transmission is by
the respiratory route in the form of air-borne droplets or by direct contact with
saliva or possibly urine.2 Before universal vaccination, mumps was primarily
a disease of childhood, the peak incidence being in the 5–9 year age group.
However, since 2000, peak rates have been reported in older adolescents and
young adults, especially the 20–24 year age group.5-7 Between 2001 and 2005, the
average notification rate for mumps in Australia was 0.6 per 100 000.8 There have
been recent outbreaks of mumps in the USA, and also in the United Kingdom,
where the peak rates of disease have been in the 18–24 year age group.9,10
Approximately 2000 cases were reported in the USA in a 2006 outbreak, parotitis
being reported in 66% of clinical cases.11 Mumps attack rates in outbreaks are
lowest in individuals who have received 2 doses of mumps-containing vaccines,
as this provides optimal long-term protection.10,11 In Australia, over the 10-year
Mumps 223
period from 1996 to 2005, mumps has been reported as the underlying cause of
death in 4 subjects, all adults aged over 80 years.5-7
Vaccines
Monovalent mumps vaccine is no longer available in Australia. Mumps
vaccination is provided using either MMR vaccine or MMRV vaccine when
available.
Clinical trials of mumps vaccine indicate 95% seroconversion after a single dose
of MMR.4 However, outbreak investigations and post-marketing studies have
reported 1-dose vaccine effectiveness to be between 60 and 90%.10 Protection
is greater in 2-dose vaccine recipients, who have seroconversion rates of up to
100%.4,10,12


+2°C to +8°C. Protect from light. Do not freeze. Reconstituted vaccine should be
used immediately, but can be stored at +2°C to +8°C for up to 8 hours before use.

For both children and adults, the dose of MMR is 0.5 mL, administered by either
SC or IM injection.
MMR can be given at the same time as other vaccines (including DTPa, hepatitis
B, MenCCV and varicella), using separate syringes and injection sites. If MMR is
not given simultaneously with other live viral parenteral vaccines (eg. varicella
vaccine), they should be given at least 4 weeks apart (see ‘Precautions’ below).
Recommendations
All children should receive 2 doses of MMR vaccine (or MMRV vaccine, when
available, if ≤12 years of age). Routine administration of MMR (or MMRV) is
now recommended at 12 months and 18 months of age in order to maximise
protection at an early age. The minimum interval between doses is 4 weeks.
In older individuals, who have received only 1 dose of mumps-containing
vaccine, a second dose can be given, as MMR, at any age.

For further information on the recommendations for MMR (and MMRV when
available) see Chapter 3.11, Measles and Chapter 3.24, Varicella.
Contraindications
3.13 Mumps
See information on MMR and MMRV vaccines in Chapter 3.11, Measles and
Chapter 3.24, Varicella.
Precautions
If MMR is not given simultaneously with other live viral parenteral vaccines (eg.
varicella vaccine), they should be given at least 4 weeks apart.
See further information on MMR and MMRV vaccines in Chapter 3.11, Measles
and Chapter 3.24, Varicella.
Adverse events
In Australia, vaccine-associated aseptic meningitis is not considered a problem.
Post-licensure surveillance of mumps vaccine recipients in Germany, over
a 2-year period, found no increase in cases of aseptic meningitis. However,
other estimates in countries using mumps vaccines with different vaccine
virus strains suggest 1 case occurs per 800 000–1 million doses.4,14 Vaccine-
associated meningoencephalitis is invariably mild or asymptomatic and resolves
spontaneously. When mumps virus is isolated from the cerebrospinal fluid in
such cases, laboratory tests can be undertaken to distinguish between wild and
vaccine strains. The assistance of State virology laboratories should be sought in
such cases.
Re-vaccination with mumps-containing vaccines is not associated with an
increased incidence of adverse events.
For further information on the adverse events associated with MMR and MMRV,
see Chapter 3.11, Measles and Chapter 3.24, Varicella.
Use of immunoglobulin to prevent mumps

Normal human immunoglobulin (NHIG) has not been shown to be of value
in post-exposure prophylaxis for mumps.1,15 Live mumps-containing vaccine
does not provide protection if given after an individual has been exposed to
mumps.1,15 However, if the exposure did not result in infection, the vaccine
would induce protection against subsequent infection.
Use in pregnancy
MMR vaccine is not recommended in pregnancy due to the theoretical risk
of transmission of the rubella component of the vaccine to a susceptible fetus
(see Chapter 3.19, Rubella). Pregnancy should be avoided for 28 days after
vaccination.16 Data on the use of MMRV vaccines in individuals >12 years of age
are not available.
Mumps 225
See information on MMR vaccines in Chapter 3.11, Measles.
References

3.14 Pertussis
Bacteriology
Pertussis (whooping cough) is caused by Bordetella pertussis, a fastidious, Gram-
negative, pleomorphic bacillus. There are other organisms (such as Bordetella
parapertussis, Mycoplasma pneumoniae and Chlamydia pneumoniae) which can cause
a pertussis-like syndrome.1 Identification of pertussis is limited by patient and
physician awareness and the limited sensitivity of diagnostic tests; it is generally
believed to be significantly under-diagnosed.
Clinical features
Pertussis is an epidemic respiratory infection with an incubation period of
7 to 20 days. In unvaccinated individuals, B. pertussis is highly infectious,
3.14 Pertussis
spreading by respiratory droplets to 80% of susceptible household contacts.2 The
characteristic paroxysmal cough with inspiratory whoop seen in unvaccinated
children is less common in older children and adults who have varying degrees
of immunity acquired from vaccination or infection. It has been estimated that
B. pertussis accounts for up to 7% of cough illness per year in adults and, each
year, more than 25% of adults experience a coughing illness of at least 5 days’
duration.2,3 Even in adults, pertussis can be associated with significant morbidity,
with cough persisting for up to 3 months, and other significant symptoms, such
as sleep disturbance or, rarely, rib fracture.4
Death due to pertussis is rare in people >10 years of age. However, the case
fatality rate in unvaccinated infants <6 months of age is estimated to be
0.8%.5,6 The most common cause of death in pertussis infection is pertussis
pneumonia, sometimes complicated by seizures and hypoxic encephalopathy.2
Both hospitalisations and deaths are likely to be under-estimated.7 In Australia
between 1993 and 2005, there were 18 deaths attributed to pertussis, all but 2 in
infants <12 months of age.8-11
Epidemiology
Epidemics occur every 3 to 4 years. In unvaccinated populations, these outbreaks
can be very large. In vaccinated populations, outbreaks are smaller, with greatly
reduced mortality and morbidity, and may continue to occur every 3 to 4 years or
be more widely spaced. Maternal antibody does not provide reliable protection
against pertussis, and the maximal risk of infection and severe morbidity is
before infants are old enough to have received at least 2 vaccine doses.7 In
recent years, among highly immunised communities, many cases of pertussis
in adults and adolescents, due to waning immunity, have been recognised due
to the increased availability of serological testing.6,12 These individuals are a
significant reservoir of infection. From 1993 to 2005, 4 epidemics of pertussis
Pertussis 227
occurred in Australia. A total of more than 84 000 cases was reported in this time,
an annual incidence of 22.8 to 57.4 cases per 100 000 population.13
Introduction of a fifth dose of diphtheria, tetanus and pertussis vaccine (DTP) for
4–5-year-old children in August 1994 was followed by a pattern of decrease in
notifications consistent with a vaccine effect, occurring first among children aged
5 and 6 years, followed by those in the 7–9-year age group.14,15 Subsequently, the
average age of those notified with pertussis has continued to increase.
In 2004–2005, more than 70% of pertussis notifications were in individuals
>15 years of age13,16 compared with 40 to 50% in the early 1990s. This supports
the need for booster doses in those >10 years of age, both to reduce individual
morbidity, and to reduce transmission to those most at risk (infants <6 months
of age).17 Vaccination of adolescents, who have a high risk of pertussis infection,
and adults in contact with very young infants, is expected to result in the greatest
health benefits. A single booster dose using an adolescent/adult formulation
acellular pertussis-containing vaccine (dTpa) has been included in the National
Immunisation Program (NIP) for 15–17-year-olds since January 2004.
Figure 3.14.1: Pertussis notifications by year of onset, Australia 1993–2005. The

percentage of notifications in those aged ≥15 years is shown (- -)

Vaccines
Acellular pertussis-containing vaccines have been used for both primary and
booster vaccination of children in Australia since 1999. There are a number
of acellular pertussis vaccines, which contain 3 or more purified components
of B. pertussis. In the 3 component vaccines, these are pertussis toxin (PT),
filamentous haemagglutinin (FHA) and pertactin (PRN). In the 5 component
vaccines, fimbrial antigens or agglutinogens are also included. Acellular pertussis
vaccines with 3 or more antigens have similar efficacy to good quality whole-
cell vaccines18 and are immunogenic and safe. Although serious adverse events
such as hypotonic-hyporesponsive episodes can still occur, they are much
less common than with whole-cell vaccines.18 Vaccines containing DTPa are
also available in various combinations with inactivated polio, hepatitis B and
Haemophilus influenzae type b vaccines.
3.14 Pertussis
The adolescent/adult formulation dTpa vaccines are immunogenic, safe and well
tolerated in adults.19-21
• Infanrix hexa – GlaxoSmithKline (DTPa-hepB-IPV-Hib; diphtheria-tetanus-

acellular pertussis-hepatitis B-inactivated poliomyelitis vaccine-Haemophilus
influenzae type b (Hib)). The vaccine consists of both a 0.5 mL pre-filled syringe
containing 30 IU diphtheria toxoid, 40 IU tetanus toxoid, 25 µg pertussis
toxoid (PT), 25 µg filamentous haemagglutinin (FHA), 8 µg pertactin (PRN),
10 µg recombinant HBsAg, 40 D-antigen units inactivated polioviruses type
1 (Mahoney), 8 D-antigen units type 2 (MEF-1) and 32 D-antigen units type 3
(Saukett) adsorbed onto aluminium hydroxide/phosphate; phenoxyethanol
as preservative; traces of formaldehyde, polymyxin and neomycin and a vial
containing a lyophilised pellet of 10 µg purified Hib capsular polysaccharide
(PRP) conjugated to 20–40 µg tetanus toxoid. The vaccine must be reconstituted
by adding the entire contents of the syringe to the vial and shaking until the
pellet is completely dissolved. May also contain yeast proteins.

Pertussis 229


streptomycin.




The dose of DTPa-combinations, dTpa and dTpa-IPV is 0.5 mL by IM injection.
Do not mix DTPa-containing vaccines with any other vaccine in the same
syringe, unless specifically registered for use in this way.
Recommendations
(i) Vaccination of children and adolescents
Acellular pertussis antigens are given in combination with diphtheria and
tetanus toxoids (DTPa) in a primary course of vaccination at 2, 4 and 6 months
3.14 Pertussis
of age. In view of the high morbidity and occasional mortality associated with
pertussis under the age of 6 months, receipt of the first dose of vaccine as soon
as possible after 2 months of age should be strongly emphasised. If the primary
course is interrupted, it should be resumed but not repeated; catch-up doses may
be given as little as 4 weeks apart. The same formulation of vaccine should be
used for each of the 3 doses. If it is not known which brand was used, vaccination
should be provided using any available brand.
For the booster dose of DTPa given at 4 years of age, all brands of DTPa-
containing vaccines are considered interchangeable. In view of the prolonged
immunity now known to result from a primary course of DTPa at 2, 4 and
6 months of age,23 the 18-month dose was omitted in 2003. It is expected that
postponing receipt of a fourth dose of DTPa until 4 years of age will reduce the
proportion of children experiencing extensive local reactions, which occurred in
2% of children following a fourth dose at 18 months of age.24,25
A second booster, between 12 and 17 years of age, using the adolescent/adult
formulation dTpa, is essential for maintaining immunity to pertussis through the
adolescent period and into early adulthood. By the age of 17 years, young adults
should have received 5 doses of a pertussis-containing vaccine. Most adolescents
would have either had at least 3 previous doses of a pertussis-containing vaccine
or been exposed to the pertussis bacterium. Therefore, if documentation of
previous vaccinations is not readily available, it can be safely assumed that a
dose of dTpa at 12–17 years is indeed a booster dose.

dTpa vaccines are recommended in Australia for booster vaccination of
individuals ≥8 years of age who have previously had a primary course of
Pertussis 231
diphtheria-tetanus-pertussis vaccine. dTpa vaccines have a lower content of
diphtheria and pertussis antigens than DTPa formulations for young children.
Primary vaccination
If a 3-dose primary course of diphtheria/tetanus toxoids is given to an
adolescent/adult without a previous history of having received pertussis-
containing vaccine, the preferred option is that dTpa replace the first dose of dT, to
provide pertussis immunity as early as possible,26 with subsequent doses as dT. In
the event that dT is not available, dTpa can be used for all primary doses, but this
is not routinely recommended as there are no data on the safety, immunogenicity
or efficacy of dTpa for primary vaccination. For detailed recommendations
regarding a primary dT course in adults, see Chapter 3.21, Tetanus.
Duration of protection and spacing of booster doses
A single booster dose of dTpa is recommended for the following groups
provided that no documented dTpa booster dose has been previously received:
• Adults planning a pregnancy, or for both parents as soon as possible
after delivery of an infant (preferably before hospital discharge), unless
contraindicated.17 Other adult household members, grandparents and carers
of young children should also be vaccinated. This recommendation is based
on evidence from several studies of infant pertussis cases, which indicated
that family members, particularly parents, were identified as the source
of infection in more than 50% of cases and were the presumed source in a
higher proportion.27-29
• Adults working with young children. Vaccination is especially recommended
for childcare workers (see Chapter 2.3, Groups with special vaccination
requirements, Table 2.3.6 Recommended vaccinations for those at risk of
occupationally acquired vaccine-preventable diseases).30,31
• All healthcare workers (see also Chapter 2.3, Groups with special vaccination
requirements, Table 2.3.6 Recommended vaccinations for those at risk of
occupationally acquired vaccine-preventable diseases). Several case reports
have documented nosocomial infection in young infants acquired from
healthcare workers.30,31
• Any adult expressing an interest in receiving a booster dose of dT vaccine
should be encouraged to do so with dTpa vaccine. At the age routinely
recommended for tetanus and diphtheria booster (50 years), dTpa produces
immune responses to tetanus and diphtheria antigens equivalent to dT
vaccine, and would also provide protection against pertussis.32
Data on the duration of immunity to pertussis following a single booster

dose of dTpa are limited in adults and adolescents.20,33 Although subsequent
doses of dTpa may prove beneficial, especially in high-risk groups such as
healthcare workers, such boosters are unlikely to be required before 10 years and
recommendations must await further data.

Minimum interval between dTpa and other tetanus/
diphtheria-containing vaccines
A single dose of dTpa can be administered at any time after a dose of a vaccine
containing tetanus and diphtheria toxoids.
Recent studies from Canada have shown that a single dose of dTpa can be safely
administered as soon as 18 months after a previous dose of a vaccine containing
tetanus or diphtheria toxoids.34-36 Where a tetanus- or diphtheria-containing
vaccine has been given even less than 18 months previously, the benefits of
protection against pertussis are likely to outweigh the risk of an adverse event,37
and justify vaccination with dTpa or dTpa-IPV.
Special considerations
Previous pertussis infection
Vaccination with pertussis vaccine in children, adolescents or adults who have
3.14 Pertussis
had laboratory-confirmed pertussis infection is safe but will not confer any
additional protection. If there is any uncertainty about a previous diagnosis
of pertussis, then vaccinate. In particular, incompletely vaccinated infants
<6 months of age who develop pertussis may not mount an adequate immune
response following infection and should receive all routinely scheduled vaccines,
including pertussis.
Pre-existing neurological disease and pertussis vaccination

Infants and children known to have active or progressive neurological disease
can be safely vaccinated with DTPa-containing vaccines. A large Canadian study
found no evidence of encephalopathy following acellular pertussis vaccines.38 For
infants and children with stable neurological disease (including cerebral palsy),
or a family history of idiopathic epilepsy or other familial neurological disorder,
the risk of adverse events following DTPa-containing vaccines are essentially the
same as for other infants of the same age.
Contraindications
The only true contraindications to acellular pertussis vaccines are:
• anaphylaxis following a previous dose of an acellular pertussis vaccine, or
Precautions
Children who have a hypotonic-hyporesponsive episode (defined in ‘Adverse
events’ below) following DTPa-containing vaccines should receive further
doses as scheduled in the National Immunisation Program. Supervision may be
required under some circumstances and specialist advice can be obtained from a
clinic specialising in the assessment and management of putative adverse events
Pertussis 233
following vaccination (see Appendix 1, Contact details for Australian, State and
A history of extensive limb swelling after a booster dose of DTPa is not a
contraindication to adolescent/adult formulation dTpa at 12–17 years of age
(or older).24 Parents of children about to receive the booster dose of a DTPa-
containing vaccine (at 4 years of age) should be informed of the small but well-
defined risk of this adverse event which, even when extensive, is usually not
associated with significant pain or limitation of movement.
Adverse events
Significant adverse events following pertussis vaccination should be reported as
set out in Section 1.5.2, Adverse events following immunisation.
• Acellular pertussis vaccines are associated with a much lower incidence of fever
(approximately 20%, very common) and local adverse events (approximately
10%, common) than whole-cell pertussis vaccines (approximately 45% and 40%,
respectively) which are no longer used in Australia).18,39
• Following the introduction of DTPa in Australia, there was an increase
in the incidence of extensive local adverse events in children receiving
booster doses at 18 months and 4 years of age.40
Extensive limb swelling, defined by swelling and/or redness involving at
least half the circumference of the limb, and the joints both above and below
the injection site, was common (occurring in 2% of vaccinees) following a
booster dose of DTPa given at 18 months of age; this was 1 reason for ceasing
this booster dose in 2003. Although it is still too early to assess the effect
that removing the 18-month booster dose has had on the incidence of local
adverse events following the booster dose at 4 years of age, recent anecdotal
reports of much less extensive swelling are encouraging.41
Such reactions commence within 48 hours of vaccination, last for 1 to 7 days
and resolve completely without sequelae.25 The pathogenesis of extensive
limb swelling is poorly understood. In an analysis of fourth and fifth dose
follow-up studies that examined 12 different DTPa vaccines, 2% (common)
of 1015 children who received consecutive doses of the same DTPa vaccine
reported entire thigh swelling, which resolved completely.25
• Children who experience a febrile convulsion after a dose of DTPa-containing
vaccines are at increased risk (albeit low) of further febrile convulsion
following a subsequent dose of DTPa-containing vaccines. These risks can be
minimised by appropriate measures to prevent fever, so vaccination is still
recommended.
Febrile convulsions are very infrequently reported following DTPa-
containing vaccines. The risk is even lower in infants who complete their
primary course at 6 months of age, as febrile convulsions are uncommon
under 6 months of age.

• Hypotonic-hyporesponsive episodes (HHE), defined by an episode of
pallor, limpness and unresponsiveness 1 to 48 hours after vaccination, often
preceded by irritability and fever, occur rarely following DTPa. Shallow
respiration and cyanosis may also occur in an HHE. The whole episode lasts
from a few minutes to 36 hours. In Australia during 2005, 1.33 cases of HHE
were reported per 100 000 doses of DTPa or DTPa-hepB vaccines given.41
Follow-up of children with HHE shows no long-term neurological or other
sequelae and they can receive further doses of DTPa-containing vaccines.42
• Pertussis vaccine does not cause infantile spasms or epilepsy.
• Sudden infant death syndrome (SIDS) is not associated with either DTPa or
any pertussis-containing vaccine.43 Some studies suggest a decreased risk of
SIDS in children who have been vaccinated (see Appendix 5, Commonly asked
questions about vaccination).
3.14 Pertussis
The public health management of pertussis
(i) Management of cases
The clinical case definition of pertussis is either (i) an acute cough lasting
≥14 days with at least one of post-tussive vomiting, apnoea or whoop, or (ii)
a cough of any duration in a person epidemiologically linked to a laboratory-
confirmed case. The diagnosis can be definitively confirmed by either culture
or PCR of a per-nasal swab or nasopharyngeal aspirate. The serological tests
available in most areas of Australia are based on detection of IgA antibodies
to B. pertussis antigens and are insensitive, so that false negative results are a
problem, especially if performed on only one occasion.44 In those who have not
received a pertussis-containing vaccine within the previous 5 years, detection
of IgA to pertussis antigens is highly specific in the presence of appropriate
symptoms. If pertussis is suspected in someone who has received a pertussis-
containing vaccine within 5 years, PCR is the diagnostic method of choice, but
has progressively decreasing sensitivity with increased duration of symptoms.
In a research setting, an IgG PT level of at least 125 EU/mL has been shown to
be indicative of a recent or active pertussis infection; however, this assay is not
available in routine pathology laboratories.45,46
A detailed history is required when a case of pertussis is suspected, including
date of onset, vaccination status and details of household contacts. To reduce the
risk of transmission, cases should be commenced on antibiotic therapy on clinical
suspicion, but only if commenced within 21 days of the onset of coryza. There
is no evidence of any reduction in pertussis transmission following antibiotic
treatment if the case has had symptoms for more than 21 days. Appropriate
macrolide antibiotics for treatment of pertussis are azithromycin, clarithromycin
and erythromycin. An alternative for those unable to take macrolides is
trimethoprim-sulfmethoxazole. Table 3.14.1 shows the dose regimens for each of
these antibiotics. (See also ‘Variations from product information’ below.)
Pertussis 235
Table 3.14.1: Recommended antimicrobial therapy and chemoprophylaxis
regimens for pertussis in infants, children and adults47-54
Age group Azithromycin Clarithromycin Erythromycin TMP-SMX*
<1 month 10 mg/kg single Not If azithromycin Not
dose for 5 days† recommended is unavailable; recommended
≤7 days old: in infants
10 mg/kg/ <2 months of age
dose 12-hourly unless macrolides
for 7 days;‡ cannot be used
8–28 days old:
10 mg/kg/
dose 8-hourly
for 7 days
1–5 months 10 mg/kg single 7.5 mg/kg/ 10 mg/kg/ ≥2 months of
dose for 5 days dose twice daily dose 6-hourly age; TMP: 4 mg/
for 7 days for 7 days kg twice daily,
SMX: 20 mg/
kg twice daily
for 7 days
Infants 10 mg/kg single 7.5 mg/kg/ 10 mg/kg/ TMP: 4 mg/kg,
(≥6 months) dose on day dose (up to a dose (up to a SMX: 20 mg/kg
and children 1, then 5 mg/ maximum dose maximum dose twice daily for
kg single dose of 500 mg) twice of 250 mg) 7 days (maximum
for days 2–5 daily for 7 days 6-hourly for 160 mg TMP and
(maximum (maximum 7 days 800 mg SMX
250 mg/day) 1 g/day) (maximum 12-hourly)
1 g/day)
Adults 500 mg single 500 mg twice Erythromycin: TMP: 160 mg
dose on day 1, daily for 7 days 250 mg 6-hourly twice daily, SMX:
then 250 mg for 7 days; 800 mg twice
single dose daily for 7 days
for days 2–5 Erythromycin
ethyl succinate
(EES): 400 mg
6-hourly for
7 days
* Trimethoprim-sulfmethoxazole
† Preferred for this age; refer to ‘(c) Pertussis in pregnancy’ and ‘(d) Use in infants and
infantile hypertrophic pyloric stenosis’ below.
‡ Please refer to ‘(d) Use in infants and infantile hypertrophic pyloric stenosis’ below.
Cases should be excluded from, for example, childcare facilities and school,
until they have taken 5 days of antibiotic treatment. All cases, both suspect and
confirmed, should be notified to the State/Territory public health authorities (see

(ii) Management of contacts of cases
(a) Vaccination
Since a primary course of 3 or more injections is required to protect against
pertussis, infant vaccination cannot be effectively used to control an outbreak.
However, unvaccinated or partially vaccinated contacts up to their 8th birthday
should be offered DTPa-containing vaccines and older individuals a single dose
of dTpa (see Section 1.3.5, Catch-up).
Passive immunisation with normal human immunoglobulin has not been shown
to be effective in the prevention of pertussis.
(b) Chemoprophylaxis
In the usual clinical setting of delayed presentation and imperfect compliance,
the benefit of chemoprophylaxis in preventing the secondary transmission
of pertussis is likely to be limited.49,55 In view of this, the well established
3.14 Pertussis
(mainly gastrointestinal) side effects of erythromycin and the cost of the newer
macrolides, the use of chemoprophylaxis for prevention of secondary cases
should be reserved for those settings where the benefit is greatest. These settings
are best defined by the chance of transmission and the high risk of severe
complications should transmission occur. Close contacts can be defined as those
who either live in the same household (but not occasional ‘sleepover’ contacts
unless they too are at increased risk of severe disease), or work in or attend
the same institutional setting (eg. maternity hospital ward, newborn nursery,
childcare centre) as a case.
Based on these principles, prophylaxis is recommended for the following ‘high-
risk’ contacts of pertussis cases:
• All household members when the household includes any child <24 months
of age who has received fewer than 3 effective doses of pertussis vaccine
(ie. commenced after 6 weeks of age with at least a 4-week interval between
doses, and the last dose given at least 14 days previously).
• Any woman in the last month of pregnancy, regardless of vaccination status
(see ‘Pertussis in pregnancy’ below).
• All other children and adults in the same care group if the case, regardless
of his/her vaccination status, attended childcare for more than 1 hour while
infectious and that care group includes 1 or more children <24 months of age
who have received fewer than 3 effective doses of pertussis vaccine.
• Healthcare staff, regardless of vaccination status, working in a maternity
hospital or newborn nursery. Chemoprophylaxis is not recommended
routinely for healthcare staff caring for older infected children or adults.
• Where a case worked in a maternity ward or newborn nursery for more than
an hour while infectious, then all babies in that ward should receive antibiotics.
Pertussis 237
Antibiotic regimens for chemoprophylaxis are the same as for cases (Table 3.14.1
above). Antibiotics should be given only if commenced either within 21 days
of the onset of any symptoms, or within 14 days of the onset of the paroxysmal
cough in the case. Childcare contacts in the same room as the case, who are not
age-appropriately vaccinated, should be excluded from childcare until the expiry
of 14 days from their last exposure to the infectious case, unless they have already
completed 5 days of a recommended antibiotic treatment, in which case they may
return.
(c) Pertussis in pregnancy
Treatment of pregnant women with pertussis onset within a month of delivery
is important for the prevention of neonatal pertussis and, if the onset is within
3 weeks of delivery, their newborn babies should also be given antibiotic therapy
(Table 3.14.1). Erythyromycin use earlier in pregnancy has well documented
safety (Category A). There are only limited data on the use of azithromycin in
pregnancy (Category B1).
(d) Use in infants and infantile hypertrophic pyloric stenosis
Several studies have shown an increased risk of infantile hypertrophic pyloric
stenosis (IHPS) when erythromycin is given for prophylaxis following exposure
to pertussis, especially in the first 2 weeks of life.56,57 While there are, as yet, no
data available on the effectiveness of azithromycin use in infants <1 month of
age, published case series report fewer adverse events following azithromycin
use when compared with erythromycin and, to date, there have been no reports
of IHPS in infants following use of azithromycin, although the size and number
of these studies is limited.58,59 Therefore, on currently available evidence,
and because of the risks of severe pertussis in this age group, azithromycin
is preferred to erythromycin for treatment and prophylaxis in infants aged
<1 month by US authorities. Azithromycin is available as a suspension and
approved for use in Australia, but treatment and prophylaxis of pertussis are not
currently referred to in the product information. Parents of newborns prescribed
either erythromycin or azithromycin should be informed about the possible risks
for IHPS and counselled about signs of developing IHPS.
Use in pregnancy


vaccines states that these vaccines are indicated for booster doses only. NHMRC
recommends that, when a 3-dose primary course of diphtheria/tetanus toxoids
is given to an adolescent/adult, that dTpa replace the first dose of dT, with 2
subsequent doses of dT. If dT is not available, dTpa can be used for all 3 primary
doses, but this is not routinely recommended.
3.14 Pertussis
recommends that a single dose of dTpa vaccine can be administered at any time
following receipt of a diphtheria and tetanus toxoid-containing vaccine.
The product information for both clarithromycin and azithromycin do not list
the treatment or prophylaxis of pertussis as an approved indication for either
antibiotic. NHMRC recommends that these antibiotics may be used for the
treatment or prophylaxis of pertussis as per Table 3.14.1 above.
References
Pertussis 239
3.15 Pneumococcal disease
Bacteriology
Streptococcus pneumoniae are lancet shaped Gram-positive streptococci. To date,
90 capsular antigenic types have been recognised, each eliciting type-specific
immunity. Some of these types are commonly carried in the upper respiratory
tract, and some are more frequently associated with invasive disease. The
emergence of antibiotic-resistant strains of this organism has become an
increasing challenge with 2004 Australian data indicating that up to 18% of
invasive strains are resistant to 2 or more classes of antibiotics.1
Clinical features
Invasive pneumococcal disease (IPD) is defined as isolation of S. pneumoniae from
a normally sterile site, most commonly blood. The major clinical syndromes of
IPD include pneumonia, meningitis and bacteraemia without focus. In adults,
pneumococcal pneumonia is the most common clinical presentation of IPD,
while, in children, bacteraemia accounts for more than two-thirds of cases.2-4
The risk of IPD is highest in patients who cannot mount an adequate immune
response to pneumococcal capsular antigens, including those with functional
or anatomical asplenia, immunoglobulin deficiency, acute nephrotic syndrome,
multiple myeloma, HIV/AIDS, chronic renal failure, organ transplantation
and lymphoid malignancies.3,4 Other groups of patients, although generally
immunocompetent, develop IPD of higher incidence and/or severity. These
include people with chronic cardiovascular or pulmonary disease, diabetes
mellitus, alcohol-related problems, cirrhosis, or CSF leak after cranial trauma
or surgery, and those who smoke.3,5 In those without predisposing medical
conditions, both frequent otitis media and recently commencing childcare are
associated with increased risk of IPD in children,6 and tobacco smoking with
increased risk in adults.
Epidemiology
The highest rates of IPD are seen in children <2 years of age and adults >85 years
of age. In 2004, 2375 cases of IPD were notified to the National Notifiable
Diseases Surveillance System, a notification rate of 11.8 per 100 000 population.1
The overall rate of IPD in Indigenous Australians was 3.2 times that in non-
Indigenous Australians.1 In 2004, after implementation of the pneumococcal
conjugate vaccine program for high-risk children in 2001, the rate of IPD in
children <2 years of age had decreased in Indigenous children (91.5 cases per
100 000) to become similar to their non-Indigenous peers (93.6 cases per 100 000).1
In the less-developed world and in some groups of Aboriginal and Torres Strait
Islander people, the incidence of IPD is as high as 200 per 100 000 per year.

However, mortality rates among Indigenous Australian people are comparable
to those in non-Indigenous people, even in remote areas. Most non-Indigenous
adults who develop IPD have at least 1 risk factor, while most cases occurring
in Indigenous adults are associated with multiple risk factors. In adults, most
IPD isolates belong to serotypes contained in the 23-valent pneumococcal
polysaccharide vaccine.7-9
Among Indigenous children in northern Australia, before the introduction of the
7-valent pneumococcal conjugate vaccine, only about one-half to two-thirds of
IPD was caused by serotypes in the 7-valent pneumococcal conjugate vaccine
compared with 85% or more among non-Indigenous children.7,8,10 Nevertheless,
in north Queensland, a decrease in the annual incidence of IPD in the <5 years
age group from 170 to 78 cases per 100 000 was documented in the 3 years after
introduction of the 7-valent pneumococcal conjugate vaccine.11 Similarly, the
annual incidence of vaccine-preventable IPD in Indigenous adults has declined
by 86% since the 23-valent pneumococcal polysaccharide vaccine was introduced
to north Queensland in 1986.11
Vaccines
There are currently 2 different types of pneumococcal vaccine available in
Australia. A 7-valent pneumococcal conjugate vaccine (7vPCV) became
available in 2001 for immunisation of infants and children aged from 6 weeks
to 9 years. 7vPCV was added to the NIP for high-risk children in 2001 and for
all children up to 2 years of age from January 2005. The 23-valent pneumococcal

polysaccharide vaccine (23vPPV) has been available since 1983. A funded
program with 23vPPV for Indigenous Australians aged ≥50 years began in
1999. Non-Indigenous Australians aged 65 years became eligible to receive the
vaccine under the NIP from January 2005. In addition, people aged <65 years
with underlying chronic conditions predisposing them to IPD can access 23vPPV
through the PBS.
Pneumococcal conjugate vaccine, 7-valent (7vPCV)
• Prevenar – Wyeth (7-valent pneumococcal conjugate vaccine; 7vPCV). Each

0.5 mL monodose pre-filled syringe contains 2 µg of pneumococcal serotypes
4, 9V, 14, 18C, 19F, 23F and 4 µg of serotype 6B, conjugated to a mutant
non-toxic diphtheria toxin (CRM197) carrier protein, adsorbed onto 0.5 mg
aluminium phosphate. Available in packs of 10 monodose pre-filled syringes.
7vPCV is approved for use in infants and children aged 6 weeks to 9 years.
Efficacy data from a pivotal trial in California found greater than 95% protective
efficacy against IPD due to the serotypes contained in the vaccine.12 A Cochrane
review of 4 trials assessing the efficacy of 7vPCV in children <2 years of age found
7vPCV to be effective in reducing the incidence of IPD due to all serotypes, the
greater effect being seen in the reduction of IPD due to vaccine-related serotypes.13
Pneumococcal disease 241

Other pneumococcal infections in children (pneumonia and otitis media), not
associated with a positive sterile site culture, are also reduced by 7vPCV, but the
estimated reduction varies with case definition and severity. For clinically defined
otitis media or pneumonia, the reduction is similar at approximately 5%.14,15
A post-licensure study of 157 471 children in California showed evidence of
disease reduction in unimmunised people, confirmed by a larger US study
showing a decline in the incidence of IPD of 52% in those 20–39 years of age and
26% in those ≥60 years of age.16-18
Pneumococcal polysaccharide vaccine, 23-valent (23vPPV)
• Pneumovax 23 – CSL Biotherapies/Merck & Co Inc (23-valent pneumococcal

polysaccharide vaccine; 23vPPV). Each 0.5 mL monodose vial contains 25 µg
of each of pneumococcal serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A,
12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F and 33F; 0.25% phenol.
23vPPV contains polysaccharides derived from the 23 most frequent or most

virulent capsular types of S. pneumoniae in the USA. These same serotypes are
responsible for most IPD cases in adults in Australia. At least 90% of healthy
adults respond to the vaccine, with a 4-fold rise in type-specific antibody within
2 to 3 weeks. Response to vaccine is diminished in patients with impaired
immunity and, in children <2 years of age, is limited to a small number of
serotypes unless there has been previous 7vPCV vaccination.19
In developing countries with high attack rates, controlled trials have shown
that pneumococcal polysaccharide vaccine reduces mortality from pneumonia
in younger adults which, in this setting, is very likely to be pneumococcal.
Among at-risk individuals in developed countries with much lower attack rates,
a Cochrane review examining vaccines for preventing pneumococcal disease
reported that 23vPPV was effective in reducing the incidence of IPD, but not
non-bacteraemic pneumonia, among adults and the immunocompetent elderly.20
Similarly, a recent retrospective study in a managed care setting in the USA studied
47 365 adults >65 years of age over 3 years, of whom 1428 were hospitalised with
community-acquired pneumonia and 61 developed documented pneumococcal
bacteraemia. Receipt of 23vPPV vaccine was associated with a significant reduction
in pneumococcal bacteraemia but not in hospitalisation for non-bacteraemic
pneumonia.21 In Australia, Victoria introduced a publicly funded 23vPPV program
for the >65 years age group in 1998, resulting in an estimated 36% reduction in the
incidence of IPD and vaccine effectiveness of 71% (95% CI: 54–82%).22

7-valent pneumococcal conjugate vaccine

23-valent pneumococcal polysaccharide vaccine

The dose is 0.5 mL by IM injection in the opposite limb to other injectable
vaccines if possible.

The dose is 0.5 mL as a single dose, by either SC or IM injection, in the opposite
limb to other injectable vaccines if possible.
Recommendations
Vaccination of children
7vPCV is recommended in the NIP for all infants from 2 months of age with a
catch-up for children up to 2 years of age.
7vPCV may be safely given at the same time as other vaccines listed on the NIP
but must be administered using a separate injection site and limb.
(i) Healthy children

7vPCV should be administered in a primary series of 3 doses at 2, 4 and 6 months
of age. Unless there is an increased risk of IPD (see below), the additional benefits
are not considered sufficient to justify a routine (fourth) booster dose. This
recommendation is based on data from the pivotal randomised controlled trial
suggesting similar efficacy against type-specific IPD with either 3 or 4 doses.12
Subsequent studies from the UK examining immunogenicity data24 and the US
examining vaccine effectiveness25 were consistent with significant protection after
2 or more doses. The US study found higher vaccine effectiveness among those
who had received a fourth dose at 12 months of age, but this was not statistically
significant.25 The current Australian dosing regimen will be regularly reviewed in
the light of trends in Australian IPD data and emerging international experience.
(ii) Aboriginal and Torres Strait Islander children living in the Northern
Territory, Queensland, South Australia and Western Australia
7vPCV should be administered at 2, 4 and 6 months of age, followed at
18–24 months of age by a dose of 23vPPV. This recommendation is based on: (i) data
from several Australian studies which showed lower serotype coverage from the
7vPCV in similar populations;7,8,10 (ii) 2 large studies which demonstrated adequate
boosting responses to serotypes contained in the 7vPCV following 23vPPV;26,27
and (iii) 2 large studies which demonstrated adequate primary responses to some
serotypes in 23vPPV, but not in 7vPCV, from 18–24 months of age.28,29

(iii) Children with underlying medical conditions (listed in Table
3.15.2) associated with greater risk or severity of IPD
7vPCV should be administered at 2, 4 and 6 months of age, followed by a fourth
dose of 7vPCV at 12 months of age and a booster dose of 23vPPV at 4–5 years of
age. This is based on data showing lower immune responses in these children to
certain serotypes in 7vPCV which can be enhanced by an additional dose, and
their continuing susceptibility to IPD at older ages, with a higher prevalence of
serotypes not contained in the 7vPCV.30
(iv) Children with asplenia (functional or anatomical)

≤9 years of age (ie. before their 10th birthday)
• with no previous history of pneumococcal vaccination with 7vPCV or
23vPPV
• 2 doses of 7vPCV given 2 months apart, followed by 23vPPV at least
2 months after the last dose of 7vPCV. This is based on an inadequate
response to 1 dose of 7vPCV among some asplenic individuals which is
enhanced by a second dose.27
• with previous history of pneumococcal vaccination with 7vPCV or 23vPPV
• where a dose of 23vPPV was given more than 6 months ago but no doses
of 7vPCV have been administered, give 2 doses of 7vPCV at least 2 months
apart. This is based on inadequate response to 1 dose of 7vPCV in some
asplenic individuals which seems unlikely to be influenced by previous
receipt of 23vPPV, although no specific data are available.
• where previous doses of 7vPCV have been administered but no 23vPPV,
give 23vPPV at least 2 months after the last 7vPCV dose. This is based on
similar considerations to those above.
NB. Children with asplenia should also be considered for other interventions (see
Chapter 2.3, Subsection 2.3.3.5, Individuals with functional or anatomical asplenia).
(v) Children ≤9 years of age (ie. before their 10th birthday) who have been
diagnosed with an underlying medical condition (listed in Table 3.15.2 below)
after they received the infant schedule of 7vPCV at 2, 4 and 6 months of age
Where a previously healthy child, currently aged >12 months, was vaccinated
according to the NIP schedule and received 7vPCV at 2, 4 and 6 months of age
but has since developed or been diagnosed with a condition listed in Table 3.15.2
below, he/she should receive a further dose of 7vPCV followed 2 months later by
a dose of 23vPPV.

Table 3.15.1: Summary table – pneumococcal vaccination schedule for children
≤9 years of age (see also Section 1.3.5, Catch-up)
For childhood immunisation schedule (children ≤5 years of age)
7vPCV 23vPPV Comments
All healthy children 2, 4 and No If delays in start of schedule
(including Indigenous 6 months of after 2 months, refer Section
children residing age (up to 1.3.5, Catch-up, Table 1.3.9.
in ACT, NSW, 2 years of age)*
TAS and VIC)
Indigenous children 2, 4 and 18–24 months If delays in start of schedule
residing in NT, QLD, 6 months of after 2 months, refer Section
SA and WA only age (up to 1.3.5, Catch-up, Table 1.3.10.
2 years of age)
Children with 2, 4, 6 and 4–5 years If delays in start of schedule
underlying medical 12 months after 2 months, refer Section
conditions (refer of age 1.3.5, Catch-up, Table 1.3.11.
Table 3.15.2)
For children 6–≤9 years of age with underlying medical conditions as listed in Table
3.15.2
7vPCV 23vPPV Comments
No history of any 2 doses, at least Give 1 dose at least For revaccination schedules
pneumococcal 2 months apart 2 months after last for children ≥10 years, refer
vaccination dose of 7vPCV to Table 3.15.3 below.

Has received 7vPCV 1 dose Give 1 dose at least For revaccination schedules
primary course at 2, 4 2 months after last for children ≥10 years, refer
and 6 months of age dose of 7vPCV to Table 3.15.3 below.
History of at least 1 dose Give 1 dose at least For revaccination schedules
2 7vPCV doses, 2 months after last for children ≥10 years, refer
and no 23vPPV dose of 7vPCV to Table 3.15.3 below.
History of 23vPPV, Give 2 doses at Refer revaccination For revaccination schedules
but no 7vPCV least 2 months schedule Table 3.15.3 for children ≥10 years, refer
apart, starting for further schedules to Table 3.15.3 below.
at least
6 months after
dose of 23vPPV
* Immunisation of healthy children (including Indigenous children residing in ACT, NSW,

VIC, and TAS) only up to 2 years of age.

Booster doses of 7vPCV
With the exception of children with underlying medical conditions (see above),
booster doses of 7vPCV are not required.
For details of catch-up schedules, please refer to Section 1.3.5, Catch up.
Table 3.15.2: Underlying medical conditions predisposing children ≤9 years of

age to IPD
Diseases compromising immune response to pneumococcal infection:

• congenital immune deficiency including symptomatic IgG subclass
or isolated IgA deficiency (but children who require monthly
immunoglobulin infusion are unlikely to benefit from vaccination),
• immunosuppressive therapy (including corticosteroid therapy ≥2 mg/kg per day
of prednisolone or equivalent for more than 2 weeks) or radiation therapy, where
there is sufficient immune reconstitution for vaccine response to be expected,
• compromised splenic function due to sickle haemoglobinopathies,
or congenital or acquired asplenia,
• haematological malignancies,
• HIV infection, before and after development of AIDS,
• renal failure, or relapsing or persistent nephrotic syndrome,
• Down syndrome.
Anatomical or metabolic abnormalities associated with higher rates or severity of IPD:
• cardiac disease associated with cyanosis or cardiac failure,
• all premature infants with chronic lung disease,
• all infants born at less than 28 weeks’ gestation,
• cystic fibrosis,
• insulin-dependent diabetes mellitus,
• proven or presumptive cerebrospinal fluid (CSF) leak,
• intracranial shunts and cochlear implants.

23vPPV may be safely given at the same time as other vaccines listed on the NIP
but must be administered using a separate injection site and limb.
(i) 23vPPV is recommended for:

• All people aged ≥65 years.
• Aboriginal and Torres Strait Islander people ≥50 years of age and those
15–49 years of age who have underlying conditions placing them at risk of IPD.
• People aged ≥10 years who have underlying chronic illnesses predisposing
them to IPD including:

• asplenia either functional (including sickle-cell disease) or anatomical;
where possible, the vaccine should be given at least 14 days before
splenectomy,
• conditions associated with increased risk of IPD due to impaired
immunity, eg. HIV infection before the development of AIDS, acute
nephrotic syndrome, multiple myeloma, lymphoma, Hodgkin’s disease
and organ transplantation,
• chronic illness associated with increased risk of IPD including chronic
cardiac, renal or pulmonary disease, diabetes, alcohol-related problems,
• CSF leak.
• Tobacco smokers.
(ii) 23vPPV ‘booster’ dose is recommended following previous 7vPCV

• At 18–24 months of age, after a primary series of 7vPCV, in Aboriginal and
Torres Strait Islander children in the Northern Territory, Queensland, South
Australia and Western Australia (see Section 1.3.5, Catch up, Table 1.3.10).
• At 4–5 years of age in children at risk of either high incidence or severity of
IPD because of underlying medical conditions (see Table 3.15.2), following a
primary series of 7vPCV (see Section 1.3.5, Catch up, Table 1.3.11).
iii) Revaccination with 23vPPV

A maximum of 3 doses (ie. 2 revaccinations) of 23vPPV are recommended, based

on data concerning adverse events and effectiveness.
Although an early study raised concerns about extensive local adverse events
following revaccination with 23vPPV,31 several recent studies have shown that 3
doses (ie. 2 revaccinations) of 23vPPV are not associated with more local adverse
events compared to 1 or 2 doses.32,33
Less clear, however, is the adequacy of the immune response after revaccination
with 23vPPV. Although an earlier study reported that there was an immune
hyporesponsiveness after a first revaccination, more recent studies suggest that
the immune responses to revaccination may be adequate.31,34

Table 3.15.3: Revaccination with 23vPPV for people ≥10 years of age
Primary dose 23vPPV First 23vPPV revaccination Second 23vPPV

given to revaccination
Non-Indigenous 5 years after first dose No
adults ≥65 years
Non-Indigenous 5 years after first dose Either 5 years after first
adults <65 years with revaccination or at 65 years
underlying chronic medical of age (whichever is later)
condition or smoker
Indigenous adults 5 years after first dose No
aged ≥50 years
Indigenous adults 5 years after first dose Either 5 years after first
aged <50 years with revaccination or at 50 years
underlying chronic medical of age (whichever is later)
condition or smoker
Asplenic individuals 5 years after first dose Either 5 years after first
revaccination or at 50 years
of age (for Indigenous
adults) or 65 years of
age (for non-Indigenous
adults), whichever is later
NB. Indigenous children in the Northern Territory, Queensland, South

Australia and Western Australia receive 23vPPV at 18–24 months of age (see
‘Recommendations’, point (ii) above). This childhood dose is not relevant to the
recommendations concerning revaccination given in Table 3.15.3.
Contraindications
The only absolute contraindications to 7vPCV are:

The only absolute contraindications to 23vPPV are:

Relative contraindications include the following:
• Age <2 years – the immune response in young children is restricted to a few
serotypes (so benefits of immunisation are limited) unless previously given 1
or more doses of 7vPCV.
• Recent use of immunosuppressive therapy or radiation of lymph nodes.
However, once it is considered that these patients are immunologically
‘stabilised’, they should be promptly vaccinated.
Adverse events
Among the most commonly reported are injection site adverse events and fever.
7vPCV is more commonly associated with local adverse events, with rates of
erythema ranging from 10.0 to 11.6% (very common) for 7vPCV, compared
with 6.7 to 11.4% (common to very common) for DTPa. There is no pattern
of increasing local reactogenicity with subsequent doses.12 A higher rate of
local adverse events has been observed in older children after a single dose.
Prophylactic antipyretic medication is recommended in children who have
seizure disorders or a previous history of febrile seizures.

About half the recipients of 23vPPV will experience some soreness after the first
dose, but pain or swelling severe enough to limit arm movement occurs in less

than 5% (common) of recipients.31 Low-grade fever occurs occasionally, but fever
above 39°C occurs in less than 0.5% (uncommon) of recipients.31
Previously, there were concerns about extensive local adverse events following
revaccination with 23vPPV31 but recent studies indicate that revaccination is
not associated with more local adverse events compared to 1 or 2 doses.32,33
Revaccination is not associated with an increase in systemic adverse events such
as fever or headache.32-34
Use in pregnancy
Vaccination during pregnancy has not been evaluated for potential harmful
effects in animals or humans. Although unlikely to result in adverse effects to
mother or fetus, it is neither indicated nor recommended.

Although 23vPPV has been administered in pregnancy in the context of clinical
trials with no evidence of adverse effects, data are limited and deferral of
vaccination is recommended unless there is an increased risk of IPD.35,36 Women
of reproductive age with known risk factors for IPD should be vaccinated before
planned pregnancy.

The product information recommends a 4-dose 7vPCV schedule for vaccination
commencing at 2 months of age with doses at 2, 4, 6 and 12 months of age,
3 doses for vaccination commencing between 7 and 12 months of age, and 2
doses for vaccination commencing between 13 and 23 months of age. However,
NHMRC recommends 1 dose less than that stated in the product information for
healthy children who are not at increased risk of IPD.

23vPPV is licensed for use only in children >24 months of age, but NHMRC
considers that it can be used from 18 months of age in children who have
previously received 7vPCV.
References

3.16 Poliomyelitis
Virology
Polioviruses are classified as enteroviruses in the family Picornaviridae.1 They
have an RNA genome, and are transient inhabitants of the gastrointestinal tract
(GIT). There are 3 poliovirus serotypes, PV1, PV2 and PV3. The virus enters
through the mouth, multiplies in the pharynx and GIT and is excreted in the
stools for several weeks. The virus invades local lymphoid tissue, enters the
blood stream and may then infect and replicate in cells of the central nervous
system.2
Clinical features
Poliomyelitis is an acute illness following gastrointestinal infection by one of the
3 types of poliovirus. Transmission is through faecal-oral and, occasionally, oral-
oral spread.3 The infection may be clinically inapparent. If symptoms occur, they
may include headache, gastrointestinal disturbance, malaise and stiffness of the
neck and back, with or without paralysis. Paralysis is classically asymmetrical.
Paralytic polio is a complication of poliovirus aseptic meningitis, and may be
spinal (79%), bulbar (2%) or bulbospinal (19%). The case-fatality rate in paralytic
polio is 2 to 5% in children, 15 to 30% in adults and up to 75% in bulbar polio.
The infection rate in households with susceptible young children can reach 100%.
The proportion of inapparent or asymptomatic infection to paralytic infection
may be as high as 1000:1 in children and 75:1 in adults, depending on the
poliovirus type and social and environmental conditions.2
The incubation period ranges from 3 to 21 days. Infected individuals are most
infectious from 7 to 10 days before to 7 to 10 days after the onset of symptoms.
The oral vaccine virus may be shed in the faeces for 6 weeks or more,2 and for up
to several years in people with impaired immunity. Oral vaccine strains shed for
many years may mutate into potentially neurovirulent strains.4-9
Epidemiology
The incidence of poliomyelitis has been dramatically reduced worldwide, but
cases still occur in developing countries in the Indian subcontinent, the eastern
3.16 Poliomyelitis
Mediterranean and Africa.10,11 The World Health Organization (WHO) aimed

to eradicate poliomyelitis by the year 2005 and, although not successful, is still
hopeful this will be achieved by 2010 or soon after.12 In 1994, the continents of
North and South America were certified to be free of polio,13 followed by the
Western Pacific region (including Australia) in 2000 and the European region
in 2002.14,15 In countries where the disease incidence is low but transmission is
still occurring, poliomyelitis cases are seen sporadically or as outbreaks among
non-vaccinated individuals. In 2005, 12 countries previously declared polio-
Poliomyelitis 251
free, including Indonesia, experienced outbreaks due to importations of wild
poliovirus from one of the remaining endemic countries: Afghanistan, India,
Nigeria and Pakistan.11
In Australia, the peak incidence of poliomyelitis was 39.1/100 000 in 1938.
There has been a dramatic fall in incidence since 1952, but epidemics occurred
in 1956 and 1961–62. The last notified case of wild poliomyelitis in Australia
occurred in 1977 due to an importation from Turkey, but 2 vaccine-associated
cases were notified in 1986 and 1995.16,17 Because of the rapid progress in
global polio eradication and diminished risk of wild virus associated disease,
inactivated poliomyelitis vaccine (IPV) is now used for all doses of polio vaccine
in Australia.3,18 This change was implemented because of concern about the risk of
causing vaccine-associated paralytic poliomyelitis (VAPP), which is about 1 case
for every 2.4 million doses of oral poliomyelitis vaccine (OPV) distributed.19 The
advantage of using IPV is that it cannot cause VAPP.
Global eradication of polio

The WHO strongly supports the use of OPV to achieve global eradication of
poliomyelitis, especially in countries with continued or recent circulation of wild-
type poliovirus.20 However, most countries which can afford IPV now use IPV
in preference to OPV, in order to eliminate the risk of VAPP and also to reduce
the risk of prolonged shedding of potentially neurovirulent strains of poliovirus
by individuals with impaired immunity.3 A vaccine-derived poliovirus (VDPV)
is derived from OPV but has a number of significant mutations due to long-
term replication in an individual with impaired immunity (iVDPV) or through
person-to-person transmission in areas of low polio vaccine coverage (circulating
VDPV or cVDPV). Outbreaks of poliomyelitis due to cVDPV have been reported
worldwide.6 People travelling to countries still using OPV are at risk of VAPP,
as was reported for an unimmunised adult from the USA who travelled to
Costa Rica in 2005.21 The WHO is planning for global OPV cessation, once the
interruption of wild poliovirus transmission has been certified, to remove the
incidence of VAPP and VDPVs.22 Further information is available from the WHO
Polio Eradication website http://www.polioeradication.org.

Vaccines
• IPOL – Sanofi Pasteur Pty Ltd (IPV; inactivated poliomyelitis vaccine). Each
0.5 mL pre-filled syringe contains poliovirus 40D antigen units of type 1, 8D
antigen units of type 2 and 32D antigen units of type 3 grown on monkey
kidney cells, inactivated with formaldehyde; traces of phenoxyethanol as
preservative, neomycin, streptomycin and polymyxin B.
Combination vaccines that include IPV



3.16 Poliomyelitis
units type 2 (MEF-1) and 32 D-antigen units type 3 (Saukett) adsorbed
onto aluminium hydroxide/phosphate; phenoxyethanol as preservative;
traces of formaldehyde, polymyxin and neomycin. May also contain
yeast proteins.
Poliomyelitis 253

pertussis- inactivated poliomyelitis vaccine). Each 0.5 mL monodose vial
FHA, 3 µg PRN, 5 µg pertussis fimbriae (FIM) 2+3; 40 D-antigen units
inactivated polioviruses type 1 (Mahoney), 8 D-antigen units type 2 (MEF-1)
and 32 D-antigen units type 3 (Saukett); 1.5 mg aluminium phosphate;
phenoxyethanol as preservative; traces of formaldehyde, polymyxin,
neomycin and streptomycin.

IPV (IPOL) and IPV-containing combination vaccines contain polioviruses of

types 1, 2 and 3 inactivated by formaldehyde. A course of 3 injections with an
interval of 2 months between each dose produces long-lasting immunity (both
mucosal and humoral) to all 3 poliovirus types. IPV produces considerably lower
levels of intestinal immunity than OPV.


The dose of IPV (IPOL) and of the IPV-containing combination vaccines is
0.5 mL. IPV is given by SC injection, whereas the IPV-containing vaccines
are administered by IM injection. If IPV (IPOL) is inadvertently given
intramuscularly, there is no need to repeat the dose.
Recommendations
Primary vaccination of infants and children
(i) IPV (IPOL) or IPV-containing vaccines are recommended for infants from
2 months of age. An open, randomised, multi-centre trial comparing the
hexavalent and pentavalent IPV-containing vaccines found that infants receiving
either vaccine at 2, 4 and 6 months of age had seroprotective levels of antibody to
polio virus types 1, 2 and 3.24

Extra doses of IPV (IPOL) or IPV-containing vaccines are not needed for babies
born prematurely.
(ii) The primary course consists of 3 separate doses of vaccine. An interval of
2 months between each dose is recommended, but the minimum interval can be
as short as 1 month for catch-up.
(iii) Interchangeability of OPV and IPV: Oral poliomyelitis vaccine (OPV)
is no longer in use in Australia. OPV and IPV are interchangeable. Children
commenced on OPV should complete their polio vaccination schedule using IPV
(IPOL) or IPV-containing vaccines.
Primary vaccination of adults

A course of 3 doses of IPV (IPOL) or IPV-containing vaccines at intervals of 1 to
2 months is recommended for the primary vaccination of adults. No adult should
remain unvaccinated against poliomyelitis.
Booster doses
Children
A booster dose of IPV (IPOL) or IPV-containing vaccine should be given at
4 years of age. A fifth dose of IPV is no longer recommended as Australia has
been declared polio free since 200014 and, as in the US, a completed poliomyelitis
vaccination schedule for children is 3 primary doses and 1 booster dose of IPV
(IPOL) or an IPV-containing vaccine.25
Adults
Booster doses for adults are not necessary unless they are at special risk, such as:
• travellers to areas or countries where poliomyelitis is epidemic or endemic
(see http://www.polioeradication.org for more information on affected
countries), or
• healthcare workers, including laboratory workers, in possible contact with
poliomyelitis cases.
For those exposed to a continuing risk of infection, booster doses are desirable every
10 years. dTpa-IPV combination vaccines can be used where otherwise indicated.
Contraindications
3.16 Poliomyelitis
The only absolute contraindications to IPV (IPOL) or IPV-containing vaccines are:

Adverse events
IPV-containing vaccines cause erythema (33%, very common), pain (13%, very
common), and induration (1%, uncommon) at the injection site. Other symptoms
reported in young babies are: fever, crying and decreased appetite (5–10%, common).
Poliomyelitis 255
Use in pregnancy

The product information for IPV suggests that the fourth dose be given 12 months
after the third dose for both adults and children, followed by a fifth dose for
children at 4 years of age. NHMRC recommends the fourth dose for children at
4 years of age and no fourth dose for adults unless they are at special risk.
The product information suggests that any sensitivity to vaccine components is a
contraindication, whereas NHMRC recommends that the only contraindication is
a history of anaphylaxis to a previous dose or to any of the vaccine components.
References

3.17 Q fever
Bacteriology
3.17 Q fever
Q fever is caused by Coxiella burnetii, an obligate intracellular bacterium,
classified in a separate genus, Coxiella. A near relative is Legionella pneumophilia.1
The organism is slightly more resistant to heat than other vegetative bacteria,
but nevertheless is inactivated at pasteurisation temperatures. It survives well in
air, soil, water and dust and may also be disseminated on fomites such as wool,
hides, clothing, straw and packing materials.2,3
Clinical features
Q fever can be acute or chronic, and there is increasing recognition of long-term
sequelae. However, in many instances, infection can be asymptomatic.4,5
Acute Q fever usually has an incubation period of 2 to 3½ weeks, depending
on the inoculum size and other variables6 (range from 4 days up to 6 weeks).
Clinical symptoms vary by country but in Australia it commonly presents with
rapid onset of high fever, rigors, profuse sweats, extreme fatigue, muscle and
joint pain, severe headache and photophobia.4,5 As the attack progresses there is
usually evidence of hepatitis, occasionally with frank jaundice; a proportion of
patients may have pneumonia which is usually mild but can require mechanical
ventilation. If untreated, the acute illness lasts 1 to 3 weeks and may be
accompanied by substantial weight loss in the more severe cases.4,5
C. burnetii may cause chronic manifestations, the most commonly reported being
subacute endocarditis. Less common presentations include granulomatous
lesions in bone, joints, liver, lung, testis and soft tissues. Infection in early
pregnancy, or even before conception, may recrudesce at term and cause fetal
damage.7-9
Recent studies have also identified a late sequel to infection, post Q fever fatigue
syndrome (QFS), which occurs in about 10 to 15% of patients with acute Q
fever.10-13 Laboratory research suggests that C. burnetii persists in most instances
of acute Q fever, regardless of clinical status, and that immunogenic variation
in the response to persistent infection leads to cytokine dysregulation and
determines whether QFS occurs.11,14,15
Epidemiology
C. burnetii infects both wild and domestic animals and their ticks, with cattle,
sheep and goats being the main source of human infection. Companion animals
such as cats and dogs may also be infected. The animals shed C. burnetii into the
environment through their products of conception (especially high numbers of
coxiellas) but also in their milk, urine, and faeces. C. burnetii is highly infectious16
and can survive in the environment. The organism is transmitted to humans via
Q fever 257
the inhalation of infected aerosols or dust. Those most at risk include workers
from the meat and livestock industries and shearers, with non-immune new
employees or visitors being at highest risk of infection. Nevertheless, Q fever is
not confined to occupationally exposed groups; there are numerous reports of
sporadic cases or outbreaks in the general population in proximity to infected
animals in stockyards, feedlots, processing plants or farms.
Use of Q fever vaccine in Australia can be considered in 3 periods. First, from
1991 to 1993 when vaccine was used in a limited number of abattoirs, then from
1994 to 2000 when vaccination steadily increased to cover large abattoirs in
most states,17 and finally from 2001 to 2006 during the period of the Australian
Government sponsored Q fever Management Program.18 This program extended
vaccination to farmers, their families and employees in the livestock-rearing
industry. With respect to abattoir workers, there has been a clear reduction
in Q fever cases and associated insurance claims since 1994.17,19 More widely,
the numbers of Q fever cases reported to the National Notifiable Diseases
Surveillance System (NNDSS) have declined over the period 1994 to 2005,
during which there has been an increasing use of vaccine (see Figure 3.17.1). This
decline is suggestive of an impact from vaccination among people not working
in abbatoirs but, as there are substantial variations in total numbers of cases from
year to year, requires confirmation over a longer period.20
Figure 3.17.1: Q fever notifications and hospitalisations, Australia, 1993 to

2005,* by month of diagnosis or admission20
100
Notifications
90
Hospitalisations
80
70
60
Number
50
40
30
20
10
0
Jan Jul Jan Jul Jan Jul Jan Jul Jan Jul Jan Jul Jan Jul Jan Jul Jan Jul Jan Jul Jan Jul Jan Jul Jan Jul
1993 1993 1994 1994 1995 1995 1996 1996 1997 1997 1998 1998 1999 1999 2000 2000 2001 2001 2002 2002 2003 2003 2004 2004 2005 2005
* Notifications where the month of diagnosis was between January 1993 and December 2005;
hospitalisations where the month of admission was between 1 July 1993 and 30 June 2005.

Vaccine4,21
• Q-VAX – CSL Biotherapies (Q fever vaccine). Each 0.5 mL pre-filled syringe
contains 25 µg purified killed suspension of Coxiella burnetii; thiomersal
3.17 Q fever
0.01% w/v. May contain egg proteins.
• Q-VAX Skin Test – CSL Biotherapies (Q fever skin test). Each 0.5 mL liquid
vial when diluted in 15 mL of sodium chloride contains 16.6 ng of purified
killed suspension of Coxiella burnetii in each diluted 0.1 mL dose; thiomersal
0.01% w/v before dilution. May contain egg proteins.
Q fever vaccine and skin test consist of a purified killed suspension of C.

burnetii. It is prepared from the Phase I Henzerling strain of C. burnetii grown
in the yolk sacs of embryonated eggs. The organisms are extracted, inactivated
with formalin, and freed from excess egg proteins by fractionation and
ultracentrifugation. Thiomersal 0.01% w/v is added as a preservative.
Phase I whole-cell vaccines have been shown to be highly antigenic and
protective against challenge both in laboratory animals and in volunteer trials.22
Serological response to the vaccine is chiefly IgM antibody to C. burnetii Phase
I antigen. In subjects weakly seropositive before vaccination, the response
is mainly IgG antibody to Phase I and Phase II antigens.23 Although the
seroconversion rate may be low, long-term cell-mediated immunity develops24
and the vaccine has been shown to be protective in open and placebo-controlled
trials, and in 2 post-licensing trials, to have a vaccine efficacy of 100%.25-28 Lack of
seroconversion is not a reliable marker of lack of vaccination.22
During recent years, with much larger numbers vaccinated, a few instances
of laboratory proven Q fever have been observed in vaccinated subjects.21 It is
important that these apparent vaccine failures are fully investigated and that
vaccination status is reported for all notified cases.
It should be noted that vaccination during the incubation period of a natural
attack of Q fever does not prevent the development of the disease.22
A useful website for Q fever vaccine providers is http://www.qfever.org/vaclist.php.

Transport the vaccine according to National Vaccine Storage Guidelines: Strive for
5.29 Store at +2°C to +8°C, and do not freeze or store in direct contact with ice
packs. If vaccine has been exposed to temperatures less than 0°C, do not use.
Protect from light.
Q fever 259
A single dose of 0.5 mL of Q-VAX is given by SC injection after ascertaining that
serological and skin testing have been performed and that both tests are negative
(see ‘Pre-vaccination testing’ below).
Recommendations
Q fever vaccine is recommended for those at risk of infection with C. burnetii.
This includes abattoir workers, farmers, stockyard workers, shearers, animal
transporters, and others exposed to cattle, camels, sheep, goats and kangaroos or
their products (including products of conception). It also includes veterinarians,
veterinary nurses, veterinary students, agricultural college staff and students
(working with high-risk animals) and laboratory personnel handling veterinary
specimens or working with the organism (see also Chapter 2.3, Groups with special
vaccination requirements, Table 2.3.6 Recommended vaccinations for those at risk of
occupationally acquired vaccine-preventable diseases).
Workers at pig abattoirs do not require Q fever vaccination.
Pre-vaccination testing
(i) Before vaccination, people with a negative history of previous Q fever must
have serum antibody estimations and skin tests to exclude those likely to have
hypersensitivity reactions to the vaccine resulting from previous (possibly
unrecognised) exposure to the organism.
(ii) If the person has a positive history of previous infection with Q fever, or has
already been vaccinated for Q fever, skin testing and serology are not required
and vaccination is contraindicated.
(iii) Note that a few subjects who have had verified Q fever in the past show no
response to serological or skin testing. However, such subjects may experience
serious reactions to administration of Q fever vaccine. Thus, it is vital to take a
detailed history and to obtain documentation of previous Q fever vaccination or
laboratory results confirming Q fever disease in all potential vaccinees; those who
have worked for more than 10 years in the livestock or meat industries should be
questioned particularly carefully. If there is any doubt about serological results
or skin testing, they should be repeated 2 to 3 weeks later (see (vi) below for
interpretation).
(iv) Antibody studies were originally done by complement fixation (CF) tests at
serum dilutions of 1 in 2.5, 5 and 10 against the Phase II antigen of C. burnetii.
Although this is generally satisfactory, many testing laboratories now use
enzyme immunoassay (EIA) or immunofluorescent antibody (IFA) to detect IgG
antibody to C. burnetii as an indicator of past exposure. Subjects CF antibody
positive at 1 in 2.5, IFA positive at 1 in 10 or more, or with a definite positive
absorbance value in the EIA, should not be vaccinated (see Table 3.17.1).

(v) Skin testing and interpretation should only be carried out by experienced
personnel. For further information on training and accredited Q fever
immunisation service providers, contact your State or Territory Health
Department (see Appendix 1, Contact details for Australian, State and Territory
3.17 Q fever
Government health authorities and communicable disease control). Skin testing is
performed by diluting 0.5 mL of the Q-VAX Skin Test in 15 mL of sodium
chloride (injection grade). Diluted Q-VAX Skin Test should be freshly prepared,
stored at +2°C to +8°C and used within 6 hours. 0.1 mL of the diluted Q-VAX
Skin Test is injected intradermally into the volar surface of the forearm.
Commercial isopropyl alcohol skin wipes should not be used. If the skin is
not visibly clean, then methylated spirits may be used. A positive reaction is
indicated by any induration at the site of injection after 7 days. Individuals
giving such a reaction must not be vaccinated, because they may develop severe
local reactions.
Table 3.17.1: Interpretation and action for serological and skin test results (with
modifications from Q fever. Your questions answered (CSL, 1999)4)
Serology Skin test Interpretation/Action

Positive antibody test* Positive †
Sensitised: do not vaccinate
Borderline‡ Sensitised: do not vaccinate
Negative§ Sensitised: do not vaccinate
Equivocal antibody test^ Positive Sensitised: do not vaccinate
Borderline Indeterminate (see (vi) below)
Negative Indeterminate (see (vi) below)
Negative antibody test #
Positive Sensitised: do not vaccinate
Borderline Indeterminate (see (vi) below)
Negative Non-immune: vaccinate
* Positive antibody test: CF antibody or IFA positive (according to criteria used by

diagnosing laboratory); or definite positive EIA absorbance value (according to
manufacturer’s instructions).
† Positive skin test: induration present.
‡ Borderline skin test: induration just palpable.
§ Negative skin test: no induration.
^ Equivocal antibody test: CF antibody or IFA equivocal (according to criteria used by
diagnosing laboratory); or equivocal EIA absorbance value (according to manufacturer’s
instructions).
# Negative antibody test: CF antibody or IFA negative (according to criteria used
by diagnosing laboratory); or definite negative EIA absorbance value (according to
manufacturer’s instructions).
(vi) Test results are indeterminate when skin test induration is just palpable and/
or there is an equivocal level of antibodies in one or other of the serological tests.
Q fever 261
An indeterminate result, which occurs in only a small proportion of subjects, may
be the consequence of past infection with Q fever. It may also merely indicate the
presence in the subject of antibodies to antigens shared between C. burnetii and
other bacteria. Australian Q fever vaccine users have dealt with this finding in
one of two ways:
(a) Repeat the skin test and interpret as per the guidelines for initial testing.
Collect serum 2 to 3 weeks later to look for a rise in titre of C. burnetii
antibodies in the IFA test, using Phase I and Phase II antigens, and
immunoglobulin class analysis. A significant increase (defined as a 4-fold rise
in titre of paired sera) indicates previous Q fever infection and vaccination is
then contraindicated.
(b) Vaccinate the subject using SC injection of a 5 µg (0.1 mL) dose instead of
a 25 µg (0.5 mL) dose of the vaccine. If there are no adverse effects (severe
local induration or severe systemic effects, perhaps accompanied by fever) 48
hours after the injection, a further 0.4 mL (20 µg) dose of the vaccine is given
within the next 2 to 3 weeks, ie. before the development of cell-mediated
immunity to the first dose.
Booster doses
Immunity produced by the vaccine appears to be long lasting (in excess of
5 years). Until further information becomes available, revaccination or booster
doses of the vaccine are not recommended because of the risk of accentuated local
adverse events.
Contraindications
Q fever vaccine is contraindicated in the following:
• individuals with a history of an illness suggestive of or proved to be Q fever,
• those shown to be immune by either serological testing or sensitivity to the
organism by skin testing,
• those who have been previously vaccinated against Q fever,
• those with known hypersensitivity to egg proteins or any component of the
vaccine (Q-VAX may contain traces of egg protein, formalin, and sucrose).21
There is no information available on the accuracy of skin testing or the efficacy

and safety of Q fever vaccine use in individuals with impaired immunity. In
general, skin testing and Q fever vaccine should be avoided in such people.
The lower age limit for Q fever vaccine is not known. However, it is not
recommended for use in those aged <15 years.

Precautions
Vaccination of subjects already immune to C. burnetii, as a result of either
previous infection or subjects being rendered hyperimmune by repeated
vaccination, may result in severe local or systemic adverse events.
3.17 Q fever
Adverse events
Non-immune subjects very commonly show local tenderness (48%) and
erythema (33%) at the vaccination site. Local induration or oedema is uncommon
(<1%). General symptoms occur commonly in about 10% of vaccinees and may
include mild influenza-like symptoms such as headache (9%), fever (up to 2%),
chills and minor sweating.4,21
There are also 2 patterns of more significant adverse events among the estimated
more than 130 000 individuals vaccinated from 1989–2004.5,17
The first and familiar pattern is the intensified local reaction at the injection
site which may occur shortly after inoculation in individuals sensitised
immunologically by previous infection or repeated vaccination. Rarely, an
immune abscess develops and requires excision and drainage. The acute
reactions may be accompanied by short-term systemic symptoms resembling the
post Q fever fatigue syndrome. Note, however, that not all those with positive
pre-vaccination skin and/or serological tests develop severe reactions. The
introduction of the pre-vaccination skin test at NIH/NIAID Rocky Mountain
Laboratory,30 later combined with antibody testing in Australia, has largely
eliminated reactions due to previous immune sensitisation. Despite this, the
adverse experience from the earlier American trials22 in which subjects were not
pre-tested, were vaccinated repeatedly or were inoculated with vaccines of a
different composition and larger bacterial mass, are still quoted in the general Q
fever literature as representative of a whole cell vaccine.
The second, much less frequent, pattern has been reported in people who were
skin and antibody test negative at the time of vaccination who did not have
any immediate reaction. Some 1 to 8 months after vaccination, some vaccinees,
predominately women, developed an indurated lesion at the inoculation site.
At the time when the indurated lesion developed, the original skin test site
often became positive, presumably indicating a late developing cellular immune
response. These lesions were not fluctuant and did not progress to an abscess.
Most gradually declined in size and resolved over some months without
treatment. A few lesions were biopsied or excised and showed accumulations of
macrophages and lymphocytes.31,32
Use in pregnancy
Not recommended. Q fever vaccine contains inactivated products and inactivated
bacterial vaccines are not considered to be harmful in pregnancy. However, safety
of the vaccine in pregnancy has not been established. No information is available
on the use of Q fever vaccine during breastfeeding.
Q fever 263
The product information for Q-VAX does not include the use of the reduced dose
of vaccine in individuals who have indeterminate results on either serological or
skin testing. However, this option has been used successfully by experienced Q
fever vaccinators.
References

3.18 Rotavirus
Virology
Rotaviruses are non-enveloped RNA viruses in the family Reoviridae.
Rotaviruses are classified according to the 2 surface proteins they contain:
VP7, the glycoprotein (G protein), and VP4, the protease-cleaved protein (P
protein). The G and P proteins are targets for neutralising antibodies thought
to be necessary for protection.1,2 Because the 2 gene segments that encode these
proteins can segregate independently, a typing system consisting of both P and
G types has been developed. Rotavirus strains are most commonly referred to
by their G serotype, with G1, G2, G3, G4 and G9 accounting for around 90% of
serotypes both globally and in Australia.3,4 The most common P types found
in combination with these G types are P1a[8] (found with all common G-types
3.18 Rotavirus
except G2) or P1b[4], usually found in combination with G2.5
Rotaviruses are shed in high concentrations in the stools of infected children and
are transmitted by the faecal-oral route, both through close person-to-person
contact and via fomites.6 Rotaviruses are probably also transmitted by other
modes, such as faecally contaminated food, water and respiratory droplets.7,8
Clinical features
Rotavirus is the predominant agent of severe dehydrating gastroenteritis in
infants and young children in both developed and developing countries.1,2
The spectrum of rotavirus illness ranges from asymptomatic infection, to mild,
watery diarrhoea of limited duration, to severe dehydrating diarrhoea with
vomiting, fever, electrolyte imbalance, shock and death. Rotavirus infections are
often more severe than other common causes of diarrhoea, and are more likely to
be associated with dehydration and hospitalisation.1,7 The incubation period is 1
to 3 days, after which illness can begin abruptly with vomiting often preceding
the onset of diarrhoea.7 Up to one-third of patients have a temperature of >39°C
in the first few days of illness. Symptoms generally resolve in 3 to 7 days.
Epidemiology
Although individuals can be infected with rotavirus several times during their
lives, the first infection, typically between 3 and 36 months of age, is most likely
to cause severe diarrhoea and dehydration.9,10 After a single natural infection,
40% of children are protected against any subsequent infection with rotavirus,
75% are protected against diarrhoea from a subsequent rotavirus infection, and
88% are protected against severe diarrhoea.10 Repeat infections provide even
greater protection. Disease is also less likely when reinfection occurs with a
serotype (G type) to which an individual has already been exposed.
Rotavirus 265
In Australia, the best available estimates are that approximately 10 000
hospitalisations due to rotavirus in children <5 years of age occur each year.11
As such, rotavirus accounts for around half the hospitalisations for acute
gastroenteritis of any cause in this age group.11,12 This translates to 3.8% of
children (1 in 27) being hospitalised with rotavirus gastroenteritis by the age
of 5 years. In addition to hospitalised children, an estimated 115 000 children
<5 years of age visit a GP, and 22 000 children require an Emergency Department
visit.11,13 On average, there is 1 death attributed to rotavirus each year in
Australia, but this is likely to be a minimum estimate.13
In temperate Australia, rotavirus infections follow a seasonal pattern, the peak
incidence being in mid to late winter. In the northern tropical and arid regions,
there is no consistent seasonal pattern and disease peaks are unpredictable.14
Epidemics of rotavirus gastroenteritis have occurred in Central Australia,
causing severe strain on healthcare services.15,16 Overall, Indigenous Australian
infants and children are hospitalised with rotavirus gastroenteritis about 3 to
5 times more commonly than their non-Indigenous peers, have a younger age
at hospitalisation, and longer duration of hospital stay (an average of 5 days
compared with 2 days for non-Indigenous infants).12,14,15,17
Children and adults with impaired immunity, such as those with congenital
immunodeficiency, or post haematopoietic or solid organ transplantation, are at
increased risk of severe, prolonged, and even fatal rotavirus gastroenteritis.1,18,19
Rotavirus is an important cause of nosocomial gastroenteritis,20-24 and can also
cause disease in adults, especially those caring for children, and outbreaks of
gastroenteritis in aged care facilities.1,25,26
Vaccines
Two oral rotavirus vaccines are available in Australia, and data on their
immunogenicity, safety and efficacy has been systematically reviewed.27 Both
vaccines are live attenuated vaccines administered orally to infants, but the
component vaccine viruses differ. Rotarix (GlaxoSmithKline) is a live attenuated
vaccine containing 1 strain of attenuated human rotavirus (G1P1[8] strain). The
human live attenuated strain protects against non G1 serotypes on the basis of
their common P[8] antigen and other epitopes involved in heterotypic immunity.
RotaTeq (CSL Biotherapies/Merck & Co Inc) is a pentavalent vaccine containing
5 human-bovine rotavirus reassortants with the human serotypes G1, G2, G3,
G4, and P1[8] and the bovine serotypes G6 and P7. The vaccine viruses replicate
in the intestinal mucosa and can be shed in the stool of vaccine recipients,
particularly after the first dose. Vaccine virus shedding is more common with
Rotarix and is detected in the stool a week after vaccination in up to 80% of first
dose recipients, and in up to 30% of second dose recipients.27-29 RotaTeq is only
shed after the first dose (in up to 13% of recipients).30 There have been no studies
to assess the implications of shedding for horizontal spread to contacts.

Current oral rotavirus vaccines are underpinned by decades of developmental
work.31 Randomised placebo-controlled studies of both vaccines have
documented their efficacy and safety in the prevention of gastroenteritis caused
by rotavirus.27,30,32 A vaccination course prevents rotavirus gastroenteritis of any
severity in approximately 70% of recipients over the following 1 to 2 years. The
efficacy against severe rotavirus gastroenteritis and against hospitalisation for
rotavirus gastroenteritis is higher, ranging from 85 to 100% in clinical trials in
many different countries.27,30,32,33 Efficacy in the prevention of hospitalisation from
rotavirus gastroenteritis ranged from 85 to 100%.27,30,32,33 Vaccination was also
highly effective in preventing Emergency Department and clinic/GP visits.30,33
Overall, rotavirus vaccination prevented around half (42–58%) of hospital
admissions for acute gastroenteritis of any cause in young children, suggesting
that rotavirus is responsible for more gastroenteritis than detected using routine
testing and admission practices.30,32,33 In randomised control trials, a degree of
3.18 Rotavirus
protection against rotavirus gastroenteritis was also observed in infants who
received fewer than the recommended number of doses of rotavirus vaccines.
In the available clinical trials, no statistically significant differences were found
between the 2 vaccines with regard to protective efficacy by serotype.27,30,32
The efficacy and safety of both rotavirus vaccines have been evaluated only
in clinical trials in which infants received vaccine within specified age limits.
There are no data on the use of rotavirus vaccines outside these age ranges (see
‘Recommendations’ and ‘Adverse events’ below).
• Rotarix – GlaxoSmithKline (live attenuated RIX4414 human rotavirus

strain expressing G1P1[8] outer capsid proteins). Each 1.0 mL monodose
of the reconstituted vaccine contains not less than 106.0 CCID50 (cell culture
infectious dose 50%) of the RIX4414 strain; sucrose; dextran 40; sorbitol;
amino acids; Dulbecco’s Modified Eagle Medium; calcium carbonate;
xanthan gum. Calcium carbonate buffer solvent (diluent) supplied for
reconstitution.
• RotaTeq – CSL Biotherapies/Merck & Co Inc (live, oral pentavalent

vaccine). Each 2.0 mL monodose pre-filled dosing tube contains rotavirus
reassortants G1, G2, G3, G4 and P1[8] each with a minimum dose level of
at least 2.0 x 106 infectious units; sucrose; sodium citrate; sodium phosphate
monobasic monohydrate; sodium hydroxide; polysorbate 80; cell culture
media; trace amounts of fetal bovine serum. Also available in packs of 10
monodose pre-filled dosing tubes.

Transport both vaccines according to National Vaccine Storage Guidelines: Strive for
5.34 Store at +2°C to +8°C. Do not freeze. Protect from light.
Rotavirus 267
Rotavirus vaccines are for oral administration only. Under no circumstances
should rotavirus vaccines be injected.
There are no restrictions on the infant’s consumption of food or liquid, including
breast milk, either before or after vaccination with either rotavirus vaccine.7,35
Rotarix is recommended for use in a 2-dose course (at 2 and 4 months of age).
It is presented as a white powder for reconstitution with a separately supplied
diluent, and a transfer adapter. The syringe/oral plunger containing the diluent
is attached to the vial of lyophilised powder via the transfer adapter, and
following reconstitution the 1 mL dose of vaccine should be administered orally
via the syringe/oral plunger onto the inside of the infant’s cheek.
RotaTeq is recommended for use in a 3-dose course (at 2, 4, and 6 months of age).
It is supplied in a container consisting of a squeezable plastic, latex-free dosing
tube with a twist-off cap, allowing for direct oral administration of the 2 mL dose
onto the inside of the infant’s cheek. RotaTeq does not require reconstitution or
dilution. RotaTeq is a pale yellow, clear liquid that may have a pink tint.
Rotavirus vaccines can be co-administered with other vaccines included on the
NIP schedule at 2 and 4 months of age (Rotarix) or 2, 4 and 6 months of age
(RotaTeq). The available evidence from clinical trials suggests co-administration
of oral rotavirus vaccines is safe and effective and does not interfere with the
immune response to the other vaccine antigens (DTPa, Hib, IPV, hepB, and
7vPCV).28,29,35
Recommendations
(i) Routine infant vaccination (Safety-Grade B)(Efficacy-
Grade B)(Immunogenicity-not assessed)27
Administration of a course of oral rotavirus vaccination is recommended for all
infants in the first half of the first year of life. Vaccination of older infants and
children is not recommended as there are theoretical concerns regarding use in
older age groups (see ‘Adverse events’ below). Vaccination should occur at either
2 and 4 months of age (Rotarix), or 2, 4 and 6 months of age (RotaTeq), according
to the following schedules (see also Table 3.18.1):
• Rotarix (human monovalent rotavirus vaccine)
The vaccination course of Rotarix consists of 2 doses at approximately 2 and
4 months of age. The first dose should be given between 6 and 14 weeks of
age, and the second dose should be given by the end of the 24th week of age
(6 months). The interval between the 2 doses should not be less than 4 weeks.
• RotaTeq (pentavalent human-bovine reassortant rotavirus vaccine)
The vaccination course of RotaTeq consists of 3 doses at approximately 2, 4, and
6 months of age. The first dose should be given between 6 and 12 weeks of age,

and all doses should be given by the end of the 32nd week of age (~7.5 months).
The interval between doses should be 4 to 10 weeks.
Table 3.18.1: Age limits for dosing of oral rotavirus vaccines

Doses Age of Age limits for dosing Minimum
routine oral interval
administration 1st dose 2nd dose 3rd dose between
doses
Rotarix 2 oral 2 and 6–14* weeks 10–24* weeks None 4 weeks

(GlaxoSmithKline) doses 4 months
(1 mL/
dose)
RotaTeq 3 oral 2, 4 and 6–12† weeks 10–32† weeks 14–32† weeks 4 weeks

(CSL Biotherapies/ doses 6 months
Merck & Co Inc) (2 mL/
dose)
3.18 Rotavirus
* The upper age limit for receipt of the first dose of Rotarix is 14.9 weeks, that is up to the
anniversary of the 15th week of age and the upper age limit for receipt of the second dose of
Rotarix is 24.9 weeks, that is up to the anniversary of the 25th week of age.
† The upper age limit for receipt of the first dose of RotaTeq is 12.9 weeks, that is up to the
anniversary of the 13th week of age. The second dose of vaccine should preferably be given
by 28 weeks of age to allow for a minimum interval of 4 weeks before receipt of the third
dose, and the upper age limit for either the second or third doses is 32.9 weeks, that is by the
anniversary of the 33rd week of age.
For infants in whom the first dose of rotavirus vaccine is inadvertently

administered at an age greater than the suggested cut-off (14 weeks for Rotarix
or 12 weeks for RotaTeq), the remaining vaccine doses should be administered
as per the schedule, providing the minimum interval between doses can be
maintained, and the course completed within the recommended age limits. The
timing of the first dose should not affect the safety and efficacy of the second and
third dose.7 Infants who develop rotavirus gastroenteritis before receiving the
full course of rotavirus vaccinations should still complete the full 2- or 3-dose
schedule (dependent on the brand of vaccine) because one rotavirus infection
only provides partial immunity.7
(ii) Catch-up (no studies)

Routine ‘catch-up’ or primary vaccination of older children is not recommended.
recommended age limits for the first dose. It is also necessary to ensure that
doses are not given beyond the upper age limits for the final dose of the vaccine
course (see (i) above). This is based on theoretical concerns regarding possible
adverse events in older age groups (see ‘Adverse events’ below), and because
the safety of rotavirus vaccination in older infants and children has not been
established.
Rotavirus 269
(iii) Premature infants (Safety-Grade C)
(Efficacy-Grade C)(Immunogenicity-not assessed)27
Vaccination of preterm infants using either available rotavirus vaccine is
indicated at a chronologic age of at least 6 weeks if clinically stable. Premature
infants (<37 weeks’ gestation) appear to be at increased risk of hospitalisation
from viral gastroenteritis.36 In clinical trials, RotaTeq or placebo was administered
to 2070 preterm infants (25–36 weeks’ gestational age; median 34 weeks) who
experienced rates of adverse events after vaccination similar to matched placebo
recipients.7,27 Efficacy against rotavirus gastroenteritis of any severity was
evaluated in only a small subset of premature infants and appeared comparable
to efficacy in term infants (70%; 95% CI: -15%–95%). These conclusions would
also be expected to apply to Rotarix vaccine. If standard infection control
precautions are maintained, administration of rotavirus vaccine to hospitalised
infants, including hospitalised premature infants, would be expected to carry a
low risk for transmission of vaccine viruses (see ‘Precautions’ below).
Contraindications
The only absolute contraindications to rotavirus vaccines are:
• anaphylaxis following a previous dose of either rotavirus vaccine, or
Precautions
(i) Acute gastroenteritis
Infants with moderate to severe acute gastroenteritis should not be vaccinated
until after recovery from their acute illness. Infants with mild gastroenteritis
(including mild diarrhoea) can be vaccinated. The use of rotavirus vaccines has
not been studied in infants with acute gastroenteritis.
(ii) Moderate to severe illness

As with other vaccines, infants with a moderate to severe illness should be
vaccinated after recovery. In addition to the factors mentioned above in (i), this
avoids superimposing potential adverse events related to vaccination with the
concurrent illness.
(iii) Underlying conditions predisposing to severe rotavirus gastroenteritis

Conditions predisposing to severe or complicated rotavirus gastroenteritis
include metabolic disorders or chronic gastrointestinal disease, such as
Hirschsprung’s disease, malabsorption syndromes or short gut syndrome.1
Although the safety and efficacy of rotavirus vaccines have not been studied in
such infants, because they are at greater risk of serious rotavirus disease over an
extended age range, the potential benefits of vaccination at an age older than the
upper limits recommended in Table 3.18.1 are likely to be substantial. Vaccination
of such children at an older age may be judged by clinicians to warrant

discussion with parents on a case by case basis (see ‘Variations from product
information’ below).
(iv) Infants with impaired immunity

There are no studies of the safety or efficacy of the currently available rotavirus
vaccines in infants with impaired immunity. As with other live viral vaccines,
there are theoretical concerns that vaccine virus-associated gastrointestinal
disease could occur in infants with severely impaired immunity who receive
rotavirus vaccines. However, the theoretical risk for vaccine virus-associated
disease in immune-impaired vaccinated infants is likely to be less than their
risk from being exposed to disease from natural infection. Risks and benefits of
vaccination should be considered in the context of the infant’s specific immune
impairment with appropriate specialist advice7 (see (v) below, and Section 2.3.3,
3.18 Rotavirus
(v) Infants living in households with people with impaired immunity
Infants living in households with people who have impaired immunity should
be vaccinated. In general, household members with impaired immunity are
afforded protection by vaccination of young children in the household. This
outweighs the small risk for transmitting vaccine virus shed in stool to the
household member with impaired immunity. The theoretical risk for vaccine
virus-associated disease in contacts with impaired immunity is considered less
than their risk of being exposed to disease from natural infection. However, there
have been no studies to specifically address this question.7 (See also Section 2.3.3,
Vaccination of individuals with impaired immunity due to disease or treatment.)
(vi) Recent administration of antibody-containing blood products

Infants who have recently received antibody-containing blood products and are
at an eligible age should be vaccinated. The interval between vaccination and
receipt of the blood product should be as long as possible, but without delaying
administration of vaccine beyond the suggested age limits for dosing (as per
Table 3.18.1 above). This recommendation for maximising the interval is based on
theoretical concern that passively acquired antibody to rotavirus may interfere
with vaccine immunogenicity.7
(vii) Hospitalised infants

If a recently vaccinated child is hospitalised for any reason, no precautions other
than routine standard precautions need be taken to prevent the spread of vaccine
virus in the hospital setting. Administration of rotavirus vaccine to hospitalised
infants, including hospitalised premature infants, is likely to carry a low risk
for transmission of vaccine viruses if standard infection control precautions are
maintained (see ‘Vaccines’ above).
Rotavirus 271
(viii) Exposure of pregnant women to vaccinated infants
Infants living in households of pregnant women can receive rotavirus vaccines.
Most pregnant women will have pre-existing immunity to rotavirus but
avoidance of wild-type infection through the vaccination of infant contacts
may benefit adults, including pregnant women, and outweighs any theoretical
concern regarding exposure to vaccine viruses.
(ix) Regurgitation of vaccine dose

Readministration of the vaccine is not necessary after regurgitation, spitting out,
or vomiting of a rotavirus vaccine. This is because there are limited data available
on the safety of administering higher than the recommended dose of rotavirus
vaccines. There are no studies of the efficacy of a partially administered dose(s).
Adverse events
(i) Intussusception (IS)
Current evidence indicates that intussusception (IS, a form of bowel obstruction)
is not associated with either Rotarix or RotaTeq vaccines, especially when given
to infants within the age limits studied in clinical trials.27,30,32 Post-licensure data
in larger numbers of children will monitor if there is an increased risk of IS
following rotavirus vaccination, particularly among those inadvertently receiving
doses outside the recommended age limits. Concern about association between
IS and rotavirus vaccines arose because a tetravalent rhesus-reassortant vaccine,
called RotaShield, licensed in the United States (but not elsewhere) in 1998–99,
was associated with IS in approximately 1 in 10 000 vaccine recipients.37 The
greatest risk of IS occurred within 3 to 14 days after the first dose, with a smaller
risk after the second dose.37,38
There is evidence that when the first dose of RotaShield was given at >3 months
of age, the risk of intussusception was increased.38 The pathogenesis of
RotaShield-associated intussusception has not been determined. However,
the current rotavirus vaccines (RotaTeq and Rotarix) differ in composition to
RotaShield, which was also more reactogenic.39-41 The large-scale safety studies
of the 2 current rotavirus vaccines included approximately 140 000 infants,
and found the risk of IS in vaccine recipients to be similar to that of placebo
recipients, and less than that estimated for RotaShield.27,30,32 To minimise
background rates of IS, the clinical trials of Rotarix and RotaTeq limited
administration of the first dose of vaccine to infants under 14 and 12 weeks
of age, respectively, and did not give subsequent doses to infants beyond a
certain age (24 weeks for Rotarix and 32 weeks for RotaTeq).27,30,32 As such,
data on safety of these vaccines in older infants is not currently available (see
‘Recommendations’ above).

(ii) Other adverse events
Vaccine recipients developed gastrointestinal symptoms such as diarrhoea or
vomiting in the week after rotavirus vaccination more commonly than placebo
recipients (increased risk of up to 3%).27,30,32 Fever was not significantly more
common in rotavirus vaccine recipients compared with placebo recipients in
clinical trials of both available vaccines.27,30,32
Interchangeability of rotavirus vaccines

Completion of a course of rotavirus vaccine should be with vaccine from the
same manufacturer whenever possible. There are no studies that address the
interchangeability of the 2 available rotavirus vaccines. However, if either dose 1
or 2 of vaccine is given as RotaTeq, a third dose of either rotavirus vaccine should
be given, provided that the upper age limit and inter-vaccine interval, as defined
above in ‘Recommendations’, Table 3.18.1, are met.
3.18 Rotavirus
The product information for Rotarix states that the vaccine should not be
administered to subjects with chronic gastrointestinal disease. NHMRC
recommends that pre-existing chronic gastrointestinal disease is not considered
to be a contraindication to rotavirus vaccination (see ‘Precautions’ above).
References
Rotavirus 273
3.19 Rubella
Virology
Rubella is an enveloped togavirus, genus Rubivirus. The virus has an RNA
genome and is closely related to group A arboviruses, but does not require
a vector for transmission. It is relatively unstable, and is inactivated by lipid
solvents, trypsin, formalin, extremes of heat and pH, amantadine and UV light.1
Clinical features
Rubella is generally a mild and self-limiting infectious disease.2 It causes a
transient, generalised, erythematous, maculopapular rash, lymphadenopathy
involving the post-auricular and sub-occipital glands, and, occasionally,
arthritis and arthralgia. Other complications, such as neurological disorders and
thrombocytopenia, may occur but are rare. Clinical diagnosis is unreliable since
the symptoms are often fleeting and can be caused by other viruses; in particular,
the rash is not unique to rubella and may be absent.1,2 Up to 50% of rubella virus
infections are subclinical or asymptomatic.1 A history of rubella should, therefore,
not be accepted without serological evidence of previous infection.1 The
incubation period is 14 to 21 days, and the period of infectivity is from 1 week
before until 4 days after the onset of the rash.2 Rubella infection in pregnancy can
result in fetal infection resulting in congenital rubella syndrome (CRS) in a high
proportion of cases (see ‘Rubella infection in pregnancy’ below).
Epidemiology
Rubella occurs worldwide and is spread from person to person by droplet
contact and possibly air-borne transmission of infectious respiratory secretions.1
In temperate climates, the incidence is highest in late winter and early spring.3
The incidence of rubella has fallen rapidly since vaccine licensure, and there
has been a shift in the age distribution of cases, with comparatively more cases
being seen in older age groups, particularly the 20–24 year age group.4 In the
early 1990s, rubella epidemics were reported in those States where rubella
was notifiable.5 Over 3000 cases per year were reported between 1992 and
1995.5 In 2004–2005, rubella notifications were the lowest yet recorded with 31
confirmed cases being reported in each year (0.15 per 100 000 per year).4 This
low notification rate most likely reflects the high vaccine coverage achieved and
sustained with the National Measles Control Campaign in late 1998.3,6,7
The number of cases of congenital rubella syndrome has also fallen rapidly
since rubella vaccine licensure in Australia. Successful vaccination campaigns
and high vaccination coverage resulted in no cases of congenital rubella
syndrome occurring in infants of Australian-born mothers between 1998 and
2002. However, 5 cases resulting from infection acquired outside of Australia

were reported during this time.8,9 Between 2003 and 2005, an additional 5 cases
were reported from infection that occurred in Australia9-11 which reinforces the
need for high vaccination coverage of women of child-bearing age (see ‘Rubella
infection in pregnancy’ below).
The rubella virus was isolated in cell culture in 1962, and vaccines prepared
from strains of attenuated virus have been approved for use in Australia since
1970. Mass vaccination of schoolgirls commenced in 1971.1,12 Non-pregnant,
seronegative adult women were also vaccinated. These programs were
successful and there was a significant reduction in the incidence of congenital
rubella syndrome from 1977.13-15 There has also been a significant increase in the
percentage of pregnant women immune to rubella (in NSW from 82% in 1971
to 96% in 1983). Based on a recent study in Melbourne, it was estimated that, in
2000, only 2.5% of all women in Australia of child-bearing age were seronegative.
However, susceptibility was higher among overseas-born women, and has been
reported as higher among some Indigenous women.16,17
Many adolescent and young adult males are not immune to rubella because
they did not receive an MMR vaccine.18 The MMR vaccination program for all
adolescents replaced the rubella program for girls in 1993/94.12 A serosurvey
conducted in 1999 showed that only 84% of males aged 14–18 years (compared to
95% of females) and 89% of males aged 19–49 years (compared to 98% of females)
were immune to rubella.18 For this reason, adolescent and young adult males,
as well as females, who do not have a documented history of receipt of 2 doses
of MMR, should receive MMR vaccine (see ‘Recommendations’ below). This is
both for their own protection and to prevent transmission of the infection in the
community (see ‘The public health management of rubella’ below).
3.19 Rubella
Rubella infection in pregnancy
Maternal rubella infection in the first 8 to 10 weeks of pregnancy results in
fetal damage in up to 90% of affected pregnancies, and multiple defects are
common.19-21 The risk of damage declines to 10 to 20% by 16 weeks’ gestation.
After this stage of pregnancy, fetal damage is rare but has been reported up to
20 weeks’ gestation.19 The characteristics of congenital rubella syndrome include
intellectual disabilities, cataracts, deafness, cardiac abnormalities, intrauterine
growth retardation and inflammatory lesions of the brain, liver, lungs and
bone marrow.19 Any combination of these defects may occur, but defects which
commonly occur alone following infection after the first 8 weeks of pregnancy
are perceptive deafness and pigmentary retinopathy. Some infected infants may
appear normal at birth, but defects, especially sensorineural deafness, may be
detected later.22
Rubella reinfection can occur in individuals who have both natural and vaccine-
induced antibody.19 Occasional cases of congenital rubella syndrome after
reinfection in pregnancy have been reported. However, fetal damage is very rare in
cases of infection in women in whom antibody has previously been detected.20,23-25
Rubella 275
All pregnant women with suspected rubella or exposure to rubella should be
serologically tested, irrespective of a history of previous vaccination, clinical
rubella or a previous positive rubella antibody result (see ‘Serological testing
for rubella’ below). This is because the rash of rubella is not diagnostic,
asymptomatic infection can occur, and acute rubella can be confirmed only by
laboratory tests.19,23,24 Pregnant women should be counselled to restrict contact
with individuals with confirmed, probable or suspected rubella for 6 weeks (2
incubation periods).26 Counselling of pregnant women with confirmed rubella
regarding the risk to the fetus should be given in conjunction with the woman’s
obstetric service.
Serological testing for rubella

A number of commercial assays for testing immunity to rubella are available.
These vary according to the method used to determine the positive cut-off value
(the WHO cut-off is 10 IU/mL but, at present, there is no recommended Australian
minimal level). Available data support the presumption that an antibody level
found by use of a licensed assay to be above the standard positive cut-off for that
assay can be considered evidence of past exposure to rubella virus.23 Antibody
levels below the cut-off are likely not to be protective, particularly if the antibodies
have been generated by vaccination rather than by natural infection, and MMR
vaccine (or MMRV if protection against varicella is required in children 12 months
to 12 years of age) should be administered according to the ‘Recommendations’
below. Expert consultation and referral of sera to a reference laboratory are
recommended if there is a difficulty interpreting results.
Acute rubella infection is indicated by presence of rubella IgM or 4-fold or
greater increase in rubella IgG. Rubella IgM may not appear until a week after
clinical symptoms. Sera for IgG testing should be taken 7 to 10 days after onset of
illness and repeated 2 to 3 weeks later. The most recent date of potential exposure
should be obtained, if possible, to calculate the potential incubation period. As
some patients may have more than 1 exposure to a person with a rubella-like
illness, and because exposure may occur over a prolonged period, it is important
to ascertain the dates of the first and last exposures.26
Seronegative women of child-bearing age should be vaccinated (see
‘Recommendations’ below) and tested for seroconversion 8 weeks after
vaccination. All women should be informed in writing of the result of their
antibody test. Women should be screened for rubella antibodies shortly before
every pregnancy, or early in the pregnancy, or if pregnancy is contemplated,
irrespective of a previous positive rubella antibody result.15,19 Very occasionally,
errors may result in patients who are seronegative being reported as seropositive.
Where possible, specimens from pregnant women should be stored until the
completion of the pregnancy.
Serological testing of pregnant women exposed to rubella should always
be performed (see ‘Rubella infection in pregnancy’ above). A blood sample

should be taken and sent to the laboratory with the date of the last menstrual
period and the date of presumed exposure (or date of onset of symptoms).26
If the woman has an antibody titre below the protective level, or a low level
of antibodies and remains asymptomatic, a second blood specimen should
be collected 28 days after the exposure (or onset of symptoms) and tested in
parallel with the first. If the woman develops symptoms, the specimen should
be collected and tested as soon as possible. A third blood specimen may be
required in some circumstances.24
Vaccines
Rubella vaccine is available as either MMR vaccine or as a monovalent rubella
vaccine. It is anticipated that combination measles-mumps-rubella-varicella
(MMRV) vaccines will become available in the near future. A single dose of
rubella vaccine produces an antibody response in more than 95% of vaccinees,
but antibody levels are lower than after natural infection.19,23,24 Vaccine-induced
antibodies have been shown to persist for at least 16 years in the absence of
endemic disease.23,24,27,28 Protection against clinical rubella appears to be long-
term in those who seroconvert.19
Monovalent rubella vaccine
• Meruvax II – CSL Biotherapies/Merck & Co Inc (rubella virus vaccine).

Each 0.5 mL monodose of the reconstituted, lyophilised vaccine contains
not less than 1000 TCID50 (tissue culture infectious dose 50%) of attenuated
rubella virus (Wistar RA 27/3 strain); 25 µg neomycin; 3 mg human serum
albumin; sorbitol and gelatin as stabilisers.
3.19 Rubella
Combination measles-mumps-rubella vaccine


Transport both vaccines according to National Vaccine Storage Guidelines: Strive for
5.29 Store at +2°C to +8°C. Protect from light. Do not freeze. Reconstituted vaccine
should be used immediately, but can be stored at +2°C to +8°C for up to 8 hours
before use.
Rubella 277
For both children and adults, the dose of MMR and monovalent rubella vaccine
is 0.5 mL, administered by either SC or IM injection.
MMR and monovalent rubella vaccine can be given at the same time as other
vaccines (including DTPa, hepatitis B, MenCCV and varicella), using separate
syringes and injection sites. If MMR or monovalent rubella vaccine is not given
simultaneously with other live viral parenteral vaccines (eg. varicella vaccine),
they should be given at least 4 weeks apart (see ‘Precautions’ below).
Recommendations
The principal aim of rubella vaccination is to prevent congenital rubella
syndrome by stopping the circulation of rubella virus in the community.
Susceptible pregnant women will continue to be at risk of rubella infection in
pregnancy until the transmission of rubella virus is interrupted by a sufficiently
high uptake of rubella-containing vaccine in children and adults of both sexes.
(i) Routine vaccination of children

Two doses of rubella-containing vaccine are recommended for all children. The
first dose should be given at 12 months of age and the second dose at 18 months
of age (MMR or MMRV when available). The minimum interval between the
first and second doses of MMR or MMRV is 4 weeks. A history of rubella is not a
contraindication to vaccination. Individuals who are already immune to rubella
have no increased risk of side effects from vaccination.19,23
(ii) Vaccination of women of child-bearing age

Every effort should be made to identify non-pregnant seronegative women of
child-bearing age. The following women are more likely to be seronegative to
rubella: women born overseas (especially in Asia, Pacific islands, sub-Saharan
Africa and South America) who have entered Australia after the age of routine
vaccination; non-English speaking women; women over the age of 35; and
Muslim women.5,13,14,16,30 Seronegative women should be given MMR vaccine
and advised not to become pregnant for 28 days after vaccination. Monovalent
rubella vaccine can be used where there is a contraindication to the measles
or mumps components of MMR. Vaccinated women should be tested for
seroconversion 6 to 8 weeks after vaccination (see ‘Serological testing for rubella’
above). Women who have negative or very low antibody levels after vaccination
should be revaccinated. If their antibody levels remain low after a second
vaccination, it is unlikely that further vaccinations will improve this.19 Although
2 doses of MMR vaccine are routinely recommended, if rubella immunity
is demonstrated after receipt of 1 dose of a rubella-containing vaccine, no
further dose is required, unless indicated by subsequent serological testing (see
‘Serological testing for rubella’ above).

(iii) Vaccination of adolescent and adult males
All males born during or after 1966 require 2 doses of MMR at least 4 weeks
apart if they have no record of receiving the vaccine, as they are especially likely
to be non-immune to rubella (see ‘Epidemiology’ above).
(iv) Vaccination post-partum

Women found to be seronegative on antenatal rubella immunity testing should
be vaccinated after delivery and before discharge from the maternity unit.
MMR vaccine is recommended, although monovalent rubella vaccine can also
be used for this purpose. These women should be tested for rubella immunity
6 to 8 weeks after vaccination (see ‘Vaccination of women of child-bearing age’
above). Anti-D immunoglobulin does not interfere with the antibody response
to vaccine.1,19 If anti-D immunoglobulin is also required, the two may be given at
the same time in different sites with separate syringes, or at any time in relation
to each other24 (see ‘Contraindications’ below).
(v) Vaccination of healthcare workers and people working with children

All healthcare staff and people working with children, born during or since 1966,
including medical, nursing, and other health professional students, either without
vaccination records or seronegative upon screening, should receive 2 doses of
MMR vaccine, both for their own protection and to avoid the risk of transmitting
rubella to pregnant patients and/or colleagues31 (see Table 2.3.6 Recommended
vaccinations for those at risk of occupationally acquired vaccine-preventable diseases).
Preferably, MMR should be used. Where necessary, those vaccinated can be tested
for seroconversion 8 weeks after vaccination and revaccinated if seronegative (see
‘Vaccination of women of child-bearing age’ above).
3.19 Rubella
For further recommendations related to MMR vaccination, see Chapter 3.11,
Measles.
Contraindications
Vaccination is contraindicated in the following circumstances:

• anaphylaxis following a previous dose of rubella, MMR or MMRV, or
(ii) People with impaired immunity

Rubella-containing vaccine should not be administered to patients with
congenital or acquired impaired immunity (see Section 2.3.3, Vaccination of
individuals with impaired immunity due to disease or treatment). This includes
those receiving high-dose corticosteroid or immunosuppressive treatment,
general radiation, malignant conditions of the reticuloendothelial system (such
as lymphoma, leukaemia, Hodgkin’s disease), or in cases where the normal
Rubella 279
immunological mechanism may be impaired, as in hypogammaglobulinaemia.1,23
Rubella vaccine or MMR may be given to HIV-positive individuals unless they
have severely impaired immunity.23 (For further information on MMR and
MMRV vaccines, see Chapter 3.11, Measles and Chapter 3.24, Varicella).
(iii) Recent administration of antibody-containing blood product

Rubella-containing vaccine should not be given within at least 3 months after an
injection of immunoglobulin, other antibody-containing blood product, or whole-
blood transfusion, because the expected immune response may be impaired.19,24
The recommended intervals for receipt of rubella-containing vaccines after receipt
of blood products are given in Table 2.3.5 Recommended intervals between either
immunoglobulins or blood products and MMR, MMRV or varicella vaccination. Rubella-
containing vaccines may be administered concomitantly with, or at any time in
relation to, anti-D immunoglobulin, but at a separate injection site. However,
women who have received anti-D immunoglobulin should be serologically tested
8 weeks after vaccination to ensure that seroconversion has occurred.1,23
(iv) Pregnant women

MMR and monovalent rubella vaccines should not be given to a woman known
to be pregnant, and pregnancy should be avoided for 28 days after vaccination
(see ‘Use in pregnancy’ below).1,32 Data on the use of MMRV vaccines in
individuals >12 years of age are not available.
Precautions
• If MMR or monovalent rubella vaccine is not given simultaneously with
other live viral parenteral vaccines (eg. varicella vaccine), they should be
given at least 4 weeks apart.
• Breastfeeding is not a contraindication to rubella vaccination. The rubella
vaccine virus may be secreted in human breast milk, and there have been
rare cases of transmission of vaccine virus through breast milk reported.
However, these infections have been mild.1
• There is no risk to pregnant women from contact with recently vaccinated
individuals. The vaccine virus is not transmitted from vaccinees to
susceptible contacts.1
For precautions related to MMR and MMRV vaccines, see Chapter 3.11, Measles
and Chapter 3.24, Varicella.
Adverse events
Mild adverse events such as fever, sore throat, lymphadenopathy, rash, arthralgia
and arthritis may occur after vaccination.1,23 Symptoms most often begin 1 to
3 weeks after vaccination and are usually transient. Joint symptoms are more
common in adults, especially women (10 to 25%, very common) than in children
(0.3%, uncommon).1,23 Thrombocytopenia, that is usually self limiting, has been

reported rarely after rubella vaccine.23 Very rarely, neurological symptoms have
been reported, but a causal relationship has not been established.23
For adverse events related to MMR and MMRV vaccines, see Chapter 3.11,
Measles and Chapter 3.24, Varicella.
The public health management of rubella

All cases of suspected rubella infection should be laboratory tested and false
positive results excluded. Infected individuals should be excluded from school/
work/institution and should avoid contact with women of child-bearing age for
at least 4 days after the onset of the rash.26
All contacts should be identified, especially those who are pregnant. If a contact
is pregnant, see ‘Rubella infection in pregnancy’ above. All contacts >12 months
of age without adequate proof of immunity should receive 1 dose of MMR (or
MMRV, when available, in those 12 months to 12 years of age). This will not
prevent rubella disease if already exposed. If vaccination is refused, the contact
should avoid further contact with cases until at least 4 days after onset of the rash
in the case.
Exposed healthcare workers without adequate proof of immunity should be
excluded from work for 21 days from exposure or for at least 4 days after the
onset of a rash.26
Use in pregnancy
Vaccination should be avoided in early pregnancy.1 However, active
surveillance in the USA, UK and Germany indicates that no case of vaccine-
induced congenital rubella syndrome occurred among more than 500 women
3.19 Rubella
inadvertently vaccinated with rubella vaccine during pregnancy, whose
pregnancies continued.33 In a recent Iranian study performed after mass
vaccination with a measles-rubella vaccine, 117 susceptible women were
inadvertently vaccinated while pregnant or became pregnant ≤3 months after
vaccination. There were no CRS-related abnormalities among the infants born
to these women.34 Based on this evidence, the vaccine cannot be considered to
be teratogenic, and termination of pregnancy following inadvertent vaccination
is not indicated1,24 (see Section 2.3.2, Vaccination of women planning pregnancy,
pregnant or breastfeeding women, and preterm infants).
Use of normal human immunoglobulin

(NHIG) to prevent rubella
Post-exposure prophylaxis with NHIG does not prevent infection in non-immune
contacts and is, therefore, of little value for protection of pregnant women
exposed to rubella.23 It may, however, prolong the incubation period, which
may marginally reduce the risk to the fetus. It may also reduce the likelihood
of clinical symptoms in the mother. NHIG should only be used if termination
Rubella 281
for confirmed rubella would be unacceptable under any circumstances. In such
cases, IM administration of 20 mL of NHIG within 72 hours of rubella exposure
might reduce – but will not eliminate – the risk for rubella.23 Serological follow-
up of recipients is essential, and should continue for up to 2 months.
There is some evidence to suggest that, in outbreak situations, pre-exposure
NHIG may be effective in preventing infection in women who are likely to be
pregnant, and its use may be indicated for such women with low antibody titres
in high-risk occupations.35

The product information recommends that women of child-bearing age should
be advised not to become pregnant for 3 months after vaccination with rubella,
MMR or MMRV vaccines, whereas NHMRC recommends 28 days.32
The product information for Meruvax II recommends the vaccine be given by SC
injection, but NHMRC recommends administration by either SC or IM injection.
The product information for Meruvax II states that there is no reason to
revaccinate individuals who were vaccinated originally when 12 months of age
or older. However, NHMRC recommends routine administration of a second
dose of rubella vaccine when given as MMR or MMRV to children.
References

3.20 Smallpox
Virology
The smallpox or variola virus is one of the poxviruses, a group characterised by
large brick-shaped virus particles, which includes the agents vaccinia, monkeypox,
mousepox and cowpox. The virus is inhaled into the respiratory tract, multiplies
in local lymph nodes and then seeds to the reticuloendothelial system. During the
clinical prodrome the virus then circulates to the skin and mucous membranes
where the cell destruction produces the characteristic vesicular lesions.1
Clinical features
An incubation period of about 12 days is abruptly followed by the prodrome, a
2 to 5 day period of high fever, malaise and severe headache. Then follows the
pharyngeal enanthum and, a day later, the skin rash begins as small red macules
before progressing to papules, vesicles and finally pustules over the next 4 to
7 days.1 Death follows in about 20% of cases. The diagnosis is made by collecting
vesicular fluid for examination by electron microscopy, or for detection of viral
nucleic acids by amplification techniques. Diseases that are most likely to mimic
smallpox in Australian populations are varicella and drug eruptions.
Epidemiology
Smallpox, a disease only of humans, was declared eradicated in 1979 after an
intense international campaign of detection and vaccination. The disease would
now be of only historical interest if not for concerns that illicit laboratory stocks
of the virus may exist and may be used as biological weapons.2 In the days of
endemic disease in rural areas, each case of smallpox would generate several
more cases among family and friends attending the victim, who was usually
bed-bound from the onset of the prodromal illness. The epidemiology of
disease spread by bioterrorists may be quite different. Patients hospitalised
in the prodromal period may widely transmit the virus during coughing, as
demonstrated in an outbreak in a German hospital after admission of one patient
with unrecognised smallpox.3
Vaccines
3.20 Smallpox
Little is known of the origin of vaccinia virus, the poxvirus used to immunise
humans against smallpox. Despite its name, which has been given generally to
compounds (vaccines) which induce artificial immunity, it is not cowpox.4-6
Australia has stocks of smallpox vaccine for use in an emergency situation only.4-6
The USA smallpox vaccine Dryvax, has been used to vaccinate Australian laboratory
personnel working with poxviruses. This vaccine contains vaccinia which produces
cross-immunity against variola. Dryvax is a freeze-dried formulation.
Smallpox 283
The duration of immunity is uncertain. A recent review, examining the frequency
of adverse events after vaccination with different vaccinia strains, reported that
the Lister strain vaccine is associated with a higher risk of severe adverse events,
in particular postvaccinal encephalopathy.7

Transport according to Guidelines for smallpox outbreak, preparedness, response and
management.4 Smallpox vaccine should be kept frozen at –30°C. The shelf life of
the vaccine is 24 hours once thawed and, once thawed, the vaccine should be
stored at +2°C to +8°C.

Only trained healthcare workers should perform smallpox vaccination. One of
several techniques can be used to place a tiny volume of the reconstituted vaccine
on the skin of the lateral surface of the upper arm. Most commonly, a bifurcated
needle is dipped into a multidose container and then positioned vertically over
the skin, which is then punctured repeatedly with sufficient vigour to produce no
more than a trace of blood at the site.4-6,8
Personal protective equipment must be used while performing smallpox
vaccination.
Smallpox vaccines must not be injected subcutaneously, intramuscularly or
intravenously.
Intradermal inoculation with smallpox vaccine results in the formation of an
erythematous papule within 3 to 5 days. It becomes a vesicle, then a pustule
reaching a maximum size of 1 to 2 cm in 8 to 12 days, then scabs and separates
by 14 to 21 days. When the procedure results in this circumscribed infection,
vaccination provides long-term protection against fatal disease. Furthermore,
vaccination very soon after exposure to smallpox markedly attenuates or
prevents clinical disease.4-6
Recommendations
The only current indication for vaccination in Australia is for workers using live
pox virus in recombinant gene research, in order to prevent infection at sites
of accidental inoculation. Currently, no vaccine is licensed for use in Australia;
however, information about sources of vaccines and their use should be obtained
from the Therapeutic Goods Administration, Canberra.4
Australian guidelines for smallpox outbreak, preparedness, response and
management may be found at http://www.health.gov.au/internet/wcms/
publishing.nsf/Content/health-pubhlth-publicat-others.htm.4

Contraindications
The vaccine is contraindicated in:4,5
• people with diseases that cause impaired immunity such as human
immunodeficiency virus (HIV) infection, acquired immune deficiency
syndrome (AIDS), leukaemia, lymphoma, generalised malignancy,
agammaglobulinaemia,
• those undergoing therapy with alkylating agents, antimetabolites, radiation
or large doses of steroids,
• those who have ever been diagnosed with eczema, even if the condition is
mild or not presently active,
• those with a history of neurological disorder,
• women who are either pregnant or trying to become pregnant,
• women who are breastfeeding,
• children aged <1 year,
• anyone living in a household with a member who has any of the conditions
listed above,
• people with serious, life-threatening allergies to the antibiotics polymyxin
B, streptomycin, tetracycline or neomycin (this may depend on brand of
vaccine used),
• those vaccinated in the past 30 days with a live vaccine,
• those with a history of cardiac disease, including:
• previous myocardial infarction,
• angina,
• congestive heart failure,
• cardiomyopathy,
• valvular disease, including rheumatic heart disease,
• stroke or transient ischaemic attack,
• chest pain or shortness of breath with activity,
• other heart conditions under the care of a doctor.
Precautions4-6
3.20 Smallpox
Individuals with acute or chronic skin conditions, such as atopic dermatitis,

impetigo and varicella-zoster (chickenpox and shingles), should not be
vaccinated until the condition resolves.
Individuals with eczema should live apart from recently vaccinated family
members who may have skin lesions.
Smallpox 285
Women should be advised to avoid pregnancy for 3 months after smallpox
vaccination.
Anyone who receives a smallpox vaccination should not receive another live
vaccine for 1 month afterwards.
Adverse events4-6,8
Smallpox vaccines have well described adverse events, which vary in frequency
according to the virus present in the seed stock. They include:
• postvaccinal encephalitis (PVE) or encephalomyelitis (PVEM), a
demyelinating disease which occurs at a rate of 1 per 300 000 vaccinations;
PVE is generally seen in those aged <1 year and PVEM in those aged
>2 years;
• progressive vaccinia (vaccinia gangrenosa) at the site of inoculation, in
vaccinees with immune impairment;
• eczema vaccinatum, being vaccinial skin disease at sites of previous or
current eczema; occurs at a rate of about 1 in 26 000 vaccinations;
• generalised vaccinia, a self-limiting condition resulting from blood-borne
dissemination of the virus to other skin sites; more serious in people with
impaired immunity; occurs at a rate of 1 in 5000 vaccinations;
• inadvertent inoculation of either the vaccinee or vaccinator in sites such as
the face, eyes or hands; occurs at a rate of 1 in 20 000 primary vaccinations;
• various skin rashes, usually self-limiting but can progress to Stevens-Johnson
Syndrome;
• fetal vaccinia is rare (<50 reported cases), greatest risk occurs during the third
trimester;
• cardiac adverse events including myocarditis, pericarditis and, possibly,
dilated cardiomyopathy.
Use in pregnancy
Smallpox vaccine is contraindicated in women who are either pregnant or trying
to become pregnant. Women should be advised to avoid pregnancy for 3 months
after vaccination.
Vaccinia immune globulin4,5

Vaccinia immune globulin (VIG) is a sterile solution of the immunoglobulin
fraction of plasma containing antibodies to the vaccinia virus, from individuals
who were previously vaccinated with smallpox vaccine. VIG and the nucleoside
analogue active against poxviruses, cidofovir, may be used to treat vaccine
complications such as inadvertent inoculation of the eye or eyelid without
vaccinal keratitis, severe generalised vaccinia if patient is toxic, eczema

vaccinatum and progressive vaccinia. VIG is not indicated for treatment of
vaccinal keratitis or postvaccinal encephalitis.
VIG is contraindicated in those with a history of anaphylactic sensitivity to
thiomersal or to other humanised monoclonal antibodies.
There are currently limited stocks of VIG and cidofovir available in Australia.
Contact the Australian Government Department of Health and Ageing or
your State/Territory Health Department for further information regarding
these products (see Appendix 1, Contact details for Australian, State and Territory
References
3.20 Smallpox
Smallpox 287
3.21 Tetanus
Bacteriology
Tetanus is caused by Clostridium tetani, a motile, non-capsulated, Gram-positive
rod that forms endospores. Spores of the bacillus are found in manured soil and
can enter wounds. Once in a wound site, the bacillus can grow anaerobically. C.
tetani produces a potent protein toxin which has 2 components, tetanospasmin (a
neurotoxin) and tetanolysin (a haemolysin).
Clinical features
Tetanus is an acute, often fatal, disease caused by the toxin produced by C. tetani.
The neurotoxin acts on the central nervous system to cause muscle rigidity
with painful spasms. The disease usually occurs after an incubation period of
3 to 21 days (range 1 day to several months), with a median time of onset after
injury of 10 days. Generally, a shorter incubation period is associated with a
more heavily contaminated wound, more severe disease and a worse prognosis.
Generalised tetanus, the most common form of the disease, is characterised
by increased muscle tone and generalised spasms. Early symptoms and signs
include increased tone in the masseter muscles (trismus, or lockjaw), dysphagia,
stiffness or pain in the neck, shoulder and back muscles. Some patients develop
paroxysmal, violent, painful, generalised muscle spasms. A constant threat
during generalised spasms is reduced ventilation or apnoea or laryngospasm.
The patient may be febrile, although many have no fever; mental state is
unimpaired. Sudden cardiac arrest sometimes occurs, but its basis is unknown.
Other complications include pneumonia, fractures, muscle rupture, deep vein
thrombophlebitis, pulmonary emboli, decubitus ulcers and rhabdomyolysis.
Death results from respiratory failure, hypertension, hypotension or cardiac
arrhythmia.
Tetanus is rare in people who have received 5 doses of a tetanus-containing
vaccine (1 in 90 cases in the United Kingdom from 1984–2000).1 However,
individual cases have been reported2,3 and clinicians should consider
tetanus when there are appropriate symptoms and signs, irrespective of the
person’s vaccination record. A high level of diagnostic awareness of tetanus
is particularly important in the elderly in industrialised countries, including
Australia, as most deaths occur in people over 70 years of age, especially
women, and may be associated with apparently minor injury.1,4
Neonatal tetanus usually occurs as the generalised form and is usually fatal
if left untreated. It develops in children born to inadequately immunised
mothers, frequently after unsterile treatment of the umbilical cord stump. Its
onset generally occurs during the first 2 weeks of life. Poor feeding, rigidity, and
spasms are typical features of neonatal tetanus.

Epidemiology
In Australia, tetanus is rare, occurring primarily in older adults who have never
been vaccinated or were vaccinated in the remote past. There were 18 notified
3.21 Tetanus
cases of tetanus during 2001–2005, but 120 hospitalisations (July 2000–June
2005) where tetanus was the principal diagnosis.4,5 This discrepancy suggests
under-notification. During 2001–2005, there were 2 deaths from tetanus.4,5 The
case-fatality rate in Australia is about 3%. Neonatal tetanus is a frequent cause of
infant mortality in parts of Asia, Africa and Latin America.
Effective protection against tetanus can be provided only by active immunisation.
Tetanus vaccine was introduced progressively into the childhood vaccination
schedule after World War II. The effectiveness of the vaccine was demonstrated
in that war; all Australian servicemen were vaccinated against tetanus and none
contracted the disease. As tetanus can follow apparently trivial, even unnoticed
wounds, active immunisation is the only certain protection.1 A completed course
of vaccination provides protection for many years.
Vaccines

Tetanus 289

Adsorbed diphtheria-tetanus vaccine
• ADT Booster – Statens Serum Institut/CSL Biotherapies (dT; diphtheria-

tetanus, adult formulation). Each 0.5 mL pre-filled syringe or monodose vial
contains ≥2 IU diphtheria toxoid and ≥20 IU tetanus toxoid adsorbed onto
0.5 mg aluminium hydroxide.


streptomycin.

3.21 Tetanus

Tetanus vaccination stimulates the production of antitoxin, which protects

against the toxin produced by the organism. The immunogen is prepared by
treating a cell-free preparation of toxin with formaldehyde, thereby converting
it into the innocuous tetanus toxoid. Tetanus toxoid is usually adsorbed onto an
adjuvant, either aluminium phosphate or aluminium hydroxide, to increase its
immunogenicity. Antigens from Bordetella pertussis, in combination vaccines, also
act as an effective adjuvant.
Complete immunisation (5 doses) induces protective levels of antitoxin lasting
throughout childhood but, by middle age, about 50% of vaccinees have low
or undetectable levels.6-8 A single dose of tetanus toxoid produces a rapid
anamnestic response in such vaccinees.9-11
Tetanus toxoid is available in combination with other antigens. Production
of the previously available tetanus toxoid vaccine was discontinued by the
manufacturer in February 2006. Production of the previous DT (CDT vaccine),
registered for use in children <8 years of age, ceased in June 2005. ADT Booster
can be used for the booster dose of dT in people aged ≥8 years or, if necessary, for
the primary dT course (see ‘Variations from product information’ below).

+2°C to +8°C. Protect from light. Do not freeze.

The dose of tetanus-containing vaccine is 0.5mL by IM injection.
Do not mix DTPa-containing vaccines, dTpa or dT vaccine with any other
vaccine in the same syringe, unless specifically registered for use in this way.
Tetanus 291
Recommendations
(i) Vaccination in childhood
Vaccination against tetanus is part of the National Immunisation Program
(NIP) schedule, with tetanus toxoid being given in combination with diphtheria
toxoid and acellular pertussis as DTPa vaccine. The recommended primary
course of vaccination is at 2, 4 and 6 months of age. A booster dose of DTPa is
given at 4 years of age. Immunity to tetanus will not be compromised before the
booster dose, as the serological response to the primary course of vaccination is
usually sufficient for those years. A second booster, using the adolescent/adult
formulation, dTpa, at 12–17 years of age, is essential for maintaining immunity
to tetanus in adults. By the age of 17 years, young adults should have received
5 doses of a tetanus toxoid-containing vaccine, and may have received an extra
dose if they have experienced a tetanus-prone wound during childhood.

Booster vaccination
Routine 10-yearly booster doses in adults who have previously received 5 doses
of a tetanus-containing vaccine have not been recommended in Australia since
2000. All adults who reach the age of 50 years and have not received a booster
dose of a tetanus-containing vaccine in the previous 10 years should be given
dT or dTpa vaccine. This stimulates further production of circulating tetanus
antibodies at an age when waning of diphtheria and tetanus immunity is
commencing in the Australian population.6 The adolescent/adult formulation
dTpa is preferred, if not given previously, as it provides additional protection
against pertussis (see Chapter 3.14, Pertussis).
Primary vaccination
Where an adult has not received a primary course of tetanus toxoid previously,
3 doses of dT should be given, at minimum intervals of 4 weeks, followed
by booster doses at 10 and 20 years after the primary course. Give the first of
these doses as dTpa, to provide boosting to natural immunity from exposure
to pertussis, which is almost universal in unvaccinated adults. In the event that
dT vaccine is not available, dTpa can be used for all primary doses. However,
this is not recommended routinely because there are no data on the safety,
immunogenicity or efficacy of dTpa in multiple doses for primary vaccination.
Tetanus-prone wounds
Adults who have sustained injuries deemed to be tetanus prone should receive
a booster dose of dT, if more than 5 years have elapsed since the last dose. In the
event that dT vaccine is not available, dTpa can be used (see Table 3.21.1 below).

(iii) Other people at special risk
Adults who were born in countries without adequate vaccination programs
may never have received primary vaccination against tetanus. Older adults may
have inadequate antitoxin levels, due to incomplete primary vaccination against
3.21 Tetanus
tetanus. Injecting drug users are at risk of tetanus, particularly if skin ‘popping’
is practised.13
Travellers to countries where health services are difficult to access should be
adequately protected against tetanus before departure. They should receive a
booster dose of dT, if more than 10 years have elapsed since the last dose, or
dTpa if not given previously.
Tetanus-prone wounds
In the event of a tetanus-prone injury (defined below), a booster dose of vaccine
should be given if more than 5 years have elapsed since the last dose. If there
is any doubt about the adequacy of previous tetanus immunisation, tetanus
immunoglobulin (see below) should be given as well as tetanus toxoid (see Table
3.21.1). In children <8 years of age, this dose of vaccine should be given as DTPa
or a DTPa-combination vaccine, consistent with the child’s vaccination history
and the NIP schedule. For details on the management of children who have
missed doses in the NIP schedule, see Section 1.3.5, Catch-up.
The definition of a tetanus-prone injury is not straightforward, as tetanus
may occur after apparently trivial injury, such as from a rose thorn, or with no
history of injury. However, there are certain types of wounds likely to favour the
growth of tetanus organisms. These include compound fractures, bite wounds,
deep penetrating wounds, wounds containing foreign bodies (especially wood
splinters), wounds complicated by pyogenic infections, wounds with extensive
tissue damage (eg. contusions or burns) and any superficial wound obviously
contaminated with soil, dust or horse manure (especially if topical disinfection
is delayed more than 4 hours). Reimplantation of an avulsed tooth is also a
tetanus-prone event, as minimal washing and cleaning of the tooth is conducted
to increase the likelihood of successful reimplantation.
Tetanus 293
General measures for treatment of tetanus-prone wounds14-19
Table 3.21.1: Guide to tetanus prophylaxis in wound management
History Time since Type of wound DTPa, DTPa- Tetanus

of tetanus last dose combinations, immunoglobulin*
vaccination dT, dTpa, as (TIG)
appropriate
≥3 doses <5 years All wounds NO NO
≥3 doses 5–10 years Clean minor NO NO
wounds
≥3 doses 5–10 years All other YES NO
wounds
≥3 doses >10 years All wounds YES NO
<3 doses or Clean minor YES NO
uncertain† wounds
<3 doses or All other YES YES
uncertain† wounds
* The recommended dose for TIG is 250 IU, given by IM injection using a 21 gauge needle, as
soon as practicable after the injury. If more than 24 hours has elapsed, 500 IU should be given.
† Individuals who have no documented history of a primary vaccination course (3 doses)
with a tetanus toxoid-containing vaccine should receive all missing doses. See Section 1.3.5,
Catch-up.
As an alternative to dT vaccine after a tetanus-prone wound, adults can receive

a single dose of dTpa vaccine to provide additional protection against pertussis
(providing they have not received a dose of dTpa previously).20
Whatever the immune status of an individual with a tetanus-prone wound,
local disinfection and, where appropriate, surgical treatment of tetanus-prone
wounds, must never be omitted. The use of antibiotics (such as penicillin or
metronidazole) for preventing infection is a matter for clinical judgement.
The recommended use of booster tetanus vaccines and the use of human tetanus
immunoglobulin are set out in Table 3.21.1. These should be administered as
soon as possible after the injury.
Tetanus immunoglobulin
Tetanus immunoglobulin (human) for intramuscular use
• Tetanus Immunoglobulin-VF (TIG) – CSL Bioplasma. 160 mg/mL solution

of immunoglobulin from selected human plasma with high concentration of
antibodies to tetanus toxin, 250 IU.

(i) TIG should be used for passive protection of individuals who have sustained
a tetanus-prone wound, where the person has not received 3 or more doses of
a tetanus toxoid-containing vaccine or where there is doubt about their tetanus
vaccination status. TIG provides immediate protection, for a period of 3 to 4 weeks.
3.21 Tetanus
(ii) The recommended dose for TIG is 250 IU by IM injection, to be given as soon
as practicable after the injury. If more than 24 hours have elapsed, 500 IU should
be given. A tetanus toxoid-containing vaccine should be given at the same time in
the opposite limb with a separate syringe, and arrangements should be made to
complete the full course of tetanus toxoid-containing vaccinations.
(iii) Because of its viscosity, TIG should be given to adults using a 21 gauge
needle. For children, it can be given slowly, using a 23 gauge needle.
(iv) For wounds not categorised as tetanus-prone, such as clean cuts that have
been treated appropriately, TIG is unnecessary.
Tetanus immunoglobulin (human) for intravenous use
• Tetanus Immunoglobulin-VF (human, for intravenous use) – CSL Bioplasma.

60 mg/mL solution of immunoglobulin fraction of selected human plasma
with high concentration of antibodies to tetanus toxin, 4000 IU.
This product is used in the management of clinical tetanus. The recommended

dose is 4000 IU given by slow intravenous infusion. Detailed protocols for
administration of this product and management of adverse events should be
consulted if its use is contemplated.
Contraindications
The only absolute contraindications to tetanus vaccine are:
If an individual has a tetanus-prone wound and has previously had a severe

adverse event following tetanus vaccination, alternative measures, including the
use of human tetanus immunoglobulin, can be considered.
Precautions
In previously vaccinated people, administration of more than 1 dose of a tetanus-
containing vaccine in a 5-year period may provoke adverse events.
Adverse events
Mild discomfort or pain at the injection site persisting for up to a few days is
common. Uncommon general adverse events following dT vaccine include
headache, lethargy, malaise, myalgia and fever. Anaphylaxis, urticaria and
peripheral neuropathy very rarely occur (brachial neuritis occurs in 0.001% of
Tetanus 295
cases). For specific adverse events following combination vaccines containing
both tetanus and pertussis antigens, see Chapter 3.14, Pertussis.
Use in pregnancy

The product information for ADT Booster states that this vaccine is indicated
for a booster dose only in children aged ≥5 years and adults who have
previously received at least 3 doses of diphtheria and tetanus vaccines. NHMRC
recommends that, where a dT vaccine is required for any person ≥8 years of
age, ADT Booster can be used, including for primary immunisation against
diphtheria and tetanus.
vaccines states that these vaccines are indicated for booster doses only.
NHMRC recommends that, where dT is unavailable for the primary course,
dTpa can be used.
recommends that dTpa vaccines can be administered at any time following
receipt of a diphtheria and tetanus toxoid-containing vaccine.
References

3.22 Tuberculosis
Bacteriology
Tuberculosis (TB) is caused by organisms of the Mycobacterium tuberculosis
complex (M.TB complex), that are slow-growing, aerobic, acid-fast bacilli. The
M.TB complex consists of Mycobacterium tuberculosis, M. bovis, M. microti, M.
canetti and M. africanum.1 M. tuberculosis is the cause of almost all TB in Australia,
whereas M. bovis, M.canetti and M. africanum are rare.2
Clinical features
As infection is usually air-borne, lung disease is the most common form of
tuberculosis, accounting for approximately 60% of notified TB cases in Australia.3
3.22 Tuberculosis
Cough, fever, sweats, weight loss and haemoptysis are common symptoms
of pulmonary TB. TB lymphadenitis is the most common extrapulmonary
manifestation, but the disease can occur in any part of the body, including the
meninges, bone and kidneys. Disseminated disease (miliary TB) and meningeal
TB are the most serious forms, particularly in children.1
Most individuals infected with M. tuberculosis remain asymptomatic, but there is
a 10% lifetime risk of developing clinical illness, sometimes many years after the
original infection. Infants, the elderly and patients with impaired immunity due
to drugs or disease or as a result of adverse socioenvironmental circumstances
(eg. malnutrition, alcoholism) are more prone to rapidly progressive or
generalised infection.1,4
Epidemiology
The World Health Organization (WHO) declared tuberculosis a global emergency
in 1993, and recent reports have reaffirmed the threat to human health.5 About
1000 cases of TB are notified to Australian health authorities each year. The
annual notification rate for TB has been relatively stable at approximately 5 to
6 cases per 100 000 population since 1985, and multi-drug resistance remains
rare, occurring in less than 2% of notified cases.2 Tuberculosis in animals (M.
bovis) has been eradicated by screening and culling programs. In Australia, most
TB cases (greater than 80%) occur in people born overseas, particularly in Asia,
southern and eastern European countries, the Pacific Islands, and north and sub-
Saharan Africa. The rates of TB in the overseas-born population have been slowly
increasing over the past decade.3 High TB rates seen in people from Ethiopia,
Somalia and the Sudan reflect recent changes in the composition of Australia’s
migrant and refugee intake.3,6 Rates of TB are also high in Aboriginal and Torres
Strait Islander people and in Papua New Guineans living in some parts of
Australia.3,7
Tuberculosis 297
Patients with impaired immunity are at high risk of developing active TB if
they are infected with M. tuberculosis.4,5 Screening programs in Australia now
concentrate on those at high risk, including contacts of notified patients.
Vaccine
• BCG vaccine – Sanofi Pasteur Pty Ltd (freeze-dried live vaccine prepared
from an attenuated strain of Mycobacterium bovis). When reconstituted with
accompanying buffered saline diluent, vaccine contains between 8–32 x
106 colony forming units per mL and monosodium glutamate 1.5% w/v.
Reconstituted vaccine provides about 10 adult or 20 infant doses.
BCG (Bacille Calmette-Guérin) vaccine is a suspension of live attenuated M. bovis.

Worldwide, there are many BCG vaccines available but they are all derived from
the strain propagated by the Institut Pasteur and first tested in humans in 1921.8
Protective efficacy ranges from 0 to 80% in controlled trials. The variation has
been attributed to differences in vaccine strains, local prevalence of (protective)
environmental mycobacteria, and host factors such as age at vaccination and
nutritional status. Geographic latitude and vaccine strains explain most of the
variation in efficacy. However, it should be noted that BCG is highly effective in
children, particularly those <5 years of age, for whom it is primarily intended.
The efficacy of BCG in adolescents and adults is less.
BCG is primarily intended for children as meta-analyses have found the
protective efficacy for preventing serious forms of TB in this group is over
80%.9 Protective efficacy in all age groups is about 50%.10,11 An Australian study
reported a protective efficacy of 30%, at best, in school-aged children.12 Protective
efficacy is difficult to quantify and may vary from 10 years to 50 years.13,14 The
WHO does not recommend repeat vaccination.
In some studies, BCG has been shown to offer some protection against leprosy.15

reconstituted vaccine at +2°C to +8°C or unreconstituted (freeze-dried) vaccine
in a freezer at –20°C. Protect vaccine from light (sunlight or fluorescent). Store
diluent at +2°C to +8°C and do not freeze. Reconstituted BCG vaccine is very
unstable and should be discarded after one working session of 8 hours. Do not
freeze reconstituted BCG vaccine.

BCG vaccine is administered as a single dose by intradermal injection. It
should be given only by specially trained medical or nursing staff who are fully
conversant with the following procedures:

Tuberculin test all individuals, except infants <6 months of age, before
vaccination. Read the test 48 to 72 hours later and, where 5 tuberculin units has
been given, give BCG only to those who have <5 mm of induration.
• Give 0.1 mL of BCG to children and adults, and 0.05 mL to infants
<12 months of age.
• Use a short (10 mm) 26–27 gauge needle with a short bevel. The risk of
spillage can be minimised by using an insulin syringe to which the needle is
already attached.
• Wear protective eye-wear. The patient and parent holding the patient (if
patient is a small child requiring restraint) should also wear protective eye-
wear. Eye splashes may ulcerate, so if an eye splash occurs, wash the eye with
saline or water immediately.
• Inject BCG into the skin over the region of the insertion of the deltoid muscle
3.22 Tuberculosis
into the humerus. This is just above the mid-point of the upper arm. This site
is recommended to minimise the risk of keloid formation. By convention, the
left upper arm is used wherever possible to assist those who subsequently
look for evidence of BCG vaccination.
• Stretch the skin between a finger and thumb and insert the bevel into the
dermis, bevel uppermost, to a distance of about 2 mm. The bevel should be
visible through the transparent epidermis.
• If the injection is not intradermal, withdraw the needle and try again at a new
site. A truly intradermal injection should raise a blanched bleb of about 7 mm
in diameter with the features of peau d’orange. Considerable resistance will
be felt as the injection is given. If this resistance is not felt, the needle may be
in the subcutaneous tissues.
• Advise the subject of adverse events which may follow the injection.
A tuberculin reaction induced by BCG usually ranges from 0 to 15 mm, but

clinical trials have not shown a consistent relationship between the size of
tuberculin reactions and the protection provided. For this reason, tuberculin
skin testing of BCG vaccinees is not routinely recommended. Because of waning
hypersensitivity, most adults who were vaccinated with BCG in early childhood
will have a negative tuberculin test.
BCG is available from State/Territory tuberculosis services.
Response to BCG vaccination

A small red papule forms and eventually ulcerates, usually within 2 to 3 weeks
of vaccination. The ulcer heals with minimal scarring over several weeks. There
may be swelling and tenderness in local lymph nodes. Subjects who are given
BCG despite previous tuberculosis infection will experience an accelerated
response characterised by induration within 24 to 48 hours, pustule formation in
5 to 7 days and healing within 10 to 15 days.
Tuberculosis 299
Recommendations
(i) Given the low incidence of TB in Australia and the variable efficacy in adults,
BCG is not used in the general population.
(ii) BCG is recommended for the following:17
• Aboriginal and Torres Strait Island neonates living in regions of high TB
incidence,
• neonates born to parents with leprosy or a family history of leprosy,
• children <5 years of age who will be travelling to live in countries of high TB
prevalence for longer than 3 months (WHO defines ‘high-risk’ countries as
those with an annual incidence of TB in excess of 100 per 100 000 population
– see http://www.who.int/tb/en/),
• embalmers,
• healthcare workers involved in conducting autopsies.
(iii) State and Territory guidelines should be consulted for advice on vaccination
of the following groups of individuals:17
• healthcare workers who may be at high risk of exposure to drug-resistant
cases,
• neonates weighing <2.5 kg,
• children ≥5 years and <16 years of age who will be travelling or living for
extended periods in countries with a high prevalence of tuberculosis.
Contraindications
The use of BCG vaccine is contraindicated in the following:
• individuals with impaired immunity due to HIV infection, corticosteroids
or other immunosuppressive agents, congenital immunodeficiencies and
malignancies involving bone marrow or lymphoid systems (because of the
risk of disseminated BCG infection) (see also Chapter 2.3, Groups with special
vaccination requirements),
• individuals with a high risk of HIV infection where HIV antibody status is
unknown,
• individuals with any serious illness including the malnourished,
• individuals with generalised septic skin diseases and skin conditions such as
eczema, dermatitis and psoriasis,
• pregnant women (BCG has never been shown to cause fetal damage, but use
of live vaccines in pregnancy is not recommended),
• individuals who have previously had TB or a large (≥5 mm) tuberculin
(Mantoux) reaction,
• individuals with significant febrile illness (administer 1 month from the time
of recovery).

Precautions
BCG should be deferred in the following:
• neonates with a birth weight <2.5 kg or those who may be relatively
malnourished,
• neonates of mothers who are HIV-positive,
• children who are currently on isoniazid preventive therapy for latent TB
infection (as the therapy can inactivate the BCG),
• a 4-week interval should be allowed after administration of another live
vaccine (MMR, varicella [and MMRV when available], yellow fever vaccine)
unless given concurrently with the BCG.
Adverse events
3.22 Tuberculosis
About 5% (common) of vaccinees experience adverse events. 2.5% develop
injection site abscesses and 1% lymphadenitis. About 1% (uncommon) may
need medical attention including surgery as a result of the adverse event.18
Anaphylactoid reactions have also been reported. Gross local or generalised
infection can be treated with antituberculous drugs. Keloid formation can occur,
but the risk is minimised if the injection is not given higher than the level of the
insertion of the deltoid muscle into the humerus.
Use in pregnancy
Use of BCG in pregnancy is not recommended. BCG has never been shown to
cause fetal damage, but use of live vaccines in pregnancy is contraindicated.
The tuberculin skin test (TST)

(i) Hypersensitivity to tuberculin Purified Protein Derivative (PPD) follows
either natural infection with either M. tuberculosis or with other mycobacteria that
induce cross-reactivity, or BCG vaccination. The skin test is used (a) to detect past
infection for epidemiological purposes, (b) to detect latent TB infection (LTBI),
especially in contacts of TB patients, (c) as an aid in diagnosing disease due to TB,
and (d) as a pre-vaccination screen before BCG to prevent vaccine reactions.
(ii) Most tuberculin testing in Australia is performed using the Mantoux
technique. The PPD preparation for this test is currently supplied by Sanofi
Pasteur Pty Ltd. The product, Tubersol, comes in multidose vials and has 5
Tuberculin units (TU)/0.1 mL (10 doses per 1 mL vial). For routine testing, 0.1 mL
of PPD (ie. a dose of 5 TU) is injected intradermally into the skin of the upper
third of the flexor surface of the left forearm, producing a peau d’orange bleb
4 to 10 mm in diameter. The reaction is examined 48 to 72 hours later, and the
diameter of the palpably indurated skin is measured across the long axis of the
forearm and recorded in millimetres. In certain circumstances, 2-step skin testing
may be required. It is used to detect individuals previously infected who may
Tuberculosis 301
test negative to tuberculin testing initially, but who show a strong reaction to
tuberculin if the same procedure is repeated 1 to 2 weeks later. The 2-step test
is important to establish the baseline reaction when future tuberculin testing is
required as part of contact tracing or monitoring of high-risk groups. Detailed
information can be accessed in the Tubersol product information and relevant
State/Territory guidelines.
(iii) Erythema without induration should be disregarded. Strongly positive
reactions may be accompanied by skin necrosis, lymphangitis and regional
adenitis. Patients with a history of such strongly positive reactions to previous
testing should not be retested.
(iv) The reaction to PPD may be suppressed by recent surgery, sarcoidosis,
immunosuppressant drugs and illnesses, such as Hodgkin’s disease, lymphoma
and HIV infection that result in impaired immunity. The reaction also wanes
with increasing age, so that most adults vaccinated with BCG in childhood have
negative tuberculin reactions.
(v) The reaction to PPD may be unreliable for 4 weeks after administration of
other live vaccines including MMR, varicella and yellow fever vaccines unless
given concurrently. The tuberculin skin test should be deferred for patients with
major viral infections or live-virus vaccination in the past month. Oral typhoid
and oral polio (OPV is no longer used in Australia but may have been received
overseas) vaccines do not necessitate a delay in testing.
(vi) The use of the Heaf gun, a multiple puncture apparatus primed with highly
concentrated PPD, is not recommended.
(vii) Although BCG is not routinely recommended, it may be offered by some
States and Territories to their healthcare staff who should be made aware that
subsequent tuberculin skin testing may be difficult to interpret.
(viii) New interferon-gamma release assays (blood tests) using specific antigens
for M. tuberculosis are now available in some laboratories. Interferon-gamma
based assays are increasingly being used to diagnose latent TB and, particularly,
to distinguish latent TB from post-BCG vaccine skin reactivity. There are
relatively few data on the sensitivity and specificity of these tests in children,
particularly those <2 years of age, or in people with impaired immunity.19

The product information states that BCG should not be frozen. NHMRC advises
that BCG can be stored unreconstituted (freeze-dried) in a freezer at –20°C.
References

3.23 Typhoid
Bacteriology
Typhoid fever is a clinical syndrome caused by a systemic infection with
Salmonella enterica subspecies enterica serovar Typhi (S. Typhi). Paratyphoid fever,
caused by infection with S. enterica serovar Paratyphi A or B, is similar to, and
often indistinguishable from, typhoid fever. The two infections are collectively
known as enteric fever; there is no vaccine against paratyphoid fever.
NB. S. Paratyphi B biovar Java does not cause typhoid-like enteric fever but
rather causes a typical gastroenteritis; it can be acquired through handling
aquarium fish.1
Clinical features
Typhoid fever has a usual incubation period of 7 to 14 days (range 3 to 60 days).2
Although clinical presentations of typhoid fever can be quite variable, a typical
case presents with a low-grade fever, dull frontal headache, malaise, myalgia,
anorexia and a dry cough.2 The fever tends to increase as the disease progresses;
constipation (more typically diarrhoea in young children), abdominal tenderness,
relative bradycardia and splenomegaly are common. Complications occur in 10
to 15% of patients and tend to occur in patients who have been ill for >2 weeks.
The more important complications include gastrointestinal bleeding, intestinal
perforation and typhoid encephalopathy.2
Relapse occurs in 5 to 10% of patients, usually 2 to 3 weeks after the initial fever
3.23 Typhoid
resolves. Chronic asymptomatic biliary carriage of S. Typhi occurs in up to 5% of
patients with typhoid fever, even after treatment. Chronic carriage is defined by
the continued shedding of the organism for >1 year, and is a public health risk
(eg. if a carrier works in the food industry).2
Because travellers are likely to seek medical advice relatively early in the illness,
severe typhoid fever with complications is rarely seen in this group of patients.
Nevertheless, travellers can still become chronic carriers of S. Typhi.
Epidemiology
Humans are the sole reservoir of S. Typhi. It is shed in the faeces of those acutely
ill and those who are chronic asymptomatic carriers of the organism; transmission
usually occurs via the ingestion of faecally-contaminated food or water.
The vast majority of typhoid fever cases occur in less-developed countries where
poor sanitation, poor food hygiene and untreated drinking water all contribute
to endemic disease with moderate to high incidence and considerable mortality.3
Geographic regions with high incidence (>100 cases per 100 000 population
Typhoid 303
per year) include the Indian subcontinent, most southeast Asian countries and
several south Pacific nations, including Papua New Guinea.
In developed countries, typhoid fever is predominantly a travel-related disease,
with a considerably greater risk following travel to the Indian subcontinent
than to other regions.4,5 Those who travel to endemic regions to visit friends and
relatives (ie. immigrants who travel to their former homelands) appear to be at
considerably greater risk of acquiring typhoid fever than other travellers.4,5 There
are approximately 50 to 80 cases of typhoid fever reported in Australia each year,
with most following travel to regions with endemic disease.
Vaccines
• Vivotif Oral – CSL Biotherapies/Berna Biotech Ltd (oral live attenuated
typhoid vaccine). Each enteric-coated capsule contains not less than 2 x 109
viable organisms of attenuated S. Typhi strain Ty21a Berna. 3 capsules in a
blister pack.
• Typherix – GlaxoSmithKline (purified Vi capsular polysaccharide vaccine).

Each 0.5 mL pre-filled syringe contains 25 µg Vi polysaccharide of S. Typhi;
phenol as preservative; phosphate buffer. 10 dose packs are also available.
• Typhim Vi – Sanofi Pasteur Pty Ltd (purified Vi capsular polysaccharide

vaccine). Each 0.5 mL pre-filled syringe contains 25 µg Vi polysaccharide of
S. Typhi; phenol as preservative; phosphate buffer.
Combination vaccine that includes both typhoid and hepatitis A (see

Chapter 3.5, Hepatitis A)
• Vivaxim – Sanofi Pasteur Pty Ltd (inactivated hepatitis A virus and typhoid
Vi capsular polysaccharide). Supplied in a unique dual-chamber syringe
which enables the 2 vaccines to be mixed just before administration. Each
1.0 mL dose of mixed vaccine contains 160 ELISA units of inactivated
hepatitis A virus antigens, 25 µg purified typhoid capsular polysaccharide;
0.3 mg aluminium hydroxide; 2.5 μL phenoxyethanol; formaldehyde; traces
of neomycin and bovine serum albumin.
The attenuated non-pathogenic S. Typhi strain Ty21a was derived by chemical

treatment attenuation of a wild-type strain. Attenuated features of Ty21a include
the absence of the enzyme, UDP-galactose-4-epimerase, and the Vi capsular
polysaccharide antigen (an important virulence determinant of S. Typhi). These
features partially contribute to the non-pathogenicity and, therefore, the safety of
the oral live vaccine.6
The oral vaccine Ty21a strain cannot be detected in faeces more than 3 days after
administration of the vaccine. It stimulates vigorous secretory intestinal IgA and
cell-mediated immune responses.6 Clinical trials, with different formulations of

the vaccine and with a variety of schedules, have been undertaken in several
countries (Egypt, Chile, Indonesia) with endemic typhoid fever. These have
documented varying degrees of protection against the disease.2,6
The parenteral Vi polysaccharide vaccine is produced by fermentation of the
Ty2 strain followed by inactivation with formaldehyde, and then extraction of
the polysaccharide from the supernatant using a detergent.6 The vaccine elicits
prompt serum IgG anti-Vi responses in 85 to 95% of adults and children >2 years
of age. The vaccine has also been used in clinical trials in endemic regions (Nepal,
South Africa, China), indicating moderate protection against typhoid fever.2,6
Neither the oral nor the parenteral vaccines have been studied in prospective
clinical trials in travellers to endemic regions. Because many travellers do not
have any naturally-acquired immunity, the protection conferred through typhoid
vaccination may be less than that documented in the clinical trials mentioned
above. However, there is circumstantial evidence that the vaccines do provide
protection to travellers to endemic regions,4,5 and that 3-yearly revaccination is
necessary to prolong the protection.7

Transport according to National Vaccine Storage Guidelines: Strive for 5.8 Store all
typhoid vaccines at +2°C to +8°C. Protect from light. Do not freeze.
Because the vaccinee will be responsible for looking after the course of the oral live
attenuated vaccine, details of how it should be transported (from the pharmacy to
the home) and stored in the refrigerator (at home) must be carefully explained.
3.23 Typhoid
Oral live attenuated vaccine
The vaccine is registered for use in individuals ≥6 years of age; it is presented
in a pack of 3 capsules. The dose (a whole capsule) is the same for both adults
and children.
It may be administered at the same time as either OPV (no longer used in
Australia), or yellow fever vaccine.6 It may also be given concurrently with
mefloquine or with atovaquone/proguanil combination (Malarone).
The vaccination schedule consists of 1 capsule of vaccine on days 1, 3, and 5,
taken 1 hour before food. The capsule must be swallowed whole with water and
must not be chewed since the organisms can be killed by gastric acid. Do not give
the vaccine concurrently with antibiotics, or other drugs that are active against
Salmonellae. If possible, antibiotics and other relevant drugs should be delayed for
3 days after the last dose of the vaccine.
A fourth capsule taken on day 7 has been shown (in a single study9) to result in a
lower incidence of typhoid fever than 3 doses. However, the use of a fourth dose
requires partial use of a second pack and, therefore, may involve considerable
extra expense.
Typhoid 305
Oral live attenuated typhoid vaccine should be separated from the
administration of inactivated oral cholera vaccine by an interval of at least 8
hours (see ‘Precautions’ below).
Parenteral Vi polysaccharide vaccines

Both vaccines (Typherix and Typhim Vi) are registered for use in individuals
≥2 years of age; the dose (0.5 mL) is the same for both adults and children. (The
dose of the combined Vi polysaccharide and hepatitis A vaccine is 1 mL.) The
vaccines are given by IM injection.
Booster doses
The optimal timing of revaccination against typhoid fever is uncertain and,
therefore, international recommendations can vary considerably.2,5,6
However, if continued exposure to S. Typhi exists (such as occurs with
either prolonged travel or residence in an endemic region) it is reasonable to
recommend a dose of the parenteral vaccine 3 years after the initial primary
parenteral vaccination. If a 3-dose schedule of the oral live attenuated vaccine
was used initially, a repeat 3-dose course can be given after 3 years; if a 4-dose
schedule of the oral vaccine was used initially, a repeat 4-dose course can be
given after 5 years.6
Recommendations
Typhoid vaccination is recommended for all travellers ≥2 years of age going to
endemic regions, where food hygiene may be suboptimal and drinking water
may not be adequately treated. Travellers include the military. Vaccination
should be completed at least 2 weeks before travel.
Individuals travelling to endemic regions to visit friends and relatives are
probably at considerable risk of acquiring typhoid fever, and vaccination is
strongly recommended for them.
NB. Travellers must also be advised about personal hygiene, food safety and
about drinking boiled or bottled water only. They should be advised that raw (or
undercooked) shellfish, salads, cold meats, untreated water and ice (in drinks)
are all potentially ‘high-risk’, as are short (day) trips away from higher quality
accommodation venues.
Laboratory personnel routinely working with S. Typhi should also be considered
for vaccination.

Contraindications
The only absolute contraindications to typhoid vaccines are:
• anaphylaxis following a previous dose of a typhoid vaccine, or
• anaphylaxis following any component of a particular typhoid vaccine.

The oral live attenuated vaccine should not be administered
• to pregnant women; parenteral Vi polysaccharide vaccine should be used
instead;
• to individuals with impaired immunity, including those known to be infected
with HIV; parenteral Vi polysaccharide vaccine should be used instead; or
• to individuals taking antibiotics; parenteral Vi polysaccharide vaccine should
be used instead.

There are no other contraindications to these vaccines.
Precautions
There should be an interval of at least 8 hours between the administration of the
inactivated oral cholera and oral typhoid vaccines, as the buffer in the cholera
vaccine may affect the transit of the capsules of oral typhoid vaccine through the
gastrointestinal tract.
The Vi polysaccharide vaccines should not be administered to children <2 years
of age.
3.23 Typhoid
The oral live attenuated vaccine should not be administered to children <6 years
of age; parenteral Vi polysaccharide vaccine should be used instead in children
2–5 years of age.
Adverse events
Typhoid vaccines, both oral and parenteral, are associated with very few adverse
events and, when adverse events do occur, they tend to be mild and transient.10

Abdominal discomfort, diarrhoea, nausea, vomiting and rashes have occasionally
been reported.

Local adverse events such as erythema, swelling and pain at the injection site
are very common (10 to 20%). Systemic adverse events are common and include
fever (3%), malaise and nausea.
Typhoid 307
Public health management of typhoid fever
Typhoid fever is a notifiable disease in all States and Territories in Australia.
Upon notification, the relevant public health authority should ascertain the likely
source of infection, and determine if the case has an occupation (eg. as a food
handler or carer of children, the elderly or of those with impaired immunity)
where there might be the potential for the spread of S. Typhi.11 Cases in such
occupations should be excluded from work until 2 consecutive faecal samples,
collected a week apart after the completion of antibiotic treatment, are negative
for S. Typhi.11 Cases not in such occupations should also be proved to have
cleared the organism from 2 consecutive faecal samples, but they can return to
work once they have recovered and any diarrhoea has ceased.
All those who have been in close contact with a case of typhoid fever in the 30 days
before the clearance of S. Typhi from the case’s faeces should have their occupation
assessed (as above). Contacts in ‘risk’ occupations should be excluded from work
until 2 faecal samples, collected at least 24 hours apart, have proved negative for
S. Typhi.11 Contacts not in such occupations can remain at work, but should have at
least 1 faecal sample collected. Further instructions about the management of cases
of typhoid fever, and their contacts, should be obtained from State/Territory public
health authorities (see Appendix 1, Contact details for Australian, State and Territory
Use in pregnancy
The oral live attenuated vaccine should not be given in pregnancy. However,
pregnancy is not a contraindication to vaccination with a parenteral Vi
polysaccharide vaccine. Refer to Chapter 2.3, Groups with special vaccination
requirements, Table 2.3.1 Vaccinations in pregnancy.

The product information for the oral live attenuated vaccine does not mention
the use of a 4-dose course of the vaccine for either primary or booster
vaccination.
Although NHMRC considers pregnancy a contraindication to the oral live
attenuated typhoid vaccine, the product information does not include pregnancy
among the listed contraindications.
The Typhim Vi product information recommends a booster dose every 2 to
3 years. However, revaccination with a dose of Vi polysaccharide vaccine 3 years
after an initial dose is recommended by NHMRC.
References

3.24 Varicella
Virology
Varicella-zoster virus (VZV) is a DNA virus within the herpes virus family.1
Primary infection with VZV causes varicella (chickenpox). Following primary
infection, VZV establishes latency in the dorsal root ganglia. Reactivation of the
latent virus manifests as herpes zoster (shingles)2 (see Chapter 3.26, Zoster).
Clinical features
Varicella is a highly contagious infection spread by air-borne transmission of
droplets from the upper respiratory tract or from the vesicle fluid of the skin
lesions of varicella or zoster infection.1 Varicella is usually a mild disease of
childhood. However, complications occur in approximately 1% of cases.3 It is
more severe in adults and in individuals of any age with impaired immunity, in
whom complications, disseminated disease, and fatal illness can occur.1
The average incubation period is 14 to 16 days (range 10–21 days), but may
be longer in those with impaired immunity, especially after receipt of zoster
immunoglobulin (ZIG).2 The period of infectivity is from 48 hours before the
onset of rash until crusting of all lesions has occurred. A short prodromal
period of 1 to 2 days may precede the onset of the rash, especially in adults.1,2
In otherwise healthy children, skin lesions usually number between 200 and
500.1,2 Acute varicella may be complicated by secondary bacterial skin infection,
pneumonia, acute cerebellar ataxia (1 in 4000 cases), aseptic meningitis,
transverse myelitis, encephalitis (1 in 100 000 cases), and thrombocytopenia. In
rare cases, it involves the viscera and joints.1
Congenital varicella syndrome has been reported after varicella infection in
pregnancy and may result in skin scarring, limb defects, ocular anomalies,
and neurologic malformations.1,4 There is a higher risk to the fetus if maternal
infection occurs in the second trimester compared with infection in the
first trimester (1.4% vs 0.55%).5 Infants with intrauterine exposure also risk
developing herpes zoster in infancy (0.8–1.7%) with the greatest risk following
exposure in the third trimester.4 Severe neonatal varicella infection can result
from perinatal maternal varicella.6 The onset of varicella in pregnant women
from 5 days before delivery to 2 days after delivery is estimated to result in
3.24 Varicella
severe varicella in 17 to 30% of their newborn infants.7

Reactivation of latent VZV as a result of waning cellular immunity results in
herpes zoster (HZ), a localised vesicular rash. HZ can occur at any age, but
is more common in older adults and individuals with impaired immunity.
Complications may include post-herpetic neuralgia, and disseminated zoster
with visceral, central nervous system and pulmonary involvement1 (see Chapter
3.26, Zoster).
Varicella 309
There is no specific therapy for uncomplicated varicella infection. Antiviral
therapy is used in the treatment of complicated or severe disease or varicella in
people with impaired immunity. An increased risk of Reye syndrome following
varicella infection has been reported in association with aspirin or other salicylate
use8-12 (see ‘Precautions’ below). Aspirin or other salicylates should not be used in
the management of varicella infection.
Epidemiology
In an unimmunised population in temperate climates, the annual number
of cases of varicella approximates the birth cohort.13 Tropical regions have a
higher proportion of cases in adults. Approximately 5% of cases are subclinical.
A serosurvey conducted in 1997–1999 found that 83% of the Australian
population were seropositive by 10–14 years of age.14 Before the introduction
of a varicella vaccination program in Australia there were about 240 000 cases,
1500 hospitalisations and an average of 7 to 8 deaths each year from varicella in
Australia.15-17 The highest rates of hospitalisation occur in children <4 years of age.18
In the USA, universal varicella vaccination since 1995 has resulted in a decline in
varicella disease by 85% and hospitalisations have declined by 70 to 88%.19-21 The
greatest decline in hospitalisation rates has been in 0–4-year-olds, who were most
likely to be vaccinated. However, a reduction in hospitalisation rates also occurred
in older children and adults, due to herd immunity.19 Surveillance of varicella
and HZ in the USA, conducted between 1992 and 2002, demonstrated that, as
vaccination coverage increased to 65% in 2002, the incidence of varicella decreased
by 65% across all age groups, and the incidence of HZ remained stable.22
Vaccines
Live attenuated varicella vaccine (VV) is currently available as a monovalent
vaccine. It is anticipated that quadrivalent combination vaccines containing
measles, mumps, rubella and varicella vaccines (MMRV) will be available in the
near future (see Chapter 3.11, Measles for information on MMRV vaccines). All
available varicella-containing vaccines are derived from the Oka VZV strain, but
have some genetic differences.23
Monovalent VVs have been available in Australia since 2000, and from
November 2005, a single dose of VV has been funded under the NIP for
all children at 18 months of age, with a catch-up dose funded for children
10–<14 years of age.24 At the time of implementation of a universal varicella
vaccination program in Australia, a single dose was considered adequate for
protection of infants and children <14 years of age. However, recent data from
the USA suggests that a second dose of varicella-containing vaccine in children
is optimal to provide an immune response more like natural infection, reducing
the risk of vaccine failure and increasing population immunity.7 Vaccine failure is
known as ‘breakthrough varicella’ and is defined as a case of wild-type varicella
≥42 days post vaccination. A majority of cases of breakthrough varicella are

mild with fewer lesions than natural infection. However, breakthrough varicella
infections can be contagious.25
Post-licensure studies in the USA have estimated the effectiveness of 1 dose of
VV in children to be 80 to 85% against any disease and 95 to 98% against severe
varicella.25-29 Although earlier data suggested persistence of immunity in most
healthy vaccinees,1 recent long-term data from the United States has shown
that, >5 years after vaccination, rates of vaccine failure increased by 2.6 times
in children who received only 1 dose of vaccine, compared with those who had
received the vaccine within 5 years.30 Data from a randomised controlled trial
in varicella-negative children 12 months to 12 years of age, comparing 1 with 2
doses of VV over a 10-year period, showed significantly higher protection with
2 doses (94.4% vs 98.3%).31 Based on current evidence, 2 doses of a varicella-
containing vaccine in children from 12 months of age will minimise the risk of
breakthrough varicella (see ‘Recommendations’ below).
Healthy adolescents (≥14 years of age ) and adults require 2 doses of varicella
vaccine, 1 to 2 months apart, as the response to a single dose of VV decreases
progressively as age increases and is insufficient to provide adequate protection.32
Monovalent varicella vaccines
• Varilrix – GlaxoSmithKline (lyophilised preparation of live attenuated Oka

strain of varicella-zoster virus). Each 0.5 mL monodose of the reconstituted,
lyophilised vaccine contains not less than 103.3 plaque-forming units of
attenuated varicella-zoster virus; human serum albumin; lactose; neomycin;
polyalcohols. Single and 10 pack of monodose vials also available.
• Varivax Refrigerated – CSL Biotherapies/Merck & Co Inc (lyophilised

preparation of live attenuated Oka/Merck strain of varicella-zoster virus).
Each 0.5 mL monodose of the reconstituted, lyophilised vaccine contains
not less than 1350 plaque-forming units; 18 mg sucrose; 8.9 mg gelatin;
3.6 mg urea; 0.36 mg monosodium glutamate; residual components of
MRC-5 cells; trace amounts of neomycin and fetal bovine serum from
MRC-5 culture media. Single and 10 pack of monodose vials also available.

Varicella vaccines are less stable than other commonly used live viral vaccines,
3.24 Varicella
and the storage temperature requirements are critical. Available monovalent VVs
have different storage requirements.
Varilrix – store at +2°C to +8°C. Protect from light. Do not freeze. After
reconstitution, use within 90 minutes at ambient temperature or for up to 8 hours
at +2°C to +8°C.
Varicella 311
Varivax Refrigerated – store at +2°C to +8°C. Protect from light. Do not freeze.
After reconstitution, use within 30 minutes at ambient temperature (+20°C to
+25°C) to maintain potency.
Transport according to National Vaccine Storage Guidelines: Strive for 5.33

The dose of monovalent VV is 0.5 mL, administered by SC injection.
If VV is given at the same time as MMR, it should be given using separate
syringes and injection sites. MMR and monovalent VV should not be mixed
before injection.
VV can be given at the same time as other vaccines (including MMR, DTPa,
hepatitis B and MenCCV), using separate syringes and injection sites. If VV is not
given simultaneously with other live viral parenteral vaccines (eg. MMR), they
should be given at least 4 weeks apart (see ‘Precautions’ below).
Recommendations
(i) Children
It is recommended that at least 1 dose of a varicella-containing vaccine be given
to all non-immune children from the 2nd year of life to <14 years of age. Children
in this age group with a reliable history of varicella infection, either by confident
clinical diagnosis or with laboratory confirmation, may be considered immune
and do not require vaccination.
Routine varicella-containing vaccine should be administered as follows (and as
per Table 3.24.1):
• One dose of monovalent VV at 18 months of age.
• When MMRV vaccines become available, 1 dose of varicella-containing
vaccine should be given as MMRV at 12 months of age.
The change in the recommended age of administration of varicella vaccine

is influenced by moving the second dose of MMR to 18 months of age,
and the anticipated availability of MMRV vaccines in the near future. The
available evidence now suggests that the administration of varicella vaccine
at the earlier age of 12 months, compared with 18 months, does not reduce
vaccine effectiveness or lead to increased rates of breakthrough varicella.34
Administration of varicella vaccine at 12 months of age will provide earlier
protection from varicella. However, until MMRV vaccines are available in
Australia, it is recommended that administration of monovalent VV at 18 months
of age continue to avoid schedule crowding (4 injections) at 12 months of age.
Receipt of 2 doses of varicella-containing vaccine provides increased protection
and minimises the chance of breakthrough varicella in children.31 However, at
this time, routine administration of 2 doses of varicella-containing vaccine at
<14 years of age is not included on the NIP schedule. If parents/carers wish to

minimise the risk of breakthrough varicella, a second dose of varicella-containing
vaccine to children <14 years of age is recommended (see ‘Vaccines’ above).
When available, use of MMRV at 18 months of age is a suitable means to provide
a second dose of varicella-containing vaccine. (For further information, see
also Chapter 3.11, Measles.) The minimum approved interval between doses of
varicella-containing vaccine in children <14 years of age is 4 weeks.
Table 3.24.1: Recommendations for varicella vaccination with monovalent VV

(currently available), and once MMRV vaccines are available
12 months 18 months Catch-up requirements*
Monovalent varicella MMR MMR + VV †
No requirement for
vaccine varicella catch-up
MMRV when available MMRV MMR‡ Use MMRV at 18 months for
children who have not yet received
at least 1 dose of varicella vaccine
* If catch-up is required for MMR, see Chapter 3.11, Measles.

† Give in separate syringes and at separate injection sites (preferably the other arm).
‡ When available, use of MMRV at 18 months of age is a suitable means to provide a second
dose of varicella-containing vaccine.
(ii) Adolescents (≥14 years of age) and adults

Vaccination is recommended in non-immune adolescents (≥14 years of age) and
adults. Immune responses are reduced in adolescents and adults compared
with young children.32,35 Therefore, adolescents and adults must receive 2 doses
of VV to achieve adequate protection from varicella. The 2 doses should be
administered at least 4 weeks apart. However, a longer interval between vaccine
doses is acceptable. Lack of immunity to varicella should be based on a negative
history of previous varicella infection and can be supplemented by serological
testing (see ‘Serological testing before varicella vaccination’ below).
VV is particularly indicated for those in the following categories:
• non-immune people in high-risk occupations where exposure to varicella
is likely (such as healthcare workers, teachers and workers in childcare
centres) (see Section 2.3, Table 2.3.6 Recommended vaccinations for those at risk of
occupationally acquired vaccine-preventable diseases),36
• non-immune women before pregnancy to avoid congenital or neonatal
3.24 Varicella
varicella,
• seronegative women immediately after delivery,
• non-immune parents of young children, and
• non-immune household contacts of all ages of people with impaired
immunity.
Varicella 313
MMRV vaccines are not recommended for use in adolescents and adults because
data are currently available only for children ≤12 years of age.
(iii) Serological testing before varicella vaccination

Vaccination is well tolerated in previously infected individuals and can be
administered if there is uncertainty regarding immunity. Serological testing
before varicella vaccination of children with a reliable history of varicella
infection, either by confident clinical diagnosis or with laboratory confirmation,
is not warranted. Reliable history of varicella infection correlates highly with
serological evidence of immunity.37,38 Those who have an uncertain history
should be considered susceptible and offered vaccination.
In adolescents and adults with a negative history of varicella infection,
serological testing before vaccination is more likely to be cost-effective,
as a majority of those with a negative history may be immune.36,39
However, vaccination can proceed without testing (provided there are no
contraindications), as the vaccine is well tolerated in seropositive people.
(iv) Serological testing after varicella vaccination

Testing to check for seroconversion after varicella vaccination is not
recommended. Commercially available laboratory tests are not always
sufficiently sensitive to detect low antibody levels following vaccination and, in
addition, the presence of detectable antibody shortly after vaccination does not
necessarily indicate complete immunity to varicella.40,41
(v) Post-exposure prophylaxis and outbreak control

Several studies have shown that VV is effective in preventing varicella infection,
particularly moderate to severe disease, following exposure. This is generally
successful when given within 3 days, and up to 5 days, after exposure, with
earlier administration being preferable.42-46 Vaccination of exposed individuals
during outbreaks has also been shown to prevent further cases and control
outbreaks (see also ‘The public health management of varicella’ below). When
available, vaccination with MMRV in children 12 months to 12 years of age could
be used for vaccination in this setting if MMR vaccination is also indicated.
In the event of an outbreak, seek advice from local public health authorities
before proceeding with vaccination of a large number of individuals (see
(vi) Household contacts of people with impaired immunity

Vaccination of household contacts of people with impaired immunity is strongly
recommended. This recommendation is based upon evidence that transmission
of varicella vaccine virus strain is extremely rare and it is likely to cause only
mild disease that can be treated with acyclovir. This compares with the relatively
high risk of severe disease in people with impaired immunity following

exposure to wild-type varicella-zoster virus.41,47 If vaccinees develop a rash, they
should cover the rash and avoid contact with people with impaired immunity
for the duration of the rash. Zoster immunoglobulin (ZIG) need not be given
to an immune impaired contact of a vaccinee with a rash because the disease
associated with this type of transmission (should it occur) would be expected to
be mild.
(vii) Vaccination of healthcare workers (HCW)

(Refer to Table 2.3.6 Recommended vaccinations for those at risk of occupationally
acquired vaccine-preventable diseases)
Pre-exposure vaccination of HCWs:
• A HCW with a negative or uncertain history of varicella infection should
undergo serological testing. If seronegative, vaccination should be offered in
a 2-dose schedule48 (see ‘Recommendations (ii)’ above).
• If a rash develops during the 6 weeks after administration of the vaccine,
the HCW should cover the rash and be reassigned to duties that require no
patient contact, or placed on sick leave.48 Reassignment or leave should be
only for the duration of the rash48 (see ‘Variations from product information’
below).
• VV-associated rash may be atypical and may not be vesicular (see ‘Adverse
events’ below). A VV-associated rash is likely to occur in less than 5% of
vaccinees, and to last for less than 1 week.49,50
• Testing to check for seroconversion after VV is not recommended (see
‘Serological testing after varicella vaccination’ above).
Post-exposure management of HCWs:
• If a previously vaccinated HCW is exposed to varicella, assume immunity
and report exposure. A vaccinated HCW should watch for a rash for 3 weeks
after exposure and report to the nominated infection control officer should
a rash develop. If HCW vaccinees develop a rash, cover the rash, reassign
duties (no patient contact) or place on sick leave until no new lesions appear
and all lesions have crusted.
• If a HCW is exposed to varicella and is unvaccinated and has a negative
or uncertain history of varicella infection, offer vaccination. This is usually
effective in preventing the development of varicella if given within 3 days,
3.24 Varicella
and up to 5 days, after exposure. In situations where facilities for rapid

testing are available, it may be possible to identify those with pre-existing
immunity before vaccination. However, serological testing should not delay
vaccination beyond the recommended 3 to 5 days after exposure. Vaccination
in the absence of serological results is acceptable (see ‘Serological testing after
varicella vaccination’ above).
Varicella 315
• If the HCW is vaccinated after exposure, as above, he/she can work but
should watch daily for any rash for 6 weeks after exposure. Note that the
VV-associated rash may be atypical, maculopapular and non-vesicular.
If a varicella-exposed and vaccinated HCW develops a rash following
vaccination, this may be due to either wild-virus or vaccine-strain varicella-
zoster virus (see ‘Adverse events’ below). In the event of a rash after
vaccination, cover the rash, reassign duties (no patient contact) or place on
sick leave until no new lesions appear and all lesions have crusted.
• If an exposed non-immune HCW does not accept vaccination, reassign duties
or place on sick leave from days 10 to 21 from the time of first exposure.
Contraindications
Varicella vaccination is contraindicated where there has been:
• anaphylaxis following a previous dose of any of the varicella vaccines, or
(ii) Pregnant women

VV should not be given during pregnancy and vaccinees should not become
pregnant for 28 days after vaccination. Since wild-type VZV poses only a very
small risk to the fetus, the risk to the fetus of the attenuated VV virus, if any,
should be even lower. Data from a registry, established in the USA to monitor the
maternal-fetal outcomes of pregnant women who were inadvertently administered
VV 3 months before or at any time during pregnancy, revealed that no birth defects
compatible with congenital varicella syndrome occurred in 254 known pregnancy
outcomes.51,52 The rate of occurrence of congenital anomalies from prospective
reports in the registry was similar to what is reported in the general USA
population (3.2%) and the anomalies showed no specific pattern or target organ.
A non-immune pregnant household contact is not a contraindication to
vaccination with VV of a healthy child or adult in the same household. The
benefit of reducing the exposure to varicella by vaccinating healthy contacts of
non-immune pregnant women outweighs any theoretical risks of transmission of
vaccine virus to these women.
Data on the use of MMRV vaccines in individuals >12 years of age are not available.
(iii) People with impaired immunity

Varicella-containing vaccines are contraindicated in subjects with primary or
acquired impaired immunity, including:
• people with impaired immunity due to HIV/AIDS. Vaccination with live
attenuated vaccine can result in a more extensive vaccine-associated rash
or disseminated infection in individuals with AIDS.53 However, varicella
vaccination of asymptomatic or mildly symptomatic HIV-infected children

may be considered (see Table 2.3.4 Immunological categories based on age-specific
CD4 counts and percentage of total lymphocytes). Since studies have not been
performed using combination MMRV vaccines in asymptomatic or mildly
symptomatic HIV-infected children, it is recommended that only MMR and
monovalent VV be considered for use in such children;54
• people with conditions in which normal immunological mechanisms may be
impaired;
• people suffering from malignant conditions of the reticuloendothelial system
(such as lymphoma, leukaemia, Hodgkin’s disease); and
• people receiving high-dose systemic immunosuppressive treatment, such as
general radiation, x-ray therapy or oral corticosteroids. Varicella-containing
vaccines are contraindicated in those taking high-dose oral corticosteroids
(in children equivalent to either >2 mg/kg per day prednisolone (≥20 mg per
day total) for >1 week or >1 mg/kg per day for >4 weeks) (see Section 2.3.3,
NHMRC also recommends that children who have been receiving high-dose
systemic steroids for 2 weeks or more may be vaccinated after steroid therapy
has ceased for at least 1 month.55 (See also Chapter 2.3, Groups with special
vaccination requirements and Chapter 3.11, Measles).
Precautions
(i) Vaccination with MMR
If VV is not given simultaneously with other live viral parenteral vaccines (eg.
MMR), they should be given at least 4 weeks apart.
(ii) Vaccination after immunoglobulin or blood products

NHMRC recommends that varicella-containing vaccines should not be given
for between 3 and 9 months after the administration of immunoglobulin-
containing blood products. The interval between receipt of the blood product and
vaccination depends on the amount of antibody in each product, and is indicated
in Table 2.3.5 Recommended intervals between either immunoglobulins or blood
products and MMR, MMRV or varicella vaccination. For further information, see
Section 2.3.5, Vaccination of patients following receipt of other blood products including
blood transfusions, and ‘Variations from product information’ below.
(iii) Administration of immunoglobulin or blood-

3.24 Varicella
derived products after vaccination

After vaccination with varicella-containing vaccines, immunoglobulin-containing
products should not be administered for 3 weeks unless the benefits exceed those
of vaccination. If immunoglobulin-containing products are administered within
this interval, the vaccinee should either be revaccinated later at the appropriate
time following the product, as indicated in Table 2.3.5, or tested for immunity
6 months later and then revaccinated if seronegative.
Varicella 317
(iv) Long-term aspirin or salicylate therapy
Individuals receiving long-term salicylate therapy should be vaccinated if
indicated, as the benefit is likely to outweigh any possible risk of Reye syndrome
occurring after vaccination. Natural varicella infection and salicylate use has
been associated with an increased risk of developing Reye syndrome. However,
there have been no reports of an association between Reye syndrome and
varicella vaccination (see ‘Variations from product information’ below).
Adverse events
• Adverse events following administration of VV are generally mild and well
tolerated.56 Fever >39°C has been observed in 15% (common) of healthy
children, but this was comparable to that seen in children receiving placebo.55
In adults and adolescents, fever has been reported in 10% (common) of VV
vaccinees. Injection site adverse events (pain, redness or swelling) are the
most common adverse events reported after varicella vaccination, occurring
in 7 to 30% (common to very common) of vaccinees, but are generally well
tolerated.2,56 Slightly higher rates of fever were observed in the clinical trials
of MMRV vaccines, as compared with giving MMR and monovalent varicella
vaccine at the same time but at separate sites.57,58 It is recommended that
parents/vaccine recipients be advised about possible symptoms, and given
advice for reducing fever, including the use of paracetamol for fever in the
period 5 to 12 days after vaccination.
• A maculopapular or papulovesicular rash may develop after vaccination
(usually within 5 to 26 days). Rashes typically consist of 2 to 5 lesions and
may be generalised (3–5%, common), or occur at the injection site (3–5%,
common).55 Most varicelliform rashes that occur within the first 2 weeks
after vaccination are due to wild-type VZV, with median onset 8 days
after vaccination (range 1–24 days), while vaccine-strain VZV rashes occur
at a median of 21 days after vaccination (range 5–42 days).59 (See also
‘Transmission of vaccine virus…’ below.)
• No serious adverse events were reported from pre-licensure trials of
VV.1 A post-licensure study reported that serious adverse events, such as
encephalitis, ataxia, thrombocytopenia and anaphylaxis, were reported
following vaccination at a rate of 2.9 per 100 000 doses distributed. However,
this does not necessarily imply a causal relationship.41
• Transmission of vaccine virus to contacts of vaccinated individuals is rare. In
the USA, where more than 56 million doses of VV were distributed between
1995 and 2005, there have been only 6 well documented cases of transmission
of the vaccine-type virus from 5 healthy vaccinees.55,60 Contact cases have
been mild and associated with a rash in the vaccinee.55,60-62

Risk of herpes zoster (shingles)
Herpes zoster (HZ) has been reported rarely in vaccine recipients and has been
attributed to both the vaccine strain and to wild-type varicella virus reactivation.59
The risk of developing HZ is currently thought to be lower after vaccination than
after natural varicella virus infection, and reported cases have been mild.2 HZ is
uncommon before the age of 45 years, and incidence increases with age.63 Rates
of herpes zoster in children 0–9 years of age after natural VZV infection were
estimated to be 30 to 74 per 100 000 per year.64,65 Vaccination results in a lower rate
of zoster with a rate of 22 per 100 000 person-years reported in a 9-year follow-up
of 7000 varicella vaccinated children (Jane Seward, US Centers for Disease Control
and Prevention (CDC), personal communication) (see Chapter 3.26, Zoster).
Zoster immunoglobulin
High-titre zoster immunoglobulin (ZIG) is available from the Australian Red
Cross Blood Service on a restricted basis for the prevention of varicella in high-
risk subjects. ZIG has no proven use in the treatment of established varicella or
zoster infection. ZIG must be given early in the incubation period (within 96
hours of exposure). ZIG is highly efficacious, but is often in short supply. Normal
human immunoglobulin (NHIG) can be used for the prevention of varicella if
ZIG is unavailable.
Zoster immunoglobulin should be given only by IM injection.
• Zoster Immunoglobulin-VF (human) – CSL Bioplasma (160 mg/mL

immunoglobulin (IgG) preparation from human plasma containing high
levels of antibody to the varicella-zoster virus). Vials contain 200 IU, with
the actual volume stated on the label on the vial. Also contains glycine.
The public health management of varicella

‘Significant exposure’ is defined as living in the same household as a person with
active varicella or HZ, or direct face-to-face contact with a person with varicella
or HZ for at least 5 minutes, or being in the same room for at least 1 hour. In the
case of varicella infection, the period of infectivity is from 48 hours before the
onset of rash until crusting of all lesions has occurred.
Immunocompetent varicella contacts should be tested for varicella-zoster
3.24 Varicella
antibodies. However, this should not delay ZIG administration after initial
contact with a case.
ZIG should be given to individuals in the following categories within 96 hours of
significant exposure to either varicella or HZ:
• Pregnant women who are presumed to be susceptible to varicella infection. If
practicable, they should be tested for varicella-zoster antibodies before ZIG is
given.4
Varicella 319
• ZIG must be given to neonates whose mothers develop varicella from 7 or
fewer days before delivery to 2 days after delivery, as the neonatal mortality
without ZIG is up to 30% in this setting. ZIG must be given as early as
possible in the incubation period.
• ZIG should be given to neonates exposed to varicella in the first month of life, if
the mother has no personal history of infection with VZV and is seronegative.
• Premature infants (born at <28 weeks’ gestation or <1000 g birth weight)
exposed to VZV while still hospitalised should be given ZIG regardless of
maternal history of varicella.
• Patients suffering from primary or acquired diseases associated with cellular
immune deficiency, and those receiving immunosuppressive therapy. While
it is recommended that varicella contacts with impaired immunity be tested
for varicella-zoster antibodies, this should not delay ZIG administration,
preferably within 96 hours and up to 10 days after initial contact with a case.66,67
NB. If a contact with impaired immunity is shown to have recent evidence of detectable
antibodies, it is not necessary to give ZIG, as its administration will not significantly
increase varicella-zoster antibody titres in those who are already positive. Note that
varicella-zoster antibodies detected in patients who have been transfused or who have
received intravenous immunoglobulin in the previous 3 months may be passively
acquired and transient.
The following dose schedule is recommended for ZIG administration:
Table 3.24.2: Zoster immunoglobulin-VF (ZIG) dose based on weight
Weight of patient (kg) Dose (IU)

0–10 200
11–30 400
>30 600
A dose of ZIG may be repeated if a second exposure occurs more than 3 weeks
after the first dose of ZIG. However, testing for varicella antibodies is also
recommended (see above). Normal human immunoglobulin can be used for the
prevention of varicella if ZIG is unavailable (see Chapter 3.8, Immunoglobulin
preparations). Patients receiving monthly high-dose intravenous NHIG are likely
to be protected and probably do not require ZIG if the last dose of NHIG was
given 3 weeks or less before exposure.
Use in pregnancy
Varicella vaccine is contraindicated during pregnancy (see ‘Contraindications
(ii) Pregnant women’ above, and Chapter 2.3, Groups with special vaccination
requirements, Table 2.3.1 Vaccinations in pregnancy).
Pregnancy should be avoided for at least 28 days after vaccination.

Varilrix vaccine is approved for use in healthy children from 9 months of age.
NHMRC recommends that routine vaccination of children against varicella
should occur at ≥12 months of age.
Varilrix and Varivax Refrigerated are registered for use as 2 doses of 0.5 mL
(1–2 months apart) in adolescents ≥13 years of age and adults. NHMRC
recommends a single dose of varicella vaccine for children <14 years of age.
In adults and adolescents where 2 doses of vaccine are required, the product
information for Varilrix states that the second dose should be given at least
6 weeks after the first. NHMRC recommends that the second dose may be given
at least 4 weeks after the first dose.
For both varicella vaccines, the product information states that pregnancy should
be avoided for 3 months after vaccination. NHMRC recommends that pregnancy
be avoided for at least 28 days after vaccination.
For both varicella vaccines, the product information recommends that vaccinees
should avoid contact with people with impaired immunity for up to 6 weeks
after vaccination. NHMRC recommends that healthcare worker vaccinees should
be reassigned to duties that involve no direct patient contact or be placed on sick
leave only if a rash develops, and that the period of leave or reassignment should
be only for the duration of the rash (not for the 4 to 6 weeks stated in the product
information) (see also ‘Vaccination of healthcare workers (HCW)’ above).
For both varicella vaccines, the product information states that salicylates should
be avoided for 6 weeks after varicella vaccination, as Reye syndrome has been
reported following the use of salicylates during natural varicella infection.
NHMRC recommends that non-immune individuals receiving long-term
salicylate therapy should receive VV as the benefit is likely to outweigh any
possible risk of Reye syndrome occurring after vaccination.
The product information for Varivax Refrigerated recommends delaying
vaccination for 5 months after receipt of NHIG by IM injection or blood
transfusion. The NHMRC recommends that VV should not be given for at least
3 months in subjects who have received immunoglobulin-containing blood
products according to the intervals contained in Table 2.3.5.
The dosage of ZIG recommended in the product information differs with that in
Table 3.24.2, which has been revised in order to minimise wastage of ZIG.
3.24 Varicella
References
Varicella 321
3.25 Yellow fever
Virology
Yellow fever is a viral haemorrhagic fever caused by a flavivirus that is
transmitted by mosquitoes. Aedes aegypti, a highly domesticated mosquito
found throughout the tropics, is the vector responsible for person-to-person
transmission of the yellow fever virus in urban and inhabited rural areas in
endemic countries.
Clinical features
The clinical spectrum of yellow fever varies from a non-specific febrile illness
to a fatal haemorrhagic fever.1 After an incubation period of 3 to 6 days, the
disease begins abruptly with fever, prostration, myalgia and headache. The
patient appears acutely ill with congestion of the conjunctivae; there is an intense
viraemia during this ‘period of infection’ which lasts 3 to 4 days.1 This may be
followed by the ‘period of remission’ in which the fever and symptoms settle
over 24 to 48 hours during which the virus is cleared by immune responses.1
Approximately 15 to 25% of patients may then relapse with a high fever,
vomiting, epigastric pain, jaundice, renal failure and haemorrhage: ‘the period
of intoxication’.1 These complications can be severe, and reflect the viscerotropic
nature of the yellow fever virus (its ability to infect the liver, heart and
kidneys). The case-fatality rate varies widely, but can be as high as 20% in local
populations.
Epidemiology
Yellow fever occurs in tropical regions of Africa and Central and South America.
In both regions the virus is enzootic in rainforest monkeys and canopy mosquito
species; sporadic human cases occur when people venture into these forests
(‘sylvatic or jungle yellow fever’).1
In moist savannah regions in Africa, especially those adjacent to rainforests, tree
hole-breeding Aedes mosquito species are able to transfer yellow fever virus from
monkeys to people and then between people, leading to small-scale outbreaks
(‘intermediate yellow fever’).
Aedes aegypti occurs in both heavily urbanised areas and settled rural areas in
tropical Africa and the Americas.1 Epidemics of ‘urban yellow fever’ occur when
a viraemic individual (with yellow fever) infects local populations of Ae. aegypti;
such epidemics can be large and very difficult to control. Although Ae. aegypti
also occurs throughout much of tropical Asia and Oceania (including north
Queensland), yellow fever has never been reported from these regions.

Although yellow fever is undoubtedly markedly under-reported, it is clear that
there has been a considerable increase in the reported number of outbreaks,
and therefore cases, of yellow fever in recent decades.2 Most of this increase has
3.25 Yellow fever
been in Africa, particularly in West African countries.2,3 Between 2000 and 2004,
18 of the 25 countries at risk in Africa reported cases of yellow fever, with 13 of
the 14 countries at risk in West Africa reporting cases.3 During this time, West
Africa experienced 5 epidemics of urban yellow fever, 3 of which affected capital
cities (Abidjan (Côte d’Ivoire, 2001), Conakry (Guinea, 2002), Dakar and Touba
(Senegal, 2002) and Bobo-Dioulasso (Burkina Faso, 2004)).3
The risk of susceptible travellers acquiring yellow fever varies considerably
with season, location, duration of travel and utilisation of mosquito avoidance
measures. There have been at least 6 reported cases of yellow fever, all fatal, in
unvaccinated travellers to Africa and South America since 1996.3
Vaccine
• Stamaril – Sanofi Pasteur Pty Ltd (live attenuated yellow fever virus
(17D-204 strain) lyophilised vaccine). Each 0.5 mL monodose of
reconstituted, lyophilised vaccine contains not less than 1000 mouse LD50
units; lactose; sorbitol. May contain traces of egg proteins. The vaccine is
supplied as a single dose ampoule with 0.5 mL diluent syringe.
Yellow fever vaccine is a live, freeze-dried preparation of the 17D attenuated

strain of yellow fever virus cultured in, and harvested from, embryonated
chicken eggs. The vaccine contains neither antibiotics nor preservatives, and does
not contain gelatin.
Vaccination elicits protective levels of neutralising antibodies in approximately
90% of adult vaccinees by day 14, and in virtually all by day 28.4 Immunity
is long-lasting and perhaps life-long; regardless, revaccination is required
after 10 years under International Health Regulations for a valid International
Certificate of Vaccination. Because the vaccine produces a transient very low
level viraemia in healthy adult recipients, they cannot serve as a source of
infection for mosquitoes.4
Although the efficacy of the yellow fever vaccine has never been determined in
prospective clinical trials, there is considerable observational evidence that it is
very effective in preventing the disease.4

Transport according to National Vaccine Storage Guidelines: Strive for 5.5 The
vaccine and diluent should be stored at +2°C to +8°C. Do not freeze. Protect from
light. The vaccine should be used within 1 hour of reconstitution.
Yellow fever 323

The vaccine can be given to those ≥9 months of age. The dose is 0.5 mL of
reconstituted vaccine regardless of age, given by either IM or SC injection.
Recommendations
Yellow fever is considered to be endemic in 32 African and 11 Central and South
American countries (Table 3.25.1). Of these, 25 African and 9 South American
countries are currently considered at risk because they have reported cases since
1950; of particular concern are the countries in West Africa (Table 3.25.1).3,6
Table 3.25.1: Yellow fever endemic countries
West African countries Other endemic countries

Benin * Angola* Guyana*
Burkina Faso * Bolivia* Kenya*
Côte d’Ivoire * Brazil* Niger
Gambia * Burundi Panama
Ghana * Cameroon* Peru*†
Guinea * Central African Republic* Rwanda
Guinea-Bissau * Chad Sao Tome and Principe
Liberia * Colombia* Somalia
Mali * Congo* Sudan*
Mauritania * Democratic Republic Suriname*
of the Congo*
Nigeria * Ecuador* Trinidad and Tobago
Senegal * Equatorial Guinea* Uganda*
Sierra Leone * Ethiopia* United Republic of Tanzania
Togo * French Guiana* Venezuela*
Gabon*
* Countries with cases reported since 1950.

† Travellers who will visit only the cities of Cuzco and Machu Picchu do not need vaccination.
The yellow fever vaccine is recommended for:

• those ≥9 months of age travelling or living in any country in West Africa (see
Table 3.25.1), regardless of where they will be in that country,
• those ≥9 months of age travelling or living outside urban areas of all other
yellow fever endemic countries (see Table 3.25.1), and
• laboratory personnel who routinely work with yellow fever virus.

All those travelling or living in endemic countries should be informed that the
mosquito vectors of yellow fever usually bite during the day, and they should be
advised of the necessary mosquito avoidance measures. These include the use of
3.25 Yellow fever
insect repellents, coils and sprays, the use of mosquito nets (preferably those that
have been treated with an insecticide), and adequate screening of residential (and
work) premises.
As well as the above recommendations, many countries outside the endemic
regions require evidence of vaccination for those travellers arriving from endemic
countries. Because Ae. aegypti exists in many of these non-endemic countries,
there is a potential for yellow fever virus transmission; a listing of these countries
is available in an annex at www.who.int/ith/en/.
Travellers >1 year of age arriving into Australia within 6 days of leaving a yellow
fever endemic country are required to have a valid International Certificate of
Vaccination against Yellow Fever (see below). Such travellers who do not have
a valid certificate are placed under quarantine surveillance until 6 days have
passed after leaving the endemic country. Quarantine surveillance does not
place restrictions on the traveller’s movements, but does require prompt medical
assessment should the traveller develop relevant symptoms.
Yellow fever vaccine can be administered only by Yellow Fever Vaccination
Centres approved by the relevant State or Territory health authorities. Each
yellow fever vaccination is to be recorded in an International Certificate of
Vaccination against Yellow Fever; the certificate must include the vaccinee’s
name and signature (or the signature of a parent or guardian if the vaccinee is a
child), and the signature of a person approved by the relevant health authority.
The date of the vaccination must be recorded in day-month-year sequence with
the month written in letters, and the official stamp provided by the State or
Territory health authority must be used. The certificate becomes valid 10 days
after vaccination, and remains valid for 10 years.
NB. People with a true contraindication to yellow fever vaccine (see below) who
intend to travel to endemic countries (as recommended above) should obtain a
letter from a doctor, clearly stating the reason for withholding the vaccine. The
letter should be formal, signed and dated, and on the practice’s letterhead.
Contraindications
(i) Known anaphylactic sensitivity
The yellow fever vaccine is contraindicated in those who have had either:
• anaphylaxis following any of the vaccine components.
In particular, the vaccine is contraindicated if there is a known anaphylaxis to eggs.
Yellow fever 325

(ii) Infants
Yellow fever vaccine is contraindicated in infants <9 months of age.
(iii) Altered immune status
As with all live virus vaccines, the yellow fever vaccine should not be given to
people with impaired immunity due to either disease or medical treatment (see
Chapter 2.3, Groups with special vaccination requirements).
(iv) Thymus disorders

People with a history of any thymus disorder, including myasthenia gravis,
thymoma, thymectomy and DiGeorge syndrome, should not be given the yellow
fever vaccine.
Precautions
(i) Adults ≥60 years of age
The risk of severe adverse events following yellow fever vaccine is
considerably greater in those aged ≥60 years than in younger adults.7,8
Adults ≥60 years of age should be given yellow fever vaccine only if they intend
to travel to endemic countries (as recommended above) and they have been
informed about the (albeit very low) risks of developing a severe complication.
(ii) Pregnancy
As with all live virus vaccines, unless there is a risk of exposure to the virus,
yellow fever vaccine should not be given to pregnant women. Pregnant women
should be advised against going to the rural areas of yellow fever endemic
areas (and to urban areas of West African countries as well). However, pregnant
women who insist on travelling, against medical advice, to endemic countries
should be vaccinated.
The yellow fever vaccine has been given to considerable numbers of pregnant
women4,9 with no evidence of any adverse outcomes. Therefore, women
vaccinated in early pregnancy can be reassured that there is no evidence of risk
to themselves and very low (if any) risk to the fetus; there are no grounds for a
termination of pregnancy.4
(iii) Administration of other vaccines on the same day

The administration of other live virus vaccines (MMR, varicella vaccine [and
MMRV when available]) should be on the same day as yellow fever vaccine, or
separated by a 4-week interval. Other vaccines relevant to travel can be given
with, or at any time before or after, yellow fever vaccine.

Adverse events
(i) Common adverse events
3.25 Yellow fever
Adverse events following yellow fever vaccine are generally mild. Vaccinees
often report mild headaches, myalgia and low-grade fevers or other minor
symptoms for 5 to 10 days post vaccination. In clinical trials in which symptoms
are actively elicited, up to 25% of vaccinees report mild adverse events and up to
1% curtail regular activities.4,10
(ii) Immediate hypersensitivity reactions

Immediate hypersensitivity reactions, including anaphylaxis, following yellow
fever vaccine are very rare with an incidence of less than 1 in 1 million and occur
principally in people with anaphylactic sensitivity to eggs.4 Although it has
been suggested that an anaphylactic sensitivity to gelatin (added as a stabiliser
to some yellow fever vaccines) may also precipitate anaphylaxis following
vaccination,11 Stamaril does not contain gelatin.
(iii) Vaccine-associated neurotropic adverse events

At least 25 cases of meningoencephalitis following yellow fever vaccination
have been reported.4 However, 15 of these cases occurred in the 1950s in infants
≤7 months of age; following recommendations in the early 1960s not to vaccinate
young infants, the incidence of vaccine-associated meningoencephalitis declined
considerably.4 Nevertheless, these adverse events, albeit very rare, still occur in
adults; the risk is greater in vaccinees ≥60 years of age.7,8
(iv) Vaccine-associated viscerotropic adverse events

Recently, an apparently very rare (and often fatal) complication, characterised
by multiorgan system failure, has been recognised following yellow fever
vaccination; it appears that overwhelming infection with the 17D vaccine-virus is
responsible for these viscerotropic adverse events.4 Up to October 2004, 25 such
cases had been reported worldwide; the exact incidence is unknown but may be
less than 1 in 400 000 doses of vaccine.4
Vaccine-associated viscerotropic adverse events do not appear to be caused by
altered virulence of the vaccine-virus, but rather appear to be related to host
factors. Although cases have occurred in younger people, it is apparent that
the risk is increased with advanced age, in particular in those aged ≥60 years.7,8
Another host factor associated with an increased risk of a viscerotropic adverse
event is pre-existing thymus disease. Four of the 25 reported cases had a history
of thymic tumour and thymectomy, both uncommon conditions.12
Use in pregnancy
Pregnant women, who insist on travelling to either a West African country, or
outside urban areas of any other endemic country, should be vaccinated (see
‘Precautions’ above).
Yellow fever 327

The product information states that pregnancy is a contraindication to the yellow
fever vaccine. However, NHMRC recommends that pregnant women who insist
on travelling, against medical advice, to endemic countries, should be vaccinated.
The product information suggests that a 0.1 mL test dose of yellow fever vaccine
can be used intradermally to assess an individual with suspected allergy to the
vaccine. However, NHMRC states that (with the exception of Q fever vaccine)
test doses should never be used.
References

3.26 Zoster (herpes zoster)
Virology
Varicella-zoster virus (VZV) is a DNA virus that is a member of the herpesvirus
family. Herpes zoster (HZ) or ‘shingles’ is caused by reactivation of latent VZV
which typically resides in the dorsal root or trigeminal ganglia following primary
infection with VZV.1 Primary infection with VZV is known as varicella or
‘chickenpox’.1
Clinical features

Reactivation of VZV causing HZ is thought to be due to a decline in cellular
immunity to the virus, and presents clinically as a unilateral vesicular rash in
a dermatomal distribution in the majority of cases. It is often painful and lasts
10 to 15 days.1,2 A prodromal phase occurs 48 to 72 hours before the appearance
of the lesions in 80% of cases.3 Associated symptoms may include headache,
photophobia, malaise, and an itching, tingling, or severe pain in the affected
dermatome.2,4 In the majority of patients, HZ is an acute and self-limiting disease.
However, complications can occur, especially with increasing age.
Post-herpetic neuralgia (PHN), the most frequent debilitating complication
of HZ, is a neuropathic pain syndrome that persists or develops after the
dermatomal rash has healed or persists longer than 3 months after the onset of
the rash.5,6 Other complications associated with HZ, such as ophthalmic disease
and neurological complications, may occur depending on the site of reactivation.
Rarely, disseminated HZ may develop with visceral, central nervous system, and
pulmonary involvement. Disseminated disease is more common in people with
impaired immunity.4 Dermatomal pain without the appearance of rash is also
documented (zoster siné herpéte). Antiviral therapy, intiated within 3 days after
the onset of HZ, reduces the severity and duration of HZ and may reduce the
risk of developing PHN.7-11 However, in many cases, PHN may persist for years,
and may be refractory to treatment.12
Epidemiology
HZ occurs most commonly with increasing age (>50 years), impaired immunity,
and a history of varicella in the first year of life. The lifetime risk of reactivation
of VZV causing HZ is estimated to be approximately 20 to 30%, and it affects
half of those who live to 85 years.1,13-15 Second attacks of HZ occur in less than
5% of immunocompetent individuals, but are more frequent in individuals with
impaired immunity.2,16 Internationally, average incidence rates of HZ in the total
population vary from 130 to 405 per 100 000 person-years depending on the
study population.17,18 Australian data on the incidence of HZ in the community
are limited. However, using general practice and other data, approximately
Zoster (herpes zoster) 329

5 cases per 1000 population (range 3.3–8.3 per 1000) are estimated to occur
annually.19-21
Overall, an estimated 13 to 26% of HZ patients develop complications.
Complications occur more frequently with increasing age, and with impaired
immunity.22,23 PHN occurs infrequently in young people but, in patients >50 years
of age, it complicates HZ in 25 to 50% of cases.1
Modelling the outcomes of the introduction of a universal infant vaccination
schedule for varicella has predicted a rise in the incidence of HZ based on the
assumption that exposure to VZV boosts immunity.24 It has been suggested that
an increase in HZ incidence rates (in the population previously infected with
wild-type VZV) will occur for approximately 40 years, based on a varicella
vaccine coverage rate of 90% and boosting preventing HZ for an average of
20 years.21,24 Surveillance in the USA has not suggested a change in the incidence
of HZ since the introduction of a universal varicella vaccination program in
1995.18 The incidence of HZ in children vaccinated with varicella vaccine is less
than in those infected with wild-type virus.1,25
In most states of Australia, surveillance for varicella and HZ is currently being
implemented in order to track the burden of disease from VZV before and after
the introduction of the varicella vaccination program.26 South Australia has
conducted passive surveillance of varicella and HZ since January 2002.
Vaccine
A frozen formulation of a live attenuated zoster vaccine is currently registered
in Australia but is not marketed. The zoster vaccine is formulated from the same
VZV strain (Oka/Merck) as the licensed varicella (chickenpox) vaccine, Varivax,
but is of higher potency (at least 14 times greater). The higher viral titre in the
zoster vaccine is required in order to elicit a sufficient cellular immune response
in adults who usually remain seropositive to VZV but have declining cellular
immunity with increasing age. The licensed varicella vaccines are not suitable for
use in the prevention of zoster in older people.
Several randomised placebo-controlled trials conducted during the clinical
development of the zoster vaccine confirmed that a vaccine at potencies above
19 400 plaque forming units (PFU) stimulated both VZV-specific antibodies and a
cell-mediated immune response.27,28 A large randomised, double-blind, placebo-
controlled efficacy and safety trial of the zoster vaccine (known as the “Shingles
Prevention Study”) was conducted among 38 546 primarily healthy adults aged
≥60 years, and demonstrated that the zoster vaccine was safe and generally well
tolerated. Vaccination significantly reduced the burden of both HZ and PHN.27
Overall, compared with placebo, vaccination reduced the incidence of HZ by
51.3% (95% CI: 44.2–57.6%), the incidence of PHN by 66.5% (95% CI: 47.5–79.2%),
and the burden of illness associated with pain from HZ by 61.1% (95% CI:
51.1–69.1%) over a median of 3.12 years of follow-up.27

No product is currently marketed in Australia (see Appendix 3, Products registered
in Australia but not currently available).
References
Zoster (herpes zoster) 331

Appendix 1: Contact details for
Australian, State and Territory
Government health authorities and
communicable disease control
Australian Government health authorities

Australian Government 02 6289 1555
Health
Australian Childhood 1800 653 809
Immunisation Register (This phone number can also be used by
enquiries (ACIR) vaccination providers to obtain information on the
vaccination history of individual children).
ACIR email: acir@medicareaustralia.gov.au
ACIR Internet site: www.medicareaustralia.gov.au;
click on Health Care Providers, then Programs & Services,
then Australian Childhood Immunisation Register
ACIR Internet Helpline: 1300 650 039
Quarterly Outcomes 1800 246 101
Payment & GPII Practice Email: gpii@medicareaustralia.gov.au
Report (ACIR020A):
Website: www.medicareaustralia.gov.au; click on Health
Care Providers, then Incentives & Allowances, then
General Practice Immunisation Incentive Scheme
State and Territory Government health authorities
Australian Capital Territory (02) 6205 2300
Immunisation Enquiry Line
New South Wales Contact your local Public Health Unit, found
under ‘Health’ in the White Pages
Northern Territory (08) 8922 8044
Queensland (07) 3234 1500
South Australia (08) 8226 7177
Immunisation http://www.dh.sa.gov.au/pehs/
Coordination Unit
Tasmania (03) 6222 7724 or 1800 671 738
http://www.dhhs.tas.gov.au/publichealth/
immunisation/index.html
Victoria 1300 882 008
http://www.health.vic.gov.au/immunisation
Western Australia (08) 9321 1312

Contact details for communicable disease control
Australian Capital Territory 24-hour Communicable Disease Control
Section: (02) 6205 2155
New South Wales Contact your local Public Health Unit, found
under ‘Health’ in the White Pages
Northern Territory 0830–1700 hrs: (08) 8922 8044 (After hours Royal Darwin
Hospital (08) 8922 8888 for CDC on-call doctor)
Queensland Contact your local Public/Population Health Unit,
phone number listed in the White Pages
South Australia 24 hour general enquiries line: (08) 8226 7177
Tasmania 24 hour Hotline: 1800 671 738
Victoria 24 hour contact number: 1300 651 160
Western Australia 0830–1700hrs: (08) 9388 4999. After hours: (08) 9382 0553
Appendices
Appendix 1 333
Appendix 2: Handbook development
Introduction
The Handbook has been developed by the Australian Technical Advisory Group
on Immunisation (ATAGI), which provides advice to the Federal Minister for
Health and Ageing on the Immunise Australia Program and other related issues.
In addition to technical experts, ATAGI’s membership includes a consumer
representative and general practitioners. ATAGI consulted with other expert
bodies, and with the National Health and Medical Research Council throughout
the development of the 9th edition of the Handbook. The Handbook does not
address the cost-effectiveness of different vaccines or different regimens;
since January 2006, the cost-effectiveness of vaccines has been assessed by
the Pharmaceutical Benefits Advisory Committee (PBAC), which advises
government on the funding of vaccines.1
The Handbook is designed as a general guide to inform clinicians on the safest
and most effective vaccination strategies, using the highest quality evidence
available in peer-reviewed literature, according to NHMRC guidelines.2-5 In
the absence of evidence at the highest level (well conducted randomised trials
and meta-analyses), recommendations were based on lower levels of evidence
such as case series. Where clinical guidelines were available on specific topics,
these were used to frame recommendations, if relevant, in the Australian
setting. Immunisation handbooks produced by comparable countries were also
consulted. If published sources were inadequate, recommendations were based
on expert opinion.
The draft of the 9th edition of the Handbook was available for public consultation
over a 6-week period from February to April 2007. The public comments received
were reviewed during an extraordinary meeting of ATAGI and, where necessary,
changes to the Handbook were incorporated.
The 9th edition of the Handbook is disseminated directly to all registered medical
practitioners. Additional hard copies are distributed to other immunisation
service providers via their State or Territory health authority. An electronic
version of the Handbook is accessible on the Immunise Australia Program website
http://immunise.health.gov.au/. Implementation of the recommendations as
stated in the Handbook is undertaken by immunisation providers in conjunction
with their State or Territory health authority, and the Immunise Australia
Program of the Australian Government Department of Health and Ageing.
Handbook literature search methodology

For each chapter, broad literature searches were conducted for the years since the
last Handbook searches were performed using up to 18 databases, listed in Table
1. The purpose of these searches was to ensure that technical writers and chapter

sponsors had access to all relevant information from the latest medical literature
in identifying important issues relating to the updating of all Handbook chapters.
Table 1: Electronic databases searched
Electronic database Time period

MEDLINE 2002–2006
PREMEDLINE (when required) 2002–2006
Cochrane Library—including Cochrane Database of Systematic 2002–2006
Reviews, Database of Abstracts of Reviews of Effects, the Cochrane
Central Register of Controlled Trials (CENTRAL), the Health Technology
Assessment Database, the NHS Economic Evaluation Database
Cumulated Index Nursing & Allied Health 2002–2006
Literature (CINAHL) (when required)
EMBASE 2002–2006
Australian focused Informit databases (AMI, APA-FT, APAIS, APAIS 2002–2006
– Health, ATSIhealth, Ausport Med, CINCH – Health, DRUG,
Informit e-library, Health and Society, HIV A, Meditext, RURAL).
For specific questions arising in individual chapters, other databases and

additional resources such as Clinical Evidence were searched as necessary. The
scope and nature of the review differed for updating of existing chapters in the
Handbook and new chapters for the 9th edition.
• Existing chapters in the Handbook
The medical and health literature was searched to identify relevant studies
Appendices
and reviews regarding individual diseases and the vaccines available using the
electronic databases in Table 1. The search period was from 2002 to September
2006. The scope of the searches was broad, to ensure maximum retrieval and
minimise the exclusion of items of interest. Previous Handbook searches were
examined to determine the scope required for the new searches, and similar
search strategies were employed to ensure consistency of information retrieval.
Various search methods were tested, including ‘explode’ and ‘focus’ options.
‘Exploded’ terms retrieve citations containing the term being searched and all the
narrower related terms in the database. ‘Focus’ searches retrieve citations that
have the search term as the major focus of the item. In the trial searches, some
items of interest were missed using the ‘focus’ method, thus ‘exploded’ searches
were utilised. All subheadings assigned to the subject headings were generally
included.
In general, the search strategy consisted of the disease topic combined with the
terms immunisation/preventive health. Boolean operators AND, OR, and NOT
were used.
Appendix 2 335
To ensure relevant and accurate retrieval, thesaurus terms (the controlled
vocabulary terms used in the database) were used whenever possible. Keyword
searching was used only in the absence of an appropriate thesaurus term or if the
database did not have thesaurus terms. To facilitate relevant retrieval and to limit
what, in some instances, are very large search result sets, the following limits
were applied to the disease topic searches:
• Publication year – searches were generally limited to items published from
2002–2006, in order to retrieve items published since the searches completed
for the 8th edition of the Handbook.
• Language – searches were limited to items in English.
• Human – items discussing only animals were removed.
• In vitro – items discussing only in vitro studies were removed.
• Abstracts – search results restricted to items containing abstracts.
The search limits were slightly modified for some of the other searches. For
example, the Australian-specific searches did not have search results limited to
abstract only, to ensure that all Australian items were retrieved, including items
such as letters to the editor and editorials. In addition, the search result files were
edited to remove irrelevant items. Files were edited, where possible, to remove
duplication across the databases. There was often substantial duplication across
databases, as databases index some of the same journals.
More specific searches were undertaken when requested by chapter sponsors or
technical writers to provide additional information on a particular aspect of a topic.
• New vaccine chapters
For the new vaccine chapters, Chapter 3.7 Human papillomavirus and Chapter
3.18 Rotavirus, search strategies employed for the existing chapters (as above)
were used. In addition, recommendations were formulated using a structured
clinical question using the PICO (Patient/population, Intervention, Comparison
and Outcome) format as per the NHMRC guidelines.3 Where possible, these
structured clinical questions informed both the searching and subsequent data
extraction processes. Search limits used for the new vaccine chapters differed
from those used for the existing chapters. To maximise retrieval and minimise
publication or other potential biases, no limitation by date, language or abstract
was applied. All papers identified as relevant from the PICO literature review
were critiqued using a standard proforma, according to whether they were
classified as studies of an intervention, diagnostic tests, prognosis, aetiology
or related to screening. Completion of a separate detailed data extraction form
was undertaken for each included study considered in the body of evidence for
each recommendation. These processes were completed in consultation with the
NHMRC-appointed Guideline Assessment Register consultant.

Complete details of the systematic literature review for the new vaccine chapters
in the Handbook may be found on the Immunise Australia website
www.immunise.health.gov.au.
The evidence presented in the included studies was assessed and classified
as described by the NHMRC.3 The consideration of important aspects of the
evidence supporting the intervention or recommendations included three main
domains:
• strength of the evidence (level, quality and statistical precision),
• size of the effect (including clinical importance), and
• relevance of the evidence.
Grades of evidence were assigned to the recommendations in the new vaccine
chapters using the NHMRC considered judgment approach for assessing a body
of evidence (see Table 2). Grade A and B recommendations are generally based
on a body of evidence which can be trusted to guide clinical practice, whereas
Grade C and D recommendations must be applied carefully to individual clinical
and organisational circumstances and should be followed with care.
Table 2: Grades of recommendations4
Grade of Description
recommendation
A Body of evidence can be trusted to guide practice
B Body of evidence can be trusted to guide practice in most situations
C Body of evidence provides some support for recommendation(s)
but care should be taken in its application
Appendices
D Body of evidence is weak and recommendation
must be applied with caution
The level of evidence for the included studies for each recommendation is also
given, according to the NHMRC additional levels of evidence. Table 3 shows the
levels that apply to intervention studies (for other study types, such as aetiology,
prognosis or diagnosis, see http://www.nhmrc.gov.au/consult/index.htm). The
level of evidence indicates the study design used by the investigators to assess
the effectiveness of an intervention. The level assigned to a study reflects the
degree to which bias has been eliminated by the study design.3
Appendix 2 337
Table 3: NHMRC Levels of evidence for intervention studies4
Intervention Level of evidence

A systematic review of level II studies I
A randomised controlled trial (RCT) II
A pseudo-randomised controlled trial (eg. alternate III-1
allocation or some other method)
A comparative study with concurrent controls: III-2
Non-randomised, experimental trial
Cohort study
Case-control study
Interrupted time series with a control group
A comparative study without concurrent controls: III-3
Historical control study
Two or more single arm study
Interrupted time series without a parallel control group
Case series with either post-test or pre-test/post-test outcomes IV
Further information of how these grades were applied is given in the detailed
description of the systematic literature reviews for the new vaccine chapters, which
is available on the Immunise Australia website, www.immunise.health.gov.au.
Establishing Selected Dissemination Information (SDI) searches

Selected Dissemination Information (SDI) searches were established to enable
the ongoing collection of new relevant items on the search topics. This process
used the same search strategies as the previous searches. Search results are
automatically generated each time the databases (MEDLINE, EMBASE) are
updated, and a report is automatically sent to a nominated e-mail address. This
allowed inclusion of the most recent literature to be evaluated and referenced
throughout the revision and updating of the Handbook, where applicable.
References

Appendix 3: Products registered in
Australia but not currently available
Products registered but not currently available

Arilvax CSL Biotherapies/Novartis Vaccines (live attenuated
yellow fever virus (17D strain) vaccine)
Gamunex Bayer Australia Pty Ltd (normal human immunoglobulin for IV use)
Pediacel Sanofi Pasteur Pty Ltd (diphtheria-tetanus-acellular
pertussis-inactivated poliomyelitis vaccine-Hib)
Priorix-Tetra GlaxoSmithKline (live measles-mumps-rubella-varicella vaccine)
ProQuad Frozen CSL Biotherapies/Merck & Co Inc (live measles-
mumps-rubella-varicella vaccine)
ProQuad CSL Biotherapies/Merck & Co Inc (live measles-
mumps-rubella-varicella vaccine)
Zostavax CSL Biotherapies/Merck & Co Inc (live varicella-
zoster vaccine, frozen vaccine formulation)
Products previously available
ADT CSL Biotherapies (diphtheria-tetanus vaccine, adult)
CDT CSL Biotherapies (diphtheria-tetanus vaccine, child)
Diphtheria antitoxin CSL Biotherapies
Diphtheria CSL Biotherapies (vaccine, adult)
Appendices
Diphtheria CSL Biotherapies (vaccine, child)
Infanrix GlaxoSmithKline (diphtheria-tetanus-
acellular pertussis vaccine, child)
Infanrix Hep B GlaxoSmithKline (diphtheria-tetanus-acellular
pertussis-hepatitis B vaccine, child)
M-M-R II CSL Biotherapies/Merck & Co Inc (measles-mumps-rubella vaccine)
Orochol CSL Biotherapies (oral live recombinant
Vibrio cholerae CVD 103-HgR)
Quadracel Sanofi Pasteur Pty Ltd (diphtheria-tetanus-acellular
pertussis-inactivated poliomyelitis vaccine, child)
Tet-Tox CSL Biotherapies (tetanus vaccine)
Tripacel Sanofi Pasteur Pty Ltd (diphtheria-tetanus-
acellular pertussis vaccine, child)
Typh-Vax (Oral) CSL Biotherapies (live attenuated typhoid vaccine)
Tuberculin PPD CSL Biotherapies (1000 units/mL)
Appendix 3 339
Appendix 4: Components of vaccines used
in the National Immunisation Program*†
For vaccines not listed in the National Immunisation Program, please refer
to individual product information leaflet as supplied with the vaccine, or the
Handbook chapter pertinent to that vaccine.
Vaccine component Vaccine brand§ Antigen
(possible cause of
an allergy)‡
Aluminium Avaxim Hepatitis A (HAV)
hydroxide COMVAX Haemophilus influenzae
type b-hepatitis B (Hib-hepB)
Engerix-B Hepatitis B (HBV) adult
Engerix-B Hepatitis B (HBV) paediatric
Havrix Junior Hepatitis A (HAV) paediatric
H-B-VAX II Hepatitis B (HBV) adult
H-B-VAX II Hepatitis B (HBV) paediatric
Infanrix-IPV Diphtheria-tetanus-acellular pertussis-
inactivated poliomyelitis (DTPa-IPV)
Liquid PedvaxHIB Haemophilus influenzae type b (Hib)
Menjugate Syringe Serogroup C meningococcal conjugate
NeisVac-C Serogroup C meningococcal conjugate
Vaqta Hepatitis A (HAV) paediatric/adolescent
Aluminium Boostrix Diphtheria-tetanus-acellular
hydroxide/ pertussis (dTpa) adult
phosphate GARDASIL Human papillomavirus (HPV)
Infanrix hexa Diphtheria-tetanus-acellular pertussis-hepatitis
B-inactivated poliomyelitis-Haemophilus
influenzae type b (DTPa-hepB-IPV-Hib)
Infanrix Penta Diphtheria-tetanus-acellular pertussis-hepatitis
B-inactivated poliomyelitis (DTPa-hepB-IPV)
Aluminium Adacel Diphtheria-tetanus-acellular
phosphate pertussis (dTpa) adult
Meningitec Serogroup C meningococcal conjugate
Prevenar 7-valent pneumococcal conjugate
Borax COMVAX Haemophilus influenzae
GARDASIL Human papillomavirus (HPV)
Liquid PedvaxHIB Haemophilus influenzae type b (Hib)

(possible cause of
an allergy)‡
Egg protein All influenza
vaccines
Fluad Influenza
Fluarix Influenza
Fluvax Influenza
Fluvirin Influenza
Influvac Influenza
Vaxigrip Influenza
Formaldehyde Adacel Diphtheria-tetanus-acellular
pertussis (dTpa) adult
Avaxim Hepatitis A (HAV)
Boostrix Diphtheria-tetanus-acellular
Fluad Influenza
Fluarix Influenza
Appendices
Vaxigrip Influenza
Gelatin Varivax Refrigerated Varicella-zoster (VZV)
Gentamicin Fluarix Influenza
Influvac Influenza
Kanamycin Fluad Influenza
Monosodium Varivax Refrigerated Varicella-zoster (VZV)
glutamate (MSG)
Appendix 4 341
(possible cause of
an allergy)‡
Neomycin Avaxim Hepatitis A (HAV)
Fluad Influenza
Fluvax Influenza
Fluvirin Influenza
Priorix Measles-mumps-rubella (MMR)
Varilrix Varicella-zoster (VZV)
Varivax Refrigerated Varicella-zoster (VZV)
Vaxigrip Influenza
Phenol Pneumovax 23 23-valent pneumococcal polysaccharide
Phenoxyethanol Adacel Diphtheria-tetanus-acellular
Avaxim Hepatitis A (HAV)
Boostrix Diphtheria-tetanus-acellular
Polymyxin Fluvax Influenza
Fluvirin Influenza

(possible cause of
an allergy)‡
Thiomersal Engerix-B Hepatitis B (HBV) adult
(contains trace <2 µg/mL)
(contains trace <2 µg/mL)
Fluad Influenza
Fluarix Influenza
Yeast COMVAX Haemophilus influenzae
Engerix-B Hepatitis B (HBV) adult
GARDASIL Human papillomavirus (HPV)
H-B-VAX II Hepatitis B (HBV) adult
H-B-VAX II Hepatitis B (HBV) paediatric
* Please note that vaccine manufacture is subject to ongoing refinement and change.
Therefore, the following information may change. This information was current at the time
of preparation.
† This table has been adapted with permission from Dr T. McGuire.1
Appendices
‡ If the person to be vaccinated has had an anaphylactic reaction to any of the vaccine
components, administration of that vaccine is contraindicated.
§ Please also refer to Appendix 5, Commonly asked questions about vaccination for more specific
information about these various constituents.
References
Appendix 4 343
Appendix 5: Commonly asked
questions about vaccination
This chapter contains information for providers to refer to when responding

to questions and concerns about immunisation. It covers general questions on
adult and childhood vaccination, including contraindications and precautions.
In addition, a discussion on some of the more recent concerns about vaccination
is included, covering issues relating to vaccine safety, vaccine content,
immunisation as a possible cause of some illnesses of uncertain origin, and the
need for vaccination.
This appendix is divided into 4 sections:
1. General questions
2. Contraindication and precautions
3. Responding to questions and concerns about immunisation
4. Where can I get more information about vaccination?
1. General questions
(i) How does vaccination work?
When a healthy person becomes infected with a virus, eg. measles, the body
recognises the virus as an invader, produces antibodies which eventually destroy
the virus and recovery occurs. If contact with the measles virus occurs again
in the future, the body’s immune system ‘remembers’ the measles virus and
produces an increase in antibodies to destroy the virus.
Vaccination is the process that is used to stimulate the body’s immune system in
the same way as the real disease would, but without causing the symptoms of
the disease. Most vaccines provide the body with ‘memory’ so that an individual
doesn’t get the disease if exposed to it.
Vaccination conveys immunity to diseases by a process called active immunity,
which can be achieved by administration of either inactivated (ie. not live) or
live attenuated organisms or their products. Live vaccines are attenuated, or
weakened, by growing the organism through serial culturing (or passaging)
steps in various tissue culture media. Inactivation is usually done using heat
or formalin (sometimes both). Inactivated vaccines may include the whole
organism (such as oral cholera vaccine), the toxin produced by the organism
(such as tetanus and diphtheria vaccines), or specific antigens (such as Hib and
pneumococcal vaccines). In some cases, the antigen is conjugated (ie. chemically
linked) with proteins to facilitate the immune response. Inactivated viral vaccines
may include whole viruses (such as IPV and hepatitis A vaccines) or specific
antigens (such as influenza and hepatitis B vaccines). Live attenuated viral
vaccines include MMR, rubella, varicella and yellow fever vaccines.

Immunity can also be acquired passively by the administration of
immunoglobulins. Such immunity is immediate and is dose-related and
transient. For example, measles or hepatitis B immunoglobulin can be used
promptly after exposure in an unimmunised person to help reduce the chance of
catching measles or hepatitis B from the exposure.
(ii) What is the correct site for vaccination of children?

The top, outer part of the thigh (the vastus lateralis muscle) is the recommended
site for injections for infants <12 months of age. The deltoid region of the upper
arm is the recommended site for vaccination of children ≥12 months of age
because it is associated with fewer local reactions and has sufficient muscle bulk
to facilitate the injection. However, the vastus lateralis muscle can also be used.
The ventrogluteal area is an alternative site. (See Section 1.4.6, Recommended
injection sites and Section 1.4.8, Identifying the injection site).
Rotavirus vaccines are administered by the oral route and must never be injected.
(iii) How many injections can be given into the

same limb in a child aged <12 months?
More than 1 vaccine can be safely given into a limb at the same immunisation
visit. Most States and Territories have routine immunisation schedules that
include 3 injections during the primary course for children <12 months of
age. In this case, 2 injections can be given into the same leg into the vastus
lateralis muscle and the third injection in the other vastus lateralis muscle (or
an alternative is the ventrogluteal site). The injections should be given at least
25 mm (2.5 cm) apart. Use separate sterile injection equipment for each vaccine
administered. The accompanying documentation should indicate clearly which
Appendices
vaccines were given into which site (eg. left leg upper/left leg lower).
(iv) When should preterm infants be vaccinated?

Babies born at <32 weeks’ gestation or <2000 g birth weight should receive
their first dose of hepatitis B vaccine either at birth (within the first few days of
life) or at 2 months of age. Immunisation schedules differ in different areas of
Australia according to which combination vaccines are routinely used in that
State or Territory. The routine 2-month vaccines containing the antigens DTPa-
IPV-Hib-hepB, 7vPCV and rotavirus should be given 2 months after birth as
normal, unless an infant is very unwell. ‘Very unwell’ can be interpreted in many
ways but, in general, reflects that the premature neonate is particularly unstable.
Delaying the 2-month vaccines is rarely required. If any preterm infant has the
2-month vaccines delayed, it should be remembered that the infant doses can
be given 1 month apart rather than 2 months. Hence, if an infant receives the
2-month vaccines at 3 months then the 4 month vaccines should still be given at
4 months of age.
Appendix 5 345
When Liquid PedvaxHIB is used in an extremely preterm baby (<28 weeks’
gestation or <1500 g birth weight), an additional dose should be given at
6 months of age.
Further explanation of the special immunisation needs of premature babies is
provided in Section 2.3.2 Vaccination of women planning pregnancy, pregnant or
breastfeeding women, and preterm infants.
(v) Do elderly people (>65 years) who have no chronic

illnesses need the influenza vaccine?
Yes. Age is an independent risk factor for influenza. Vaccination of those aged
>65 years, regardless of the presence or absence of chronic illness, reduces
mortality by up to 50% in the winter period in this age group (see Chapter 3.9,
Influenza).1,2 The healthy elderly should also receive the 23-valent pneumococcal
polysaccharide vaccine (see Chapter 3.15, Pneumococcal disease).
(vi) Should adults receive pertussis (whooping cough) vaccine boosters?

Yes. Two brands of acellular pertussis vaccines, both combined with tetanus and
diphtheria antigens, are now available for adolescents and adults. dTpa vaccines
are recommended in Australia for booster vaccination of individuals ≥8 years of
age who have previously had a primary course of diphtheria-tetanus-pertussis
vaccine. dTpa vaccines have a lower content of diphtheria and pertussis antigens
than DTPa formulations for young children.
A recent study showed that adults can be protected against pertussis after a
single dose of dTpa. No recommendations about the need for further boosters
using adolescent/adult formulation dTpa have been made at this time.
A single dose of dTpa is recommended for the following groups (unless
contraindicated or they have already received a previous dose of dTpa):
• adults working with young children. Vaccination is especially recommended
for childcare workers;
• all healthcare workers;
• adults planning a pregnancy, or for both parents as soon as possible
after delivery of an infant (preferably before hospital discharge), unless
contraindicated.3 Other adult household members, grandparents and carers
of young children should also be vaccinated. This recommendation is based
on evidence from several studies of infant pertussis cases, which indicated
that family members, particularly parents, were identified as the source of
infection in more than 50% of cases and were the presumed source in a higher
proportion;
• any adult expressing an interest in receiving a booster dose of dTpa.
Adults ≥50 years of age who have not previously received dTpa vaccine should
also be offered vaccination. See Chapter 3.3, Diphtheria, Chapter 3.14, Pertussis or
Chapter 3.21, Tetanus in this Handbook.

Contraindications to adolescent/adult formulation dTpa are discussed in
Chapter 3.3, Diphtheria, Chapter 3.14, Pertussis and Chapter 3.21, Tetanus in this
Handbook and include previous anaphylactic reaction to any vaccine component.
If the patient has never received a primary course of dT, see Chapter 3.3,
Diphtheria, Chapter 3.14, Pertussis or Chapter 3.21, Tetanus in this Handbook.
(vii) A parent wants a child to receive his/her vaccines

separately. Why can’t they do this?
There is no scientific evidence or data to suggest that there are any benefits in
receiving vaccines such as MMR or DTPa as separate monovalent vaccines.
Using the example of MMR vaccine, there is no individual mumps or measles
vaccine licensed for use in Australia. If these vaccines were to be administered
individually it would require 3 separate vaccines which would unnecessarily
increase discomfort for the child. In addition, if these monovalent vaccines were
not given on the same day, they would need to be spaced 1 month or more apart
which would increase the risk of that child being exposed to serious vaccine-
preventable diseases. A policy of providing separate vaccines would cause some
children to not receive the entire course, and combination vaccines can offer a
reduced amount of vaccine stabiliser and adjuvant compared to 3 individual
vaccine doses.
(viii) Is vaccination compulsory? What happens

if children do not get vaccinated?
Vaccination is not compulsory in Australia.
The Maternity Immunisation Allowance and Child Care Benefit are parent
incentive payments that are paid where a child is up-to-date with his/
Appendices
her immunisations or the parent has obtained an appropriate medical or
philosophical exemption.
If a parent decides not to have a child vaccinated and, if cases of certain vaccine-
preventable diseases occur at that child’s day-care centre or school, the parent
may, in some circumstances, be required to keep the unvaccinated child at home
until the incubation period for that particular disease has passed or no further
cases have occurred in that setting.
2. Contraindications and precautions

If you have any concerns about whether to proceed with vaccination, please
seek expert advice. See Appendix 1, Contact details for Australian, State and
Territory Government health authorities and communicable disease control.
(i) What are the absolute contraindications to childhood vaccination?

True contraindications to the childhood vaccines are extremely rare (see relevant
chapters), and include only anaphylaxis to any of the particular vaccine’s
components, and anaphylaxis following a previous dose of that vaccine.
Appendix 5 347
NB. Anaphylaxis following ingestion of eggs does not contraindicate MMR
vaccine, as the vaccine viruses are not grown in eggs and the vaccine does not
contain any egg protein4 (see Chapter 3.11, Measles).
(ii) What are the contraindications to further doses

of pertussis-containing vaccines?
Further doses of DTPa are contraindicated in those who have had a previous
immediate severe allergic or anaphylactic reaction to vaccination with DTPa.
A previous simple febrile convulsion or pre-existing neurological disease is not a
contraindication to pertussis-containing vaccines.
(iii) What are the precautions to childhood vaccination?

In general, children with impaired immunity or on immunosuppressive therapy
should not be given live vaccines (see (vii) to (ix) below).
(iv) Should a child with an intercurrent illness be vaccinated?

A child with a minor illness (without systemic illness and with a temperature
<38.5°C) may be safely vaccinated. Infants and children with minor coughs and
colds without fever, or those receiving antibiotics in the recovery phase of an
acute illness, can be vaccinated safely and effectively. In a child with a major
illness or high fever ≥38.5°C, vaccination should be postponed until the child is
well. If vaccination were to be carried out during such an illness, the fever might
be confused with vaccine side effects and might also increase discomfort to the
child. In such cases, it is advisable to defer vaccination and arrange for the child
to return for vaccination when well again.
(v) Should children with epilepsy be vaccinated?

Yes. Stable neurological disease (such as epilepsy) is not a reason to avoid giving
vaccines like pertussis (whooping cough). Children who are prone to fits should
have paracetamol before and for 48 hours after vaccination to reduce the chance
of a fever after vaccination bringing on a convulsion. A family history of fits or
epilepsy is not a reason to avoid vaccination.
(vi) Should children with neurological disease receive

the normal vaccination schedule?
Yes. Children with neurological disease are often at increased risk of
complications from diseases like measles, influenza and whooping cough, as they
can be more prone to respiratory infections and chest problems. It is important
that these children be immunised, on time, as recommended in the National
Immunisation Program schedule.
(vii) Are steroids a contraindication to vaccination?

Live vaccines such as MMR, BCG and varicella-zoster vaccines, should
not be given to children or adults receiving high dose oral or parenteral
corticosteroid therapy for more than 2 weeks. High dose oral corticosteroid

therapy is defined as more than 2 mg/kg per day prednisolone for more than
1 week. This is because steroids, in large doses, greatly suppress the immune
system which means that, not only is the vaccine unlikely to be effective, but
there is an increased chance of an adverse event occurring as a result of the
immunosuppression.
Inactivated vaccines, eg. DTPa-hepB-IPV, may be less effective in this group but
are not contraindicated. Therapy with inhaled steroids is not a contraindication
to vaccination.
(viii) Should vaccines be given to children who have

problems with their immune systems?
Children with impaired immunity or those on immunosuppressive therapy should
not be given live viral vaccines such as MMR, varicella, and rotavirus vaccines.5
HIV-infected children may be given MMR vaccine provided they do not have
severely impaired immunity (see Table 2.3.4 Immunological categories based on
age-specific CD4 counts and percentage of total lymphocytes). The contacts of children
with impaired immunity can be given MMR without any risk of transmission.
The rash seen in a small percentage of MMR vaccine recipients, usually
between days 5 to 12 post vaccination, is not infectious.
It is highly recommended that non-immune household contacts of children with
impaired immunity receive varicella vaccine. There is an almost negligible risk
of transmitting varicella vaccine virus from a vaccine-related vesicular rash to
contacts. However, vaccine-related rash occurs in 3 to 5% of vaccinees either
locally at the injection site or generalised, with a median of only 25 lesions.
This small infection risk of the less virulent attenuated vaccine strain is far
Appendices
outweighed by the high risk of non-immune contacts catching wild varicella
infection and transmitting the virus to the household member with impaired
immunity via respiratory droplets or from the large number of skin lesions that
occur with wild varicella infection (a median of 300 to 500 lesions).
Live viral vaccines can be given to children with leukaemia and other
malignancies who have been on chemotherapy at least 3 months after they have
completed chemotherapy, provided there are no concerns about their immune
status. Such measures would normally be carried out under the supervision of
the child’s oncologist (see Section 2.3.3, Vaccination of individuals with impaired
immunity due to disease or treatment).
(ix) What vaccines should children with HIV infection receive?

Children with HIV (human immunodeficiency virus) infection should have all
routine inactivated vaccines on the National Immunisation Program schedule.
Varicella vaccine is generally contraindicated in children with HIV, as it can cause
disseminated varicella infection. However, it may be considered for asymptomatic
or mildly symptomatic HIV-infected children, after weighing up the potential
risks and benefits. This should be discussed with the child’s specialist.
Appendix 5 349
MMR vaccine can be given to children with HIV, depending on their CD4 counts
(see point (viii) above). Children with HIV infection should also be vaccinated
against pneumococcal disease (see Chapter 3.15, Pneumococcal disease). Influenza
vaccine is also recommended for HIV-infected children. They should not be given
BCG, due to the risk of disseminated infection (see Section 2.3.3, Vaccination of
individuals with impaired immunity due to disease or treatment).
(x) Should chronically ill children be vaccinated?

In general, children with chronic diseases should be vaccinated as a matter of
priority because they are often more at risk from complications from vaccine-
preventable diseases. Annual influenza vaccine is highly recommended for
chronically ill children and their household contacts.
Care is needed with the use of live attenuated viral vaccines in situations where
the child’s illness, or its treatment, may result in impaired immunity. Advice
may need to be sought on these patients to clarify the safety of live viral vaccine
doses.
(xi) Should children be vaccinated while the child’s mother is pregnant?

There is no problem with giving routine vaccinations to a child whose mother
is pregnant. MMR vaccine viruses are not transmissible. Administration of
varicella vaccine to household contacts of non-immune pregnant women is safe.
Transmission of varicella vaccine virus is very rare. There is an almost negligible
risk of transmitting varicella vaccine virus from a vaccine-related vesicular rash
to contacts. However, vaccine-related rash occurs in 3 to 5% of vaccinees either
locally at the injection site or generalised, with a median of only 25 lesions.
Furthermore, vaccinating the child of a pregnant mother will reduce the risk of
her being infected by her offspring with the more virulent wild virus strain if she
is not immune.
(xii) Should children with allergies be vaccinated? What precautions

are required for atopic or egg-sensitive children?
Asthma, eczema and hay fever are not contraindications to any vaccine on the
childhood schedule unless the child is receiving high-dose steroid treatment (see
point (vii) above). For other allergies, see Appendix 4, Components of vaccines
used in the National Immunisation Program, and the relevant vaccine product
information (PI) enclosed in the vaccine package. Unless the child (or person
being vaccinated) has an allergy to a specific constituent of a vaccine (or has
another contraindication) there is no reason not to vaccinate.
An important exception is anaphylactic sensitivity to eggs, characterised by
generalised hives, swelling of the mouth or throat, difficulty breathing, wheeze,
low blood pressure, and shock. If a person has a history of severe egg allergy,
influenza, yellow fever and Q fever vaccines should not be given. Because MMR
vaccine viruses are not cultured in eggs and the vaccine does not contain egg
protein, MMR can be given safely to those with anaphylactic sensitivity to eggs.4

Simple dislike of eggs or having diarrhoea or stomach pains after eating eggs
are not reasons to avoid MMR and these children require no special precautions.
These children can also have all other routine vaccines without special
precautions.4
Families with questions about allergies and vaccines are encouraged to discuss this with
their immunisation service provider to have any questions promptly answered to avoid
unnecessary delays of vaccine doses.
3. Responding to questions and concerns about immunisation

Some people express concerns about immunisation. These mostly relate to
whether the vaccine is safe and whether vaccines weaken the immune system
of the child. Providers should listen to and acknowledge people’s concerns.
Providers should discuss the risks and benefits of immunisation with parents/
carers honestly and in a non-defensive manner. Parents/carers and adult
vaccine recipients should receive accurate information on the risks from vaccine-
preventable diseases and information about vaccine side effects and adverse
events (see table inside the front cover Comparison of the effects of diseases and the
side effects of vaccines). The following section responds to some concerns raised
about the safety of immunisation, and examines the scientific evidence in order
to assist providers and parents in making an informed choice about the risks and
benefits of vaccination.
a) Vaccine safety
(i) How safe are vaccines?
Before vaccines are made available for general use they are tested for safety and
efficacy in clinical trials and then in large trials, otherwise known as Phase 2 and
Appendices
3 trials. All vaccines marketed in Australia are manufactured according to strict
safety guidelines and are evaluated by the Therapeutic Goods Administration
to ensure they are efficacious and are of adequate quality and safety before
marketing approval is granted.
After introduction into vaccination schedules, there is continuing surveillance of
efficacy and safety through trials and post-marketing surveillance. In Australia,
there are regional and national surveillance systems actively seeking any adverse
events following immunisation. This is necessary, as sometimes problems occur
after vaccines are registered for use. Regular Australian surveillance reports are
published in the journal Communicable Diseases Intelligence.6
(ii) Can too many vaccines overload or suppress the natural immune system?
No. The increase in the number of vaccines and vaccine doses given to children
has led to concerns about the possible adverse effects of the aggregate vaccine
exposure, especially on the developing immune system. In day-to-day life, all
children and adults confront enormous numbers of antigens and the immune
system responds to each of these in various ways to protect the body. Studies of
Appendix 5 351
the diversity of antigen receptors indicate that the immune system can respond
to an extremely large number of antigens. In addition, the number of antigens
received by children during routine childhood vaccination has actually decreased
compared with several decades ago. This has occurred in spite of the increase in
the total number of vaccines given, and can be accounted for by the removal of 2
vaccines – smallpox vaccine (which contained about 200 different proteins), and
whole-cell pertussis vaccine (about 3000 distinct antigenic components) from
routine vaccination schedules. In comparison, the acellular pertussis vaccine
currently used in Australia has only 3 to 5 pertussis antigens.7
(iii) Do vaccines cause disease?

Some studies have suggested a temporal link between vaccinations and
certain medical conditions, such as asthma, multiple sclerosis, and diabetes.
The allegations of a link are often made for a disease of unknown cause. The
appearance of a certain medical condition after vaccination does not necessarily
imply that they are causally related. Importantly, however, once an issue is raised
it needs prompt research, discussion and then education to avoid propagating a
myth. In many cases, subsequent epidemiological studies have indicated that the
association is due to chance alone. The following is a list of concerns that have
been raised.
• Does MMR vaccine cause inflammatory bowel disease or autistic spectrum
disorder?8
In 1998, Wakefield et al (Royal Free Hospital, London)9 published a case series
study with 12 children suggesting that MMR vaccine caused inflammatory bowel
disease (IBD), which then resulted in decreased absorption of essential vitamins
and nutrients through the intestinal tract. They proposed that this could result in
developmental disorders such as autism.
Following the study’s publication, Wakefield suggested that it may be 3 live
viruses in the 1 vaccine which was causing the development of the subsequent
disorders. He suggested it was preferable to provide MMR vaccination as 3
separate vaccines, a suggestion with no supportive evidence.9
This study had several weaknesses. First, finding out whether or not MMR
causes autism is best determined by comparing the incidence of autism in
vaccinated versus unvaccinated children. However, the researcher included
only vaccinated children. Second, the author claimed that gastrointestinal
inflammation contributes to autism. However, in several of the children,
their behavioural problems appeared before the onset of bowel disease.10,11
Furthermore, the study was primarily based on parental recall of when the bowel
disease and developmental disorders first appeared, and people are more likely
to have linked changes in behaviour with memorable events such as vaccination.
The Royal Free Hospital study was conducted on a very selective group of
patients, all referred to the hospital for gastrointestinal ailments, and such a case
series analysis is unable to determine causal links.

The onset of autism and MMR vaccination may coincide because the average age
at which parents report concerns about child development is 18 to 19 months,
and more than 90% of children in the UK receive MMR vaccine before their 2nd
birthday.12 More rigorous and larger epidemiological studies have found no
evidence of an association.13-16
A review by the World Health Organization concluded that current scientific data
do not permit a causal link to be drawn between the measles virus and autism
or IBD.17An extensive review published in 2004 by the Institute of Medicine,
an independent expert body in the United States, concluded that there is no
association between the MMR vaccine and the development of autism.18 Reviews
by the American Academy of Pediatrics, The British Chief Medical Officer, the
UK Medical Research Council, Canadian experts, and numerous other scientific
experts have stated that there is no link between autism or IBD and the measles
vaccine.14,19-21
See Chapter 3.11, Measles for further information. There is also an
MMR vaccine decision aid designed for parents available at
http://www.ncirs.usyd.edu.au/decisionaid/index.html.
• Do childhood immunisations cause asthma?
There is no evidence that vaccination causes or worsens asthma. It is especially
important that children with asthma be vaccinated like other children, as
catching a disease like whooping cough can make an asthma attack worse.
Although influenza vaccine is not routinely recommended for all asthmatics,
it is recommended for severe asthmatics, such as those requiring frequent
hospitalisation.22
• Does hepatitis B vaccine cause multiple sclerosis?
Appendices
There is no reliable evidence that the hepatitis B vaccine causes multiple sclerosis
(MS). With millions of hepatitis B vaccinations administered worldwide, it is
likely that surveillance systems in some countries will receive some reports of
MS, which seem to be related in time to vaccinations. As with all such reports,
however, they suggest only the possibility of an association. Subsequent studies
have found no increase in incidence of MS, or even relapse of MS, after hepatitis
B vaccination.23-27
In response to a single study by Hernán et al,28 the World Health Organization
Global Advisory Committee on Vaccine Safety released the following statement:
“multiple studies and review panels have concluded that there is no link between
MS and hepatitis B vaccination”.29
In addition, a review by the Institute of Medicine Immunization Safety Review
Committee in 2003 found no link between hepatitis B vaccine and certain
neurological disorders such as MS.30 A systematic review from the Cochrane
Vaccines Field in 2003 also found no evidence of an association between hepatitis
B vaccine and MS.31 Recent statements by the World Health Organization and the
US Centers for Disease Control and Prevention support this position.29,32,33
Appendix 5 353
• Do some vaccines cause ‘Mad Cow Disease’?
Variant Creutzfeldt-Jakob disease (vCJD) is considered to be the human
equivalent of bovine spongiform encephalopathy (BSE, also known as ‘mad
cow disease’). There is no evidence that any case of vCJD has resulted from the
administration of any vaccine product, despite millions of doses of vaccine being
administered worldwide. Concerns about the risk of transmission of this disease
arose because the production of some vaccines requires bovine derivatives such
as fetal bovine serum. In Australia, the Therapeutic Goods Administration has
confirmed that the vaccines available in this country contain bovine materials
preferentially sourced from BSE-free areas, and that they undergo appropriate
purification treatment. Therefore, although some vaccines carry a theoretical risk
of transmissible spongiform encephalopathies, this risk is infinitesimally small
(estimated at less than 1 in a billion).34 The benefits of vaccination are considered
to far outweigh any theoretical risk of BSE transmission.35
• Is there a link between vaccination and Sudden Infant Death Syndrome
(SIDS)?
Despite extensive studies, there is no evidence that vaccination causes SIDS (cot
death). Deaths do occasionally occur shortly after vaccination but the relationship
is a chance association, since SIDS tends to happen in babies of 2–6 months of
age, whether they are vaccinated or not.36 Many studies have conclusively shown
that SIDS is not caused by immunisation. In addition, some studies have found a
lower rate of SIDS in immunised children.37-39
• Does immunisation cause diabetes?
In 1997, a study from Finland suggested a link between Hib vaccination and type
1 diabetes.40 However, subsequent reanalysis of the data did not support such a
link.41,42 The conclusion that there is no causal link between any of the childhood
vaccines and diabetes has also been supported by a subsequent review of the
literature, and the conclusions of 2 workshops held in the USA in 1998.8,41-43
• Does influenza vaccine cause flu?
No. It is not possible for influenza vaccine to cause ‘flu’ as it is not a live viral
vaccine. As some people experience side effects such as a mild fever after the
vaccine, it is understandable that they may confuse these symptoms with
actually having the flu. In addition, the influenza vaccine is recommended to
be given at the commencement of the flu season. Hence, it is possible that a
person who has contracted, and is incubating, influenza during vaccination
will mistakenly believe the vaccine to be causal. In addition, influenza vaccine
is given at the very time of year when there are a lot of upper respiratory tract
infections (URTIs) around. It is not uncommon for someone to attribute an URTI
within a week of an influenza vaccine to the vaccine dose. Importantly, URTI
symptoms occurring after influenza vaccine should not put people off having the
vaccine the following year.

b) Vaccine content44
(See also Appendix 4 for a list of vaccines used in the NIP which contain these
compounds and refer to the relevant vaccine product information (PI) enclosed
in the vaccine package.)
• Preservatives
Preservatives are used to prevent fungal and or bacterial contamination of the
vaccine. They include thiomersal, phenoxyethanol, and phenol.
(i) Thiomersal
Thiomersal (or thimerosal) is a compound which is partly composed of mercury,
ethylmercury. It has been used in very small amounts in vaccines for about
60 years, to prevent bacterial and fungal contamination of vaccines. In the past,
the small amount of thiomersal in vaccines was one of several potential sources
of mercury. Diet (such as some seafood) and other environmental sources are also
possible sources of mercury. Vaccines used in the past, such as DTP, contained
only 25 µg of thiomersal per dose.
Mercury causes a toxic effect after it reaches a certain level in the body. Whether
or not it reaches a toxic level depends on the amount of mercury consumed
and the person’s body weight; individuals with very low body weight are
usually more susceptible to toxic effects from a certain intake of mercury.
Thus, the possibility existed that vaccination of newborn babies, particularly
those of very low birth weight, with repeated doses of thiomersal-containing
vaccines, might have resulted in levels of mercury above the recommended
guidelines. Thiomersal was removed from vaccines in response to the above
theoretical concern and to reduce total exposure to mercury in babies and young
Appendices
children in a world where other environmental sources may be more difficult to
eliminate.45-47
Currently, all vaccines on the NIP for children <5 years of age are now either free
of thiomersal, or contain a reduced (trace) amount of thiomersal.
There are certain vaccines that are still most effectively manufactured using a
trace amount of thiomersal as the preservative, eg. influenza vaccine. Infants
from 6 months of age can be given influenza vaccine safely.
(ii) Phenoxyethanol
2-Phenoxyethanol is an aromatic ether alcohol used as a preservative in many
vaccines. It is also used as a preservative in cosmetics. 2-Phenoxyethanol is used
in vaccines as an alternative preservative to thiomersal.
Appendix 5 355
(iii) Phenol
Phenol is an aromatic alcohol used as a preservative in a few vaccines.
• Adjuvants
Adjuvants are compounds used to enhance the immune response to vaccination
and include various aluminium salts such as aluminium hydroxide, aluminium
phosphate and potassium aluminium sulphate (alum). A recent review of all
available studies of aluminium-containing diphtheria, tetanus and pertussis
vaccines (either alone or in combination) found no evidence that aluminium salts
in vaccines cause any serious or long-term adverse events.48
Aluminium
A small amount of aluminium salts has been added to some vaccines for
about 60 years. Aluminium acts as an adjuvant, which improves the protective
response to vaccination by keeping antigens near the injection site so they can
be readily accessed by cells responsible for inducing an immune response. The
use of aluminium in vaccines means that, for a given immune response, less
antigen is needed per dose of vaccine, and a lower number of total doses are
required. Although aluminium-containing vaccines have been associated with
local reactions and, less often, with the development of subcutaneous nodules at
the injection site, other studies have reported fewer reactions with aluminium-
adsorbed vaccines than with unadsorbed vaccines. Concerns about the longer-
term effects of aluminium in vaccines arose after some studies suggested a link
between aluminium in the water supply and Alzheimer’s disease, but this link
has never been substantiated. The amount of aluminium in vaccines is very
small and the intake from vaccines is far less than that received from diet or
medications such as some antacids.49,50
• Additives
Additives are used to stabilise vaccines in adverse conditions (temperature
extremes of heat and freeze drying) and to prevent the vaccine components
adhering to the side of the vial.
Examples of additives include:
• lactose and sucrose (both sugars);
• glycine and monosodium glutamate or MSG (both are amino acids or salts of
amino acids);
• gelatin, which is partially hydrolysed collagen usually of bovine or porcine
origin. Some members of the Islamic and Jewish faiths may object to
vaccination, arguing that vaccines can contain pork products. Scholars of
the Islamic Organization for Medical Sciences have determined that the
transformation of pork products into gelatin will sufficiently alter them
thus making it permissible for observant Muslims to receive vaccines, even
if the vaccines contain porcine gelatin. Likewise, leaders of the Jewish faith

have also indicated that pork-derived additives to medicines are permitted.
Further information may be obtained from the following websites
http://vaccinesafety.edu/Porcine-vaccineapproval.htm and
http://www.immunize.org/concerns/porcine.pdf;
• human serum albumin (protein).
• Manufacturing residuals
Manufacturing residuals are residual quantities of reagents used in the
manufacturing process of individual vaccines. They include antibiotics (such
as neomycin or polymyxin), inactivating agents (eg. formaldehyde) as well
as cellular residuals (egg and yeast proteins), traces of which may be present
in the final vaccine. Antibiotics are used during the manufacturing process to
ensure that bacterial contamination does not occur; traces of these antibiotics
may remain in the final vaccine. Inactivating agents are used to ensure that
the bacterial toxin or viral components of the vaccine are not harmful, but will
result in an immune response. Cellular residuals are minimised by extensive
filtering. However, trace amounts may be present in the final product. The most
commonly found residual is formaldehyde.
Formaldehyde
Formaldehyde is used during the manufacture of many vaccines. For example,
with tetanus vaccines, formaldehyde is used to detoxify the tetanus toxin protein
produced. The non-toxic protein which becomes the active ingredient of the
vaccine is further purified to remove contaminants and any excess (unreacted or
unbound) formaldehyde. The current standard applicable to vaccines for human
use in Australia is less than 0.02% w/v of free formaldehyde. The maximum
Appendices
amount of free formaldehyde detected by the Therapeutic Goods Administration
during testing of vaccines registered in Australia has been 0.004% w/v, which is
well below the standard limit.
• Other
Vaccines also may be made up in sterile water or sterile saline (salt-water).
(c) The need for immunisation

(i) Isn’t natural immunity better than immunity from vaccination?
While vaccine-induced immunity may diminish with time without boosters
(vaccine or contact with wild-type infection), ‘natural’ immunity, acquired by
catching the disease, is usually life-long, with the exception of pertussis. The
problem is that the wild or ‘natural’ disease has a higher risk of serious illness
and occasionally death. Children or adults can be revaccinated (with some but
not all vaccines) if their immunity from the vaccines falls to a low level or if
previous research has shown that a booster vaccination is required for long-term
protection. It is important to remember that vaccines are many times safer than
the diseases they prevent.
Appendix 5 357
(ii) Diseases like measles, polio, whooping cough and diphtheria
have already disappeared from most parts of Australia. Why do we
need to keep vaccinating children against these diseases?
Although these diseases are much less common now, they still exist. The
potential problem of disease escalation is kept in check by routine vaccination
programs. In countries where vaccination rates have declined, vaccine-
preventable diseases have sometimes reappeared. For example, Holland has one
of the highest rates of fully vaccinated people in the world. However, in the early
1990s, there was a large outbreak of polio among a group of Dutch people who
belonged to a religious group that objected to vaccination. While many of these
people suffered severe complications like paralysis, polio did not spread into the
rest of the Dutch community. This was due to the high rate of vaccination against
polio, which protected the rest of the Dutch community.
There have been recent outbreaks of whooping cough, measles and rubella in
Australia, and a number of children have died. Cases of tetanus and diphtheria,
although rare, still occur. Thus, even though these diseases are much less common
now than in the past, it is necessary to continue to protect Australian children, so
that the diseases cannot re-emerge to cause large epidemics and deaths.
Also, many of the diseases which we vaccinate our children against are still
common in other areas of the world. For example, measles still occurs in many
Asian countries and many people take holidays or travel for business to these
areas. Therefore, it is possible for non-immune individuals to acquire measles
overseas, and with the speed of air travel, arrive home and be able to pass
measles onto those around them if they are unprotected. Measles is highly
infectious and can infect others for several hours after an infected person has left
a room. Vaccination, while not 100% effective, can minimise a person’s chance
of catching a disease. The more people who are vaccinated the less chance of a
disease, such as measles, spreading widely in the community. This is referred to
as herd immunity.
(iii) Why do some children get the disease despite being vaccinated?
This is possible, since no vaccine is 100% effective. A small proportion of those
who are vaccinated will remain susceptible to the disease. However, in the cases
in which illness does occur in vaccinated individuals, the illness is usually much
less severe than in those who were not vaccinated. The protection provided by
the same vaccine to different individuals can differ. For example, if 100 children
are vaccinated with MMR, 5 to 10 of the fully vaccinated children might still
catch measles, mumps or rubella (although the disease will often be less severe
in vaccinated children). If 100 children are vaccinated with a full schedule of
pertussis-containing vaccines, 20 of the children might still get whooping cough
but, once again, the disease is often less severe in these vaccinated children. To
put it another way, if you do not vaccinate 100 children with MMR vaccine, and
the children are exposed to measles, all of them will catch the disease with a

risk of high rates of complications like pneumonia or encephalitis. The reason
why fewer children become infected than these figures suggest is due to the
high vaccine coverage rates in the community. If there are high coverage rates,
there is less chance of contact with the infection and, although children may be
susceptible, they have a low chance of contact with the infection.
(iv) What about homeopathic ‘immunisation’?

Homeopathic ‘immunisation’ has not been proved to give protection against
infectious diseases; only conventional vaccination produces a measurable
immune response. The Council of the Faculty of Homeopathy, London, issued a
statement in 1993, which reads: “The Faculty of Homeopathy, London, strongly
supports the conventional vaccination program and has stated that vaccination
should be carried out in the normal way, using the conventional tested and
proved vaccines, in the absence of medical contraindications”.51
4. Where can I get more information about vaccination?

More information about vaccination can be found in the following publications
produced by the Australian Government Department of Health and Ageing:
• Understanding childhood immunisation
• Immunisation myths and realities – responding to arguments against immunisation:
a guide for providers
The following two websites include further publications, fact sheets, etc. and are
recommended for both immunisation service providers and the general public:
• Immunise Australia website http://www.immunise.health.gov.au
Appendices
• The National Centre for Immunisation Research and Surveillance of Vaccine
Preventable Diseases (NCIRS) website www.ncirs.usyd.edu.au
Also, check with your local State or Territory public health unit or local council,
maternal child health nurse, or public health vaccination clinic for more
information (see Appendix 1, Contact details for Australian, State and Territory
References
Appendix 5 359
Appendix 6: Definitions of adverse
events following immunisation
Notify any events that the reporter considers serious and which may be related
to the vaccine or vaccines administered. See Section 1.5.2, Adverse events
following immunisation.
Abscess
Occurrence of a fluctuant or draining fluid-filled lesion at the site of injection,
with or without fever.
• Bacterial: purulent collection.
• Sterile abscess: no evidence of bacterial infection.
Acute flaccid paralysis [diagnosis must be made by a physician]

Acute onset of flaccid paralysis of one or more limbs following any vaccine.
Allergic reaction (generalised)
A non-anaphylactic, generalised reaction characterised by 1 or more symptoms
or signs of skin and/or gastrointestinal tract involvement WITHOUT respiratory
or cardiovascular involvement.
(NB. See also ‘Anaphylaxis’).
Anaphylaxis
A rapidly evolving generalised multi-system allergic reaction characterised by
1 or more symptoms or signs of respiratory and/or cardiovascular involvement
AND involvement of other systems such as the skin or gastrointestinal tract.
• Respiratory: difficulty/noisy breathing, swelling of the tongue, swelling/
tightness in the throat, difficulty talking/hoarse voice, wheeze or
persistent cough.
• Cardiac: loss of consciousness, collapse, pale and floppy (babies),
hypotension.
Arthralgia
Joint pain without redness or swelling.
Arthritis
Joint pain with redness and/or swelling.
Brachial neuritis
Pain in arm causing persisting weakness of limb on side of vaccination.
Death
Any death of a vaccine recipient temporally linked to vaccination, where no
other clear cause of death can be established.

Disseminated BCG
Disseminated infection occurring after BCG vaccination and confirmed by
isolation of Mycobacterium bovis BCG strain.
Encephalopathy [diagnosis must be made by a physician]

Encephalopathy is an acute onset of major neurological illness temporally
linked with vaccination and characterised by any 2 or more of the following 3
conditions:
• seizures,
• severe alteration in level of consciousness or mental status (behaviour and/or
personality) lasting for 1 day or more, and/or
• focal neurological signs which persist for 1 day or more.
Encephalitis [diagnosis must be made by a physician]

Encephalitis is characterised by the above-mentioned symptoms and signs
of cerebral inflammation and, in many cases, CSF pleocytosis and/or virus
isolation.
Extensive limb swelling

Swelling of the limb, with or without redness, which:
• extends from the joint above to the joint below the injection site, or beyond a
joint (above or below the injection site), or
• results in the circumference of the limb being twice the normal size.
Faint
See ‘Vasovagal episode’.
Appendices
Fever
Only very high fever should be reported, eg. >40.5°C.
Guillain-Barré Syndrome (GBS) [diagnosis must be made by a physician]

Acute onset of rapidly progressive, ascending, symmetrical flaccid paralysis,
without fever at onset of paralysis and with or without sensory loss. Cases
are diagnosed by cerebrospinal fluid (CSF) investigation showing dissociation
between cellular count and protein content.
Hypotonic–hyporesponsive episode (shock, collapse)

The sudden onset of pallor or cyanosis, limpness (muscle hypotonia), and
reduced responsiveness or unresponsiveness occurring after vaccination,
where no other cause is evident such as a vasovagal episode or anaphylaxis.
The episode usually occurs 1 to 48 hours after vaccination and resolves
spontaneously.
Appendix 6 361
Injection site reaction (severe)
Reaction (redness and/or swelling) at site of injection which:
• persists for more than 3 days AND is associated with ongoing symptoms
such as pain or an inability to use the limb (see ‘Brachial neuritis’ above), and
• does not fulfil the case definition for extensive limb swelling (see ‘Extensive
limb swelling’ above), or
• requires hospitalisation.
Intussusception [diagnosis must be made by a hospital physician]

The invagination of a proximal segment of bowel into the distal bowel lumen.
Lymphadenitis (includes suppurative lymphadenitis)

Occurrence of either:
• at least 1 lymph node, 1.5 cm in diameter or larger, or
• a draining sinus over a lymph node.
Meningitis [diagnosis must be made by a physician]

Acute onset of major illness with fever and often neck stiffness/positive
meningeal signs (Kernig, Brudzinski) and with CSF pleocytosis.
Nodule
A discrete or well demarcated soft tissue mass or lump that is firm and is at the
injection site in the absence of abscess formation, warmth and erythema.
Orchitis
Swelling with pain and/or tenderness of testes.
Osteitis
Inflammation of the bone due to BCG vaccination.
Osteomyelitis
Proven bacterial infection of bone.
Parotitis
Swelling and/or tenderness of parotid gland or glands.
Rash
Severe or unusual rash.
Screaming (persistent)
The presence of crying which is continuous and unaltered for longer than 3 hours.
Seizure
Witnessed sudden loss of consciousness and generalised, tonic, clonic, tonic-
clonic, or atonic motor manifestations.
• febrile seizures: with fever ≥38.5°C,
• afebrile seizures: without fever,
• syncopal seizures: syncope/vasovagal episode followed by seizure(s).

Sepsis
Acute onset of severe, generalised illness due to bacterial infection and confirmed
by positive blood culture.
Subacute sclerosing panencephalitis [diagnosis must be made by a physician]

Degenerative central nervous system (CNS) condition with laboratory
confirmation of abnormal serum and CSF measles antibodies.
Syncope
See ‘Vasovagal episode’.
Thrombocytopenia
Platelet count <50 x 109/L.
Toxic shock syndrome [diagnosis must be made by a physician]

Abrupt onset of fever, vomiting, watery diarrhoea and shock within a few hours
of vaccination as can be associated with other conditions listed here.
Vaccine-associated paralytic poliomyelitis

See ‘Acute flaccid paralysis’.
Vasovagal episode (syncope, faint)

Episode of pallor and unresponsiveness or reduced responsiveness or feeling
light headed AND
• occurring while vaccine being administered or shortly after (usually within
5 minutes), AND
• bradycardia, AND
• resolution of symptoms with change in position (supine position or head
Appendices
between knees or limbs elevated).
(See Table 1.5.1 to distinguish from anaphylaxis).
Other severe or unusual events

Any unusual event that does not fit into any of the categories listed above, but
is of medical or epidemiological interest, should be reported with a detailed
description of the clinical features.
Report by telephone to State or Territory Health Department or notify by the blue
card to ADRAC (see Section 1.5.2, Adverse events following immunisation).
Note: The Brighton Collaboration is an international group considering
definitions of adverse events following immunisation. Its website is:
http://www.brightoncollaboration.org.
Appendix 6 363
Appendix 7: Glossary of technical terms
Adjuvant
a preparation which may be added to a vaccine to improve the immune response
to that vaccine.
ADT
adult diphtheria and tetanus vaccine (also referred to as dT). Trade name used
for diphtheria-tetanus vaccine previously made by CSL for use in adults.
Adverse event following immunisation (AEFI)

an unwanted reaction following administration of a vaccine, which may or may
not be caused by the vaccine; adverse events may be at the site of injection, or
may be a general illness or a general allergic reaction.
Anaphylaxis
a sudden and severe allergic reaction, which results in a serious fall in blood
pressure and/or respiratory obstruction and may cause unconsciousness and
death if not treated immediately.
Attenuation
the process of modifying a virus or bacteria to reduce its virulence (disease-
inducing ability) while retaining its ability to induce a strong immune response
(immunogenicity).
Bacteria
microorganisms that are smaller than a blood cell but bigger than a virus; examples
of bacterial infections are diphtheria, tetanus, pertussis, Hib and tuberculosis.
BCG
Bacillus of Calmette-Guérin, a vaccine that protects against tuberculosis.
Carrier
a person who has an infection which, although not necessarily causing symptoms,
may still be active and may spread to others; the carrier state may last for years;
examples of infections that can result in the carrier state are hepatitis B and typhoid.
Conjugate
some bacterial vaccines (eg. Hib and pneumococcal conjugate vaccines) are made
from the chemical linking (conjugation) of a tiny amount of the ‘sugar’ (correctly
known as the polysaccharide) that makes up the cell coat of the bacteria with a
protein molecule, in order to improve the immune response to the vaccine.
Contraindication
a reason why a vaccine or drug must not be given.
Corticosteroid
a drug used to reduce inflammation and other immune responses.

dT
diphtheria-tetanus vaccine for use in adults (ADT).
DTP/DTPa
a vaccine that protects against diphtheria, tetanus and pertussis (whooping
cough). The DTP used in Australia and many other industrialised countries
is DTPa, which contains an acellular pertussis component made of refined
pertussis extracts instead of inactivated whole pertussis bacteria. The acronym
DTPa, using capital letters, signifies child formulations of diphtheria, tetanus
and acellular pertussis-containing vaccines, and denotes the substantially larger
amounts of diphtheria toxoid and pertussis antigens in these formulations than
in the adolescent/adult formulations.
dTpa
adolescent/adult formulation diphtheria-tetanus-acellular pertussis vaccine.
dTpa contains substantially lower concentrations of diphtheria toxoid and
pertussis antigens than the child formulations (which are signified by using all
capital letters (DTPa)).
Effectiveness
the extent to which a vaccine produces a benefit in a defined population in
uncontrolled or routine circumstances.
Efficacy
the extent to which a vaccine produces a benefit in a defined population in
controlled or ideal circumstances.
Encephalitis
Appendices
inflammation of the brain.
Encephalopathy
a general term to describe a variety of illnesses that affect the brain, including
encephalitis.
Endemic
endemic infections are present all the time in a community.
Epidemic
epidemic infections are those that spread rapidly in a community; measles and
influenza viruses are common causes of epidemics in Australia; small epidemics
are often called outbreaks.
Febrile
related to a fever, as in febrile illness and febrile convulsions.
HAV
abbreviation for hepatitis A virus, the cause of hepatitis A, a common food-borne
infection in travellers to developing countries.
Appendix 7 365
HBsAg
hepatitis B surface antigen; a marker in the blood that indicates that the person is
a carrier of active hepatitis B virus infection.
HBV
abbreviation for hepatitis B virus, a virus that is spread in body fluids in various
ways including blood-to-blood contact through sharing injection equipment, and
through sexual intercourse.
Hepatitis
an inflammation of the liver; can be caused by viral infections.
Hib
Haemophilus influenzae type b; a bacterium that causes meningitis and other
serious infections in young children.
HIV
human immunodeficiency virus, or the AIDS virus; people with HIV infection
may have weakened immunity and need special vaccinations to protect them
against other infections.
Human papillomavirus
a group of viruses, some of which have been associated with some forms of
cervical cancer; some can also cause genital warts.
Hypotonic-hyporesponsive episode (HHE)

a rare adverse event which may follow some hours after DTPa vaccination; the
child becomes pale, limp and unresponsive; the condition may last from a few
minutes to hours but causes no long-term serious problems.
Immunisation
the process of inducing immunity to an infectious agent by administering a
vaccine.
Immunity
the ability of the body to fight off certain infections; immunity can result from
natural (‘wild’) infections or from vaccination.
Immunogenicity
the ability (or the degree) to which a particular substance, in this context a
vaccine, may provoke an immune response.
Immunoglobulin
a protein extract from blood, sometimes called ‘antibody’, which fights off
infection; injection of immunoglobulins provides temporary immunity against
certain infections.

Incubation period
after a person is infected with bacteria or viruses, it often takes days or weeks
for the infection to cause an obvious illness; the time between exposure to the
infectious agent and development of the disease is called the incubation period.
Infection
an infection occurs when bacteria or viruses invade the body; if the body cannot
fight the infection, it may cause an illness.
Intradermal injection
an injection into the surface layers of the skin; this is used for the administration
of BCG, the tuberculosis vaccine.
Intramuscular (IM) injection

an injection into the muscle; vaccines are usually injected into a muscle of the
upper outer thigh, or a muscle in the upper arm.
IPV
inactivated poliomyelitis vaccine; an injectable vaccine formerly known as Salk
vaccine.
Invasive disease
this term is often used when talking about pneumococcal or meningococcal
disease. This term means that the bacteria (or germs) have been found in the
blood, spinal fluid or another part of the body which would normally be sterile
(or germ free).
Jaundice
yellow skin colour that may result from severe hepatitis.
Appendices
JE
Japanese encephalitis; a viral encephalitis.
MMR
measles-mumps-rubella vaccine.
MMRV
measles-mumps-rubella-varicella vaccine.
OPV
oral poliomyelitis vaccine; also known as Sabin vaccine. This vaccine is no longer
routinely used in Australia.
Pandemic influenza
a global epidemic that results when a new strain of influenza virus appears in the
human population. It causes more severe disease in the population because there
is little immunity to this new strain.
Appendix 7 367
Paracetamol
a medicine that helps reduce fever; it may be given to minimise fevers following
vaccination.
Pertussis
whooping cough, an illness caused by a bacterium, Bordetella pertussis.
Polysaccharide
a group of complex carbohydrates (sugars) which make up the cell coating
present in some bacteria.
Polyvalent vaccine
a combination vaccine which protects against more than one disease; examples
are DTPa and MMR.
PRP-OMP
a type of Hib vaccine.
PRP-T
a type of Hib vaccine.
Rotavirus
a virus that is a common cause of diarrhoea (and often vomiting as well) in
young children. The diarrhoea can be severe in very young children, such that
they may need intravenous fluids (ie. through a vein in the arm) in hospital.
Rubella
a viral illness, sometimes also known as German measles.
Subcutaneous (SC) injection

an injection into the tissue between the skin and the underlying muscle.
Vaccination
the administration of a vaccine; if vaccination is successful, it results in immunity.
Vaccine
a product often made from extracts of killed viruses or bacteria, or from live
weakened strains of viruses or bacteria; the vaccine is capable of stimulating an
immune response that protects against natural (‘wild’) infection.
Varicella
chickenpox, an infection caused by the varicella-zoster virus.
Virus
a tiny living organism, smaller than a bacterium, that can cause infections;
measles, rubella, mumps, polio, influenza and hepatitis B are examples of viruses.
Zoster
an abbreviation for herpes zoster infection (also known as shingles); a painful
rash and illness caused by the varicella-zoster (chickenpox) virus.

Appendix 8: List of commonly
used abbreviations
ABL Australian bat lyssavirus

ACIP Advisory Committee on Immunization Practices
ACIR Australian Childhood Immunisation Register
ADRAC Adverse Drug Reactions Advisory Committee
AEFI adverse event following immunisation
AFP acute flaccid paralysis
AIDS acquired immunodeficiency syndrome
anti-HBs hepatitis B surface antibody
ATAGI Australian Technical Advisory Group on Immunisation
BCG Bacillus of Calmette-Guérin
BSE bovine spongiform encephalopathy
CCM cold chain monitor
CDT diphtheria-tetanus vaccine for children (no longer in use)
cm centimetre
CSF cerebrospinal fluid
dT diphtheria-tetanus vaccine for use in adults
DTPa child formulation diphtheria-tetanus-acellular pertussis vaccine
Appendices
dTpa adolescent/adult formulation diptheria-tetanus-acellular
pertussis vaccine
ELISA/EIA enzyme-linked immunosorbent assay
GVHD graft versus host disease
HAV hepatitis A virus
HBIG hepatitis B immunoglobulin
HBsAg hepatitis B surface antigen
HBV hepatitis B virus
HCW Healthcare worker
HepA hepatitis A
HepB hepatitis B
HHE hypotonic-hyporesponsive episode
Hib Haemophilus influenzae type b
HIV human immunodeficiency virus
HPV human papillomavirus
Appendix 8 369
HRIG human rabies immunoglobulin
HSCT haematopoietic stem cell transplant
HZ herpes zoster
IM intramuscular
IMD invasive meningococcal disease
IPD invasive pneumococcal disease
IPV inactivated poliomyelitis vaccine
ITP idiopathic thrombocytopenia purpura
IU international units
IV intravenous
JE Japanese encephalitis
kg kilogram
ng nanogram
μg microgram
mg milligram
mL millilitre
mm millimetre
4vMenPV meningococcal polysaccharide vaccine (tetravalent)
MenCCV meningococcal C conjugate vaccine
MMR measles-mumps-rubella
MMRV measles-mumps-rubella-varicella
MS multiple sclerosis
NHIG normal human immunoglobulin
NHMRC National Health and Medical Research Council
NIP National Immunisation Program
OMP outer membrane protein
OPV oral poliomyelitis vaccine (no longer in use)
PHN post-herpetic neuralgia
PI product information
7vPCV 7-valent pneumococcal conjugate vaccine
PPD purified protein derivative
23vPPV 23-valent pneumococcal polysaccharide vaccine
PRP polyribosylribitol phosphate
SC subcutaneous

SIDS sudden infant death syndrome
SOT solid organ transplant
TB tuberculosis
TGA Therapeutic Goods Administration
TIG tetanus immunoglobulin
VAPP vaccine-associated paralytic poliomyelitis
vCJD variant Creutzfeldt-Jakob disease
VV varicella vaccine
VZV varicella-zoster virus
WHO World Health Organization
ZIG zoster immunoglobulin
Appendices
Appendix 8 371
Appendix 9: Dates when vaccines
became available in Australia
Public sector Vaccine

Australia Exceptions
1945-46 Tetanus toxoid
1953 DTPw (diphtheria/tetanus/pertussis whole cell)
1956 May Poliomyelitis (SALK)
1966 Sep Poliomyelitis (OPV) (oral Sabin)
1969 Measles
1971 Feb Rubella (adolescent girls)
1975 CDT (child diphtheria/tetanus)
1981 Jul Mumps
1982 ADT (adult diphtheria/tetanus)
1983 Measles/Mumps
1986 CDT-DTP 4th dose introduced (1st pertussis booster)
1987 Nov NT 1988 Jan Hepatitis B (for at-risk infants)
SA 1996
1989 SA 1996 MMR (infant dose)
1992 May Hib (for children 18 months to 5 years of age)
1993 Apr Hib (all infants born from Feb 1993)
1993 Jul Hepatitis A (Havrix) (unfunded)
1994 MMR (males and females in Grade 6)
1995 CDT-DTP 5th dose introduced (2nd pertussis booster)
1997 Oct Tas 1997 Oct DTP acellular (Infanrix) boosters for infants aged
Qld 1997 Dec 18 months and 4–5 years to replace DTP 4th and 5th doses
1997 Influenza (program for over 65s)
1998 Jan Qld 1998 Mar Hepatitis B (adolescent dose)
Tas 1998 Mar
NT 1998 Apr
NSW 1999
SA 1999
1998 MMR (Primary School program)
1998 MMR/OPV 4-year-old booster (DTP, MMR, OPV)
program before commencing school

1998 Pneumococcal polysaccharide 23-valent
vaccine (over 65s) (unfunded)
1999 Feb NT 1997 Aug DTPa (Infanrix) for infants aged 2, 4 and 6 months
SA 1997 Aug
Qld 1999 Apr
1999 MMR (18–30-year-old program)
2000 COMVAX (Hep B/Hib) available
2000 Adult diphtheria/tetanus 10-yearly boosters ceased
2000 May NT 1990 Aug Hepatitis B (universal infant dose)
2000 Hepatitis B booster doses no longer recommended
2001 Pneumococcal conjugate 7-valent vaccine (for
Aboriginal and Torres Strait Islander children
and all children in Central Australia only)
2001 Dec Meningococcal C conjugate vaccine (Meningitec) (unfunded)
2001 Varicella (chickenpox) (unfunded)
2001 HibTITER vaccine ceased
2002 Aug Meningococcal C conjugate vaccine (NeisVac-C) (unfunded)
2002 Oct Meningococcal C conjugate vaccine (Menjugate) (unfunded)
2003 Sep DTPa 4th dose at 18 months of age ceased
2003 Jan Meningococcal C conjugate vaccine (at 12 months of
Appendices
age and catch-up until May 2007 for 1–19-year-olds)
2003 Sep Pneumococcal conjugate 7-valent vaccine (for
children with medical risks <5 years of age)
2004 Jan dTpa (Boostrix) for 15–17 years (Year 10
school program) replaced ADT
2004 Sep Combination vaccines with 4, 5 and 6 antigens available
2005 Jan Pneumococcal conjugate 7-valent vaccine (for
infants aged 2, 4 and 6 months and medical at-risk
children plus catch-up in 2005 for children born
between 1 January 2003 and 31 December 2004)
2005 Jan Pneumococcal polysaccharide 23-valent
vaccine (funded for adults aged >65 years)
2005 Nov Inactivated polio (IPV) vaccine (given in
combination with DTPa scheduled at 2, 4 and
6 months and 4 years in place of OPV)
Appendix 9 373
2005 Nov Hepatitis A vaccine (for all Indigenous children
aged ≤5 years living in Queensland, the Northern
Territory, Western Australia and South Australia)
2005 Nov Varicella vaccine scheduled at 18 months and 13 years of age
2007 Apr Human papillomavirus vaccine (for girls aged
12–13 years plus a 2-year catch-up period to end
of June 2009 for girls aged 14–26 years)
2007 May NT 2006 Oct Rotavirus vaccine (for all children born from 1 May 2007)

Appendix 10: Summary table – procedures
for a vaccination encounter
This table summarises the information provided in Chapters 1.3–1.5 and provides
an overview of the requirements before, during and after a vaccination encounter.
This table can also be photocopied and used as an audit tool, if required.
Pre-vaccination procedures (Chapter 1.3)
• Prepare anaphylaxis response kit: check availability of the protocols,

equipment and drugs necessary for the management of anaphylaxis, before
each vaccination session. (1.3.1)
• Only vaccine that has been transported and stored at the correct cold chain
temperature of between +2°C to +8°C should be administered. Follow the
National Vaccine Storage Guidelines: Strive for 5. (1.3.2)
• Perform pre-vaccination screening to determine the person’s medical
fitness for vaccination, and possible need for additional vaccines. Any
concern about the person’s eligibility for vaccination must be discussed
with a medical practitioner, paediatrician or public health physician with
expertise in vaccination (see Appendix 1 for phone numbers for State/
Territory health authorities.) If a person’s health status or suitability for
vaccination cannot be determined, defer vaccination and seek advice. (1.3.4)
• Review the individual’s vaccination history and, based on documented
evidence, decide on the appropriate vaccine(s) to be administered. If the
recommended vaccination schedule for age has not been completed, plan
and document a ‘catch-up’ schedule and discuss this with the person or
Appendices
parent/carer. (1.3.5)
• Obtain valid consent from the person to be vaccinated, or that person’s
parent/carer: this includes providing the appropriate information about
the risks and benefits of vaccination and the risks of vaccine-preventable
diseases. (Written vaccination information can be provided to parents as
early as the last trimester of pregnancy or at the well-baby check.) Advise
the person to be vaccinated, or the parent/carer of a child, of the incidence of
common adverse events that may occur following vaccination. This advice
and the parent’s consent should be documented. It is important that the
parent be given a contact phone number in case a significant adverse event
occurs within 24 to 48 hours of the vaccination. (1.3.3)
Appendix 10 375

Administration of vaccines (Chapter 1.4)
• Follow standard occupational health and safety guidelines to minimise

the risk of needle-stick injury. (1.4.1)
• Depending on the vaccine(s) that are to be administered, and the age and
size of the person to be vaccinated, decide on the appropriate injection site
and route, and the injection equipment required (ie. syringe size, needle
length and gauge) as recommended in the current NHMRC immunisation
guidelines. Use a new, sterile, disposable syringe and needle for each
injection. (1.4.2–1.4.6)
• Prepare the vaccine (check whether the vaccine is injectable or oral):
• Check each individual dose (ie. ampoule, pre-filled syringe or vial) to see
that the expiry date has not lapsed, and that there is no particulate
matter or colour change in the vaccine.
• Reconstitute the vaccine as needed immediately before administration,
preferably using a separate needle to draw up the diluent or as
recommended by the manufacturer. Use only the diluent supplied with
the vaccine. Mix fully, and draw up the vaccine.
• Locate the injection site by fully uncovering the appropriate limb(s) and
visualising the correct anatomical markers. Position the limb for vaccination
so that the muscles are relaxed (usually a flexed position). Keep the limb as
immobile as possible without using excessive restraint. Ensure that the skin
is visibly clean. (1.4.7–1.4.8)
• Administer the vaccine(s) using the recommended technique (IM,
SC or Oral). For injectable vaccines, follow the recommendations for
administering more than 1 vaccine into a limb during the encounter. Do not
inject oral vaccines. Remove the needle briskly after IM injection. (1.4.5, 1.4.9)

Post-vaccination procedures (Chapter 1.5)
• Immediate after-care
• Dispose of used needles, syringes and vaccine vials/ampoules in
accordance with standard infection control guidelines.
• Cover the puncture wound quickly with a dry cotton wool ball and
hypoallergenic tape as needed. Apply gentle pressure for 1–2 minutes
but do not massage.
• Remove the cotton wool and tape after a few minutes.
• Continue using comfort and distraction techniques to alleviate any
distress and pain. Note: paracetamol is not used routinely at the time
of vaccination but may be recommended as required for fever or pain.
(1.5.1)
• Managing adverse reactions, documentation and follow-up
• Remind the vaccinated person, or the parent/carer of a child, about the
possible common adverse events following immunisation and how to
manage them. It is preferable to provide this as written information (see
inside back cover of this Handbook).
• Before departure, inform the person or the parent/carer, preferably in
writing, of the date of the next scheduled vaccination.
• The vaccinated person and/or parent/carer should be advised to
remain in a nearby area for a minimum of 15 minutes after the
vaccination. The area should be close enough to the vaccinator, so that
the child/person can be observed and medical treatment can be readily
Appendices
obtained if needed.
• Take the opportunity to check the vaccination status of other
family members (as appropriate) and provide (or refer) for catch-up
vaccination.
• Document the details of vaccination:
(i) on a record to be retained by the person, or the parent/carer of a child,
(ii) on the relevant clinical record (electronic or hard-copy), and
(iii) on an ACIR (or equivalent) encounter form, for children <7 years of age.
• Remind the vaccinated person, or the parent/carer of a child,
to promptly report any significant adverse event following
immunisation to the vaccinator, so that it can be reported to either the
Adverse Drug Reactions Advisory Committee (TAS) or to the relevant
State/Territory health authorities (ACT, NSW, NT, QLD, SA, VIC and
WA). (1.5.2–1.5.4)
Appendix 10 377

Index hepatitis B vaccine, 162–3
how to report, 64–5
human papillomavirus (HPV)
vaccine, 173–4
A immunoglobulins, 177–81
abattoir workers, 107, 258, 260 in children and infants, 84
abbreviations list, 369–71 influenza vaccine, 193–4
ABL see Australian bat lyssavirus (ABL) Japanese encephalitis (JE) vaccine,
infection 199–200
Aboriginal and Torres Strait Islander management of, 61–4
people, 70–4 measles-containing vaccine, 208–9
children and infants, meningococcal vaccine, 220
BCG vaccine, 70–1, 300 mumps-containing vaccine, 225
catch-up, 32, 34–5 pertussis-containing vaccine, 234–5
Haemophilus influenzae type b, 71, pneumococcal vaccine, 247, 249
132, 135 poliomyelitis vaccine, 255
hepatitis A, 72, 144 Q fever vaccine, 262–3
pneumococcal disease, 34–5, 72, rabies vaccine, 118
240–1, 243, 247 reporting, 64–5
hepatitis A, 142 rotavirus vaccine, 269, 272–3
influenza, 190 rubella vaccine, 280–1
Japanese encephalitis (JE), 73 smallpox vaccine, 285–6
pneumococcal disease, 73, 240–1, 246 tetanus-containing vaccine, 295
service delivery to, 73–4 tuberculosis vaccine, 301
tuberculosis, 297 typhoid vaccine, 307
ACIR, 67 see also Australian Childhood varicella vaccine, 317–8
Immunisation Register yellow fever vaccine, 327
Adacel, 42, 126, 230, 290 see also dTpa Afghanistan, 77
Adacel Polio, 42, 126, 230, 254, 290 Africa
see also dTpa-IPV avian influenza, 184
additives in vaccines, 341, 356–7 cholera, 120
adjuvants, 341, 356 hepatitis B, 77, 150
administration see dosage and measles, 202
administration meningococcal disease, 79, 214
adoption of children overseas, 159 poliomyelitis, 251
adrenaline, 64 rabies, 110, 115
ADT Booster, 42, 126, 290 see also dT; rubella, 278
diphtheria; tetanus yellow fever, 75, 79, 322, 324, 326
Adverse Drug Reactions Advisory aged see older people
Committee (ADRAC), 65 agricultural college staff and students,
adverse events following immunisation 107, 258, 260
(AEFI), 58–66 allergy, 205, 279, 316, 350–1 see also egg
cholera vaccine, 123 protein allergy
definition(s) of, 360–3, 364 aluminium in vaccines, 341, 356
diphtheria-containing vaccine, 128 ambulance personnel, 105, 159, 192
Haemophilus influenzae type b Americas
vaccine, 137 cholera, 120
hepatitis A vaccine, 146 poliomyelitis, 251

rabies, 110, 115 rabies, 110, 115, 119
rubella, 278 rubella, 278
yellow fever, 75, 322, 323, 324 tuberculosis, 297
anaesthesia, 104 typhoid, 304
anaphylactoid see anaphylaxis; aspirin therapy, 191, 207, 318
contraindications asplenia (functional or anatomical), 16,
anaphylaxis, 61–4 see also 19, 36, 87, 93, 100–1, 136, 138, 213, 218,
contraindications 244, 246–7
adrenaline use, 64 asthma, 61, 191, 350, 353
differentiation from vasovagal Australian bat lyssavirus (ABL)
episode, 62 infection, 107, 110–9 see also rabies
management of, 63–4 post-exposure prophylaxis,
pre-vaccination screening, 17 vaccine, 42, 114–6
signs of, 62 rabies immunoglobulin (HRIG),
anaphylaxis response kit, 8, 375 116–7
animals pre-exposure prophylaxis, 112–4
human rabies from, 110–1 Australian Childhood Immunisation
occupational risks and, 107 Register (ACIR), 22–3, 67–9, 202, 332
Q fever from, 258, 260 Australian Red Cross Blood Service
anthrax, 3 (ARCBS), 176, 319
antibiotics Australian Standard Vaccination
diphtheria, 128 Schedule (ASVS), 3
false contraindications and, 21, 348 Australian Technical Advisory Group on
haematopoietic stem cell Immunisation (ATAGI), 334
transplantation and, 97 autism, 61, 209, 352
Haemophilus influenzae type b, 137–8 autistic spectrum disorder, 209, 352
manufacturing residuals, 341, 357 autoimmune diseases, 101–2 see also
meningococcal disease, 220 impaired immunity, individuals with
pertussis, 235–9 Avaxim, 42, 140 see also hepatitis A (HAV)
smallpox, 285 avian influenza, 184, 186–7
splenic dysfunction and, 101 azithromycin, 235–6, 238, 239
tetanus, 294
typhoid vaccine, oral and, 83, 305, B
307 babies (neonates) see also preterm babies
antibody deficiency disorders, 180 bronchopulmonary dysplasia (BPD),
anti-HAV IgG, 139, 142 182
anti-HAV IgM, 139, 142, 146 hepatitis B, 156–7, 162, 163
anti-HBs, 31, 90, 149, 153, 157, 158, 160–1 influenza, 185
armed forces personnel, 106, 159, 297, measles, 211
306 see also travellers pertussis, 236, 237, 238
Asia respiratory syncytial virus (RSV), 182
avian influenza, 184 tetanus, 288, 289
Index
cholera, 120 tuberculosis, 300

hepatitis B, 77, 150 varicella, 309
Japanese encephalitis (JE), 75, 78, 82, bacteraemia, 240
195, 197–8, 199 Bali
measles, 358 Japanese encephalitis (JE) virus in,
meningococcal disease, 214 198
Index 379
rabies in, 119 rotavirus vaccine, 268
bats see Australian bat lyssavirus (ABL) rubella vaccine and, 280
infection smallpox vaccine and, 285
BCG vaccine, 298 see also tuberculosis bronchopulmonary dysplasia (BPD), 182
bleeding disorders, 104, 159, 178, 207–8 BSE see bovine spongiform
blood and organ donors, 150, 159, 175 encephalopathy
blood products/transfusions, 102–3, 159,
206, 271, 280, 317 C
live vaccines and, interval between, cancer chemotherapy, 92–4
102–3 cardiac disease, 190, 246, 247
body-piercers, 107, 159 cardiovascular disease, 122
bone marrow transplantation carers, 106
see haematopoietic stem cell carriers
transplantation (HSCT) hepatitis B, 149–50, 151, 156, 157, 158
boosters and revaccination meningococcal disease, 213, 220–1
diphtheria, 127, 128, 129 typhoid, 308
Haemophilus influenzae type b, 134, catch-up, 21–38
136, 138 children aged <8,
hepatitis A, 142, 145 guidelines, 31–2
hepatitis B, 156, 161–3 Haemophilus influenzae type b, 33
human papillomavirus (HPV), 170 minimum age, 30
Japanese encephalitis (JE), 198, 200 minimum interval, 29
meningococcal disease, 218 number of doses required, 28
pertussis, 228, 231–3, 238, 346–7 pneumococcal vaccination, 34–6
pneumococcal disease, 243, 246, 247 worksheet, 27
poliomyelitis, 255 children aged ≥8, adolescents and
Q fever, 262 adults, 37–8
rabies, 113 immigrants, 108
tetanus, 292–4 ceftriaxone, 137, 221
typhoid, 145, 306 CERVARIX, 42, 169 see also human
Boostrix, 42, 126, 230, 291 see also dTpa papillomavirus (HPV)
Boostrix-IPV, 42, 126, 230, 254, 291 see also cervical cancer, 164, 167–8
dTpa-IPV chemoprophylaxis see antibiotics
Bordetella pertussis see pertussis chemotherapy, 92–4
botulism antitoxin, 181 chickenpox see varicella
Botulism Immune Globulin (BIG), 181 childcare facilities
bovine spongiform encephalopathy Haemophilus influenzae type b, 138
(BSE), 354 see also mad cow disease hepatitis A, 147
brachial neuritis, 61 see also adverse hepatitis B, 160
events following immunisation (AEFI) measles, 178
breakthrough varicella, 310–1, 312–3 pertussis, 232, 236, 237, 238
breastfeeding and lactation, 21, 89, 174 rubella, 279
see also pregnancy and vaccination childcare workers, 87, 104, 105, 144, 147,
cholera vaccine and, 123 160, 232, 313, 346
human papillomavirus (HPV) children and infants
vaccine and, 174 asplenia, 100–1
meningococcal vaccine and, 222 bleeding disorders, 104
Q fever vaccine and, 263 catch-up for, 22–3, 25–30, 33–8

consent, 12–3 hepatitis B-containing, 152
deceased, notification to ACIR of, 68 measles, mumps and rubella, 203,
HIV-infected, 99 224, 277
injection sites, 45–6, 345 pertussis-containing, 229–30
living overseas, 68 poliomyelitis-containing, 253–4
multiple injections, 24, 56–7, 345 tetanus-containing, 289–91
positioning for vaccination, 47–51 typhoid-containing, 304
vaccination after AEFI, 84 communicability period see infectious
with intercurrent illnesses, 348 period
cholera, 42, 78, 120–3 communicable disease control, telephone
adverse events, 123 contact details for, 333
contraindications, 123 compatibility see interchangeability of
dosage and administration, 122 vaccines
precautions, 123 compulsory vaccination, 347
pregnancy, 87, 123 COMVAX, 31, 42, 71, 133 see also
recommendations, 122 Haemophilus influenzae type b
chronic conditions and vaccination, 350 concurrent vaccination see simultaneous
chronic graft-versus-host disease administration
(cGVHD), 97 congenital rubella syndrome (CRS),
chronic inflammatory demyelinating 274–5, 278
polyneuropathy, 180 congenital varicella syndrome, 309
hepatitis A, 144 conjugate vaccines see Haemophilus
hepatitis B, 150, 158 influenzae type b; meningococcal
liver disease, 144, 145, 159 disease; pneumococcal disease
neurological conditions see consent, 12–4, 375
neurological disease contacts (disease)
renal disease, 90, 191, 246, 247 diphtheria, 128–9
respiratory conditions, 190–1, 246, Haemophilus influenzae type b, 137–8
247 hepatitis A, 146–7
cidofovir, 286–7 hepatitis B, 158
ciprofloxacin, 231 measles, 209–10, 211
clarithromycin, 235–6, 239 meningococcal disease, 213, 218, 219,
Clostridium tetani see tetanus 220–1
CMV Immunoglobulin-VF (human), pertussis, 232, 237–8
182 see also cytomegalovirus; rotavirus, 271
immunoglobulins varicella, 314, 318
coadministration see simultaneous contraindications, 14, 20, 60, 347–51
administration anaphylaxis and, 20, 347–8
cold chain, 8–12 BCG vaccine, 300
combination vaccines cancer patients, 92–4
diphtheria-containing, 125–6 cholera vaccine, 123
dT, 126, 290 corticosteroids, 92, 118, 205, 207,
Index
DTPa-containing, 125–6, 152, 134, 348–9

253, 229–30, 289–91 diphtheria-containing vaccine, 128
dTpa-containing, 126, 254, 290–1, false, 21
Haemophilus influenzae type Haemophilus influenzae type b
b-containing, 134 vaccine, 137
hepatitis A-containing, 141 hepatitis A vaccine, 146
Index 381
hepatitis B vaccine, 162 D
HIV-infected individuals, 20, 99, 349 day-care see childcare facilities
human papillomavirus (HPV) deltoid area, 54–5 see also injection site
vaccine, 173 dentists and dental students, 105, 145,
immunoglobulins, 178, 180 159
individuals with impaired immunity, Department of Health and Ageing, 334,
91, 349 359
influenza vaccine, 193 diabetes, 122, 191, 246, 247, 354
Japanese encephalitis (JE) vaccine, diarrhoea, 60, 62, 63, 78, 122, 123, 270,
199 273, 307, 308
live attenuated vaccines and, 20–1, diphtheria, 124–30, 358 see also DT; dT;
91 dTpa; DTPa
measles-containing vaccine, 205–6 adverse events, 128
meningococcal vaccine, 219 contraindications, 128
mumps-containing vaccine, 205–6 diphtheria antitoxin, 129
pertussis-containing vaccine, 233, dosage and administration, 127
348 public health management, 128–9
pneumococcal vaccine, 248–9 pregnancy, 87, 129
poliomyelitis vaccine, 255 recommendations, 127–8
pregnancy, 85, 86, 206 variations from product information,
pre-vaccination screening for, 17–20 129–30
Q fever vaccine, 262 diplomats see travellers
rabies vaccine, 117 distraction techniques, 43
rotavirus vaccine, 270 doctors see healthcare workers (HCW)
RSV immunoglobulin, 182 dosage and administration, 39–57, 375–7
rubella vaccine, 279–80 adrenaline, 64
smallpox vaccine, 285 BCG vaccine, 298–9
solid organ transplant (SOT) cholera vaccine, 122
recipients, 94–6 diphtheria-containing vaccine, 127
tetanus-containing vaccine, 295 documentation, 66, 377
typhoid vaccine, 307–8 Haemophilus influenzae type b, 135,
varicella vaccine, 316–7 137–8
yellow fever vaccine, 325–6 hepatitis A vaccine, 142–3
correctional facility inmates, 108, 159 hepatitis B vaccine, 153–62
correctional facility staff, 106, 159, 192 hepatitis B vaccine accelerated
corticosteroids, 16, 20, 92, 118, 205, 207, schedule, 156
246, 279, 300, 317, 348–9 human papillomavirus (HPV)
Corynebacterium diphtheriae see diphtheria vaccine, 171
coughing illness see pertussis immunoglobulins, 146, 163, 176, 178,
Creutzfeldt-Jakob disease (vCJD), 354 179, 182, 183, 210–2, 282, 294–5, 319
see also mad cow disease; bovine influenza vaccine, 189–90
spongiform encephalopathy (BSE) injection sites, 45–6, 51–2
cystic fibrosis, 190, 246 Japanese encephalitis (JE) vaccine,
cytomegalovirus see also 197
immunoglobulins measles-containing vaccine, 203,
CMV immunoglobulin, 181–2 210–2
meningococcal vaccine, 217–8
multiple injections, 56–7

mumps-containing vaccine, 224 typhoid, 78, 303–4, 305, 306
pertussis-containing vaccine, 231 yellow fever, 79, 322–3, 324–5, 326
pneumococcal vaccine, 243 Engerix-B, 42, 151, 156, 340, 343 see also
poliomyelitis vaccine, 254 hepatitis B (HBV)
Q fever vaccine, 260 epidemic diseases see also endemic
rabies immunoglobulin (HRIG), 112, diseases
116 influenza, 184–6
rabies vaccine, 112, 115–7 Japanese encephalitis (JE), 195
rotavirus vaccine, 268 meningococcal disease, 214, 219
rubella vaccine, 278 pertussis, 227–8
smallpox vaccine, 284 rubella, 274
tetanus-containing vaccine, 291 yellow fever, 323–4
travellers, 76, 80–1, 82–3 epilepsy see neurological disease
typhoid vaccine, 305–6 equipment for vaccination, 39–41
varicella vaccine, 312, 320 erythromycin, 235–6, 237, 238
yellow fever vaccine, 324 essential service providers, 106, 159, 192
drug users see injecting drug users Europe
Dryvax, 283 see also smallpox avian influenza, 184
dT, 38, 81, 126–7, 292–4 diphtheria, 128
DT (CDT vaccine), 127, 291, 339 poliomyelitis, 251
dTpa, 38, 81, 96, 98, 125, 126–7, 229, 290 rabies, 110
DTPa-containing vaccines, 96, 98,125, tuberculosis, 297
126–7, 229, 290
catch-up, 31 F
DTPa-hepB-IPV, 125, 152, 229, 253, 290 fainting see vasovagal episodes
DTPa-hepB-IPV-Hib, 125, 134, 152, 230, farmers, 107, 260
253, 289 Far North Queensland and Torres Strait
DTPa-IPV, 125–6, 229, 253 290 Islands, 106, 195, 196, 198
dTpa-IPV, 126, 230, 254, 290 febrile convulsion, 208, 234, 249
Dukoral, 42, 121, 122 see also cholera febrile illness, acute, 17, 123, 300, 348
febrile seizure see febrile convulsion
E fetus see pregnancy and vaccination
egg protein allergy, 117, 193, 194, 207–8, fever, 59–60, 85, 199, 207–8, 220, 223, 234,
262, 325, 327, 341, 348, 350–1 249
elderly people see older people flu see influenza
embalmers, 107, 159, 300 Fluad, 42, 187, 189 see also influenza
emergency workers, 106, 159, 192 Fluarix, 42, 187, 189, 194 see also influenza
encephalitis, 75, 201, 225, 286–7, 318, 327, Fluvax, 42, 187, 189 see also influenza
365 see also Japanese encephalitis (JE) Fluvirin, 42, 187, 189, 194 see also
endemic diseases see also epidemic influenza
diseases food-handlers, 120, 147, 303, 308
cholera, 120, 122 formaldehyde, 341, 357
Index
hepatitis A, 78, 144, 147 frequently asked questions (FAQ),

hepatitis B, 156, 159 344–59
Japanese encephalitis (JE), 195, 198 funeral industry workers see embalmers
measles, 201, 205
poliomyelitis, 252, 255
rabies, 78, 110, 111, 113, 115, 117
Index 383
G hay fever, 350
GARDASIL, 42, 169 see also human HBcAg, 149
papillomavirus (HPV) HBeAg, 149
gastroenteritis, 265–6, 270 see also HbOC, 133, 135 see also Haemophilus
rotavirus influenzae type b
gelatin, 341, 356 HBsAg, 149, 150, 157, 162
General Practice Immunisation Incentive HBV see hepatitis B (HBV)
(GPII) scheme, 69, 332 H-B-VAX II, 42, 151 see also hepatitis B
genital warts, 164, 168, 171 (HBV)
global epidemiology healthcare workers (HCW), 105, 144, 145,
polio eradication, 252 159, 160, 161, 162, 163, 204, 221, 232,
smallpox eradication, 283 237–8, 255, 279, 281, 300, 313, 315–6,
tuberculosis, 297 321, 346
glossary of technical terms, 364–8 hepatitis A (HAV), 72, 78, 105, 106, 107,
graft-versus-host disease (GVHD), 97, 98 139–48
Guillain-Barré Syndrome (GBS), 16, 18, adverse events, 146
162, 180, 193–4, 361 contraindications, 146
dosage and administration, 142–3
immunoglobulin, 146, 177
H pregnancy, 88, 148
haematological malignancy, 93, 240, 246,
public health management, 146–7
247
recommendations, 143–5
haematopoietic stem cell transplantation
hepatitis B (HBV), 77, 135, 144, 149–63,
(HSCT), 97–8, 137, 138
353
haemodialysis patients, 158
adverse events, 162–3
haemoglobinopathy, 191, 246
catch-up, 31, 38
Haemophilus influenzae type b, 131–8
contraindications, 162
Aboriginal and Torres Strait Islander
dosage and administration, 153–6
children, 71, 132, 135
immunoglobulin, 151, 157, 163
adverse events, 137
non-responders, 160–1
asplenia (functional or anatomical),
post-vaccination serology testing,
101, 136
160
catch-up, 31, 33
pregnancy, 88, 163
contraindications, 137
preterm babies, 31, 90
dosage and administration, 135
variation from product information,
haematopoietic stem cell
163
transplantation, 97, 137
hepatitis B immunoglobulin (HBIG), 151,
pregnancy, 87, 138
157, 163, 176 see also hepatitis B (HBV)
preterm babies, 31, 90, 136
Hepatitis B Immunoglobulin-VF, 163
see also hepatitis B (HBV)
herpes zoster (HZ) see zoster
Hib see Haemophilus influenzae type b
138
Hiberix, 42, 31, 133, 134 see also
Hajj, 79, 219
Haemophilus influenzae type b
HAV see hepatitis A (HAV)
Hib (HbOC), 133, 135 see also Haemophilus
Havrix, 42, 140, 146 see also hepatitis A
influenzae type b
(HAV)
Hib (PRP-D), 133 see also Haemophilus
Havrix Junior, 42, 140 see also hepatitis A
influenzae type b
(HAV)

Hib (PRP-OMP)-hepB, 133 see also intramuscular NHIG, 178–9
Haemophilus influenzae type b intravenous NHIG, 180
Hib (PRP-T), 133, 134 see also Haemophilus availability, 176
influenzae type b botulism antitoxin, 181
Hirschsprung’s disease, 270 cytomegalovirus immunoglobulin,
HIV-infected individuals, 99–100, 122, 181–2
146, 158, 191, 199, 205, 206, 349–50 dosage and administration, 177, 179
Hodgkin’s disease, 92, 93, 205, 247, 279, normal human immunoglobulin
302, 317 see also lymphoma (NHIG), 175, 176–7, 179
homeless people, 192 prophylaxis, 177–8
homeopathic immunisation, 359 recommendations,
homosexual men see sexual contact intramuscular NHIG, 177–8
HPV infection see human papillomavirus intravenous NHIG, 180
(HPV) respiratory syncytial virus
human diploid cell vaccine (HDCV), 42, immunoglobulin, 182–3
111, 117, 118, 119 see also rabies specific diseases and, 175, 181
human immunoglobulin see hepatitis A, 146, 177
immunoglobulins hepatitis B, 151, 157, 163, 177
human papillomavirus (HPV), 59, 164–74 measles, 177, 210
adverse events, 173–4 rabies (HRIG), 112, 114–7, 176
contraindications, 173 rubella, 280
dosage and administration, 171 smallpox, 286–7
males, 173 tetanus, 294–5
precautions, 173 varicella, 178, 317
pregnancy, 88, 174 zoster immunoglobulin (ZIG), 178,
recommendations, 171–3 309, 319–20
human rabies immunoglobulin (HRIG), immunosuppressed see impaired
112, 114–7, 176 see also rabies immunity, individuals with
hyperimmune globulin, 88, 102 immunosuppressive agents, 118, 205,
hypotonic-hyporesponsive episode 279, 300, 317
(HHE), 233, 235 Imogam Rabies, 112 see also rabies
HZ see zoster impaired immunity, individuals with,
90–2, 349
I cholera, 122, 123
immigrants, 22, 75, 108 contacts of, 20, 91, 192, 209, 271, 285,
hepatitis B, 150 308, 313, 314–5, 320, 321
rubella, 278 Haemophilus influenzae type b, 132
immune thrombocytopenia, 180 see also hepatitis B, 158, 160, 161
bleeding disorders human papillomavirus (HPV), 173
Immunisation History Statements, 22, 68 immunoglobulins, 178, 180
immunocompromised see impaired influenza, 90, 91, 92, 191
immunity, individuals with Japanese encephalitis (JE), 199
Index
immunodeficient see impaired immunity, measles, 91, 205, 211

individuals with mumps, 91
immunoglobulins, 102–3, 175–83 see also pneumococcal disease, 90–1, 240, 247
normal human immunoglobulin rotavirus, 266, 271
(NHIG) rubella, 91, 279–80
adverse events, smallpox, 91
Index 385
tuberculosis, 91, 298 varicella, 309
typhoid, 91 inflammatory bowel disease, 61, 122, 209,
varicella, 91, 309, 316–7 352–3
yellow fever, 91, 326 influenza, 72–3, 77, 184–94, 354
zoster (herpes zoster) (HZ), 329 adverse events, 193–4
inactivated poliomyelitis vaccine (IPV), contraindications, 193
42, 77, 253–4 see also poliomyelitis dosage and administration, 189–90
inactivated vaccines, 87–8 precautions, 193
cholera, 121 pregnancy, 88, 192, 194
diphtheria-containing, 125–6 preterm babies, 90
dT, 126, 290 recommendations, 190–3
DTPa-containing, 125–6, 152, 134, variation from product information,
253, 229–30, 289–91 194
dTpa-containing, 126, 254, 290–1, Influvac, 42, 187 see also influenza
Haemophilus influenzae type injecting drug users, 109, 139, 144, 145,
b-containing, 134 158, 293
hepatitis A-containing, 141 injection site nodules, 60, 356
human papillomavirus (HPV), 169 see also adverse events following
influenza, 187–8 immunisation (AEFI)
Japanese encephalitis (JE), 196 injection site, 45–6, 51–5 see also dosage
meningococcal, 215, 216 and administration; intradermal
pertussis-containing, 229–30 injections; intramuscular injections;
pneumococcal, 241, 242 subcutaneous injections
poliomyelitis-containing, 253–4 injection technique, 42, 44–5 see also
rabies, 111 dosage and administration;
typhoid, polysaccharide vaccine, 304 intradermal injections; intramuscular
incomplete dose see interruption to a injections; subcutaneous injections
vaccination; regurgitation of vaccine intellectually disabled people, 144, 145,
India 159
poliomyelitis, 251, 252 interchangeability of vaccines
typhoid, 304 Haemophilus influenzae type b, 31, 136
Indigenous people see Aboriginal and hepatitis A, 141–2
Torres Strait Islander people hepatitis B, 161
Indonesia poliomyelitis, oral and inactivated,
JE virus, 198 255
poliomyelitis, 252 rotavirus, 273
rabies, 119 interferon-gamma release assays, 302
Infanrix hexa, 42, 125, 134, 152, 230, 253, interruption to a vaccination, 25 see also
289 see also DTPa-hepB-IPV-Hib regurgitation of vaccine
Infanrix-IPV, 42, 125, 230, 254, 290 see also intradermal injections, 113–4
DTPa-IPV Intragam P, 179, 180 see also
Infanrix Penta, 42, 125, 152, 229, 253, 290 immunoglobulins
see also DTPa-hepB-IPV intramuscular injections, 42, 44–55
infants see children and infants intussusception (IS), 272, 362
infectious period invasive pneumococcal disease (IPD), 72,
hepatitis A, 146 240–1, 246, 247
measles, 201 IPOL, 42, 253 see also poliomyelitis
pertussis, 235–6

J local anaesthetic, vaccinations and
Japanese encephalitis (JE), 73, 78, see topical anaesthetics
195–200 lockjaw, 288 see also tetanus
adverse events, 199–200 lymphoma, 93, 205, 247, 279, 285, 302,
contraindications, 199 317 see also Hodgkin’s disease
precautions, 199 M
pregnancy, 88, 200 mad cow disease, 354 see also bovine
recommendations, 197–8 spongiform encephalopathy (BSE)
variation from product information, Mantoux technique see tuberculin skin
200 test (TST)
jaundice, false contraindication, 21 manufacturing residuals, 340–3, 357
JE-VAX, 42, 196 see also Japanese maternity hospital staff, 105, 237–8
encephalitis (JE) Maternity Immunisation Allowance, 67,
68, 347
K measles, 77, 105, 201–12 see also MMR
Kawasaki disease, 103, 179, 180 adverse events, 208–9
catch-up, 32, 38
contraindications, 205–6
L dosage and administration, 203
laboratory personnel, 106, 113, 198, 218,
immunoglobulin, 177–8, 210–2
219, 255, 260, 284, 306, 324
precautions, 206–8
lactation see breastfeeding and lactation
pregnancy, 86, 212
latent TB infection (LTBI), 301
Latin America see Americas
leprosy, 298, 300
transmissibility, 209
leukaemia, 16, 93, 94, 178, 205, 279, 285,
317, 349
212
limb swelling, 59, 234
measles-mumps-rubella vaccine
Liquid PedvaxHIB, 42, 31, 71, 133, 134
see MMR
see also Haemophilus influenzae type b
measles-mumps-rubella-varicella
live attenuated vaccines, 20–1, 85, 91
vaccine see MMRV
BCG, 298
meat industry, 106, 258, 260
contraindications and, 20, 85, 86, 91
medical students, 105, 145, 279
immunoglobulins/blood products
Medicare, 67, 332
and, 16, 18, 102–3, 175–6, 271
men who have sex with men see sexual
interval between, 17, 206, 225, 280,
contact
301
Mencevax ACWY, 42, 216, 222 see also
MMR, 201, 223, 274
meningococcal disease
rotavirus, 267
Meningitec, 42, 215, 222 see also
smallpox, 284
meningococcal disease
surgery and, 104
meningococcal disease, 79, 101, 213–22
Index
typhoid (oral), 304

asplenia (anatomical or functional)
varicella, 309
and, 101, 218, 219
yellow fever, 323
early clinical management and, 220
liver transplant recipients, 94, 144, 159
meningococcal C conjugate vaccine
livestock industry, 107, 258, 260
(MenCCV), 215
adverse events, 220
Index 387
catch-up, 32 catch-up, 32, 38
contraindications, 219 contraindications, 205–6, 225
dosage and administration, 217 dosage and administration, 224
recommendations, 218 immunoglobulin, 225
meningococcal polysaccharide precautions, 225
vaccine (4vMenPV), 215 pregnancy, 86, 225
adverse events, 220 recommendations, 224–5
contraindications, 219 variation from product information,
dosage and administration, 217 212, 226
recommendations, 219 Mycobacterium tuberculosis
pregnancy, 87, 221–2 see tuberculosis
variation from product information, N
222 National Centre for Immunisation
Menjugate Syringe, 42, 215, 222 see also Research and Surveillance of Vaccine
meningococcal disease Preventable Diseases (NCIRS), iii, iv,
Menomune, 42, 216, 222 see also 13, 353, 359
meningococcal disease National Immunisation Program (NIP),
mercury, 355 see also thiomersal-free 127, 215, 228
vaccines; thiomersal in vaccines components of vaccines used in,
Mérieux Inactivated Rabies Vaccine, 42, 340–3
111 see also Australian bat lyssavirus National Measles Control Campaign,
(ABL) infection; rabies 202, 274
Meruvax II, 42, 277 see also rubella National Meningococcal C Vaccination
Middle East see also Hajj Program, 215
cholera, 120 needles, 44 see also dosage and
meningococcal disease, 219 administration
military personnel see armed forces Neisseria meningitidis see meningococcal
minimum ages for vaccination, 30 disease
minimum dose intervals for National NeisVac-C, 42, 215, 222 see also
Immunisation Program (NIP) vaccines, meningococcal disease
29 neurological disease, 21, 90, 191, 195,
MMR (measles-mumps-rubella), 77, 199–200, 233, 348
352–3, 358–9 newborn nurseries, 237–8, 271
catch-up, 32 normal human immunoglobulin (NHIG),
for measles, 202 146–7, 175, 177, 176, 179
for mumps, 224 see also immunoglobulins
for rubella, 275 Normal Immunoglobulin-VF (human)
immunoglobulin/blood products (NHIG), 177 see also immunoglobulins
interval, 94, 102–3, 147, 175–6, nurses see healthcare workers (HCW)
210–2 nursing home residents, 188, 192
MMRV (measles-mumps-rubella- nursing home staff, 106, 192
varicella), 202–4, 206, 224, 310, 312 nursing students, 105, 145, 279
multiple injections, 24, 56–7, 345
multiple sclerosis (MS), 61, 101–2, 163,
191, 352, 353, 370
O
occupational risks, 104–7
mumps, 202, 223–6 see also MMR
hepatitis A, 144, 145, 147
adverse events, 225
hepatitis B, 159–60, 161, 162, 163

influenza, 192–3 Papua New Guinea, 75, 78, 82, 198, 304
Japanese encephalitis (JE), 198 paracetamol, 58, 60, 207, 209, 318, 348
measles, 204 pertussis, 31, 87, 96, 98–9, 105–7, 125, 127,
meningococcal disease, 218–9, 221 134, 227–39, 346–7, 358 see also DTPa-
pertussis, 232, 237, 346 containing vaccines
poliomyelitis, 255 adverse events, 234–5
Q fever, 258, 260 contraindications, 233
rabies, 113 dosage and administration, 231
rubella, 279, 281 minimum interval between dTpa
smallpox, 284 and dT, 233
typhoid, 306, 308 precautions, 233–4
varicella, 313, 315–6, 321 pregnancy, 87, 238
yellow fever, 324 public health management, 235–8
occupation health and safety, 39 see also recommendations, 231–2
standard precautions special considerations, 233
Oceania (includes Pacific Islands) variation from product information,
cholera, 120 238–9
hepatitis B, 77, 150 Pharmaceutical Benefits Advisory
poliomyelitis, 251 Committee (PBAC), 334
rabies, 110 phenol, 342, 356
rubella, 278 phenoxyethanol, 342, 355
tuberculosis, 297 plague, 3
typhoid, 78, 304 pneumococcal disease, 72, 240–50
yellow fever, 322 asplenia (functional or anatomical),
Octagam, 179 see also immunoglobulins 100–1
older people invasive pneumococcal disease
influenza, 77, 188, 190, 193, 346 (IPD), 72, 240–1, 246, 247
pertussis, 19, 232, 346 pneumococcal conjugate vaccine
pneumococcal disease, 77, 101, 246, (7vPCV), 135, 241–2, 243–6
248 Aboriginal and Torres Strait
tetanus, 288 Islander children, 34–5, 72,
varicella 330 240–1, 243, 245, 247
yellow fever, 326 adverse events, 249
zoster (herpes zoster) (HZ), 329, 330 catch-up, 32, 34–6
oncology patients, 92–4 see also impaired contraindications, 248
immunity, individuals with dosage and administration, 243
oral poliomyelitis vaccine (OPV), 60–1, impaired immunity, individuals
252, 254, 255, 302, 305 with, 90–1, 92
oral vaccines, 42 Infanrix hexa and, 134
organ donors see blood and organ donors recommendations, 243–6
outbreak control see public health pneumococcal polysaccharide
management vaccine, (23vPPV) 241, 242, 246–8
Index
overseas travel see travellers Aboriginal and Torres Strait

Islander children, 72, 245, 247
P Aboriginal and Torres Strait
Pacific Islands see Oceania Islander people, 73, 241, 246, 248
palivizumab (Synagis), 176, 182–3 see also adverse events, 249
immunoglobulins contraindications, 248
Index 389
dosage and administration, 243 human papillomavirus (HPV), 173
impaired immunity, individuals immunoglobulins, 178, 180
with, 91 influenza, 193
recommendations, 246–8 Japanese encephalitis (JE), 199
revaccination with, 247–8 measles, 206–8
pregnancy, 87, 249 mumps, 225
preterm babies, 89, 246 pertussis, 233–4
travel and, 77 Q fever, 263
variation from product information, rotavirus, 270–2
250 rubella, 280
pneumonia, 72–3, 190, 240, 242 smallpox, 285
Pneumovax 23, 42, 242 see also tetanus, 295
pneumococcal disease tuberculosis, 301
police, 106, 159, 192 typhoid, 307
poliomyelitis, 251–6 see also DTPa-hepB- varicella, 317–8
IPV-Hib; dTpa-hepB-IPV, inactivated yellow fever, 326
poliomyelitis vaccine (IPV); oral prednisolone, 92, 205, 207, 246, 317, 349
poliomyelitis vaccine (OPV); vaccine- pre-exposure prophylaxis
derived poliovirus (VDPV) Australian bat lyssavirus (ABL)
adverse events, 255 infection, 112–4
catch-up, 32 immunoglobulins, 177
contraindications, 255 rabies, 78, 81, 82, 112–4, 119
dosage and administration, 254 pregnancy and vaccination, 16, 18–20,
pregnancy, 88, 255 84–90, 350
recommendations, 254–5 BCG vaccine, 86, 300–1
variation from product information, cholera vaccine, 87, 123
256 contacts, vaccination in, 18, 86, 89,
polysaccharide vaccines see 350
meningococcal disease; pneumococcal diphtheria-containing vaccine, 87
disease; typhoid Haemophilus influenzae type b
positioning for vaccination, 47–51 vaccine, 87
post-exposure treatment hepatitis A vaccine, 88
Australian bat lyssavirus (ABL) hepatitis B vaccine, 88
infection, 114–7 human papillomavirus (HPV)
hepatitis A, 146–7 vaccine, 88, 174
hepatitis B, 161–2 immunoglobulins, 88
immunoglobulins, 177–8 influenza vaccine, 88, 192, 194
measles, 209–12 Japanese encephalitis (JE) vaccine,
meningococcal disease, 220–1 88, 200
mumps, 225 measles-containing vaccine, 86, 206,
pertussis, 237–8 212
rabies, 112, 114–7 meningococcal vaccine, 87, 221–2
varicella, 314, 315–6 mumps-containing vaccine, 86, 225
post-vaccination procedures, 58–69, 377 pertussis-containing vaccine, 87,
see also serology 232, 346
poultry industry, 107, 192 pneumococcal vaccine, 87, 249
precautions, 14, 40, 348, 350–1 poliomyelitis, 88
cholera, 123 Q fever vaccine, 87, 263

rabies vaccine, 88, 118 pertussis-containing vaccine, 238–9
rotavirus vaccine, 86 pneumococcal vaccine, 250
rubella vaccine, 86, 278, 280, 281, 282 poliomyelitis vaccine, 256
smallpox vaccine, 86, 285, 286 Q fever vaccine, 264
tetanus-containing vaccine, 87 rabies vaccine, 119
typhoid vaccine, 86, 87, 307, 308 rotavirus vaccine, 273
varicella vaccine, 86, 313, 316, 320, rubella vaccine, 282
321 tetanus-containing vaccine, 296
yellow fever vaccine, 86, 326, 327, typhoid vaccine, 308
328 varicella vaccine, 321
preschool see childcare facilities yellow fever vaccine, 328
preservatives in vaccines, 340–3, 355–6 products previously available, 339
preterm babies, 18, 45, 89 see also babies products registered but not currently
(neonates) available, 339
catch-up and, 31 public health management
Haemophilus influenzae type b diphtheria, 128–9
vaccine, 90, 136 Haemophilus influenzae type b, 137–8
hepatitis B vaccine, 90, 157 hepatitis A, 146–7
influenza vaccine, 90 measles, 209–12
pneumococcal vaccine, 89, 246 meningococcal disease, 220–1
poliomyelitis vaccine, 255 pertussis, 235–8
rotavirus vaccine, 270 rubella, 281
vaccination and, 345–6 typhoid, 308
pre-vaccination procedures, 14–38, 375 varicella, 319–20
pre-vaccination screening, 8–21, 60, 375 purified chick embryo cell vaccine
see also serology (PCECV), 42, 111, 117, 118 see also
checklist, 16, 375 rabies
Q fever, 260–2, 263 Purified Protein Derivative (PPD), 301–2
tuberculosis, 299, 301–2 see also tuberculosis
Prevenar, 42, 241 see also pneumococcal
disease Q
Priorix, 42, 203 see also MMR; measles, Q fever, 106, 107, 257–64
mumps; rubella adverse events, 263
prisoners and staff see correction facility contraindications, 262
inmates; correction facility staff dosage and administration, 260
product information, variations from precautions, 263
BCG vaccine, 302 pregnancy, 87, 263
diphtheria-containing vaccine, pre-vaccination testing, 259, 260–2
129–30 recommendations, 260–2
Haemophilus influenzae type b serology, 260–2
vaccine, 138 skin testing, 261–2
hepatitis B vaccine, 163 variation from product information,
Index
influenza vaccine, 194 264

Japanese encephalitis (JE) vaccine, Q fever fatigue syndrome (QFS), 257
200 Q Fever Management Program, 258
measles-containing vaccine, 212 Q-VAX, 42, 259 see also Q fever
meningococcal vaccine, 222 Q-VAX Skin Test, 259 see also Q fever
mumps-containing vaccine, 212
Index 391
R rubella, 105, 274–82, 358 see also MMR
rabies, 78, 106, 107, 110–9 adverse events, 280–1
adverse events, 118 blood products and MMR, 102–3, 206
contraindications, 117 contraindications, 279–80
dosage and administration, 112 dosage and administration, 278
endemic, 110, 111, 113, 115, 117 immunoglobulins, 281–2
in Indonesia, 119 males, 279
post-exposure prophylaxis, precautions, 280
vaccine, 114–7 pregnancy, 86, 281
rabies immunoglobulin (HRIG), public health management, 281
103, 116–7 recommendations, 278–9
pre-exposure prophylaxis, 78, 81, 82, serological testing for, 276–7
112–4 variation from product information,
pregnancy, 88, 118 282
119 S
Rabipur Inactivated Rabies Vaccine, 42, salicylates see aspirin therapy
111 see also Australian bat lyssavirus Salmonella Typhi see typhoid
(ABL) infection; rabies Sandoglobulin NF liquid, 179 see also
refrigerators, 9–12 immunoglobulins
refugees see immigrants Saudi Arabia, 79, 219
regurgitation of vaccine, 25, 272 see also screening see pre-vaccination screening;
interruption to a vaccination serology
renal disease see chronic conditions seizures or convulsions, history of, 191,
respiratory disease see chronic conditions 207, 249, 348 see also febrile convulsion
respiratory syncytial virus (RSV), 176 serology
RSV immunoglobulin (RSVIG), post-vaccination, 113, 116, 142, 160,
182–3 276, 278, 314
respiratory syncytial virus pre-vaccination, 84, 97, 108, 143,
immunoglobulin (RSVIG) see 260–1, 276–7, 314, 315
respiratory syncytial virus (RSV) sexual contact
Reye syndrome, 191, 207, 310, 318, 321 hepatitis A, 146
rheumatoid arthritis (RA), 101–2 hepatitis B, 150–1, 158, 160, 162
rifampicin, 137–8, 221 HPV infection, 165
Rotarix, 42, 266, 267, 268 see also rotavirus men who have sex with men, 108,
RotaShield, 272 139, 144, 145, 158
RotaTeq, 42, 266, 267, 268 see also shearers, 107, 258, 260
rotavirus shingles see zoster
rotavirus, 265–73 simultaneous administration of vaccines,
adverse events, 272–3 56–7 see also multiple injections
catch-up, 32 BCG vaccine, 301
dosage and administration, 268 cholera vaccine, 122
pregnancy, 86, 272 Haemophilus influenzae type b, 135
recommendations, 268–70 hepatitis A vaccine, 144
regurgitation of vaccine, 25, 272 hepatitis A/hepatitis B vaccine, 145
variation from product information, hepatitis A/typhoid vaccine, 145
273 human papillomavirus (HPV)
route of administration, 41–2 vaccine, 171

immunoglobulins/blood products systemic lupus erythematosus (SLE),
and, 103 101–2
inactivated vaccines and
immunoglobulins, 176 T
influenza vaccine, 190 tattooists, 107, 159
meningococcal vaccine, 217, 222 technical terms, glossary of, 364–8
MMR vaccine, 203, 224, 225, 278, 280 tetanus, 77, 288–96, 358 see also DT; dT;
oral cholera and oral typhoid DTPa; dTpa
vaccines, 122 adverse events, 295–6
pneumococcal vaccine, 243, 246 contraindications, 295
Rh (D) immunoglobulin (anti-D) dosage and administration, 291
and, 176, 206, 279 precautions, 295
rotavirus vaccine, 268 pregnancy, 87, 88, 296
rubella vaccine, 278 recommendations, 292–3
typhoid, 305 tetanus-prone wounds, treatment of,
varicella vaccine, 312, 317 292, 293–5
yellow fever vaccine, 326 variation from product information,
skin cleaning, 43 296
smallpox, 85, 91, 106, 283–7 Tetanus Immunoglobulin-VF (for
adverse events, 286 intravenous use), 295 see also tetanus
contraindications, 285 Tetanus Immunoglobulin-VF (TIG),
dosage and administration, 284 294–5 see also tetanus
immunoglobulin, 286 tetravalent meningococcal
precautions, 285 polysaccharide vaccines
pregnancy, 86, 286 see meningococcal disease
recommendations, 284 Therapeutic Goods Administration, 284,
smokers 354
pneumococcal disease, 247, 248 thimerosal see thiomersal-free vaccines;
pregnancy and, 84, 87 thiomersal in vaccines
solid organ transplant (SOT) recipients, thiomersal-free vaccines, 153, 156, 157,
94–6, 145 355
splenectomy, 16, 19, 36, 93, 100–1, 136, thiomersal in vaccines, 153, 188, 343, 355
247 see also asplenia (functional or thrombocytopenia, 207–8
anatomical) tick-borne encephalitis, 79
Stamaril, 42, 323 see also yellow fever topical anaesthetics, 41, 43, 116
standard precautions, 39, 105, 159, 270 Torres Strait Islanders see Aboriginal and
stem cell transplants see haematopoietic Torres Strait Islander people
stem cell transplantation (HSCT) Torres Strait Islands and Far North
steroids see corticosteroids Queensland see Far North Queensland
stockyard workers, 107, 258, 260 and Torres Strait Islands
Streptococcus pneumoniae transmission, live vaccines and, 85–9, 91
see pneumococcal disease measles, 209, 212, 349, 350
Index
subcutaneous injections, 42, 55 mumps, 225, 349, 350

sudden infant death syndrome (SIDS), rotavirus, 270, 271
61, 235, 354 rubella, 280, 349, 350
surgery, 21, 104 typhoid (oral), 307
Synagis (palivizumab), 176, 182–3 see also varicella, 314–5, 318, 349, 350
respiratory syncytial virus (RSV)
Index 393
transplants see haematopoietic stem cell poliomyelitis, 77, 88, 252, 255
transplantation (HSCT); solid organ rabies, 78, 88, 111, 113, 115, 117
transplant (SOT) recipients tetanus, 77, 293
transport, storage and handling of tick-borne encephalitis, 79
vaccines see also cold chain tuberculosis, 79, 300
BCG vaccine, 298 typhoid, 78, 86, 91, 303, 305, 306
cholera vaccine, 121 varicella, 77
diphtheria-containing vaccine, 127 yellow fever, 79, 86, 91, 323, 324–5,
Haemophilus influenzae type b 326, 327, 328
vaccine, 135 tuberculin skin test (TST), 207, 299, 300,
hepatitis A vaccine, 142 301–2
hepatitis B vaccine, 153 live vaccines and, 302
human papillomavirus (HPV) tuberculosis (TB), 70–1, 79, 207, 297–302
vaccine, 171 adverse events, 301
immunoglobulins, 176 contraindications, 300
influenza vaccine, 189 dosage and administration, 298–9
Japanese encephalitis (JE) vaccine, precautions, 301
197 pregnancy, 86, 301
measles-containing vaccine, 203 recommendations, 300
meningococcal vaccine, 217 tuberculin skin test, 301–2
mumps-containing vaccine, 224 variation from product information,
pertussis-containing vaccine, 231 302
pneumococcal vaccine, 242–3 Tubersol, 301–2 see also tuberculin skin
poliomyelitis vaccine, 254 test (TST)
Q fever vaccine, 259 Twinrix, 141 see also hepatitis A (HAV);
rabies vaccine, 112 hepatitis B (HBV)
rotavirus vaccine, 267 Twinrix Junior, 141 see also hepatitis A
rubella vaccine, 277 (HAV); hepatitis B (HBV)
smallpox vaccine, 284 Typherix, 42, 304 see also typhoid
tetanus vaccine, 291 Typhim Vi, 42, 304 see also typhoid
typhoid vaccine, 305 typhoid, 78, 123, 303–8
varicella vaccine, 311–2 adverse events, 307
yellow fever vaccine, 323 contraindications, 307
travellers, 75–83, 91, 100 see also Africa; dosage and administration, 305–6
Americas; armed forces, Asia; Europe; hepatitis A/typhoid, 143, 145, 304
Hajj; Middle East; Oceania precautions, 307
cholera, 78, 120, 122 pregnancy, 86, 87, 308
diphtheria, 128 public health management, 308
hepatitis A, 78, 88, 144 recommendations, 306
hepatitis A/typhoid, 145 variation from product information,
hepatitis B, 77, 159 308
infections acquired by, 75–6
influenza, 77, 193 V
Japanese encephalitis (JE), 78, 197–8 Vaccination, commonly asked questions,
measles, 77, 204–5, 358 344–59
meningococcal disease, 79, 219 vaccine-associated paralytic
MMR, 204–5 poliomyelitis (VAPP), 60–1, 252
pneumococcal disease, 77

vaccine-associated viscerotropic adverse ventrogluteal area, 45, 46, 48, 51, 53–4, 56,
events, 327 57, 345 see also injection site; injection
vaccine-derived poliovirus (VDPV), 252 technique
vaccines veterinarians, students and staff, 107,
components used in NIP, 340–3 113, 260
dates when available in Australia, Vibrio cholerae see cholera
372–4 Vivaxim, 42, 141, 304 see also hepatitis A
failures, 136, 259, 310–1, 312–3 (HAV); typhoid
vaccinia immune globulin (VIG), 286–7 Vivotif Oral, 42, 304 see also typhoid
see also smallpox
vaccinia virus (smallpox), 85, 106, 283 W
see also smallpox whooping cough see pertussis
VAQTA, 42, 141 see also hepatitis A women see also breastfeeding and
(HAV) lactation; pregnancy and vaccination
VAQTA Paediatric/Adolescent of child-bearing age and rubella
formulation, 42, 141, 146 see also vaccination, 275–7, 278, 279
hepatitis A (HAV) World Health Organization (WHO), 22,
varicella, 77, 98, 99, 104, 105, 207, 309–21 78, 79, 83, 108, 163, 202, 219, 251, 252,
adverse events, 60, 318 297, 353
breakthrough varicella, 310–1, 312–3
catch-up, 32
contraindications, 91, 92, 96, 316–7
Y
yellow fever, 75, 79, 106, 322–8
dosage and administration, 44, 312
adverse events, 327
immunoglobulin/blood product
contraindications, 91, 100, 325–6
interval, 94, 102–3, 147, 175–6,
320–1
endemic countries, 324
precautions, 92, 94, 317–8
International Certificate of
pregnancy, 86, 320
Vaccination against Yellow Fever,
public health management, 178,
323, 325
319–20
precautions, 326
pregnancy, 86, 327
serological testing for, 314
321
328
varicella-zoster virus (VZV), 309, 329,
yellow fever vaccination centres, 325
330 see also zoster
Varilrix, 42, 311 see also varicella
Varivax Refrigerated, 42, 311–2, 330 Z
see also varicella zoster (herpes zoster) (HZ), 309, 319,
vasovagal episodes, 61–2 329–31
vastus lateralis, 45, 46, 47, 51–2, 345 vaccine, 330–1, 339
see also injection site; injection zoster immunoglobulin (ZIG), 178, 309,
Index
technique 315, 319–20 see also varicella

Vaxigrip, 42, 187 see also influenza Zoster Immunoglobulin-VF (human),
Vaxigrip Junior, 42, 188, 189 see also 319–20 see also varicella
influenza
Index 395

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5IF"VTUSBMJBO

Australian Government health authorities

COMPARISON OF THE EFFECTS OF DISEASES AND THE SIDE EFFECTS OF VACCINES

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In children the following may also occur:

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What to do to manage injection site discomfort

Managing fever after immunisation

ii The Australian Immunisation Handbook 9th Edition

Members of the Australian Technical

Secretariat support, Australian Technical

Handbook Technical Support

iv The Australian Immunisation Handbook 9th Edition

PART 1: VACCINATION PROCEDURES  1

PART 2: Vaccination for special risk groups 70

vi The Australian Immunisation Handbook 9th Edition

PART 3: Vaccines listed by disease 110

viii The Australian Immunisation Handbook 9th Edition

Table 1.3.1: Pre-vaccination screening checklist 16

x The Australian Immunisation Handbook 9th Edition

Figure 1.3.1: Catch-up Worksheet for children <8 years of age 27

Introduction to The Australian

2 The Australian Immunisation Handbook 9th Edition

Changes introduced in this edition of the Handbook

1.1 What’s new?

New chapters and chapters which no

Overview of major changes to existing

4 The Australian Immunisation Handbook 9th Edition

1.1 What’s new?

Chapter 3.6 Hepatitis B

Chapter 3.8 Immunoglobulin preparations

Chapter 3.9 Influenza

Chapters 3.11 Measles, 3.13 Mumps and 3.19 Rubella

Chapter 3.14 Pertussis

Chapter 3.15 Pneumococcal disease

Chapter 3.24 Varicella

Chapter 3.25 Yellow fever

6 The Australian Immunisation Handbook 9th Edition

The following sections of Part 1 (Chapters 1.3–1.5) describe chronologically the

An overview of vaccination – preface to Chapters 1.3–1.5 7

1.3.1 Preparing an anaphylaxis response kit

Section 1.5.2 provides details on recognition and treatment of adverse events

1.3.2 Effective cold chain: transport,

8 The Australian Immunisation Handbook 9th Edition

10 The Australian Immunisation Handbook 9th Edition

Cold chain breaches

Do not use vaccines exposed to temperatures below +2°C or above +8°C

1.3.3 Valid consent

For consent to be legally valid, the following elements must be present:8

Consent on behalf of a child or adolescent

12 The Australian Immunisation Handbook 9th Edition

Consent on behalf of people with impaired decision-making ability

Resources to help communicate the risks and benefits of vaccines

See also Appendix 5, Commonly asked questions about vaccination.

1.3.4 Pre-vaccination screening

For some individuals, alterations to the routinely recommended vaccines may be

14 The Australian Immunisation Handbook 9th Edition

Pre-vaccination screening checklist

A different vaccine schedule may be recommended if the person to be vaccinated:

16 The Australian Immunisation Handbook 9th Edition

Table 1.3.2: Responses to relevant conditions or circumstances identified by the

18 The Australian Immunisation Handbook 9th Edition

* Live attenuated vaccines are classified in Table 1.3.3 below.

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PART 1: VACCINATION PROCEDURES 1

PART 2: Vaccination for special risk groups 70

PART 3: Vaccines listed by disease 110

Table 1.3.1: Pre-vaccination screening checklist 16

Figure 1.3.1: Catch-up Worksheet for children <8 years of age 27